atmospheric p~llution,'~~ the need for vaporizersS and eliminates problems ..... reception area adjacent to the operating theatre. All patients had EMLA cream ...
Anaesthesia, 1990, Volume 45, pages 865-870
Forum Total intravenous anaesthesia with propofol and buprenorphine
R. S. Kamal, MB, BS, FFARCS, Professor, F. A. Khan, MB, BS, FFARCS, Assistant Professor, F. H. Khan, MB, BS, Senior Resident, Department of Anaesthesiology, The Aga Khan University Hospital and Medical College, Stadium Road, P.O. Box 3500, Karachi 74800, Pakistan.
Summary A combination of propofol infusion and two bolus doses of buprenorphine, 2.5 or 5.0 pg/kg were evaluated in a total intravenous anaesthesia technique in 36 patients of ASA grade I or 2 undergoing cholecystectomy. Additional boluses of propofol were given intravenously if needed. Systolic blood pressure after tracheal intubation increased significantly only in those who received the smaller dose of buprenorphine. Patients in both groups remained haemodynamically stable throughout surgery with minimal side effects. Recovery was fast even with prolonged infusions and without major side effects. No patient reported awareness on postoperative questioning. Key words: Analgesic narcotic; buprenorphine. Anaesthetic intravenous; propofol.
Propofol may be given by bolus injection or continuous infusion’s2 and is a suitable agent for total intravenous anaesthesia. Research has focused on the advantages of total intravenous anaesthesia, a method which avoids atmospheric p~llution,’~~ the need for vaporizersS and eliminates problems associated with nitrous oxide anaesthesia in middle ear disease,6 gut surgery,’ and its effect on the nervous and haemopoietic systems.* It has an added advantage in war situations9 and in parts of the Third World where medical gases may be unavailable. Propofol possesses many of the properties required for total intravenous anaesthesia,loJ1particularly a short recovery time in spite of evidence of accumulation in long procedures.lZThe present study was designed to evaluate the use of propofol with one of two doses of buprenorphine as a method of total intravenous anaesthesia. Methods
The study was approved by the hospital Ethics Committee. Male or female patients classified as ASA 1 and 2 aged between 16 and 60 years scheduled for cholecystectomy were studied. Informed patient consent was obtained and the patients were randomly allocated into two groups of 18 each. None of the patients had clinical or suspected hepatic disease. Patients in both groups were premedicated with diazepam 0,15 mg/kg orally 2 hours before operation. On arrival in the operating room an 18-gauge intravenous cannula was inserted in a large hand vein. Baseline measurements of systolic, diastolic and mean arterial blood pressure were obtained using a noninvasive monitor @atex). Continuous monitoring of CM5 lead of the ECG, and oxygen saturation (Ohmeda 1400) were established.
An anaesthetist unconnected with the study gave a bolus of intravenous buprenorphine so that the observer was blinded to the dose received. Group A patients received 2.5 pg/kg and group B 5.0 pg/kg. The propofol dose regimen was that described by Roberts et al.” and was the same for both the groups. An initial dose of 1 mg/kg was given over 20 seconds followed by an infusion of 10 (mg/kg)/hour for the first 10 minutes. Pancuronium 0.1 mg/kg was injected after the loss of eyelash reflex. The patients’ lungs were ventilated via a mask and Magill system with oxygenenriched air (no,0.4) to normocapnia and the trachea was intubated 3 minutes after the injection of pancuronium. Propofol infusion was continued at a rate of 8 (mg/kg)/ hour for the next 10 minutes and then reduced to 6 (mg/ kg)/hour for the duration of surgery. The infusion was discontinued at the time of the last skin stitch. The patients’ lungs were ventilated throughout with oxygen-enriched air using a Manley Servoventilator. The mco, was kept between 0.05 and 0.055. Muscle relaxation was maintained with incremental doses of pancuronium as judged by a nerve stimulator. Stability and depth of anaesthesia were evaluated with regard to need for additional bolus doses of propofol 10 mg. The criteria used to judge the depth of anaesthesia were the presence of two out of four signs: increase in systolic arterial blood pressure 15% above baseline; increase in heart rate 15% above baseline; lacrimation; and sweating. The blood pressure was monitored one minute after buprenorphine injection, 2 minutes after induction with propofol, every minute after tracheal intubation for 3 minutes and every 5 minutes thereafter. ECG, oxygen saturation and nasopharyngeal temperature were displayed continuously. Visual monitoring of train-offour stimulus was charted every 15 minutes. The residual
Accepted 6 October 1989. 3-2409/90/100865
+ 15 $03.00/0
@ 1990 The Association of Anaesthetists of Gt Britain and Ireland
865
866
Forum Table 1. Patient data. Values expressed as mean (SD) or number of patients.
Group A Group B @ropofol/ @ropofol/ buprenorphine buprenorphine 2.5 P d W 5 Ptg/kg) (n = 18) (n = 18) Age; years Weight; kg MalesJfemales ASA, grade 112 Pre-induction systolic arterial blood pressure; mmHg Pre-induction heart rate; beats/minute Duration of anaesthesia; minutes
40.88 (10.61)
59.35 (14.34) 1/17 4/14 137.44 (16.98) 89.38 (17.02) 139.88 (61.82)
41.22 (12.06) 59.33 (8.05) 2/16 6/12
142.89 (16.99) 91.83 (15.95)
166.44 (64.02)
There was no significant difference between the groups (Student’s t-test).
neuromuscular blockade at the end of surgery was reversed with neostigmine. The time from cessation of propofol infusion until the patients opened their eyes to command and the interval before the correct date of birth given were recorded. An overall assessment of the quality of anaesthesia was made by the anaesthetist in charge of the case. Statistical analysis. The demographic details and duration of anaesthesia were compared using Student’s ttest. Arterial blood pressure and heart rate data were subjected to analysis of variance applied to each time point. The incidence of side effects within the two groups was compared by Chi-squared test with Yates’ correction. Values of p < 0.05 were considered to indicate statistical significance. Results
Thirty-six patients (three males and 33 females) aged between 24 and 64 years who weighed between 35 and 88 kg were studied. The demographic data are given in Table 1 . There was no significant difference between the groups with regard to weight, age, distribution of males and females, ASA classification, pre-operative blood pressures, pre-operative pulse rate, duration of infusions and duration of anaesthesia.
Complications during induction are shown in Table 2. The highest incidence was that of pain on injection of propofol bolus. The frequency of this complaint was higher in group A. The changes in the systolic blood pressure associated with the various stages of the procedure are shown in Figure 1. The blood pressure remained stable after buprenorphine injections in both groups, but after propofol it decreased slightly in both groups. Group B showed a greater percentage decrease compared to baseline values, 7% compared to 1.3%. Both groups showed an increase above baseline values after tracheal intubation, but the increase was statistically significant only in group A, 3 minutes after intubation. This pressor response did not correlate with age, sex or ASA grade. The systolic blood pressures then returned to below the baseline values in both groups. The pressures recorded one minute after incision in group B showed a significant decrease compared to baseline values (- 12%). The blood pressures then remained stable throughout the rest of the procedure. No statistical difference was observed between the groups at any stage. The changes in the heart rate are shown in Figure 2. The heart rate remained stable after induction in both groups. Tracheal intubation produced a significantly greater increase compared to the baseline in group A patients, where the pulse rate remained significantly elevated until
Table 2. Side effects observed in the two groups.
Group A Group B (propofolf @ropofol/ buprenorphine buprenorphine 2.5 Pg/k& (n = 18)
5Pg/W (n = 18)
Induction
Pain on injection Involuntary movements Skin rash Tachycardia (beta blockers given for control) Bronchospasm Maintenance Bronchospasm Movements not related to light anaesthesia
8 2 0 1 1
1 1
0 0
Recovery Nausea
Confusion and restlessness Vomiting Bradycardia (heart rate < 60Jminute) There was no significant difference between the groups (Chi-Squared test with Yates’ correction).
Forum
0
867
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,201
I
Fig. 1. Mean systolic arterial pressure (mmHg) during propofol infusion+ buprenorphine 2.5 pg/kg (0)compared with propofol infusion+buprenorphine 5 pg/kg ( 0 )at indicated stages. -i-= p < 0.05 statistically significant difference from baseline value.
after the incision and did not return to control values. In group B there were clinically similar changes in the heart rate after tracheal intubation, but the percentage increase in heart rate was not statistically signficant. There was no statistical difference observed between the two groups. One patient in group A had a sinus tachycardia immediately after the bolus of propofol and a /I-adrenoceptor blocker
(propranolol) was necessary. None of the patients had sinus bradycardia ( < 60 beats/minute) intra-operatively. The range and the mean dosages of propofol used in the two groups during induction and maintenance are shown in Table 3. Total induction dose was calculated as the (bolus dose+the initial fast phase infusion rates of 10 (mg/kg)/ hour for 10 minutes and 8 (mg/kg)/hour for the next 10
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Fig. 2. Mean heart rate changes (beats/minute) during propofol infusion + buprenorphine 2.5 pg/kg ( 0 )compared with propofol infusion+buprenorphine 5 jig/kg ( 0 )at indicated stages. -i-= p i0.05 statistically significant difference from baseline value.
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Forum Table 3. Mean (SD) propofol dosages in both groups.
Group A Group B (propofol/ (propofol/ buprenorphine buprenorphine 5PBh) 2.5 Pg/kg) (n = 18) (n = 18) Duration of infusion; minutes Range; minutes Total mean induction dose of propofol; mg Total mean maintenance dose of propofol; mg Range of total dose of propofol used; mg Mean rate of utilisation during maintenance; (mg/kg)/hour Mean rate of utilisation during induction and maintenance; (mg/kg)/hour
135.88 (62.66) 157.61 (65.46) 80-326 86325 236.47 (57.42) 235.95 (35.09) 704.47 (434.03) 846.66 (443.5) 433-1763 53 1-2080 6.15
6.24
6.91
7.093
There was no significant difference between the groups. minutes). Total maintenance dose was calculated at 6 (mg/ kg)/hour for the duration of infusion. The mean rate of utilisation during induction and maintenance was calculated as the total dose (including induction dose) divided by the duration of infusion. The mean rate of utilisation during maintenance was calculated by the total dose minus (induction dose +initial fast phase infusion) divided by the duration of infusion. No significant difference was observed between the groups as regards their mean rate of utilisation, the total induction dose and the maintenance dose. It was necessary to administer supplementary boluses of propofol in one patient in group A and four in group B. The incidence of side effects observed in the maintenance period are given in Table 2. Table 4 shows the recovery data. The indices of immediate recovery studied were times from end of infusion to opening eyes to command and the ability to give name and date of birth correctly. The mean time to opening eyes to command was 10.38 (SD 4.23) minutes in group A and 11 (SD 3.75) minutes in group B. No significant difference was observed between the two groups in either indices of recovery. No correlation was observed between the duration of propofol infusion and opening eyes to command after termination of infusion (Fig. 3). The overall incidence of untoward effects observed in recovery remained low in both groups (Table 2). Postoperative nausea occurred in only one patient in group A and two in group B. One patient in group B vomited. Two hours after the end of surgery the patients were specifically asked about awareness during anaesthesia. None of the patients reported any awareness. The anaesthetic was rated either good or satisfactory by the consultant anaesthetist involved with the case in all the patients in both groups. Discussion
The main objective of our study was to develop a technique of total intravenous anaesthesia which would provide satis-
factory anaesthetic conditions for major abdominal surgery. An infusion of propofol was shown to provide satisfactory anaesthesia with nitrous oxide-oxygen mixtures in both spontaneously breathing patients or combined with a muscle ela ax ant,'^,^^ but little work has been done on total intravenous techniques using propofol infusions combined with air-oxygen mixtures and narcotic drugs, especially in major abdominal s ~ r g e r y , ' ~although ,'~ Steegers and Foster have used the method for orthopaedic surgery.18There is also no published work on the effect of buprenorphine on the quality of anaesthesia with propofol in major abdominal surgery. No marked hypotension was seen after the bolus injection of propofol. Other studies have commented on the hypotensive effect of 2 mg/kg bolus doses due to a decrease in systemic vascular resistance in healthy subjects? Our results are in agreement with the studies using 1 mg/kg as induction dose.I3Buprenorphine was shown to be a suitable narcotic for use in major abdominal surgery, since it is associated with cardiovascular stability; it was shown to attenuate the hypertensive response to laryngoscopy and intubation in adult patients if given before induction. Propofol also attenuates the haemodynamic effect of laryngoscopy and intubation,"21 and the combination of two may result in a smoother induction. This effect was observed in our study especially with buprenorphine 5 pg/ kg. The heart rates remained fairly stable in group B but increased significantly above baseline in group A patients. The commonest side effect observed at induction was pain on injection. Eight of the patients in group A and three in group B complained of pain. The fewer number who complained in group B may be because of the analgesic effect of 5 pg/kg buprenorphine given before induction. One patient with a history of asthma developed severe bronchospasm soon after injection of propofol. This was treated with injection of aminophylline 125 mg intravenously followed by an infusion of 250 mg in 500 ml dextrose for the next 3 hours. One ASA 2 patient aged 28 years, with a baseline blood
Table 4. Mean (SD) recovery from end of propofol infusion.
Group A (propofol infusion/ buprenorphine 2.5 P8/k)
Group B (propofol infusion/ buprenorphine 5 Pg/kg)
10.38 (4.23)
11.0 (3.75)
18.37 (9.34)
25.5 (14.9)
(n = 18)
Time to opening eyes on command from end of infusion; minutes Time to orientation from end of infusion; minutes
(n = 18)
Forum
869
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0 360
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300
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4 6 8 10 12 14 16 18 Recovery time ( i n minutes from end of infusion to opening eyes on command)
I 20
Fig. 3. Recovery time (in minutes from termination of infusion to opening eyes on command) plotted against duration of propofol infusion. Symbols as for Figs 1 and 2.
pressure of 129/83 and heart rate of 117/minute, developed a sinus tachycardia of 180 beats/minute immediately after the injection of propofol and responded t o intravenous propranolol. The continuous infusion of propofol with buprenorphine produced stable anaesthesia. The total dose of propofol and the average infusion rates did not vary significantly between the groups. The patients with the smaller dose of buprenorphine did not require additional supplementation with propofol. However, patients in group B did show more cardiovascular stability. We found that the assessment of depth of anaesthesia according t o the four criteria described were reliable; only five patients required bolus doses of propofol, one in group A and four in group B. Recovery was rapid in both groups and there was a low incidence of side effects. Three patients in group A and three in group B had infusions lasting for more than 3 hours, but awoke within 15 minutes of discontinuation of infusion. None of the patients reported awareness when questioned postoperatively. In conclusion, the data in our study suggest that propofol is a suitable agent for continuous infusion in total intravenous anaesthesia, with buprenorphine as the analgesic component in paralysed patients undergoing abdominal surgery. We recommend a 5.0 pg/kg bolus dose of buprenorphine because of its greater haemodynamic stability when combined with propofol.
Acknowledgment The authors are grateful t o ICI Pharmaceutical (Pakistan) Limited for supplies of Propofol.
References 1. KAYNH, SEARJW, UPPINGTON J, COCKSHOTT I, DOUGLAS EJ. Disposition of propofol in patients undergoing surgery. A comparison in men and women. British Journal of Anaesthesia 1986; 58: 1075-9. 2. COATS DP, PRYS-ROBERTS C, SPELINA KR, MONKCR, NORLEY I. Propofol (Diprivan) by intravenous infusion with nitrous oxide: dose requirements and haemodynamic effects. Postgraduate Medical Journal 1985; 61 (Suppl. 3): 76-9. 3. SIMMONS K. Some sobering facts about laughing gas. Journal of the American Medical Association 1985; 253 2334-5.
4. EGEREI 11. Should we use nitrous oxide? In: EGEREI 11, ed.
Nitrous oxide. New York: Elsevier, 1985: 33943. 5. KNELLPJW. Total intravenous anaesthesia by an intermittent technique. Use of methohexitone, ketamine and a muscle relaxant. Anaesthesia 1983; 38: 586-7. 6. MAN A, SEGALS, EZRAS. Ear injury caused by elevated intratympanic pressure during general anaesthesia. Acta Anaesthesiologica Scandinavica 1980; 2 4 224-6. 7. NUNNJF. Clinical relevance of the B,,/N,O interaction. A report of a seminar. Anaesrhesia 1988; 43: 587-9. 8. DUNDEE JW. Total intravenous anaesthesia. British Journal of Anaesthesia 1978; 50: 89-90. 9. RESTALLJ, TULLY AM, WARD PJ, KIDD AG. Total intravenous anaesthesia for military surgery. A technique using ketamine, midazolam and vecuronium. Anaesthesia 1988; 43: 46-9. 10. SCHLJTTLER J, STOECKEL H, SCHWILDEN H. Pharmacokinetic and pharmacodynamic modelling of propofol (Diprivan) in volunteers and surgical patients. Postgraduate Medical Journal 1985; 61 (Suppl. 3): 53-4. 11. COCKSHOTT ID, BRIGS LP, DOUGLASEJ, WHITE M. Pharmacokinetics of propofol in female patients. Studies using single bolus injections. British Journal of Anaesthesia 1987; 5 9 1103-10. 12. DE GRWDPMRM, RUYSAHS, VANEGMOND J, Boou LHDJ, CRULJF. Propofol (Diprivan) emulsion for total intravenous anaesthesia. Postgraduate Medical Journal 1985; 61 (Suppl. 3): 65-9. 13. ROBERTSFL, DIXONJ, LEWISGTR, TACKLEY RM, PRYSROBERTSC. Induction and maintenance of propofol anaesthesia. A manual infusion scheme. Anaesthesia 1988; 43 (Suppl): 14-7. 14. SEARJW, S m w I, WOLFA, a y NH. Infusion of propofol to supplement nitrous oxide-oxygen for maintenance of anaesthesia. A comparison with halothane. Anaesthesia 1988; 43 (Suppl.): 18-22. E. An open comparison of propofol and 15. HARTUNG E, FREYE enflurane for prolonged abdominal operations. Anaesthesia 1988; 43 (Suppl.): 105-7. 16. SCHUTTLER J, K L ~ S,S SCHWILDEN H, STOECKEL H. Total intravenous anaesthesia with propofol and alfentanyl by computer assisted infusion. Anaesthesia 1988; 43 (Suppl.): 2-7. 17. GALLETLY DC, SHORTTG. Total intravenous anaesthesia using propofol infusion-50 consecutive cases. Anaesthesia and Intensive Care 1988; 16 15&7. 18. STEEGERS PA, FOSTERPA. Propofol in total intravenous anaesthesia with nitrous oxide. Anaesthesia 1988; 43 (Suppl.): 94-7. C, TURTLEMJ. 19. COATIS DP, MONK CR, PRYS-ROBERTS Hemodynamic effects of infusions of the emulsion formulation
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of propofol during nitrous oxide anesthesia in humans. Anesthesia and Analgesia 1987; 66:64-70. 20. HARRISCE, MURRAYAM, ANDERSONJM, GROUNDSRM, MORGAN M. Effects of thiopentone, etomidate and propofol on the haemodynamic response to tracheal intubation. Anaesthesia 1988; 43 (Suppl.): 32-6.
21. MONK CR, COATESDP, PRYS-ROBERTS C, TURTLEMJ, SPELINA K. Haemodynamic effects of a prolonged infusion of propofol as a supplement to nitrous oxide anaesthesia. Studies in association with peripheral arterial surgery. British Journal of Anaesthesia 1987; 5 9 954-60.
Anaesthesia, 1990, Volume 45, pages 870-872 Oral premedication in children A comparison of trimeprazine with a trimeprazine, droperidol and methadone mixture
G. H. Phillips,* FCAnaes, Senior Registrar, T. Mian, FCAnaes, U. Becker, FCAnaes, Registrars, P. A. Stone, FRCSE, FCAnaes, Senior Registrar, H. M. Jones, FCAnaes, Consultant, Royal Gwent Hospital, Newport, Gwent NPT 2UB.
Summary One hundred children who presented for minor general surgical procedures were randomly assigned to receive one of two oral premedications, Those in group A (n = 50) were given 3 mg/kg of trimeprazine and those in group B (n = 50) a mixture of trimeprazine 1.0 mglkg, droperidolO.15 mglkg and methadone 0.08 mglkg. Patients in group B were more likely to be asleep on arrival in the anaesthetic room ( p < 0.02) and were less likely to be distressed at induction of anaesthesia ( p < 0.02). Thiopentone requirements were less in group B ( p < 0.001). The incidence of side effects was similar in the two groups. It is concluded that the mixture produces more satisfactory sedation than trimeprazine. Key words Anaesthesia; paediatric, premedication. Premedication; trimeprazine, droperidol, methadone.
Trimeprazine tartrate syrup has become a standard paediatric premedication in British hospitals. Oral sedation is more acceptable to children than an intramuscular injection and it has been shown to provide good sedation in most cases.l4 However, the effect of trimeprazine on individual children given the same mg/kg dose can vary greatly. Some children arrive in the anaesthetic room wide awake while others are deeply sedated. Other drugs have been added to the trimeprazine syrup in an effort to provide more reliable sedation. It was shown that droperidol and trimeprazine combinations are superior to trimeprazine alone; sedation is more uniform, postoperative vomiting less frequent and analgesic requirements are reduced.’ In contrast, a comparison of trimeprazine with a trimeprazine, droperidol and methadone mixture, failed to show any difference in sedation.* A mixture of trimeprazine, droperidol and methadone (known as TDP) has been in use in this hospital for some time. We have found it to give more reliable sedation than trimeprazine. We compared these two premedications in a randomised double-blind study in order to determine if this impression was correct. Methods
Ethics committee approval was given and informed consent obtained from the parents of children enrolled in the study.
One hundred healthy children presenting for minor surgical procedures were included. They were randomly allocated into trial groups A or B to receive one of two raspberryflavoured syrups that were made up by the hospital pharmacy. One syrup contained trimeprazine 12 mg/ml (group A); the other syrup TDP (trimeprazine 4 mg/ml, droperidol 0.6 mg/ml and methadone 0.32 mg/ml; group B). Each child received 0.25 ml/kg of the appropriate mixture. This was equivalent to 3 mg/kg in the trimeprazine-only group and 1 mg/kg of trimeprazine combined with 0.15 mg/kg of droperidol and 0.08 mg/kg of methadone in the other group. Syrup A or B was given some 2.5 hours before induction of anaesthesia so that sedation was present when the patients were transferred with their parents to a children’s reception area adjacent to the operating theatre. All patients had EMLA cream applied to the back of both hands at the time that the premedication was given. On arrival in the anaesthetic room patients were recorded as being either asleep or awake by an anaesthetist who was unaware of the premedication given. If awake it was noted if they were calm or distressed. Anaesthesia was induced, after insertion of a 23-gauge intravenous cannula, with thiopentone 5 mg/kg given over 10 seconds. Supplemental increments of 1 mg/kg were given as required using loss of eyelash reflex to indicate adequate depth of anaesthesia. The behaviour of the child at induction was noted as
*Present position: Consultant Anaesthetist at the Princess Royal Hospital, Telford TF6 6TF. Correspondence should be addressed to Dr Jones please. Accepted 29 March 1990.
