1Department of Anaesthesiology and Intensive Care Medicine, University of Saarland, D-66421 Homburg/Saar, Germany. 2Department of Neurology, University of Saarland, D-66421 Homburg/Saar, Germany*Corresponding author
Accepted for publication: August 30, 2000
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Abstract |
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Br J Anaesth 2001; 86: 449
Keywords: analgesics opioid, remifentanil; analgesics opioid, fentanyl; anaesthetics volatile, desflurane; surgery, carotid endarterectomy; recovery, postoperative
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Introduction |
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Patients and methods |
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Induction and maintenance
On the morning of surgery, all patients were given 5 mg of diazepam orally 90 min before induction. In the operating room, two intravenous catheters were inserted and the radial artery was cannulated. Standard monitors were applied. Before induction, all patients were given 5 ml kg1 of a 3% gelatin infusion intravenously.
In the fentanyldesflurane group, induction started with a dose of fentanyl 2 µg kg1. Five minutes later etomidate was given for hypnosis, initially starting at 0.15 mg kg1 and then at 2 mg every 10 s until the patient was unresponsive to verbal command. The desflurane vaporizer was then set to 3 vol% and ventilation with desflurane in oxygen was given as required. Patients were then given 0.1 mg kg1 of cisatracurium, the trachea was intubated 3 min later and the lungs were ventilated to achieve normocapnia, using desflurane and 66% nitrous oxide in oxygen. Five minutes before skin incision, another 2 µg kg1 bolus dose of fentanyl was injected and desflurane was added as needed for maintenance, starting at an end-tidal concentration of 4 vol% (=2/3 MAC).
In the remifentanildesflurane group, all patients were given atropine 5 µg kg1 followed by remifentanil 1 µg kg1, injected over 30 s, and an infusion of remifentanil was started simultaneously at 0.1 µg kg1 min1. Five minutes later, etomidate was given, followed by desflurane and cisatracurium as described above. Five minutes after intubation remifentanil was reduced to 0.05 µg kg1 min1 and then readjusted to 0.1 µg kg1 min1 3 min before skin incision. Maintenance of anaesthesia consisted of remifentanil infused at 0.1 µg kg1 min1, with desflurane added to obtain an end-tidal concentration of 2 vol% (=1/3 MAC).
In both groups, according to our departments policy, nitrous oxide was discontinued 5 min before the carotid artery was cross-clamped; the lungs were then ventilated with desflurane in oxygen until the end of the operation.
Monitoring and haemodynamic control
Continuous monitoring included heart rate (HR), systemic arterial pressure, respiratory rate, oxygen saturation and end-tidal concentrations of carbon dioxide and desflurane. Arterial blood gases were analysed intermittently and the PaCO2 was maintained between 4.85.9 kPa (3644 mm Hg). The oxygen saturation was measured by pulse oximetry and maintained above 95%. Transcranial Doppler ultrasound was continuously applied, by a neurologist (M.M.), to the ipsilateral middle cerebral artery to measure mean blood velocity during surgery and cross-clamping (for the exact technique see ref. 4).
Baseline systolic arterial pressure (SAP) was defined as the lower of the two measurements obtained the day before surgery and immediately before induction of anaesthesia. The definition of adverse haemodynamic responses was adapted from Garrioch and Fitch:1 responses of 1 min of duration were classified as hypertension (SAP>40 mm Hg from baseline or >200 mm Hg), hypotension (SAP<40 mm Hg from baseline or <100 mm Hg), tachycardia (HR>100 beats min1) and bradycardia (HR<45 beats min1). Inadequate anaesthesia was defined as hypertension, tachycardia or patient movement, eye opening, swallowing, grimacing, lacrimation or sweating.
In the fentanyldesflurane group, if anaesthesia was inadequate the end-tidal desflurane concentration was increased in steps of 0.5 vol% as necessary. If this was judged insufficient, then an additional bolus dose of 0.5 µg kg1 fentanyl could be injected. Hypotension was initially treated with i.v. fluid replacement; desflurane was then reduced in steps of 0.5 vol%, and finally, an i.v. vasopressor (cafedrine/theodrenaline) was given at a dose chosen by the investigator. In the remifentanildesflurane group, if anaesthesia was inadequate the infusion rate was increased by 0.05 µg kg1 min1 or a bolus dose of 1 µg kg1 was injected; both interventions were repeated as necessary. If this was insufficient, desflurane was increased by 0.5 vol% end-tidal. Hypotension was initially treated with i.v. fluids; the remifentanil infusion rate was then reduced to a permitted minimum of 0.05 µg kg1 min1; finally, an i.v. vasopressor was used as described above. In both groups bradycardia was treated with 0.25 mg of atropine.
Recovery period
Fifteen minutes before the expected end of surgery, complete neuromuscular recovery was ensured by neuromuscular monitoring; all patients received a 100 ml infusion of 0.9% NaCl containing metamizol 25 mg kg1 for postoperative pain relief. The end of surgery was defined as the final surgical suture, when anaesthetic delivery was stopped. During recovery, a post-anaesthetic recovery score (PARS), as defined by Aldrete and Kroulik,5 was recorded continuously. Oxygenation was maintained by intermittent positive pressure ventilation using a fresh gas flow of 10 litres min1 of 100% oxygen until spontaneous respiration returned. Emergence from anaesthesia was assessed by measuring the times to return of spontaneous ventilation, extubation, response to verbal command (opening eyes, stating name and date of birth) and when the Aldrete score became 9 or above.
All patients were then moved to the post-anaesthesia care unit (PACU), where observation was continued by an investigator and a PACU nurse, neither of whom was aware of the anaesthetic regimen. If further pain relief was requested, patients could be given bolus doses of 3 mg piritramide at the discretion of the attending nurse. Each patient was continuously observed for neurological deficits, and the times (expressed as minutes from end of surgery) taken for the patient to be able to perform the arm and the leg holding tests were recorded. The depth of sedation was assessed for the first 60 min after the end of surgery using a five-point scale for observer assessment of alertness/sedation: 1=asleep, unarousable; 2=asleep, difficult to rouse; 3=asleep, easy to rouse; 4=awake and calm; 5=awake but anxious.
Intermediate recovery was assessed by the Trieger dot test (TDT), in which individuals are asked to connect a series of 50 dots of a geometrical figure,6 and by the digit symbol substitution test (DSST), in which individuals are asked to match numbers with predefined symbols during a 120 s period (adapted from refs 7 and 8). All patients had completed a first series of these tests on the day before surgery, with the results serving as baseline values. Thirty, 60 and 90 min after the end of surgery, both tests were repeated; the results are expressed as a percentage of baseline.
End-points and statistical analysis
The primary end-point of this study was defined as the time taken to respond to verbal command (state the correct name). Applying an a priori power analysis, at least 17 patients had to be enrolled in each treatment group to provide 80% power to detect a difference of 3 min at =0.05. Statistical analysis was performed by means of the MannWhitney U-test for numerical data and Fishers exact test for nominal data. All tests were two-tailed with statistical significance defined as P<0.05; data are presented as mean and standard deviation (SD) in the tables or standard error (SEM) in the figures. Statistical analysis was planned and performed in collaboration with a statistician of the Institute of Medical Biometrics, Epidemiology and Informatics, University of Saarland, using SPSS computer software (version 7.5.2G; SPSS Inc.).
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Results |
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Discussion |
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These results are of current interest since CEA is increasingly being performed in patients with carotid stenosis, and randomized clinical studies have shown that strokes can be reduced.9 However, CEA may cause postoperative neurological deficits, which should be diagnosed and treated promptly. In some techniques, the use of opioids is reduced whenever possible to allow rapid postoperative awakening and early neurological assessment.2 Other techniques use an opioid-based anaesthetic because of the prevalence of co-existing coronary artery disease in these patients.1
Remifentanil is rapidly broken down by non-specific esterases to nearly inactive metabolites, so recovery from intraoperative opioid analgesia can be rapid.10 After remifentanil, about 2 min elapsed from the onset of spontaneous ventilation to the moment that patients could state their name and date of birth correctly, and 2 min later patients could be examined neurologically by the arm holding test. The sedation score, DSST and TDT results, showed that intermediate recovery was also shorter.
The properties of remifentanil allow high-dose opioid use throughout the operation, and reduce the amount of desflurane needed, which is a reason for the difference in recovery seen when remifentanil is used. The impact of the amount of the inhaled anaesthetic on awakening from anaesthesia is known from animal and human studies: Eger and Johnson11 investigated rats that were anaesthetized for 2 h with different volatile anaesthetics and at different multiples of their MAC values. Awakening was typically most rapid with the lowest concentration of the inhaled anaesthetic; this also applies to the results of our study: At the end of surgery, the mean end-tidal desflurane concentration was 3.5 vol% in the fentanyl group, but only 1.9 vol% in the remifentanil group. Similar results were obtained by Smiley and co-workers12 in patients undergoing elective surgery with desflurane or isoflurane anaesthesia with 0.65x or 1.25xMAC: recovery was faster with the lower anaesthetic concentration.
In addition to the difference in desflurane concentration, the opioid itself will influence the time course of awakening. Glass and colleagues13 argued that only small amounts of fentanyl or remifentanil are necessary to reduce the MAC, and this also applies to the alveolar concentration of the volatile anaesthetic, at which patients will awake from anaesthesia. Thus, the duration of pharmacodynamic interaction will depend on the duration of the opioid effect; this will clearly be longer with fentanyl than with remifentanil.
A similar anaesthetic technique was proposed by Gerhardt and Grichnik3 who reported the use of remifentanil in a 60 yr old patient undergoing combined CEA and coronary artery bypass grafting. Their dosage regimen was nearly identical to ours: a remifentanil infusion was titrated to clinical needs and 1/3 MAC (i.e. 0.4 vol%) of isoflurane was added (we used 1/3 MAC of desflurane, i.e. 2 vol%). The authors concluded that remifentanil may retain the haemodynamic stability of an opioid-based anaesthetic technique while allowing for early extubation and neurological examination.
A potential shortcoming of the present study is the question of equivalent levels of anaesthesia in the two groups. The dosage regimens used in this study are comparable to that of other remifentanil-based anaesthesia studies and have been empirically effective. All anaesthetics were delivered by the same experienced anaesthesiologist, who relied on standard clinical signs as described in Patients and methods. Apart from a better reduction in the haemodynamic response to intubation with remifentanil, the haemodynamic characteristics were very similar in the two groups (Table 2). This suggests the equivalence of anaesthesia in the two treatment groups, especially at the end of surgery when the assessment of recovery characteristics was started.
In conclusion, rapid postoperative awakening, quicker recovery and earlier neurological examination suggest that remifentanildesflurane is a suitable alternative to fentanyldesflurane as a general anaesthetic for patients undergoing carotid artery surgery.
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Acknowledgements |
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References |
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