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International Brain Hypothermia Symposium

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					   International Brain Hypothermia
   Symposium 2004
    Scientific meeting for brain protection and
    resuscitation with hypothermia                   Program &
    for physicians and researchers                   Abstracts




                                                  2004
February 5 – 6, 2004
Tokyo Dome Hotel, Tokyo, JAPAN
                                                  PROGRAM AT A GLANCE
        Wednesda
DATE    y, February                   Thursday, February 5                                                          Friday, February 6
                4

ROOM                                TENKU-A           TENKU-BAURORA                                TENKU-A                         TENKU-B           AURORA
TIME

8:45                      8:45                                    Breakfast                                                                          Breakfast
                                 Opening Remarks
                          8:50
9:00                      8:50                                                           9:00
                                 "Basic Science"
                                     Lecture                                              "ICU Management"
9:30                            John T. Povlishock                                              Lecture
                          9:50 W. Dalton Dietrich                                        9:50 M. Ross Bullock
10:00                     10:00                                                          10:00                           10:00


10:30                            "Neurotrauma"                                                     "Stroke"                 "Basic Science"




                                                                                                                                                        Poster Exhibition
                                    Lecture
                                                                     Poster Exhibition




                                                                                                    Lecture
11:00                              Barth A. Green                                                 Stefan Schwab              Oral Presentation
                                  Donald W. Marion                                              Oral Presentation
11:30                            Oral Presentation
                          12:00                                                          11:50                           11:50
12:00                     12:10                                                          12:00                           12:00
                                 Luncheon Seminar                                               Luncheon Seminar            Luncheon Seminar
12:30                             Hubert Rosomoff                                                Anthony Marmarou                Thorsten Steiner
                          13:00                                                          12:50                           12:50
13:00                     13:10                                                          13:00                           13:00   "Monitoring"
                                   "Emergency
                                                                                             "Intraoperative
                                   Hypothermia"                                                                                    Lecture
13:30                                                                                          Hypothermia"                      Urban Ungerstedt
                                      Lecture
                          14:00 Patrick M. Kochanek
                                                                                             Oral Presentation
                                                                                         14:00                           14:00 Oral   Presentation
14:00                                                             14:10                                                                              14:10
                                                                   Poster                                                                             Poster
14:30                                                             Viewing                                                                            Viewing
        15:00                                                     14:50                                                                              14:50
                          15:00                                                          15:00                           15:00
                                                                                                                                                               Poster Exhibition
15:00
                                                                                                  "Pediatrics"              "New Therapies"
                            Lecture by President
15:30                                                                                               Lecture                     Lecture
                                  Nariyuki Hayashi
                                                                                                 P. David Adelson                   Ryo Noda
                          15:50
                                                                                                                                 Nariyuki Hayashi
16:00                     16:00                                                                 Oral Presentation
                             "Postresuscitative                                                                              Oral Presentation
                                                                                         16:20                           16:20                       16:30
                                                                     Poster Exhibition




16:30                          Hypothermia"                                              16:30
                                  Lecture
           Registration




                               Stephen A. Bernard                                                Summary Table
17:00
                           Michael Holzer / Ken Nagao                                              Discussion
                          17:20   Oral Presentation                                               Nariyuki Hayashi
17:30                     17:30                                                                  Anthony Marmarou

                           "Cooling Technique"                                           18:00
18:00                             Lecture
                                 William Coplin
                          18:30 Stefan Schwab
18:30
                                                        19:00     19:00
19:00
                                                         Dinner
                                                          Party
CONTENTS

        Greetings ………………………………………………………………                3
        Organizers ………………………………………………………………               4
        Acknowledgements …………………………………………………….            5
        General Information       ……………………………………………….     6
        Dinner Party     …………………………………………………………           9
        Luncheon Seminars …………………………………………………….           9
        Poster Exhibition    …………………………………………………….        9
        Technical Exhibition      ……………………………………………….     9
        Information for Presenters    ………………………………………….. 10
        Floor Plan ……………………………………………………………… 10
        Transportation & Maps ………………………………………………. 11
        Scientific Program ……………………………………………………. 13
               Oral Presentations     ………………………………………….. 13
               Poster Presentations ………………………………………….. 25
        Introduction of Main Speakers   …………………………………….. 33
        Abstracts ……………………………………………………………… 53
               Special Lectures ………………………………………………. 53
               Oral Presentations ………………………………………………. 76
               Poster Presentations …………………………………………. 103




                                      CONTACT ADDRESS

ADDRESS DURING THE IBHS2004
  IBHS2004 Secretariat
  Tokyo Dome Hotel
  1-3-61 Koraku, Bunkyo-ku, Tokyo 112-8562, Japan
  Tel: +81-3-5805-2111
  Fax: +81-3-5805-2220
  Please give the hotel staff the name of the symposium “IBHS2004”, and they will connect you to us.

ADDRESS BEFORE AND AFTER THE IBHS2004
  IBHS2004 Secretariat
  c/o Bilingual Group Ltd.
  4-7-22-2F Kudan-minami, Chiyoda-ku, Tokyo 102-0074, Japan
  Tel: +81-3-3263-1261
  Fax: +81-3-3263-1264
  E-mail: ibhs2004@bc.iij4u.or.jp




                                                  2
GREETINGS

Dear Colleague,

Brain hypothermia has long been seen as a promising method that may
overcome current limitations on brain resuscitation in patients with
severe brain damage. However, although excellent results have been
obtained in experimental animal models, for some reason brain
hypothermia has not necessarily been a success in patients, and
resolving this problem has been a major challenge facing physicians
specializing in brain therapies. Recent research has uncovered new
mechanisms of brain damage not seen in animal models, including
intracranial temperatures remaining at over 40ºC at the time of severe
brain damage and insufficient oxygen reaching damaged nerve cells due
to hemoglobin dysfunction. This research has generated useful results
that may support the application of brain hypothermia in patients with
external injuries, stroke, or cardiac arrest, through a better understanding of appropriate treatment
targets, management of hypothermic insult, and mechanisms behind the onset of vegetative states.
This International Symposium has come at just the right time to explore this latest research. The
program titles show that there are numerous presentations on specific treatment methods of an
extremely sophisticated nature that may be useful in the social rehabilitation of brain damaged
patients. I hope that the increased understanding and knowledge brought about by this Symposium
will contribute to the improved care of as many patients as possible.




Nariyuki Hayashi, M.D., PhD.

President of the Organizing Committee
International Brain Hypothermia Symposium 2004
Professor and Chairman
Department of Emergency and Critical Care Medicine
Nihon University School of Medicine


Supported by:     Nihon University School of Medicine
                  Japan Brain Foundation
                  The Society for Treatment of Coma
                  Japanese Association for Acute Medicine (JAAM)
                  Japan Society for Critical Care Medicine
                  The Japanese Society of Intensive Care Medicine
                  The Japanese Circulation Society
                  The Japanese Society of Neurotraumatology
                  The Japanese Congress on Neurological Emergencies
                  The Japanese Society of Reanimatology
                  The Japan Neurosurgical Society
                  The Japanese Society of Neurosurgical Emergency
                  Japanese Research Conference of Cerebral Resuscitation and Brain Death
                  Japanese Association of Brain Hypothermia
                  Japanese Society for Emergency Medicine




                                                   3
ORGANIZERS

      INTERNATIONAL COMMITTEE                  PROGRAM COMMITTEE

       P. David Adelson (USA)                      M. Ross Bullock (USA)
       Stephen A. Bernard (Australia)              W. Dalton Dietrich (USA)
       M. Ross Bullock (USA)                       Nariyuki Hayashi (Japan)
       W. Dalton Dietrich (USA)                    Tsuyoshi Maekawa (Japan)
       Barth A. Green (USA)                        Akira Tamura (Japan)
       Nariyuki Hayashi (Japan)
       Michael Holzer (Switzerland)
       Tsuyoshi Maekawa (Japan)
       Anthony Marmarou (USA)
       John T. Povlishock (USA)
       Hubert Rosomoff (USA)
       Shuji Shimazaki (Japan)
       Akira Tamura (Japan)


                       ORGANIZING COMMITTEE

                             Advisory Committee

                                 Yukiyasu Sezai
                                Kintomo Takakura
           Shuji Dohi                               Hiroaki Naritomi
           Hitoshi Furuya                           Tsutomu Ohno
           Nobuo Hashimoto                          Tomio Ohta
           Nariyuki Hayashi (President)             Takashi Ohwada
           Hiroyuki Hirasawa                        Yasuhiro Okada
           Satoshi Ibara                            Toshisuke Sakaki
           Yukio Ikeda                              Teruo Sakamoto
           Nobuo Kaku                               Minoru Shigemori
           Masamitsu Kaneko                         Hisashi Sugimoto
           Tetsuo Kanno                             Michiyasu Suzuki
           Kiyoshi Kataoka                          Akira Tamura
           Yoichi Katayama                          Takaya Tanaka
           Takeshi Kawase                           Morikazu Ueda
           Takaaki Kirino                           Yasuhiro Yamamoto
           Tsuyoshi Maekawa                         Akira Yamaura
           Kazuhisa Mori                            Nobuyuki Yasui
           Seigo Nagao


                             Steering Committee

           Mayuki Aibiki                             Ken Nagao
           Syunichi Harada                           Akira Sato
           Yoko Kato                                 Yoshio Takasato
           Nobuyuki Kawai                            Yukio Tanaka
           Takao Kitahara                            Takashi Tokutomi
           Kazuhisa Mori                             Hiroyuki Yokota




                                          4
ACKNOWLEDGEMENTS

We wish to express our sincere appreciation to the following for their generous support of this
symposium:
(in alphabetical order)

 Osaka Pharmaceutical Manufacturers Association
 The Pharmaceutical Manufacturer’s Association of Tokyo
 Future Generations Alliance Foundation
 Inoue Foundation for Science
 Sanwa Kai

Abbott Japan Co., Ltd.                      Mitsubishi Pharma Corporation
AJINOMOTO PHARMA Co., Ltd.                  MOCHIDA PHARMACEUTICAL CO., LTD.
Amgen Ltd.                                  MORINAGA MILK INDUSTORY CO., LTD.
Asahi Kasei Corporation                     NIHON CHEMICALS CO., Ltd.
Astra Zeneca                                NIHON KOHDEN CORPORATION
Aventis Behring Japan                       Nihon Schering K. K.
AZWELL Inc.                                 NIKKEN CHEMICALS CO., Ltd.
BANYU PHARMACEUTICAL CO., LTD.              Nippon Boehringer Ingelheim Co., Ltd.
Baxter Limited                              Nippon Chemiphar Co., Ltd.
Bayer Yakuhin, Ltd. Bayer HealthCare        NIPPON KAYAKU CO., LTD.
BAS Inc.                                    NIPPON SHINYAKU CO., LTD.
Bristol Pharmaceuticals K. K.               Nippon Zoki Pharmaceutical Co., Ltd.
CHUGAI PHARMACEUTICAL CO., LTD.             NIPRO PHARMA CORPORATION
DAIICHI PHARMACEUTICAL CO., LTD.            Novartis Pharma K.K.
Daiichi Suntory Pharma Co., Ltd.            ONO PHARMACEUTICAL CO., LTD.
DAINIPPON PHARMACEUTICAL CO., LTD.          OTSUKA PHARMACEUTICAL CO., LTD.
Edwards Lifesciences Corporation            Otsuka Pharmaceutical Factory Inc.
Eiken Chemical Co., Ltd.                    PENTAX Corporation
Eisai Co., Ltd.                             Pfizer Japan Inc.
Elmed Eisai Co., Ltd.                       Philips Medical Systems
Fujisawa Pharmaceutical Co., Ltd.           ROHTO Pharmaceutical Co., Ltd.
Fukujin Co., Ltd.                           Sankyo Co., Ltd.
Fuso Pharmaceutical Industries, Ltd.        Santen Pharmaceutical Co., Ltd.
Gaymar Industries, Inc.                     SANWA KAGAKU KENKYUSHO CO., LTD.
Glaxo Smith Kline K. K.                     SATO PHARMACEUTICAL CO., LTD.
GRELAN PHARMACEUTICAL CO., LTD.             Sawai Pharmaceutical Co., Ltd.
IMI Co., LTD.                               Schering-Plough K. K.
Japan Medical Dynamic Marketing, INC.       Shionogi & CO., LTD.
Japan Tobacco Inc.                          Snow Brand Milk Products Co., Ltd.
KAKEN SHOYAKU CO., LTD.                     SSP CO., LTD.
Kaken Pharmaceutical Co., Ltd.              Sumitomo Pharmaceuticals Co., Ltd.
Kanebo, Ltd.                                TAIHO Pharmaceutical Co., Ltd.
KENKOSHA MEDICAL INSTRUMENTS MFG. CO., LTD. Takeda Chemical Industries, Ltd.
KIRIN BREWERY CO., LTD.                     Tanabe Seiyaku Co., Ltd.
Kissei Pharmaceutical Co., LTD.             TEIJIN PHARMA LIMITED
Kowa Company, Ltd.                          TEIKOKU HORMONE MF G. CO., LTD.
KYORIN PHARMACEUTICAL CO., LTD.             TERUMO CORPORATION, JAPAN
KYOWA HAKKO KOGYO Co., Ltd.                 Tisho Toyama Pharmaceutical Co., Ltd.
Laboratory & Medical Supplies               TOA EIYO LTD.
Laerdal Medical Japan K.K.                  TOKIBO CO., LTD.
Mac Eight Co., Ltd.                         TOP CORPORATION
Maruho Co., Ltd.                            TORII PHARMACEUTICAL CO., LTD.
Maruishi Pharmaceutical Co., Ltd.           Towa Pharmaceutical CO., LTD.
MEDICO’S HIRATA Inc.                        Tsumura & Co.
MEDIVANCE INC.                              Tyco Healthcare Japan
MEIJI DAIRIES CORPORATION                   WAKAMOTO PHARMACEUTICAL CO., LTD.
MEIJI SEIKA KAISHA, LTD.                    Wyeth K. K.
Merck Hoei Ltd.                             Yakult Honsha Co., Ltd.
Mikasa Seiyaku Co., Ltd.                    Yamanouchi Pharmaceutical Co., Ltd.
Minophagen Pharmaceutical Co., Ltd.         ZERIA Pharmaceutical Co., Ltd.
                                      5
GENERAL INFORMATION

DATES

February 5 (Thursday) – February 6 (Friday), 2004

The Registration Desk will open on the 1st floor of the Tokyo Dome Hotel from 15:00 to 17:00 on February 4.
On February 5 and 6, the desk will be located on the B1 floor from 8:00 to 18:00.

VENUE

Tokyo Dome Hotel
Address:   1-3-61 Koraku, Bunkyo-ku, Tokyo 112-8562, Japan
Tel:       +81-3-5805-2111
Fax:       +81-3-5805-2220
URL:       http://www.Tokyodome-hotels.co.jp/e/ (English)
           http://www.Tokyodome-hotels.co.jp/ (Japanese)

LANGUAGE

The official language for the symposium will be English, and no simultaneous interpretation will be
provided.

REGISTRATION FEES
                                                           Registration Fees
                                   Before October 31, 2003               On or after October 31, 2003
   Participant                              ¥35,000                                ¥40,000
   Nurse                                    ¥15,000                                ¥20,000
   Accompanying Person                                         ¥10,000

The fees for participant/nurse participant include unlimited access to all scientific sessions, dinner party,
access to exhibitions, and refreshments. The fee for accompanying persons includes the dinner party.
Please note: Fees do not include accommodation.

For those who would like to register, please contact the symposium secretariat (see page 1).


CANCELLATION AND REFUND POLICY

A refund of 80% of the registration fees (minus bank transfer charges) will be provided following a
written notice of cancellation received by the symposium secretariat by December 5, 2003. After this date
no refund will be possible.




                                                      6
HOTEL ACCOMMODATION AND TRAVEL ARRANGEMENT

Please contact the official travel agency at the addresses below if you require further information
regarding accommodation and/or travel.

    Before and after the symposium:
    Sanki Travel Service Co., Ltd.
    7th floor, Sugamo 1st Building
    1-20-9 Sugamo, Toshima-ku, Tokyo 170-0002, Japan
    Tel: +81-3-3947-1511
    Fax: +81-3-3947-1529
    E-mail: tsdicic@alpha.ocn.ne.jp

    During the symposium:
    Sanki Travel Service will be present at the travel desk in the registration area on both February 5 and
    6. (See “TRAVEL DESK”)

REGISTRATION / INFORMATION DESK

Hotel lobby (1st floor of the hotel) on February 4
“TENKU” Room lobby (B1 floor of the hotel) on February 5 and 6

Presenting your written confirmation will help to identify names at the desk. Symposium materials will be
available to registered participants. All general information services, including lost-and-found articles,
also can be obtained at this desk.

   Wednesday, February 4         15:00 – 17:00
   Thursday, February 5          08:00 – 18:00
   Friday, February 6            08:00 – 18:00

SYMPOSIUM NAME TAGS

All participants are requested to wear their name tags throughout the symposium. Name tags will be
required for admission to symposium functions, so be sure to notify the Registration Desk in the event of
loss. Name tags are color-coded as follows:

         – Regular participant             Yellow
         – Nurse participant               White
         – Accompanying person             Pink
         – Secretariat personnel           Green

TRAVEL DESK

“TENKU” Room lobby (B1 floor of the hotel)

This desk is staffed by the symposium’s official travel agent, Sanki Travel Service Co., Ltd. Participants
can obtain travel information at this desk.

   Thursday, February 5          08:00 – 18:00
   Friday, February 6            08:00 – 18:00




                                                    7
SERVICES AVAILABLE

Please feel free to make use of the following services that will be available during the symposium.

    Refreshments
    Complimentary refreshments will be served in the foyer of the “TENKU” Room (B1F). Light
    breakfast is available.

    Notice Board
    Information for participants will be posted on the Notice Board in the registration area (B1F). Please
    be sure to check it each day during the symposium.

    Message Board
    Please use this board placed in the registration area (B1F) for messages and notes between symposium
    participants.

    Lost Property
    The Information Desk will handle all inquiries concerning lost property.

MEDICAL EMERGENCIES

Please contact the symposium secretariat in the case of illness, injury or medical emergency.

CURRENCY

Currency exchange can be made at the hotel counter (1F). The counter will change foreign currency
traveler’s checks and banknotes into Japanese yen only.

POSTAL SERVICES

Postage services are available at the hotel counter (1F).

SYMPOSIUM LIABILITY

Each participant, upon registration, acknowledges that he/she has no right to lodge claims against the
symposium organizers should the holding of the symposium or part thereof be hindered or prevented due
to unforeseen events, or should the non-appearance of speakers or other reasons necessitate program
changes.



                                               USEFUL INFORMATION
 Currency
 Foreign currency or traveler’s checks can be changed into Japanese yen (¥) at major banks, hotels, and airports (1 US
 dollar = 109 yen as of December 2003). Banks are open 9:00 – 15:00 from Monday to Friday.

 Credit Cards
 Visa, MasterCard, American Express, and Diners Club are widely accepted at hotels, department stores, shops, restaurants,
 and nightclubs.

 Tipping
 There is no custom of individual tipping anywhere in Japan, even at hotels and restaurants. Tips are usually included in the
 bill as a service charge, when required.

 Electrical Appliances
 The voltage in Japan is 100 – 110 volts for electrical appliances. The frequency is 50Hz in Tokyo, Hakone, and other parts
 of eastern Japan (60Hz in western parts of Japan). Electrical sockets usually accept only two-pronged (vertical) plugs.



                                                             8
DINNER PARTY
Date: Thursday, February 5, 2004, 19:00 – 21:00
Venue: “Tenku-B” Room (B1 floor of the Tokyo Dome Hotel)
Fee:   Included in the registration fee
       (Please give advance notice to the symposium secretariat if you plan to attend.)
Dress: Informal


LUNCHEON SEMINARS
 Date           Time            Room                Speaker                                Topic
Feb. 5                                       Hubert Rosomoff         Historical review of development of brain
           12:10 – 13:10     TENKU-A
(Thu.)                                           (U.S.A.)            hypothermia

Feb. 6                                      Anthony Marmarou         Neurotrauma management of the head injured
           12:00 – 13:00     TENKU-A
(Fri.)                                           (U.S.A.)            patient: Pathophysiology and treatment

Feb. 6                                       Thorsten Steiner        The management of cerebral stroke by brain
           12:00 – 13:00     TENKU-B
(Fri.)                                          (Germany)            hypothermia treatment


Fee:     Included in the registration fee
Please note that the number of lunch boxes is limited and will be distributed on a first-come basis.


POSTER EXHIBITION
The Poster Exhibition will be held at the “AURORA” Room (B1F) under the following schedule. Poster
viewing will take place 14:10 – 14:50 each day. Please come and join the discussions with the authors.
Poster presenters will be wearing nametags with a ribbon attached.

    Thursday, February 5            09:00 – 19:00
    Friday, February 6              08:00 – 16:30


TECHNICAL EXHIBITION
The Technical Exhibition will be held at the “AURORA” Room and the foyer of the “TENKU” Room
(B1F) under the following schedule. The exhibition will feature companies showcasing the latest in
pharmaceuticals, diagnostic equipment, laboratory equipment and supplies, electronic medical equipment
and so on.

    Thursday, February 5            09:00 – 19:00
    Friday, February 6              08:00 – 16:30




                                                       9
INFORMATION FOR PRESENTERS
CHECK-IN FOR SPEAKERS
“TENKU” Room Lobby (B1 floor of the hotel)
All speakers are requested to check in at least one hour before the beginning of their session. Speakers
using a PC are strongly recommended to confirm that the presentation data that they sent to the
symposium secretariat appears properly on the computer screen. (Please note that presenters are required
to use the computers provided at the symposium site.) To avoid congestion, early check-in would be
appreciated. If you would like to have your submitted materials returned, please pick them up at the desk
after your presentation. This room will open during the following hours:
    Thursday, February 5          08:00 – 18:00
    Friday, February 6            08:00 – 16:30

NOTE: Speakers whose presentations are scheduled in the morning of February 6 are kindly asked to check-in
by 18:00 on February 5.

POSTER MOUNTING AND REMOVAL
“AURORA” Room (B1 floor of the hotel)
Authors of poster presentations are requested to mount/remove their posters during the following hours:
   Mounting time:      Thursday, February 5, 07:00 – 09:00
   Removal time:       Friday, February 6, 16:30 – 19:00

All the materials needed for mounting posters will be provided on site. Your presentation number
indicates the location of your poster board.

MANUSCRIPT SUBMISSION

Please submit your manuscript, floppy disk and other required documents to the Registration Desk at the
symposium site by 16:00 on the last day of the symposium, Friday, February 6, 2004. For submission
details, visit the symposium website (http://www.brain-hypothermia.com/ibhs2004/).
Please note: Late submissions will not be accepted.




                                                   10
TRANSPORTATION & MAPS
The two main international airports in Japan are the New Tokyo International Airport (Narita Airport) and
Kansai International Airport (Osaka). Narita Airport is closest to the symposium site.

All transportation arrangements are the responsibility of the participant.




FROM NARITA AIRPORT TO TOKYO DOME HOTEL

 Airport Limousine Bus
 Airport limousine buses run between the airport and the Tokyo Dome Hotel. The buses leave 08:00,
 10:10, 14:15, 15:15, 16:10 and 17:10. The bus ride usually takes 90 minutes, longer if traffic is heavy.
 The fare is ¥3,000, and tickets can be purchased at the limousine bus counter.

 Train
 1. When you arrive at Narita Airport, go down to Narita Airport Station (basement of Terminal 1) or
    Airport Terminal 2 Station (basement of Terminal 2). At the JR ticket office, purchase tickets to
    Suidobashi Station.
 2. Take the JR “Narita Express (NEX)” train to Tokyo Station (approx. 60 min.). The train leaves every
    30 to 60 minutes from 07:43 to 21:43.
 3. Upon arrival at Tokyo Station, take the JR Chuo Line to Ochanomizu Station (2nd stop/ 4 min.)
 4. Change to the JR Sobu Line and get off at Suidobashi Station (1st stop/ 2 min.) From the East Exit,
    the hotel is a 2-minute walk.




                                                     11
FROM KANSAI INTERNATIONAL AIRPORT (OSAKA) TO TOKYO DOME HOTEL

 1. When you arrive at Kansai Airport, go to Kansai Airport Station, which is next to the airport terminal
    building on the 2nd floor. At the JR ticket office, purchase tickets to Suidobashi Station.
 2. Go to Track 4 and take the JR "Haruka" express train to Shin-Osaka Station (approx. 50 min.).
 3. Upon arrival at Shin-Osaka Station, go up to the JR Shinkansen (Bullet Train) tracks (Tracks 11–18).
 4. Take the “Hikari” or “Nozomi” Shinkansen to Tokyo Station (2.5 hr. – 3 hr.)
 5. Upon arrival at Tokyo Station, take the JR Chuo Line to Ochanomizu Station (2nd stop/ 4 min.)
 6. Change to the JR Sobu Line and get off at Suidobashi Station (1st stop/ 2 min.) From the East Exit,
    the hotel is a 2-minute walk.

Please note: All transportation information is current as of December 2003.




                                                   12
SCIENTIFIC PROGRAM


                Oral Presentations
February 5 (Thursday) – February 6 (Friday)
     “TENKU-A” AND “TENKU-B” ROOMS
                                  February 5 (Thursday)
                                    “TENKU-A” Room


8:50 - 9:50       Basic Science

Chairs: W. Dalton Dietrich (Department of Neurological Surgery, The Miami Project to Cure Paralysis,
        University of Miami School of Medicine, Miami, FL, USA)
        Kiyoshi Kataoka (Ehime University, Japan)

Lectures
       L-1        John T. Povlishock (Department of Anatomy and Neurobiology, Medical College of
                  Virginia Campus of Virginia Commonwealth University, Richmond, VA, USA)
                  A review of hypothermia's cerebrovascular and brain parenchymal protective effects
                  following experimental traumatic brain injury (TBI)

         L-2      W. Dalton Dietrich (Department of Neurological Surgery, The Miami Project to Cure
                  Paralysis, University of Miami School of Medicine, Miami, FL, USA)
                  Factors regulating hypothermic protection in experimental models of brain injury.



10:00 - 12:00 Neurotrauma
         Sponsored by Edwards Lifescience LTD. and International Brain Hypothermia Society


Chairs: M. Ross Bullock (Department of Neurosurgery, Virginia Commonwealth University Health
        System, USA)
        Minoru Shigemori (Department of Neurosurgery, Kurume University School of Medicine,
        Japan)

10:00 - 10:35     Oral Presentations (selected papers)

        O-1      Tomoya Miyagi (Department of Neurosurgery, Kurume University School of Medicine,
                 Japan)
                 Clinical evaluation of mild hypothermia for severe head-injured patients

        O-2      Martin Smrčka (Neurosurgical Department, University Hospital Brno, Czech
                 Republic)
                 The use of mild hypothermia in the prevention of the secondary brain injury

        O-3      Mayuki Aibiki (Department of Emergency Medicine, Ehime University School of
                 Medicine, Japan)
                 Biphasic concentration change during continuous midazolam administration in
                 brain-injured patients undergoing therapeutic moderate hypothermia




                                               14
                                    February 5 (Thu.) – “TENKU-A”



10:35 - 10:55      Hypothermia for Head Injury Study Group in Japan

          L-3      Tsuyoshi Maekawa (Hypothermia for Head Injury Study Group in Japan)
                   A randomized controlled trial of mild hypothermia therapy in severe head injured
                   patients in Japan.

11:00 - 12:00      Lectures

          L-4      Barth A. Green (Department of Neurological Surgery, University of Miami School of
                   Medicine, USA)
                   Practical application of modest hypothermia for neuroprotection in spinal cord injury
                   and spinal cord surgery, 2004

          L-5      Donald W. Marion (Department of Neurological Surgery, Boston University School of
                   Medicine, USA)
                   Is hypothermia beneficial by preventing fever?



12:10 - 13:00 Luncheon Seminar
          Sponsored by Mitsubishi Pharma Co., Ltd. and International Brain Hypothermia Society


Chair:    Hiroyuki Hirasawa (Department of Emergency and Critical Care Medicine, Chiba University
          Graduate School of Medicine, Japan)

Lecture
          L-6      Hubert Rosomoff (The Rosomoff Comprehensive Pain and Rehabilitation center,
                   South Shore Hospital, Miami, USA)
                   Historical review of development of brain hypothermia



13:10 - 14:00 Emergency Hypothermia
          Sponsored by Laerdal Medical Japan K.K. and International Brain Hypothermia Society


Chair:    Shuji Shimazaki (Department of Trauma and Critical Care Medicine, Kyorin University School
          of Medicine, Japan)

Lecture
          L-7     Patrick M. Kochanek (Department of Critical Care Medicine, The Safar Center for
                  Resuscitation Research, University of Pittsburgh School of Medicine, USA)
                  Novel potentials for emergency hypothermia: suspended animation with delayed
                  resuscitation from exsanguination cardiac arrest



(14:10 - 14:50 Poster Viewing at the “AURORA” Room)




                                                 15
                                     February 5 (Thu.) – “TENKU-A”



15:00 - 15:50 Lecture by President

Chair:    Hubert Rosomoff (The Rosomoff Comprehensive Pain and Rehabilitation center, South Shore
          Hospital, Miami, USA)

Lecture
          P-1      Nariyuki Hayashi, President of IBHS2004 (Department of Emergency and Critical Care
                   Medicine, Nihon University School of Medicine, Japan)
                   The new concept and pitfall of brain hypothermia treatment.



16:00 - 17:20 Postresuscitative Hypothermia
          Sponsored by BAYER YAKUHIN Co., Ltd. and International Brain Hypothermia Society


Chairs: Michael Holzer (University of Vienna, Vienna General Hospital, Wien, Austria)
        Kazuo Okada (Teikyo University, Japan)

16:00 - 16:11     Oral Presentation (selected paper)

          O-4     Kazuhisa Mori (Department of Traumatology & Critical Care Medicine, Sapporo
                  Medical University, Sapporo, Japan)
                  Indication for brain hypothermic therapy in cardiac arrest patients

16:15 - 17:20     Lectures

          L-8      Stephen A. Bernard (The Intensive Care Unit, Dandenong Hospital, David St.
                   Dandenong Victoria, Australia)
                   Hypothermia after cardiac arrest: An update

          L-9      Michael Holzer (University of Vienna, Vienna General Hospital, Wien, Austria)
                   Hypothermia after cardiac arrest

          L-10     Ken Nagao (Department of Emergency and Critical Care Medicine, Nihon University
                   School of Medicine, Tokyo, Japan)
                   B-type natriuretic peptide for advanced challenge in therapeutic hypothermia




                                                16
                                     February 5 (Thu.) – “TENKU-A”



17:30 - 18:30 Cooling Technique
         Sponsored by Ono Pharmaceutical Co., Ltd. and International Brain Hypothermia Society


Chairs: Masamitsu Kaneko (Sapporo Medical University, Japan)
        Donald W. Marion (Department of Neurological Surgery, Boston University School of Medicine,
        USA)

Lectures
       L-11       William Coplin (Departments of Neurology and Neurological Surgery, Wayne State
                  University, USA)
                  Treatment of refractory fever in the neurosciences critical care unit using a novel,
                  water-circulating cooling device: A single center pilot experience

         L-12     Stefan Schwab (Department of Neurology, University of Heidelberg, Germany)
                  Methods of cooling on the Neuro ICU




                                               17
                                     February 6 (Friday)
                                     “TENKU-A” Room


9:00 - 9:50      ICU Management
          Sponsored by NIHON KOHDEN Corporation and International Brain Hypothermia Society


Chair:    Barth A. Green (Department of Neurological Surgery, University of Miami School of Medicine,
          USA)

Lecture
          L-13     M. Ross Bullock (Neurosurgery and Neurointensive Care Unit, Medical College of
                   Virginia, Hospital of Virginia Commonwealth University, USA)
                   ICU management of brain hypothermia



10:00 - 11:50      Stroke

Chairs: John T. Povlishock (Department of Anatomy and Neurobiology, Medical College of Virginia
        Campus of Virginia Commonwealth University, USA.)
        Nobuyuki Yasui (Research Institute for Brain and Blood Vessels Akita, Japan)

10:00 - 11:00      Oral Presentations (selected papers)

          O-5      Tom Skyhøj Olsen (The Stroke Unit, Hvidovre University Hospital, DK-2650
                   Hvidovre, Denmark)
                   Body temperature in stroke: Secondary stress phenomenon or causal relationship?

          O-6      Tamiki Taniguchi (Department of Neurosurgery, Saitama Medical Center/ School,
                   Saitama, Japan)
                   Neuroprotective effect of selective brain hypothermia (SBH) on permanent focal
                   cerebral ischemia in rats

          O-7      Hitoshi Kobata (Osaka Mishima Emergency and Critical Care Medical Center,
                   Takatsuki, Japan)
                   Ultra-early Induction of brain hypothermia for patients with poor-grade subarachnoid
                   hemorrhage.

          O-8      Martin Smrčka (Neurosurgical Department, University Hospital Brno, Czech
                   Republic)
                   The influence of mild hypothermia on the incidence of vasospasm in patients after the
                   severe subarachnoid hemorrhage

          O-9      Yoko Kato (Department of Neurosurgery, Fujita Health University, Aichi, Japan)
                   Mild hypothermic therapy: Its application and limitation as brain protection



                                                18
                                    February 6 (Fri.) – “TENKU-A”



11:00 - 11:50      Lecture

          L-14     Stefan Schwab (Department of Neurology, University of Heidelberg, Germany)
                   Hypothermia in the therapy of ischemic stroke



12:00 - 12:50 Luncheon Seminar
          Sponsored by International Brain Hypothermia Society and BANYU Pharmaceutical Co., Ltd.


Chair:    Akira Tamura (Teikyo University School of Medicine, Japan)

Lecture
          L-15     Anthony Marmarou (Neurosurgery at the Medical College of Virginia, Virginia
                   Commonwealth University, USA)
                   Neurotrauma management of the head injured patient: Pathophysilogy and treatment



13:00 - 14:00 Intraoperative Hypothermia

Chairs: Patrick M. Kochanek (Department of Critical Care Medicine and The Safar Center for
        Resuscitation Research, University of Pittsburgh School of Medicine, USA)
        Seigo Nagao (Department of Neurological Surgery, Kagawa Medical University, Japan)

Oral Presentations (selected papers)

          O-10     Akira Satoh (Department of Neurosurgery, Saitama Medical School, Japan)
                   Hypothermic anesthesia in surgery for cerebral aneurysm

          O-11     Tsuneyoshi Eguchi (Department of Neurosurgery, Kameda General Hospital,
                   Kamogawa, Japan)
                   Mild hypothermia in neurosurgery

          O-12     Teruyasu Hirayama (Department of Neurological Surgery, Nihon University
                   Hospitals, Tokyo, JAPAN)
                   Usefulness of intraoperative mild hypothermia for vascular disease.

(14:10 - 14:50 Poster Viewing at the “AURORA” Room)


15:00-16:20        Pediatrics

Chairs: Thorsten Steiner (Department of Neurology, University of Heidelberg, Germany)
        Morikazu Ueda (Second Department of Neurosurgery, Toho University, Japan)




                                                19
                                        February 6 (Fri.) – “TENKU-A”



15:00 - 15:30        Oral Presentations (selected papers)

            O-13     Masaki Shimizu (Division of Neonatology, Saitama Children’s Medical Center,
                     Saitama, Japan)
                     Clinical study of brain MRI in infants treated with brain hypothermia

            O-14     Hiroshi Dohgomori (Division of Emergency Medicine, Ryuku University Hospital,
                     Japan)
                     Adjunctive application of hyperbaric oxygen therapy in children already treated with
                     mild hypothermia for disturbance of consciousness

15:25 - 16:20        Lecture


            L-16     P. David Adelson (Department of Neurosurgery, University of Pittsburgh School of
                     Medicine, USA)
                     Moderate hypothermia in children following severe TBI



16:30 - 18:00 Summary Table Discussion

Chairs: Nariyuki Hayashi (Department of Emergency and Critical Care Medicine, Nihon University
        School of Medicine, Japan)
        Anthony Marmarou (Neurosurgery at the Medical College of Virginia, Virginia Commonwealth
        University, USA)

Panelists
  Basic Science
            W. Dalton Dietrich (Department of Neurological Surgery, The Miami Project to Cure Paralysis,
            University of Miami School of Medicine, Miami, FL, USA)
  Trauma
            M. Ross Bullock (Department of Neurosurgery, Virginia Commonwealth University Health
            System, USA)
            Donald W. Marion (Department of Neurological Surgery, Boston University School of Medicine,
            USA)
  CPA
            Stephen A. Bernard (The Intensive Care Unit, Dandenong Hospital, David St. Dandenong
            Victoria, Australia)
  Emergency
            Patrick M. Kochanek (Department of Critical Care Medicine, The Safar Center for
            Resuscitation Research, University of Pittsburgh School of Medicine, USA)
  Stroke
            Stefan Schwab (Department of Neurology, University of Heidelberg, Germany)
  Pediatrics
            P. David Adelson (Department of Neurosurgery, University of Pittsburgh School of Medicine,
            USA)


                                                  20
                                    February 6 (Friday)
                                    “TENKU-B” Room


10:00 - 11:50    Basic Science

Chairs: Urban Ungerstedt (Department of Physiology and Pharmacology, Karolinska Institute,
        Stockholm, Sweden)
        Yoichi Katayama (Department of Neurological Surgery, Nihon University School of Medicine,
        Japan)

Oral Presentations (selected papers)

        O-15     Said Hachimi-Idrissi (Critical Care Department and Cerebral Resuscitation Research
                 Group, Brussels, Belgium)
                 Resuscitative mild hypothermia attenuates the excitatory amino acids overflow and
                 diminishes the nitric oxide synthase activity during reperfusion after asphyxial cardiac
                 in rats.

        O-16     Yuko Mihara (Department of Emergency and Critical Care Medicine, Showa
                 University School of Medicine, Japan)
                 A novel method of oxidative stress monitoring in neuronal injury during brain
                 hypothermia therapy – ex vivo electron spin resonance study –

        O-17     Yasuhiro Okada (Department of Physiology, Kobe University School of Medicine,
                 Kobe, Japan)
                 Effect of mild and deep hypothermia on the neuronal activity and energy metabolism in
                 the brain slices in vitro

        O-18     Nam Nguyen (Critical Care Department and Cerebral Resuscitation Research Group,
                 Brussels, Belgium)
                 Effect of resuscitative mild hypothermia and oxygen concentration on the survival time
                 during lethal uncontrolled hemorrhagic shock in mechanically ventilated rats.

        O-19     Nobuyuki Kawai (Kagawa Medical University)
                 Effects of brain hypothermia on brain edema formation after intracerebral hemorrhage
                 in rats.

        O-20     Masaharu Sakoh (Department of Neurosurgery, Tokyo Women's Medical University,
                 Japan)
                 Hypothermia prolong the viability of ischemic brain tissue due to neuroprotection
                 linked to redistribution of oxygen in brain: PET study of the critical first 6 hours after
                 stroke in pigs.




                                                21
                                      February 6 (Fri.) – “TENKU-B”



          O-21     Gerrit A. Schubert (Department of Neurosurgery and Neuroradiology, Mannheim
                   Campus, University of Heidelberg, Germany)
                   Neuroprotection delivered by moderate hypothermia in experimental SAH: A
                   microdialysis, diffusion-weighted imaging and magnetic resonance spectroscopy study
                   in rats



12:00 - 12:50 Luncheon Seminar
          Sponsored by DAIICHI Pharmaceutical Co., Ltd. and International Brain Hypothermia Society


Chair:    Takashi Yoshimoto (Tohoku University, Japan)

Lecture
          L-17     Thorsten Steiner (Department of Neurology, University of Heidelberg, Germany)
                   The management of cerebral stroke by brain hypothermia treatment



13:00 - 14:00 Monitoring

Chairs: Helen M. Bramlett (Miami Project to Cure Paralysis, University of Miami, USA)
        Tsuyoshi Maekawa (Department of Stress and Bio-response Medicine, Yamaguchi University
        Graduate School of Medicine, Japan)

13:00 - 13:30      Oral Presentations (selected papers)

          O-22     Shunichi Harada (Department of Neurosurgery, Fujita Health University, Japan)
                   In-vivo microdialysis measurements for patients with brain damage treated by mild
                   hypothermic therapy

          O-23     Takashi Karukaya (Department of Neurosurgery, Kurume University School of
                   Medicine, Japan)
                   Microdialysis and brain tissue O2 (Pti O2) study in mild hypothermia

13:30 - 14:00      Lecture

          L-18    Urban Ungerstedt (Department of Physiology and Pharmacology, Karolinska Institute,
                  Stockholm, Sweden)
                  Important regional differences in brain tissue susceptibility to secondary damage after
                  traumatic brain injury

(14:10 - 14:50 Poster Viewing at the “AURORA” Room)




                                                22
                                     February 6 (Fri.) – “TENKU-B”



15:00 - 16:20 New Therapies

Chairs: Stephen A. Bernard (The Intensive Care Unit, Dandenong Hospital, David St. Dandenong
        Victoria, Australia)
        Tetsuo Kanno (Department of Neurosurgery, Fujita Health University, Japan)

15:00 - 15:40    Oral Presentations (selected papers)

        O-24     Alexander M. Zeitlin (Department of Anesthesiology, Burdenko Neurosurgery
                 Institute, Moscow, Russia)
                 Combination of forced air cooling, cooling by circulating water mattress and
                 intravenous bolus infusion of iced saline is effective and safe technique for induction of
                 mild hypothermia during cerebral aneurysm surgery

        O-25     Xiaojiang Xu (U.S. Army Research Institute of Environmental Medicine, USA)
                 Mathematical analysis of digit immersion cooling technique for brain temperature
                 management

        O-26     Hidetoshi Wakamatsu (Biophysical System Engineering, Tokyo Medical and Dental
                 University, Tokyo, Japan)
                 Automatic air-cooling incubating system for adult brain hypothermia treatment.

15:40 - 16:20    Lectures

        L-19     Ryo Noda (Department and Institution / Arts Planning Department, Osaka University
                 of Arts)
                 Brain hypothermia treatment and a synchronized musico- kinetic therapy (SMK)

        L-20     Nariyuki Hayashi (Department of Emergency and Critical Care Medicine, Nihon
                 University School of Medicine, Japan)
                 The prevention of vegetation and memory disturbances for severe brain damage by
                 combination of brain hypothermia and intracerebral dopamine replacement therapy




                                                23
                                Sponsored Sessions


                                 Session: Neurotrauma
                  February 5 (Thursday), 10:00 - 12:00, “TENKU-A” Room
    Sponsored by Edwards Lifescience Ltd. and International Brain Hypothermia Society


                        Luncheon Seminar: Hubert Rosomoff
                 “Historical review of development of brain hypothermia”
                  February 5 (Thursday), 12:10 - 13:00, “TENKU-A” Room
   Sponsored by Mitsubishi Pharma Co., Ltd. and International Brain Hypothermia Society


                           Session: Emergency Hypothermia
                  February 5 (Thursday), 13:10 - 14:00, “TENKU-A” Room
  Sponsored by Laerdal Medical Japan K. K. and International Brain Hypothermia Society


                        Session: Postresuscitative Hypothermia
                  February 5 (Thursday), 16:00 - 17:20, “TENKU-A” Room
   Sponsored by BAYER YAKUHIN Co., Ltd. and International Brain Hypothermia Society


                              Session: Cooling Technique
                  February 5 (Thursday), 17:30 - 18:30, “TENKU-A” Room
  Sponsored by Ono Pharmaceutical Co., Ltd. and International Brain Hypothermia Society


                              Lecture: ICU management
                     February 6 (Friday), 9:00 - 9:50, “TENKU-A” Room
 Sponsored by NIHON KOHDEN Corporation and International Brain Hypothermia Society


                     Luncheon Seminar: Anthony Marmarou
    “Neurotrauma management of the head injured patient: pathophysilogy and treatment”
                    February 6 (Friday), 12:00 - 12:50, “TENKU-A” Room
Sponsored by BANYU Pharmaceutical Co., Ltd. and International Brain Hypothermia Society


                       Luncheon Seminar: Thorsten Steiner
            “The management of cerebral stroke by brain hypothermia treatment”
                    February 6 (Friday), 12:00 - 12:50, “TENKU-B” Room
Sponsored by DAIICHI Pharmaceutical Co., Ltd. and International Brain Hypothermia Society




                                         24
            Poster Presentations

February 5 (Thursday) – February 6 (Friday)
                        “AURORA” ROOM
                                            Basic Science



PB-1.   Masanobu Okauchi (Department of Neurological Surgery, Kagawa Medical University, Japan)
        Effects of mild hypothermia and alkalizing agents on brain injuries in rats with acute subdural
        hematomas.


PB-2.   Takamoto Suzuki (The Miami Project to Cure Paralysis, University of Miami School of
        Medicine, USA)
        The effects of post-traumatic hypothermia and hyperthermia in female rats following traumatic
        brain injury.


PB-3.   Izumi Yuzawa (Department of Neurosurgery, Kitasato University School of Medicine, Japan)
        Mild hypothermia attenuates the endothelium-dependent pial arteriole dilatation.


PB-4.   Rainer Kollmar (Department of Neurology, University of Heidelberg, Germany)
        Combination     therapy of      moderate   hypothermia   and   thrombolysis   in   experimental
        thromboembolic stroke - an MRI study


PB-5.   Masahiko Kawanishi (Department of Neurological Surgery, Kagawa Medical University,
        Japan)
        Effect of hypothermia on brain edema formation following intracranial hemorrhage in rats.


PB-6.   Said Hachimi-Idrissi (Critical Care Department and Cerebral Resuscitation Research Group,
        Brussels, Belgium)
        Postischemic mild hypothermia reduces neurotransmitter release during reperfusion after
        asphyxial cardiac arrest in rats.


PB-7.   Said Hachimi-Idrissi (Critical Care Department and Cerebral Resuscitation Research Group,
        Brussels, Belgium)
        A decreased astroglial S-100 β protein may explain the neuroprotective effects of resuscitative
        mild hypothermia.


PB-8.   Said Hachimi-Idrissi (Critical Care Department and Cerebral Resuscitation Research Group,
        Brussels, Belgium)
        Combination of mild hypothermia and delayed fluid resuscitation improved the survival after
        hemorrhagic shock in mechanical ventilated rats.


PB-9.   Kensuke Okubo (Department of Pediatrics, Kagawa Medical University, Japan)
        Estimation of cerebral blood flow using multichannel near-infrared spectroscopy during
        hypothermia after the hypoxic-ischemic insult in newborn piglets

                                                   26
PB-10.   Vladimir I. Kulinsky (Department of Biochemistry, Irkutsk State Medical University, Russia)
         Influence of hypothermia on neuroprotective effects (NPEs) of inhibiting neurotransmitters
         (INTs) and agonists of their receptors.


PB-11.   Susumu Yamashita (Advanced Medical and Critical Care Center, Yamaguchi University,
         Japan)
         A computer supported multi-channel long term hypothermia device for free moving rats.


PB-12.   Larisa S. Kolesnichenko (Departments of Bioorganic Chemistry1 and Biochemistry, Irkutsk
         State Medical University, Russia)
         Correlation of hypothermia with decrease of glutathione concentration and tolerance to cerebral
         ischemia.




                                                   27
                                    Traumatic Brain Injury



PT-1.   Takanori Hayakawa (Department of Neurosurgery, National Disaster Medical Center, Japan)
        Effect of mild hypothermia on neuropsychological outcome in severe head injury.


PT-2.   Yuji Ueda (Department of Neurosurgery, Shuto General Hospital, Japan)
        Posttraumatic hypothermia provides persisting cerebrovascular protection.


PT-3.   Akira Utagawa (Department of Emergency and Critical Care Medicine, Nihon University
        School of Medicine, Japan)
        Immune enhancing effect of arginine on severe traumatic brain injury.


PT-4.   Hiroyuki Masaoka (Department of Neurosurgery, National Disaster Medical Center, Japan)
        Evaluation and optimal temperature of three-day cooling hypothermia in patients with severe
        traumatic brain injury.


PT-5.   Yi Yan (Department of Neurosurgery, Chongqing University of Medical Sciences, China)
        Influence of mild hypothermia on evoked potential, PbO2, serum and CSF biochemical factors
        in the severe head injury


PT-6.   Eiichi Suehiro (Department of Neurosurgery, Clinical Neuroscience, Yamaguchi University
        School of Medicine, Japan)
        Hypothermia may attenuate not only IL-6 but also MMP-9 (matrix metalloproteinase-9) of
        systemic and internal jugular blood from the inflammatory response to traumatic brain injury in
        humans.


PT-7.   Shoji Yokobori (Department of Neurosurgery, Musashino Red Cross Hospital, Japan)
        Neuropsychological recovery in pediatric patients with acute subdural hematoma treated with
        mild hypothermia therapy: Report of two cases.


PT-8.   Hirosuke Fujisawa (Department of Neurosurgery, Yamaguchi University School of Medicine,
        Japan)
        Management of patients with traumatic brain injury: Hypothermia therapy and importance of
        temperature management.


PT-9.   Kosaku Kinoshita (Department of Emergency and Critical Care Medicine, Nihon University
        School of Medicine, Japan)
        Survival from an acute subdural hematoma with accidental hypothermia and cardiac arrest: A
        case report



                                                28
                                      Postresuscitaiton



PP-1.   Ryuzo Abe (Department of Emergency and Critical Care Medicine, Graduate School of
        Medicine, Chiba University, Japan)
        Influence of brain hypothermia on blood IL-6 levels on the post- resuscitated patients after
        cardiac arrest.


PP-2.   Yoshihiro Takeyama (Department of Traumatology & CCM, Sapporo Medical University,
        Japan)
        Brain hypothermic therapy following cardiopulmonary bypass for cardiac arrest patients who
        did not respond to ACLS.


PP-3.   Eiji Nitobe (Department of Clinical engineer, Surugadai Nihon University Hospital, Japan)
        Advanced challenge in resuscitative hypothermia in patients with cardiac arrest on arrival at the
        emergency room.


PP-4.   Shinichi Shirai (Department of Cardiology, Kokura Memorial Hospital, Japan)
        Mild hypothermia for brain resuscitation combined with coronary revasculization therapy for
        cardiopulmonary arrest caused by acute myocardial infarction using external cooling blanket.


PP-5.   Takashi Moriya (Department of Emergency and Critical Care Medicine, Nihon University
        School of Medicine, Japan)
        Reversible changes of potassium, phosphate and magnesium during induced hypothermia.




                                                 29
                                             Stroke



PS-1.   Takashi Moriya (Department of Emergency and Critical Care Medicine, Nihon University
        School of Medicine, Japan)
        Time course of extracellular glutamate using a microdialysis for poor grade aneurysm patients
        —Preliminary reports—


PS-2.   Kyoko Ikakura (Department of Critical Care Medicine, Tama-Nagayama Hospital, Nippon
        Medical School, Japan)
        The evaluation of result of transcranial Doppler sonography in the postoperative brain
        hypothermia therapy for severe cases of subarachnoid hemorrhage


PS-3.   Uno J. Weber (NOCSS, Gentofte University Hospital, Hellerup, Denmark)
        Low body-temperature has been associated with more favorable outcome.


PS-4.   Kentaro Kuwamoto (Department of Emergency and Critical Care Medicine, Nippon Medical
        School, Japan)
        A survival case of the subarachnoid hemorrhage using brain hypothermia after the recovery of
        spontaneous circulation from cardiopulmonary arrest: Case report


PS-5.   Yutaka Hirashima (Department of Neurosurgery, Toyama Medical and Pharmaceutical
        University, Japan)
        Brain temperature in patients with chronic hydrocephalus after subarachnoid hemorrhage




                                                30
                                           Neonate



PN-1.   Kazumasa Kumazawa (Division of Neonatology, Perinatal Medical Center, Kagoshima City
        Hospital, Japan)
        The changes of blood glutamate levels in hypoxic ischemic encephalopathy (HIE) cases with
        brain hypothermia (BHT).


PN-2.   Kosuke Kobayashi (Department of Obstetrics and Gynecology, Asahi General Hospital, Japan)
        Body temperature monitoring during brain hypothermia for newborn infants with
        hypoxic-ischemic encephalopathy.


PN-3.   Takuya Tokuhisa (Division of Neonatology, Perinatal Medical Center, Kagoshima City
        Hospital, Japan)
        The change of brain oxygen extraction ratio and CO2 production in term infants with hypoxic
        ischemic encephalopathy during brain hypothermia.




                                               31
                               Management and Monitoring



PM-1.   Yuko Shimizu (Department of Emergency and Critical Care Medicine, Nihon University
        School of Medicine, Japan)
        The automatic temperature management system in patients with mild hypothermia; Three-case
        report.


PM-2.   Yuki Sato (Department of Emergency and Critical Care Medicine, Nihon University School of
        Medicine, Japan)
        Significance of musico-kinetic therapy for patients with severe brain injury following brain
        hypothermia therapy.


PM-3.   Hiroshi Kimura (Kimura Clinic, Saitama, Japan)
        The definition of hypothermic therapy and the meaning of anesthesia


PM-4.   Kenji Okuno (Department of Emergency Medicine, Jikei University School of Medicine,
        Japan)
        Gut movement of patients treated with brain hypothermia


PM-5.   Masato Iwata (Department of Anesthesiology, Nara Medical University, Japan)
        A comparison of jugular venous bulb oxygen saturation during propofol anesthesia in
        normothermic and mildly hypothermic neurosurgical patients.


PM-6.   Motomasa Furuse (Department of Neurosurgery, Osaka Medical College, Japan)
        Rapid induction of brain hypothermia by intra-arterial perfusion of crystalloid solution in
        canines


PM-7.   Yasuhiro Kuroda (Division of Intensive and Critical Care Medicine, Tokushima University
        Hospital, Japan)
        Evaluation of cerebral and systemic flow / metabolism during brain hypothermia therapy.


PM-8.   Atsushi Sakurai (Department of Emergency and Critical Care Medicine, Nihon University
        School of Medicine, Japan)
        Significance of temperature gradient between brain and bladder in patients with severe brain
        damage.


PM-9.   Harumi Nishio (Department of Emergency and Critical Care Medicine, Nihon University
        Hospital, Japan)
        Requirements for nursing management of hypothermia therapy.



                                                32
INTRODUCTION OF
 MAIN SPEAKERS
Nariyuki Hayashi, M.D., D.S. Sc.

Professor and Chairman
Department of Emergency and Critical Care Medicine
Nihon University School of Medicine
Tokyo, Japan




Educational Background and Academic Titles:

1966   M.D.: Nihon University, Tokyo
1965   Resident (Surgery): Nihon University Itabashi Hospital
1970   D. M. Sc. (Neurosurgery): Nihon University, School of Medicine
1971   Department of Neurosurgery, Nihon University Itabashi Hospital
1973   Board of Japan Neurological Surgery
         Assistant Professor: Department of Neurological Surgery, Nihon University School
         of Medicine
1991   Associated Professor: Department of Neurological Surgery, Nihon University School
         of Medicine
1995   Board of Japan Emergency
1996   Professor: Department of Neurosurgery, Miami University, Miami, Florida
1996   Professor: Department of Emergency & Critical Care Medicine, Nihon University
         School of Medicine


Fields of Research:

Brain injury
Spinal cord injury
ICU management
Brain hypothermia treatment
Stroke




                                         34
P. DAVID ADELSON, M.D., F.A.C.S., F.A.A.P.

Professor of Neurosurgery and Vice Chairman for Research
for the Department of Neurosurgery,
University of Pittsburgh School of Medicine
U.S.A.




Dr. Adelson received his medical degree in 1986 from Columbia University and completed the
neurosurgical residency program at the University of California, Los Angeles, School of Medicine in
1993. He then pursued additional specialty training as a fellow in pediatric neurosurgery at Children’s
Hospital of Boston and Harvard Medical School in 1993-1994. He joined the faculty of the University
of Pittsburgh School of Medicine in 1994.

David Adelson, MD is a Professor of Neurosurgery and Vice Chairman for Research for the
Department of Neurosurgery, University of Pittsburgh Medical Center located in Pittsburgh,
Pennsylvania. In addition, he is also director of pediatric neurotrauma at Children’s Hospital of
Pittsburgh, director of surgical epilepsy at the University of Pittsburgh School of Medicine and the
director of Children’s Hospital of Pittsburgh’s Epilepsy Center. He is also co-director of the Center for
Brachial Plexus and Peripheral Nerve Injuries at Children’s Hospital of Pittsburgh.

His areas of special interest are epilepsy, brain injury and plasticity and brachial plexus injury. He
maintains an active clinical and laboratory research program that focuses on the comprehensive
aspects of traumatic brain injury and recovery in children.

Dr. Adelson is a nationally and internationally recognized expert in head injury and epilepsy in
children. He has been the recipient of multiple awards, including The Best Doctors in America, Young
Investigators Award of the Brain Injury Association, Congress of Neurological Surgeons Clinical
Investigation Award and Outstanding Physician Award. His research has resulted in numerous
publications and awards in the area of pediatric epilepsy and brain injury. He has authored 80
publications in refereed journals, 26 book chapters and has edited 6 books.




                                                35
STEPHEN A. BERNARD, M.D., F.A.C.E.M., F.J.F.I.C.M.

The Intensive Care Unit
Dandenong Hospital
Australia




Dr Stephen Bernard MD is an Intensive Care Physician at three hospitals in Victoria, Australia. He
originally trained in Emergency Medicine, followed by Intensive Care Medicine. He is the Medical
Director of Ambulance Services in Victoria and a Senior Lecturer at the Monash University
Department of Epidemiology and Preventive Medicine

His major research interest is the use of induced hypothermia after resuscitation from out-of-hospital
cardiac arrest. He has published the results of a number of clinical trials in this area, more recently
examining the role of large-volume, ice-cold intravenous crystalloid fluid for the induction of
hypothermia. This strategy is currently being used by paramedics immediately after resuscitation from
cardiac arrest.

Dr Bernard has other funded research programs, including a clinical trial of rapid sequence intubation
after severe head injury by paramedics and the role of Medical Emergency teams in hospitals.




                                               36
HELEN BRAMLETT, Ph.D.

Research Assistant Professor of Neurological Surgery
Miami Project to Cure Paralysis
University of Miami
U.S.A.




Dr. Helen Bramlett received both a Master of Science degree in Psychology and a PhD in
Behavioral Neuroscience from the University of Miami. She completed postdoctoral training
in the area of Neurotrauma at the University of Miami School of Medicine. She is currently a
Research Assistant Professor of Neurological Surgery in the Miami Project to Cure Paralysis
at the University of Miami. She has extramural funding from NINDS and the US Department
of Defense. Her studies concentrate on the pathophysiology of TBI with an emphasis on
gender. Also, her laboratory is investigating the pathophysiology of progressive white matter
damage as well as the benefits of therapeutic hypothermia.




                                           37
M. ROSS BULLOCK, M.D., Ph.D.

Reynolds Professor of Neurosurgery and Director,
Neurointensive Care Unit, Medical College of Virginia
Hospital of Virginia Commonwealth University
U.S.A.




EDUCATION/TRAINING                   DEGREE         YEAR(s) FIELD OF STUDY

University of Birmingham, England     MBCLB          1975      Medicine/Surgery
University of Natal, South Africa     Ph.D.          1987      Neuroscience


ACADEMIC APPOINTMENTS

1984- 1986      Senior Lecturer in Neurosurgery, Natal, South Africa
1986 -1991      Senior Lecturer/ Associate Professor, Neurosurgery, University of Glasgow, UK
1991- 1992      Acting Chairman, Neurosurgery, University of Glasgow, Scotland, UK
1992 -1997      Associate Professor, Neurosurgery, Virginia Commonwealth University, USA
1997- Present   Reynolds Professor of Neurosurgery and Director, Neurointensive Care Unit, Medical
                College of Virginia Hospital of Virginia Commonwealth University, USA

HONORS

Vice Chairman, Brain Trauma Foundation 2002 - present
Vice President, Neurotrauma Society, 1994
President, Neurotrauma Society, 1998-1999
Editorial Boards, 14 Journals Neurosurgery, J. CBP and Metabolism, J. Neurotrauma (Deputy Editor)
Chairman, Head Injury Committee, AANS Joint Section on Neurotrauma and Critical Care, 1997-
1998
Chairman, AANS Joint Section on Neurotrauma and Critical Care, 1999-2001




                                             38
WILLIAM M. COPLIN, M.D.

Associate Professor in the Departments of Neurology
and Neurological Surgery at Wayne State University,
Chief of Neurology and Medical Director of Neurotrauma
and Critical Care at Detroit Receiving Hospital
and The Detroit Medical Center
U.S.A.




William M. Coplin, MD, attended college at The University of Chicago and medical school at Baylor
College of Medicine. He did an internship in Internal Medicine, residency in Neurology, and
fellowships in Pulmonary and Critical Care Medicine and in Neurosurgical Critical Care, all at the
University of Washington. He has been in Detroit the past seven years, where he is now Associate
Professor in the Departments of Neurology and Neurological Surgery at Wayne State University. He is
also Chief of Neurology and Medical Director of Neurotrauma and Critical Care at Detroit Receiving
Hospital and The Detroit Medical Center. He serves on an NIH study section, is the Chair-elect for the
Neuroscience Section at the Society of Critical Care Medicine, is a founding member and sits on the
Board of Directors for the Neurocritical Care Society, and is on the editorial board for Neurocritical
Care.




                                              39
WILLIAM DALTON DIETRICH, III, Ph.D.

Kinetic Concepts Distinguished Chair in Neurosurgery
Professor of Neurological Surgery,
Neurology, and Cell Biology and Anatomy
Scientific Director, The Miami Project to Cure Paralysis
Vice Chairman for Academic Affairs,
Department of Neurological Surgery
University of Miami School of Medicine
U.S.A.



Dr. Dietrich received his B.S. in Biology from Virginia Polytechnic Institute and State University in
1974, and his Ph.D. in Anatomy (in the laboratory of Dr. J. T. Povlishock) from the Medical College
of Virginia in 1979. Following completion of his Ph.D. requirements, Dr. Dietrich completed a
postdoctoral fellowship in the Department of Pharmacology (Dr. O. H. Lowry) at Washington
University, St. Louis, MO, 1981. In 1981, Dr. Dietrich joined the Department of Neurology at the
University of Miami School of Medicine as an Assistant Professor, with a joint appointment in Cell
Biology and Anatomy; in 1986, he was promoted to Associate Professor with Tenure, and in 1993
attained the rank of Professor.     Dr. Dietrich served as Vice-Chairman for Basic Science in the
Department of Neurology from 1995 to 1997, when he accepted the position of Scientific Director of
The Miami Project to Cure Paralysis.


Dr. Dietrich has published 42 book chapters, 203 refereed journal articles, 231 abstracts, and 20
editorial comments. He has been a thesis/dissertation advisor to 12 predoctoral students and has
trained 24 postdoctoral fellows in his laboratory.


Dr. Dietrich is a neuroscientist who utilizes animal models of brain and spinal cord injury to
investigate the cellular, biochemical, and molecular events associated with cell death and recovery. In
addition to testing new drugs in animal models, he has also investigated temperature-sensitive
pathophysiological mechanisms. Ongoing studies target apoptotic and inflammatory processes to limit
secondary injury mechanisms. Most recently, strategies to repair the brain and spinal cord have been
initiated and include growth factor infusion and cellular transplantation strategies.




                                                40
Barth A. Green, M.D., F.A.C.S.

Chairman of Department of Neurological Surgery
University of Miami School of Medicine
U.S.A.




Academic (Institutions, rank/status, dates)

                 1994 - Present          Chairman
                                                Department of Neurological Surgery
                                                University of Miami School of Medicine
                                                Miami, Fl.

                 1985 - Present          Professor
                                                 Department of Neurological Surgery
                                                 University of Miami School of Medicine
                                                 Miami, FL

                 1985 - Present          Professor
                                                 Department of Orthopaedics and Rehabilitation
                                                 University of Miami School of Medicine
                                                 Miami, FL

                 1986 - Present         Director
                                                Applied Research
                                                The Miami Project to Cure Paralysis
                                                University of Miami School of Medicine
                                                Miami, FL
Hospital Appointments (Institutions, dates)

                 1988 - Present          Director
                                                 Neurosurgery Service
                                                 Jackson Memorial Hospital/University of Miami
Medical Center
                                                  Miami, FL

                 1988 - Present          Director
                                                 Neurosurgical Spine Service
                                                 Jackson Memorial Hospital/University of Miami
Medical Center
                                                  Miami, FL

                 1986 - 1989             Chief
                                                  Neurological Surgery Service
                                                  Veterans Administration Hospital Medical Center
                                                  Miami, FL




                                                 41
MICHAEL HOLZER, M.D.

University of Vienna,
Vienna General Hospital
Wien, Austria




EDUCATION & TRAINING


Undergraduate:       1986: Reifezeugnis (School-leaving examination)
Graduate:            1994: Dr.med.univ. Universitat Wien, School of Medicine (Austria)
Postgraduate:
                     1994-1996:      Internship
                     1996-1998:      Research Fellow, Department of Emergency Medicine,
                                     University Hospital of Vienna (Austria)
                     1998-present:   Training for Degree of Specialist in Internal Medicine,
                                     University Hospital of Vienna (Austria)




                                           42
PATRICK KOCHANEK, M.D.

Professor and Vice Chairman of the Department of Critical Care Medicine,
Director of the Safar Center for Resuscitation Research,
University of Pittsburgh School of Medicine
U.S.A.




Patrick Kochanek, MD, is Professor and Vice Chairman of the Department of Critical Care Medicine
at the University of Pittsburgh School of Medicine, and is Director of the Safar Center for
Resuscitation Research at the University of Pittsburgh School of Medicine. He is also Associate
Director of the Pediatric Intensive Care Unit, at Children’s Hospital of Pittsburgh and the Brain
Trauma Research Center at the University of Pittsburgh. Dr. Kochanek has studied traumatic and
ischemic brain injury for twenty years, with an emphasis on mechanisms of secondary damage and
pediatric issues. He is the PI of a T-32 funded training program entitled “Training in Pediatric
Neurointensive Care and Resuscitation Research,” and is the Editor-in-Chief of the journal Pediatric
Critical Care Medicine.




                                             43
Tsuyoshi Maekawa, M.D., Ph.D.

Professor, Department of Emergency and Critical Care Medicine
Yamaguchi University School of Medicine
and
Director, Advanced Medical Emergency and Critical Care Medicine
Yamaguchi University Hospital




PROFESSIONAL EXPERIENCE
1984.7-1991.3  Associate professor, Division of Emergency Medicine, Yamaguchi University
               Hospital
1991.4-1995.1  Professor, Division of General Physician, Yamaguchi University Hospital
1995.2-present Professor, Department of Emergency and Critical Care Medicine,
               Yamaguchi University School of Medicine
1999.4-present Director, Advanced Medical Emergency and Critical Care Medicine, Yamaguchi
               University Hospital

MEDICAL LISENCE
1972.6       Medical Doctor (#214545)
1977.12      Fellow (Japanese Society of Anesthesiologists (# 515)
1978.7       Philosopher of Doctor (Medicine, Yamaguchi University #216)
1986.9       Board Certified Member (Japanese Association for Acute Medicine, #695)
1989.2       Board Qualified Intensivist (Japanese Society of Intensive Care Medicine, #890066)
1995.1       Fellow (Japanese Association for Acute Medicine, #201)

MAIN RESEARCH FIELD
Emergency Medicine
Critical Care Medicine
    Cerebral blood flow and metabolism, Neurochemistry, Neuro-intensive care

ACTIVITY OF SOCIETY
Board member of Japanese Association for Acute Medicine
Councilor of Japanese Society for Emergency Medicine
President and board member of Japanese Society of Intensive Care Medicine
Councilor of Japanese Society of Cerebral Blood Flow and Metabolism
Member of Japanese Society of Anesthesiologists
Councilor of Japanese Society of Clinical Monitoring

1990-present     Board member, Division of Emergency Medicine, Organizing Committee of
                 Medical Directive (Yamaguchi Prefecture)
1993-1997        Examiner, Japanese National Board of Emergency Paramedics
1996-2001        Board member, Yamaguchi Medical Association
1996-present     Director, Association for Emergency Medical Field Works (Yamaguchi Prefecture)

AWARD
1982             International Research Fellowship Award (NIH)
1988             Award of Nakamura, Yamaguchi University Medical Association




                                            44
DONALD W. MARION, M.D., Ms.C., F.A.C.S.

Professor and Chairman
Department of Neurological Surgery
Boston University School of Medicine
and
Neurosurgeon-in-Chief
Boston Medical Center
U.S.A.


On November 1, 2002 Dr. Donald Marion was appointed Chairman of the Department of Neurological
Surgery at Boston University School of Medicine. Prior to this appointment Dr. Marion was professor
and vice-chairman of the Department of Neurological Surgery at the University of Pittsburgh Medical
Center, and Director of both the Brain Trauma Research Center and the Center for Injury Research
and Control at the University of Pittsburgh. In addition, Dr. Marion was professor of Rehabilitation
Science and Technology at University of Pittsburgh Medical Center.

Dr. Marion is an international expert on the surgical and medical management of trauma to the head
and spine. He founded the Brain Trauma Research Center in 1991 at the University of Pittsburgh after
receiving a National Institutes of Health Head Injury Center Award. In 1998 he was appointed
director of the Center for Injury Research and Control at the University of Pittsburgh and received a
$5 million dollar grant from the Centers for Disease Control to support this effort.

Dr. Marion’s research interests have focused on the cellular, molecular and physiologic mechanisms
responsible for secondary brain injury, and identifying new therapies that can limit those mechanisms.
In 1997 he published a study in the New England Journal of Medicine showing that therapeutic
hypothermia could improve outcomes following severe traumatic brain injury. Dr. Marion has
published a book on traumatic brain injury and nearly 200 peer-reviewed journal articles and book
chapters. He serves on the Editorial Boards of Neurosurgery, Journal of Neurotrauma, and the Journal
of Trauma. He is an Ad-hoc reviewer for the New England Journal of Medicine and Lancet as well as
the Journal of Neurosurgery and Journal of Critical Care Medicine. Dr. Marion has served as
President of the National Association of Injury Control and Research Centers, and currently is
Chairman of the Joint Section on Neurotrauma and Critical Care of the American Association of the
Neurological Surgeons and Congress of Neurological Surgeons.

Recent honors include listings in Who’s Who in America, Castle Connolly’s Guide to America’s Top
Doctors, and the Consumer Research Council for America Guide to America’s Top Surgeons. In
addition, Dr. Marion was named the 2003 Charles Fager Lecturer at the Lahey Hitchcock Clinic, and
has served as Visiting Professor at a number of major institutions.

Dr. Marion graduated from St. John’s University, Collegeville, MN in 1975. He received a Bachelor
of Science in Medicine from the University of North Dakota School of Medicine in 1980, and his
Medical Doctorate degree from the University of California – San Francisco in 1982. His hometown
is Hettinger, North Dakota.




                                              45
ANTHONY MARMAROU, Ph.D.

Professor and Vice Chairman,
Director of Research, Division of Neurosurgery,
Virginia Commonwealth University's Medical College of Virginia Campus
U.S.A.




Dr. Marmarou, founder of the American Brain Injury Consortium, is Professor and Vice- Chairman of
Neurosurgery at the Medical College of Virginia, Virginia Commonwealth University. He began his
studies in neurotrauma at the Einstein College of Medicine, Bronx, New York, in the early seventies
and joined MCV in 1982, where he has continued to focus in traumatic brain injury and specifically
brain edema and intracranial pressure. He received his training at Drexel University, Philadelphia, in
electrical engineering in 1959 and joined the Franklin Institute Laboratories of the State of
Pennsylvania where he headed the Biosystems Laboratories. After graduate work at the University of
Pennsylvania in 1962, he returned to Drexel University and Temple Medical School and received his
Ph.D. in Biomedical Engineering. In 1983 he was named a Javits Scholar by the National Institutes
of Health and received support to continue his research in brain swelling. Dr. Marmarou has over 200
publications in the field of traumatic brain injury and serves on the international boards of
Neurotrauma, Intracranial Pressure and Brain Edema. In 1997, he was awarded the Caveness medal
by the National Brain Injury Foundation for outstanding achievement in research. Dr. Marmarou is
currently the Technical Director of the American Brain Injury Consortium where he continues his
clinical and laboratory studies in neurotrauma.




                                                  46
JOHN T. POVLISHOCK, Ph.D.

Professor and Chair of the Department of Anatomy and Neurobiology,
Co-Director, VCU Neuroscience Center, and Director,
Commonwealth Center for the Study of Brain Injury,
Medical College of Virginia Campus of Virginia
Commonwealth University, Richmond, Virginia,
U.S.A.




Dr. John Povlishock is currently Chair of Anatomy and Neurobiology and Co-Director of the

Neuroscience Center on the Medical College of Virginia Campus of Virginia Commonwealth

University. He serves as Editor in Chief of the Journal of Neurotrauma, as well as the Director of the

Commonwealth Center for the Study of Traumatic Brain Injury. His research focuses on traumatic

brain injury, with emphasis on neuroprotection, including the use of hypothermic interventions to

protect the brain parenchyma and its intrinsic vasculature. His work has been reported in over 170

papers, reviews, books and chapters. For his research accomplishments, he has received two Javits

Neuroscience Investigator Awards from the National Institutes of Neurological Disorder and Stroke,

which also awarded him their Gold Metal for Brain Injury Research. He has also received the

Caveness Award from the National Head Injury Foundation and the Brain Trauma Lecture Award

from the Joint Congress of Neurological Surgery.




                                              47
HUBERT L. ROSOMOFF, M.D.

The Rosomoff Comprehensive Pain and Rehabilitation center,
South Shore Hospital,
Miami, U.S.A.




HUBERT ROSOMOFF interned at Hahnemann Hospital, 1952-1953, Columbia-Presbyterian Medical
Center for General Surgery and Neurological Surgery at the Neurological Institute of New York,
1954-1959. There he began his research in hypothermia which earned him The American Academy of
Neurological Surgery Award in 1956. He was stationed at the United States Navel Hospital and the
naval Medical Research Institute in Bethesda where research in hypothermia continued along with
hospital duties in Neurology. He was consultant from the United States to The Institute for Artificial
Hibernation and Resuscitation in Moscow, U.S.S.R. He returned to the Neurological Institute in 1957
to complete training in 1959, adding a D. Med. Sci. in Physiology from Columbia University College
of Physicians and Surgeons in 1960. During this time, hypothermia was introduced clinically as an
adjunct to the neurosurgery of vascular lesions, and the treatment of brain injuries. While still a
resident, he was a guest lecturer at The Royal Society of Medicine, London, and participated, by
invitation, in the opening plenary session of The First International Congress of Neurological Surgery
in Brussels, Belgium. After training, Dr. Rosomoff went to the University of Pittsburgh School of
Medicine as Clinical Assistant Professor and Chief of Neurological Surgery at The Veterans
Administration Hospital. He remained at the University of Pittsburgh from 1959 to 1966, leaving with
the rank of Clinical Associate Professor to become Professor and Chairman at the Albert Einstein
College of Medicine in New York.

The University of Miami Comprehensive Pain and Rehabilitation Center was established by Dr.
Rosomoff in 1974. He was the founding Medical Director and has continued to be Director through
his tenure as chairman of the Department of Neurological Surgery until the present. Dr. Rosomoff
stepped aside to become Chairman and Professor Emeritus of the Department in 1994 to devote
fulltime effort to the Pain Center, which was then established as a Center of Excellence by the
University of Miami. He further has served as Vice Chairman of the State of Florida Pain
Management Commission, 1995 to the present. He served on the Executive Council of the AANS
Section on Pain, 1989-1993. From 1971 to 1994, he was Professor and Chairman of the Department of
Neurological Surgery at The University of Miami, School of Medicine.

He is now Professor and Chairman Emeritus and Medical Director of the Comprehensive Pain and
Rehabilitation center. HE is the author of 250 published articles or books, editor of several journals,
and is Founder of two American and one international Pain Societies. He has been prominent in the
effort to develop the specialty of Pain Medicine which has been recognized by the American Board of
Medical Specialties. It should also be noted that during his tenure as Chairman, the Neurosurgical
Research Laboratories advanced to become the Miami Project to Cure Paralysis which has gone on to
become an Institute of Neuroscience for the University of Miami.




                                               48
RYO NODA

Professor of Music, Osaka University of Arts,
Arts Planning Department, Osaka, Japan.
President of NODA Music Institute.
Musico-Kinetic Therapiste at Ishikiriseiki Hospital
Osaka, Japan




1972           Degree of BM Osaka College of Music
1972-73        Study at Northwestern University GraduateSchool , USA
1973-74        Study at Bordeaux Conservatory ( grand prix of composition & saxophone) France
1974           SACEM Awards by French Composer's association.
1975           Prize of Bordeaux City. Appears on residence in Paris, France.
               Official recognition of composer / performer well known over the world.
1976-83        Osaka Culture Festival Awards Gold Prize, Silver Prize and three Bronze Prize
1984           Osaka Prefecture Festival Awards
1986           Grants, NHK Foundation, Japan. Grants, France Radio and Art Museum in Paris.
1987           Grants, Asian Culture Council, USA
1988           Musico-Kinetic Therapy development
1989           Grants, Japan Foundation to Contemporary Noh presentation in New York, USA
               Montreal, CANADA.
1993           Assistant Professor, Art Planning Department, Osaka University of Arts
1999-present   Current position

RYO NODA graduated from the Osaka College of Music as a saxophonist.He pursued advanced
music studies at Northwestern University, Evanston,Illinois, under Fred L.Hemke, and at the
Bordeaux Conservatory, in France,under Jean-Marie Londeix. He was five time awarded the Osaka
City Art Festival Prize, and, in 1986, won the Osaka Prefecture Gold Award. Also had many grants for
the composer/performer which includes NHK Broad-casting Association, Yomiuri Shinbun, Japan,
Radio France, and Asian Culture Cuncil, USA.etc. Noda 's work as a composer was recognized in
1973 by the award of the SACEM Composition Prize. While his repertoire includes literature from the
Baroque, Classical and Romantic periods, it was his own avant-garde improvisations and inventive
new techniques for the saxophone that he offered on extensive tour throughout Europe.Regarded as
one of the most colorful and creative performing artists and composers active in Japan & Europe.
 Recentry, he is known for his successful new methode of Musico-Kinetic Therapy blending of
Phosiology, Medicine and Music. Method of the Musico-Kinetic Therapy which it studied for 30 years
complete after return Japan in 1986, and to demonstrate an effect of a Syncronized Musico-Kinetic
Therapy for a consciousness disturbance at Ishikiriseiki Hospital in Osaka. Also, Scientifically
practicing at the Aichi Medical School in Nagoya and the Nihon University, Department of
Emergency and Critical Care Medicine in Tokyo. Those result is introduced in NHK synthesis TV
news eleven, NHKTV, BS 1 & 2, Nippon Television Yomiuri TV others much.




                                             49
STEFAN SCHWAB, M.D.

Vice Chairman of the Department of Neurology
University of Heidelberg
Germany




Education and positions:
1982-1988              School of Medicine University of Erlangen
1988-1990              Dept. of Neurology University of Würzburg
1990-1991              Dept. of Neuropathology University of Aachen
1991-1995              Dept of Neurology University of Heidelberg
1995                   Dept of Psychiatry University of Heidelberg
since 1.1.96           Staff member of the Dept. of Neurology, University of Heidelberg
1998                   Associate Professor of Neurology
2000                   Vice chairman of the Department of Neurology


Research:              Experimental stroke research, Critical care of Stroke,
                       Neuroplasticity after stroke, Memory disorders, Neuropsychology after CNS
                       lesions (experimental and clinical)


Grants:                3 DFG, 1 BmBF, 5 grants University of Heidelberg, Industry grants from
                       AMGEN, Cepahlon and others


Awards:                Spatz-Preis of the German Neurological society 1998




                                             50
THORSEN STEINER, M.D., Ph.D.

Associate Professor of Neurology
University of Heidelberg
Germany




Thorsten Steiner is Associate Professor of Neurology at the University of Heidelberg, Germany. He
gained his physician’s licence at Heidelberg in 1992, and his MD in 1992. Since then, Professor
Steiner has also gained licenses in neurology and neurological intensive care. Professor Steiner’s
clinical experience includes emergency medicine, psychiatry, general neurology and stroke
management, in Germany and the USA. He has also spent 6 years in the ‘front-line’, practicing in
neurological intensive care units. He has a special interest in stroke and has published a number of
papers dealing with aspects of stroke management.




                                             51
URBAN UNGERSTEDT, Ph.D.

Professor of Neuropsychopharmacology
Department of Physiology and Pharmacology
Karolinska Institute
Sweden




EDUCATION:                         Graduate in medicine 1964

                                   PhD (Hons) in Histology 1971:
                                   “On the anatomy, pharmacology and function of
                                         nigro-striatal dopamine system”

WORK EXPERIENCE:                   Dept of Histology, Karolinska institute
                                   1963-1978

                                   Dept of Physiol, and Pharmacol, Karolinska institute
                                   1978-

                                   Doctorate grant 1967- 1970

                                   Director of Graduate Studies, Karolinska institute
                                   1971-1974

                                   Visiting scientist at the Dept of Physiology,
                                   University of Aberdeen 1971

                                   Consultant at the National Institute of Mental Health,
                                   Washington 1972

                                   Assistant Prof in Histology 1974- 1978

                                   Professor in Neuropsychopharmacology 1978-

                                   Chairman, Dept of Pharmacology, Karolinska Institute
                                   1987- 1988

                                   Member of the Nobel Assembly for the Nobel Prize in
                                   Medicine 1987-

                                   Chairman of the Nobel Prize assembly in Physiology and
                                   Medicine 2004




                                         52
                 ABSTRACTS

Abstracts for Oral Presentations

  February 5 (Thursday) – February 6 (Friday)
      “TENKU-A” AND “TENKU-B” ROOMS
                                                                                   Lecture by President
                                                                                        February 5 (Thu)
                                                                                              TENKU-A
P-1


The new concept and pitfall of brain hypothermia treatment.

Nariyuki Hayashi, M.D., PhD.
Nihon University, Department of Emergency and Critical Care Medicine, Tokyo, Japan


         There is no doubt of effectiveness of neuroprotection to the ischemic brain insults by brain
hypothermia in animal studies. However, in clinical studies, similar effects of hypothermia were not
obtained like animal studies in previously. The reasons of these different results have been considered
to be   hypothermia is too much stressful to the human body . The experience of more than 500 cases
of brain hypothermia treatment in trauma, stroke and cardiac arrest produced breakthrough in different
understanding of human brain injury mechanism, precise control technique of brain tissue temperature,
prevent of complications associated with hypothermia, pitfall of brain hypothermia treatment,
mechanism of fall in vegetation, and diagnostic method of reversibility from vegetate state. The
activation of glutamate neurotoxicity by insulin resisted hyperglycemia, neuronal hypoxia by difficulty
to release of oxygen from binding hemoglobin in injured brain tissue with reducing hemoglobin 2,3
DPG, BBB dysfunction associated with vasopressin excess release, delayed neuronal restoration by
estrogen suppression, and elevation of brain tissue temperature by brain thermo-pooling should be
include in brain hypothermia treatment. The previous concept of neuro-protection by hypothermia
with control of ICP, CBF, and brain edema is not enough for new finding of brain damage mechanism
by stress associated hypothalamus-pituitary-thyroid-adrenal axis neuro-hormonal reactions at acute
stage. With ought understanding of these stress associated brain injury mechanism, brain hypothermia
treatment is not useful.
         The management of brain hypothermia is benefits for neuronal restoration. However,
negative effects are also recorded in brain hypothermia. Metabolic shift from glucose to lipid
metabolism, immune suppression associated with reducing growth hormone, easy complication of
systemic infections, unstable cardio-pulmonary circulation by reduced catecholamine, and re-warming
stress are negative effects on the brain hypothermia treatment. To success of brain hypothermia
treatment, confiscated these management care techniques are required.
Selected brain damage of hippocampus and amygdale nucleus and or diffuse brain damage are main
cases of vegetation. Early induction of brain hypothermia for prevent of radical attack to dopamine
A10nervous system at acute stage and cerebral dopamine replacement therapy by pharmacological,
electrophysiological stimulation and music therapy at chronic stage are very effective for reducing
vegetation in severe brain damage.




                                                54
                                                                                    Lecture -- Basic Science
                                                                                           February 5 (Thu)
                                                                                                   TENKU-A
L-1


A review of hypothermia's cerebrovascular and brain parenchymal protective effects
following experimental traumatic brain injury (TBI)

John T. Povlishock, Yugi Ueda, Eiichi Suehiro, Hiro Koizumi
Department of Anatomy and Neurobiology, Medical College of Virginia Campus of Virginia
Commonwealth University, Richmond, VA, USA and Department of Neurosurgery and Clinical
Neuroscience, Yamaguchi University School of Medicine, Yamaguchi, Japan


      In this review, we focus upon our laboratory's study of different durations, periods of initiation and
re-warming rates in the use of post-traumatic hypothermia in two different rodent models of TBI.
Anesthetized rodents were subjected to either fluid-percussion or impact acceleration TBI followed by
moderate hypothermia that was initiated 30 min to 2h post TBI, with the hypothermic durations ranging
from 1 to 2 h, and the post hypothermic re-warming rates spanning either 20m (rapid re-warming) or 90
m (slow re-warming). TBI-induced axonal damage was assessed through the use of antibodies targeting
either impaired axonal transport (amyloid precursor protein) or neurofilament damage, while the pial
arteriolar microcirculation was functionally assessed via implanted cranial windows, allowing for the
assessment of the pial vascular responses to known vasodilators such as CO2, acetylcholine, pinacidil,
and sodium nitroprusside. In both animal models, normothermic TBI led to extensive axonal damage as
well as altered vascular responsiveness to multiple vasodilators. Both axonal and vascular protection were
provided by early post TBI hypothermia. Although this protection declined as the time of hypothermic
onset was delayed, this protection was restored by the use of delayed, yet more prolonged, periods of
hypothermia. In the case of both the axonal and vascular responses, rapid post TBI re-warming reversed
any hypothermic protective effect and in fact, exacerbated the amount of axonal damage, while leading to
persistent vascular abnormalities that could be linked to both endothelial and smooth muscle cell
dysfunction. In these paradigms, the delayed use of radical scavengers and/or immunophilin ligands
restored many of hypothermia's protective effects. The overall implications of these studies for continued
evaluation in animal models as well as ongoing human clinical trials will be addressed. Supported by
NIH grant NS20193.




                                                 55
                                                                                  Lecture -- Basic Science
                                                                                         February 5 (Thu)
                                                                                                 TENKU-A
L-2


Factors regulating hypothermic protection in experimental models of brain injury.

W. Dalton Dietrich, Helen M. Bramlett, Takamoto Suzuki, Yoshitaro Matsushita, Jessie Truettner
Department of Neurological Surgery, The Miami Project to Cure Paralysis, University of Miami School
of Medicine, Miami, FL, USA


[Objective] The importance of small variations in brain temperature on ischemic and traumatic outcome
has been demonstrated in a large number of experimental models.            Although improvements with
therapeutic hypothermia are demonstrated in some patient populations, negative findings have also been
reported. The effectiveness of hypothermia may be related to several factors, including therapeutic
window, optimal levels and duration of cooling, re-warming protocol, injury severity, and gender. The
purpose of this study was to investigate optimal conditions for therapeutic hypothermia in an established
model of fluid-percussion (F-P) brain injury.
[Materials and Methods] Male and female Sprague-Dawley rats underwent moderate F-P brain injury
with or without periods of secondary hypoxia.      Brain hypothermia was initiated 30 min after TBI and
maintained for a four or 24-hour period.        Following hypothermic treatment, animals were rapidly
re-warmed (30 min) or slowly re-warmed (90 min). Three days following TBI, rats were perfusion
fixed and quantitatively assessed for contusion volume, numbers of NeuN-positive cortical neurons, and
axonal pathology ( -APP).     Hypothermic protection (4hrs) was observed in TBI animals that underwent
a secondary hypoxic insult when slow but not rapid re-warming was conducted.               Post-traumatic
hypothermia significantly reduced contusion volume and protected against selective neuronal damage in
male, but not female, rats.     Ovariectomized rats demonstrated protection with hypothermia.             In
reference to mechanisms underlying hypothermic protection, evidence was generated that hypothermia
reduced the activation of transcriptional factor NF-6B and matrix metalloprotease activation after TBI.
[Conclusions] Taken together, these experiments emphasize several factors that may be important in
determining the efficacy of therapeutic hypothermia in experimental models of TBI and head injured
patients. (Supported by NIH NS30291, NS42133 and NS43233)




                                                 56
                                                                                    Lecture -- Neurotrauma
                                                                                          February 5 (Thu)
L-3                                                                                               TENKU-A


A randomized controlled trial of mild hypothermia therapy in severe head injured patients
in Japan.

Tsuyoshi Maekawa, Nariyuki Hayashi, Keiki Ogino, Jun Takezawa, Seigo Nagao, Yasuo Ohashi, Susumu
Yamashita, Kiyoshi Okabayashi
Hypothermia for Head Injury Study Group in Japan


Protection against brain insults is one of the hardest aspects of clinical practice. Recently, mild
hypothermia was applied to cardiopulmonary resuscitated victims and was proved to have brain
protective effects by two randomized controlled trials (RCT). While Clifton’s group had applied mild
hypothermia therapy in severe head injured cases (GCS     8), but they failed to prove the effectiveness.
We have applied mild hypothermia therapy as a RCT in 300 severe head injured cases in 38 medical
centers in Japan. Inclusion criteria are (1) 4 GCS 8, except best motor response of 6, (2) core body
temperature must be controlled to 35.5°C at 6 hours after head injury in the mild hypothermia group (3)
15y.o.   age < 70y.o.   Patients are randomized into either control (35.5~37.0°C, 100 cases) group or
mild hypothermia (32.0~34.0°C, 200cases) group. Core body temperature must be controlled for at least
72 hours and may be able to prolong, if necessary. Brain oriented intensive care is required and his
physiologic parameters are qualified by cardiac index, and internal jugular venous oxygen saturation and
temperature, taken and stored in every one minute. Evaluations of the mild hypothermia therapy are
performed by GOS at 3 and 6 months, and by biochemical parameters such as cytokines, free radical
products and neurotoxic excitatory amino acids between the two groups. At this point, 22 cases are
enrolled and an interim report will be presented at the meeting.




                                                57
                                                                                       Lecture -- Neurotrauma
                                                                                             February 5 (Thu)
                                                                                                     TENKU-A
L-4


Practical application of modest hypothermia for neuroprotection in spinal cord injury and
spinal cord surgery, 2004

Barth A. Green, M.D., F.A.C.S.
Professor and Chairman Department of Neurological Surgery, University of Miami School of Medicine,
Miami, FL

Although, the pioneering work in hypothermia for brain neuroprotection goes back to the 1950’s, it
wasn’t until the 1960’s and 1970’s that specific laboratory and clinical research focused on spinal cord
injury. Work done in the 1960’s -70’s involved the use of local hypothermia following laminectomy as a
treatment for acute spinal cord injury. Profound local hypothermia dropped spinal cord temperatures to
as low as 20 degrees centigrade as measured by intramedullary thermistor probes. Laboratory
experiments showed great promise for restoring function. Unfortunately, this approach never panned
out clinically. Detailed histopathological studies in rats, cats and primates showed a differential
protection gradient with the maximum benefit described in the dorsal columns exposed by the
laminectomy. Diminished tissue protection was noted in gray matter and lateral and ventral columns.
Clinical studies done in the United States at that time demonstrated preservation only of dorsal column
function and there was also no evidence of motor recovery in primate laboratory studies. The clinical
application of spinal cord cooling lost favor until intriguing work came out of the University of Miami in
the late 1980’s suggesting that modest hypothermia was potentially more effective and safer than the
profound degrees of cooling utilized by earlier researchers. There are pros and cons of systemic vs.
local hypothermia for spinal cord neuroprotection. In the last decade several different externally and
internally applied techniques have been designed to optimize treatment. As far as implantable devices,
the intravascular catheter or cooling probe works by cooling the patient’s blood and thereby the spinal
cord. External devices include special coolant packages applied to specific areas of skin or the use of
the conventional cooling blankets and ice. The use of cooled ventilator air during surgery has also been
an important adjunct. The Jackson Memorial/University of Miami Medical Center does approximately
2500 neurosurgical operations a year with approximately half of those being spinal procedures.
Recently, it has become widely accepted that there are no proven protective effects of high dose steroids
for spinal cord injury or neuroprotection and there are no other effective pharmacological alternatives.
Therefore, over the last five-year period, we have been increasingly utilizing modest hypothermia, not
only for the management of acute post-traumatic and ischemic spinal cord injury but also for
perioperative neuroprotection. We are utilizing cooling blankets in the Trauma Center and ICU and a
combination of cooling blankets and cold gases for intubated patients on ventilators in the operating room.
It is our present protocol to lower the body temperature from 37 degrees centigrade to 33-34 degrees
centigrade within a 1-2 hour period. We maintain the modest hypothermia for 24 hours post injury or
postoperatively and then begin a slow reheating process to normothermia over the next 24-48 hour
period.
This paper will discuss some of the practical techniques we utilize to treat this select group of patients as
well as the challenges and barriers to treatment both physiologically and logistically. We have also had
a limited experience in patients suffering spinal cord ischemia from trauma or surgical injury.
Postoperative randomized clinical trials are now being initiated and will be presented along with
preliminary data on patient outcome.

                                                 58
                                                                                   Lecture -- Neurotrauma
                                                                                         February 5 (Thu)
L-5                                                                                              TENKU-A


Is hypothermia beneficial by preventing fever?

Donald W. Marion, MD
Professor and Chairman, Boston University School of Medicine


Laboratory investigations conducted over the last 20 years have provided compelling evidence that
post-injury hypothermia (32-34ºC) leads to improved functional outcomes following experimental
traumatic brain injury (TBI).   While small single center clinical trials completed during the 1990’s also
found benefit of this treatment for subsets of patients with TBI, a large multicenter trial completed in
2001 did not.   One possible explanation is that the control group in the multicenter study had their
temperatures tightly controlled at 37-38ºC. Fever that occurred in the smaller studies may have caused
worse outcomes for the control groups in those studies.     Several experimental studies of ischemia and
TBI have found a log increase in the number of ischemic neurons for animals with brain temperatures
above 39ºC following the insult, and this effect have been observed for up to 24 hours after the injury.
Clinical retrospective studies of patients with subarachnoid hemorrhage, stroke and spontaneous
intracerebral hemorrhage also have found worse outcomes in those patients who had fevers as compared
to those that did not.   Unfortunately, fever is very common after TBI, subarachnoid hemorrhage and
other acute neurological diseases.   In one prospective study of patients in the neuro-ICU, nearly 50%
had at least one febrile episode, and fever was observed in 93% of those who were in the ICU more than
2 weeks despite the use of surface cooling techniques and acetomenophen to try to prevent fever. The
problem is compounded by the fact that brain temperatures are likely to be higher than rectal or bladder
temperatures.   Several studies that compared rectal, bladder and brain temperatures in patients with TBI
found as much as a 2ºC difference, with brain temperatures always higher. Thus, when the rectal
temperature is 38ºC, the brain temperature may be 40ºC.     Invasive temperature modulation recently has
been introduced as a means to more effectively prevent fever. In a recent study sponsored by the Alsius
Corporation, the use of a subclavian intravenous heat exchange catheter was shown to significantly
reduce the incidence of fever in patients with TBI, stroke or subarachnoid hemorrhage as compared to
conventional surface cooling and medical attempts to prevent fever. It remains to be shown whether or
not this improved ability to prevent fever will result in improved outcomes for these patients.




                                                 59
                                                                                           Luncheon Seminar
                                                                                             February 5 (Thu)
                                                                                                   TENKU-A
L-6

Historical review of development of brain hypothermia

Hubert L. Rosomoff, M.D., D. MED. SC., F.A.A.P.M.
The Rosomoff Comprehensive Pain and Rehabilitation center, South Shore Hospital, Miami, USA


        The search for the prolongation of life by lowering body temperature, cheating death by profound
cooling, has intrigued man for centuries. Cells can be frozen to a temperature where life can be suspended
indefinitely and resuscitated at will by re-warming; however, the freezing of large animals or man with
resuscitation has yet to be achieved. Hypothermia has been found to be protective in many pathological
situations, specifically, vascular or traumatic injuries to the brain. The protective role of hypothermia is
created by a decrease in metabolic rate, a principle which led to the exclusion of circulation to the brain
for open cardiac surgery to protect against anoxia globally or focally. The introduction of surface cooling
as an adjunct to anesthesia for open heart surgery in the 1950s occurred before the perfection of the
heart-lung machine. Reduction of metabolism to the brain by cooling was the only means of excluding
arterial circulation to the brain. Respiration of the brain which was studied later was a prelude to the
introduction of hypothermia for neurosurgery. It should be noted that protection by hypothermia was used
by the Frenchman, Laborit for the management of massive injuries during the French-Indochina Wars.
Prior to this, a neurosurgeon, Temple Fay, utilized lowered body temperature to slow the growth of cancer
and to relieve pain. The effect on cancer growth after re-warming was only temporary, but pain relief
lasted 3 months. Hypothermia protects ATP in the brain. Oxygen requirements of the brain decrease
linearly with decreasing temperature at a rate of 5% for each degree C, as does the blood flow. The brain
is protected against cerebral edema and ischemia. The volume of the brain decreases during cooling.
Cerebrospinal fluid pressure is decreased and high intracranial pressure can be reduced. The brain is
protected against brain injury even when achieved within 3 hours after injury. The utilization of body
cooling with anoxia and strokes based on the early research efforts of the 1950s through the 1970s has
been reborn, along with cooling of the brain for cerebral aneurysms, arteriovenous malformations and
vascular tumors. Spinal cord hypothermia was also effective to arrest severe neurologic changes after
injury. These early efforts were stymied by the crudity of methodology then, but the concepts and work
have been kept alive by neuroscientists using temperature as a basic parameter to study biological
systems and pathologic physiology. The persistence of this effort, new sophisticated techniques, will be
the subject of this Conference, hopefully, to establish a platform from which to proceed to a new fund of
knowledge for treatment of diseases of mankind, specifically, disorders of the nervous system.




                                                 60
                                                                        Lecture -- Emergency Hypothermia
                                                                                          February 5 (Thu)
                                                                                                TENKU-A
L-7


Novel potentials for emergency hypothermia: Suspended animation with delayed
resuscitation from exsanguination cardiac arrest

Patrick M. Kochanek1,2, Samuel Tisherman1,2,3, S. William Stezoski1,4, Ala Nozari1, Xianren Wu1 and
*Peter Safar1,4
Safar Center for Resuscitation Research1, Departments of Critical Care Medicine2, Surgery3, and
Anesthesiology4, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA


[Objective]   Most combat fatalities result from rapid exsanguinations in the field and resuscitation with
fluid administration is generally unsuccessful. In a series of experiments over the past five years, we have
developed a novel approach targeting the use of rapid induction of profound hypothermia by aortic flush
to produce a state of suspended animation after experimental exsanguination cardiac arrest in dogs.
[Materials and methods] In over 200 experiments in dogs, exsanguination cardiac arrest of durations
ranging between 15 min and 120 min was induced by rapid hemorrhage over ~5 min.            After the 5 min
hemorrhage and 2 additional min of cardiac arrest, hypothermia (8-20°C) was induced by aortic or
femoral flush of ice-cold saline via a balloon catheter.   The specific temperature selected depended on
the insult and paradigm.    Delayed resuscitation after the predefined suspended animation interval was
achieved using cardiopulmonary bypass, mild hypothermia (34°C to 12 hrs) and 72-90 hrs of continuous
intensive care.    In some studies, the insult also included laparotomy, splenectomy, and thoracotomy–to
simulate trauma.     In other studies, pharmacological agents were combined with hypothermia to test for
therapeutic synergy.    Final neurologic outcome was assessed at 72-90 hrs by overall performance
category and neurological deficit scores. Brain histopathology was also evaluated.[Results] Normal
neurologic outcome with minimal histopathologic damage was routinely achieved after a cardiac arrest of
90 min using this suspended animation approach. In some dogs, good neurologic outcome was achieved
even after a cardiac arrest of 120 min       A delay of 5-8 min in the induction of suspended animation
attenuates its preservative effect.   Of 14 drugs tested, only the antioxidant tempol produced a synergic
effect with hypothermia.     The addition of trauma worsened organ function without affecting brain
histopathology. [Conclusions]         Suspended animation with delayed resuscitation represents a
revolutionary approach to resuscitation of the trauma victim with otherwise lethal exsanguination cardiac
arrest.   Our studies suggest additional benefit from the combination of antioxidants with hypothermia
and challenge the previously posed limits of hypothermic protection and preservation of the brain.       In
ongoing studies we are testing suspended animation after prolonged shock, evaluating the mechanisms of
hypothermic protection using proteomics, and probing beyond the 2 hr theoretical limit for cardiac arrest
duration with intact survival.
Supported by DAMD 17-01-2-0038 from the United Sates Army
*Dr. Peter Safar died on August 3, 2003.     This presentation is made in his honor.




                                                 61
                                                                   Lecture -- Postresuscitative Hypothermia
L-8                                                                                         February 5 (Thu)
                                                                                                   TENKU-A

Hypothermia after cardiac arrest: An update

Stephen A. Bernard MD FACEM FJFICM
The Intensive Care Unit, Dandenong Hospital, David St Dandenong Victoria, Australia


Following resuscitation from out-of-hospital cardiac arrest, most patients remain comatose due to the
anoxic brain injury (1).      Recent clinical studies have suggested improved outcome if hypothermia
(32°C-34°C) is induced following resuscitation from pre-hospital cardiac arrest and maintained for 12-24
hours (2,3,4) and this treatment is now endorsed by the Advanced Life Support Committee of ILCOR (5).
Previous studies (3,4) used surface cooling with ice packs or cooling blankets to induce hypothermia and
it was found that this technique leads to core cooling at a rate of only 0.4°C-0.9°C per hour. Surface
cooling is also inconvenient for medical and nursing staff and restricts the use of hypothermia to the
in-hospital environment.      Since there is evidence of improved outcome if hypothermia is induced
immediately after resuscitation from cardiac arrest, alternative strategies for rapid induction of
hypothermia are required.
We have recently studied the use of a rapid infusion (100 ml/min) of large-volume (30 ml/kg), ice-cold
(4°C), intravenous crystalloid fluid in 22 patients and have found that this technique induces mild
hypothermia over 25 minutes (6). In addition, there were significant improvements in vital signs and
biochemical parameters, without pulmonary edema.
We are currently using this approach in the pre-hospital setting in cardiac arrest patients. After successful
return of a spontaneous circulation, paramedics administer a muscle relaxant followed by 2000 ml of
ice-cold crystalloid fluid.   Further cooling measures are then undertaken in the Emergency Department.
References:
(1). Bernard SA. Emerg Med 1998; 10:25
(2). Bernard SA et al. Ann Emerg Med 1997; 30:146
(3). Bernard SA et al. NEJM 2002; 346:557
(4). HACA study group. NEJM 2002; 346:549.
(5). Nolan et al. Circulation 2003; 108:118
(6). Bernard SA et al. Resuscitation 2003.




                                                 62
                                                                 Lecture -- Postresuscitative Hypothermia
                                                                                          February 5 (Thu)
                                                                                                 TENKU-A
L-9

Hypothermia after cardiac arrest

Michael Holzer, M.D.
University of Vienna, Vienna General Hospital, Wien, Austria


Sudden death from cardiac arrest is a major health problem that still receives too less publicity. Current
therapy after cardiac arrest concentrated on resuscitation efforts as until now no specific therapy for brain
protection after restoration of spontaneous circulation was available. Therapeutic mild or moderate
resuscitative hypothermia is a novel, etiology - specific therapy with multifaceted chemical and physical
effects by preventing or mitigating of all components of the post resuscitation syndrome derangement’s.
Recently two prospective randomized studies on hypothermia after cardiac arrest have shown improved
outcomes in comatose survivors after resuscitation. In the Australian trial 77 comatose survivors of
cardiac arrest of cardiac origin were randomly assigned to hypothermia (33° C, core temperature over 12
hours, cooled with ice packs) or normothermia. Of the 43 patients treated with hypothermia 21 (49
percent) survived and had a good neurological outcome as compared with 9 of the 34 treated with
normothermia (26 percent, P=0.046). The odds ratio for a good outcome with hypothermia after
adjustment for base-line differences was 5.25 (95 percent confidence interval, 1.47 to 18.76; P=0.011). In
the European multicenter trial patients after cardiac arrest due to ventricular fibrillation or pulseless
ventricular tachycardia were randomized to hypothermia therapy (32-34°C bladder temperature, cooled
with cold air, 24 hours) or to standard treatment with normothermia. Of the 136 patients in the
hypothermia group 75 (55 percent) had a favorable neurological outcome, as compared with 54 of 137
(39 percent) in the normothermia group (risk ratio, 1.40; 95 percent confidence interval, 1.08 to 1.81).
Mortality at six months was 41 percent in the hypothermia group (56 of 137 patients died), as compared
with 55 percent in the normothermia group (76 of 138 patients; risk ratio, 0.74; 95 percent confidence
interval, 0.58 to 0.95). In both studies the complication rate did not differ significantly between the two
groups. Several issues of resuscitative cooling are still unanswered and should be further studied. This
includes the best timing when to initiate cooling,           the optimal period of cooling, the optimal
temperature level and re-warming strategy. Even such important questions as which cooling technique
will be available in the near future, which should combine ease of use with high efficacy are not answered
yet.
Despite this unsolved questions and following the recommendations of the ILCOR ALS Task Force all
unconscious adult patients with spontaneous circulation after out-of-hospital cardiac arrest should be
cooled to 32-34 °C for 12-24 h when the initial rhythm was ventricular fibrillation. Such cooling may also
be beneficial for other rhythms or in-hospital cardiac arrest.




                                                 63
                                                                   Lecture -- Postresuscitative Hypothermia
                                                                                            February 5 (Thu)
                                                                                                   TENKU-A
L-10

B-type natriuretic peptide for advanced challenge in therapeutic hypothermia

Ken Nagao1, Nariyuki Hayashi1, Katsuo Kanmatsuse2, Kimio Kikushima2, Kazuhiro Watanabe2,
Kiyoshi Iida2, Takeo Mukoyama1, Yoshiteru Tominaga1, Katsushige Tada1, Mitsuru Ishii1, Nobutaka
Chiba1
Department of Emergency and Critical Care Medicine1, Cardiology2, Nihon University School of
Medicine, Tokyo, Japan


  Background     In 2002, two randomized studies of therapeutic hypothermia after            out-of-hospital
cardiac arrest, one in Europe and the other in Australia, showed a neurologic benefit with a low risk of
complications. However, no studies on cardiac neurohormone of B-type natriuretic peptide (BNP) are
available for patients treated with hypothermia.
  Methods We conducted a prospective study of 109 patients treated with mild hypothermia          (34     for
2 days or more) by extracorporeal cooling methods whose BNP was measured                  on arrival at the
emergency room after suffering out-of-hospital cardiac arrest due to cardiac causes, and who were treated
with emergency cardiopulmonary bypass and/or emergency coronary revascularization if needed. The
primary endpoint was a favorable neurologic outcome at the time of hospital discharge.
  Results A total of 45 of the 109 patients had a favorable neurologic outcome, and the BNP level was
lower among these patients than among those who had an unfavorable neurologic outcome (median, 30
vs 243 pg/ml; p<0.001). The BNP levels from 2 to 1510 pg/ml, with a mean (±SD) of 227±301 pg/ml, a
median of 119 pg/ml, and 25th and 75th percentile values of 30.4 and 278 pg/ml, respectively. The
unadjusted rate of the primary endpoint decreased in a stepwise fashion among patients in increasing
quartiles of BNP levels with quartile 1 at 85.2% vs. quartile 2 at 55.6% vs. quartile 3 at 21.4% vs. quartile
4 at 3.7% (p<0.001). This association remained significant in subgroups of patients with witnessed arrest
by bystander, bystander-initiated cardiopulmonary resuscitation, ventricular fibrillation or pulseless
ventricular tachycardia as the initial cardiac rhythm and cardiac arrest due to acute coronary syndrome
(p<0.001, respectively). The accuracy of BNP for primary endpoint at a cutoff of 80 pg/ml was 87.2%.
The negative predictive value of BNP at levels of 300 pg/ml or more was100%. In a multiple
logistic-regression analysis for independent predictors of the primary endpoint, a BNP value of more than
80 pg/ml was the strongest independent predictor of an unfavorable neurologic outcome with an adjusted
odds ratio of 131.
  Conclusions        The measurement of BNP was found to provide valuable information regarding the
neurologic outcome in patients treated with mild hypothermia after resuscitation from cardiac arrest due
to cardiac causes. This study may therefore extend the boundaries for the usefulness of therapeutic
hypothermia after cardiac arrest.




                                                   64
                                                                              Lecture -- Cooling Technique
                                                                                           February 5 (Thu)
                                                                                                  TENKU-A
L-11

Treatment of refractory fever in the neurosciences critical care unit using a novel,
water-circulating cooling device: A single center pilot experience

J. Ricardo Carhuapoma, MD*‡¶; Kapil Gupta, BS*; William M. Coplin, MD*‡¶;
Salman M. Muddassir, MD*; Muhammad M. Meratee, MD*.
Neurosciences Critical Care Program‡, Departments of Neurology* and Neurological Surgery¶, Wayne
State University School of Medicine, Detroit, Michigan.


Acknowledgments:
• The authors thank the attending physicians, residents, fellows and nursing staff of the Neuroscience
Critical Care Unit at Detroit Receiving Hospital for their help in the management of these patients.
• The authors wish to gratefully acknowledge the continuous support by Medivance for this study by
providing the Arctic Sun™ Temperature Management System used in this study.
• Dr. Coplin supported in part by NIH NINDS 1R01 NS38905


Abstract:
Summary: Fever after acute brain injury affects neuronal function and recovery. Standard therapies have
proven to be inadequate in treating hyperthermia in this patient population. We report on safety/efficacy
pilot data collected using a non-invasive, novel, water-circulating cooling device in febrile acute brain
injury patients. From February to May 2002 we enrolled patients who developed fever (rectal temperature
≥ 38°C) refractory to pharmacological therapy. The treatment device uses an ice water circulating system
embedded in hydrogel coated, energy transfer pads. Its thermoregulatory feedback control uses cold water
(4-42°C) and was set at 36.5°C for this study. We analyzed the temperature response during 600
consecutive minutes of treatment. Six consecutive patients were enrolled and 7 episodes of fever were
recorded, mean age: 59.7 (46-71) years, M/F ratio 5:1. Diagnoses were: Subarachnoid hemorrhage (2),
severe traumatic brain injury (2), massive cerebral infarction (1), and intracerebral/intraventricular
hemorrhage (1). Hand warming was applied at treatment onset on all patients, shivering only responsive
to meperidine occurred in 5 of them. Fever of 38.4 (38-38.9)°C was reduced to 36.9 (36-38)°C after 120
minutes (p<0.001). Core temperature remained “locked” during the remaining of the treatment (36.6°C,
p=0.5; 36.6°C, p=0.9; and 36.5°C, p=0.9 at 180, 300 and 600 minutes, respectively). Skin integrity under
the pads was preserved in all study subjects. Our results indicate that use of this novel technique is safe,
rapidly effective and able to maintain sustained normothermia following fever in a cohort of critically ill
neurological/neurosurgical patients.




                                                 65
                                                                             Lecture -- Cooling Technique
                                                                                          February 5 (Thu)
L-12                                                                                             TENKU-A


Methods of cooling on the Neuro ICU

Stefan Schwab M.D.
Department of Neurology, University of Heidelberg


Trauma subarachnoid hemorrhage cerebrovascular disease and spontanial intracranial hemmorhage cause
severe brain injury. Several studies could show that fever in association with the neuronal injury leads to
a significant worsening of the clinical course. Recent data show, that lowering the patients temperature
has therapeutic benefits, for instants after cardiac arrest, and some subtypes of traumatic brain injury.
Conventional treatment for fever in the ICU usually is done “reactive," the therapy consists of
Acetaminophen or other antipyretic drugs given either orally or rectally. There is a lot of controversy
about the effectiveness of such techniques. In the last few years intravascular cooling technique has
shown to be easily manageable and effective. The so-called "fever burden" is less than in the group of
patients treated with conventional fever management.
Compared to surface cooling intravascular cooling seems to be more effective and better to control.
Based on phase I trials it appears that intravascular cooling is a promising new method for avoiding fever
in the neuro ICU.




                                                66
                                                                             Lecture -- Cooling Technique
                                                                                          February 5 (Thu)
L-13                                                                                             TENKU-A


ICU management of brain hypothermia

R. Bullock, M.D., Ph.D., Reynolds Professor
Department of Neurosurgery, Virginia Commonwealth University Health System


Introduction
The use of hypothermia as a therapeutic modality for preventing secondary brain damage in traumatic
brain injury global brain ischemia (cardiac arrest), and stroke remains highly controversial.        Recently,
two important clinical trials in traumatic brain injury have shown negative results for prophylactic
hypothermia for traumatic brain injury.     In contrast, however, two major international trials have shown
positive results for early hypothermic treatment of out-of-hospital cardiac arrest – global brain ischemia.
In spite of these controversial results, hypothermia is effective in the control of intracranial pressure after
TBI, and is in widespread use in many centers. Although mild hypothermia is associated with few
major complications, moderate hypothermia carries significant risks and demands rigorous intensive care
management.       These will be reviewed in detail.
Methods of Moderate Hypothermia
Traditionally, surface cooling with ice water blankets, alcohol sponging, fans, and gastric ice water lavage
have been used to achieve hypothermia.        Laboratory and clinical information indicates, however, that
the rapidity of onset of cooling is important in achieving the best results, and that cooling should be
attempted as early as possible after the patient is injured.       New technologies have, therefore, been
developed such as the “inner-cool” catheter, and other technologies which allow rapid cooling
piezoelectric technologies to be linked with a vena cava catheter. This allows cooling as rapidly as 1˚ per
hour.   Such catheters can be implanted in the emergency room, and can allow intraoperative cooling also.
Trials are underway to demonstrate the feasibility and safety of the use of such devices.
Duration of Cooling
Cooling should be started as early as possible, but the optimal duration of cooling to improve outcome is
unknown.       Therapeutic hypothermia to control ICP usually requires several days of hypothermic therapy,
while cardiac arrest cooling periods may be shorter.
Monitoring – In addition to standard critical care monitoring, optimal monitoring will include a brain
temperature sensor and a core body temperature sensor, e.g. a bladder sensor, or a thermastore associated
with a Swan-Gins catheter.
Experience has shown that brain temperature, which is the target temperature, may lag up to 1˚ behind
body core temperature, and that the wider this differential, especially in traumatic brain injury cases, the
worse the prognosis. This is because brain temperature is determined to a large extent by the degree of
cerebral blood flow.
In addition to invasive brain temperature monitoring, ICP monitoring is mandatory in patients with
traumatic brain injury, and may also be desirable in those with global ischemia and brain swelling as
judged by CT scan. More recently, brain oxygen tensions, and microdialysis monitoring have been used
and give useful information about the effects of hypothermia on the brain.In addition, during cooling and

                                                  67
re-warming periods, electrolytes must be checked at least every 6 hours, to prevent potassium and sodium
shifts, which may cause dangerous arrthymias if not rapidly corrected.   Central venous line and arterial
lines are mandatory in such patients also.       EEG monitoring is useful, especially when adjunctive
sedation with propofol or barbiturates is to be used.
Dangers and Complications of Moderate Hypothermia
These include “over shoot severe hypothermia (less than 33˚C), electrolyte abnormalities especially hyper
and hypokalemia, cardiac arrhythmias, occult severe infections, and renal failure. Such complications
make be especially frequent when hypothermia is combined with barbiturate therapy, ammino glycoside
antibiotics, and frequent mannitol use.   Nursing personnel and ICU physicians must be educated about
how to carry out surveillance for such complications – for example, blood cultures every 24 or 48 hrs are
mandatory. Methods for correcting hyperkalemia (insulin glucose infusion) must be readily available.
Kayexylate resin may also be used, to reduce dangerously high potassium levels.
Re-Warming – Re-warming must be slow, e.g. over 2-3 days.      If this is not observed, over-shoot increase
in ICP may occur, and electrolyte shifts become more likely.
Conclusion – There is an urgent need of a large scale randomized controlled trial of therapeutic moderate
hypothermia, for control of intracranial pressure after TBI.        In addition, hypothermia trials in
subarachnoid hemorrhage and stroke are on going. The results of these are awaited.




                                                 68
                                                                                           Lecture -- Stroke
                                                                                            February 5 (Thu)
                                                                                                   TENKU-A
L-14

Hypothermia in the therapy of ischemic stroke

Stefan Schwab M.D.
Department of Neurology, University of Heidelberg
Im Neuenheimer Feld 400, 69120 Heidelberg, Germany


The first clinical trial on the effect of MH (33° Celsius) in patients with severe MCA infarction was
published in 1998. Hypothermia was induced at a mean of 14 hours after symptom onset and maintained
over 72 hours. Mortality was only 44%, while survivors reached a favorable outcome, with a mean
Barthel index of 70, despite the fact that all patients fulfilled the criteria for diagnosis of a "malignant"
MCA infarction. Although hypothermia significantly reduced ICP, a secondary rise of ICP, occasionally
exceeding initial ICP levels and requiring additional treatment with osmotherapeutics was observed on
rewarming. Similar results were recently published from a multicenter observational study, which
described 50 prospective patients with cerebral infarction involving at least the complete MCA territory
treated with MH (33° Celsius). Overall mortality was 38%, divided in 8% during hypothermia and 30%
during rewarming, due to uncontrollable ICP increase. Neurological outcome was 28 (NIHSS) and 2.9
(Rankin scale) 4 weeks and three months after stroke, respectively. Krieger et al reported initial results
from 10 patients with acute ischemic stroke (NIHSS 19.8±3.3), who were treated with MH (32° Celsius)
after thrombolysis. Mortality was 33%, while the mean modified Rankin Scale score at 3 months was
3.1±2.3. Pneumonia was the only severe side effect of MH in the study of Schwab et al. The most
frequent complications of MH described in the multicenter trial described above were thrombocytopenia
(70%), bradycardia (62%) and pneumonia (48%). Four patients (8%) died during hypothermia, due to
severe coagulopathy, cardiac failure or uncontrollable intracranial hypertension.
Hemicraniectomy (CE) and MH constitute promising treatment modalities for space occupying cerebral
infarction. Up to date, only one study has compared their effectiveness in controlling intracranial
hypertension and reducing mortality. A total of 36 patients with severe acute ischemic stroke were treated
with CE (n=17) or MH (n=19). Mortality was 12% for CE and 47% for MH, respectively, whereby one
patient treated with MH died on treatment complications (sepsis) and 3 on ICP crises, which occurred
during rewarming. It was concluded that in patients with acute ischemic stroke CE results in a lower
mortality and lower complication rates as compared to MH. Still, this result remains to be confirmed in
large-scale trials.




                                                 69
                                                                                      Luncheon Seminar
                                                                                         February 6 (Fri)
                                                                                              TENKU-A
L-15

Neurotrauma management of the head injured patient: Pathophysilogy and treatment

A Marmarou, Ph.D.
Founder of the American Brain Injury Consortium, Professor and Vice- Chairman of Neurosurgery at the
Medical College of Virginia, Virginia Commonwealth University.

The contribution of brain edema to brain swelling in cases of traumatic injury, ischemia and tumor
remains a critical problem for which there is no effective clinical treatment at present. It is well
documented that in head injury, swelling leads to elevations in intracranial pressure which are a frequent
cause of death, and very poor prognosis in survivors
Our experimental and clinical studies provide strong evidence that edema is primarily responsible for the
swelling process. For the past several decades, it has been generally accepted that the swelling process
accompanying traumatic brain injury is mainly due to vascular engorgement with blood volume providing
the increase in brain bulk and subsequent rise in ICP. Edema was thought to play a minor role. However,
our recent findings indicate that edema and not vascular engorgement is responsible for brain swelling
and that blood volume is actually reduced following TBI Thus it is important to shift our attention to
brain edema and understand the pathophysiological mechanisms responsible for water movement into
brain.
 Traumatic brain injury triggers a cascade of events including mechanical deformation, neurotransmitter
release mitochondrial dysfunction and membrane depolarization which lead to alterations in normal
ionic gradients. Excitatory Amino Acids (EAAs) released via mechanical deformation and membrane
depolarization activate ligand-gated ion channels, which allow ions to move down their electrochemical
gradients. In addition, membrane depolarization resulting from ionic flux and trauma trigger
voltage-sensitive ion channels, providing further routes for ionic movement . These ionic disturbances are
identified by an increase in extracellular potassium ([K+]ecs) with a concomitant decrease in extracellular
sodium ([Na+]ecs), calcium, and chloride. In traumatic brain injury, the initiating factors which result in
the movement of ions, may differ from those primarily responsible in ischemia. For example, ATP
reduction may not be due to decreased CBF since blood flow in TBI persists and delivery of substrate is
maintained
We hypothesize that mitochondrial dysfunction prevents the restoration of ionic and cell volume
homeostasis. .NAA was discovered in 1956 by Tallan, More and Stain and is represented by the
largest peak in a proton spectra (1H MRS). It is synthesized in mitochondria from L-aspartate and
acetyl-CoA in a reaction catalyzed by an N-acetyltransferase NAA has been found histochemically to be
a constituent of neurons and axons with lesser amounts in glial cells. Large numbers of studies show
NAA absent or reduced in brain tumor (glioma), ischemia, degenerative disease and inborn errors of
metabolism. and it is accepted fact that NAA levels correspond to tissue damage. Studies of NAA in
severe brain injury are relatively few and the temporal course of NAA changes in trauma in association
with ADC values has not been studied.         As NAA is synthesized by the mitochondria, it is reasonable
to posit that reduced tissue NAA will be associated with regions of low ADC, low ATP, ionic dysfunction
and brain edema. This presentation will descriabe the most recent information available on NAA
reduction in human head injury and the implications with regard to management of the head injured
patient.




                                                70
                                                                                            Lecture -- Pediatrics
                                                                                                 February 6 (Fri)
L-16                                                                                                   TENKU-A


Moderate hypothermia in children following severe TBI

P. David Adelson, MD
Dept. of Neurosurgery, University of Pittsburgh, Pittsburgh, PA, USA


  Despite preventative measures, traumatic brain injury (TBI) remains the leading cause of death and
disability in children. Laboratory studies of hypothermia (HYPO) in experimental models have
consistently shown it to be neuroprotective and efficacious in alleviating secondary brain injury and
swelling typically seen following acute brain insults including TBI. HYPO following adult experimental
TBI has been shown to reduce behavioral deficits, lessen mortality, and reduce histologic damage; lower
temperatures (30°C) being more effective than 33°C or 36°C. Although the mechanism(s) by which
HYPO preserves tissue, improves physiology, and/or enhances outcome have not been clearly established,
HYPO is believed to attenuate the numerous pathophysiologic responses and biochemical cascade that
potentiate secondary brain injury. HYPO has been shown to attenuate high levels of glutamate,
acetylcholine and dopamine, to preserve the blood brain barrier and reduce cell death, and to diminish the
inflammatory response. While most of these studies have been in adult animal models, we and others
have shown efficacy of HYPO in experimental models of TBI in the immature with re: to behavior,
biochemical, molecular, and histologic outcomes, as well as observed age at injury and long lasting
effects, and efficacy despite delay in initiation of treatment.
  Clinical studies of HYPO after TBI in children have been limited. There has been previous success of
adult Phase II and III studies after TBI and trials in children of HYPO following hypoxia-ischemic brain
injuries. While the recent adult trial of HYPO did not show overall efficacy, younger patients tended
toward improved outcome compared to older patients. Recently we studied 48 h of HYPO following
severe TBI in children. Of 46 patients randomized, [HYPO (n=22), NORM (n=24)], the mean time to
cooling initiation= 4.8+1.3 h (mean+SD) and mean time to target temp (33°C) = 7 h from injury. There
was a mean of 2 deviations (>2oC) from target temp/ patient and mean time to complete re-warming= 22h.
Our results to date have not shown differences between HYPO and NORM with re: to complications:
coagulation parameters-average PT/PTT (HYPO) 14.6+3.2/ 31.3+4.0 sec, (NORM) 13.6+1.2/ 29.5+3.9
sec; arrhythmia- HYPO- one incident of infrequent ventricular ectopy, resolved spontaneously without
intervention, re-warming not required, o/w no other EKG abnormalities or cardiac arrhythmias; mortality-
HYPO- 2 deaths, NORM- 5 deaths. External review has indicated no safety concerns. Additionally,
HYPO lowered mean (+SD) ICP acutely after injury (<72h), HYPO 13.2+2.9 mmHg, NORM 17.8+2.5
mmHg.
  While promising, HYPO following TBI in children remains to be studied in a multicenter randomized
trial to determine potential efficacy. Stratification by age, time to cooling, and severity will be required.




                                                  71
                                                                                      Luncheon Seminar
                                                                                         February 6 (Fri)
                                                                                              TENKU-B
L-17

The management of cerebral stroke by brain hypothermia treatment

Thorsten Steiner, MD PhD
University of Heidelberg, Germany


There are 2 main objectives of hypothermia in stroke patients: neuroprotection and treatment of elevated
intracranial pressure. It is important to have these in mind, because they influence criteria that
characterize certain features of hypothermia like the method used, time until hypothermia should be
initiated, complications and supportive treatment. The first method, which was successfully used in stroke
patients, was surface cooling. Treatment target was elevated intracranial pressure (ICP) in patients with
space occupying infarction of the middle cerebral artery (MCA). This study was successful in lowering
ICP. However, the re-warming period was the crucial point, when one fifth of the patients died from
transtentorial herniation because of ICP crises. Better control of ICP and cerebral perfusion pressure
could be achieved, when re-warming was performed in a controlled fashion. The neuroprotective effect of
hypothermia has not been proven in a prospective study yet. Though there are a couple of supportive
uncontrolled small studies. One other problem is the physiological reaction of the patient to the cold.
Discomfort, shivering, and agitation have been the reasons for that patients had to intubated and
mechanically ventilated. These were the reasons for the high rate of infectious complications. With the
application of new anti-shivering protocols intubations may not be necessary in the future for performing
hypothermia.




                                                72
                                                                                      Lecture -- Monitoring
                                                                                           February 6 (Fri)
                                                                                                  TENKU-B
L-18


Important regional differences in brain tissue susceptibility to secondary damage after
traumatic brain injury

Ungerstedt U
Dept of Physiology and Pharmacology, Karolinska institute, Stockholm


INTRODUCTION: The treatment of patients with Traumatic Brain Injury (TBI) is relying on the
monitoring of global parameters such as ICP and CPP. CT is the only technique that routinely provides us
with an understanding of the extent and severity of regional damage. However, none of these techniques
provide information on differences in regional energy metabolism and sensitivity to secondary insults
during the course of intensive care. However, the technique of microdialysis offers a unique opportunity
to monitor the regional availability of glucose and the effect of ischemia and hypoglycaemia on local
brain biochemistry. This paper is an account of 50 patients studied with gold tip microdialysis catheters
visible on CT.
METHODS: Microdialysis catheters (CMA70) were routinely implanted in all patients with severe
traumatic brain injury. The catheter was inserted into cerebral cortex via a separate burr hole in front of
the ICP catheter (“better” tissue). In patients with focal brain lesions catheters were inserted into the
“penumbra” defined as a region about 1 cm from the border of the lesion. Samples were analysed every
hour on a bedside analyzer. The Lund University ethical committee has approved of the use of
intracerebral microdialysis as a routine procedure during neurointensive care.
RESULTS: The pathology of brain tissue was evaluated by analyzing glucose (hypoglycaemia), the
lactate/pyruvate ratio (ischemia, redox state) and glycerol (cell membrane degradation) in the dialysate.
Our results show a pronounced difference in the sensitivity of brain tissue in “better” locations as
compared to the penumbra tissue. Changes in e.g. CPP, ICP, hematocrit and periods of seizures that had
no effect on brain chemistry in the “better” tissue had severe pathological effects on lactate/pyruvate ratio
and glycerol levels in the penumbra.
CONCLUSION: Our results demonstrate a great heterogeneity in the pathology of brain tissue after TBI.
Relatively small changes in e.g. CPP have profound effects on the vulnerable penumbra tissue. Local
monitoring of penumbra tissue in the brain of TBI patients gives an early warning of imminent secondary
damage and helps the clinician to individualize the treatment of the patient. It is suggested that
microdialysis monitoring of penumbra tissue may be the best way to evaluate the effect of hypothermia
on the survival of vulnerable brain tissue. Furthermore, we consider it axiomatic that improved tissue
outcome as evaluated by microdialysis translates into improved patient outcome after TBI.




                                                 73
                                                                                  Lecture -- New Therapies
                                                                                             February 6 (Fri)
L-19                                                                                              TENKU-B


Brain hypothermia treatment and a Synchronized Musico- Kinetic therapy (SMK)

Ryo Noda
Department and Institution / Arts Planning Department, Osaka University of Arts


Introduction
As for the Synchronized Musico-Kinetic therapy (SMK), the effect was checked as a treatment of a
Persistent Vegetative State patient.
However, it is the present conditions that a treatment effect before society returning is not provided.
It includes the cause that time was over a treatment by enforcement from the onset.
Furthermore, it is supposed that the reason is because function recovery of a brain cannot attend it only
by an operation of conventional surgery.
Thus I thought that a treatment effect was provided more if I executed SMK from Brain hypothermia
treatment and subacute period we protected a brain function as a new treatment strategy, and to treat.
A method
I made a common use of it by progress time from the onset traumatic this time to a treatment and
compared Synchronized Musico- Kinetic therapy (SMK) of a patient only for a treatment of conventional
surgery with a patient of the Brain hypothermia treatment back.
A result
By a conventional therapy, recovery of an intellectual function included a limit, and, as for the patient
who underwent a Brain hypothermia treatment for it, recovery was early, and, besides, intellectual
understanding and recovery of a body function were raised more.
A conclusion
We can save a lot of persistent vegetative state patients by the Brain hypothermia treatment and
Synchronized Musico- Kinetic therapy (SMK).




                                                 74
                                                                            Lecture -- New Therapies
                                                                                       February 6 (Fri)
                                                                                            TENKU-B
L-20

The prevention of vegetation and memory disturbances for severe brain damage by
combination of brain hypothermia and intracerebral dopamine replacement therapy.

Hayashi N. Moriya T, Kinoshita K, Utagawa A, and Sakurai A
Department of Emergency and Critical Care Medicine, Nihon University School of Medicine,
Tokyo, Japan


The prevention of vegetation after severe brain damage by trauma, stroke, hypoxia and cardiac arrest is
major issue on the brain hypothermia treatment. The finding of mechanism of fall in vegetation and
diagnostic method for reversibility from vegetate state are necessary for success of brain hypothermia
treatment. The clinical signs and symptoms, electrophysiological changes (EEG, trend EEG, evoked
potential for N20 and auditory brain stem response), CSF chemical analysis such as neuron-transmitters,
hypothalamus-pituitary adrenal hormones and NO2/NO3 ratio, brain tissue metabolism by microdialysis
analysis, sequential CT and MRI changes of the hippocampus and amygdale nucleus, and responsiveness
by music therapy and median nerve stimulation were studied on 500 cases who received brain
hypothermia treatment.
These multiple meta-analysis suggested that diffuse cortical brain mantle brain damage and
simultaneously selective brain damage of hippocampus and amygdale nucleus is main reasons of
occurrence of vegetation. As causes of promoting factors for damage of these specific areas,
selective radical damage of dopamine A10 nervous system by dopamine release, stress
associated insulin resisting hyperglycemia, neuronal hypoxia by hemoglobin DPG reduction, and
elevation of brain tissue temperature by brain thermo-pooling were demonstrated at acute stage.
Therefore the induction timing of hypothermia, quality of brain hypothermia treatment, suitable
management for stress associated brain injury mechanism and prevent of release of dopamine
with anti-radical treatment for selective damage of dopamine A10 nervous system are important
for prevent of vegetation at acute stage. After acute stage, the reversibility from vegetate state
and memory disturbances are diagnosed by responsiveness of dopamine A10 nervous system.
The elevation of prolactin / dopamine ratio in CSF by treatment, no finding of severe low density
of hippocampus and amygdale nucleus on CT, presence of responsiveness of emotional muscles
around mouth or eye, and elevation of neurotransmitters in CSF are good criteria for reversibility
from vegetate state. The cerebral dopamine replacement therapy by combination of
pharmacological treatment such as amantadine and dopamine, patch therapy of estrogen, median
nerve electrical stimulation and emotional stimulation by music is useful for presence of good
criteria as described previously. However, effectiveness of these therapies in chronic stage was
limited in who received early induction of brain hypothermia treatment. The clinical result of
severe brain trauma demonstrated very limited fall in vegetation; 1 of 21 (5%) in GCS 4, 2 of
27(7%) in GCS5, and 2 of 38 (5%) in GCS. In brain resuscitation after cardiac arrested, social
recovery was 25/52 (48%), mild disability was 1/52(2%), severe disability was 1/52 (52%),
vegetate state was 11/52 (21%) and death was 45/52 (27%).

                                              75
                                                                     Oral Presentations (selected papers)
                                                                                             Neurotrauma
                                                                                         February 5 (Thu)
O-1                                                                                             TENKU-A


Clinical evaluation of mild hypothermia for severe head-injured patients

Miyagi T, Shiomi N, Karukaya T, Tokutomi T, Shigemori T
Department of Neurosurgery, Kurume university school of Medicine, Fukuoka, Japan


  Purpose The effects of neuroprotection by hypothermia and barbiturate were studied in 82 patients
with GCS score of 5 or less at admission managed by 3    different protocol between 1989-2003.
  Material and methods      24 patients received barbiturate (1989-1994), 31 patients with moderate
hypothermia (33     of brain temperature, 1995-1999), and 27 patients with mild hypothermia (35        of
brain temperature, 2000-2003) in the acute stage of injury. Among these 3 groups of patients, the effect
on ICP, CPP and other variables and the outcomes were studied comparatively.
  Results    There were no significant differences between the three groups in age and severity of injury.
Maintenance of mean ICP and CPP were better in the groups of hypothermia than those with barbiturate.
There were no significant differences between three groups in hematological findings and frequency of
systemic complications. Although there were no significant difference in the overall outcomes between
three groups, the rate of favorable outcome was much higher in the group with mild hypothermia than
those with moderate hypothermia and barbiturate.
  Conclusion Moderate and mild hypothermia favorably affect on ICP and CPP and mild hypothermia
possibly improve the patients outcome.




                                               76
                                                                    Oral Presentations (selected papers)
                                                                                            Neurotrauma
                                                                                        February 5 (Thu)
O-2                                                                                            TENKU-A


The use of mild hypothermia in the prevention of the secondary brain injury

Martin Smrčka1, Milan Vidlák1, Karel Máca1, Vladimír Smrčka1, Roman Gál2
Neurosurgical Department, University Hospital Brno, Czech Republic1, Anaesthesiological Department,
University Hospital Brno, Czech Republic2


Introduction: The influence of therapeutic mild hypothermia on intracranial and cerebral perfusion
pressure in severely head injured patients has been already proved, however, the effect on neurological
outcome has not. According to our hypothesis, only a subgroup of patients with a lesser extent of the
primary brain damage (particularly those with extracerebral hematomas) may benefit from this
neuroprotection.
Methods: We have prospectively analyzed 60 patients with severe head injury who were randomized into
a group with and without hypothermia (30 patients in each group). Hypothermia 34°C was maintained for
78 hours. The influence of hypothermia on ICP, CPP and neurological outcome 6 months after the injury
was analyzed in the context of the extent of the primary brain damage (patients with diffuse injuries and
primary lesions versus patients with extracerebral hematomas).
Results: Patients with normothermia and primary lesions (n = 12)- average values: GCS in admission:
4,66, ICP 18,3, CPP 73,7, GOS 3,5. Patients with normothermia and extracerebral hematomas (n = 18):
GCS: 4.0, ICP 16.7, CPP 70.9, GOS 2.88. Patients with hypothermia and primary lesions (n = 18): GCS
4.66, ICP 10.8, CPP 78.8, GOS 3.77. Patients with hypothermia and extracerebral hematomas (n = 12):
GCS 4.5, ICP 13.3, CPP 78.5, GOS 4.83.
Conclusions: Hypothermia was able to decrease ICP and increase CPP in both groups of patients
regardless to the type of brain injury. Hypothermia was not able to improve outcome in patients with
primary brain lesions, however it was able to significantly improve outcome in patients with extracerebral
hematomas who were threatened by the secondary brain damage.


Aknowledgement: This study has been supported by a grant of the Internal Grant Agency of the Ministry
of Health of the Czech Republic No. 6844-3.




                                                77
                                                                  Oral Presentations (selected papers)
                                                                                          Neurotrauma
                                                                                      February 5 (Thu)
O-3                                                                                          TENKU-A


Biphasic concentration change during continuous midazolam administration in
brain-injured patients undergoing therapeutic moderate hypothermia

Mayuki Aibiki and Noriyasu Fukuoka.
Dept of Emerg Med, Ehime Univ, Sch of Med, 454 Shitsukawa, Shigenobu, Onsen, Ehime.

Objective: To define the pharmacokinetics of midazolam, a probe for monitoring cytochrome 3A 4
activity, during moderate hypothermic therapy.
Design: A prospective randomized study
Setting: The intensive care unit of a medical university hospital
Patients and Interventions: In fifteen consecutive brain-injured patients, midazolam concentrations
were measured serially using high-performance liquid chromatography (HPLC). Under continuous
administration of the agent, eight patients underwent moderate hypothermia of 32-34 (hypothermia
group) and seven received normothermic therapy (normothermia group). A one-compartment model
was selected for pharmacokinetic analyses for the continuous administration. Data represent mean±SD.
Statistical analysis was performed using ANOVA followed by Scheffe's F-test or the Mann-Whitney
U-test (p<0.05).
Measurement and Main Results: Serum midazolam concentrations in the hypothermia group increased
linearly until the body temperature (BT) reached 35 without plateauing, even during continuous
administration, after which the levels decreased remarkably when BT rose to 36 . However, the
concentrations in the normothermia group remained on a plateau, which lasted until the end of the
study. In the hypothermia group, elimination rate constant (ke) and clearance (CL) in the phase below
35     BT were much lesser than those above 35 BT, whereas distribution volume (Vd) during the
hypothermic phase was greater than that during the period above 35      BT.
Conclusion: This study has demonstrated for the first time that midazolum concentration changes
biphasically even during continuous infusion in hypothermic therapy. The mechanisms for the change
are unclear. Thus, further studies including confirmation of cytochrome 3A 4 activity are required,
while monitoring for the development of undesirable effects from over-dosing is also needed.




                                               78
                                                                  Oral Presentations (selected papers)
                                                                        Postresuscitative Hypothermia
                                                                                      February 5 (Thu)
                                                                                             TENKU-A
O-4


Indication for brain hypothermic therapy in cardiac arrest patients

Kazuhisa Mori, Yoshihiro Takeyama, Hitoshi Kano, Masamitsu Kaneko, Yasufumi Asai
Department of Traumatlogy & Critical Care Medicine, Sapporo Medical University, Sapporo, Japan


[Objectives] Brain hypothermic therapy (BHT) improves neurological recovery after resuscitation from
cardiac arrest; although it has not yet been determined which patients are most likely to benefit from this
therapy. In 2000, we presented indications for BHT in cardiac arrest patients by a multivariate analysis of
prognostic factors. In the present investigation we sought to verify the indications for BHT in cardiac
arrest patients used in the prospective study.
[Materials and Method] In the 2000 study, we determined the indications for BHT in cardiac arrest
patients as arrest time of less than 20 min and GCS greater than 5. Patients were rapidly cooled by an ice
mounted blanket decreased to 34         within 2 hours, BHT (34 ) was continued for three days after
resuscitation, and the patient was then rewarmed 1 /day to 36       . We evaluated the patients in the ED
who conformed to the above criteria, in terms of neurological outcome (dead, vegetative state, severe
disabilities, moderate disabilities, good recovery) as measured by one-month Glasgow outcome scale
(GOS)
[Results] BHT was performed in the 15 patients (Age: 56.4+/-13.7, 10 male, 5 female) after resuscitation
from cardiac arrest. The average duration of time onset of cardiac arrest to return of heart beat was
29.3+/-12.6 min. Eleven patients obtain good neurological outcome (MD+GR/ 73.3%), no patient died
during BHT, and one patient died on 12th hospital day. This outcome rate (73.3%) was statistically the
same as the previous rate (70.6%) in the prospective study between 1996 and 2000.
[Conclusion] The results of this study confirmed that the hypothesized indications for BHT in cardiac
arrest patients employed in the previous prospective study (1996-2000) were adequate.




                                                 79
                                                                      Oral Presentations (selected papers)
                                                                                                    Stroke
O-5                                                                                        February 6 (Fri)
                                                                                                 TENKU-A

Body temperature in stroke: Secondary stress phenomenon or causal relationship?

Tom Skyhøj Olsen, Lars P. Kammersgaard, Uno J. Weber, Christian Fischer
The Stroke Unit, Hvidovre University Hospital, DK-2650 Hvidovre, Denmark


[Objective] Body temperature (BT) in stroke is thought to be directly related to stroke severity. Whether
increase of stroke severity is the result of raised BT or raised BT is a secondary phenomenon provoked by
the stroke is still debated.
We studied the relation between BT and time from stroke onset. If BT increases as a function of time
from stroke onset this would support the hypothesis that raised BT was the result of the stroke i.e. a
secondary stress phenomenon.
[Material and method] In 1155 consecutive unselected acute stroke patients (pts) BT was measured on
admission. An infrared aural thermometer was used. Clinical characteristics incl. stroke severity
measured by the Scandinavian Stroke Scale (SSS, 0-58), stroke subtype, and cardiovascular risk factor
profile were recorded on admission. Pts with infection diagnosed clinically or by chest X-ray or analysis
of urine, on the day of admission were recorded (4 patients had missing values).
[Results] Mean age was 74 ± 11 years, 46% were females, 9% had hemorrhagic stroke. Initial stroke
severity measured by SSS was 37 ± 17; severe (SSS < 30) in 32% and mild/moderate (SSS ≥ 30) in 68%.
Mean admission BT in all 1155 pts was 37.2 ± 0.7        . In pts admitted within 0-6 h (n=389) it was 37.2 ±
0.7   , within 6-12 h (n=166) 37.3 ± 0.7 , within 12-18 h (n=68) 37.0 ± 0.6        and after more than 18 h
(n=532) 37.3 ±     0.7 . In pts who had infection (n=224) mean admission BT was 37.7 ± 0.7 . In pts
admitted within 0-6 h (n=60) it was 37.8 ± 0.70 C, within 6-12 h (n=28) 37.8 ± 0.90 C, within 12-18 h
(n=20) 37.3 ± 0.6       and after more than 18 h (n=116) 37,8 ± 0.7 . In pts without infection (n= 927)
mean admission BT was 37.1 ± 0.6 . In pts admitted within 0-6 h (n=326) it was 37.1 ± 0.6           , within
6-12 h (n=138) 37.2 ± 0.6 , within 12-18 h (n=48) 36.9 ± 0.6        and after 18 h (n=415) 37.1 ± 0.6    . In
pts with severe strokes mean BT was 37.5 ± 0.9 ; with infection (34%) 37.8 ± 0.8               and without
infection (66%) 37.3 ± 0.9. No increase of BT over time was seen. In moderate/mild strokes mean BT
was 37.1 ± 0.5      , with infection (13%) 37.6 ± 0.7      and without infection (87%) 37.1 ± 0.5       . No
increase of BT over time was seen.
[Discussion] Clinically meaningful increase of BT did not occur within the first 18 h. Even in pts with
infection on admission BT did not change over time. BT in pts with severe and moderate/mild strokes
neither changed over time. Hence, our findings do not support the hypothesis that raised BT in stroke is
just a secondary stress response. BT was 0.2    higher in severe strokes without infection. As infection is
more frequent in severe strokes (34%><13%) this might reflect more subclinical infections instead of
being caused by the stroke lesion itself.




                                                80
                                                                    Oral Presentations (selected papers)
                                                                                                  Stroke
                                                                                         February 6 (Fri)
O-6                                                                                            TENKU-A


Neuroprotective effect of selective brain hypothermia (SBH) on permanent focal cerebral
ischemia in rats

Tamiki Taniguchi, Toru Matsui, Takao Asano
Department of Neurosurgery, Saitama Medical Center/School, Saitama, Japan


This study is aimed at examining whether the postischemic transient hypothermia is neuroprotective
against permanent cerebral ischemia in rats. A total of 81 male Sprague-Dawley (SD) rats were subjected
to the left proximal middle cerebral artery occlusion (MCAo) under general anesthesia and assigned into
3 groups (group A: hypothermia, n = 32; B: control, n = 29; C: sham, n = 20). In group A, rats received
selective brain hypothermia (SBH) for 6 hours with the use of a surface coil on the head. The temperature
of the basal ganglia was kept at 30       in the hypothermia group, in comparison with 36         in the
normothermia groups. In the hypothermia group, animals were further assigned into three subgroups
according to the time of sacrifice, 6 in A1, 48 in A2 and 168 hours in A* after MCAo. Also in the
normothermia groups, animals were divided into the above subgroups (B1, B2 and B*; C1, C2 and C*).
Neurological findings and body weights were recorded until sacrifice. Trans-cardiac perfusion fixation
was carried out at the end of each study. The fixed brain was sliced and stained by hematoxylin-eosin
(H-E) for measuring the volume of infarction. Data obtained from this study were analyzed with analysis
of variance (ANOVA), and a value of p < 0.05 was considered as statistically significant.
There were no significant differences in the physiological parameters except for the temperature among
the groups. SBH significantly attenuated hemispheric infract volume at each time-point after MCAo (6
hours, A1: 86 ± 25 vs. B1: 136 ± 15 mm3, p = 0.01; 48 hours, A2: 41 ± 19 vs. B2: 117 ± 33 mm3, p =
0.003; 168 hours, A*: 38 ± 21 vs. B*: 102 ± 41 mm3, p = 0.0001). Especially, SBH acted
neuroprotectively in both the cortex and the basal ganglia. These special remarks on methodology are
addressed in order to draw the usefulness of transient SBH against prolonged focal ischemia. The
temperature in the basal ganglia was declined to 30         within half an hour after MCAo and was
maintained at this level until 4 hours after the ischemia, then was kept below 34   until the end of SBH.
It is very important that the mean arterial blood pressure (MABP) is kept above 90 mmHg throughout
SBH. We conclude that postischemic transient hypothermia elicits its neuroprotection for a week even on
the present model of prolonged ischemia leading to a large infarction.




                                                81
                                                                   Oral Presentations (selected papers)
                                                                                                 Stroke
                                                                                        February 6 (Fri)
O-7                                                                                           TENKU-A


Ultra-early induction of brain hypothermia for patients with poor-grade subarachnoid
hemorrhage.

Hitoshi Kobata, Akira Sugie, Isao Nishihara, Hiroshi Morita
Osaka Mishima Emergency and Critical Care Medical Center, Takatsuki, Japan


[Background and purpose] Induced hypothermia has been recently applied in various neurological
emergencies, but its efficacy in subarachnoid hemorrhage (SAH) is unknown. We attempted to evaluate
the feasibility, safety, and potential of brain hypothermia for poor-grade SAH.
[Patients and Methods] Thirty-five prospective patients (14 men and 21 women; mean age 58 +/-
12years; range 25 to 70 years) with SAH classified in Grade V by World Federation of Neurosurgical
Society were included. Hypothermia was induced immediately after diagnosis of SAH with the use of
cooling blanket and nasogastric lavage with iced saline and was followed by urgent surgical obliteration
of the ruptured aneurysm. The body temperature was maintained at 33 to 34 degrees centigrade at least 48
hours; subsequently, patients were rewarmed 1 degree centigrade per day. Clinical outcome was assessed
with Glasgow Outcome Scale (GOS).
[Results] The Glasgow Coma Scale (GCS) at admission was 3 in fifteen, including five resuscitated from
cardiopulmonary arrest, 4 in three, 5 in nine, and 6 in eight patients. CT scan revealed diffuse thick SAH
in all patients, in addition, 12 of them showed massive intracerebral or subdural hematoma associated
with significant deviation of the midline structure. Blood glucose level of the patients, as an indicator of
systemic catecholamine surge, was 200 mg/dl in average. Electrocardiogram revealed specific change of
ST-T segment in 14 patients, 4 of them showed stunned myocardium. Median time from onset to arrival,
cerebral angiography, and surgery was 32, 86, and 171 minutes, respectively. The core temperature
(degrees centigrade, mean +/- standard deviation) was 35.8 +/- 1.0 on arrival, and reached 34.8 +/- 1.0
just before surgery, 34.0 +/- 0.7 at the beginning of microsurgery, and 33.7 +/- 0.8 at the end of surgery.
Hypothermia and aneurysm treatment were completed in all patients including those with
cardiopulmonary complications; duration of hypothermia was from 6 to 22 days, with a mean of 9.4 days.
GOS assessed 3 months after onset was as follows: four, good recovery (GR); six, moderate disability
(MD); nineteen, severe disability (SD); two, vegetative state (VS); four, death (D). Poor outcome was
mostly related to primary brain damage; and cerebral infarction due to vasospasm occurred in 4 patients.
[Conclusions] Our preliminary observation suggests that ultra-early induction of brain hypothermia is
feasible in patients with poor-grade SAH without increasing morbidity and mortality.




                                                 82
                                                                    Oral Presentations (selected papers)
                                                                                                  Stroke
                                                                                         February 6 (Fri)
O-8                                                                                            TENKU-A


The influence of mild hypothermia on the incidence of vasospasms in the patients after
severe subarachnoid hemorrhage

Smrčka M., M. Juráň V., Gál R., Smrčka V.
Neurosurgical Department, University Hospital Brno, Czech Republic


Objective: Vasospasms occur in 30% of patients after the subarachnoid hemorrhagie (SAH). The most
severe spasms are in patients with Hunt and Hess IV and V who have usually a lot of blood in the basal
cisterns. According to some reports, hypothermia could decrease the incidence and severity of
vasospasms in these patients.
Material: We have analyzed 15 patients (HH IV and V) after SAH from a ruptured intracranial aneurysm.
In 8 patients the aneurysm was coiled during the first 4 days, 3 patients were operated because of an
intraparenchymal hematoma and their aneurysm was clipped, other 4 patients were initialy treated
conservatively. In all patients mild hypothermia (34 °C for 78 hours) had been started immediately after
their admission by the means of cooling blankets. Monitoring of ICP (intraventricular), CPP and jugular
bulb oxymetry was instituted and everyday TCD examination was performed.
Results: ICP, CPP and jugular bulb oxymetry were maintained in the normal range in all patients. In 10
patients, however, (6 coiled and 4 conservatively treated) severe vasospasms with infarctions on the CT
scan occured (during day 5 and16 after SAH). TCD showed increased velocities only in 6 of these
patients. All 10 patients with vasospasms died within 6 months after SAH. 1 patient remained vegetative,
1 severely disabled and 3 had a good outcome (2 of them had intraparenchymal hematoma)
Conclusion: Hypothermia applied immediately after SAH does not seem to decrease neither the incidence
nor the severity of vasospasms in HH IV and V patients after SAH.


This study is supported by the grant of the Internal Grant Agency of the Czech ministry of health No
7671-3.




                                               83
                                                                       Oral Presentations (selected papers)
                                                                                                     Stroke
                                                                                            February 6 (Fri)
O-9                                                                                               TENKU-A


Mild hypothermic therapy: Its application and limitation as brain protection

Y. Kato, S. Harada, H. Sano, J. Hayashi, S. Watanabe, M. Yoneda, Sinha V. D. and T. Kanno
Department of Neurosurgery, Fujita Health University, Aichi, Japan


Introduction: Mild Hypothermic Therapy (MHT) can be used as an emergency medical service system to
rescue dying neuronal cells because it prevents thermopooling in the brain, inhibition of release of free
radicals and excitatory amino acids and prevention of increased intracellular Ca levels.
Objective: To elucidate the real advantageous effects, indications and pitfalls. We reviewed our cases
who underwent MHT so far with low GCS score (below 8) on admission. All the cases seem to be fatal
otherwise any other definitive therapeutic option might have been offered.
Method:       MHT was induced as quick as possible for the patients who manifested with low GCS score
at admission. Of these 21 cases were trauma, 30 poor grade subarachnoid hemorrhage and 18
hypertensive intracerebral hemorrhage. Thirty nine cases underwent either of surgical procedure, clipping
of aneurysm or endovascular coil embolization using GD coil and hematoma evacuation whereas other
cases treated conservatively. The patients temperature was kept around 34 degree Celsius through the
blanket roll covering over the body for three days and rewarming started through approximately five days
until the original temperature. Monitoring parameters were intracranial pressure jugular venous oximetry,
cerebral temperature and cardio-pulmonary monitoring. Immunological activity and free radical products
were evaluated in some cases. New monitoring parameter collecting machine was introduced to calculate
and summarize.
Results: One quarter of the cases had favorable outcome especially young patients whereas three quarter
had poor outcome. Quick induction had favorable outcome.
Conclusion: MHT is recommended for the therapeutic option for brain resuscitation under certain
conditions.




                                                84
                                                                    Oral Presentations (selected papers)
                                                                             Intraoperative Hypothermia
                                                                                          February 6 (Fri)
O-10                                                                                           TENKU-A


Hypothermic anesthesia in surgery for cerebral aneurysm

Akira Satoh*, Hiroshi Nakamura**, Akihiro Miyata**, Shigeki Kobayashi**, Masao Matsutani*
*Department of Neurosurgery, Saitama Medical School,
**Department of Neurosurgery, Chiba Emergency Medical Center


  Purpose     There might be numbers of insults to the brain caused by surgical manipulations to the brain
tissue and/or vascular structures during aneurysm surgery.   Those are ischemic ones by using temporary
clips or compressing large veins, or mechanical one by retracting the brain. Hypothermic anesthesia
(HTA) can be used not only as a pre-morbid protective aid for these surgical insults but also as an early
brain protection for vulnerable brain tissue damaged by subarachnoid hemorrhage (SAH) in case of acute
surgery for ruptured aneurysms.   In this report, we will discuss metabolic and hemodynamic condition in
HTA and efficacy of HTA.
  Materials and Methods      Two hundred and eight consecutive cases, 69 males and 139 females aged 58
in average, who underwent direct surgery for cerebral aneurysm under HTA were studied.            HTA is
divided into two groups, mild HTA (35-33      , comprising 111 cases) and moderate HTA (33-27        , 97
cases).    One hundred and sixty-eight cases receiving acute surgery after SAH were studied in
comparison to those underwent early operation under normothermic anesthesia (NTA) in the same period
as a control group.
  Results     Hemodynamic and metabolic changes in HTA : Cardiac output is reduced to 50% and TPR is
elevated up to 160% of pre-HTA one at 30 . This condition is well coupled with 50% reduced oxygen
consumption at 30 , resulting in maintaining DO2/VO2 value at a constant rate to indicate that general
metabolic suppression during HTA at this level is quite safe.     SjO2 increases up to 80-90% at 30      ,
while     CBF decreases to the level around 25ml/100g/min.       This suggests that the suppression of
oxygen consumption in the brain is deeper than that of CBF, which may produce a tolerance to hypoxic
insult to the brain caused, for example, by a placement of temporary clip to the parent arteries.
Comparative study in acute surgery: Intraoperative premature bleeding is less frequent in the HTA group
than in the NTA (P<0.01). Postoperative brain damage caused by surgical maneuvers such as retraction
hematoma or infarction is less frequently seen in the HTA than in the NTA as well (P<0.05).




                                                85
                                                                    Oral Presentations (selected papers)
                                                                             Intraoperative Hypothermia
                                                                                          February 6 (Fri)
O-11                                                                                           TENKU-A


Mild hypothermia in neurosurgery

Eguchi T, Hara T, Kanazawa K, Sakata Y, Yamashita A, Kin T, Takahashi M
Dept. of neurosurgery, Kameda General Hospital, Kamogawa, Japan


     INTRODUCTION          Mild hypothermia is now in the limelight again in the field of Neurosurgery. In
our institute, we have used this method almost routinely for the operative treatment of cerebral aneurysms
and occlusive cerebrovascular diseases (CVD) since 1995. This mild hypothermia has been virtually
effective especially in severe situations of operations for these diseases.
     MATERIALS AND METHOD              For more than 500 cases of cerebral aneurysms and occlusive CVD,
we have used the mild hypothermia technique intraoperatively (32-33           for an aneurysm surgery and
34     for an occlusive CVD surgery : bypass or carotid endarterectomy). We cooled down the patients'
body temperature with the circulating water blankets. The temperature was measured continuously in the
bladder, at the tympanic membrane or on the surface of the brain. The temporary clamp of a parent artery
has been used in a risky situation of an aneurysm surgery in order not to develop a premature rupture. The
patients were put in re-warming just after the completion of a clipping procedure or a reconstructive
procedure.
     RESULTS      The postoperative outcomes were good. We have never experienced the essential
complications due to this mild hypothermia. The longest clamp time of the basilar artery was 30 min.
This SAH patient recovered smoothly from the anesthesia without delay or neurological deficits. The
outcome of SAH patients with a severe vasospasm was also good although they were operated on in the
period of severe vasospasm. Aged (more than 80 years old) or highly poor grade SAH patients could be
also operated on well without the operative complications due to the temporary clamp of the parent artery
or the brain retractions. The outcome of the patients of an occlusive CVD was similarly good even though
the artery was clamped during the reconstructive surgery under highly poor collateral circulations.
     DISCUSSION       Mild hypothermia can be a method of brain protection against ischemia during
surgery. For the aneurysm surgery, we use this intraoperative mild hypothermia routinely in almost all
cases including unruptured aneurysms.         We could perform an EC/IC bypass surgery or carotid
endarterectomy without fear of developing ischemia due to temporary clamp of the cerebral arteries or the
internal carotid artery.




                                                  86
                                                                   Oral Presentations (selected papers)
                                                                            Intraoperative Hypothermia
                                                                                         February 6 (Fri)
O-12                                                                                          TENKU-A


Usefulness of intraoperative mild hypothermia for vascular disease.

Teruyasu Hirayama, Takeshi Maeda, Tsuneo Kano and Yoichi Katayama
Department of Neurological Surgery, Nihon University Hospitals, Tokyo,173-8610, JAPAN


  Purpose    At our institute, we have used mild hypothermia during surgery for several kinds of vascular
diseases since 1994. We will attempt here to evaluate the outcome of these cases and to discuss the
usefulness and limitations of this method in the neurosurgical field.     Materials and methods      In 229
cases (aneurysm, 147; arteriovenous malformation, 30; other vascular lesions, 52), we employed the mild
hypothermia method intraoperatively. After the onset of anesthesia, surface cooling was performed with
double water-cooling blankets. The core body temperature was maintained at between 32 and 34 . Once,
when the microsurgery finished, the patient was actively rewarmed using a warm air blanket in
combination with a warm water blanket. The warm air blanket was employed in the intensive care unit to
complete rewarming to 36 . Although most patients were extubated in the operating room, some
patients remained intubated in the neurosurgical intensive care unit, without muscle relaxant reversal,
until the core temperature exceeds 35       .   Results   In general, the clinical outcome in our mild
hypothermic patients with difficult intracranial and extracranial vascular lesions was excellent. No skin or
peripheral nerve injury resulted from the surface cooling. Among the physiological data, the heart rate
was significantly lower in the hypothermia group. No thrombocytopenia was observed. No other patients
experienced any clinical bleeding problems intraoperatively. While premature ventricular contraction was
noted in 3 (1.3%) of the 229 hypothermic patients, this did not have any major influence on the clinical
course.   Conclusion Mild hypothermia may provide an effective method of brain protection against
ischemia during microsurgery. It is considered especially useful in surgery for the clipping of aneurysms,
carotid endarterectomy and STA-MCA anastomosis when temporary clips are utilized.




                                                 87
                                                                   Oral Presentations (selected papers)
                                                                                              Pediatrics
                                                                                        February 6 (Fri)
                                                                                              TENKU-A
O-13


Clinical study of brain MRI in infants treated with brain hypothermia

Masaki Shimizu, Tsutomu Ohno, Hirofumi Kimoto
Division of Neonatology, Saitama Children’s Medical Center, Saitama, Japan


[Objective] To evaluate the brain MRI clinically in infants with hypoxic ischemic encephalopathy (HIE)
ensued after neonatal asphyxia that was treated with the brain hypothermia (BHT).
[Material and method] 26 infants were enrolled in this study, and divided into three groups. Three groups
are 1) BHT group; 10 infants were born at gestational age of 39.8±1.1wks who was treated with BHT,
and was examined brain MRI at 12 month old. 2) HIE group; 10 infants were born at term who was
treated only with conventional therapies excluding BHT, and was examined brain MRI at 12 month old.
3) C group (Control); 6 infants were born at term, and was examined brain MRI due to otolaryngologic
disease (media otitis) at 12 month old.
Method of BHT was a selective head cooling by a cooling cap. The infants were cooled to
nasopharyngeal temperature of 34       for 2-3 hours, and maintained 34      until recovering of brain echo
findings. BHT was started within 6 hours and the duration was 9.6 days.
The area ratio of the cerebral cortex, medulla and basal ganglia to the cerebral hemisphere were
calculated with the brain MRI by the image analyzing software.
[Result]    1)   The   area   ratios   of   cerebral   cortex/   cerebral   medulla   were    as   follows.
BHT/HIE/C=1.93±0.43/ 5.14±3.10/ 1.59±0.36. There was no difference between BHT group and C group,
and the ratios in HIE group were significantly higher than the ones in the other two groups. Although the
volume of cerebral medulla in HIE group was obviously decreased due to subcortical necrosis by HIE,
the volume of cerebral medulla was almost protected in BHT group.           It was speculated there was a
possibility that subcortical necrosis was inhibited by BHT. 2) The area ratios of basal ganglia/ cerebral
hemisphere were as follows. BHT/HIE/C=0.14±0.03/ 0.12±0.03/ 0.16±0.02. There was no statistical
difference between the area ratios in three groups. There were two reasons for it. In BHT group, necrosis
of basal ganglia was not almost observed. HIE group had no difference between the other groups, because
the ratio was kept normally according to be decreased proportionally the both areas due to the cerebral
necrosis.
[Conclusion]It is suggested that because the cerebral medullal volume is kept normally in BHT group
compared with non BHT, there is the possibility that subcortical necrosis in HIE is reduced by BHT. But,
even if the cerebral medullal volume is kept normally by BHT, the neurological prognosis on the case
which caused the basal ganglia necrosis was poor. In this study, the brain MRI in infants at 1year old who
were treated with BHT was useful to evaluate the effectiveness and to elucidate the mechanism of BHT.




                                                 88
                                                                   Oral Presentations (selected papers)
                                                                                              Pediatrics
                                                                                        February 6 (Fri)
O-14                                                                                          TENKU-A


Adjunctive application of hyperbaric oxygen therapy in children already treated with mild
hypothermia for disturbance of consciousness

Hiroshi Dohgomori 1), Kazuhiro Arikawa 2), Hiroaki Iwaya 2), Ri Matsubayashi 3),
Yuichi Kanmura 3)
1) Division of Emergency Medicine, Ryuku University Hospital
2) Division of Emergency Medicine, Kagoshima University Hospital
3) Department of Anesthesiology, Kagoshima University School of Medicine


Introduction
Hypothermia (HYT) is potentially useful for treating a variety of diseases, but in some cases its results
remain unsatisfactory and there are still some limitations to its clinical use. We report three children who
were treated with hyperbaric oxygen therapy (HBOT) because they had exhibited poor recovery after
HYT.
Patients and Methods
Between 1999 and 2002 in Kagoshima University Hospital, three children with hypoxic encephalopathy
were treated with HBOT after previously undergoing mild HYT. They exhibited various degrees of
disturbance even several days after completion of HYT. Case-1 was a 10-year-old boy (JCS-3), Case-2
was a 4-year-old boy (JCS-30), and Case-3 was a 1-year-old girl (JCS-200). Each had suffered cardiac
arrest (Case-1 from arrhythmia, Case-2 from suffocation, and Case-3 from near-drowning), and all
exhibited neurological disturbances. They received HBOT once a day as follows: pressure was increased
to 2 ATA over a period of 10 min, maintained at 2 ATA for 60 min, then decreased to 1 ATA over a period
of 15 min. The number of HBOT sessions was determined according to the patients condition.
Main Results and Conclusion
The number of sessions of HBOT ranged from 10 to 29. Two patients [Case-1 (10 HBOT sessions) and
Case-3 (29 HBOT sessions) left our hospital without neurological disturbance, but the other (16 HBOT
sessions) exhibited continued disturbance. Although the mechanism underlying such HBOT-induced
improvement is still not clear, this procedure appears to be useful for patients who do not exhibit full
recovery from disturbance, as we and others have reported for influenza encephalopathy and air gas
embolism R-1,2). In conclusion, HBOT may be capable of further improving neurological disturbances
that remain after HYT. Employed in combination with HYT, HBOT may improve recovery from
neurological disturbance, and even delayed HBOT appears to be one clinical option for treating any
neurological disturbance remaining after HYT.
References
R-1) Dohgomori H, Arikawa. K, Kanmura Y. Hyperbaric oxygen therapy (HBOT) in a child with
suspected influenza-associated encephalopathy. Can J Anesth 2003; 50:204.
R-2) Wherrett GG, Mehran RJ, Beaulien MA. Cerebral arterial gas embolism following diagnostic
bronchoscopy: delayed treatment with hyperbaric       oxygen. Can J Anesth 2002; 49:96-9.


                                                 89
                                                                    Oral Presentations (selected papers)
                                                                                          Basic Science
                                                                                         February 6 (Fri)
O-15                                                                                           TENKU-B

Resuscitative mild hypothermia attenuates the excitatory amino acids overflow and
diminishes the nitric oxide synthase activity during reperfusion after asphyxial cardiac
in rats.

S. Hachimi-Idrissi, N. Nguyen, A. Van Hemelrijk , I. Smolders, S. Sarre, G. Ebinger Y. Michotte, L.
Huyghens.
Critical Care Department and Cerebral Resuscitation Research Group, Brussels


Neurotransmitter overflow into the extracellular space and activation of nitric oxide synthase were
implicated in neuronal death after cerebral ischemia. A small temperature reduction induced before and
during the insult crucially mitigated the neuronal death. But only a few are known about the effect of mild
hypothermia (34°C) when induced after the insult (resuscitative mild hypothermia). To elucidate this
mechanisms, glutamate, dopamine as marker of excitatory amino acid overflow and also
citrulline/arginine ratio as marker of nitric oxide synthase were measured during reperfusion after
asphyxial cardiac arrest in sham operated group, normothermic group and hypothermic group. Also the
effect of resuscitative mild hypothermia on the histological data yield from the rat’s brain 24 hours and 7
days post insult were studied.
 After the insult, the release of glutamate and dopamine increased significantly in the normothermic
group. However, in the hypothermic group this release was not significantly different from the sham
group. The citrulline/ arginine ratios increased up to 5-fold the basal value in the normothermic group and
only 2.5-fold in the hypothermic group. However in sham operated group, this ratio remained stable
throughout the experiment. At 24 hours after the insult, the ischemic brain damage was significantly
higher in the normothermic group than in the hypothermic group, and it increased further at day 7-post
insult.
 In conclusion, mild hypothermia (34°C) induced after asphyxial cardiac arrest attenuates the
extracellular amino acid overflow, diminishes nitric oxide synthase activity, and reduces brain damage at
24 hours and 7 days post insult.




                                                90
                                                                        Oral Presentations (selected papers)
                                                                                              Basic Science
                                                                                             February 6 (Fri)
                                                                                                   TENKU-B
O-16


A novel method of oxidative stress monitoring in neuronal injury during brain
hypothermia therapy- ex vivo electron spin resonance study -

Yuko Mihara MD1, Kenji Dohi MD PhD1, Yasuhumi Miyake MD1, Hiroshi Moriwaki MD1, Masaharu
Yagi MD1, Kazue Satoh PhD2, Tohru Aruga MD PhD1
Department of Emergency and Critical Care Medicine1, Anatomy2, Showa University School of Medicine


[Introduction] Recent experimental studies have demonstrated that oxygen free radicals have important
roles of brain tissue injury and brain edema in neurotrauma patients, and one of the most important
purposes of brain hypothermia therapy is to control the generation of free radicals. However, it is difficult
to detect free radicals directly in human, and the effect of brain hypothermia therapy is still not clear. This
study directly detects and quantifies injury-induced intravenous oxygen free radical generation during
hypothermia therapy by ex vivo electron spin resonance (ESR) spectroscopy. [Patients and methods] Five
patients who were admitted to Showa University Hospital with severe neurotrauma were enrolled in the
present study. All the patients were treated with mild hypothermia therapy (brain temperature of 33 ).
Blood samples were taken from the catheter of the internal jugular bulb on admission and during brain
hypothermia therapy, and the relation between free radical intensity and brain temperature was assessed.
In three patients blood samples of internal jugular bulb were compared with those of central vein or the
radial artery. The control samples were also taken from five healthy volunteers. The free radical intensity
was measured by ex vivo ESR spectrometry using 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) as a spin
trap obtained from Dojin Chemical (Tokyo, Japan). The detection of the spin adduct was performed at
room temperature using a JESREIX X-band spectrometer (JEOL, Tokyo, Japan). [Results] Oxygen free
radical intensity in whole-blood was detected in all samples. ESR demonstrated that the free radical
intensity of severe neurotrauma patients was significantly higher than that of healthy volunteers (control
31.9±19.5 vs. neurotrauma patients 88.5±31.0, p<0.005, student t test). The free radical intensity in blood
samples of jugular vein was greater than that of central vein or radial artery on admission, suggesting that
the free radicals originated from injured brain tissues or endothelial cells of brain vessels. The free radical
intensity was increased in first several hours, but was controlled during the course of brain hypothermia
therapy. [Conclusion] This study proved the generation of intravenous free radical in severe neurotrauma
patients and the effect of brain hypothermia therapy on suppression of free radical using ex vivo ESR
spectroscopy. This method is useful to monitor the free radical intensity at bedside and it will enable to
estimate the oxidative stress level and the severity of brain damage.




                                                  91
                                                                 Oral Presentations (selected papers)
                                                                                       Basic Science
                                                                                      February 6 (Fri)
                                                                                            TENKU-B
O-17


Effect of mild and deep hypothermia on the neuronal activity and energy metabolism in
the brain slices in vitro

Yasuhiro OKADA
Emeritus Prof. Dept. Physiology, School of Medicine, Kobe University, Chuoku, Kobe and Health
Science Center   Kobe Heath-Life-Plaza     Hyogoku, Kobe, Japan


  Objective   Using hippocampal slices effect of hypothermia on the neuronal activity and energy
metabolism was studied during deprivation of oxygen and/or glucose. Materials Brain slices could be a
good tool for studying the resistance and reversibility of the neuron per se against anoxia and aglycemia
under hypothermic condition because neural activity is easily recorded in slices with distinct neural
circuit, slices are easily supplied with oxygen and glucose through perfusion medium, the temperature of
the medium can be precisely controlled and slice tissue is instantly fixed for chemical analysis for the
assay of metabolites such as ATP and phosphocreatine (Pcr) and further slices are free from the
postanoxic circulatory disturbances such as ‘no reflow phenomenon’ observed in in-vivo study.
 [Effects of hypothermia on the neural activity—synaptic field potential (PS) and intracellular recording
study of pyramidal neuron in CA3 region of guinea pig hippocampal slices during cooling and
re-warming (8-37 ) of the perfusion medium.] During gradual cooling the perfusion medium from 37
to 15     PS amplitude transiently increased at 31    , and decayed with further cooling to extinction
During re-warming, PS reappeared , while the amplitude increasing to maximum at 31                 and then
decreased to the original level with further warming to 37             In the intracellular recording study,
hypothermia reduced the EPSP slope in a temperature dependent manner, but the EPSP amplitude was
enhanced transiently between 33−28         Neuronal activities including membrane properties recovered
fully when the temperature was raised to 37C even after long-term deep hypothermia (8       ).
 [Protective effect of hypothermia (at 37, 28, 21 ) on reversibility of in the neuronal function during
long lasting deprivation of oxygen and/or glucose]During deprivation of oxygen and glucose the survival
time, the period of deprivation of oxygen and glucose during which neuronal activity of tissue slice can
show full recovery, was 10, 15 and 45 min at 37, 28 and 21 , respectively.           During deprivation of
glucose only it was 1.5 , 3 and 5 hour at 37, 28, and 21 . During deprivation of oxygen only it was 2.5
5, and 15 hours at 37, 28 and 21 . The concentration of ATP and Pcr showed good recovery in the slices
with full neuronal reversibility. Deep hypothermia (21 ) prolonged tremendously the survival time of
neurons of tissue slice during deprivation of oxygen and/or glucose.




                                                92
                                                                    Oral Presentations (selected papers)
                                                                                          Basic Science
                                                                                         February 6 (Fri)
O-18                                                                                           TENKU-B


Effect of resuscitative mild hypothermia and oxygen concentration on the survival time
during lethal uncontrolled hemorrhagic shock in mechanically ventilated rats.

N. Nguyen, Y. Xin, S. Hachimi-Idrissi, L. Huyghens.


Objective: To test the hypothesis that resuscitative mild hypothermia (MH) (34°C) or breathing FiO2 of
1.0 would prolong the survival time during lethal uncontrolled hemorrhagic shock (UHS) in mechanically
ventilated rats.
Methods: Forty Wistar rats were anaesthetised with halothane, N2O and O2 (70/30%), intubated and
mechanically ventilated. UHS was induced by volume-controlled blood withdraw of 3 mL/100 g over 15
minutes, followed by 75% tail amputation of it length. The animals were randomised into four UHS
treatment groups (10 rats in each group): group 1 was maintained on FiO2              of 0.21 and rectal
temperature of 37.5 °C. Group 2 was maintained on FiO2 of 0.21 and induced MH. Group 3 was
maintained on FiO2 of 1.0 and 37.5 °C. Group 4 was maintained on FiO2 of 1.0 and MH. Rats were
observed otherwise untreated until death.
Results: During the initial blood withdraw, MAP decreased up to 40 mmHg, and the heart rate (HR)
increased up to 400 beats /min. Induction of MH increased MAP to 60 mmHg and the survival time.
Moreover, it reduced the HR to 300 beats/min but did not increase bleeding. Ventilation with FiO2 of 1.0
did not influence the MAP, the blood loss or the survival time, but increased the PaO2. The mean survival
time was 62, 202, 68 and 209 min in-group 1, 2, 3 and 4 respectively. Blood loss from tail was 1.0, 1.2,
0.9 and 0.7 ml respectively in groups 1, 2, 3 and 4.
Conclusion: MH prolonged the survival time during UHS in mechanically ventilated rats. However FiO2
of 1.0 did not influence the survival time or the blood loss from the tail.




                                                  93
                                                                    Oral Presentations (selected papers)
                                                                                          Basic Science
                                                                                         February 6 (Fri)
O-19                                                                                           TENKU-B


Effects of brain hypothermia on brain edema formation after intracerebral hemorrhage in
rats.

N. Kawai
Kagawa Medical University


Patients with intracerebral hemorrhage (ICH) may deteriorate progressively after the initial ictus because
of the brain edema around the hematoma. Recently, thrombin has known to play an important role in
brain edema formation after ICH. Animal research suggests that moderate brain hypothermia reduces
brain injury in various models. In this study, we have examined the effect of brain hypothermia on brain
edema formation after ICH and thrombin injection into the brain in rats.
Anesthetized adult Sprague-Dawley rats (n=59) received an injection of 70 µl of autologous blood or 10
units of bovine thrombin into the basal ganglia. Animals were divided into the normothermic and
hypothermic groups, which were housed in a room maintained at 25           (brain temperature 38 ) and 5
(brain temperature 34     ) respectively. After 24 hours, brain water content was examined with
drying-weighing method in both groups. To clarify the mechanisms of brain hypothermia on
thrombin-induced brain edema formation, blood-brain barrier (BBB) permeability to Evan’s blue and
polymorphonuclear (PMN) leukocyte accumulation (myeloperoxidase activity) were also examined after
24 hours.
Brain water content was significantly reduced with brain hypothermia in the basal ganglia (84.5±0.6 vs.
82.2±0.4%; p<0.01), accompanied with a significant reduction in BBB permeability to Evan’s blue
(29.4±5.3 vs. 11.6±3.0 ng/g wet tissue; p<0.05) and in accumulation of PMN leukocyte (3.03±0.79 vs.
0.27±0.16 U/g wet tissue; p<0.01) at 24 hours after thrombin injection. Brain edema formation was also
reduced with brain hypothermia in the cortex (81.5±0.7 vs. 80.0±0.2%; p<0.05) at 24 hours after
hematoma induction.
This study indicates that brain hypothermia significantly reduced the brain edema formation after ICH
and thrombin injection in rats. Inhibition of thrombin-induced BBB breakdown and inflammatory
response by hypothermia appear to contribute to brain protection in this model.




                                                94
                                                                      Oral Presentations (selected papers)
                                                                                            Basic Science
                                                                                           February 6 (Fri)
O-20                                                                                             TENKU-B


Hypothermia prolong the viability of ischemic brain tissue due to Neuroprotection linked
to redistribution of oxygen in brain: PET study of the critical first 6 hours after stroke in
pigs.

Masaharu Sakoh1, Tomokatsu Hori1, Albert Gjedde2
1Department of Neurosurgery, Tokyo Women's Medical University, Japan
2Center of Functionally Integrative Neuroscience, Aarhus University, Denmark


Background: Hypothermia improves the outcome of acute ischemic stroke, traumatic injury, and
inflammation of brain tissue. We verified that hypothermia reduces the energy metabolism of brain tissue
to a level that is commensurate with the prevailing blood flow and hence allows adequate distribution of
oxygen to the entire tissue using PET in pigs. However, reperfusion therapy of acute stroke is known to
be ineffective in severe ischemia, even in the first few hours after the onset. We investigated the benefit of
32 degrees hypothermia following reperfusion in severe ischemia in the acute stage.
Methods: Permanent middle cerebral artery occlusion (MCAO) (n=11), reperfusion after a 2-hour MCAO
(n=9), 8-hour 32 degrees hypothermia of the intact brain (n=10), and 8-hour hypothermia initiated 30
minutes into a 2-hour MCAO and the following reperfusion (n=5) were induced in pigs. CBF and
CMRO2 were measured before and every hour until 7 hours after MCAO, reperfusion, or hypothermia,
using PET. Thereafter, histological examination was performed. Eight hours of hypothermia were
induced by a forced-air cooling system. The air of the cooling system was additionally cooled to -20
degrees with dry ice. The brain temperature was reduced to 32 degrees and maintained at that level during
the experiments.
Results: The viability of ischemic tissue depended on the CMRO2 in relation to the residual flow as a
function of time. The threshold of ischemic viability was 100 mircomol/100g/min for CMRO2 and 30
ml/100g/min for CBF in permanent MCAO. Reperfusion saved the previously ischemic regions with
CMRO2 above 100 micromol/100g/min or CBF above 23 ml/100g/min 2 hours after MCAO. The 32
degrees hypothermia reduced CBF and CMRO2 to 50% of the baseline in 3 and 5 hours, respectively, thus
elevating the oxygen extraction fraction (OEF) to 140% of the baseline at 3 hours, and reducing the
driving pressure of oxygen. The hypothermia following reperfusion saved the previously ischemic
regions with CMRO2 above 80 micromol/100g/min or CBF above 18 ml/100g/min, and suppressed the
postischemic hyperperfusion. The volume of infarction in severely ischemic pigs was significantly
decreased due to the hypothermia. (permanent MCAO: 18.8±1.7 ml; reperfusion only: 13.2±4.0 ml,
hypothermia following reperfusion: 6.1±4.7 ml).
Conclusions: Thirty two degrees hypothermia prolongs the therapeutic time window even in severe
ischemia in the acute stage by reducing base CMRO2, that is, the neuroprotection linked to redistribution
of oxygen in brain.




                                                  95
                                                                  Oral Presentations (selected papers)
                                                                                        Basic Science
                                                                                       February 6 (Fri)
O-21                                                                                         TENKU-B


Neuroprotection delivered by moderate hypothermia in experimental SAH: A
microdialysis, diffusion-weighted imaging and magnetic resonance spectroscopy study in
rats

Schubert GA, Poli S, Mendelowitsch A, Schilling L, Schmiedek P, Thomé C
Dept. of Neurosurgery and Neuroradiology, Mannheim Campus, University of Heidelberg, Germany


Objective: Acute cerebral vasospasm and consecutive accumulation of detrimental metabolites have been
shown to contribute significantly to acute brain injury following SAH. The purpose of this study was to
investigate the effects of moderate hypothermia on the metabolic derangements following massive
experimental SAH.
Material and Methods: SAH was induced in 47 anesthetized rats by injection of 0.5ml arterial blood into
the cisterna magna within 60s. In 19 animals two microdialysis probes were implanted stereotactically in
the frontoparietal cortex and samples were collected for HPLC analysis of glucose, lactate and amino
acids every 30min for 3h following SAH in normothermia (NT: 37.0±0.2°C) or hypothermia (HT:
32.0±0.2°C). In a second group including a total of 28 animals, magnetic resonance spectroscopy (MRS)
and diffusion-weighted imaging were used to quantify the changes in concentrations of lactate, creatine
and NAA in NT or HT and to describe the regional development of the apparent diffusion coefficient
(ADC) respectively.
Results: SAH lead to an initial reduction in glucose to 57±22% in NT and remained at 100%±26% in HT
(p<0.01). Hypothermia reduced the increase of lactate after SAH to 118±24% vs. 193±118% in NT. The
increase in glutamate (196±135%) was abolished in HT (111         28%) and the release of aspartate was
significantly reduced (215±67% in NT) vs. (151±41% in HT).
MRS revealed lactate accumulation to 192±72% (NT) vs. 117±34% (p<0.01). No significant changes
could be detected when examining NAA (115±38% NT vs. 112±50% HT) whereas creatine was found to
increase significantly in NT (165±66% vs 89±29% HT).
Finally, a significant decrease of the ADC in NT could be observed in different anatomical regions (basal,
cortical and in the hippocampus; average 9% vs. 4% in HT) corresponding to development of cytotoxic
edema more pronounced in normothermia.
Conclusions: The acute phase of experimental SAH is characterized by lactate accumulation, increased
glucose utilization, release of excitatory amino acids and formation of cytotoxic edema, changes
contributed to or aggravated by a compromise in cerebral perfusion. Hypothermia reduces these changes
significantly as now confirmed by microdialysis, MRS and diffusion-weighted imaging.




                                                96
                                                                        Oral Presentations (selected papers)
                                                                                                  Monitoring
                                                                                             February 6 (Fri)
                                                                                                   TENKU-B
O-22


In-vivo microdialysis measurements for patients with brain damage treated by mild
hypothermic therapy

Shunichi Harada, Hirotoshi Sano, and Tetsuo Kanno
Department of Neurosurgery, Fujita Health University


Mild hypothermic therapy (MHT) for patients with severe brain damage remains a matter of controversy.
This is partly because of the ignorance of the real effects of hypothermia when applied to human beings.
We measured the neurochemical substances by means of an in-vivo microdialysis methods during
hypothermia and after hypothermia. Four patients underwent MHT according to our protocol, two of
them were sustained trauma case, one post-resuscitation after cardiac arrest due to ventricular fiblliration,
and one poor grade subarachnoid hemorrhage. MHT was conducted immediately after the onset or
surgery. Target temperature was 34 degree of centigrade and it was maintained for three days followed by
slow re-warming with the rate of 0.5        per day. During MHT including the re-warming period, we
checked intracranial pressure, jugular venous oxygen saturation, brain temperature, together with
systemic and cardio-pulmonary physiological condition. Subarachnoid hemorrhage case showed sudden
increase of lactate and glutamate at the time of vasospasm after clipping. These neurochemical substance
increases preceded the elevation of intracranial pressure. Two trauma cases resulted in dead brain due to
uncontrollably increased intracranial pressure. Both two cases showed an extreme increase of glutamate
and decrease of dopamine. Post-resuscitation case showed a decrease of glutamate and slowly increase of
lactate but finally suppressed. This patient showed a normal cerebral blood flow at first, however, resulted
in very low level after a couple of month. The final outcome was vegetative state. In conclusion,
neurochemical monitoring using in-vivo microdialysis methods is an useful tool which provide the
metabolic information that might occur in advance of physiological change.




                                                 97
                                                                        Oral Presentations (selected papers)
                                                                                                  Monitoring
                                                                                             February 6 (Fri)
                                                                                                   TENKU-B
O-23


Microdialysis and brain tissue O2 (Pti O2) study in mild hypothermia

Takashi Karukaya, Tomoya Miyagi, Ryo Doi,Naoto Shiomi, Takashi Tokutomi, Minoru Shigemori
Department of Neurosurgery, Kurume university school of Medicine


  Purpose The findings of microdialysis and Pti O2 were studied in patients who received            mild
hypothermia(35      of brain temperature) in the acute stage of brain injury.
  Material and methods The study was performed in 7patients with severe brain injury ( GCS score of 5
or less on admission, 5 of TBI and 2 of SAH ). Intracranial pressure(ICP), cerebral perfusion
pressure(CPP), jugular venous oxygen saturation(SjO2) monitaring and changes in the concentration of
glutamate, glycerol, pyruvate, lactate and glucose in the extracellular space and cortex by use of
intracerebral microdialysis as well as Pti O2 were studied.
  Results    ICP, CPP, SjO2,and Pti O2 were well maintained during mild hypothermia. In dyalysate,
concentration of extracellular glutamate and glycerol was lower at 35-36            of brain temperature
compared to other levels of temperatures. Concentration of extracellular pyruvate and glucose was higher
at 35-36    of brain temperature compared to other levels of brain temperatures.     Under 50 mmHg of
CPP, Pti O2 and the neurochemical parameters showed significant changes.
  Conclusion Microdialysis and Pti O2 are at clinically useful to detect the abnormal neurochemical
events in severe brain injury , and to determine the optimum temperature in mild hypothermia.




                                                 98
                                                                      Oral Presentations (selected papers)
                                                                                           New Therapies
                                                                                           February 6 (Fri)
                                                                                                 TENKU-B
O-24


Combination of forced air cooling, cooling by circulating water mattress and intravenous
bolus infusion of iced saline is effective and safe technique for induction of mild
hypothermia during cerebral aneurysm surgery

A. M. Zeitlin and A. Y. Loubnine
Departament of Anesthesiology, Burdenko Neurosurgery Institute, 4th Tverskaya-Yamskaya, 16th,
Moscow, Russia


Background and Objective: Mild hypothermia is currently considered as effective mode of brain
protection in cerebral aneurysm surgery [1]. Core temperature of 32°C provides best balance between
effective brain protection and avoidance of major adverse effects. Surface cooling is often fails to reach
this target. We performed study for assessment of efficacy and safety of intraoperative induction of mild
hypothermia to core temperature of 32°C by combination of forced air cooling, cooling by circulating
water mattress, and intravenous bolus infusion of iced saline. Methods: We included in study 20
consecutive patients underwent cerebral aneurysm surgery. Weight of the patients was ≤ 90 kg. For core
temperature monitoring used nasopharyngeal probe. After induction of anaesthesia we begun forced air
cooling (ambient air) and cooling by circulating water mattress (upper body; set to 4°C), and after
stabilization infused iced saline (4 °C) through two lines (central 14-16G and peripheral 18G) until
approaching target temperature or advent of unacceptable adverse effects. We adjusted ventilation to keep
PaCO2 between 30 and 35 mmHg; type pH management was pH-stat. Results. All patients were
successfully cooled to 32°C; expended volume of iced saline was 15-30 ml/kg. Time interval from
beginning of the cooling to achieving target temperature was 2 to 3 hours. After completion of infusion of
iced saline temperature decreased additionaly by 0.2-0.7°C. Most frequent adverse effects: bradycardia
(responsive to atropine); hyperglycemia to 7-11 mmol/l; cold diuresis; retarded emergence with shivering,
prolonged intubation and mechanical ventilation in ICU. Conclusions and Discussion: combination of
forced air cooling, cooling by circulating water mattress and intravenous bolus infusion of cold saline is
effective and safe technique for induction of mild hypothermia (to 32°C) during cerebral aneurysm
surgery. Profile of associated adverse effects is acceptable in face of brain ischemia. In our opinion, bolus
infusion of iced saline can be useful adjunct to modern catheter techniques of hypothermia in case if
patient is large/obese or in fever.
1 Hindman BJ, Todd MM, Gelb AW, et al. Mild hypothermia as a protective therapy during intracranial
aneurysm surgery: a randomized prospective pilot trial. Neurosurgery 1999 Jan; 44(1):23-32




                                                 99
                                                                 Oral Presentations (selected papers)
                                                                                      New Therapies
                                                                                      February 6 (Fri)
                                                                                            TENKU-B
O-25


Mathematical analysis of digit immersion cooling technique for brain temperature
management

X. Xu, W. Santee, L. Berglund, R.Gonzalez
USARIEM, Kansas Street, Natick, MA, USA


Because heat conductivity of most body tissues is low, surface cooling methods for the management of
the brain temperature during medical treatment usually have limited utility. A more effective mechanism
is application of convective heat exchange via the blood. Since the level of blood flow (BF) in digits
(hand or foot) is high when vasodilatation occurs and the arteriovenous anastomoses (AVA) are open,
digits become important organs for heat exchange between the body and the environment. In this paper, a
mathematical approach was used to simulate effects of digit immersion in cold water on brain and core
temperature response. METHODS The scientific basis for this work is a six cylinder thermoregulatory
model. An AVA response model was added to the base model. The AVA is assumed to be controlled by a
combination of core and skin temperature. The magnitudes (0~1) of AVA openness in hands and feet are
calculated from the deviations from set points for core and mean skin temperatures. When the AVAs are
fully open, the openness will equal 1 and the AVA BF will be equal to a maximum value of
30ml/min100ml tissue. When AVAs are closed, the openness will equal 0 and the AVA BF will also be
zero. Simulation scenario: resting in a hot environment of 40˚C/RH50% until the core temperature rises
to 39˚C, then resting in one of the following conditions for 1 hour: A) hands immersion in 10˚C water; B)
feet immersion in 10˚C water; C) hands and feet immersion in10˚C water. RESULTS AND
DISCUSSION The simulation results demonstrated that within the first 30 min, hands, feet and
hands/feet immersion cooling resulted in a drop in brain temperature of 1.6, 2.1 and 3.6˚C respectively.
The corresponding cooling rates during the first hour are 0.04, 0.06, and 0.063˚C/min. These predicted
cooling rates are reasonable in comparison with cooling rates of 0.05~0.07˚C/min with hand or foot
immersion reported in the literature. The BF values are critical to the predicted results. The predicted
maximum BF in the hand and foot are 53 and 48 ml/min100ml tissue, respectively. These values are
below the reported maximum values of 70 to 120 ml/min100ml tissue. The prediction may underestimate
the cooling rates. Results of prediction modeling shows that digit cooling is a reasonable mechanism
applicable for simple and effective means of controlling brain temperature. This model construct has
application for knowledge of individual physiological state. DISCLAIMER The views, opinions, and/or
findings contained in this report are those of the authors and should not be construed as an official
Department of the Army position, policy, or decision, unless so designated by other official
documentation. Citation of trade names in this report does not constitute an official Department of the
Army endorsement or approval of the use of such commercial items.




                                               100
                                                                       Oral Presentations (selected papers)
                                                                                            New Therapies
                                                                                            February 6 (Fri)
                                                                                                  TENKU-B
O-26


Automatic air-cooling incubating system for adult brain hypothermia treatment.

Hidetoshi Wakamatsu1, Lu Gaohua1
Biophysical System Engineering1, Tokyo Medical and Dental University, Tokyo, Japan


[Objective] A new automatic brain hypothermia system is proposed using an air-cooling incubator to
replace the manual water-cooling blanket, which has ever been used for the cooling of the brain tissue
temperature (BTT).
[Methods] A biothermal model of adult patient is first introduced for the air incubating system based on
its geometric structure and physical parameter database. Its theoretical rationality is confirmed through
the precise investigation of its dynamics by the simulation experiments of its step response and feedback
control. The incubating system is adaptively controlled to follow up the reference using the adaptive
signal synthesis mechanism. Thus, the accurate regulation of BTT is automatically realized, where the
unified human biothermal model with the therapeutic cooling blanket is regarded as a first order lag
system estimated from the clinical experience. For this purpose, the optimal regulator of the BTT is
discussed for the calculation of effective input of air condition in the therapy.
[Result] It is shown that the temperature of circulating air in the incubator is controlled to realize the BTT
in critical phases of hypothermia. The proposed air incubating system is controlled by the adaptive
control mechanism, which yields the following up of the BTT to the reference temperature course, even if
there exists possible change in the therapeutic system including individual difference of patients and
uncertain condition. For example, temperature change caused by the shivering under the inadequate
anesthesia in the integrated life-support of hypothermia treatment is successfully controlled by the
adaptive algorithm, even though any precise information about patients and their environment cannot be
practically given beforehand.
[Discussion] Not only decubitus and bedsore can be avoided by the proposed automatic air-cooling
method in the clinical treatment and rehabilitation, but also the high cost performance is expected from
the easy manipulation, observation and sanitation of the patients with their less environmental disturbance
and less physical and mental burden on medical staffs.
The proposed automatic air-cooling incubating system is thought useful for the automatic regulation of
BTT to follow up the desired cooling schedule in clinical practice, as its cooling efficiency is comparable
with the conventional one. Thus, the present work ensures the highly possible development of the air
incubating system for the better automatic regulation of the adult BTT in ICU.




                                                 101
Abstracts for Poster Presentations

     February 5 (Thursday) – February 6 (Friday)
                             “AURORA” ROOM
                                             Basic Science



PB-1.


Effects of mild hypothermia and alkalizing agents on brain injuries in rats with acute
subdural hematomas.

Masanobu Okauchi
Department of Neurological Surgery, Kagawa Medical University, Japan


Brain ischemia is the leading pathopysiological mechanism in the development of secondary brain
damage after acute subdural hematoma (SDH). Hypothermia has been employed as an effective
cerebroprotective treatment on brain injuries, but the control of the general condition is very difficult
under hypothermia, and various severe complications have been reported. Cerebral acidosis in the
ischemic area is one of the important factors augmenting the brain edema formation.
Tris-(hydroxymethyl)-aminomethane (THAM) has been used as an alkalizing agent for acidosis on
brain injury and is reported to be effective. In the present study, we used a rat acute SDH model to
assess the effect of mild (35 degrees C) hypothermia and THAM combined treatment on brain water
content, brain ischemia, and blood-brain barrier (BBB) permeability at 4 h after hematoma induction.
Mild hypothermia did not significantly reduce the brain water content beneath the hematoma (79.5 +/-
0.2%) compared to normothermia (80.2 +/- 0.2%), but mild hypothermia combined to THAM resulted
in a significant reduction (78.7 +/- 0.0%; p < 0.01). Combined with mild hypothermia, THAM
treatment significantly reduced the Evan's blue extravasation (35 +/- 7 ng/g wet tissue; p < 0.05)
compared to normothermia (63 +/- 7 ng/g wet tissue). Furthermore, the volume of infarction at 24 h
after the hematoma induction (54 +/- 3 mm3; p < 0.01) was significantly smaller by the combined
treatment compared with normothermia (70 +/- 2 mm3). The present findings indicate that mild
hypothermia of 35 degrees C combined with THAM presents a potent cerebroprotective strategy. The
protection of the BBB is one of the possible cerebroprotective mechanisms in this rat acute SDH
model.




                                                  104
                                              Basic Science



PB-2.


The effects of post-traumatic hypothermia and hyperthermia in female rats following
traumatic brain injury

Takamoto Suzuki, Helen M. Bramlett, W. Dalton Dietrich
Department of Neurological Surgery/The Miami Project to Cure Paralysis, University of Miami
School of Medicine, Miami, Florida, USA


Objective: The benefits of posttraumatic hypothermia as well as the detrimental consequences of
hyperthermia have been described in many experimental studies. However, no studies have determined
if these consequences of temperature are gender-specific. The purpose of this study was, therefore,
to determine the effects of gender on the histopathological consequences traumatic brain injury (TBI)
under posttraumatic hypothermic and hyperthermic conditions.
Materials and methods: Intubated and anesthetized male and female Sprague-Dawley rats (n=64) were
subjected to moderate (1.7-2.2 atm) fluid-percussion injury.   Animals were subjected to a 4 hr period
of normothermia (37°C), hypothermia (33°C), or hyperthermia (40°C) beginning 30 min after TBI
(n=8/group). Some female rats were ovariectomized 10 days prior to TBI. At 72 hr following TBI,
animals were perfusion-fixed for quantitative histopathological and immunocytochemical analysis.
Results:    Post-traumatic hypothermia significantly reduced overall contusion volume in males
(p<0.05), while not significantly reducing contusion volume in females.       Ovariectomized females
showed contusion volumes comparable to those seen in males, as well as demonstrating significant
reduction in contusion volumes following post-traumatic hypothermia.         Although post-traumatic
hyperthermia increased contusion volume in both intact and ovariectomized females, the effects of
induced hyperthermia were more severe in ovariectomized animals.
Conclusion:      These data demonstrate that post-traumatic hypothermia (4 hr) does not affect
short-term histopathological outcome in female rats.       Also, while female rats are sensitive to
post-traumatic hyperthermia, neuronal hormones including estrogen and progesterone appear to
protect against both primary and secondary insults. These findings emphasize the importance of
gender in studying the pathogenesis of TBI and the development of neuroprotective strategies that may
be tested in clinical trials.
Supported by NIH/NINDS NS30291, NS42133 and NS43233




                                                 105
                                          Basic Science




PB-3.


Mild hypothermia attenuates the endothelium-dependent pial arteriole dilatation but
not the endothelium-independent response in rats.

Izumi Yuzawa, M. Yamada, R Tanaka, K. Fujii
Department of Neurosurgery, Kitasato University School of Medicine, Sagamihara Japan


OBJECTIVES: Hypothermia is a tool providing cerebral protection in the management for traumatic
brain injury and cardiovascular bypass surgery. However, alteration in vasodilatory function of
cerebral pial arteriole under hypothermic condition is not fully understood. We studied the
cerebrovascular response to topically administered vasodilators under normo- and hypothermic
condition.
METHODS: All animals were anesthetized by the urethane/α-chloralose (i.p.), tracheostomized and
ventilated, and the physiological parameters (rectal temperature, ET CO2, blood pressure, pulse rate
and arterial blood gas analysis) were monitored. By closed cranial window method with video
microscopy pial arteriolar caliber change was monitored before and after superfusion of
endothelium-dependent vasodilator, acetylcholine, endothelium-independent nitric oxide donor,
sodium nitroprusside, and cAMP phosphodiesterase inhibitor cilostazol. Experiments were carried out
first under normothermia, then hypothermic condition (rectal temperature 30 degrees C with α-stat
respiratory management ) was introdued and protocol was repeated.
RESULTS: Under normothermia topical application of acetylcholine caused a dose-dependent increase
in arteriolar diameter, that was absent after hypothermia induction. Sodium nitroprusside and
cilostazol stimulated vasodilation in the normothermia to a maximum of 37±14% and 21±11%,
respectively. Under hypothermia that was 47±11% and 26±10%, respectively.
CONCLUSIONS: Hypothermia did not alter the vasodilation in response to sodium nitroprusside and
cilostazol. The specific loss of acetylcholine-induced vasodilation suggests endothelial cell
dysfunction rather than impaired ability of vascular smooth muscle to respond to nitric oxide. cAMP
phosphodiesterase inhibitor cilostazol can dilate cerebral arterioles both in normo- and hypothermic
condition.




                                                106
                                                Basic Science




PB-4.


Combination therapy of moderate hypothermia and thrombolysis in experimental
thromboembolic stroke - an MRI study

Rainer Kollmar
Department and Institution / Department of Neurology, University of Heidelberg, Germany


Background and Purpose: The use of thrombolysis is limited by reperfusion associated injury and the
short therapeutic window after stroke onset. Therecent study investigates the influence of hypothermia
and its combination with thrombolysis after thromboembolic stroke in rats by new MRI-techniques..
Methods: Wistar rats (n=60) were subjected to thromboembolic occlusion (TE) of the middle cerebral
artery (MCA). Thrombolysis (T) was performed 1 hour (early T) or 3 hours (late T) after TE by
intravenous rt-PA. Hypothermia (Hy) was applied for 4 hours at 33 degrees C started 1 hour after TE.
Experimental groups included control (C), early thrombolysis (ET), late thrombolysis (LT),
hypothermia (Hy), early thrombolysis plus hypothermia (ET+Hy), and late thrombolysis plus
hypothermia (LT+Hy). All animals were investigated by serial MRI and silver infarct staining (SIS)
for cerebral cerebral infarct size and edema.
Results: All animals of group Hy survived, while the survival rate in the other groups ranged from
87.5 % (group ET+Hy) to 42% (group C). Three hours after TE, PWI was normalised for ET and
ET+Hy in contrast to all other groups. Infarct volumes measured by T2, DWI and SIS of all treatment
groups showed a significant difference after 24 hours vs. the control group (p<0.05). The lesion
volume calculated from T2 was significantly smaller in ET+Hy after 3 hrs and 6 hrs (10.8+4.8%) vs.
group compared to C (12.3+5.6%;42.7+15.5%), ET (13.6+12.4%; 16.6+5.7 %), and LT+Hy (9.2+5%;
20.5+9%).
Conclusions: Hypothermia and its combination with thrombolysis improved the survival after TE and
reduced the infarct volume compared to the control group. Hypothermia did not affect PWI when
combined with T. MRI data implies that longer cooling periods may prevent the deleterious effects of
early rewarming.




                                                  107
                                              Basic Science




PB-5.


Effect of hypothermia on brain edema formation following intracranial hemorrhage in
rats.

Masahiko Kawanishi, Nobuyuki Kawai, Seigo Nagao
Department of Neurological Surgery, Kagawa Medical University, Japan


Introduction
Spontaneous intracerebral hemorrhage (ICH) is a relatively common neurosurgical emergency
associated with significant morbidity and mortality. Brain edema is an important clinical complication
of ICH. Despite much effort directed at clarifying the roles of surgical and medical therapy for ICH,
the most appropriate management is still controversial. Hypothermia has been employed as an
effective neuroprotective treatment in clinical and laboratory studies on cerebral ischemic and
contusional brain injuries. In this study, therefore, we attempted to evaluate the effects of mild
hypothermia (35℃) on brain edema formation at 48 hours after the hematoma induction in the rat with
ICH.
Method
Anesthetized adult rats received a stereotactic injection of 100µl of autologous arterial blood into the
basal ganglia. Animals were separated into the normothermic(n=7) and hypothermic group, which
were housed in a room maintained at 25℃ and in a cold room maintained at 5℃. The brain
temperature in rats housed in a cold room was approximately 35℃. Brain hypothermia was started at 6,
12 and 24 hours after the induction of hematoma (HT6; n=6, HT12; n=11 and HT24; n=6). The rats
were killed by decapitation under deep pentobarbital anesthesia at 48h after the injection of arterial
blood. Brain water contents were measured with wet and dry weight method. The integrity of the
blood-brain barrier was investigated using Evan's blue dye extravasation.
Results
Brain water contents in the basal ganglia was significantly reduced in rats treated with mild
hypothermia compared to the normothermic rats (82.0±0.01% vs. HT6:78.6±0.02%; p<0.01、
HT12:79.7±0.02%; n.s. HT24:79.7±0.01%; p<0.01). Differences in the brain water content were not
significant among the hypothermic subgroups (HT6, HT12, HT24). There was significant BBB
permeability in the hypothermic group (HT6;n=6).
Conclusion
This study indicates that hypothermic treatment significantly reduces the brain edema formation after
ICH in rats. The decrease of brain water content was accompanied with a significant reduction in BBB
permeability to Evan's blue dye. Although hypothermic treatment may provide an approach to
potentially reduce ongoing edema formation after ICH, detailed mechanism of hypothermia must be
studied before applying on clinical use.




                                                  108
                                              Basic Science




PB-6.


Postischemic mild hypothermia reduces neurotransmitter release during reperfusion
after asphyxial cardiac arrest in rats.

S. Hachimi-Idrissi, N. Nguyen, I. Smolders, A. Van Hemelrijk , S. Sarre, G. Ebinger, Y. Michotte, L.
Huyghens.
Critical Care Department and Cerebral Resuscitation Research Group, Brussels, Belgium


The present study attempted to ascertain whether postischemic mild hypothermia attenuated the
ischemia induced striatal glutamate and dopamine release and microglial cell proliferation.
Anesthetized rats were exposed to 8 min of asphyxiation including 5 min of cardiac arrest. The cardiac
arrest was reversed to restoration of spontaneous circulation, by brief external heart massage and
ventilation within a period of 2 min.
After the insult and during reperfusion, the extracellular glutamate and dopamine concentrations were
significantly higher in the normothermic group than in the sham operated animals and resulted in brain
edema. However, when hypothermia was induced for a period of 60 min after the insult and restoration
of spontaneous circulation, the glutamate and dopamine concentrations were not significantly higher
than in the sham group. The histological analysis of the brain showed that postischemic mild
hypothermia reduced brain edema, as well as microglial proliferation. Postischemic mild hypothermia
reduced the excitotoxicity process as well as microglial cell proliferation during reperfusion. Moreover,
these results emphasize the trigger effect of dopamine on the excitotoxic pathway.




                                                  109
                                              Basic Science




PB-7.


A decreased astroglial S-100 β protein may explain the neuroprotective effects of
resuscitative mild hypothermia.

S. Hachimi-Idrissi, N. Nguyen, L. Huyghens.
Critical Care Department and Cerebral Resuscitation Research Group, Brussels, Belgium


Background and purpose: The S-100 b protein is reported to regulate neuronal differentiation and
apoptosis in vitro.   In humans increased serum S-100 b protein levels correlated with brain damage
following a cardiac arrest. Resuscitative mild brain hypothermia during cardiac arrest mitigated the
ensuing neurological damages; therefore we investigated the effects of this mild hypothermia on the
evolution of serum concentrations of S-100 b protein in patients who survived cardiac arrest.
Methods: 61 resuscitated patients were prospectively randomized in two different studies, known as
HELMET (33 patients) and HACA (28 patients). In the HELMET study, patients older than 18 years
of age and surviving an asystole or pulseless electrical activity were included. In the HACA study,
only patient displayed a cardiac arrest with ventricular fibrillation or non-perfusing ventricular
tachycardia and aged between 18 and 75 years were studied. In each of the study groups the patients
were further randomized into either normothermic or hypothermic subgroups. The standard treatment
was similar, only the devices used to reduce the body temperature and the period of hypothermia were
different. Serum samples for the measurement of S-100 b were collected at admission and 24 hours
later.
Results: During the first 24 hours after the cardiac arrest, the serum S-100 b concentration decreased
significantly in the hypothermic cohort. However in the normothermic cohort, the decrease of serum
S-100 b was less pronounced and even increased in the normothermic HACA group.
Conclusion: Induced mild hypothermia reduced the 24 hours evolution of the serum S-100 β protein
concentrations and thereby might play a neuroprotective effect after cardiac arrest.




                                                  110
                                            Basic Science




PB-8.


Combination of mild hypothermia and delayed fluid resuscitation improved the survival
after hemorrhagic shock in mechanical ventilated rats.

S. Hachimi-Idrissi, N. Nguyen, Y. Xin, L. Huyghens.
Critical Care Department and Cerebral Resuscitation Research Group, Brussels, Belgium


Mild hypothermia (MH) prolonged the survival time during uncontrolled hemorrhagic shock (UHS) in
mechanically ventilated rats. The aim of our current study was to evaluate the effect of mild
hypothermia combined with delayed fluid resuscitation on the survival rate in mechanically ventilated
UHS rats. After an initial blood withdrawal of 3 ml/100 g over 15 min of time, we amputated 75% tail
length to induce UHS phase I. Followed by homeostasis of the tail wound, we maintained the mean
arterial pressure (MAP) of 40 versus 100 mmHg according to the assigned study group, during
resuscitation phase II. The phase III is an observational phase up to 72 hours. Rats were anaesthetised,
mechanically ventilated and randomised into four groups. Group 1 received immediate fluid
resuscitation and normothermia; group 2 received immediate fluid resuscitation and mild hypothermia.
Group 3 received limited Ringer's solutions to maintain MAP of 40 mm Hg and normothermia. Group
4, the rats received also limited Ringer's solution to maintain a MAP of 40 mm Hg but were subjected
to mild hypothermia. At the end of the observational phase III, the animal’s brains were fixed and
histologically analysed.
The blood loss from the tail during the phase I was significantly higher in groups where immediate
fluid resuscitation was performed. The group 4 required the lowest fluid resuscitation. The survival
rate was 33.3, 83.3, 58.3 and 91.7 % respectively in group 1, 2, 3 and 4. In all survivors rats no brain
histological damage was observed.
These results indicate that Mild hypothermia or delayed fluid resuscitation increases the survival rate.
However, when mild hypothermia and limited fluid resuscitation were combined, the survival rate was
the highest.




                                                  111
                                              Basic Science




PB-9.


Estimation of cerebral blood flow using multichannel near-infrared spectroscopy during
hypothermia after the hypoxic-ischemic insult in newborn piglets

Kensuke Okubo1, Tadashi Imai1, Masanori Namba1, Kou Kawada2, Takashi Kusaka2, Kenichi Isobe1,
Susumu Itoh1
Department of Pediatrics1 and Maternal Perinatal Center2, Kagawa Medical University, Kagawa, Japan


[Objective] The objective of the study was to determine the usefulness of measurement of cerebral
blood flow (CBF) using multichannel near-infrared spectroscopy (MNIRS) as a new brain function
monitoring system during hypothermia treatment after the hypoxic-ischemic insult (HI) in newborn
piglets.
[Materials and methods] Newborn piglets within 24 hours of birth were used in this study (7 for a
control group and 7 for a hypothermia group). For an ischemic load, a blood pressure cuff was
wrapped around the neck of each newborn piglet and pressurized to 300 mmHg. Simultaneously, for a
75-minute hypoxic load, the fraction of inhaled oxygen was decreased to 10% for 30 min and then to
8% for 45 min. Intensive care with cardiorespiratory support was continued over a period of 24 hours
after the HI. In the hypothermia group, whole body cooling was started 30 min after the HI, and rectal
and nasopharyngeal temperatures were maintained at 35°C. CBF was measured using MNIRS with
indocyanine green as a tracer before the HI and 3, 6, 18 and 24 hrs after resuscitation. Cerebral energy
metabolism     was     also   determined     by     31P-magnetic     resonance     spectroscopy     and
electroencephalography. Perfusion fixation of brain tissues in 4% paraformaldehyde was performed at
24 hours after resuscitation. Moreover, for determination of neuron damage, morphological
observation was carried out using 40 µm thick frozen sections that had been stained with Nissl’s stain.
[Results] The mean±SD of CBF (ml/100g/min) in the control and hypothermia groups were 13.9±4.5
and 15.4±6.3 respectively before the HI, 11.3±12.5 and 9.7±6.1 at 3 hours after resuscitation, 4.5±5.2
and 5.1±3.6 at 6 hours after resuscitation, 12.6±19.6 and 3.1±3.6 at 18 hours after resuscitation, and
8.5±12.8 and 2.2±3.0 at 24 hours after resuscitation. Changes in CBF in the control group indicated
post-ischemic reflow at 18 hours after resuscitation, but no increase at 18 hours was seen in the
hypothermia group. Results of histological examination of specimens from the control group revealed
the existence of neurons showing pyknosis and shrinkage of the cytoplasm over a wide area of the
brain, particularly in the cerebral cortex and hippocampus, but few such neurons were observed in
specimens from the hypothermia group.
[Conclusion] Changes in CBF after HI can be evaluated accurately during hypothermia treatment by
using MNIRS. Moreover, hypothermia therapy reduces CBF and suppresses reperfusion after
hypoxic-ischemic insult.




                                                  112
                                              Basic Science




PB-10.


Influence of hypothermia on neuroprotective effects                        (NPEs)      of   inhibiting
neurotransmitters (INTs) and agonists of their receptors

V. I. Kulinsky
Department of Biochemistry, Irkutsk State Medical University, Irkutsk, Russia


Different INTs have greate NPEs not only in focal or incomplete global cerebral ischemia, but in
complete global one. These NPEs are realized through their selective receptors: adenosine and its
analogs act via A-receptors (superiority A-1 subtype), GABA-ergic substances – through GABA-A
and GABA-B receptors, catecholamines analogs - via alpha-2 receptors. Dopamine D-2 antagonistic
antipsychotics also have NPE.
We studied possible mechanisms of these effects in experiments on the mice. A-1 agonists CPA,
CCPA, CHA and ADAC, GABA-A agonists muscimol and THIP, GABA-B agonists baclofen and
isonipecotate, GABA-ergic drugs valproate and progabide, alpha-2 agonists clonidine, guanabenz and
alpha-methyldopa, and also D-2 receptors antagonists haloperidol, chlorpromazine, chlorprothixene,
clozapine, periciazine and zuclopenthixol induce prominent hypothermia: body temperature decreases
on 3-20 degrees C and cerebral cortex temperature on 3-12 degrees C. Hypothermic effects (HTEs) of
A-2A agonists CGS 21680 and DPMA and I-1 agonist moxonidine are smaller, A-3 agonist IB-MECA,
alpha-1 agonist phenylephrine and beta-agonist isoprenaline do not have influence. These HTEs are
decreased or prevented correspondently by selective blockers of these receptors: A-1 antagonist
DPCPX, A-2 antagonists ZM 241385 and chlorosteryl caffeine, GABA-A antagonists bicuculine and
picrotoxine, GABA-B antagonists 2-hydroxysaclofen and 5-aminovalerate, alpha-2 antagonists
rauwolscine and !id!azoxan. NPEs and HTEs of INTs and agonists of their receptors are not connected
with the changes of cerebral blood flow and as a rule have central mechanism thus they are reproduced
by cerebroventricular injection of the doses smaller on 1-2 orders and are not blocked by peripherally
acting antagonist. The close correlation of NPEs and HTEs is revealed for temporary and dose curves,
summary data for each agonists, blocking effects of antagonists and summary data for every type of
receptors. Direct prevention both hypothermia of body by thermoneutral conditions (32 degrees C) and
cerebral hypothermia by the local warming of the head decreases or even prevents NPEs of A-1,
GABA-A, GABA-B and alpha-2 agonists.
 Thus hypothermia is of great importance for NPE. However we have some data that tolerant strategy
induced by INTs and agonists of their receptors is not limited by hypothermia and latter is not the sole
mechanism.




                                                  113
                                               Basic Science




PB-11.


A computer supported multi-channel long term hypothermia device for free moving rats

Susumu Yamashita, Frederick Colbourne*, Motoki Fujita, Takeshi Inoue, Norimichi Matsuyama,
Yasutaka Oda, Hisaki Yamashita, Syunji Kasaoka, Kiyoshi Okabayashi, Daikai Sadamitsu, Tsuyoshi
Maekawa
Advanced Medical and Critical Care Center, Yamaguchi University Hospital, Japan
* Department of Psychology, University of Alberta, Canada


In animal experiment for brain hypothermia, it is extremely difficult to maintain little animals like rats
in a hypothermia state for a long term. Researchers have to operate temperature control devices every
few minutes and it is extremely hard over 24 hours. An automated system for regulating brain
temperature in awake and freely moving rodents was developed by F. Colbourne in 1996. We made a
same system in Japan and have started some experiments.
The tip of telemetry brain probe (model VM-FH, Mini-Mitter Co, Inc.) is implanted in a rat brain
under general anesthesia with isoflurane and is fixed it to the skull by cyanoacrylate glue and dental
composite resin. This probe is a tiny thermometer and it can transmit temperature to a telemetry
receiver. Received brain temperature is input into a computer (OS /2) and analyzed by "Data Quest
IV"(Data Sciences, Int.).
"ThermoRegulator" program written by F. Colbourne, takes temperature data from Data Quest IV and
automatically controls devices - an infrared lamp, a fan, and a water misting spray. Temperature is
collected every 30 seconds and compared with the setpoint which is programmed in advance.
The fan works to get the body temperature down at first and if it does not cool enough, the water spray
works for short time. Spray duration get longer and longer if it needs. The fan and the spray are turned
off and the lamp is turned on when the rat should be warmed. The algorithm for maintaining
temperature including the duration time of spray was based upon manual experience by F. Colbourne
with gerbils.
A computer can control five rats at the same time. We have examined the brain damage of septic rats
with hypothermic or normothermic state with this system.




                                                   114
                                             Basic Science




PB-12.


Correlation of hypothermia with decrease of glutathione concentration and tolerance to
cerebral ischemia

Kolesnichenko L.S.1, Kulinsky V.I.2, Sotnikova L.S.1
Departments of Bioorganic Chemistry1 and Biochemistry2, Irkutsk State Medical University, Russia


The significance of body temperature for the tolerance to cerebral ischemia is well known but its
biochemical mechanisms are insufficiently investigated. The purpose of this work is a study of
reduced glutathione (GSH) role and quantitative estimation of correlation of these 3 parameters in
experiments on the mice.
Buthionine sulfoximine and diethylmaleate, two GSH depletors with different mechanism of action,
decrease considerably GSH in the brain (on 32 and 61%) and liver (on 56 and 70%), induce
hypothermia (-9 degrees C) and a big increase of tolerance to global cerebral ischemia (in 2.2 - 2.9
times). Activities of glutathione metabolism enzymes (glutathione S-transferase, glutathione
peroxidase and glutathione reductase) are not changed, that confirms significance of GSH
concentration itself but not its metabolism. The close correlation of all the four investigated
parameters are determined both the average (P <0.01)and individual data (P < 0.001): positive
correlations of cerebral and hepatic GSH level with body temperature and negative correlationsof
these three parameters with tolerance to cerebral ischemia. The multiple correlation coefficient R of
the individual tolerance to cerebral ischemia with the combined influence of GSH concentration and
body temperature is + 0.791. It is!significantly higher than both pair Spearman's correlation
coefficients (P < 0.05). Five GSH prodrugs (diethyl, n-propyl, isopropyl and butyl GSH esters and
oxothiazolidine carboxilate) and GSH itself usually decrease only slightly body temperature but in the
most series do not influence on cerebral GSH level and the tolerance to cerebral ischemia. The
correlation of these parameters is absent.
The increase of ischemic tolerance and considerable hypothermia connected with not GSH
accumulation, but its decrease. The posible cause may be the two facts that GSH is a potential source
of neurotoxic amino acids (glutamate and cysteine) and it has neuromodulator and neurotransmitter
activities in the brain.




                                                 115
                                         Traumatic Brain Injury




PT-1.


Effect of mild hypothermia on neuropsychological outcome in severe head injury

Takanori Hayakawa, Yoshio Takasato, Hiroyuki Masaoka, Yoshihisa Ohta, Hiroshi Yatsushige,
Toshiya Momose, Susumu Hirota, Mutsumi Fujii
Department of Neurosurgery, National Disaster Medical Center, Tokyo, Japan


[Objective] Recovery of cognitive function after head injury is important for the patients to be
reintegrated in the society. The effect of mild hypothermia for severe head injury is still controversial,
and little is known about the effect of hypothermia on cognitive function. We examined the results of
neuropsychological assessment and its serial change for severely head injured patients treated with
mild hypothermia.
[Patients and methods] The subjects were 10 cases selected from total 71 consecutive cases of severe
head trauma treated with mild hypothermia. The mean age of the patients was 26.1 (range 14 to 64).
They consisted of 5 males sand 5 females, the mean Glasgow Coma Scale (GCS) score was 4.7 (range
3 to 8). Abnormal pupillary response was seen in 8 cases. All the patients received hematoma removal
with decompresssive craniectomy. The target brain temperature was maintained at 33 to 35 ℃ for 3
days. Each patient received neuropsychological examination twice. The first examination was
administered at discharge (mean Day 66) and the second was 1 year after injury (mean Day 372).
Neuropsychological test to measure general impairment included the Wechsler Adult Intelligence
Scale - Revised (WAIS-R) for the adult and WISC-R for a 14 years old patient. The tests for frontal
lobe were also performed by Wisconsin card sorting test: Keio version (KWCST) and verbal fluency
test.
[Results] The score of full-scale intelligence quotient (FIQ) was 68.6±5.8, verbal IQ (VIQ) was
70.9±3.8 and performance IQ (PIQ) was 73.7±6.4 at discharge (IQ data: mean ±standard error). Only
one case was within the average normal range (90 to 109) and 7 cases were below 80. At the second
examination, all cases improved in FIQ, VIQ and PIQ except one patient who showed excellent result
at the first test. The score of FIQ was 85.3±4.4 at the second test. 8 patients reached the level over 80.
VIQ improved to 82.5±2.8 and the improvement of PIQ to 96.3±6.2 was prominent at the second test.
7 patients could return to previous social activity.   Frontal lobe function was poor in 4 cases out of 6
examined cases at discharge, but at the later time, 5 out of 8 examined cases achieved good results.
[Conclusion] Even in the good outcome cases, cognitive impairment was common at discharge
among the severely head injured patients treated with mild hypothermia. However, the cases with poor
neuropsychological performance at discharge showed steady recovery at one year later. Further
research is necessary to clarify the effect of hypothermia on neuropsychological outcome.




                                                   116
                                         Traumatic Brain Injury




PT-2.


Posttraumatic hypothermia provides persisting cerebrovascular protection

Yuji Ueda1, Enoch Wei2, John T.Povlishock2
Department of Neurosurgery1, Shuto General Hospital, Yamaguchi, Japan
Department of Anatomy and Neurobiology2, Medical College of Virginia Campus of Virginia
Commonwealth University, Richmond, VA, USA.


[Objective] Recently, our group demonstrated, in rats, that moderate hypothermia followed by gradual
re-warming exerts profound cerebrovascular-protection when assessed up to six hours following
traumatic brain injury (TBI) via the use of cranial windows. However as these studies were confined
to the acute post injury period, we questioned whether this same cerebrovascular protection extended
into more chronic survival periods.
[Materials and methods] 18 Male SD rats were randomized to three groups, TBI without hypothermia,
TBI with posttraumatic hypothermia, and sham TBI. Seven days later, the pial arteriolar
responsiveness to various vasodilator agents (acetylcholine, pinacidil, sodium nitroprusside and
hypercapnea) were assessed through a closed cranial window.
[Results] The sham TBI and TBI with hypothermia groups showed normal vasoreactivity to all
vasodilator agents, however, the non-hypothermic animals showed significantly reduced
responsiveness to these agents. [Conclusion] These results confirm that TBI causes prolonged
cerebrovascular impairment to various known vasodilator agents. Moreover, this study also
demonstrates that the use of posttraumatic moderate hypothermia followed by slow rewarming
provides enduring protective effects for the injured pial microcirculation.




                                                  117
                                        Traumatic Brain Injury




PT-3.


Immune enhancing effect of arginine on severe traumatic brain injury

Akira Utagawa, Atsushi Sakurai, Kosaku Kinoshita, Takashi Moriya, and Nariyuki Hayashi
Department of Emergency and Critical Care Medicine, Nihon University School of Medicine, Tokyo,
Japan


Objective: The purpose of this study was to evaluate the immune enhancing effect of arginine (IEEA)
in severe traumatic brain injury patients performed brain hypothermia, and to evaluate the impact of
IEEA on neurologic outcome.
Methods: Thirty two severe closed head injured patients (a score of 3 to 8 on the Glasgow Coma
Scale) were enrolled. They were cooled to 32-33°C after injury, kept at 32 to 33°C for 48 hours at
least, and then re-warmed. Patients were assigned randomly to intravenous arginine (0.3g/kg; n=16) or
a placebo (intravenous saline; n=16) during re-warming phase.
Measurements and Main Results: Immune enhancing effects were evaluated by measurement of (1)
peripheral lymphocyte cell counts, CD subsets, and PHA response, (2) HPA axis related hormones, (3)
blood glucose, and (4) nitric oxide metabolite (NOx). Peripheral blood samples were collected at 2
time points: at cooling phase (32-33°C) and the endpoint of re-warming (36°C). At the endpoint of
re-warming, lymphocyte cell counts, CD3 and CD4 subset, and PHA response were significantly
higher in arginine infusion group (AI group) than placebo group (p<0.05). The concentration of
growth hormone (AI group, 6.5 ± 1.4 ng/ml; placebo group, 2.2 ± 1.3 ng/ml)and prolactin (AI group,
4.1 ± 1.6 ng/ml; placebo group, 1.4 ± 0.4 ng/ml) were also significantly increased in AI group(p<0.05).
In regard to peripheral concentration of blood glucose and NOx, there was no significant difference
between the groups. The patients in placebo group had more hospital days with infectious
complications than the patients in AI group.
Conclusions: In severe closed head injured patients performed brain hypothermia treatment,
intravenous infusion of arginine promotes immune enhancing effect and improves hospital days with
infectious complications.




                                                 118
                                        Traumatic Brain Injury




PT-4.


Evaluation and optimal temperature of three-day cooling hypothermia in patients with
severe traumatic brain injury.

Hiroyuki Masaoka1, Yoshio Takasato1, Yoshihisa Ohta1, Takanori Hayakawa1, Hiroshi Yatsushige1,
Toshiya Momose1, Shin Hirota1, Mutsumi Fujii1, Masato Homma2
Department of Neurosurgery1, Critical Care Medicine2, National Disaster Medical Center, Tokyo,
Japan


[Objective] Although the NABISH denied the effect of moderate hypothermia in improving the
outcome of patients with severe traumatic brain injury (TBI), hypothermia has been widely used as a
last resort added to conventional therapies. Since 1997, we have adopted a present protocol of
hypothermia for those patients to prevent many hazardous complications. Although our target
temperature start at 35℃, if their intracranial pressure (ICP) remained higher than 20mmHg at 35℃,
we lower their target temperature stepwise to 32℃ until getting ICP under 20mmHg. In the present
study, we evaluated the effect and safety of this cooling protocol (ICP-oriented stepwise temperature
lowering method strating at 35℃) and clarify its optimal temperature retrospectively.
[Materials and methods] A total of 41 patients with severe TBI, 9 to 73 years of age, were enrolled.
The initial Glasgow Coma Scale scores of all patients ranged from 3 to 8 (average: 5.1). All patients
but one who had intracranial mass lesions and significant brain swelling underwent hematoma
removal operations and/or craniectomies (SDH 27 cases, EDH 3, and brain swelling 11). Mild
hypothermia was induced by surface cooling and continued for 3 days at the target temperature as
mentioned above. Then, the patients were rewarmed gradually at a rate 0.5℃/ day. The outcome of all
patients was assessed at discharge according to the Glasgow Outcome Scale.
[Results] The target temperature was 16 cases at 35℃, 10 at 34℃, 5 at 33℃, and 10 at 32℃. At
discharge, the mortality rate was 39% (16 of 41 patients) and the rate of functional recovery (good
recovery and moderate disability) was 37% (15 of 41) in all patients. Mild cooling patients at 34-35℃
(26 cases) had the mortality rate by 26% and the functional recovery rate by 54%. In this group, more
than half of the patients achieved good outcomes. Moderate cooling patients at 32-33℃ (15 cases)
had the mortality rate by 60% and the functional recovery by 7%. In this group, all patients except one
had poor outcomes. Regarding complications, one patient died of septic shock. The remaining patients
had no lethal complications.
[Conclusion] These results suggest that mild hypothermia continued for 3-day using a cooling blanket
is a safe and effective measure for severe TBI. Delayed gradual decreasing of body temperature below
34℃, however, cannot improve the prognosis. Thus, taking account of these results, 34 to 35℃ seems
to be the optimal temperature at the present time.




                                                     119
                                        Traumatic Brain Injury




PT-5.


Influence of mild hypothermia on evoked potential, PbO2, serum and CSF biochemical
factors in the severe head injury

Yan Yi, Tang Wenyuan, He Jianguo, Huang Hailin.
Department of Neurosurgery, The First Affiliated Hospital of Chongqing University of Medical
Sciences, Chongqing, China.


Objective: To observe the changes of multiple factors after severe brain injury and the effect of mild
hypothermia on acute severe brain injury.
Methods: 86 patients with acute severe head injury (GCS 3-8, admitted within 10 hours from injury)
were selected for this study. All patients were admitted into the intensive care unit and divided into 2
groups, Group A (GCS6-8) and Group B (GCS3-5). Patients were also randomly assigned to either
hypothermia and normothermia subgroups. Patients in the hypothermia subgroup were cooled to 33℃
and kept at 32-34℃ for 3-5 days. Patients in the Normothermia subgroup received ordinary treatment.
Brain tissure PO2 (PbO2) was continuously monitored. Median nerve short-latency somatosensory
evoked potentials (SLSEP) and brain stem auditory evoked potentials (BAEP) were recorded before
cooling and 4, 24, 48, 72, 96 and 120 hours, respectively after cooling and temperature resuming.
Serum electrolytes, CSF PH and CSF lactate level were examined before cooling, 24, 48, 72 hours
after cooling and temperature resuming. The changes of all factors were analyzed by statistical
methods.
Results: In the Group A, N20 amplitudes in SLSEP and I/V amplitudes in BAEP after mild
hypothermia treatment in the hypothermia group differed significantly from those in the control group
(P<0.05). CSF lactate level and PbO2 were lower significantly in hypothermia subgroup than that in
nomorthermia subgroup (P<0.05). However, in the Group B, no significant difference in above
parameters was found. In both group (A and B), serum K+, Ca++ was decreased in hypothermia
subgroup significantly, PaO2 was higher during cooling than that before cooling. CSF PH was in
acidosis condition from beginning to end, and serum Na+ showed no difference in hypothermia and
nomorthermia subgroup.
Conclusions: Treatment with mild hypothermia (32-34℃) in patients with severe brain injury and
GCS of 6-8 has a significant neuroelectrophysiological effect and decrease CSF lactate level and
PbO2.Nevertheless, the effect of mild hypothermia in the GCS 3-5 group is not apparent. Mild
hypothermia may lead to decreased serum K+, Ca++.




                                                  120
                                         Traumatic Brain Injury




PT-6.


Hypothermia may attenuate not only IL-6 but also MMP-9 (matrix metalloproteinase-9)
of systemic and internal jugular blood from the inflammatory response to traumatic
brain injury in humans.

Eiichi Suehiro1, Hirosuke Fujisawa1, Tatsuo Akimura1, Hideyuki Ishihara1, Michiyasu Suzuki1,
Susumu Yamashita2, Tsuyoshi Maekawa2
Department of Neurosurgery, Clinical Neuroscience1 and Advanced Medical Emergency & Critical
Care Center2, Yamaguchi University School of Medicine, Yamaguchi, Japan


[Objective] Recently some experimental data have shown that matrix metalloproteinase-9 (MMP-9)
are increased after traumatic brain injury (TBI) which degrade components of the basal lamina,
causing disruption of the blood brain-barrier. However, posttraumatic secretional patterns of MMP-9
in humans are unknown. In this study, we investigated the pattern of increased MMP-9 in plasma after
TBI in the hypothermic therapy and at the same time, we investigated the pattern of IL-6 levels of
serum, because both of them will be activated during inflammatory states. [Materials and methods]
Using the enzyme immunoassay (EIA), MMP-9 and IL-6 levels in blood from the systemic artery and
internal jugular vein in 8 patients of TBI were measured at 0, 1 and 3 days post-injury. All patients
underwent hypothermia of 32-35 degrees C ranged from 3-10 days post-injury dependent on
intracranial pressure. [Results] Before inducing hypothermia, MMP-9 levels in the arterial and internal
jugular venous blood exceeded the normal range. Specifically, the presence of MMP-9 levels in
internal jugular vein greater than arterial levels was detected in most of the patients (6 out of 8). After
inducing hypothermia, MMP-9 levels in the arterial and internal jugular venous blood decreased
significantly to normal range at 1 and 3 days post-injury. While IL-6 levels in the arterial and internal
jugular venous blood before inducing hypothermia exceeded the normal range with the levels in
internal jugular vein greater than arterial levels in all patients. Persistent with previous reports, after
inducing hypothermia, levels of IL-6 decreased significantly at 3 days post-injury. In addition to these
changes, a significant correlation between levels of MMP-9 and IL-6 in internal jugular venous blood
was seen during investigating period. [Conclusion] These results indicate that MMP-9 is elevated in
patients with acute TBI. This enzyme may play an important function in the traumatic brain damage.
This elevation of MMP-9 is associated with inflammatory events following TBI.                Furthermore,
hypothermic intervention may suppress this elevation of MMP-9 with suppression of inflammatory
response followed by neuroprotection to TBI.




                                                   121
                                        Traumatic Brain Injury




PT-7.


Neuropsychological recovery in pediatric patients with acute subdural hematoma
treated with mild hypothermia therapy: Report of two cases

Shoji Yokobori, Hiroki Tomita, Osamu Tone, Masashi Tamaki, Youhei Sato, Motoaki Nakabayashi,
Shinji Inada, * Atsushi Katsumi, * Shinichirou Suzaki, * Tomoko Yamazaki, * * Hiroyuki
Yokota,*** and Yasuhiro Yamamoto,***
Department of Neurosurgery,
*Department of Emergency and Critical Care Medicine,
**Department of Psychiatry, Musashino Red Cross Hospital, Tokyo, Japan
***Department of Emergency and Critical Care Medicine, Nippon Medical School, Tokyo, Japan


Purpose: We studied the neuropsychological outcome of pediatric patients with severe head injuries
who were treated with mild hypothermia.
Methods: Two children were treated with mild hypothermia after the evacuation of acute subdural
hematomas (ASDH). Neuropsychological examinations were conducted six months and one year after
injury. WISC-Ⅲ and the social maturity scale were used to score total intellect and social behavior.
Case 1. An 11-year-old boy who fell from a height of 2.5 m, striking the occiput, was admitted with a
Glascow Coma Scale (GCS) of 4 and both pupils dilated. Computed tomography (CT) on admission
showed a right ASDH, necessitating emergency decompressive craniectomy and hematoma removal.
He was treated with mild hypothermia for 5 days, which controlled intracranial pressure (ICP)
satisfactorily.
Case 2. The condition of a 6-year-old girl admitted with severe head injuries sustained in a traffic
accident deteriorated and her GCS fell to 5 (E1V1M3), and both pupils were dilated. Emergency CT
showed a left ASDH and acute brain swelling, necessitating decompressive craniectomy and
hematoma removal.     She was treated with hypothermia for 22 days, resulting in moderately high ICP.
Results: Both patients regained consciousness and were discharged without motor deficits. The mean
WISC-Ⅲ year after injury in the two cases was FIQ±SD, 119.5±9.2; VIQ±SD, 119.5±5.0; and PIQ±
SD, 116.5±13.4; and their social maturity scale scores indicated adequate social behavior.
Conclusion: Our results show that mild hypothermia is a beneficial therapy in preserving
neuropsychological function in pediatric patients with severe head injuries. Further study is now
needed with a large population.




                                                 122
                                        Traumatic Brain Injury




PT-8.


Management of patients with traumatic brain injury: Hypothermia therapy and
importance of temperature management.

Hirosuke Fujisawa, Eiichi Suehiro, Hiroshi Yoneda, Tatsuo Akimura, Michiyasu Suzuki, Susumu
Yamashita, Tsuyoshi Maekawa
Departments of Neurosurgery and Emergency Medicine, Yamaguchi University School of Medicine,
Japan


In our institute, patients with severe head injury were treated using various approaches such as
barbiturate coma prior to 1994. At that time, we did not recognize the importance of temperature
management. Brain hypothermia therapy was initiated in our institute in 1994. And, at the same time,
we managed the temperature of patients. On the basis of our experience from 1989 to 2003, we report
the results and the problems associated with managing patients with severe head injury including
hypothermia therapy. We focus on the first 5 years (1989-1993), the next 6 years (1994-1999), and
recent experience (2000-2003), and compare outcomes among these eras. Recently, our management
of patients with severe head injuries has matured. Intracranial hematomas are evacuated, and external
decompression is performed. In patients for whom hypothermia therapy is appropriate, brain and body
temperatures are maintained at 32-33℃ for 3-8 days under generalized neuroleptanalgesia (NLA).
Intracranial pressure, temperatures of brain, jugular vein, bladder, pulmonary artery and palm, and O2
saturation in the jugular vein are measured continuously. Systemic circulation is monitored using a
Swan-Ganz catheter. Blood gas, blood cells, and chemical data are frequently checked. Although
complete maintenance of hematocrit, hemoglobin, and albumin at the target values is difficult,
infection and liver dysfunction can be easily managed. Intensive care using various monitoring tools is
necessary for patient management during hypothermia or even normothermia therapy. Frequent mouth
care by brushing with a disinfectant seems to be important for protecting against infection. NLA is
useful for inducing and maintaining hypothermia, and for maintaining peripheral circulation, which
seems to be helpful for protecting against infection. Monitoring cardiac function and systemic
circulation using a Swan-Ganz catheter is very useful for patient management. We believe that patient
selection for hypothermia therapy and temperature management for whom hypothermia is not applied
is important for managing patients with severe head injuries.




                                                 123
                                        Traumatic Brain Injury




PT-9.


Survival from an acute subdural hematoma with accidental hypothermia and cardiac
arrest: A case report

Kosaku Kinoshita, Akira Utagawa, Takashi Moriya, Atsushi Sakurai, Makoto Furukawa and Nariyuki
Hayashi
Department of Emergency and Critical Care Medicine, Nihon University School of Medicine, Japan


 A 57-year-old man was admitted to the emergency and critical care department after resuscitation
cardiopulmonary arrest (CPA) with accidental hypothermia. A brain CT scan revealed an acute
subdural hematoma, which was considered to be the cause of the accidental hypothermia (31.5
centigrade) and CPA. The active core re-warming until 33 centigrade using intravenous infusion of hot
crystalloid performed. The patient underwent craniotomy after admission, and the bladder temperature
was controlled at 33 to 34 centigrade during surgery.        Mild hypothermia (34 centigrade) was
continued for 3 days, and the patient was gradually re-warmed. After rehabilitation, the patient was
transferred to the satellite hospital with a partially dependent daily life. Although traumatic brain
injury with CPA is extremely unfavorable outcome, successful recovery from an acute subdural
hematoma that presented with accidental hypothermia and CPA is less reported. This case illustrates
the ability and possibility of therapeutic hypothermia after active core re-warming until 33 centigrade
from an accidental hypothermia.




                                                 124
                                            Postresuscitation




PP-1.


Influence of brain hypothermia on blood IL-6 levels on the post-resuscitated patients
after cardiac arrest.

Ryuzo Abe, Hiroyuki Hirasawa, Shigeto Oda, Hidetoshi Shiga
Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba
University


Introduction: Although the neuroprotective mechanism of hypothermia is not well known, there are
reports that hypothermia may attenuate the inflammatory response which plays a central role in the
pathophysiology of cerebral ischemia- reperfusion injury. In our institution mild hypothermia has been
applied to the post- resuscitated patients after cardiac arrest, where rectal temperature has been
maintained at 34°C for 72 hours. In the ICU we routinely measure blood IL-6 level as a sensitive
indicator to evaluate the magnitude of inflammatory response. Therefore, the present study was
undertaken to investigate the influence of hypothermia on the blood IL-6 level to elucidate the
mechanism of neuroprotective effects of hypothermia. Methods: The background and clinical course
of post- resuscitated patients after cardiac arrest were examined. Blood IL-6 level was measured each
day and the influence of hypothermia on blood IL-6 level was examined by comparing that of patients
who received hypothermia (hypothermia group:HG) and that of patients who did not (NHG).
Results: During the past three years, 31 patients after cardiopulmonary resuscitation were admitted to
the ICU and 13 underwent mild hypothermia. Eight of those 13 patients (62%) survived. The average
age of the 13 patients was 50.5 years old and the mean length of their ICU stay was 18.4 days. The
cause of cardiac arrest included arrhythmia, asphyxia, bronchial asthma attack, multiple trauma,
hanging and hyperpotassemia due to chronic renal failure. The background of the patients who had
undergone hypothermia differed from that of patients who had not because the indication of
hypothermia was decided depending on many factors such as patient's age, presence of bystander CPR,
time from cardiac arrest to return of spontaneous circulation (ROSC), and neurological findings after
ROSC. Logarithmic value of blood IL-6 level on admission was 2.08±0.67 pg/mL in HG, that tended
to be higher than that of 1.79±0.44 in NHG. However, on the 4th day, at the end of the maintenance of
body temperature at 34°C, it was 1.72±0.45 in HG and 1.93±0.51 in NHG. On the 7th day when
hypothermia and re-warming had completed, it was 1.68±0.51 in HG and 1.97±0.41 in NHG. Thus,
blood IL-6 levels in HG tended to be lower on each day during hypothermia compared with that in
NHG even though it was not significantly different. Conclusion: Though the patients were not divided
randomly and the number of objects in both groups was small, it suggests that the beneficial effect of
hypothermia might be through the inhibition of inflammatory response. These data warrant further
investigation.




                                                 125
                                            Postresuscitation




PP-2.


Brain hypothermic therapy following Cardio pulmonary bypass for cardiac arrest
patients who did not respond to ACLS

Yoshihiro Takeyama, Kazuhisa Mori, Hitoshi Kano, Satoshi Nara, Yasushi Itoh, Mamoru Hase,
Hitoshi Imaizumi, Masamitsu Kaneko, Yasufumi Asai
Department of traumatology & CCM, Sapporo Medical University, Sapporo, JAPAN


Study objective: Cardiac arrest patients who do not respond to ACLS have a poor neurological
outcome. However, some patients obtain good neurological recovery with a cardiac support device.
We sought to determine the usefulness of BHT (brain hypothermic therapy) following CPB (cardio
pulmonary bypass) in cardiac arrest patients.
  Methods: We performed a retrospective chart review of cardiac arrest patients with CPB who could
not respond to ACLS between 1999 and 2003 in the ED. We have done BHT (34℃,2-3days)
following CPB in patients who conformed to the following inclusion criteria. 1. their cardiac arrest
was witnessed. 2. failure to respond to ACLS. 3. successful intervention for original cause of cardiac
arrest was performed. 4. circulation was stabilized following intervention. We evaluated their ECG on
admission (VF or non-VF) and neurological outcome (dead, vegetative state, severe disabilities,
moderate   disabilities, good recovery) as measured by one-month Glasgow outcome scale (GOS).
  Results: Resuscitation with CPB was attempted in thirty patients (age 52:male 26, female 4),and
successfully achieved in 17 of them (57%). 8 of 15 patients who received BHT following CPB (53%)
obtained a good neurological outcome (MD and GR), and 2 (13%) died during BHT. 9 of twenty-four
patients who were VF on admission obtained a good neurological outcome (MD and GR: 38%). Six
patients were non-VF, and none of them had a good neurological outcome.
  Conclusion: we concluded that BHT following CPB is useful for cardiac arrest patients with VF
who could not respond to ACLS.




                                                 126
                                          Postresuscitation




PP-3.


Advanced challenge in resuscitative hypothermia in patients with cardiac arrest on
arrival at the emergency room.

Eiji Nitobe1, Ken Nagao2, Kazuhiko Okamoto1, Takahiro Miki1, Nariyuki Hayashi2
Department of Clinical engineer Surugadai Nihon University Hospital1, Department of emergency and
critical care medicine Nihon University School of Medicine2, Tokyo Japan


[Background] We have performed an invasive cardiopulmonary resuscitation (CPR) with emergency
cardiopulmonary bypass (CPB), coronary reperfusion therapy and mild hypothermia in patients with
out-of-hospital cardiac arrest due to cardiac causes since 1996. In out pilot study, mild hypothermia
could not be induced in three guarters of patients undergoing emergency CPB after failed standard
CPR and approximately half of patients undergoing mild hypothermia had an unfavorable neurologic
outcome. Therefore, we set about the advanced challenge in resuscitative hypothermia first.
[Methods] A prospective preliminary study was performed in 3 patients with cardiac arrest on arrival
at the emergency room meeting the criteria of deep hypothermia. Immediate deep hypothermia (28℃
or lower for 2 hours or shorter) was induced as soon as possible. Procedure of hypothermia was
performed by extra corporeal cooling methods with emergency CPB. During deep hypothermia,
emergency coronary angiography was performed, followed by percutaneous coronary intervention
(PCI) if needed. Active re-warming was conducted rapidly until core temperature at 34℃ after PCI.
Subsequently, mild hypothermia (34℃) was maintained for 2 days or more. Then, re-warming took at
least 2 days. The endpoint was a return of spontaneous circulation and a favorable neurologic outcome
at the time of hospital discharge.
[Results] Principal event-to-event intervals (mean±SD) were as follows. Collapse-to-emergency room
arrival ; 43±6 min, emergency room arrival-to-initiation of emergency CPB ; 24±7 min, initiation of
emergency CPB-to-28℃ ; 13±3 min, duration of deep hypothermia ; 43±8 min, 28℃-to-34℃ ; 20±6
min, emergency room arrival-to-return of spontaneous circulation; 106±10 min. All of the patients
achieved return of spontaneous circulation after attainment of a core temperature at 34℃ . However,
they died in hospital.
[Conclusions] Advanced challenge in resuscitative hypothermia which made a change from 28℃ to
34℃ was successful as cardiac resuscitation, but failed in cerebral resuscitation.




                                                  127
                                           Postresuscitation




PP-4.


Mild hypothermia for brain resuscitation combined with coronary revasculization
therapy for cardiopulmonary arrest caused by acute myocardial infarction using
external cooling blanket.

Shinichi Shirai, Masashi Iwabuchi, Jiro Ando, Keiji Ando, Takashi Yamada, Kei Nishiyama,
Hiroyoshi Yokoi, Hideyuki Nosaka, Masakiyo Nobuyoshi,
Department of Cardiology, Kokura Memorial Hospital, Japan


Background) Several lines of evidences show that revascularization therapy for acute myocardial
infarction (AMI) can improve on mortality and morbidity.                However, patients (pts) with
cardiopulmonary arrest (CPA) out-of-hospital caused by AMI (AMI-CPA) have still high mortality
rates and neurological disability even after successful revascularization therapy.
Methods) We evaluated the efficacy of mild hypothermia therapy for brain resuscitation combined
with revasculization therapy. Mild hypothermia was performed with cooling temperature of 34℃ by
external cooling blanket more than 2 days. Enrolled pts were comatose survivors (GCS≦6) who had
suffered cardiac arrest (CA) and return of spontaneous circulation (ROSC). All pts (N=10) were
underwent emergency coronary angiography and coronary revascularization therapy was performed
after ROSC. Survival rates and social recovery rates (recovery without neurological disabilities) were
compared between mild hypothermia therapy and conventional therapy (revasculization therapy
without hypothermia).
 Results) In the conventional treatment group, from May 1998 to May 2001, 20 AMI-CPA pts (All
CPA, N=168) were treated. The mean time from onset of CPA to start of cardio-pulmonary
resuscitation (CPR) was 6±5 min, and mean time until ROSC 30±18 min. Survival at hospital
discharge was 9 pts (45 %), and social recovery was achieved only 2 pts (10%). From June 2001 to
June 2002, 10 pts were enrolled for mild hypothermia therapy. CA origin was Vf in 8 pts, asystole in 2
pts. Culprit of AMI was LMT in 3 pts, LAD in 2 pts, RCA in 4 pts and LCx in 1 pt. Percutaneous
cardio-pulmonary bypass system was used in 1 pt, and intra-aortic balloon pumping in 5pts. The mean
time of CA-CPR was 8±5 min (p=N.S ,compared to conventional group) and mean time until ROSC
29±16 min (p=N.S). Survival at hospital discharge was 6 pts (60%, p=N.S). Successful social recovery
was achieved in 5pts (50%,p<0.05).
Conclusion) There were no significant statistical differences in survival rate between conventional
therapy group and hypothermia group.
However, revasculization therapy combined with mild hypothermia for brain resuscitation is
considered to be effective to achieve social recovery for the pts with AMI-CPA.




                                                  128
                                            Postresuscitation




PP-5.


Reversible changes of potassium, phosphate and magnesium during induced
hypothermia.

Takashi Moriya, Mitsuru Ishii, Atsushi Sakurai, Akira Utagawa, Kosaku Kinoshita and Nariyuki
Hayashi
Nihon University School of Medicine, Department of Emergency and Critical Care Medicine, Japan


【Objective】
It is well known that hypokalemia is one of the abnormalities in electrolyte balance that occur when
brain hypothermia is induced.       In addition, abnormalities in magnesium and phosphorus have been
pointed out severe traumatic brain injuries.   In the present study, we examined changes in electrolyte
balance when brain hypothermia was induced after cardiopulmonary resuscitation, and we investigated
its clinical significance, methods of treatment, and standards for management.
【Methods】
In 15 cases in which brain hypothermia was induced after cardiopulmonary resuscitation, magnesium
and phosphorus were evaluated, first at a patient’s admission, then within 6 hours after tympanic
membrane temperature (or bladder temperature) reached 34        due to induction of brain hypothermia,
and finally when normal body temperature was restored.
【Results】
(1) Urine volume increased significantly from 163        39 mL before induction of brain hypothermia
to 371      54 mL after induction. (2) Magnesium decreased significantly from 1.0         0.22 mmol/L
within 6 hours after induction of brain hypothermia.     Phosphorus also decreased significantly from
1.1      0.22 mmol/L at admission to 0.5        0.22 mmol/L after induction of brain hypothermia. (3)
Out of 8 cases (53 %) of hypomagnesemia, improvement to the normal value was observed in only 3
cases despite vigorous treatment. (4) Magnesium and phosphorus increased in all 6 cases in which
examination was possible after recovery of body temperature.
【Conclusion】
Abnormalities in electrolyte balance during induction and maintenance of brain hypothermia were
considered most likely to occur in relation to hypothermia-induced diuresis. Frequent checking is
necessary in electrolyte balance.




                                                   129
                                                Stroke




PS-1.


Time course of extracellular glutamate using a microdialysis for poor grade aneurysm
patients ―Preliminary reports― ―

Takashi Moriya, Atsushi Sakurai, Akira Utagawa, Kosaku Kinoshita and Nariyuki Hayashi
Nihon University School of Medicine, Department of Emergency and Critical Care Medicine, Japan


【Introduction】To objectively evaluate primary brain damage, we endeavored to measure the
concentration of extracellular glutamate using microdialysis within a few hours of onset and to analyze
criteria to carry out aggressive treatment for poor grade aneurysm patients.
【Materials and methods】Four consecutive patients, 4 case, 42-52 years of age, 2 male and 2 female,
poor grade SAH without intracerebral hematoma, WFNS Grade 5, were enrolled in the study.            As
early as possible, ICP monitoring and microdialysis probes were implanted (after informed consent
from patients’ families), and both were continuously measure.      Direct surgery was selected for all
patients within 48 hours.
【Results】(1) The ruptured aneurysm was in the anterior circulation in all cases. (2) The initial ICP
before ventriculostomy and brain hypothermia ranged from 18 to 38 mmHg. (3) The initial
concentration of glutamate varied widely, from 52 to 482 mmol/L. Four patients with controllable ICP
were divided into two groups.    One group had low levels of glutamate (n=2) and the other had high
levels (n=2).   In the low level group, the outcome was GR in 1, MD in 1.      Although the high level
group transiently showed controllable ICP, they reverted to uncontrollable ICP, with brain swelling on
day 4-10.   The outcome was D in 2.
【Conclusion】Ventriculostomy and brain hypothermia would be useful to control ICP.            However,
these results suggest that the measurement of extracellular glutamate using microdialysis within
several hours would be useful in detecting a contraindication for aggressive therapy including brain
hypothermia for poor grade aneurysm patients.




                                                  130
                                                Stroke




PS-2.


The evaluation of result of transcranial doppler sonography in the postoperative brain
hypothermia therapy for severe cases of subarachnoid hemorrhage.

Kyoko Ikakura, Yasutaka Naoe, Akiko Kitahashi, Kengo Onodera*, Motoaki Nakabayashi*, Akira
Fuse*, Hidetaka Satoh*, Hiroyuki Yokota*, Akira Kurokawa*, Yasuhiro Yamamoto*
Department of Emergency and Critical Care Medicine, Tama-Nagayama hospital, Nippon Medical
School
Department of Emergency and Critical Care Medicine, Nippon Medical School*, Japan


[Objectives] Transcranial Doppler ultrasonography (TCD) is a noninvasive monitoring technique that
can determine the direction and the velocity of blood flow in the large cerebral areteries, and can be
used to detect the cerebral vasospasm. The authors analyzed the 17 cases of the mild or very-mild
hypothermia therapy for severe aneurysmal subarachnoid hemorrhage to evaluate the influence on the
TCD findings by body cooling. [Method] Among the 104 patients of surgically treated cases of
subarachnoid hemorrhage, 28 cases were severe enough to have a score 3 to 6 on the Glasgow coma
scale .The brain hypothermia therapy was administrated to the 17 of 28 patients, 36-67 years of age,
because of their pupilary dilatation, delayed circulation time on cerebral angiography, or intraoperative
cerebral swelling.   Their body was cooled in the range of 32 and 35 ℃ using cool water blanket
technique before or soon after clipping of the aneurysm and maintained at the same temperature for
3-7 days .     TCD was monitored intermittently after admission, and mean flow velocity (MFV) of
middle cerebral artery and pulsatility index (PI) was recorded.   Continuous monitoring of intracranial
pressure (ICP) and jugular venous oxygen saturation were also performed.       The incidence of delayed
ischemic neurological deficits (DIND) was manifested by the appearance of ischemic lesion on the CT
finding. The outcome of each patient was assessed according to Glasgow Outcome Scale (GOS).
[Results] The DIND occurred in 4 patients.      DIND appeared on 4 of the 17 patients (23.5%), that is
slightly higher than that of all cases of subarachnoid hemorrhage (19.2%), but is not statistically
significant.   As for the period of hypothermia including the rewarming stage, the cases of DIND
required longer (15 days) than other cases (10.5 days). The uncontrollable elevation of ICP arose in
one case of DIND case. The acceleration of MFV was parallel to the appearance of DIND even in
the condition of body cooling. But, the PI was not useful to detect the vasospasm because of the
influence of ICP elevation or increased blood viscosity by low body temperature. The outcome of
DIND cases were GOS1: 1, GOS2: 1, and GOS3: 2, and that of non-DIND cases were GOS1: 3,
GOS2: 2, GOS4: 3, and GOS5: 4 cases. [Conclusion] The data of TCD should be influenced by the
mild hypothermia therapy, but the findings of MFV acceleration might be still useful.




                                                  131
                                                Stroke




PS-3.


Low body-temperature has been associated with more favorable outcome.

U.J. Weber, C. Fischer, B. Indredavik, B. Norrving, T. S. Olsen, A. Tere'nt, P. Wester.
The Nordic Cooling Stroke Study - NOCSS. Gentofte University Hospital, Hellerup, Denmark.


[Objective] Low body-temperature has been associated with more favorable outcome in patients with
acute stroke. Even minor differences in body-temperature are of significance. It is now widely
recommended to avoid fever in acute stroke. In experimental animals fever enhances ischemic brain
damage while hypothermia protects the brain from damage during ischemia. The protective effect of
hypothermia is even there when instituted hours after onset of the ischemic event. This is the basis for
the growing interest of investigating therapeutic hypothermia in patients with acute stroke.
Complications such as hypotension and cardiac arrhythmias often accompany induced mild
hypothermia (32-33 C) in anesthetized stroke patients. Feasibility and safety of surface cooling to 35.5
C in awake acute stroke patients has recently been demonstrated. Hypotension or cardiac arrhythmias
of clinical importance were not seen. We have now launched a controlled randomized multicenter
study of very mild hypothermia in stroke induced by surface cooling
[Study design] The study is designed as a multicenter, controlled, randomized study. Mild hypothermia
is induced by surface cooling. The target temperature is 35 C. The active cooling period is 9 hours
resulting in an average of 12 hours of hypothermia. Pethidin (meperidine) is injected intravenously to
treat shivering and discomfort. Re-warming of the patient is passive.
Inclusion criteria: Patients more than 18 years of age admitted within 6 hours with a
moderate-to-severe ischemic stroke (Scandinavian Stroke Scale 10 to 44) and with a Premorbid
Modified Rankin Scale score of no more than 2, are eligible for the study.
Exclusion criteria: Patients with severe heart conditions (NYHA Class III or IV), daily medication for
COLD, pregnancy, weight above 120 kilos, door to cooling time above 2 hours, significantly reduced
consciousness level (Scandinavian Stroke Scale sub score for level of consciousness 0 or 2), severe
aphasia.
Primary outcome parameters are: The 90-day clinical outcome, defined by SSS, NIHSS, MRS, Index
(BI) scores, SF-36, and mortality rates.




                                                  132
                                                Stroke




PS-4.


A survival case of the subarachnoid hemorrhage using brain hypothermia after the
recovery of spontaneous circulation from cardiopulmonary arrest: Case report

Kuwamoto K, Yokobori S, Takayama Y, Shiga N, Sato H, Yokota H, Yamamoto Y
Department of Emergency and Critical Care Medicine, Nippon Medical School.


 A 55-year-old woman was admitted to our intensive care unit with cardiopulmonary arrest(CPA). A
brain CT scan revealed a subarachnoid hemorrhage(Fisher group 3) and brain swelling.
After admission, the elevated intracerebral pressure was controlled by the moderate hypothermia
(34℃). On the next day after admission, the light reflex was appeared and electroencephalogram was
showed the burst and suppression. A cerebral angiography demonstrated a ruptured anterior
communicating artery aneurysm and an unruptured aneurysm located at the basilar tip. The neck
clipping was performed to the aneurysms with moderate hypothermia(32℃). During the surgical
procedure, the brain swelling was moderate enough to clip the aneurysms. After the operation, the
patient was gradually re-warmed. The patient moved to the other hospital with severe disability. The
aneurysmal SAH is one of the most common caused of CPA, but survival of SAH patients after CPA is
rare. In this case, a life was suspended by controlling ICP in the moderate hypothermia and performing
a clipping of the aneurysms. As a medical treatment strategy over a ruptured aneurysm, the moderate
hypothermia is considered to be one of the attractive cures.




                                                  133
                                              Stroke




PS-5.


Brain temperature in patients with chronic hydrocephalus after subarachnoid
hemorrhage

Yutaka Hirashima,    Michiyasu Takaba,      Kazuhiko Yamashita,       Kanehito Nogami,      Ryoichi
Masuda, Yoshiki Mino, Shunro Endo
Department of Neurosurgery, Toyama Medical and Pharmaceutical University, Japan


The relationships between temperature indices and clinical condition on admission or improvement
after ventriculoperitoneal (VP) shunting were evaluated in patients with subarachnoid hemorrhage
(SAH).   Brain temperatures were measured at intervals of 1 cm from the brain surface to the lateral
ventricle at shunt operation. Rectal temperature was also measured. The difference between
intraventricular and rectal temperatures was correlated with age (p=0.0486), Glasgow Coma Scale
(p=0.0129), Hunt and Hess grade (p=0.0101), and improvement score after VP shunting (p=0.0104).
Measurement of brain temperature may predict the outcome of VP shunting in patients with SAH.




                                                134
                                               Neonate




PN-1.


The changes of blood glutamate levels in hypoxic ischemic encephalopathy (HIE) cases
with brain hypothermia (BHT).

Kazumasa Kumazawa, Satoshi Ibara, Kousuke Kobayashi, Hideki Maruyama, Yoshinobu Maede,
Ryuichi Shimono, Takuya Tokuhisa, Eiji Kato, Yuko Maruyama
Division of Neonatology, Perinatal Medical Center, Kagoshima City Hospital, Japan


(Objective) Recently brain hypothermia (BHT) has been performed for hypoxic ischemic
encephalopathy (HIE) of severe asphyxiated infants, but the effect of BHT for HIE has not been
established. BHT is thought to affect metabolism of glutamate in the brain tissue. Therefore we have
studied changes of glutamate metabolism in HIE infants with BHT.
(Methods) Seven infants had been performed BHT. Entry criteria was as follows, 1) over 36 weeks’
gestation, 2) over 2000g, 3) pH at birth or on admission < 7.00, 4) Apgar score < 5 at 10 minutes, 5)
vigorous resuscitation including manual bagging over 10 minutes after birth, 6) clinical
encephalopathy such as coma, seizure and abnormal EEG. All infants were inserted a catheter from
internal jugular vein for the head side in order to monitor intracerebral temperature and collect blood
samples. Four infants with severe cardiopulmonary insufficiency had been referred for extracorporeal
membrane oxygenation (ECMO), and enrolled whole-body cooling by circulating cooled blood by
heat exchanger in ECMO circuit. Three infants had been performed selective head cooling by using
thermo-exchanger blanket around head. BHT had been performed for 72 hours to keep intracerebral
temperature around 35℃. Blood samples of radial artery and internal jugular vein (head side) were
obtained before and during BHT. We have measured blood glutamate levels in each case and evaluated
the differences of those between internal jugular vein (head side) and radial artery (∆ blood glutamate
level) which seems to indicate glutamate production in brain tissue.
(Results) Before BHT blood glutamate level in radial artery were 446.753±467.178nmol/ml, blood
glutamate level in internal jugular vein were 1094.521±1114.748nmol/ml. During BHT blood
glutamate level in radial artery were 192.129±185.032nmol/ml, blood glutamate level in internal
jugular vein were 387.736±425.490nmol/ml. It seems that blood glutamate level in internal jugular
vein and radial artery during BHT were low compared with before BHT. The ∆ blood glutamate levels
before BHT were 647.769±719.637nmol/ml,and the Δblood glutamate levels during BHT were
195.607±289.357nmol/ml. The ∆ blood glutamate levels during BHT were significantly low compared
with before BHT (p=0.0465).
(Conclusion) It was suggested that BHT seems to inhibit release of glutamic acid from nerve cell in
HIE cases with BHT.




                                                 135
                                             Neonate




PN-2.


Body temperature monitoring during brain hypothermia for newborn infants with
hypoxic-ischemic encephalopathy.

Kosuke Kobayashi 1), Satoshi Ibara 2), Hideki Maruyama 2), Eiji Kato 2), Yuko Maruyama 2)
1) Department of Obstetrics and Gynecology, Asahi General Hospital
2) Diviosion of Neonatology, Perinatal Medical Center, Kagoshima City Hospital


【OBJECT】 adult, brain hypothermia (BHT) is becoming popular strategy for resuscitation of brain
        In
damage. During BHT, brain temperature is routinely estimated by internal jugular vein (IJV)
temperature. But, in neonate, during BHT, definite method of monitoring brain temperature has not
been established. In order to estimate the optimal body temperature monitoring during BHT, we have
investigated the changes of cephalic vein blood (CVB) temperature, and the other temperatures such
as the tympanic membrane (TM), nasopharyngeal (NP), esophageal (EP), and rectal temperatures for
severe asphyxiated infants with hypoxic-ischemic encephalopathy (HIE) during BHT.【METHODS】
We have performed BHT for 5 severe asphyxiated infants with HIE. Selective head cooling by using
thermo-exchanger had been performed for 3 cases. The IJV catheter was cannulated at the induction of
cooling, and the CVB temperatures were monitored. General body cooling using ECMO for
respiratory and circulatory support had been performed for 2 cases. The CVB temperatures were aloso
monitored in these cases. In all cases, the TM, NP, EP, and rectal temperatures were continuously
monitored, and compared with the CVB temperatures statistically. 【RESULTS】(1)The temperatures
during BHT(mean±SEM);CVB temperatures 35.02±0.05℃, TM temperatures 34.00±0.07, NP
temperatures 34.49±0.07, EP temperatures 34.59±0.06, rectal temperatures 34.59±0.05. The CVB
temperatures were significantly higher than the other temperatures (p<0.05). (2) The differences
between the CVB temperatures and the other temperatures during BHT;the CVB temperatures - TM
temperatures 1.09 ± 0.06 ℃ , the CVB temperatures - NP temperatures 0.60 ± 0.07, the CVB
temperatures - EP temperatures 0.46±0.06, the CVB temperatures - rectal temperatures 0.44±0.06.
【CONCLUSION】Generally, BHT for infants have been performed with monitoring of body
temperature such as the TM, NP, EP, and rectal temperatures. But, this study suggest that such body
temperatures are not likely to be markers of brain tissue temperature. Therefore, during BHT,
monitoring the CVB temperatures is recommended.




                                                136
                                               Neonate




PN-3.


The change of brain oxygen extraction ratio and CO2 production in term infants with
hypoxic ischemic encephalopathy during brain hypothermia.

Takuya Tokuhisa, Satoshi Ibara, Kousuke Kobayashi, Hideki Maruyama, Yoshinobu Maede, Ryuichi
Shimono, Kazumasa Kumazawa, Eiji Kato, Yuko Maruyama
Division of Neonatology, Perinatal Medical Center, Kagoshima City Hospital, Japan


Objective. To determine whether Brain hypothermia (BHT) has any effects on Oxygen Extraction
Ratio (O2ER) and CO2 production (∆CO2) of brain tissue in term infants with hypoxic ischemic
encephalopathy (HIE).
Methods. Eleven infants had been performed BHT. Entry criteria was as follows, 1)over 36 weeks’
gestation, 2)over 2000g, 3)pH at birth or on admission < 7.00, 4) Apgar score < 5 at 10 minutes,
5)vigorous resuscitation including manual bagging over 10 minutes after birth, 6)clinical
encephalopathy such as coma, seizure and abnormal EEG. All infants were inserted a catheter from
internal jugular vein for the head side in order to monitor intracerebral temperature and collect blood
samples. Five infants with severe cardiopulmonary insufficiency had been referred for extracorporeal
membrane oxygenation (ECMO), and enrolled whole-body cooling by circulating cooled blood by
heat exchanger in ECMO circuit. Six infants had been performed selective head cooling by using
thermo-exchanger blanket around head. BHT had been performed for 72 hours to keep intracerebral
temperature around 35℃. Blood samples of radial artery and internal jugular vein (head side) were
obtained before, during and after BHT. We evaluated brain O2ER and Δ CO2 as follows.
O2ER:VO2/DO2×100, VO2 (O2 consumption)=C(a-v)O2×CO×10, DO2 (O2 delivery) =CaO2×CO×10.
∆CO2=PvCO2- PaCO2.
Results. 1) ECMO group (n=5): Before BHT O2ER was 21.1±7.0%, during 7.1±2.8% and after
13.8±8.2%. O2ER was significantly decreased during BHT compared with before BHT (p=0.03).
Before BHT ∆CO2 was 6±1.6mmHg, during 1.86±1.8mmHg and after 4.52±1.8mmHg.∆CO2 was
significantly decreased during BHT compared with before BHT (p=0.004).
2) Selective head cooling group (n=6): Before BHT O2ER was 25.6±10.9%, during 9.1±6.8% and after
19.3±10.5%. O2ER was significantly decreased during BHT compared with before BHT (p=0.01).
Before BHT ∆CO2 was 8.3±1.6mmHg, during 2.3±1.5mmHg and after 7.5±2.7mmHg. ∆CO2 was
significantly decreased during BHT compared with before BHT (p<0.0001).
Conclusions. Brain hypothermia with whole-body cooling by ECMO and selective head cooling were
performed for eleven infants who had moderate to severe hypoxic ischemic encephalopathy.O2ER and
∆CO2 were decreased during BHT compared with before BHT in both procedures. After BHT, O2ER
and ∆CO2 tended to increase. It was suggested that during BHT brain metabolism were suppressed in
infants




                                                 137
                                       Management and Monitoring


PM-1.


The automatic temperature management system in patients with mild hypothermia;
Three-case report

Yuko Shimizu, Noriko Sakurai, Yoko Hoshiya, Toshie Sasaki, Mieko Agata, Midori Matuzuki
Nihon University Itabashi hospital, Emergency and Critical Care center, Tokyo, Japan


Purpose: The managements of core temperature require the advanced skill during therapeutic
hypothermia in patients with severe brain damage. The authors had an experience using of new
cooling device (Arctic Sun Model 200), which is automatically acted according as changing in
patient’s temperature.   We report, here, the safe and simple automatic temperature management
system during mild therapeutic hypothermia
Materials and Methods: Six patients were registered in this study.      The bladder temperature was
measured every 20 minutes and controlled at 34°C for 48-72 hours using cooling device during
hypothermia.   After hypothermic therapy, the patients were gradually re-warmed at a rate of 1°C per
day. Patients were retrospectively divided into 2 groups: the automatic controlled group (n= 3) and the
manual controlled group (n= 3) during hypothermia. The speed (hours) that reached to target
temperature and the numbers of deviation (0.5°C or more) from target temperature were investigated
between groups at the first 24 hours
Results: All patients of the automatic controlled group reached to the target temperature within one
hour from hypothermia induction, and 2 episodes of the deviation of temperature > 0.5°C was
observed.   In the manual controlled group, the numbers of deviation from the target temperature were
counted 9 at the first 24 hours, respectively. No cardiac dysfunction and arrhythmias due to rapid
forced cooling using this system were observed.
Conclusion: Automatic temperature control system is very simple and useful for therapeutic
hypothermia after server brain damage.




                                                  138
                                       Management and Monitoring




PM-2.


Significance of musico-kinetico therapy for patients with severe brain injury following
brain hypothermia therapy

1
 Yuki Sato, 1Yukako Kobayashi, 1Akiko Yoshida, 1Midori Matsuzuki, 2Takashi Moriya, 3Ryo Noda and
1
 Nariyuki Hayashi
1
 Emergency and Critical Care Center, Nihon University Itabashi Hospital
2
 Department of Emergency and critical Care Medicine, Nihon University School of Medicine
3
 Art Planning Department, Osaka University of Arts


【Objective】Decreased catecholamines, including dopamine, in the cerebrospinal fluid can be a
causal pathophysiology underlying prolongation of unconsciousness after the completion of brain
hypothermia treatment, and this has been reported to be improved by administration of
neurotransmitters, the median nerve stimulation, etc. We have been performing musico-kinetico
therapy using trampoline, piano and saxophone since 2001 to reinforce treatments following intensive
care. In the present study, we performed neurochemical evaluations based on changes in clinical
symptoms and cerebrospinal fluid examination to investigate the clinical effects of musico-kinetico
therapy.
【Case reports】Case 1: A 78-year-old woman with a diagnosis of acute subdural hematoma and acute
myocardial infarction; treated with brain hypothermia up to the 4th day of the present illness; treated
with musico-kinetico therapy 8 times in total, starting on the 30th day of the present illness.
Case 2: A 56-year-old man with acute subdural hematoma and cerebral contusion; treated with brain
hypothermia up to the 9th day of the present illness; treated with musico-kinetico therapy starting on
the 35th day of the present illness.
Case 3: A 64-year-old woman with acute subdural hematoma, acute epidural hematoma and cerebral
contusion; treated with brain hypothermia up to several days of the present illness; treated with
musico-kinetico therapy starting on the more 3 months of the present illness.
【Results】(1) Facial expressions and limb movement were observed as changes in clinical symptoms.
Improvements were observed during musico-kinetico therapy in one case. 2. In cases in which
symptoms were improved, catecholamines in cerebrospinal fluid were elevated after musico-kinetico
therapy.
【Conclusion】Musico-kinetico therapy could be candidate therapeutic measures for recovery of brain
function following intensive care during the acute phase in patients with severe brain injuries who
were treated with brain hypothermia.




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PM-3.


The definition of hypothermic therapy and the meaning of anesthesia

Hiroshi Kimura
Kimura clinic, Saitama, Japan


[Objective] In 1950, Prof. Bigelo (Toronto University, Canada) presented the first definition of the
hypothermic anesthesia. The following fact gave him a hint; drown drunk-lady into the cold river in
severe winter made a miracle recovery from temporary death. Using of anesthesia made a same
condition as animal winter sleeping (hibernation) and he gave the proof by animal experiment.
Additionally it has been known that using major tranquilizers can induce the artificial hibernation to
the human on the anesthesia and that the artificial hibernation induced by major tranquilizers can
prevent sympathetic effects in the hypothermia, for example shivering, hyper-secretion and
hypermetabolism etc.
[Method] In 1960’s, based on this definition, the hypothermic therapy had been undergone in
Japanese neurosurgical clinical field. The hypothermia was induced with the artificial hibernation as
the hypothermic therapy for trauma and neurosurgical operation etc. The artificial hibernation was
induced by anesthesia using major tranquilizers, artificial morphine and anti-histamic drug. The
hypothermic therapy did not have major complication (pneumonia etc). And it was possible that the
hypothermic therapy was kept for a long time. In our experience, maximum period was 3 month
without pneumonia.
[Conclusion]
This anesthesia is very important in inducing and keeping a hypothermic therapy.
The merit of this hypothermic therapy:
1.        without major complication (Pneumonia etc)
2.        long time possible
3.        simple way
4.        low cost
Unless we use Winter Sleeping Anesthesia, it is difficult to say Hypothermic Therapy.




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PM-4.


Gut movement of patients treated with brain hypothermia

Kenji Okuno1, Kosaku Kinoshita 2, Takeki Ogawa 1, Nariyuki Hayashi 2
1
    Department of Emergency Medicine, Jikei University School of Medicine, Tokyo, Japan.
2
    Department of Emergency and Critical Care Medicine, Nihon University School of Medicine, Tokyo,
Japan.


Objective: Severe brain damaged patients treated with brain hypothermia occasionally suffered from
problems of infections and multiple organ failure. On the other hand, early enteral neutrition is
correlated with improvable of clinical outcome and enhanced immunocompetence. We compared
trans-gastric with trans-jejunal feeding for severe brain damaged patients treated with brain
hypothermia in acute phase.


Method: Seven severe brain damaged patients (GCS          8) treated with brain hypothermia were
examined. Within 24hours from the beginning of brain hypothermia, two kinds of X-ray absorbed
markers were putted into the stomach and jejunam. We examined the movement of markers, at 3hours,
6hours, 12hours, and 24 hours by using abdominal X-ray.


Results: All intra-jejunal markers moved from jejunum to anal-side. At 12 hours since markers were
putted in, 57 percent of intra-jejunal markers passed through small intestine, and a few markers were
even evacuated within 24 hours. However, all intra-gastric markers were remained more than 24 hours
in the stomach.


Conclusion: Trans-jejunal feeding in acute phase for severe brain damaged patients treated with brain
hypothermia can be one of the useful methods for their nutrition. Furthermore, early trans-jejunal
feeding could reduce the occurrence of complications associated with severe brain damage.




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                                        Management and Monitoring




PM-5.


A comparison of jugular venous bulb oxygen saturation during propofol anesthesia in
normothermic and mildly hypothermic neurosurgical patients

Masato Iwata,1 Masahiko Kawaguchi, 1 Satoki Inoue, 1 Masahiro Takahashi, 1 Toshinori Horiuchi, 1
Hitoshi Furuya, 1 Toshisuke Sakaki, 2
Departments of 1Anesthesiology and 2Neurosurgery, Nara Medical University, Nara, Japan


It has been shown that jugular venous bulb oxygen saturation (SjO2) is lower and the incidence of
desaturation of SjO2 (<50%) is higher during propofol anesthesia compared with inhalational
anesthesia under normothermic and mildly hypothermic conditions. However, dose-related influences
of propofol on SjO2 have not been clearly investigated. In the present study, we compared the
dose-related influences of propofol on SjO2 under normothermic and mildly hypothermic conditions in
neurosurgical patients.
Methods: After institutional approval and informed consent, 15 adult patients undergoing elective
craniotomy were studied. Patients were randomly allocated to either normothermic (NT) or mildly
hypothermic (HT) group. In the NT group (n=8), tympanic membrane temperature was maintained
between 36-37℃. In the HT group (n=7), patients were cooled and tympanic membrane temperature
was maintained at 34.5℃. All patients received target-controlled infusion (TCI) of propofol with
fentanyl administration. PaCO2 was maintained in normocarbia (35-40mmHg). After the induction of
anesthesia, the catheter was retrogradely inserted into the jugular bulb and SjO2 was analyzed. SjO2
was measured at predicted propofol concentrations of 3, 5, 7 µg/ml during the target temperature. All
values were expressed as mean±SD.
Results: There were no differences in demographic variables between the groups. At 3 µg/ml of
propofol concentration, SjO2 values were similar between the NT and HT groups (55±5% and 56±6%,
respectively) and the incidence of desaturation of SjO2 was similar between the NT and HT groups
(25%, 14 %, respectively). With an increase of propofol concentration to 5 and 7µg/dl, SjO2 values
and the incidence of desaturation of SjO2 did not change significantly.
Conclusion: These results indicate that propofol concentration at a level of clinical usage did not affect
SjO2 values under normothermic and mildly hypothermic conditions.




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PM-6.


Rapid induction of brain hypothermia by intra-arterial perfusion of crystalloid solution
in canines

1
 Motomasa Furuse, M.D., 2Tomio Ohta, M.D., 3Yoshihiko Kinoshita, 1Naofumi Isono, M.D., 1Kentaro
Nishihara, M.D., 1Toshihiko Kuroiwa, M.D., 4Mark C. Preul, M.D.
1
 Department of Neurosurgery, Osaka Medical College, Takatsuki, Japan
2
 Department of Neurosurgery, Tominaga Neurosurgical Hospital, Osaka, Japan
3
 Medical Intelligence Department, Nikkiso Company Limited, Tokyo, Japan
4
 Division of Neurosurgery Research, Barrow Neurological Institute, St. Joseph Hospital and Medical
Center, Phoenix, Arizona, USA


We have developed an extracorporeal cooling-filtration system for rapid induction of brain
hypothermia and investigated the safety and feasibility of the system in an animal model.
    Ringer’s solution cooled to about 7℃ was infused into the right common carotid artery through an
angiographic catheter via the right femoral artery in five adult canines (13.06 ±1.84 kg). Hypothermic
perfusion continued at a rate of 3 ml/kg/min for 30 minutes. Excessive fluid was ultrafiltrated through
a venovenous extracorporeal circuit via the right femoral vein. Temperature was monitored in both
cerebral hemispheres and rectum. Blood samples were obtained from the right jugular vein. Brain
tissue oxygen tension was measured in the right frontal lobe in three cases.
    The right brain temperature decreased to 33.9 ± 2.0 ℃ from 37.8 ± 1.4 ℃ 30 minutes after
initiation of perfusion, while left brain and rectal temperatures were 34.6 ± 1.6 ℃ and 34.3 ±
1.4 ℃, respectively. The cooling rate of the right cerebral hemisphere was advanced compared to that
of the rectum (3.9 ± 0.8 ℃/30min versus 2.7 ± 0.4 ℃/30min, P<0.05). Thirty minutes after
initiation of perfusion, jugular venous saturation increased to 96.6 ± 6.1 % from 89.8 ± 4.0 %,
although jugular venous hemoglobin and hematocrit decreased at the same time compared with
preperfusion values. Brain tissue oxygen tension increased 30 minutes after initiation of perfusion in
two out of three cases. In the rest case, brain tissue oxygen tension decreased slightly 30 minutes after
perfusion. The brain and rectal temperatures increased to almost preperfusion values 210 minutes after
initiation of perfusion. Animals awakened without neurological deficits.
    This study demonstrated that the extracorporeal cooling-filtration system safely and rapidly induced
brain hypothermia. This method may be potentially combined with endovascular surgery or therapy,
e.g., in intra-arterial thrombolysis for middle cerebral artery occlusion, or for selective brain region
cooling.




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                                    Management and Monitoring




PM-7.


Evaluation of cerebral and systemic flow/metabolism during brain hypothermia therapy

Yasuhiro Kuroda, Kazuhito Nitta, Muneyuki Ota, Jun Ohto, Yasushi, Fukuta, Toshiya Okahisa,
Tadashi Abe, Tetsuya Kitagawa, Shinji Nagahiro, Shuzo Oshita
Division of Intensive and Critical Care Medicine, Tokushima University Hospital, Tokushima, Japan.


<Introduction>
We evaluate the cerebral and systemic flow/metabolism by analyzing jugular venous and mixed
venous blood gases during brain hypothermia therapy.
<Patients and methods>
Five patients (26-63 years, male 3, female 2) with brain injury (1 subarachnoid hemorrhage, 3 cerebral
infarction, 1 postresuscitation encephalopathy) were included. Admission GCS scores were < 8.
Patients were sedated and mechanical ventilation was performed.     In all patients, brain hypothermia
therapy was applied: cooling periods for 1 day, maintenance period for 3 days at 33°C of jugular
venous temperature, and re-warming period for 3 days. Arterial, mixed venous, and jugular venous
blood was sampled.
<Results>.
There are no significant differences of jugular/mixed venous blood ratio for Pco2 (JV/V Pco2) and for
So2 (JV/V So2) between hypothermia period (32-34 °C) and re-warming period (35-37 °C).          JV/V
Pco2 was 1.13±0.1 (1.0-1.4) and cerebral hypo perfusion status was suggested if JV/V Pco2 decreased
under 1.0.   JV/V So2 was 0.82 ±0.13 (0.6-1.0) and JV/V So2 over 1.0 indicated brain hernia.
Jugular venous-arterial Pco2 difference (JAPco2) and mixed venous-arterial Pco2 difference (VAPco2)
values were significantly correlated with jugular venous So2 (Sjvo2) and mixed venous So2 (Svo2)
values inversely, respectively. JAPco2 values during cerebral no perfusion status in the patients with
poor (GOS: D) outcome (n=3) were significantly decreased compared than those in the patients with
good (GOS: MD and SD) outcome (n=2).
<Conclusion>
In addition to the absolute values, JV/V Pco2 and JV/V So2 were useful monitor of cerebral and
systemic blood flow/metabolism during brain hypothermia therapy.




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                                      Management and Monitoring




PM-8.


Significance of temperature gradient between brain and bladder in patients with severe
brain damage.

Atsushi Sakurai, Kosaku Kinoshita, Takashi Moriya, Akira Utagawa and Nariyuki Hayashi
Department of Emergency and Critical Care Medicine, Nihon University School of Medicine, Japan


Objective: A gradient between brain and core body temperatures is frequently observed in severely
brain-injured patients. We reported that jugular venous blood saturation (SjO2; %) was inversely
related to the temperature gradient between brain and bladder in a significant manner (Brain edema
2002, Hakone Japan). However, the threshold of temperature gradient is not well known. The aim of
this study was to identify the threshold of the temperature gradient between brain and bladder using
SjO2 and cerebral perfusion pressure (CPP)
Design: Prospective, observational study.
Setting: Neurosurgical intensive care unit of a university hospital.
Materials and method: Brain and bladder temperatures were measured in 16 (185 points) patients with
severe brain injury (7 patients with subarachnoid hemorrhage, 5 with cerebral hemorrhage, 4 with
traumatic brain injury). Brain – bladder temperature was used in calculation of temperature gradient.
SjO2 and CPP (mmHg) were also measured concomitantly. The mean value of SjO2 and CPP were
estimated at each temperature gradient.     Statistical significance was defined as p<0.05.
Result: An adverse temperature CPP under 50 mmHg was tended to be low in adverse temperature
gradient, however there were no significant differences at CPP with each temperature gradient. SjO2
was significantly higher in adverse or zero temperature gradient than others. SjO2 was significantly
lower at the temperature gradient 0.4℃ or more.
Discussion: We reported previously that temperature gradient between the brain and the bladder had a
significant inverse correlation with SjO2. The fluctuation of temperature differences between brain
and bladder temperature may occur in brain ischemia. Current study showed that SjO2 was
significantly higher at temperature gradient < 0℃ and lower at > 0.4℃. It suggests that the threshold
of the temperature gradient may be < 0℃ and > 0.4℃ in brain oxygen metabolism. Measuring brain
and bladder temperature could be useful monitoring for brain oxygen metabolism.
Conclusion: Increased temperature gradients (0.4 degree centigrade or more) may indicate brain
ischemia. Temperature gradient between brain and bladder could be useful for monitoring brain
oxygen metabolism.




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                                      Management and Monitoring




PM-9.


Requirements for nursing management of hypothermia therapy

Harumi Nishio, Midori Matuzuki, Yoshiko Yamamoto
Nihon University Itabashi hospital, Emergency and Critical Care center, Tokyo, Japan


The most important thing to manage the patients with brain hypothermia is the collaboration with the
medical doctors, clinical pharmacist, and each co-medical staffs in making the best use each
knowledge and skill.
The nurses, who work in their bedside all day, play the important roles for detecting the patient’s little
abnormalities through the nursing care. The nursing managements during the hypothermia for severe
brain damage are mainly consisted of three important points. They are 1) observation and monitoring
of the patient’s condition; 2) keep the target temperature; and 3) prevention of the medical
complications.
1) Observation and monitoring of the patient’s condition
The patients underwent the various monitoring, such as intracranial pressure, hemodynamics, EKGs,
and cardiac performance, during hypothermia.       If the patients have the some abnormalities of their
conditions, we evaluate that it is an urgent or not and report to the medical doctor very quickly.
2)   Keep the target temperature
To detect the excess fluctuations of the body temperatures, the temperatures of patients were
monitored every 20 minutes in the various portions, which are brain tissue, the blood of jugular vein or
pulmonary artery, and the bladder. In addition, we contrive the special nursing care methods, which
do not cause temperature fluctuations.
2) Prevention of the medical complications
Concerning the pulmonary complication, we have been executed the planed respiratory care. As a
result, the incidence of the pulmonary complications on cooling and re-warming period was
dramatically decreased.
Furthermore, when executing three points, the education for nurses is the most important.             We
periodically hold the lectures about the nursing care during hypothermia to acquire the knowledge and
skill. We support that the nurses have experience by practice under the guidance of expert nurses on
medical site. As for the remedy strategy of hypothermia is progressive, keeps pursuing safety and
effective nursing practice and management is required for us.




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