Method of intracranial pressure monitoring and cerebrospinal fluid

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Method of intracranial pressure monitoring and cerebrospinal fluid Powered By Docstoc
					Method of intracranial pressure monitoring and
cerebrospinal fluid sampling in swine

Gernot M Kaiser and Nils R Fruhauf
Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Germany

Cerebral oedema and encephalopathy have been noted to occur frequently in patients
severely ill or dying after trauma, ischaemia, infections or even metabolic disorders. The
objective of the present study was to establish continuous monitoring of the intracranial
pressure (ICP) and sampling of cerebrospinal fluid (CSF) for further investigations in swine.
  ICP monitoring was established in eight pigs by using a ventricular drainage system,
implemented after paramedian trepanation of the os frontale. CSF and serum samples were
taken for measurement of the levels of glucose and protein.
  Operating time was 2178 min for the trepanation until ICP monitoring was performed.
No complications occurred during surgery. Continuous monitoring of ICP and CSF sampling
was easy to perform, and without any side-effects in any animal. At autopsy, no iatrogenic
lesions were found and monitoring catheters were still in place.
  For several types of research requiring ICP monitoring and sampling of CSF, this method
can be used successfully.

Keywords Intracranial pressure; cerebrospinal fluid; sampling method; surgery;
ventriculography; swine

During the last decades various animal                     metabolic disorders is associated with high
models have been used for studying                         morbidity and mortality (Trevisani et al. 1994,
pathophysiology and new therapeutic                        Rosenthal et al. 1997, van Hulst et al. 2002,
strategies in patients with encephalopathy.                Alessandri et al. 2003, Lutsar et al. 2003,
Up to now, reports about standardized                      Anthonypillai et al. 2004, Domoki et al. 2004,
methods describing the technique for pigs in               Fruhauf et al. 2004, Galinkin et al. 2004,
detail accounting for encephalopathy are rare              Hilgard & Gerken 2004, Schmidt et al. 2005).
in the literature.                                         The best way to diagnose and to follow the
  Studies needing adequate intracranial                    time course of cerebral oedema and elevated
pressure (ICP) monitoring and serial                       ICP is continuous ICP monitoring (van de
cerebrospinal fluid (CSF) sampling have                     Kerkhove et al. 2004). Therefore, experi-
been required by investigators from internal               mental and obviously also clinical
medicine, virology, microbiology, neurology,               investigations of the pathopysiology and
neurosurgery, anaesthesiology, trauma and                  treatment opportunities should include ICP
transplantation surgery. Overall, cerebral                 monitoring and CSF sampling for further
oedema caused by infections, trauma,                       understanding of the pathogenesis of the
ischaemia, acute liver failure and even                    condition. Recently described animal
                                                           models in rats, rabbits, guineapigs and pigs
Correspondence: Dr med. Gernot M Kaiser, Klinik fu ¨r      have proven to be useful for investigations
Allgemein, Viszeral und Transplantationschirurgie,
         ¨tsklinikum Essen, Hufelandstrasse 55, 45147
                                                           of encephalopathy (Boogerd & Peters 1986,
Essen, Germany. Email:            Ostrup et al. 1987, Jho et al. 2003,
Accepted 16 February 2006                               r Laboratory Animals Ltd. Laboratory Animals (2007) 41, 80–85
ICP monitoring and CSF sampling in swine                                                         81

Anthonypillai et al. 2004, Fruhauf et al.       continuously administered (8–12 mg/kg/h),
2004). However, these reports did not focus     and boli of fentanyl (0.0025 mg/kg) were
in detail on the technique of ICP monitoring.   given to maintain the intravenous anaesthesia.
  This report aims at the description of a      Monitoring of the cardiopulmonary system
standardized technique for ICP monitoring       was based on continuous pulse oximetry,
and CSF sampling. The technique allows          invasive blood pressure measurement, serial
judgement of the severity and time course       blood gas analysis and clinical observation.
of cerebral oedema following these              Depth of anaesthesia was further monitored
requirements: the model has to be highly        by the reflex status of the animal.
reproducible, a safe procedure is essential,
continuous ICP monitoring should be
possible, serial CSF sampling is required       Surgical procedure and ventriculometry
and the application of the technique should     Surgery was performed with the animal
be simple.                                      in a prone position as a standardized
                                                procedure under sterile conditions. A
                                                commercially available ventricular catheter
Methods                                         device was used for ICP monitoring
                                                (Codman-Microsensor Sets, Johnson and
Animals and study groups
                                                Johnson, LLC, Raynham, MA, USA). A skin
Eight female pigs of the ‘German landrace’      incision was applied 1 cm paramedian of
with a mean body weight of 40.574.5 kg          the sagittal suture, which runs in the
were utilized for this study. Animals were      rostrocaudal axis in the midline of the skull.
adapted to climate and light-cycle controlled   Subcutaneous tissue and periosteum were
environment for at least 14 days prior to       cleared gently by blunt dissection. A bur
investigation. Animals were allowed             hole of 9 mm (Martells and Trepans,
standard laboratory food and water              Aesculap, Tuttlingen, Germany) was placed
ad libitum, and no solid food was given 24 h    at the upper part of the os frontale at a
prior to surgery. All procedures were           distance of 1 cm from the sagittal suture at
performed acutely, and catheters were used      an angle of 901 (Figures 1a, b and 2a). Where
for investigations up to 24 h (Fruhauf et al.   necessary, bipolar coagulation or even
2004). The study had been approved by the       sutures (Prolenes 4-0, Ethicon, Norderstedt,
local committee of animal use and care,         Germany) were used to control bleeding
and was performed under control of the          in this highly vascularized region (Figure 2b).
institutional committee for the humane care     A small incision was applied to the dura
of experimental animals. Animal welfare         mater avoiding contact or damage to the
aspects were respected.                         sagittal sinus, which is a possible major
                                                complication of the procedure and can
                                                be avoided easily. Through the opening
Anaesthesia                                     of the dura mater, the catheter was then
Premedication (10 mg/kg body weight             introduced into the third ventricle of
azaperone and 0.025 mg/kg body weight           the pig. The catheter was slowly and
atropinsulfate) was applied intramuscularly     carefully advanced using a guide-wire
in all animals. For oral intubations the        antegrade 5–7 cm to prevent trauma to the
animals received thiopental (12.5 mg/kg         underlying brain tissue. After removal
intravenous) and fentanyl (0.005 mg/kg          of the guide-wire, clear CSF dripping from
intravenous). After intubation, the animals     the catheter indicated a successful access
were ventilated by intermittent positive        to the ventricle system. The catheter was
pressure with 1/3 oxygen using a ventilog       fixed in place, and the opening was sealed
respirator (Drager, Germany). The tidal
              ¨                                 using bone cement (Palacoss, Biomet
volume was kept between 300 and 450 mL,         Merck, Berlin, Germany) to prevent leakage
the ventilation rate was between                of CSF and movement of the catheter’s
10 and 15 per minute. Thiopental was            tip. Prior to skin closure, using a simple
                                                                        Laboratory Animals (2007) 41
82                                                                          G M Kaiser & N R Fruhauf

                                               Figure 2 Operative situation from side (a) and
                                               frontal situs prior to introduction of the catheter (b)

                                               General measurements and sampling
                                               Haemodynamic and respiratory para-
                                               meters (MAP, pulse saturation, respirator
                                               ventilation) were continuously monitored.
                                               Blood gas analysis, pH, glucose and
                                               electrolyte status (ABL 700, Radiometer
                                               Medical, Denmark) were measured
Figure 1 Cranium of pig with angle (a) and
location (b) of drilling                       preoperatively and during the investigation.
                                               CSF samples of 1 mL were taken directly
                                               after catheter implantation and 1 h later.
                                               Glucose and protein levels were determined,
interrupted technique (Resolons 3-0,           and the results were compared with the
Resorba, Nurnberg, Germany), the catheter
            ¨                                  blood samples at the same time point. Serial
was tunnelled subcutaneously for at least      CSF sampling was easily performed three
5 cm and connected to a pressure gauge using   times within 1 h after implantation of the
a closed system to avoid contamination         intracranial catheter and was compared with
and infection. Finally, the catheter was       blood samples. Blood and CSF samples
additionally protected by taping it to the     were measured and analysed by standard
skin. Aspiration of clear CSF is a must for    laboratory techniques according to the
the functional testing of the system. ICP      manufacturer’s recommendation (ADVIAs
and mean arterial pressure (MAP) were          1650, Bayer, Fernwald, Germany and
monitored to calculate cerebral perfusion      Dimensions, Dade Behring, Bad
pressure (CPP).                                Schwalbach, Germany). Anaesthesia was

Laboratory Animals (2007) 41
ICP monitoring and CSF sampling in swine                                                            83

maintained for 10–36 h, after which the
animals were killed by administration of a
lethal dose of pentobarbital (Eutha 77, Essex
Pharma, Friesoythe, Germany) and necropsy
performed. Laboratory analyses were
performed, and results are presented as mean
values and standard deviation (7SD).

Computed tomography
The favoured position of the catheter’s tip
in the third ventricle was confirmed by a
contrast enhanced computer tomography
of the cranium (cCT). Additionally, the
space of cerebral fluid was accentuated by
ventriculography and three-dimensional
(3-D) reconstruction was elaborated using
the company software (Sensation 16,
Siemens Medical Solution, Erlangen,

Mean operation time was 2178 min.
Anaesthesia was uneventful in all animals.
Surgical blood loss was less than 20 mL in all
cases; bipolar coagulation to stop bleeding
was used where needed. The ventricular
catheter was successfully implemented with
a penetration depth of 5–7 cm, and clear CSF
was aspirated. Intraoperative surgical
complications such as bleeding or trauma
of the surrounding soft tissue, bone and
brain were not observed. No catheter-related
bleeding occurred. ICP monitoring was             Figure 3 Cranial computed tomography using
feasible within the first hour after               ventriculograpy and three-dimensional reconstruc-
implementation. Thereby, establishment            tion: (a) side view and (b) front view
of the surgical technique and the feasibility
of using a ventricular device for ICP             and CPP of 5978 mmHg. Directly after
monitoring and CSF sampling were key              successful implantation of the ventricle
issues. The position of the tip of the catheter   catheter, mean values (7SD) of serum and
in the third ventricle was successfully           CSF levels were of glucose: 102722 mg/dL
confirmed by a contrast enhanced cCT.              and 56714 mg/dL and of protein 6.572.7 g/L
The ventriculography and the 3-D recon-           and 0.2470.11 g/L. No changes occurred
struction of the side view (Figure 3a) and        concerning the results of blood and CSF
front view (Figure 3b) show the anatomy           sampling within the first hour after starting
of the ventricle system of the pig. Mean          the ICP monitoring.
values (7SD) of ICP and resulting CPP
were assessed at 874 and 6176 mmHg
directly after establishing pressure              Discussion
monitoring. One hour later, minimal               Various interrelated hypotheses are
changes resulted in an ICP of 774 mmHg            postulated for the pathophysiological
                                                                           Laboratory Animals (2007) 41
84                                                                            G M Kaiser & N R Fruhauf

mechanisms in encephalopathy. Trauma               previously published by other groups
or even toxic substances compromise                (Boogerd & Peters 1986, Ostrup et al. 1987,
autoregulation of the cerebral blood flow and       Trevisani et al. 1994, Khalili et al. 2001,
increase permeability of the blood–brain barrier   Gardenfors et al. 2004, King et al. 2004).
leading to cerebral oedema (Domoki et al.             According to the recommendations of
2004, Gardenfors et al. 2004, Hilgard &            the American Association of Neurological
Gerken 2004, King et al. 2004). The clinical       Surgeons, epidural and ventricle catheters
features of encephalopathy vary from mild          are commonly used types of ICP monitoring,
personality change and confusion to deep           but direct access to the brain tissue is also
coma. The progression of encephalopathy to         possible (The Brain Trauma Foundation
stage 3 and stage 4 is commonly associated         2000). The epidural catheters are easy to
with increasing ICP (Blei 1995). Up to now, a      insert and have the lowest complication
standardized animal model for the preclinical      rate. Ventriculometry, in general, offers
testing of new therapeutic options has been        highly accurate monitoring and the
missing. The available data from different         opportunity for CSF sampling.
studies are barely comparable due to the           Therapeutically, ICP can be reduced by
efficacy of new therapeutic strategies. Additio-    draining the CSF. However, intracranial
nally, many animal models are known to             haemorrhage is a risk which has to be
be poorly reproducible. However, strong            minimized in the experimental setting.
individual difference in tolerance to trauma       Ventriculometry seems to be the most
and metabolic changes results in very              accurate way of measuring ICP with the
variable rates of cell damage and cerebral         abovementioned advantages (The Brain
oedema, and therefore the clinical outcome         Trauma Foundation 2000). By applying the
differs enormously.                                bur hole to the upper part of the os frontalis
   Swine are a predictable and large animal        paramedian trauma of both the sinus
model and most suitable for many experi-           frontalis and the sagittal sinus is avoided.
mental studies, the similarity in many             In the present study, the catheter was
aspects of anatomy and physiology to the           successfully placed into the third ventricle
human being is well documented (Swindle            without any complications. In all cases,
et al. 1998, Kaiser et al. 2006). Previously       these results were confirmed at autopsy.
described techniques for CSF sampling and          Evidence of bleeding of the trepanation or
ICP monitoring in animal models in the rat,        dislocation of the intracranial catheter was
rabbit and guineapig have proven to be useful      not observed. Overall, from the surgical
for investigations of encephalopathy               point of view, our operative technique allows
(Kusumi & Plouffe 1979, Ostrup et al. 1987,        the required reproducibility by a technically
Hall et al. 1993, Jho et al. 2003, Lutsar et al.   easy and safe procedure to be achieved.
2003, Anthonypillai et al. 2004). In the
literature available, large animal models          Acknowledgement We are grateful to Hilmar Kuhl
                                                   MD, for performing the cCT scan and the 3-D
focus more on results of the therapeutic
                                                   reconstructions shown in Figures 3a and b.
regimens than on the specific technique
for ICP monitoring and CSF sampling
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ICP monitoring and CSF sampling in swine                                                                     85

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