ALFENT ANIL-OXYGEN ANAESTHESIA FOR CORONARY ARTERY SURGERY

Transcription

1 Br.J. Anaesth. (191), 53, 1291 ALFENT ANIL-OXYGEN ANAESTHESIA FOR CORONARY ARTERY SURGERY S. DE LANGE, T. H. STANLEY AND M. J. BOSCOE SUMMARY The anaesthetic properties of alfentanil were evaluated in 15 patients undergoing coronary artery bypass grafting operations. Alfentanil was infused at a rate of 3.0mgmin~' until the patients (breathing pure oxygen) became unconscious. Additional alfentanil mg i.v. was given if systolic arterial pressure increased by 15% or more from control values. Alfentanil produced unconsciousness in 75± 1s, but muscle rigidity occurred in 27% of patients. Cardiovascular dynamics were minimally altered during the induction of anaesthesia and throughout most of the operation, although 60% of patients became hypertensive during sternotomy and 73% during sternal spread. Recovery from anaesthesia was rapid with patients regaining consciousness after 1.4±0.6h and fulfilling our criteria for extubation of the trachea 4.1 ± 1.2 h after operation. No patient was aware of laryngoscopy, tndotracheal intubation jr any aspect of the operation. Fentanyl anaesthesia is used frequently in seriously ill patients because it produces adequate anaesthesia with little or no change in cardiovascular dynamics and appears to block the metabolic and cardiovascular "stress responses" during operation (Dubois-Primo, 1975; Hall et al., 197; Stanley and Webster, 197; Stanley, Philbin and Coggins, 1979; Hall, 190; Stanley et al., 190). Unfortunately, chest wall rigidity can occur during the induction of anaesthesia with fentanyl (Hill et al., 190; de Lange, Stanley and Boscoe 190a) and respiratory depression persists for some hours after operation following the administration of anaesthetic doses (Stanley and Webster, 197; Lunn et al., 1979; Stanley, Philbin and Coggins, 1979; de Lange, Stanley and Boscoe, 190a). In this study alfentanil, (N- [l-[2-(4 ethyl-4,5-dihydro-5-oxo-lh-tetrazol-lyl-ethyl]-4-(methoxymethyl)-4-piperidinyl]-nphenyl-propanamide) (fig. 1) a new, shortacting narcotic, structurally related to fentanyl but with only one-third of its potency and duration of activity (de Castro et al., 1979) was evaluated as the sole anaesthetic in 15 patients undergoing coronary artery bypass grafting (CABG) operations. SIMON DE LANGE, M.B.B.S., F.F.A.R.CS.; THEODORE H. STANLEY,* M.D.; MICHAEL J. BOSCOE, M.B.B.S., F.F.A.R.CS.; Department of Cardiothoracic Anaesthesiology, University of Leiden Hospital, Leiden, The Netherlands. Correspondence to T.H.S., Department of Anaesthesiology, University of Utah College of Medicine, 50 North Medical Drive, Salt Lake City, Utah 4132, U.S.A /1/ , \ CH2-C-CH3 N-CH2-CH2 2 -N X 0 X N-C-CH 2 -O N.=. N FIG. 1. Structural formula of alfentanil. PATIENTS AND METHODS The study was approved by the Leiden University Human Experimentation Committee and informed consent was obtained from each patient at the time of the preoperative visit (14 male patients and one female patient with multi-vessel coronary artery disease about to undergo CABG operation). Fourteen of the patients were taking propranolol or another beta-adrenergic blocking compound and 12 nitroglycerin or other oral vasodilator for hypertension or angina, or both. The patients were premedicated with lorazepam 0.0 mg kg" 1, by mouth 2h before operation and atropine 0.1 mg 15 kg"' i.m. 30min before arrival in the operating room. Patients taking a betaadrenergic blocker received their usual dose of the compound at the time of premedication. On arrival in the operating room catheters were placed in a hand vein and a radial artery, and a bipolar lead II electrocardiogram was recorded continuously. Before the induction of anaesthesia, a thermodilution flow-directed balloon-tipped pulmonary artery catheter (Instrument Laboratories triple-lumen 110 cm model F) was introduced percutaneously to the pulmonary Macmillan Publishers Ltd 191

2 1292 BRITISH JOURNAL OF ANAESTHESIA artery through an antecubital vein using a 7- French gauge Cordis introducer. Following preparatory procedures and a 10-min stabilization period, control measurements of the heart rate (beat min" 1 ), cardiac output (litre min"') (measured by thermodilution with 10 ml of C 5% dextrose in water as the injectate), systolic and mean arterial pressures (mmhg) were obtained and patients given 100% oxygen to breathe. Two minutes later pancuronium 0.02 mg kg" 1 was administered i.v. Three minutes after pancuronium the patients were given alfentanil 0.5 mg ml" 1 at a rate of 3 mg min" 1 until they became unconscious. Respirations were first spontaneous, then assisted and finally controlled, using a face-mask and a semi-closed system. Pa,^ was maintained at kpa as measured in radial arterial blood every min. During the infusion of alfentanil the patients were asked to open the eyes and take a deep breath every 5-10 s. Failure to respond to three consecutive commands was equated with unconsciousness. Once consciousness had been abolished suxamethonium 1.5mgkg~' was administered i.v., the trachea intubated with a cuffed Portex endotracheal tube and the lungs ventilated with 100% oxygen. After the onset of unconsciousness, but before intubation, additional alfentanil was given (1-2 mg i.v. bolus doses) if the patient opened the eyes, moved an extremity, or responded in any fashion which suggested that anaesthesia may not be adequate. Following intubation of the trachea and throughout operation, alfentanil was given i.v. in bolus doses of mg whenever systolic arterial pressure increased by more than 15% of its preanaesthetic (control) value. When three successive supplementary doses of the drug failed to decrease systolic arterial pressure to within 15 % of the preanaesthetic value before or during cardiopulmonary bypass, the patients were given phentolamine in 1-3 mg divided doses until arterial pressure decreased to control. After bypass 50% nitrous oxide in oxygen was added to the mixture of gases to treat hypertension not responding to supplementary doses of alfentanil. If nitrous oxide was ineffective in decreasing postbypass hypertension to within 15% of control systolic arterial pressure, an infusion of sodium nitroprusside ug kg" 1 min" 1 was started. The frequency of increases in systolic arterial pressure to more than % of the preanaesthetic values during endotracheal intubation, chest incision, sternotomy and maximum sternal spread was recorded. Neuromuscular blockade was induced with pancuronium 0.0 mg kg" 1 slowly, i.v. 15- min after the induction of anaesthesia and maintained with mg kg" 1 increments of pancuronium every min throughout the remainder of the operation. A balanced solution of 4.5% glucose in 0.1% physiological saline was administered at a rate of 1 litre h" 1 during the preparations before anaesthesia and ml h"' for the duration of the operative procedure. Whole blood was given after cardiopulmonary bypass and in the period after operation to maintain right atrial pressure at preanaesthetic values. The extracorporeal system was primed with Ringer's solution 1500 ml, glucose 5% in water 500 ml and 500 ml of a solution containing albumin loog and heparin 500 unit. Patients were cooled to 26-2 C during extracorporeal support and rewarmed to 37 C at its conclusion. Cardiovascular dynamics were recorded before the induction of anaesthesia (control), at the onset of unconsciousness, 1 min after intubation, immediately before and 5 min after chest incision, before sternotomy and 5 and 10 min after sternal spread. The presence of muscle rigidity during induction was evaluated by the following scoring system: none = no difficulty with ventilation during manual positive pressure ventilation and no clinical evidence of abdominal wall (palpation) or upper limb stiffness (manual elbow flexion); mild = possible to ventilate, but with some difficulty associated with mild abdominal wall upper stiffness or both; severe = virtually impossible to ventilate before administration of suxamethonium associated with marked abdominal wall, face, neck, and upper limb muscle stiffness. The lungs were ventilated mechanically until the morning after surgery. During the first h after operation the possibility of return of consciousness was assessed every 15 min. Patients were considered conscious when they could give correct response to three consecutive questions. Once conscious, the ability to sustain adequate spontaneous ventilation was determined every 30 min. Patients were not considered ready for possible extubation of the trachea until they had a period of stable cardiovascular measurements for 2h. Following this, extubation was considered

3 ALFENTANIL-OXYGEN ANAESTHESIA 1293 possible if patients could maintain a spontaneous respiratory rate of at least -10 b.p.m., could generate a negative inspiratory pressure of mmhg and could sustain Pa^, of less than 6 kpa and a Pa Oi of 13 kpa or more while breathing spontaneously (without encouragement) 40% oxygen via a T-piece apparatus for min. The trachea was not extubated until the morning after surgery because of intensive care unit practice. To facilitate mechanical ventilation after our test period, sedatives or analgesics were administered throughout the night as deemed necessary. All patients were interviewed 4 h after operation. Questions were specifically directed at determining the presence or absence of pain and memory of laryngoscopy, endotracheal intubation and any aspect of the operative procedure. Data were analysed for statistical significance using Student's paired t test. RESULTS The patients' mean age was 56±6yr (range yr) and mean weight 1 kg (range 60-9 kg). Unconsciousness was produced with an average of alfentanil 3.±0.9mg (46ugkg~') in 75 ± 1 s (fig. 2). However, additional alfentanil was required for intubation in 0% of patients and by the time of incision the total dose of alfentanil End of Intubate Sternal operation split FIG. 2. Cumulative doses of alfentanil administered to 15 patients undergoing coronary artery bypass operations. given was almost 10 times the induction dose. It was necessary to administer alfentanil throughout the operation to keep patients adequately anaesthetized and to maintain arterial pressures within 15% of preanaesthetic (control) values. An average of alfentanil mg or 1.22±0.02mgkg~' was required for the entire operation (fig. 2). Muscle rigidity occurred in four patients (27%). However, in only one patient was rigidity so severe that positive pressure ventilation was impossible without suxamethonium. The induction of anaesthesia with alfentanil produced small but significant decreases in systolic and mean arterial pressure but did not significantly change any other variable measured (table I). The changes in systolic and mean arterial pressures were transient and all pressures were similar to control at the time of incision. Heart rate, cardiac output and mean pulmonary artery pressure remained unaltered throughout the entire study. Arterial pressures were not significantly changed before cardiopulmonary bypass with the exception of lomin following maximal sternal spread when they, and right atrial pressures, were significantly increased. These increases responded rapidly to additional alfentanil so that phentolamine was never required before bypass (table II). However, increases in arterial pressure occurred suddenly and were often dramatic with stressful stimulation (sternotomy and sternal spread). As a result, although arterial pressures were not significantly increased 5min after sternal spread, and only slightly increased 5 min later, 60% of patients had transient increases in systolic arterial pressure greater than 25% following sternotomy and 73% following maximal sternal spread (table III). Phentolamine was required to control arterial pressure in four patients (27%) during bypass. Forty-seven per cent of patients received nitrous oxide and 33% nitroprusside in addition after cardiopulmonary bypass to control arterial pressure. All patients but one were conscious within 3h of the end of operation and fulfilled the criteria for endotracheal extubation within 5 h: consciousness returned, on average, 1.4±0.6h after operation and patients fulfilled the criteria for extubation after 4.1 ± 1.2 h in the intensive care unit. When interviewed after operation no patient remembered laryngoscopy, endotracheal intubation or any aspect of the anaesthetic or surgical procedure.

4 1294 BRITISH JOURNAL OF ANAESTHESIA TABLE I. Cardiovascular responses during anaesthesia and operation (mean ± SD). *P < 0.05, Student's paired t test compared with control Control Unconscious Intubation Before Incision 5 min ijeiore stemotomy After sterna1 spread 5min lomin Heart rate (beat min ') Cardiac output (litre min"') Systolic arterial pressure (mmhg) Mean arterial pressure (mmhg) Mean right atrial pressure (mmhg) Mean pulmonary artery pressure (mmhg) ± ± * ±10 7* ± ±0.9 1 ± ± ± ± ± ± ± ± ± ± ± * ±12 97* 10* 1 TABLE II. Per cent of patients requiring supplementation with phentolamine, nitrous oxide or nitroprusside during CABG operations tenth alfentanil-oxygen anaesthesia Phentolamine Before 0 During bypass 27 Nitrous oxide after bypass 47 Nitroprusside after bypass TABLE III. Per cent of patients with increases in systolic arterial pressure greater than % of control values during CABG operations with alfentanil oxygen anaesthesia Intubation Incision Stemotomy Sternal spread DISCUSSION This study demonstrated that large doses of alfentanil, like equivalent doses of fentanyl, produce unconsciousness with little change in cardiovascular dynamics. The data suggest that, when compared with fentanyl-oxygen anaesthesia in a similar group of patients from a similar population (de Lange, Stanley and Boscoe, 190a), the induction of anaesthesia and recovery from anaesthesia are more rapid with alfentanil, but the frequency of muscle rigidity at induction is similar and systemic hypertension during severe surgical stress is more common. Recent work has confirmed the cardiovascular stability originally described by Stanley and coworkers (Stanley and Webster, 197; Lunn et al., 1979; Stanley, Philbin and Coggins, 1979) with high-dose fentanyl-oxygen anaesthesia (Hill et al., 190; de Lange, Stanley and Boscoe, 190a, b; Waller, Hug and Nagle, 191) but has also suggested that muscle rigidity, intra-operative hypertension and prolonged respiratory depression after operation are occasional problems associated with this technique. The frequency of these problems appears to be related to the total dose and rate of infusion of fentanyl, the time of administration of the neuromuscular blocker, population differences, prior drug therapy and experience with the technique (de Castro, 1976; Hill et al., 190; de Lange, Stanley and Boscoe, 190a, b). We have found that by using lorazepam 0.0 mgkg" 1 orally as premedication, and by pretreating patients with pancuronium 0.02mgkg~', i.v. before anaesthesia, muscle rigidity during the induction of anaesthesia with fentanyl at an infusion rate of 400 jig min" 1 was decreased to approximately 10-% (de Lange, Stanley and Boscoe, 190a, b). At this infusion rate unconsciousness occurs in 4-5 min (de Lange, Stanley and Boscoe, 190a). It is possible to decrease the duration of induction by infusing the fentanyl more rapidly or by using a bolus of at least 50ugkg~'. However, the frequency of muscle rigidity increases significantly and bradycardia and hypotension may occur (Hill et al., 190; de Lange and Stanley, unpublished observations). Other workers have attempted to expedite induction and minimize rigidity by administering a full neuromuscular blocking dose of pancuronium

5 ALFENTANIL-OXYGEN ANAESTHESIA 1295 with a large bolus of fentanyl (BovilJ and Sebel, 190; Hill et al., 190; Waller et al., 191). Although this technique prevents rigidity, hypotension and bradycardia, it may induce tachycardia and hypertension instead (Waller et al., 191). It was hoped that, when compared with fentanyl, alfentanil would maintain cardiovascular stability, decrease the duration of induction and recovery and decrease the frequency of muscle rigidity. In animals equipotent doses of alfentanil have little effect on cardiovascular dynamics, result in shorter onset and recovery times and possess a greater ED 50 : LD SO ratio than fentanyl (de Castro et al., 1979; C. Niemeggers, unpublished data). Although anaesthesia was induced in approximately 75 s with alfentanil 3.0mgmin~' in this study, this resulted in a 27% frequency of muscle rigidity. Rapid administration of a 10-mg bolus of alfentanil and a full neuromuscular blocking dose of pancuronium resulted in a more rapid induction of anaesthesia than observed in this study without evidence of rigidity, but was likely to produce tachycardia or hypertension, or both (de Castro et al., 1979). Increase in systolic arterial pressure of % or more occurred in 60% of our patients during sternotomy and in 73% during sternal spread. This was significantly greater than occurred in similar patients anaesthetized with large doses of fentanyl and oxygen (de Lange, Stanley and Boscoe, 190a). However, most of the hypertensive episodes in this study responded quickly to additional alfentanil. As a result, the need for supplements (phentolamine, nitrous oxide, sodium nitroprusside) before, during and after bypass was not significantly different than we have reported duriqg high-dose fentanyl anaesthesia (de Lange, Stanley and Boscoe, 190a). However, need for these supplements, which we regard as an undesirable feature of narcotic-oxygen anaesthetic techniques, was still greater than with sufentanil-oxygen anaesthesia (de Lange, Stanley and Boscoe, 190a). Problems with hypertension during coronary artery surgery with alfentanil-oxygen anaesthesia may have occurred because of the extremely short duration of action of alfentanil. This suggests that the frequency of intraoperative hypertension may be decreased or perhaps even eliminated by the administration of a continuous infusion of the compound. Return of consciousness occurred approximately 1 h after the end of operation. Patients fulfilled our criteria for possible extubation approximately 3 h later. These time are significantly shorter than were noted in similar patients anaesthetized with fentanyl or sufentanil and oxygen (Lunn et al., 1979; Stanley, Philbin and Coggins, 1979; de Lange, Stanley and Boscoe, 190a, b). Speedy recovery after even large doses of alfentanil is probably related to rapid dissociation of the compound from central nervous system opiate receptors (J. Leysen, personal communication). The dissociation constant of alfentanil from rat brain opiate receptors is significantly lower than fentanyl or any other natural or synthetic narcotic currently available (J. Leysen, unpublished observations). REFERENCES Bovill, J. G.,and Sebel, P. S. (190). Pharmacokinetics of highdose fentanyl. A study in patients undergoing cardiac surgery. Br. J. Anaesth., 52, 795. de Castro, J. (1976). Practical applications and limitation of analgesic anaesthesia. Acta Anaesthttiol. Btlg., 27, 107. Van de Water, A., Wouters, L., Xhonneux R., Reneman, R., and Kay, E. (1979). Comparative study of cardiovascular, neurological and metabolic side-effects of eight narcotics in dogs. Acta Anaesthesiol. Btlg., 30, 5. Dubois-Primo, J. (1975). 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H., Eisele, J., Webster, L. R., and Woodward, A. (1979). High-dose fentanyl anesthesia for coronary artery surgery: Plasma fentanyl concentrations and influence of nitrous oxide on cardiovascular responses. Anesth. Analg. (Cleve.), 5, 390. Stanley, T. H., Berman, L., Green, A., and Robertson, D. (190). Plasma catecholamine and corrisol responses to fentanyl-oxygen anesthesia for coronary artery operations. Anesthesiology, 53, 250.