1 Peninsula Medical School, C310 Portland Square, University of Plymouth, Drake Circus, Plymouth PL4 8AA, UK. 2 Department of Anaesthesia, Pain Management and Critical Care Medicine, Derriford Hospital, Plymouth PL6 8DH, UK
* Corresponding author. E-mail: robert.sneyd{at}pms.ac.uk
Accepted for publication February 10, 2005.
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Abstract |
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Methods. Fifty unpremedicated patients undergoing elective craniotomy received remifentanil 1 µg kg1 followed by an infusion commencing at 0.5 µg kg1 min1 reducing to 0.25 µg kg1 min1 after craniotomy. Anaesthesia was induced with propofol, and maintained with either a target-controlled infusion of propofol, minimum target 2 µg ml1 or sevoflurane, initial concentration 2%ET. Episodes of mean arterial pressure (MAP) more than 100 mm Hg or less than 60 mm Hg for more than 1 min were defined as hypertensive or hypotensive events, respectively. A surgical assessment of operating conditions and times to spontaneous respiration, extubation, obey commands and eye opening were recorded. Drug acquisition costs were calculated.
Results. Twenty-four and twenty-six patients were assigned to propofol (Group P) and sevoflurane anaesthesia (Group S), respectively. The number of hypertensive events was comparable, whilst more hypotensive events were observed in Group S than in Group P (P=0.053, chi-squared test). As rescue therapy, more labetolol [45 (33) vs 76 (58) mg, P=0.073] and ephedrine [4.80 (2.21) vs 9.78 (5.59) mg, P=0.020] were used in Group S. Between group differences in recovery times were small and clinically unimportant. The combined hourly acquisition costs of hypnotic, analgesic, and vasoactive drugs appeared to be lower in patients maintained with sevoflurane than with propofol.
Conclusion. Propofol/remifentanil and sevoflurane/remifentanil both provided satisfactory anaesthesia for intracranial surgery.
Keywords: anaesthetics i.v., propofol ; anaesthetics volatile, sevoflurane ; surgery, neurosurgery, craniotomy
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Introduction |
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Methods |
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Anaesthesia
After establishment of standard monitoring and arterial and venous cannulation, all patients received a bolus of remifentanil 1 µg kg1 followed by an infusion of 0.5 µg kg1 min1 reducing to 0.25 µg kg1 min1 after craniotomy. Patients were questioned about the onset of drug effect and when they began to feel light-headed or sleepy anaesthesia was induced with propofol. In patients randomized to receive propofol anaesthesia (Group P) anaesthesia was induced with a target-controlled infusion of propofol (Graseby 3500 infusion pump, Diprifusor® software, initial plasma concentration target, 1 µg ml1), which was increased progressively until satisfactory anaesthesia was achieved. Anaesthesia was maintained by the target-controlled infusion of propofol with a minimum target concentration of 2 µg ml1.
In the patients randomized to receive sevoflurane (Group S) anaesthesia was induced with a bolus injection of propofol, 0.5 mg kg1 with supplementary doses of 10 mg every 10 s until loss of consciousness. Anaesthesia was then maintained with sevoflurane, initial end tidal concentration 2%, minimum concentration 1%. Tracheal intubation was facilitated with atracurium given as a bolus and followed by an infusion until dural closure. All patients were artificially ventilated to normocapnia using a circle breathing system and a fresh gas flow of 0.5 litre min1 oxygen and 1.0 litre min1 air during anaesthesia. At the end of surgery, residual neuromuscular blockage was then antagonized with 2.5 mg neostigmine and 0.5 mg glycopyrrolate. Remifentanil infusion was stopped after skin closure whilst sevoflurane and propofol were continued until head bandaging was completed. Mannitol 1 g kg1 was given between induction of anaesthesia and craniotomy unless clinically contraindicated. Additional mannitol was given if clinically indicated. The surgeons, blind to anaesthetic technique, evaluated the state of brain as tight, adequate, or soft. The dose of mannitol was recorded.
Hypertensive episodes, defined as mean arterial pressure (MAP) more than 100 mm Hg for more than 1 min, were treated with remifentanil 1 µg kg1 and the infusion rate increased by 0.125 µg kg1 min1. If the response was present 2 min later this was repeated. If the haemodynamic response persisted for a further 2 min the propofol target concentration or sevoflurane concentration were increased. Labetolol or hydralazine was given, if clinically appropriate. Hypotensive episodes, defined as MAP less than 60 mm Hg for more than 1 min, which did not respond to a fluid bolus, were treated by reducing the propofol target or sevoflurane concentration. A vasopressor was administered if necessary. Hypertensive and hypotensive episodes were recorded.
Arterial pressure was recorded on the ward using an automated sphygmomanometer and before induction of anaesthesia and continuously thereafter using an arterial cannula.
Times to adequate respiration, extubation, eye opening and obeying commands were recorded. Analgesia in the recovery area was provided by bolus injections of morphine 2 mg, given at 5-min intervals according to standard hospital protocol. Nausea and vomiting and the time of discharge from recovery were recorded by the nursing staff.
Statistical analysis
Data were recorded on specially produced paper record forms and then transferred to a database (Microsoft Access, Version 7.0). Statistical analysis was performed using Statview (version 5.0), and Excel Version 7 running on a personal computer. The size of the study was determined by a priori power calculation using data from a previous study,7 which suggested that enrolment of 20 patients per group would determine a difference in time to tracheal extubation of 4 min with a power of 80% and P<0.05. The comparison of continuous variables was performed by MannWhitney U-test. Categorical valuables were analysed using the chi-squared test. P<0.05 was considered statistically significant. Drug acquisition costs were calculated post-hoc.
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Results |
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Propofol, sevoflurane, and remifentanil are expensive agents with associated equipment costs. Although this was not a health economic study, we conducted a post-hoc calculation of drug acquisition costs (Table 4). Propofol acquisition cost was £3.83 per 20 ml ampoule for Group S and £9.58 per 50 ml syringe for Group P. Remifentanil cost £5.98 per mg. The cost of sevoflurane was calculated by the method of Rosenberg16 with an acquisition cost of £137.30 per 250 ml and total flow 1.5 litre min1. The total hypnotic and analgesic drug acquisition costs of Group P were significantly higher than in Group S, median cost £58.63 vs £39.03. Group S required more vasoactive medications (labetolol, £2.94 per 100 mg; hydralazine, £1.62 per 20 mg; and ephedrine £1 per 30 mg). Even after allowing for this, the combined hourly costs of hypnotic, analgesic, and vasoactive medications were higher in Group P than in Group S, median values £19.31 and £15.52 h1, respectively, P=0.016.
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Discussion |
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We observed an increased number of hypotensive episodes in Group S, which also received a larger total dose of ephedrine as rescue therapy. One possible explanation is that the sevoflurane group was simply more deeply anaesthetized. Although doses of individual inhalation agents can readily be compared by describing them as fractions of the MAC, it is not possible to make a direct comparison with an i.v. agent. The CP50 of propofol for depression of bispectral index is 5.45 µg ml1,8 whereas the IP50 of sevoflurane for depression of bispectral index was 1.14%.9 In our study, the average target propofol concentration was 3.67 (0.46) µg ml1, and average end-tidal sevoflurane concentration was 1.13 (0.19)%. Viewed against the above data for bispectral index, Group S may have been slightly more deeply anaesthetized than Group P. The sevoflurane group contained more posterior fossa cases than the propofol group (5 vs 2). Posterior fossa surgery poses different problems to supratentorial surgery and haemodynamic disturbance may be more common in these patients. We explored our data and found no excess of haemodynamic instability in the patients undergoing posterior fossa surgery who were anaesthetized with sevoflurane.
We found small and clinically unimportant differences in recovery between Group P and Group S. There are many reports to compare recovery characteristics between propofol and sevoflurane anaesthesia. These reports concluded sevoflurane anaesthesia gave faster,10 11 similar,12 or slower7 13 recovery than propofol anaesthesia. Yli-Hankala and colleagues reported no difference of recovery time between propofol/fentanyl/nitrogen oxide and sevoflurane/fentanyl/nitrogen oxide anaesthesia under bispectral index control.14 We explored our data to evaluate whether hypotensive episodes, which might be a result of a deeper anaesthesia were associated with delayed recovery and found no correlation. The experiences of the two groups of patients whilst in the recovery area were similar, perhaps because this phase is dominated by clinical and nursing factors rather than the small differences between short-acting hypnotic agents.
Many studies have reported that sevoflurane caused postoperative nausea and vomiting (PONV) more frequently than propofol anaesthesia.7 10 12 PONV occurs in about 30% of patients receiving sevoflurane.7 10 12 15 In the present study, PONV occurred in only 15% of patients with no difference between propofol and sevoflurane.
Although there was a small difference in drug acquisition costs between the two groups, these differences in costs are very small in relation to the total cost of a neurosurgical procedure and should be interpreted cautiously as they ignore associated costs of equipment and disposables.
We selected realistic doses of propofol and sevoflurane, which recognize the strong synergism between these agents and remifentanil. We have evaluated previously remifentanil alone and as a sequential infusion following alfentanil in neuroanaesthesia practice.15 Common clinical doses of remifentanil give substantial sparing of sevoflurane and propofol when these agents are used for induction and maintenance of anaesthesia.17 18 In our previous study,15 the propofol infusion rate (100 µg kg1 min1) was probably too high.
We have carefully evaluated sevoflurane and propofol as maintenance agents with remifentanil for elective intracranial surgery. Both agents were satisfactory.
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Acknowledgments |
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References |
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