The Comparative Effects of Sevoflurane Versus Propofol in the

Document Sample
The Comparative Effects of Sevoflurane Versus Propofol in the Powered By Docstoc
					The Comparative   Effects of Sevoflurane Versus Propofol                                                                                                   in
the Induction and Maintenance    of Anesthesia in
Adult Patients
W. Scott Jell&h, MD, PhD*, Cynthia                             A. Lien,         MDt,   H. Jerrel Fontenot,         MD,     PhDS,      and
Richard Hall, MD, FRCPC, FCCP§
*Department   of Anesthesiology, Loyola University Medical Center, Maywood,       Illinois; tDepartment      of Anesthesiology,
The New York Hospital, Cornell Medical Center, New York, New York; SDepartment              of Anesthesiology,    University
Hospital of Arkansas, Little Rock, Arkansas; and SDepartments   of Anesthesiology       and Pharmacology       and of Surgery,
Dalhousie University, Victoria General Hospital, Halifax, Nova Scotia, Canada

         A randomized,       prospective     study was performed         at            groups. However, side effects involving airway excite-
         four institutions      to compare anesthetic         induction,               ment were more prevalent during mask induction with
         maintenance,      and recovery characteristics         between                sevoflurane as compared to propofol. Patients in the
         sevoflurane- and propofol-based         anesthesia in 186 ASA                 sevoflurane group were oriented and required postop-
         physical status I and II patients undergoing            elective              erative analgesia much earlier than those who received
         surgical procedures of l-3 h. Group 1 (n = 93) patients                       propofol. Both groups were hemodynamically           stable
         received sevoflurane-nitrous        oxide for both induction                  throughout    the study period. The incidence of postop-
         and maintenance of anesthesia while Group 2 (n = 93)                          erative nausea, vomiting,     and pain-discomfort    scores
         received propofol-nitrous       oxide anesthesia. Induction                   were similar between the two groups. Urinary specific
         of anesthesia and tracheal intubation times were signif-                      gravity decreased in the sevoflurane-treated         group
         icantly shorter with propofol (2.2 % 0.2 min, 5.1 ? 0.3                       while serum creatinine       and urinary    pH were un-
         min, respectively) than with sevoflurane (3.1 ? 0.2 min,                      changed from preoperative        values in both groups.
         7.2 + 0.3 min, respectively).          Emergence times after                  Sevoflurane compared favorably with propofol when
         sevoflurane (8.8 ? 1.2 min) were significantly           shorter              used for anesthesia for elective procedures       of l-3 h
         than with propofol(13.2       t 1.2 min). Overall frequency                   duration.
         of complication-free        induction,     maintenance,       and
         emergence did not differ between the two anesthetic                                                    (Anesth Analg        1996;82:479-85)

    nhaled volatile anesthetics are widely used for                                    diminished negative postoperative outcomes (nausea,
    maintenance of general anesthesia because of their                                 vomiting, depression) (3-5). Sevoflurane, a new in-
    ease of administration and predictable intraopera-                                 haled anesthetic, has a low blood solubility which
tive and recovery characteristics. Since the introduc-                                 provides for both rapid induction and recovery times
tion of propofol in the late 198Os, intravenous anes-                                  (6). The nonpungent odor of the drug makes it agree-
thesia is also now commonly used. The kinetics of                                      able for most patients, especially during an inhaled
propofol allow for rapid induction of anesthesia, ad-                                  induction of anesthesia.
equate maintenance, and rapid recovery of conscious-                                      This study was designed to compare the induction,
ness (1,2). Studies comparing propofol with inhaled                                    maintenance, emergence, and safety characteristics of
anesthetics generally have found propofol to be                                        sevoflurane anesthesia with those of propofol in pa-
superior in both recovery characteristics (times to                                    tients undergoing elective surgical procedures lasting
orientation, command response, eye opening) and                                        up to three hours.

   This work was supported           in part by a grant from Abbott         Labo-      Methods
    Presented   in part at the 1994 Annual           Meeting    of the American        After approval by the institutional review boards of
Society of Anesthesiologists,         San Francisco,      CA.                          the four participating study centers, 186 ASA physical
    Accepted   for publication      November      9,1995.                              status I and II patients provided informed, written
    Address   correspondence        and reprint    requests to W. Scott Jellish,
MD, PhD, Department            of Anesthesiology,      Loyola University     Med-      consent and were admitted to the study. All were
ical Center, 2160 S. First Ave., Maywood,             Illinois.                        older than 18 yr and were undergoing elective surgical

01996 by the International   Anesthesia   Research   Society
0003~2999/96/$5.00                                                                                                       Anesth   Analg   1996;82:479-85        479
480    JELLISH  ET AL.                                                                                                           ANESTH        ANALG
       COMPARISON      OF SEVOFLURANE     WITH   PROPOFOL                                                                            1996;82:479-85

procedures expected to last for up to 3 h. Patients were                  sympathomimetic         drugs were also recorded. Intraop-
excluded from the study if they had a history of neu-                     erative time intervals         recorded      included       induction
rologic disease, malignant hyperthermia,                preexisting       (start of anesthetic until loss of eye lash reflex), endo-
renal insufficiency,     had general anesthesia within the                tracheal intubation       (start of anesthetic until intuba-
last 2 wk, had a positive pregnancy test, or were breast                  tion), extubation (end of anesthetic until extubation),
feeding at the time of surgery.                                           command response (end of anesthetic until the patient
    Separate randomizations            were performed        at each      squeezed the independent              observer’s     hand on com-
study center in randomly             allocated equal blocks of            mand and demonstrated             purposeful      movement),        and
two, four, and six patients. Group 1 (n = 93) received                    orientation (end of anesthetic until the patient stated
sevoflurane as their primary anesthetic while Group 2                     his or her name, date of birth, and age).
(n = 93) received a propofol-based            anesthetic. Patients           Successful induction and emergence from anesthe-
were not randomized           until l-2 h prior to the surgery            sia were defined as the absence of any common side
when sealed randomized              envelopes were opened to              effects (coughing, breath holding, excitement, laryn-
reveal the treatment assignment for each patient. En-                     gospasm, excessive secretions, shivering, or any other
rollment occurred simultaneously               at all centers from        untoward      event) during that time period. The presur-
March 10 to October 28, 1993. Preoperative                   medica-      gical period was defined as the start of study drug
tions were administered          at the discretion of the anes-           administration      to the start of the surgical procedure,
thesiologist    and included metoclopramide               10 mg in-       i.e., skin incision, and the emergence period was from
travenously     (IV), ranitidine 50 mg IV, and midazolam                  the end of anesthesia to orientation. Successful main-
1-2 mg IV, given shortly before induction of anesthe-                     tenance of anesthesia was defined as the absence of
sia. Standard monitoring           was used. Patients received            any study drug-related          adverse hemodynamic             events
fentany12 pg/kg IV 2 min prior to induction of anes-                      (hypertension      [MAP > 15% above preinduction                    val-
thesia. In most instances, after loss of eyelash reflex,                  ues], hypotension        [MAP > 15% below preinduction
vecuronium       0.1 mg/kg IV was given prior to tracheal                 values],     premature       ventricular        contractions,       and
intubation.    After denitrogenation,           Group 1 patients          bradycardia      or tachycardia       judged subjectively        to be
had anesthesia induced by mask with sevoflurane                           significant for the patient by the anesthesiologist).
starting at 0.5% and incrementally             increased to 3.5%-             At the completion of surgery, neuromuscular                 block-
4.0% inhaled concentration            with 67% N,O in oxygen              ade was assessed for residual paralysis and, if found,
at a total gas flow of 6 L. Group 2 patients received                     was antagonized with neostigmine 70 pg/kg and gly-
propofol1.5-2.0       mg/kg IV for induction of anesthesia.               copyrrolate 15 pg/kg IV. Thereafter, administration                    of
Maintenance       anesthesia consisted of the primary an-                 the anesthetic was discontinued            and patients breathed
esthetic, along with 67% N,O in oxygen at a total gas                     100% 0,. To reproducibly            assess emergence time, the
flow of 3 L, titrated to maintain hemodynamic                    vari-    patient was asked in a normal tone of voice by an
ables within 15% of preinduction            levels. If the depth of       independent       observer to open his or her eyes. This
 anesthesia was considered            inadequate (indicated by            was repeated every minute until an appropriate                        re-
movement,       swallowing,       tearing, sweating,       tachycar-      sponse was obtained. Then when clinically appropri-
 dia, or mean arterial pressure [MAP] increases > 15%                     ate, tracheal extubation was performed.                The patient’s
 of that obtained 1 min prior to induction [preinduc-                     were then asked to squeeze the hand of the observer
 tion]), vital signs were recorded and the level of pri-                  every minute after tracheal extubation until a positive
 mary anesthetic was increased. If the patient did not                    response was again noted.
 respond to increases in the level of primary anesthetic,                     In the postoperative        period the patient was moni-
 additional doses of fentanyl up to l-3 pg . kg-’ . h-i                   tored for approximately           2 h by the independent             ob-
 were permitted.                                                          server. Levels of consciousness            were assessed and re-
    Demographic       data including        age, weight,      height,     corded every 5 min until all of the following discharge
 and duration of surgery were recorded for each pa-                       criteria were met: vital signs stable for 0.5 h; the pa-
 tient. In addition to the standard anesthetic record, an                 tient was conversant,        cooperative, alert, and oriented
 independent      observer recorded MAP and heart rate                    to time and place; and the patient had no intractable
 (HR) at baseline          (prestudy),      preinduction,       every     side effects. Once these criteria were met, the respon-
 minute from induction to incision, every minute for                      sible anesthesiologist        at each institution         discharged
 5 min after incision, and every 15 min thereafter until                  the patient. Additional          recovery      variables recorded
 the anesthetic was discontinued.             These values were           from the time the anesthetic was terminated included
 also measured after admission             to the postanesthesia          time to first postoperative        analgesia and the time until
 care unit and every 10 min thereafter until discharge                    eligible for discharge.         During the recovery            period,
 from the postanesthesia         care unit. The number of hy-              scores for the Objective Pain-Discomfort                 Scale were
 potensive episodes (MAP decrease of greater than 15%                     recorded upon admission              to the postanesthesia          care
 of preinduction       values) and the administration                of   unit and every 10 min thereafter up to 120 min. The
ANESTH ANALG                                                                                                             JELLISH ET AL.          481
1996;82:479-85                                                            COMPARISON         OF SEVOFLURANE            WITH PROPOFOL

Pain-Discomfort Scale was based on a total score be-         Table 1. Patient Characteristics,  Use of Preoperative
tween 0 and 10 where 0 = best and 10 = worst. The            Antiemetics,  and Surgical Subsets
total score was the sum of five subsections which                                                      Sevoflurane                  Propofol
evaluated blood pressure (hypo- or hypertension),
                                                             Sex (M/F)                                     40/53                     37/56
crying, movement, agitation, and verbal evaluation.
                                                             Age                                          44 2 13                   42 + 14
Each subsection was scored between 0 and 2. If pa-           Height (cm)                                 169 + 11                  167 + 12
tients required analgesia, morphine was administered         Weight (kg)                                  75 + 20                   76 + 18
and recorded. Meperidine was also used for analgesia         Metoclopramide                            36/93 (39%)               35/93 (38%)
or, if necessary, to control shivering. The incidence of     Ranitidine                                40/93 (43%)               37/93 (40%)
postoperative vomiting was recorded while the sever-         Midazolam                                 25/93 (27%)               26/93 (28%)
ity of nausea was assessed using a loo-mm visual             Surgery type
                                                                Musculoskeletal                             32%                        34%
analog scale system. The number and dose of anti-
                                                                Intraabdominal                              20%                        31%
emetics administered (usually after the first episode of        Genitourinary                               25%                        16%
vomiting/retching      or complaints of severe nausea>          Other                                       23%                        19%
was also recorded.
                                                                 Values are means t- SEM.
   Pre- and postoperative renal function was assessed            No significant differences between      anesthetics    were noted for any vari-
from blood obtained to measure serum creatinine and          able.
urinary samples for pH and specific gravity.
   Age, weight, and height were compared between
the two study groups using one-way analysis of vari-         Table     2. Anesthetic       Induction      Times and Side Effects
ance (ANOVA). Efficacy of the two anesthetic tech-
                                                                                                                Sevoflurane           Propofol
niques was analyzed by comparing induction, intuba-
                                                                                                                  (n = 93)            (n = 93)
tion, extubation, emergence, command response, and
orientation times along with times to first requirement      Time to induction   (min)                            3.1 ? 0.2  2.2 ? 0.2*
                                                             Time to tracheal intubation            (min)         7.2 ? 0.3  5.1 ? 0.3*
for postsurgical analgesia and time eligible for dis-
                                                             Complication-free  induction                       72/93 (77%) 74/93 (80%)
charge from recovery by two-way ANOVA with study             Induction side effects
center, treatment, and the interaction between study            Breath holding                                     3    (3%)          0      (0%)
center and treatment as covariates. Urinary pH, spe-            Cough                                              1    (1%)          0      (0%)
cific gravity, serum creatinine, HR, and MAP were               Excitement                                         8    (9%)          0      (0%)
compared at specified times between the two study               Laryngospasm                                       2    (2%)          0      (0%)
groups using one-way ANOVA. Incidences of nausea                Other”                                            13    (14%)        19      (20%)
and vomiting were analyzed by Fisher’s exact test.               Values are means t sBra
Comparisons were made of the Objective Pain-                     a Hypotension,  hypertension,   bradycardia,     hypoxia,   hyperthermia,     hypo-
                                                             thermia, injection site pain.
Discomfort Scale scores between groups by totaling               *P < 0.05.
the score at each evaluation time point and perform-
ing a nonparametric one-way analysis (Kruskal-
                                                             The requirements for fentanyl administration were
Wallis) test for significance. All values shown are rep-
                                                             similar between the groups (Table 3). Extubation time,
resented as mean + SEM with statistical significance
                                                             response to command time and time to orientation
determined at P < 0.05.
                                                             were significantly shorter for the sevoflurane group
                                                             (Table 4). Patients in the sevoflurane group required
Results                                                      administration of postoperative analgesia earlier than
                                                             those in the propofol group (Table 4). No significant
Patient characteristics and surgical duration did not dif-   differences were noted in the type and incidence of
fer between groups (Table 1). Thirty-nine percent            administration of postoperative analgesics, emergence
(72/186) of all patients studied were ASA classI. Shorter    complications, and time eligible for discharge from
times for induction of anesthesiaand tracheal intubation     recovery between the two groups (Table 4). The most
were observed for the propofol group as compared to          common adverse experiences after surgery were those
the sevoflurane group. The overall frequency of induc-       associated with the digestive system. Sevoflurane and
tion side effects between groups did not differ (Table 2).   propofol patients experienced a similar frequency of
The sevoflurane group, however, had a much larger            vomiting and nausea (Table 4). The number of pa-
clustering of airway excitatory side effects as compared     tients requiring antiemetics postoperatively did not
to the propofol group. Surgical and anesthetic durations     differ between groups (56/93 vs 53/93 for sevoflurane
were similar between groups (Table 3). The incidence         and propofol, respectively). The incidence of nausea
of intraoperative hypotension, use of sympathomi-            and vomiting was also determined in patients who
metics and other less common complications during            received anticholinesterases (Table 4) and no differ-
maintenance of anesthesia did not differ (Table 3).          ence was detected. No differences were observed
482        JELLISH  ET AL.                                                                                                                                                           ANESTH       ANALG
           COMPARISON      OF SEVOFLURANE                        WITH    PROPOFOL                                                                                                        1996;82:479-85

Table 3. Intraoperative     Time Intervals,                              Hemodynamic                 Table 4. Emergence Times, Recovery                                      Events, and
Stability, and Complications                                                                         Emergence Complications
                                                     Sevoflurane                     Propofol                                                         Sevoflurane                       Propofol
Surgical duration                                        104 + 6                     108 + 6         Time required for
      (min)                                                                                             Extubation     (min)         921                                               13 + 1
Anesthetic duration                                      132 + 7                     134 + 7            Command                     11 -c 1                                            14 -c 1
      (min)                                                                                                response (min)
  Fentanyl (2 pg/kg)                                78/93        (83%)          87/93        (94%)      Orientation     (min)       15 ? 2                                          20 2 2
  Neostigmine                                       71/93        (76%)          73/93        (78%)   Complication-free          60/93 (65%)                                     61/93 (66%)
  Glycopyrrolate”                                   68/93        (73%)          72/93        (77%)         Emergence
  Sympathomimeticsb                                 13/93        (15%)          19/93        (21%)      Emergence
Complication-free                                   82/93        (88%)          80/93        (86%)         complications
      maintenance                                                                                       Breath holding               1 (1%)                                             2      (2%)
Complications                                                                                           Cough                       12 (13%)                                           16      (17%)
  Hypotension                                       11/93       (12%)               6/93     (6%)       Excitement                   5 (5%)                                             5      (5%)
  Bradycardia                                          3      (3%)                    2    (2%)         Excess salivation            2 (2%)                                             6      (7%)
  Shivering                                            0      (0%)                     1   (1%)         Shivering                    4 (4%)                                             8      (9%)
  Hypertension                                          1     (1%)                    4    (4%)         Other@                       7 (8%)                                             7      (8%)
  Increased salivation                                 0      (0%)                    1    (1%)      Recovery
  Tachycardia                                           1     (1%)                    0    (0%)         First postoperative         38 ? 3                                             49 + 3*
  Ventricular                                           1     (1%)                    0    (0%)             analgesia (min)
      extrasystoles                                                                                     Morphine                71/93 (76%)                                     75/93 (80%)
                                                                                                        Meperidine              42/93 (45%)                                     39/93 (42%)
     Values are means 2 SEM.
     No differences        between     groups      were detected.
                                                                                                        Eligible for               148 -c 9                                        141 5 9
     a Patients   received      &opine      during     administration      of neostigmine.                  discharge (min)
     b Includes     treatment      for adverse       hemodynamics        and as part of surgical        Somnolence              16/93 (17%)                                     16/93 (17%)
preparation      for hemostasis.                                                                        Nausea                  41/93 (44%)                                     37/93 (40%)
                                                                                                        Vomiting                18/93 (19%)                                     18/93 (19%)
between the two treatment groups with respect to                                                        Received anticholinesterase
mean total scores on the Objective Pain-Discomfort                                                          Nausea              34/71 (48%)                                     31/73 (43%)
                                                                                                            Vomiting            13/71 (18%)                                     14/73 (19%)
Scale. The mean scores ranged from a high of 1.7 t 0.1
                                                                                                        No anticholinesterase
vs 1.4 + 0.1 for sevoflurane and propofol, respectively,                                                    Nausea               7/22 (31%)                                       6/20 (30%)
at 20 min after recovery room admission, to a low of                                                        Vomiting             5/22 (23%)                                       4/20 (20%)
0.6 2 0.1 vs 0.5 -+ 0.1 for sevoflurane and propofol,
                                                                                                         Values are mean k sEM.
respectively, at 120 min after recovery room admis-                                                      a Includes     drowsiness,        hyperthermia,      hypotension,      tachycardia,      bradycar-
sion. The number of patients who received either post-                                               dia, hypertension,         dizziness,      hypoxia,   and apnea.
                                                                                                         *P < 0.05.
operative morphine or meperidine was similar be-
tween the two groups.
   Prestudy HR and MAP were not significantly dif-                                                      No significant intergroup differences were noted
ferent between groups (Table 5). Significant, but clin-                                              between baseline serum creatinine, urinary pH, or
ically unimportant, changes were noted in HR and                                                     specific gravity (Table 6). Serum creatinine values in-
MAP in the propofol group at induction compared to                                                   creased from baseline in 7% of patients in the propofol
values obtained 1 min prior to anesthesia. These                                                     group and only 1% of patients receiving sevoflurane.
changes were not seen in the sevoflurane group (Table                                                However, the overall mean change from baseline was
5). On admission to the postanesthesia care unit the                                                 not significant for either group. In addition, no differ-
HR was increased from that observed at the 1-min                                                     ence was observed in either group for mean changes
prior to induction of anesthesia value in both groups,                                               from baseline to first postanesthesia assessment for
whereas the MAP was relatively unchanged. At dis-                                                    urinary pH (Table 6). Within the sevoflurane group,
charge from the postanesthesia care unit, HR values                                                  however, a significant mean decrease from baseline
were similar to the prestudy and 1-min prior to induc-                                               was observed for specific gravity (Table 6). No differ-
tion of anesthesia values in both groups while MAP                                                   ences were noted between the groups when compar-
was significantly decreased in the sevoflurane group.                                                ing change from baseline values for either serum cre-
At the 24-h postanesthesia interval, HR was increased                                                atinine, urinary pH, or specific gravity (Table 6).
from prestudy values in both groups, while MAP was
decreased (Table 5). Comparisons between groups re-                                                  Discussion
vealed a significant reduction in MAP at induction of
anesthesia in the propofol group and a larger increase                                               This study demonstrates that sevoflurane anesthesia
in HR after admission to the postanesthesia care unit                                                compares favorably with propofol in both ease of
in patients receiving sevoflurane (Table 5).                                                         induction and recovery after surgical procedures lasting
ANESTH ANALG                                                                                                                    JELLISH ET AL.   483
1996;82:479-85                                                                                  COMPARISON   OF SEVOFLURANE   WITH I’ROPOFOL

Table 5. Hemodynamic      Variables; Summary                 of Changes                the titration of anesthetic to hemodynamic effect. In
from Baseline in All Treated Patients                                                  one study (3) the primary anesthetic was stopped five
                               Sevofhxane                    Propofol                  minutes before the end of the procedure, whereas our
    Variable/                                                                          study design only allowed for the discontinuation of
 evaluation time           n     Mean        + SEM     II    Mean        5 SEM         primary anesthetic at the end of surgery.
Heart rate                                                                                 Since both groups received similar amounts of
  Prestudy                93        77 + 1            93         75 + 1                perioperative opioids, the earlier requirement for
  1 min prior to          90        79 2 2            92         74 2 2                postoperative analgesia in the sevoflurane group was
     anesthesia                                                                        not due to a larger opioid use intraoperatively in the
  Induction               90        79   -c   2       86         76     -c 2*
  Admit RR                92        88   +    2**     92         79     2 2*+*         propofol group. The shorter time for requesting post-
  D/C RR                  92        77   +    1       92         75     + 2            operative analgesics in the sevoflurane group proba-
  Postanesthesia          a5        81   -t   1”      86         81     _c 1*$         bly reflects its rapid recovery profile and lack of tissue
     24 h                                                                              solubility and accumulation. It has been speculated
MAP                                                                                    (12) but not substantiated (13) that propofol may have
  Prestudy                93        91 + 1.0          93         91 + 1                some analgesic effects. After long infusions, propofol’s
  1 min prior to          90        95 + 1*           92         92 -c 2               terminal elimination half-life is increased which is
  Induction               90        93   2    2       83         90     +     2+t      thought to occur from drug accumulation in poorly
  Admit RR”               77        97   k    2*      80         94     k     2        perfused peripheral tissue compartments (14). This
  D/C RR”                 84        88   t    1**     83       90.0     t     1        might produce a delayed recovery from propofol an-
  Postanesthesia          85        87   +    1*$     86         89     -c    1*       esthesia. In addition, some patients have been re-
     24 h                                                                              ported to have small secondary increases in propofol
    Values are mean + SEM.                                                             blood concentrations during the early postoperative
    Change in n observed at different time points    due to exclusion        of data   period which may reflect return of propofol from stor-
collected-at times other than specified.       _
    RR = recovery room; D/C = discharge.                                               age sites to the blood (15). Although of no apparent
    * P < 0.05 versus urestudv.                                                        clinical significance, this small increase in propofol
    t P < 0.05 versus ‘sevofluiane at same time.
    $ P < 0.05 versus 1 min prior to anesthesia.                                       levels might be enough to reduce the need for imme-
                                                                                       diate analgesia.
up to three hours. Induction side effects occurred                                         Propofol has an antiemetic effect, particularly after
with equal frequency. However, airway excitement                                       operations documented to produce nausea and vom-
was more prevalent with sevoflurane than propofol.                                     iting (16). It is somewhat surprising that both groups
Although the time required for an inhaled induction                                    had similar and high incidences of emesis. Many fac-
and intubation was longer with sevoflurane anes-                                       tors influence postoperative nausea and vomiting.
thesia compared to IV induction with propofol, re-                                     Young age, obesity, and diabetes have all been linked
covery from anesthesia (extubation and command                                         to postoperative emesis (17). These factors were ne-
response) was shorter after sevoflurane. In addition,                                  gated by the fact that our study population had few
the sevoflurane-treated group required postoperative                                   diabetics, had similar average ages, were in good
analgesia earlier than the propofol-treated group.                                     physical health, and of similar body habitus. Addi-
   The time required for induction of anesthesia with                                  tional factors that could influence nausea and vomit-
sevoflurane was longer than the 109 seconds found by                                   ing include type and site of surgery (17). No large
Smith et al. (7). This difference reflects the method of                               differences were noted in the types of surgery done
anesthetic induction. We incrementally increased                                       between study groups. Orthopedic procedures pre-
sevoflurane concentrations over the course of anes-                                    dominated along with intraabdominal procedures
thetic induction until control of ventilation was ob-                                  especially cholecystectomy. Female gender is asso-
tained while Smith et al.‘s group started induction of                                 ciated with three times the incidence of postopera-
anesthesia using 5% sevoflurane and maintained this                                    tive emesis (18). Our study groups, however, had
concentration until anesthetic induction was complete.                                 approximately      equal ratios of male to female pa-
Recovery times seen here compared well with the                                        tients. Reversal of neuromuscular blockade by neo-
seven-minute times noted by Wiesner et al. (8) but are                                 stigmine may influence the incidence of postoperative
double those of Smith et al. (7). All recovery times                                   emesis (19). We compared patients who received
noted in this study are within the range of five to nine                               neostigmine with those who did not and found no
minutes previously reported (9,lO). The recovery                                       significant difference in the incidence of nausea and
times after propofol administration seen here are sim-                                 vomiting between groups (Table 4). Finally, patients in
ilar to those reported by Doze et al. (11) but are double                              both study groups received perioperative analgesics
those of others (3,4) and probably reflect methodologic                                with equal frequency. Possibly the improved inci-
differences concerning opioid administration (none                                     dence in postoperative nausea and vomiting with
administered), time of anesthetic discontinuation, and                                 propofol, as compared to inhaled anesthetics, is lost
484    JELLISH ET AL.                                                                                                                              ANESTH       ANALG
       COMPARISON     OF SEVOFLURANE        WITH I’ROI’OFOL                                                                                            1996;82:479-85

Table 6. Analysis of Changes from Baseline to Postanesthesia Determinations                               of Renal Function
           Variable                               Treatment group                                    Baseline                                Postanesthesia
   Creatinine (mmol/L)                                 Sevoflurane                                83.22   2   1.98                            85.79   -c 3.73
                                                       Propofol                                   78.12   ?   1.78                            78.83   ? 2.03
   Urine pH                                            Sevoflurane                                 6.05   2   0.11                             6.25   -c 0.11
                                                       Propofol                                    5.94   +   0.10                             6.13   5 0.13
   Specific gravity                                    Sevoflurane                                1.018   +   0.001                           1.015   t 0.001*
                                                       Propofol                                   1.017   2   0.001                           1.016   + 0.001
  Values are mean 2 SEM. No sienifkant   differences   were found between   groups.
  * P < 0.05 versus baseline.

when opioids are added (11). It is also possible that                                 that result in higher fluoride levels than seen after anes-
sevoflurane       has less emetic potential compared                  to              thesia with isoflurane, halothane, and desflurane (21).
other inhaled anesthetics because it is less pungent                                  Fluoride levels in excess of 50 pmol/L have been shown
and has a short emergence time which may be asso-                                     to reduce renal concentrating ability (24). Although in-
ciated with less depression of cognitive function in the                              organic fluoride was not determined           in the present
postoperative       period. The nausea and vomiting data                              study, fluoride levels after one to one and one-half hours
from this study can be criticized, however,                  because                  of sevoflurane exposure are reported to reach 19-26
control     over some of the confounding                   variables                  pmol/L (7,21). This is well below the threshold consid-
known to affect these symptoms was not strictly main-                                 ered harmful (24). In this study of similar duration, no
tained.                                                                               outward clinical signs of renal toxicity were noted in the
   The group that received propofol for induction of                                  sevoflurane      group compared to preoperative       evalua-
anesthesia      had increased HR and decreased MAP                                    tions. However,       subtle changes would not have been
when compared to the sevoflurane                group. This is not                    detected by our methods of assessing renal function. A
surprising,     considering     the now well documented              ef-              small but significant decrease in specific gravity, an in-
fect of an induction dose of propofol in producing                     a              direct method of measuring renal concentrating ability,
15%-30% decrease in MAP, especially when adminis-                                     was noted from baseline after sevoflurane exposure. Al-
tered with an opioid analgesic (20). The incidence of                                 though this change was small, it was not observed in the
bradycardia       and hypotension        during maintenance of
                                                                                      group that received propofol. No attempt was made to
anesthesia was not appreciably different between the
                                                                                      control other factors known to affect renal function and
groups. These results are similar to other studies
                                                                                      the implications of this is unclear. However, it is possible
which show both sevoflurane              (7,8) and propofol (3,4)
                                                                                      that the metabolism of sevoflurane during anesthesia
to be anesthetics which maintain MAP and HR close to
                                                                                      with approximate fresh gas flows of 3 L produced a
preinduction       values, especially in healthy ASA phys-
                                                                                      small change in renal concentrating ability.
ical status I and II individuals.             All patients had a
significant increase in HR from initial values on ad-                                      In conclusion, we have demonstrated        that sevoflu-
mission to the postanesthesia           care unit. This increase                      rane compares favorably with propofol for both ease
was higher in patients treated with sevoflurane which                                 of induction and emergence from anesthesia. Postop-
may be a reflection of the more rapid emergence seen                                  eratively, both groups had an equal incidence of nau-
with the drug. These patients may have been more                                       sea and vomiting. Sevoflurane had a quicker immedi-
awake and oriented than their counterparts                 receiving                   ate emergence        as compared      to propofol,   but no
propofol as reflected by the fact that the sevoflurane-                                differences were noted in eligible time to discharge or
treated group required postoperative              analgesia sooner                     ambulation. Sevoflurane may be a useful alternative to
than those who received propofol. The clinical impor-                                 propofol in providing        anesthesia where rapid emer-
tance of these hemodynamic             differences are minimal,                        gence and recovery of cognitive function are desired.
with both groups            demonstrating        marked      stability
throughout       the study period.
   Sevoflurane undergoes biotransformation               and degra-                   References
dation at a rate of approximately            3.3% +- 1.7% of total
                                                                                       1. Kay NH, Sear JW, Uppington J, et al. Disposition of propofol in
uptake (21). Although this is not its main elimination                                    patients undergoing surgery. Br J Anaesth 1986;58:1075-9.
pathway, a byproduct of this metabolism is the produc-                                 2. Gepts E, Camu F, Cockshott ID, et al. Disposition of propofol
tion of inorganic and organic fluoride. While fluoride-                                   administration as constant-rate infusions in humans. Anesth
related nephrotoxicity        has not been observed in clinical                           Analg 1987;66:1256-63.
                                                                                       3. Korttila     K, Ostman P, Faure E, et al. Randomized       comparison      of
assessments       of sevoflurane     in Japan (22) and North                              recovery      after propofol-nitrous  oxide versus thiopentone-isoflu-
America       (23), there are still questions            concerning                       rane-nitrous       oxide anaesthesia  in patients undergoing       ambula-
 sevoflurane      biotransformation       and degradation        rates                    tory surgery.       Acta Anaesthesiol   Stand 1990;34:400-3.
ANESTH         ANALG                                                                                                                                                          JELLISH     ET AL.          485
1996;82:479-85                                                                                                           COMPARISON           OF SEVOFLURANE               WITH     PROI’OFOL

 4. Marshall       CA, Jones RM, Bajorek                   PK, Cashman           JN. Recovery            14. Beller JP, Pottecher          T, Mangin        I’, et al. Long-term          sedation       with
    characteristics        using isoflurane            or propofol       for maintenance           of        propofol      during intensive          care. Preliminary           results of the recov-
    anaesthesia:        a double-blind           controlled       trial. Anaesthesia          1992;          ery and pharmacokinetics.                Ann Fr Anesth Reanim 1987;6:334-5.
    47461-6.                                                                                             15. Shafer A, Doze VA, Shafer SL, et al. Pharmacokinetics                                        and
 5. Kalman        SH, Jensen AG, Ekberg                   K, Eintrei       C. Early and late                 pharmacodynamics               of propofol         infusions      during      general anes-
    recovery       after major abdominal                surgery.      Comparison          between            thesia. Anesthesiology             1988;69:348-56.
    propofol      anaesthesia        with and without            nitrous oxide and isoflu-               16. McCollum         JS, Milligan     KR, Dundee JW. The antiemetic                       action of
    ;a& anaesthesia.            Acta Anaesthesiol            Stand 1993;37:730-6.                            propofol.      Anaesthesia        1988;43:239-40.
 6. Yasuda N. Lockhart              SH. Ever EI II, et al. Comuarison                  of kinetics       17. Watcha MF, White PF. Postoperative                          nausea and vomiting,               its
    of sevoflurane          and isoflu&e             in humans.         Ahesth       Analg 1991;
                                                                                                             etiology,      treatment        and prevention.              Anesthesiology            1992;77:
 7. Smith I, Ding Y, White I’. Comparison                            of induction,         mainte-
                                                                                                         18. Palazzo MGA, Strunin L. Anesthesia                        and emesis. I. Etiology           Can
    nance, and recovery                 characteristics         of sevoflurane-N,O              and
    propofol-sevoflurane-N,O                   with propofol-isoflurane-N,O                   anes-          Anaesth       Sot J 1984;31:178-87.
    thesia. Anesth Analg 1992;74:253-9.                                                                  19. King MJ, Milazkiewicz                F, Carli F, Deacock               AR. Influence            of
 8. Wiesner       G, Schwurzer            S, Horauf        K, Hobbhahn            J. Emergence               neostigmine        on postoperative         vomiting.       Br J Anesth 1988;61:40%6.
    times, hemodynamics                  and adverse         effects of sevoflurane             and      20. Grounds       RM, Morgan          M, Lumley            J. Some studies on the prop-
    isoflurane:        an open, randomized                cooperative         phase III study.               erties of the intravenous                anesthetic,         propofol      (“Diprivan”)-
    Anaesthetist         1994;43:587-93.                                                                     a review.       Postgrad      Med J 1985 (suppl 3);61:90-5.
 9. Inada       Y, Ikeda        K, Mori         M, et al. Clinical               evaluation         of   21. Shiraishi     Y, Ikeda K. Uptake             and biotransformation                 of sevoflu-
    sevoflurane-a            multicenter        clinical trial. Masui-          Japanese Jour-               rane in humans:            a comparative           study of sevoflurane              with hal-
    nal of Anesthesiology               1987;36:866-74.                                                      othane, enflurane           and isoflurane.           J Clin Anesth 1990;2:381-6.
10. Inada Y, Ikeda K, Mori K, et al. Clinical                        evaluation       of sevoflu-        22. Kobayashi         Y, Ochiai R, Takeda J, et al. Serum and urine inor-
    rane vs enflurane-a               multi-center        well-controlled          study. Masui              ganic     fluoride      concentrations            after prolonged             inhalation        of
    Jpn J Anesthesiol           1987;36:875-89.                                                              sevoflurane        in humans.        Anesth Analg 1992;74:753-7.
11. Doze VA, Shafer A, White PF. Propofol-nitrous                                  oxide versus          23. Frink     EJ Jr, Malan          TP Jr, Isner J, et al. Renal concentrating
    thiopental-isoflurane-nitrous                  oxide for general anesthesia.                An-          function      with prolonged           sevoflurane         or enflurane        anesthesia       in
    esthesiology         1988;69:63-71.                                                                      volunteers.        Anesthesiology          1994;80:1019-25.
12. Briggs LP, Dundee JW, Bahar M, et al. Comparison                                 of the effect
                                                                                                         24. Cousins MJ, Greenstein              LR, Hitt BA, Mazze RI. Metabolism                        and
    of the diisopropyl              phenol       (ICI 35 868) and thiopentone                      on
                                                                                                             renal effects of enflurane            in man. Anesthesiology                1976;44:44-53.
    response       to somatic pain. Br J Anaesth                   1982;54:307-11.
13. Jellish WS, Leonetti             JP, Murdoch          JR, Fowles S. Propofol-based
    anesthesia        as compared          with standard          anesthetic       technique      for
    middle ear surgery. Otolaryngol                    Head Neck Surg 1995;112:262-7.

Shared By: