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ALFENTANIL AND PROPOFOL INFUSIONS FOR SURGERY IN THE BURNED PATIENT
Br. J. Anaesth. (1989), 63, 418-^22
ALFENTANIL AND PROPOFOL INFUSIONS FOR SURGERY IN THE BURNED PATIENT C. J. REYNEKE, M. F. M. JAMES AND R. JOHNSON
PATIENTS AND METHODS
We studied 24 patients (age 18-60 yr, ASA I—III) who had sustained burns involving a minimum of 20 % of body surface area requiring skin grafting, and having elective surgery of more than 45 min duration (table I). The study was approved by the C. J. REYNEKE, M.B., CH.B., D.A.(S.A.), F.F.A.(S.A.); M . F . M . JAMES*, M.B., CH.B.(BIRM.), F.F.A.R.C.S. (ENG.); R. JOHNSON,
M.B., CH.B. ; Department of Anaesthesia, Hillbrow Hospital, Johannesburg, S. Africa. Accepted for Publication: March 21, 1989. 'Present address for correspondence: Department of Anaesthesia, University of Cape Town, Medical School, 7925 Observatory, Cape, Republic of South Africa.
SUMMARY We have studied combinations of alfentanil and propofol for total i.v. anaesthesia in 24 severely burned patients. No inhalation agents were used. After a loading dose of alfentanil 100 ng kg'1, the intraoperative requirement was 1.24 (SEM 0.7) ng kg'1 min'1. and after a propofol induction dose of 2 mg kg'1 the maintenance rate was 100 fig kg'1 min'1. Initial hypotension occurred after induction of anaesthesia, but during the operation, cardiovascular variables were stable. After adequate antagonism of neuromuscu/ar block, respiratory depression persisted in three patients when the two agents were discontinued simultaneously; this was not seen when alfentanil was discontinued 15 min before propofol. Quality of recovery was good, and satisfactory postoperative analgesia was present in the majority of patients 2 h after operation. This study indicates that total i.v. anaesthesia with a combination of alfentanil and propofol appears to be satisfactory in burned patients.
Ethics Committee of the University of the Witwatersrand, and Hillbrow Hospital, and informed patient consent was obtained. All concurrent medications were continued in the perioperative period as indicated clinically. All patients were premedicated with diazepam 10-15 mg orally, 90 min before operation. Apart from a small quantity of water which accompanied the premedication, all patients were fasted for at least 8 h before surgery. Before induction of anaesthesia, a large peripheral vein was cannulated and an arterial cannula inserted when clinically indicated. A loading dose of alfentanil 100 |ig kg"1 was administered over 6.6 min using a syringe pump supplied by Janssen Pharmaceuticals. During this period, the patient breathed 100 % oxygen via a Mapleson
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Burned patients frequently need extensive debridement and multiple skin grafts. Anaesthesia for these compromised patients must avoid any additional debilitating factors. Repeated exposure to halothane may cause hepatic damage [1], and enflurane may produce similar hepatic injury, although less commonly [2]. It is well known that severe burn injury is accompanied by suppression of most components of immunity [3]. The inactivation of vitamin B12 by nitrous oxide and subsequent possible depression of the immune response by this agent [4] is a potential disadvantage of inhalation anaesthesia when this gas is used. Total i.v. anaesthesia has potential advantages in that liver damage does not seem to be a risk, renal damage should not occur, and the problems associated with the use of nitrous oxide may be avoided. It is also possible that the technique may have less deleterious effects on the immune response, but there are currently no clinical data on this subject. The purpose of this study was to evaluate the safety and efficacy of a combination of alfentanil with propofol for total i.v. anaesthesia in severely burned patients.
419
INFUSIONS IN BURNED PATIENTS TABLE I. Details of patients studied. TIVA = Total i.v. anaesthesia
Burn to surgery interval
% Burn Range
No.
20-29 30-39 40-^9 50-59
17 2 3 2
Multiple TIVA
Range (days)
Initial (No.)
Study (No.)
No. of anaesthetics
Patients (No.)
1-7
14 5 5 —
9 4 6 4 1
2 3 4
3 2 1
8-14 15-21 21-28 28 +
In the first three patients of the study, propofol and alfentanil were discontinued simultaneously at the end of surgery, but because of early postoperative respiratory depression, in the remaining patients propofol was stopped at the end of surgery, but the alfentanil was discontinued 15 min earlier. Residual neuromuscular block was antagonized at the end of anaesthesia before tracheal extubation, and adequate antagonism confirmed by the use of a nerve stimulator. All patients who were not breathing adequately at the end of surgery underwent mechanical ventilation and boluses of naloxone 0.5 ug kg"1 administered until adequate tidal volume and rate of ventilation were present. Time to tracheal extubation, time to eye opening in response to command, and time to full orientation were recorded. Pain scoring was performed at the time of orientation, 20 min later and 120 min after orientation. Pain was classified on a 5-point scale (none, minimal, mild, moderate and severe). Parenteral analgesics were administered to patients with moderate or severe pain. Awareness and amnesia were assessed in all patients by direct questioning at the time of awareness and 2 h after operation for his/her last preoperative recollection (in the ward before operation, journey to the operating room, in the operating room, falling asleep), recall of perioperative events, and first postoperative memory—for example in the operating room, in the recovery room or back in the ward. Changes in measured variables were compared with baseline values using Student's t test with the Bonferroni modification for multiple comparisons. Significance was defined as P < 0.05. RESULTS
Numerical data are presented as means (SEM). Total i.v. anaesthesia was successful in pro-
Downloaded from http://bja.oxfordjournals.org/ at McMaster University Library on June 28, 2015
A system and ventilation of the lungs was performed manually as the patient became drowsy, or respiratory depression occurred. Anaesthesia was induced with propofol 2.5 mg kg"1 and neuromuscular block produced with pancuronium 0.1 mgkg"1. Tracheal intubation was performed 3 min after induction with propofol. Non-invasive arterial pressure, heart rate and ECG were monitored continuously in all patients and recordings made at the following times: before any anaesthetic drugs; immediately after the preinduction dose of alfentanil; immediately after induction; immediately after tracheal intubation; immediately after incision; and at 5-min intervals throughout the anaesthetic. Routine clinical monitoring was performed also. Anaesthesia was maintained with an infusion of propofol 100 ng kg"1 min"1 delivered by syringe pump, combined with an infusion of alfentanil 1 ug kg"1 min"1. Ventilation was maintained using oxygen enriched air (Fi0]i 0.5) and the minute volume adjusted to produce normocapnia as assessed by capnography. Additional neuromuscular blocker was given as indicated clinically. If arterial pressure or heart rate exceeded 20 % of control values in response to surgical stimulation, a bolus dose of alfentanil 7.5 ug kg"1 was given; if the patient was still judged to be anaesthetized inadequately after two bolus injections of alfentanil given over a 5-min period, the infusion rate of alfentanil was increased by 0.25 ug kg"1 min"1. Clinical indications other than cardiovascular changes for increasing the depth of anaesthesia included patient movement, lachrymation and sweating. If an adequate depth of anaesthesia was not achieved, inhalation agents were used. The alfentanil and propofol infusion rates were decreased or discontinued as indicated clinically by a decrease in arterial pressure or heart rate, or when the surgery was close to termination.
420
BRITISH JOURNAL OF ANAESTHESIA TABLE II. Cardiovascular changes (mean (SEAT) [range]) in the perioperative period. SAP, DAP = Systolic and diastolic arterial pressures; "Light" = Maximum arterial pressure and heart rate when the patient was assessed clinically to be inadequately anaesthetized. Significant differences from baseline values: *P < 0.001; | P < 0.005 SAP (mm Hg) Baseline After alfentanil After induction After intubation Incision "Light"
130.2 (3.1) 1158-99] 123.7 (3.7) [177-90] 109.6| (4.1) [155-80] 99.5* (3.8) [139-61] 128.0 (5.1) [163-77] 139.0 (4.8) [179-100]
79.5 (1.5) 75.8 (2.4) 67.2+ (2.5) 58.8* (2.6)
97.5 (5.0) [142-55] 92.6 (4.6) [138-53] 106.4 (3.9) [142-62] 97.5 (4.0) [137-59] 103.3 (4.1) [134-52] 110.7 (4.1) [142-80]
[101-66] [110-53] [95-46] [89-37]
76.5 (3.1) [104-49] 86.6 (3.3) [112-63]
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ducing clinically adequate levels of anaesthesia in all patients and inhalation agents were not required. Only four patients received total i.v. anaesthesia as their first anaesthetic, and several were studied on more than one occasion (table I). Although all patients found the method acceptable, none expressed a preference for total i.v. or conventional anaesthesia. There were no significant changes in arterial pressure or heart rate following the loading dose of alfentanil. Propofol induction produced a mean reduction in systolic pressure of 23.4 (2.4) %(P < 0.01) and a mean reduction of 25.9 (2.8) % (P < 0.01) in diastolic pressure, but no significant change in heart rate. Both systolic and diastolic pressures increased slightly, to approximately 15 % below baseline, with tracheal intubation, but both remained significantly depressed (P < 0.01). At the time of incision the systolic pressure remained stable and at times when the patients were judged to be clinically light no significant changes in cardiovascular variables occurred. There were no significant changes in heart rate throughout the procedure (table II). Peaks of arterial pressure above baseline values occurred in six of 24 patients during surgery. In the remainder, the maximum arterial pressure was recorded either before intubation or after completion of surgery.
Heart rate (beat min"1)
DAP (mm Hg)
TABLE III. Numbers of patients requiring additional doses or changes of infusion rate of alfentanil No change
1 bolus
2 boluses
>2 boluses
Rate change
7 29
6 25
5 21
3 12.5
5 21
No. 0/
/o
sequent to the loading dose of alfentanil, the mean intraoperative requirement for alfentanil, including supplementary boluses and changes of infusion rate, was 1.24 (0.07) |ig kg"1 min"1. The mean infusion time of propofol was 73.71 (27.75) min. After an initial dose of O.lmgkg" 1 , 10 patients needed additional doses of pancuronium to ensure adequate neuromuscular block. Naloxone was administered to three patients who had postoperative respiratory depression. In all three, alfentanil and propofol had been discontinued simultaneously at the end of surgery (table III).
Recovery
The mean time for commencement of spontaneous ventilation was 15.1 (6.9) min (range 7-31 min) after the discontinuation of the propofol infusion. Spontaneous eye-opening occurred 13.2 Drug usage (5.3) min (range 7-31 min), and extubation was Seven patients required no alfentanil additional performed at a mean of 18.3 (6.5) min after the to the initial maintenance rate of 1 ng kg"1 min"1, discontinuation of the anaesthetic. The mean time and five patients required a single increase of the for orientation after termination of the anaesthetic infusion rate to 1.25 ngkg"1 min"1. No patient was 23.3 (10.6) min (range 15-68 min). The required a second increase in infusion rate. It was patients remained an average time of 27.8 (16.9) not necessary to reduce the infusion rate of min in the recovery room (which was not alfentanil either from its initial value, or following necessarily a reflection of the adequacy of rea rate increase until the end of surgery. Sub- covery).
421
INFUSIONS IN BURNED PATIENTS TABLE IV. Percentages of patients experiencing pain at three intervals after operation. Only patients with moderate or severe pain required additional analgesia
After full recovery
No pain Minimal pain Mild pain Moderate pain Severe pain
Recovery
20min
120 min
87.5
48.3 20.9 30.8
12.5 12.5 45.9 20.8
4.2 8.3 0 0
0 0
8.3
At the time of full orientation the majority of patients had no pain and the few patients who exhibited pain at this time had only minimal or mild pain (table IV). At 20 min, almost 50 % of the patients remained pain free, and no patient complained of moderate or severe pain. At 120 min after extubation, 29 % of patients needed parenteral analgesics. Awareness and amnesia
No patients remembered falling asleep or had recollection of intraoperative events. In five patients, last recollection was before leaving the ward, in 11 it was transfer to theatre and in eight patients, arriving in theatre. No patient recalled needing ventilatory assistance during the alfentanil infusion. On recovery, 11 patients remembered awakening in theatre, and the remaining 13 patients' first recall was in the recovery room.
Complications
Rigidity occurred in 17 of 24 patients during the loading infusion of alfentanil at a mean dose of 72.7 (18) |ag kg"1. Respiratory inadequacy, because of either central depression or muscle rigidity, and requiring manual ventilatory assistance, occurred in 14 of 24 patients during the alfentanil preload, but was not sufficiently severe to make manual ventilation impossible. At the end of the procedure, secretions in the upper airways were excessive and required active suctioning in 18 patients. Three of the 24 patients needed naloxone to antagonize respiratory depression at the end of the procedure.
Until recently, total i.v. anaesthesia has been limited by the relatively prolonged action of the agents available. Alfentanil has been studied in balanced anaesthetic techniques [5]. It has an onset of action within 1 min of administration, a potency approximately 20 % that of fentanyl, and a shorter elimination half-life of 90 min, with a small volume of distribution [6,7]. These characteristics suggest that alfentanil is particularly suitable for total i.v. anaesthesia [8]. Propofol has a redistribution half-life of 1.8-8.3 min following i.v. administration. The drug is metabolized by conjugation in the liver with a (3elimination half-life of 34-64 min, although some studies have used a three-compartment model with a similar T£ but a terminal elimination halflife of 200-300 min. Inactive metabolites are excreted by the kidney. With the usual maintenance regimens, significant cumulation of propofol does not occur [9, 10]. Since the advent of alfentanil and propofol, total i.v. anaesthesia with a combination of these agents has been investigated widely, but few studies have excluded all inhalation agents; those which have used only i.v. agents have been for relatively short procedures such as microlaryngeal surgery. The propofol infusion rate in our study was comparable to that used elsewhere [5, 11, 12] and it was not necessary to vary this rate during surgery. The dose of alfentanil used also corresponded well with those described previously [13, 14]. Several of our patients needed additional boluses of alfentanil, and a few required adjustment of the alfentanil rate during the operation, suggesting that a higher initial maintenance infusion rate may be more appropriate. Administration of the alfentanil bolus after the induction dose of propofol may avoid pre-intubation complications, such as rigidity and respiratory depression. The cardiovascular changes observed on induction of anaesthesia are similar to those reported by other investigators for propofol [15, 16], and it is reasonable to conclude that alfentanil did not contribute significantly to these changes. Intraoperative cardiovascular stability was notable. Most of the patients required blood transfusions during operation and this interfered with the flow of drugs intravenously. This necessitated
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Pain scores
DISCUSSION
422
BRITISH JOURNAL OF ANAESTHESIA
1.
2.
3. 4. 5.
11. REFERENCES A study of the possible association between halothane anesthesia and postoperative hepatic necrosis. In: Bunker JP, Forrest WH, Mosteller F, Vandam LD, eds. National 12. Halothane Study. Washington D.C.: U.S. Govt. Printing Office, 1969. Hussey AJ, Aldridge LM, Paul D, Ray DC, Beckett GJ, 13. Allan LG. Plasma glutathione s-transferase concentration as a measure of hepatocellular integrity following a single general anaesthetic with halothane, enflurane or iso- 14. flurane. British Journal of Anaesthesia 1988; 60: 130-135. Munster AM. Immunologic alterations following injury. In: Advances in Orthopaedic Surgery 1985; 328. Koblin DD, Waskell L, Watson JE, Stokstad ELR, Eger 15. EL II. Nitrous oxide inactivates methionine synthetase in humans. Anesthesia and Analgesia 1982; 61: 75-78. 16. Kay B. Propofol and alfentanil infusion. A comparison with methohexitone and alfentanil for major surgery. Anaesthesia 1986; 41: 589-595.
Kay B, Healy TEJ. Propofol (Diprivan) for outpatient cystoscopy. Efficacy and recovery compared with Althesin and methoxitone. Postgraduate Medical Journal 1985; 61 (Suppl. 3): 108-114. Redfern N, Stafford MA, Brooker J, Hull CJ. Incremental propofol for short procedures. British Journal of Anaesthesia 1985; 57: 349P. Hug CC, Chaffman CC. Dosage and administration of alfentanil. In: Alfentanil: Pharmacology and Uses in Anaesthesia. Auckland: ADIS, 1984; 101-104. Schuttler J, Stoeckel H, Lauven PM. Pharmakokinetsch begrundete infusionsmodelle fur die narkose fuhrung mit alfentanil. In: Doenicke A, ed. Alfentanil. Berlin: Springer-Verlag, 1983. Kay B, Stephenson DK. ICI 35865 (Diprivan). A new intravenous anaesthetic. Anaesthesia 1980; 35: 1182. Coates DP, Monk CR, Prys-Roberts C, Turtle M. Hemodynamic effects of the emulsion formulation of propofol during nitrous oxide anesthesia in humans. Anesthesia and Analgesia 1987; 66: 64-70.
Downloaded from http://bja.oxfordjournals.org/ at McMaster University Library on June 28, 2015
a second i.v. cannula which may be a disadvantage 6. Bower S, Hull CJ. Comparative pharmacokinetics of fentanyl and alfentanil. British Journal of Anaesthesia in view of the problems of obtaining venous access 1982; 54: 871-877. in severely burned patients. 7. Bovill JC, Sebel PS, Blackburn CL, Heykants J. The Recovery from anaesthesia was rapid. No pharmacokinetics of alfentanil (R39209): A new opiate complications occurred related to anaesthesia and analgesic. Anesthesiology 1982; 57: 439-443. no patient had any unpleasant sequelae during the 8. (Anon.) Alfentanil in anaesthesia. Drugs and Therapeutics Bulletin 1986; 24: 51-52. recovery period. Although eye opening occurred 9. Cockshot ID. Propofol (Diprivan) pharmacokinetics and usually before spontaneous ventilation commetabolism—an overview. Postgraduate Medical Journal menced, and thus before extubation, no patient 1985; 61 (Suppl. 3): 45-50. had unpleasant recollections related to this se- 10. Grant IS, Mackenzie N. Recovery following propofol (Diprivan) anaesthesia—a review of three different anquence of events. Residual analgesia appeared to aesthetic techniques. Postgraduate Medical Journal 1985; contribute to the quality of recovery. 61 (Suppl. 3): 133-136.
ALFENTANIL AND PROPOFOL INFUSIONS FOR SURGERY IN THE BURNED PATIENT C. J. REYNEKE, M. F. M. JAMES AND R. JOHNSON
PATIENTS AND METHODS
We studied 24 patients (age 18-60 yr, ASA I—III) who had sustained burns involving a minimum of 20 % of body surface area requiring skin grafting, and having elective surgery of more than 45 min duration (table I). The study was approved by the C. J. REYNEKE, M.B., CH.B., D.A.(S.A.), F.F.A.(S.A.); M . F . M . JAMES*, M.B., CH.B.(BIRM.), F.F.A.R.C.S. (ENG.); R. JOHNSON,
M.B., CH.B. ; Department of Anaesthesia, Hillbrow Hospital, Johannesburg, S. Africa. Accepted for Publication: March 21, 1989. 'Present address for correspondence: Department of Anaesthesia, University of Cape Town, Medical School, 7925 Observatory, Cape, Republic of South Africa.
SUMMARY We have studied combinations of alfentanil and propofol for total i.v. anaesthesia in 24 severely burned patients. No inhalation agents were used. After a loading dose of alfentanil 100 ng kg'1, the intraoperative requirement was 1.24 (SEM 0.7) ng kg'1 min'1. and after a propofol induction dose of 2 mg kg'1 the maintenance rate was 100 fig kg'1 min'1. Initial hypotension occurred after induction of anaesthesia, but during the operation, cardiovascular variables were stable. After adequate antagonism of neuromuscu/ar block, respiratory depression persisted in three patients when the two agents were discontinued simultaneously; this was not seen when alfentanil was discontinued 15 min before propofol. Quality of recovery was good, and satisfactory postoperative analgesia was present in the majority of patients 2 h after operation. This study indicates that total i.v. anaesthesia with a combination of alfentanil and propofol appears to be satisfactory in burned patients.
Ethics Committee of the University of the Witwatersrand, and Hillbrow Hospital, and informed patient consent was obtained. All concurrent medications were continued in the perioperative period as indicated clinically. All patients were premedicated with diazepam 10-15 mg orally, 90 min before operation. Apart from a small quantity of water which accompanied the premedication, all patients were fasted for at least 8 h before surgery. Before induction of anaesthesia, a large peripheral vein was cannulated and an arterial cannula inserted when clinically indicated. A loading dose of alfentanil 100 |ig kg"1 was administered over 6.6 min using a syringe pump supplied by Janssen Pharmaceuticals. During this period, the patient breathed 100 % oxygen via a Mapleson
Downloaded from http://bja.oxfordjournals.org/ at McMaster University Library on June 28, 2015
Burned patients frequently need extensive debridement and multiple skin grafts. Anaesthesia for these compromised patients must avoid any additional debilitating factors. Repeated exposure to halothane may cause hepatic damage [1], and enflurane may produce similar hepatic injury, although less commonly [2]. It is well known that severe burn injury is accompanied by suppression of most components of immunity [3]. The inactivation of vitamin B12 by nitrous oxide and subsequent possible depression of the immune response by this agent [4] is a potential disadvantage of inhalation anaesthesia when this gas is used. Total i.v. anaesthesia has potential advantages in that liver damage does not seem to be a risk, renal damage should not occur, and the problems associated with the use of nitrous oxide may be avoided. It is also possible that the technique may have less deleterious effects on the immune response, but there are currently no clinical data on this subject. The purpose of this study was to evaluate the safety and efficacy of a combination of alfentanil with propofol for total i.v. anaesthesia in severely burned patients.
419
INFUSIONS IN BURNED PATIENTS TABLE I. Details of patients studied. TIVA = Total i.v. anaesthesia
Burn to surgery interval
% Burn Range
No.
20-29 30-39 40-^9 50-59
17 2 3 2
Multiple TIVA
Range (days)
Initial (No.)
Study (No.)
No. of anaesthetics
Patients (No.)
1-7
14 5 5 —
9 4 6 4 1
2 3 4
3 2 1
8-14 15-21 21-28 28 +
In the first three patients of the study, propofol and alfentanil were discontinued simultaneously at the end of surgery, but because of early postoperative respiratory depression, in the remaining patients propofol was stopped at the end of surgery, but the alfentanil was discontinued 15 min earlier. Residual neuromuscular block was antagonized at the end of anaesthesia before tracheal extubation, and adequate antagonism confirmed by the use of a nerve stimulator. All patients who were not breathing adequately at the end of surgery underwent mechanical ventilation and boluses of naloxone 0.5 ug kg"1 administered until adequate tidal volume and rate of ventilation were present. Time to tracheal extubation, time to eye opening in response to command, and time to full orientation were recorded. Pain scoring was performed at the time of orientation, 20 min later and 120 min after orientation. Pain was classified on a 5-point scale (none, minimal, mild, moderate and severe). Parenteral analgesics were administered to patients with moderate or severe pain. Awareness and amnesia were assessed in all patients by direct questioning at the time of awareness and 2 h after operation for his/her last preoperative recollection (in the ward before operation, journey to the operating room, in the operating room, falling asleep), recall of perioperative events, and first postoperative memory—for example in the operating room, in the recovery room or back in the ward. Changes in measured variables were compared with baseline values using Student's t test with the Bonferroni modification for multiple comparisons. Significance was defined as P < 0.05. RESULTS
Numerical data are presented as means (SEM). Total i.v. anaesthesia was successful in pro-
Downloaded from http://bja.oxfordjournals.org/ at McMaster University Library on June 28, 2015
A system and ventilation of the lungs was performed manually as the patient became drowsy, or respiratory depression occurred. Anaesthesia was induced with propofol 2.5 mg kg"1 and neuromuscular block produced with pancuronium 0.1 mgkg"1. Tracheal intubation was performed 3 min after induction with propofol. Non-invasive arterial pressure, heart rate and ECG were monitored continuously in all patients and recordings made at the following times: before any anaesthetic drugs; immediately after the preinduction dose of alfentanil; immediately after induction; immediately after tracheal intubation; immediately after incision; and at 5-min intervals throughout the anaesthetic. Routine clinical monitoring was performed also. Anaesthesia was maintained with an infusion of propofol 100 ng kg"1 min"1 delivered by syringe pump, combined with an infusion of alfentanil 1 ug kg"1 min"1. Ventilation was maintained using oxygen enriched air (Fi0]i 0.5) and the minute volume adjusted to produce normocapnia as assessed by capnography. Additional neuromuscular blocker was given as indicated clinically. If arterial pressure or heart rate exceeded 20 % of control values in response to surgical stimulation, a bolus dose of alfentanil 7.5 ug kg"1 was given; if the patient was still judged to be anaesthetized inadequately after two bolus injections of alfentanil given over a 5-min period, the infusion rate of alfentanil was increased by 0.25 ug kg"1 min"1. Clinical indications other than cardiovascular changes for increasing the depth of anaesthesia included patient movement, lachrymation and sweating. If an adequate depth of anaesthesia was not achieved, inhalation agents were used. The alfentanil and propofol infusion rates were decreased or discontinued as indicated clinically by a decrease in arterial pressure or heart rate, or when the surgery was close to termination.
420
BRITISH JOURNAL OF ANAESTHESIA TABLE II. Cardiovascular changes (mean (SEAT) [range]) in the perioperative period. SAP, DAP = Systolic and diastolic arterial pressures; "Light" = Maximum arterial pressure and heart rate when the patient was assessed clinically to be inadequately anaesthetized. Significant differences from baseline values: *P < 0.001; | P < 0.005 SAP (mm Hg) Baseline After alfentanil After induction After intubation Incision "Light"
130.2 (3.1) 1158-99] 123.7 (3.7) [177-90] 109.6| (4.1) [155-80] 99.5* (3.8) [139-61] 128.0 (5.1) [163-77] 139.0 (4.8) [179-100]
79.5 (1.5) 75.8 (2.4) 67.2+ (2.5) 58.8* (2.6)
97.5 (5.0) [142-55] 92.6 (4.6) [138-53] 106.4 (3.9) [142-62] 97.5 (4.0) [137-59] 103.3 (4.1) [134-52] 110.7 (4.1) [142-80]
[101-66] [110-53] [95-46] [89-37]
76.5 (3.1) [104-49] 86.6 (3.3) [112-63]
Downloaded from http://bja.oxfordjournals.org/ at McMaster University Library on June 28, 2015
ducing clinically adequate levels of anaesthesia in all patients and inhalation agents were not required. Only four patients received total i.v. anaesthesia as their first anaesthetic, and several were studied on more than one occasion (table I). Although all patients found the method acceptable, none expressed a preference for total i.v. or conventional anaesthesia. There were no significant changes in arterial pressure or heart rate following the loading dose of alfentanil. Propofol induction produced a mean reduction in systolic pressure of 23.4 (2.4) %(P < 0.01) and a mean reduction of 25.9 (2.8) % (P < 0.01) in diastolic pressure, but no significant change in heart rate. Both systolic and diastolic pressures increased slightly, to approximately 15 % below baseline, with tracheal intubation, but both remained significantly depressed (P < 0.01). At the time of incision the systolic pressure remained stable and at times when the patients were judged to be clinically light no significant changes in cardiovascular variables occurred. There were no significant changes in heart rate throughout the procedure (table II). Peaks of arterial pressure above baseline values occurred in six of 24 patients during surgery. In the remainder, the maximum arterial pressure was recorded either before intubation or after completion of surgery.
Heart rate (beat min"1)
DAP (mm Hg)
TABLE III. Numbers of patients requiring additional doses or changes of infusion rate of alfentanil No change
1 bolus
2 boluses
>2 boluses
Rate change
7 29
6 25
5 21
3 12.5
5 21
No. 0/
/o
sequent to the loading dose of alfentanil, the mean intraoperative requirement for alfentanil, including supplementary boluses and changes of infusion rate, was 1.24 (0.07) |ig kg"1 min"1. The mean infusion time of propofol was 73.71 (27.75) min. After an initial dose of O.lmgkg" 1 , 10 patients needed additional doses of pancuronium to ensure adequate neuromuscular block. Naloxone was administered to three patients who had postoperative respiratory depression. In all three, alfentanil and propofol had been discontinued simultaneously at the end of surgery (table III).
Recovery
The mean time for commencement of spontaneous ventilation was 15.1 (6.9) min (range 7-31 min) after the discontinuation of the propofol infusion. Spontaneous eye-opening occurred 13.2 Drug usage (5.3) min (range 7-31 min), and extubation was Seven patients required no alfentanil additional performed at a mean of 18.3 (6.5) min after the to the initial maintenance rate of 1 ng kg"1 min"1, discontinuation of the anaesthetic. The mean time and five patients required a single increase of the for orientation after termination of the anaesthetic infusion rate to 1.25 ngkg"1 min"1. No patient was 23.3 (10.6) min (range 15-68 min). The required a second increase in infusion rate. It was patients remained an average time of 27.8 (16.9) not necessary to reduce the infusion rate of min in the recovery room (which was not alfentanil either from its initial value, or following necessarily a reflection of the adequacy of rea rate increase until the end of surgery. Sub- covery).
421
INFUSIONS IN BURNED PATIENTS TABLE IV. Percentages of patients experiencing pain at three intervals after operation. Only patients with moderate or severe pain required additional analgesia
After full recovery
No pain Minimal pain Mild pain Moderate pain Severe pain
Recovery
20min
120 min
87.5
48.3 20.9 30.8
12.5 12.5 45.9 20.8
4.2 8.3 0 0
0 0
8.3
At the time of full orientation the majority of patients had no pain and the few patients who exhibited pain at this time had only minimal or mild pain (table IV). At 20 min, almost 50 % of the patients remained pain free, and no patient complained of moderate or severe pain. At 120 min after extubation, 29 % of patients needed parenteral analgesics. Awareness and amnesia
No patients remembered falling asleep or had recollection of intraoperative events. In five patients, last recollection was before leaving the ward, in 11 it was transfer to theatre and in eight patients, arriving in theatre. No patient recalled needing ventilatory assistance during the alfentanil infusion. On recovery, 11 patients remembered awakening in theatre, and the remaining 13 patients' first recall was in the recovery room.
Complications
Rigidity occurred in 17 of 24 patients during the loading infusion of alfentanil at a mean dose of 72.7 (18) |ag kg"1. Respiratory inadequacy, because of either central depression or muscle rigidity, and requiring manual ventilatory assistance, occurred in 14 of 24 patients during the alfentanil preload, but was not sufficiently severe to make manual ventilation impossible. At the end of the procedure, secretions in the upper airways were excessive and required active suctioning in 18 patients. Three of the 24 patients needed naloxone to antagonize respiratory depression at the end of the procedure.
Until recently, total i.v. anaesthesia has been limited by the relatively prolonged action of the agents available. Alfentanil has been studied in balanced anaesthetic techniques [5]. It has an onset of action within 1 min of administration, a potency approximately 20 % that of fentanyl, and a shorter elimination half-life of 90 min, with a small volume of distribution [6,7]. These characteristics suggest that alfentanil is particularly suitable for total i.v. anaesthesia [8]. Propofol has a redistribution half-life of 1.8-8.3 min following i.v. administration. The drug is metabolized by conjugation in the liver with a (3elimination half-life of 34-64 min, although some studies have used a three-compartment model with a similar T£ but a terminal elimination halflife of 200-300 min. Inactive metabolites are excreted by the kidney. With the usual maintenance regimens, significant cumulation of propofol does not occur [9, 10]. Since the advent of alfentanil and propofol, total i.v. anaesthesia with a combination of these agents has been investigated widely, but few studies have excluded all inhalation agents; those which have used only i.v. agents have been for relatively short procedures such as microlaryngeal surgery. The propofol infusion rate in our study was comparable to that used elsewhere [5, 11, 12] and it was not necessary to vary this rate during surgery. The dose of alfentanil used also corresponded well with those described previously [13, 14]. Several of our patients needed additional boluses of alfentanil, and a few required adjustment of the alfentanil rate during the operation, suggesting that a higher initial maintenance infusion rate may be more appropriate. Administration of the alfentanil bolus after the induction dose of propofol may avoid pre-intubation complications, such as rigidity and respiratory depression. The cardiovascular changes observed on induction of anaesthesia are similar to those reported by other investigators for propofol [15, 16], and it is reasonable to conclude that alfentanil did not contribute significantly to these changes. Intraoperative cardiovascular stability was notable. Most of the patients required blood transfusions during operation and this interfered with the flow of drugs intravenously. This necessitated
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Pain scores
DISCUSSION
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11. REFERENCES A study of the possible association between halothane anesthesia and postoperative hepatic necrosis. In: Bunker JP, Forrest WH, Mosteller F, Vandam LD, eds. National 12. Halothane Study. Washington D.C.: U.S. Govt. Printing Office, 1969. Hussey AJ, Aldridge LM, Paul D, Ray DC, Beckett GJ, 13. Allan LG. Plasma glutathione s-transferase concentration as a measure of hepatocellular integrity following a single general anaesthetic with halothane, enflurane or iso- 14. flurane. British Journal of Anaesthesia 1988; 60: 130-135. Munster AM. Immunologic alterations following injury. In: Advances in Orthopaedic Surgery 1985; 328. Koblin DD, Waskell L, Watson JE, Stokstad ELR, Eger 15. EL II. Nitrous oxide inactivates methionine synthetase in humans. Anesthesia and Analgesia 1982; 61: 75-78. 16. Kay B. Propofol and alfentanil infusion. A comparison with methohexitone and alfentanil for major surgery. Anaesthesia 1986; 41: 589-595.
Kay B, Healy TEJ. Propofol (Diprivan) for outpatient cystoscopy. Efficacy and recovery compared with Althesin and methoxitone. Postgraduate Medical Journal 1985; 61 (Suppl. 3): 108-114. Redfern N, Stafford MA, Brooker J, Hull CJ. Incremental propofol for short procedures. British Journal of Anaesthesia 1985; 57: 349P. Hug CC, Chaffman CC. Dosage and administration of alfentanil. In: Alfentanil: Pharmacology and Uses in Anaesthesia. Auckland: ADIS, 1984; 101-104. Schuttler J, Stoeckel H, Lauven PM. Pharmakokinetsch begrundete infusionsmodelle fur die narkose fuhrung mit alfentanil. In: Doenicke A, ed. Alfentanil. Berlin: Springer-Verlag, 1983. Kay B, Stephenson DK. ICI 35865 (Diprivan). A new intravenous anaesthetic. Anaesthesia 1980; 35: 1182. Coates DP, Monk CR, Prys-Roberts C, Turtle M. Hemodynamic effects of the emulsion formulation of propofol during nitrous oxide anesthesia in humans. Anesthesia and Analgesia 1987; 66: 64-70.
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a second i.v. cannula which may be a disadvantage 6. Bower S, Hull CJ. Comparative pharmacokinetics of fentanyl and alfentanil. British Journal of Anaesthesia in view of the problems of obtaining venous access 1982; 54: 871-877. in severely burned patients. 7. Bovill JC, Sebel PS, Blackburn CL, Heykants J. The Recovery from anaesthesia was rapid. No pharmacokinetics of alfentanil (R39209): A new opiate complications occurred related to anaesthesia and analgesic. Anesthesiology 1982; 57: 439-443. no patient had any unpleasant sequelae during the 8. (Anon.) Alfentanil in anaesthesia. Drugs and Therapeutics Bulletin 1986; 24: 51-52. recovery period. Although eye opening occurred 9. Cockshot ID. Propofol (Diprivan) pharmacokinetics and usually before spontaneous ventilation commetabolism—an overview. Postgraduate Medical Journal menced, and thus before extubation, no patient 1985; 61 (Suppl. 3): 45-50. had unpleasant recollections related to this se- 10. Grant IS, Mackenzie N. Recovery following propofol (Diprivan) anaesthesia—a review of three different anquence of events. Residual analgesia appeared to aesthetic techniques. Postgraduate Medical Journal 1985; contribute to the quality of recovery. 61 (Suppl. 3): 133-136.