1 Department of Chemical Physics and Physicochemical Separation Methods, Faculty of Chemistry, Maria Curie-Skodowska University, 20031 Lublin, pl. Marii Curie-Sk
odowskiej 3, Poland. 2 Department of Anaesthesiology and Intensive Therapy and 3 Department of Neurosurgery and Paediatric Neurosurgery, University School of Medicine, 20090 Lublin, Jaczewskiego 8, Poland E-mail: dawid@hermes.umcs.lublin.pl
Accepted for publication: August 24, 2002
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Abstract |
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Methods. Thirty-nine patients (ASA IIII) scheduled for elective intracranial procedures, were studied. Propofol was infused initially at 12 mg kg1 h1 and then reduced in steps to 9 and 6 mg kg1 h1. During anaesthesia, bolus doses of fentanyl and cis-atracurium were administered as necessary. After tracheal intubation the lungs were ventilated to achieve normocapnia with an oxygen-air mixture (FIO2=0.33). Arterial blood and CSF samples for propofol examination were obtained simultaneously directly after intracranial drainage insertion and measured using high-performance liquid chromatography. The patients were divided into two groups depending on the type of neurosurgery. The Aneurysm group consisted of 13 patients who were surgically treated for ruptured intracranial aneurysm. The Tumour group was composed of 26 patients who were undergoing elective posterior fossa extra-axial tumour removal.
Results. Blood propofol concentrations in both groups did not differ significantly (P>0.05). The propofol concentration in CSF was 86.62 (SD 37.99) ng ml1 in the Aneurysm group and 50.81 (26.10) ng ml1 in the Tumour group (P<0.005).
Conclusions. Intracranial pathology may influence CSF propofol concentration. However, the observed discrepancies may also result from quantitative differences in CSF composition and from restricted diffusion of the drug in the CSF.
Br J Anaesth 2003; 90: 846
Keywords: anaesthetic techniques, i.v. total; anaesthetics i.v., propofol; cerebrospinal fluid
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Introduction |
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Methods and results |
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All patients received oral diazepam 10 mg 2 h before anaesthesia. After pretreatment with fentanyl 0.2 mg, anaesthesia was induced with propofol 2 mg kg1 and then maintained with a continuous infusion of propofol at the following rates: 12 mg kg1 h1 for the first 15 min; 9 mg kg1 h1 for the next 30 min and then 6 mg kg1 h1 until the end of the procedure. Tracheal intubation was facilitated by cis-atracurium 0.15 mg kg1. After tracheal intubation, the lungs were ventilated to achieve normocapnia with an oxygen-air mixture (FIO2=0.33). In addition to the constant infusion of propofol, anaesthesia was maintained with repeated doses of fentanyl and cis-atracurium as necessary.
After induction of anaesthesia, a cannula was placed in the radial artery for blood pressure monitoring and blood sampling. As part of the surgical procedure, an External Drainage System (Codman, Johnson and Johnson Medical Ltd, UK) for CSF drainage was inserted into the subarachnoid cisterns in patients in the Aneurysm group and into a lateral ventricle in the Tumour group.
Arterial blood and CSF samples for propofol examination (5 and 2.5 ml respectively) were obtained simultaneously at the moment of CSF drainage insertion. Only CSF samples free from red blood cells were saved for further analysis.
The concentration of propofol in the samples was measured by high-performance liquid chromatography with fluorescence detection, according to the procedure previously described.7 The detection limit of the assay was 1.1 ng ml1.
The patient characteristics and the propofol concentration results are listed in Table 1. Statistical analysis was performed by means of the Students t-test for independent samples. Differences were considered significant with a P-value of <0.05.
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Comment |
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The results presented in Table 1 confirm the earlier data.5 6 The calculated propofol concentration in CSF from the pooled data of all our patients is 1.64% of the analogous average concentration of the drug in blood. Moreover, the division of the patients into two groups depending on the type of neurosurgical procedure shows significant differences in CSF propofol concentrations (P<0.005).
The difference in propofol concentrations in CSF between the Aneurysm and Tumour groups may be attributed to differences in intracranial pathology. In a variety of pathological conditions, including vascular brain diseases and tumours, abnormal permeability of the blood brain barrier can be observed.8 It is well-known that the passage of drugs from the blood to the CSF is increased after rupture of an intracranial aneurysm. Conversely, an intracranial tumour modifies the bloodbrain barrier permeability only when it grows up from the brain parenchyma, whereas an extra-axial location keeps the bloodbrain barrier intact.
There are quantitative differences, however, in composition of CSF originating from different sampling sites.9 10 For example, CSF from the ventricles of the brain contains less protein and more glucose than that from the subarachnoid cisterns. Variation in protein binding within the CSF may lead to differences in propofol concentration. The same mechanisms that are responsible for the differences in concentrations of proteins and glucose in CSF (e.g. restricted diffusion in a slowly circulating medium) may also cause the formation of a propofol concentration gradient within the CSF space (a gradient between different intracranial regions). These factors may also contribute to the differences in CSF propofol concentration found between the Aneurysm and Tumour groups.
In conclusion, our data indicate that intracranial pathology may influence CSF propofol concentration. However, the observed discrepancies may also result from quantitative differences in CSF composition and from restricted diffusion of the drug in the CSF.
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Acknowledgement |
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References |
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