Anaesthesia, 1991, Volume 46, pages 24-27
Ketamine as analgesic for total intravenous anaesthesia with propofol
J. B. M. GUIT, H. M. KONING, M. L. COSTER, R. P. E. NIEMEIJER
AND
D. P. MACKIE
Summary
A prospective study of 18 patients who underwent noncardiac surgery was performed to study the use of ketamine as an analgesic during total intravenous anaesthesia with propojd. A comparison was made with the combination propofollfentanyl. The propo follketamine combination resulted in haemodynamically stable anaesthesia without the need f o r additional analgesics. Postoperative behaviour was normal in all patients and none of the patients reported dreaming during or after the operation. Propofol seems to he effective in eliminating side efects of a subanaesthetic dose of ketamine in humans. We recommend the propofr)llketaniine combination for total intravenous anaesthesia for surgery when stable haemodynamics are required.
Key words Total intravenous unaesthesia. Anaesthetics, intravenous; propofol, ketamine. Ketamine is a powerful analgesic, even in doses insufficient to induce anaesthesia.‘ It has many of the attributes of the ‘ideal’ analgesic agent for longer routine operations: a very high margin of safety, no irritation of the veins and no negative influence on ventilation or circulation. Its main disadvantages are that it produces hypertension and precipitates psychomimetic emergence phenomena. These effects can be mitigated by judicious medication, particularly by administering benzodiazepines. The combination of midazolam with ketamine has been recommended previously ror total intravenous anaesthesia in military surgery, general civilian practice and cardiac s ~ r g e r y . ~ - ~ In this study, the combination of propofol/ketamine was compared to the combination propofol/fentanyl in a double-blind, prospective trial in patients undergolng general anaesthesia for elective surgery. Haemodynamic variables, the time to recovery and patient acceptability were compared.
Methods
A prospective study of 18 patients who underwent noncardiac surgery was performed. Patients gave informed consent to a protocol approved by the medical ethics committee of our hospital. All patients were ASA grade 1 or 2 and scheduled for operations longer than 15 minutes (Table I ) . Patients received oral oxazepam (0.25-0.3
mg/kg) as premedication 2 hours before surgery and were allocated randomly to one of two groups to receive propofol with ketamine ( n = 9) or propofol with fentanyl ( n = 9) for total intravenous anaesthesia. Standard lead I1 of the electrocardiogram was monitored and an intravenous cannula inserted on arrival of the patient in the operating theatre. Heart rate was detected by electrocardiogram and calculated electronically on a beatto-beat basis. The pulse rate was timed for at least 30 seconds. One person recorded all arterial pressure measurements by auscultation (diastolic reading as Korotkoff phase V) using an anaeroid sphygomanometer previously calibrated at zero and 150 mmHg against a mercury column. Anaesthesia was induced with propofol (2 mg/kg) and either fentanyl (3 pg/kg) or ketamine (I mg/kg). Vecuronium (0.15 mg/kg) was administered. Anaesthesia was maintained with propofol 12 mg/kg/hour during the first 30 minutes, followed by 9 mg/kg/hour for 30 minutes and then 6 mg/kg/hour combined with fentanyf 1.5 pg/kg/hour or with ketamine 2 mg/kg hour. The patient’s lungs were ventilated with oxygen-enriched air with an no2of 0.35. The postinduction arterial pressure and heart rate were recorded one minute after induction, and direct laryngoscopy with a curved blade was initiated 2 minutes after induction. None of the patients received topical or intravenous lignocaine before laryngoscopy, and tracheal intubation was always accomplished within 20 seconds.
J.B.M. Guit, MD, H.M. Koning, MD, M.L. Coster, MD, R.P.E. Niemeijer, MD, Department of Anaesthesia, Medical Centre Leeuwarden, Henri Dunantweg 2, 8934 AD Leeuwarden, The Netherlands, D.P. Mackie, FFARCS, Rode Kruis Ziekenhuis, Vondellaan 13, 1942 LE Beverwijk, The Netherlands. Correspondence should be addressed to Dr H.M. Koning please. Accepted 4 June 1990. 0003-2409/9 I /O 10024+ 04 $03.00/0
@) 1991 The Association of Anaesthetists of Gt Britain and Ireland
24
Ketamine analgesia for intravenous propofol anaesthesia
25
Table 1. The distribution of surgical procedures in the two groups.
Propofol/fentanyl
Propofol/ketamine
9
9
Abdominal G ynaecological Orthopaedic
Plastic Ear, nose and throat Total
Arterial pressure and heart rate were recorded again one minute after tracheal intubation. Ventilation was set to achieve a n end-tidal carbon dioxide concentration of 4 % with a frequency of 12 breaths/minute. The tidal volume and the respiratory pressures were noted. The anaesthetist did not know whether fentanyl o r ketamine had been used. Increments of analgesics were given during anaesthesia if analgesia was judged clinically to be adequate as assessed by: a sudden increase of systolic blood pressure of more than 20 mmHg; an increase in heart rate of more than 10 beats/minute, in the absence of hypovolaemia; and signs of sweating and lacrimation. Additional vecuronium in a dose of 0.04 mg/kg was administered when muscle relaxation was judged to be inadequate. The continuous administration of drugs was stopped at the end of surgery and residual neuromuscular blockade was antagonised with intravenous atropine (0.01 mg/kg) and neostigmine (0.03 mg/kg). The time to awakening was noted. The trachea was extubated when the patient was able to maintain an adequate airway and good respiratory minute volume. Arterial pressure, heart rate, the reaction of the patient to command and an assessment of whether the patient was awake o r drowsy were noted in the recovery room by a nurse who was unaware of the type of anaesthesia. Five questions were asked 30 minutes after operation: the name of the patient, the date of birth, where the patient was, and the date and the time. Each patient was interviewed on the day after surgery by a doctor who was unaware whether fentanyl or ketamine was used. Patients were asked about side effects, awareness, and their opinion about the anaesthetic. The Chi-square test was computed for dichotomous variables. The Wilcoxon rank sum test was used for continuous variables5 A p-value of less than 0.05 was considered significant. Results The pre-operative variables in both groups were compared (Table 2). No statistically significant differences in gender,
age, height, weight, arterial pressure or heart rate were found. The haemodynamic variables throughout the peri-operative period for both groups are shown in Figure I . Stable arterial pressure and heart rate were seen in the patients who received propofol/ketamine, except for a temporary increase directly after tracheal intubation. Systolic pressure increased by 13%, diastolic pressure by 11 YOand heart rate by 14%. Decreases in systolic and diastolic blood pressure were observed after induction in patients who received propofol/ fentanyl. Arterial pressure returned to baseline values after intubation. The heart rate was stable, except for an increase in mean heart rate by 24% after intubation. Patients who received propofol/fentanyl tended to have a lower systolic pressure than patients who received propofol/ketamine. The intra-operative variables for both groups are shown in Table 3 . The lowest systolic pressure found in the patients with propofol/ketamine was statistically significantly higher than that observed in patients with propofol/ fentanyl. No extra analgesics were required in the propofol/ ketamine group, but patients who received propofol/ fentanyl required a mean additional dose of fentanyl 0.72 pg/kg/hour. No statistically significant difference in the duration of surgery, respiratory variables, muscle relaxation or awakening after surgery were found. The postoperative variables are shown in Table 4. Patients who received propofol/ketamine demonstrated a significantly longer recovery time than patients given propofol/fentanyl. The time to an adequate reaction and the duration of drowsiness were longer, and the responses to the five questions 30 minutes after surgery were significantly less adequate. There were increased incidences of dizziness and confusion in patients given propofol/ketamine, but in all cases the confusion was reported by the patient himself and judged to be minor. No confusion was observed by medical personnel. Postoperative behaviour was normal in all patients, and none reported dreaming during o r after surgery. All patients judged the propofol/ ketamine combination to be pleasant, compared to 89Oh of the patients with propofol/fentanyl.
Table 2. Pre-operative variables. Data are presented as mean (SD).
Propofol-ketamine
Propofol-fentanyl
7:2 35 (12) 172 (10)
6: 3 39 (12) 169 (6) 72 (11)
Females :males Age; years Height; crn Weight; kg
Arterial pressure; rnrnHg Systolic Diastolic Heart rate; beats/minute ~
~
There were no significant differences.
70 (11) 130 (11) 80 (10) 80 (16)
126 (11) 84 (9)
72 (9)
26
J.B.M. Guit et al.
40
I
I
Preoperative Arrival
I
I
I
I
After induction
After intubation
Average during surgery
Average during recovery
I
J
1
Operating theatre
Fig. 1. Haemodynamic variables throughout the peri-operative period in patients anaesthetised with propofol/ketamine (a),or propofol/fentanyl (*). *, statistical significance.
Table 3. Intra-operative variables. Data are presented as mean (SD). Propofol-ketamine Duration of surgery; minutes Respiratory minute volume; litres/minute Compliance; ml/kPa Static Dynamic Arterial pressure; mmHg Highest systolic Lowest systolic Highest diastolic Lowest diastolic Heart rate; beats/minute Highest Lowest Muscle relaxation maintenance dose; mg/kg/hour Extra dose of fentanyl; pg/kg/hour Awakening after stopping TIVA; minutes
Propofol-fentanyl
p-value
60 (27) 7.2 (0.5)
78 (27) 7.1 (1.1)
ns ns
6.2 (1.1) 3.2 (0.4)
6.0 (1.8) 2.8 (0.7)
ns ns
144 (12) 118 (17) 85 (9) 64 (11)
137 99 81 59
(19) (10) (10) (15)
ns 0.030 ns ns
81 66
(14) (14)
ns ns
0.03 (0.03) 0.72 (0.72) 13 (18)
ns
92 73
(17) (18)
0.02 (0.02) _
17
_
(5)
ns
TIVA, total intravenous anaesthesia. ns, not significant.
Table 4. Postoperative variables. Data are presented as mean (SD). Propofol-ketamine Recovery-room Time until adequate reaction; minutes Time to awakening; minutes Duration of drowsiness; minutes Good response on five questions Nausea; % Patients’ interview Duration of awakening; hours Nausea; % Vomiting; % Dizzy; ‘/o Confused; % General judgement as good; YO ns, not significant.
Propofol-fentan yl
p-value
(26) (23) (22) (2) 0
1 (4) 9 (10) 11 (17) 5 (0) 11
0.027 ns 0.036 0.024 ns
3.4 (2.7) 0 0 44 33 100
2.2 (3.0)
ns ns ns ns ns ns
19 22 36 3
11
11 11 11 89
Ketamine analgesia for intravenous propofol anaesthesia Discussion Ketamine in subanaesthetic doses has recently gained more attention as an analgesic for total intravenous anaesthesia. Ketamine is a powerful analgesic although the mechanism and site of action of its analgesic effect remain to be fully elucidated. I t possesses local anaesthetic properties6 and has a direct inhibitory action on the dorsal horn neurones of lamina I and V.' Antagonism of the analgesic effect of ketamine with nalaxone in rats suggests that an endogenous opioid neuronal pathway in the central nervous system is involved.8 However, a n opioid component in the analgesic action of a subanaesthetic ketamine dose in humans has not been found, and blockade of the N-methyl-aspartate receptor has been suggested as a n alternative mode of action.' N-methyl-aspartate receptors may represent a subgroup of the sigma opioid receptors which block spinal nociceptive reflexes. Several other neuronal systems may be involved in the antinociceptive action of ketamine, since blockade of the noradrenaline and serotonin receptor also attenuates the analgesic action of ketamine in animals.'O The advantages of the use of ketamine as an analgesic include a powerful action at small doses without myocardial or respiratory depression, a broad therapeutic range and no organotoxic effects. The cardiocirculatory stimulation includes increases in heart rate, cardiac index and arterial pressure. However, the high incidence of adverse reactions limits its use. The main adverse reactions are stimulation of the sympathetic nervous system resulting in hypertension and emergence reactions (delirium, nightmares, hallucinations), both of which cause problems in patient acceptance and in postoperative nursing care. Various methods have been proposed t o overcome the adverse reactions. The combination of ketamine with benzodiazepines reduces the incidence of side effects and a continuous infusion of midazolam with ketamine has been recommended for military surgery, general civilian practice and cardiac ~ u r g e r y . ~Anaesthesia -~ is characterised by stable haemodynamics, after a temporary initial increase in heart rate and systolic arterial pressure. U p to 15% of patients report dreaming. The object of this study was to investigate whether propofol could eliminate the side effects of ketamine. The propofol/ketamine combination resulted in a stable arterial pressure and heart rate during surgery. Slow recovery was observed, but the postoperative behaviour was normal in all patients and no patient reported dreaming during or
27
after the operation. Propofol therefore seems to be effective in eliminating the side effects of a subanaesthetic dose of ketamine in humans. The advantage of using ketamine as the analgesic in combination with propofol for total intravenous anaesthesia is the achievement of stable haemodynamics during surgery. A stable arterial pressure throughout the operative period was observed, compared with the lower blood pressure found in the patients given propofol/fentanyl. The maintenance dose of fentanyl was not sufficient for analgesia in all patients in the propofol/fentanyl group and a dose of2.0 to 2.5 pg/kg/hour might have been more appropriate. However, a higher dose of fentanyl might have depressed the circulation even more. Side effects of the propofol/ketamine combination were the prolonged duration of the action of ketamine, resulting in a slower awakening and recovery, dizziness, and minor confusion directly after surgery. However, all patients judged anaesthesia to be good. We recommend the propofol/ketamine combination for total intravenous anaesthesia when stable haemodynamics are warranted. References 1. REICHDL, SILVAYG. Ketamine. An update on the first twenty-five years of clinical experience. Canadian Journal of Anaesthesia 1989; 36: 186-97.
2. RESTALLJ, TULLYAM, WARD PJ, KIDD AG. Total intravenous anaesthesia for military surgery. A technique using ketamine, midazolam and vecuronium. Anaesthesia
1988; 4 3 46-9. 3. BAILIE R, CRAIG G, RESTALL J. Total intravenous anaesthesia for laparoscopy. Anaesthesia 1989; 44: 60-3. 4. CHAI M, THANGA D, MORGAN E, VILJOEN J. Ketamine-midazolam continuous infusion in cardiac surgical patients. Anaesthesia 1989; 44: 364. 5 . NOETHER GE. Introduction to statistics. Boston: Houghton Mifflin, 1976. 6. AMIOTJF, Bourou PH, PALACCI JH, BALLINERE. Intravenous regional anaesthesia with ketamine. Anaesthesia 1985; 4 0 899-901. I . KITAHATA LM, TAUB A, KOSAKAY. Lamina-specific suppression of dorsal-horn unit activity by ketamine hydrochloride. Anesthesiology 1973; 3 8 4-1 1. 8. SMITHDJ, PEKOEGM, MARTINLL, COALGATE B. The interaction of ketamine with the opiate receptor. Lqe Sciences 1980; 2 6 789-95. 9. MAURSET A, SKOGLUND LA, HUSTVEIT 0, OYEI. Comparison of ketamine and pethidine in experimental and postoperative pain. Pain 1989; 38: 37-41. 10. PEKOEGM, SMITHDJ. The involvement of opiate and monoaminergic neuronal systems in the analgesic effects of ketamine. Pain 1982; 12: 57-73.
Ketamine as analgesic for total intravenous anaesthesia with propofol
J. B. M. GUIT, H. M. KONING, M. L. COSTER, R. P. E. NIEMEIJER
AND
D. P. MACKIE
Summary
A prospective study of 18 patients who underwent noncardiac surgery was performed to study the use of ketamine as an analgesic during total intravenous anaesthesia with propojd. A comparison was made with the combination propofollfentanyl. The propo follketamine combination resulted in haemodynamically stable anaesthesia without the need f o r additional analgesics. Postoperative behaviour was normal in all patients and none of the patients reported dreaming during or after the operation. Propofol seems to he effective in eliminating side efects of a subanaesthetic dose of ketamine in humans. We recommend the propofr)llketaniine combination for total intravenous anaesthesia for surgery when stable haemodynamics are required.
Key words Total intravenous unaesthesia. Anaesthetics, intravenous; propofol, ketamine. Ketamine is a powerful analgesic, even in doses insufficient to induce anaesthesia.‘ It has many of the attributes of the ‘ideal’ analgesic agent for longer routine operations: a very high margin of safety, no irritation of the veins and no negative influence on ventilation or circulation. Its main disadvantages are that it produces hypertension and precipitates psychomimetic emergence phenomena. These effects can be mitigated by judicious medication, particularly by administering benzodiazepines. The combination of midazolam with ketamine has been recommended previously ror total intravenous anaesthesia in military surgery, general civilian practice and cardiac s ~ r g e r y . ~ - ~ In this study, the combination of propofol/ketamine was compared to the combination propofol/fentanyl in a double-blind, prospective trial in patients undergolng general anaesthesia for elective surgery. Haemodynamic variables, the time to recovery and patient acceptability were compared.
Methods
A prospective study of 18 patients who underwent noncardiac surgery was performed. Patients gave informed consent to a protocol approved by the medical ethics committee of our hospital. All patients were ASA grade 1 or 2 and scheduled for operations longer than 15 minutes (Table I ) . Patients received oral oxazepam (0.25-0.3
mg/kg) as premedication 2 hours before surgery and were allocated randomly to one of two groups to receive propofol with ketamine ( n = 9) or propofol with fentanyl ( n = 9) for total intravenous anaesthesia. Standard lead I1 of the electrocardiogram was monitored and an intravenous cannula inserted on arrival of the patient in the operating theatre. Heart rate was detected by electrocardiogram and calculated electronically on a beatto-beat basis. The pulse rate was timed for at least 30 seconds. One person recorded all arterial pressure measurements by auscultation (diastolic reading as Korotkoff phase V) using an anaeroid sphygomanometer previously calibrated at zero and 150 mmHg against a mercury column. Anaesthesia was induced with propofol (2 mg/kg) and either fentanyl (3 pg/kg) or ketamine (I mg/kg). Vecuronium (0.15 mg/kg) was administered. Anaesthesia was maintained with propofol 12 mg/kg/hour during the first 30 minutes, followed by 9 mg/kg/hour for 30 minutes and then 6 mg/kg/hour combined with fentanyf 1.5 pg/kg/hour or with ketamine 2 mg/kg hour. The patient’s lungs were ventilated with oxygen-enriched air with an no2of 0.35. The postinduction arterial pressure and heart rate were recorded one minute after induction, and direct laryngoscopy with a curved blade was initiated 2 minutes after induction. None of the patients received topical or intravenous lignocaine before laryngoscopy, and tracheal intubation was always accomplished within 20 seconds.
J.B.M. Guit, MD, H.M. Koning, MD, M.L. Coster, MD, R.P.E. Niemeijer, MD, Department of Anaesthesia, Medical Centre Leeuwarden, Henri Dunantweg 2, 8934 AD Leeuwarden, The Netherlands, D.P. Mackie, FFARCS, Rode Kruis Ziekenhuis, Vondellaan 13, 1942 LE Beverwijk, The Netherlands. Correspondence should be addressed to Dr H.M. Koning please. Accepted 4 June 1990. 0003-2409/9 I /O 10024+ 04 $03.00/0
@) 1991 The Association of Anaesthetists of Gt Britain and Ireland
24
Ketamine analgesia for intravenous propofol anaesthesia
25
Table 1. The distribution of surgical procedures in the two groups.
Propofol/fentanyl
Propofol/ketamine
9
9
Abdominal G ynaecological Orthopaedic
Plastic Ear, nose and throat Total
Arterial pressure and heart rate were recorded again one minute after tracheal intubation. Ventilation was set to achieve a n end-tidal carbon dioxide concentration of 4 % with a frequency of 12 breaths/minute. The tidal volume and the respiratory pressures were noted. The anaesthetist did not know whether fentanyl o r ketamine had been used. Increments of analgesics were given during anaesthesia if analgesia was judged clinically to be adequate as assessed by: a sudden increase of systolic blood pressure of more than 20 mmHg; an increase in heart rate of more than 10 beats/minute, in the absence of hypovolaemia; and signs of sweating and lacrimation. Additional vecuronium in a dose of 0.04 mg/kg was administered when muscle relaxation was judged to be inadequate. The continuous administration of drugs was stopped at the end of surgery and residual neuromuscular blockade was antagonised with intravenous atropine (0.01 mg/kg) and neostigmine (0.03 mg/kg). The time to awakening was noted. The trachea was extubated when the patient was able to maintain an adequate airway and good respiratory minute volume. Arterial pressure, heart rate, the reaction of the patient to command and an assessment of whether the patient was awake o r drowsy were noted in the recovery room by a nurse who was unaware of the type of anaesthesia. Five questions were asked 30 minutes after operation: the name of the patient, the date of birth, where the patient was, and the date and the time. Each patient was interviewed on the day after surgery by a doctor who was unaware whether fentanyl or ketamine was used. Patients were asked about side effects, awareness, and their opinion about the anaesthetic. The Chi-square test was computed for dichotomous variables. The Wilcoxon rank sum test was used for continuous variables5 A p-value of less than 0.05 was considered significant. Results The pre-operative variables in both groups were compared (Table 2). No statistically significant differences in gender,
age, height, weight, arterial pressure or heart rate were found. The haemodynamic variables throughout the peri-operative period for both groups are shown in Figure I . Stable arterial pressure and heart rate were seen in the patients who received propofol/ketamine, except for a temporary increase directly after tracheal intubation. Systolic pressure increased by 13%, diastolic pressure by 11 YOand heart rate by 14%. Decreases in systolic and diastolic blood pressure were observed after induction in patients who received propofol/ fentanyl. Arterial pressure returned to baseline values after intubation. The heart rate was stable, except for an increase in mean heart rate by 24% after intubation. Patients who received propofol/fentanyl tended to have a lower systolic pressure than patients who received propofol/ketamine. The intra-operative variables for both groups are shown in Table 3 . The lowest systolic pressure found in the patients with propofol/ketamine was statistically significantly higher than that observed in patients with propofol/ fentanyl. No extra analgesics were required in the propofol/ ketamine group, but patients who received propofol/ fentanyl required a mean additional dose of fentanyl 0.72 pg/kg/hour. No statistically significant difference in the duration of surgery, respiratory variables, muscle relaxation or awakening after surgery were found. The postoperative variables are shown in Table 4. Patients who received propofol/ketamine demonstrated a significantly longer recovery time than patients given propofol/fentanyl. The time to an adequate reaction and the duration of drowsiness were longer, and the responses to the five questions 30 minutes after surgery were significantly less adequate. There were increased incidences of dizziness and confusion in patients given propofol/ketamine, but in all cases the confusion was reported by the patient himself and judged to be minor. No confusion was observed by medical personnel. Postoperative behaviour was normal in all patients, and none reported dreaming during o r after surgery. All patients judged the propofol/ ketamine combination to be pleasant, compared to 89Oh of the patients with propofol/fentanyl.
Table 2. Pre-operative variables. Data are presented as mean (SD).
Propofol-ketamine
Propofol-fentanyl
7:2 35 (12) 172 (10)
6: 3 39 (12) 169 (6) 72 (11)
Females :males Age; years Height; crn Weight; kg
Arterial pressure; rnrnHg Systolic Diastolic Heart rate; beats/minute ~
~
There were no significant differences.
70 (11) 130 (11) 80 (10) 80 (16)
126 (11) 84 (9)
72 (9)
26
J.B.M. Guit et al.
40
I
I
Preoperative Arrival
I
I
I
I
After induction
After intubation
Average during surgery
Average during recovery
I
J
1
Operating theatre
Fig. 1. Haemodynamic variables throughout the peri-operative period in patients anaesthetised with propofol/ketamine (a),or propofol/fentanyl (*). *, statistical significance.
Table 3. Intra-operative variables. Data are presented as mean (SD). Propofol-ketamine Duration of surgery; minutes Respiratory minute volume; litres/minute Compliance; ml/kPa Static Dynamic Arterial pressure; mmHg Highest systolic Lowest systolic Highest diastolic Lowest diastolic Heart rate; beats/minute Highest Lowest Muscle relaxation maintenance dose; mg/kg/hour Extra dose of fentanyl; pg/kg/hour Awakening after stopping TIVA; minutes
Propofol-fentanyl
p-value
60 (27) 7.2 (0.5)
78 (27) 7.1 (1.1)
ns ns
6.2 (1.1) 3.2 (0.4)
6.0 (1.8) 2.8 (0.7)
ns ns
144 (12) 118 (17) 85 (9) 64 (11)
137 99 81 59
(19) (10) (10) (15)
ns 0.030 ns ns
81 66
(14) (14)
ns ns
0.03 (0.03) 0.72 (0.72) 13 (18)
ns
92 73
(17) (18)
0.02 (0.02) _
17
_
(5)
ns
TIVA, total intravenous anaesthesia. ns, not significant.
Table 4. Postoperative variables. Data are presented as mean (SD). Propofol-ketamine Recovery-room Time until adequate reaction; minutes Time to awakening; minutes Duration of drowsiness; minutes Good response on five questions Nausea; % Patients’ interview Duration of awakening; hours Nausea; % Vomiting; % Dizzy; ‘/o Confused; % General judgement as good; YO ns, not significant.
Propofol-fentan yl
p-value
(26) (23) (22) (2) 0
1 (4) 9 (10) 11 (17) 5 (0) 11
0.027 ns 0.036 0.024 ns
3.4 (2.7) 0 0 44 33 100
2.2 (3.0)
ns ns ns ns ns ns
19 22 36 3
11
11 11 11 89
Ketamine analgesia for intravenous propofol anaesthesia Discussion Ketamine in subanaesthetic doses has recently gained more attention as an analgesic for total intravenous anaesthesia. Ketamine is a powerful analgesic although the mechanism and site of action of its analgesic effect remain to be fully elucidated. I t possesses local anaesthetic properties6 and has a direct inhibitory action on the dorsal horn neurones of lamina I and V.' Antagonism of the analgesic effect of ketamine with nalaxone in rats suggests that an endogenous opioid neuronal pathway in the central nervous system is involved.8 However, a n opioid component in the analgesic action of a subanaesthetic ketamine dose in humans has not been found, and blockade of the N-methyl-aspartate receptor has been suggested as a n alternative mode of action.' N-methyl-aspartate receptors may represent a subgroup of the sigma opioid receptors which block spinal nociceptive reflexes. Several other neuronal systems may be involved in the antinociceptive action of ketamine, since blockade of the noradrenaline and serotonin receptor also attenuates the analgesic action of ketamine in animals.'O The advantages of the use of ketamine as an analgesic include a powerful action at small doses without myocardial or respiratory depression, a broad therapeutic range and no organotoxic effects. The cardiocirculatory stimulation includes increases in heart rate, cardiac index and arterial pressure. However, the high incidence of adverse reactions limits its use. The main adverse reactions are stimulation of the sympathetic nervous system resulting in hypertension and emergence reactions (delirium, nightmares, hallucinations), both of which cause problems in patient acceptance and in postoperative nursing care. Various methods have been proposed t o overcome the adverse reactions. The combination of ketamine with benzodiazepines reduces the incidence of side effects and a continuous infusion of midazolam with ketamine has been recommended for military surgery, general civilian practice and cardiac ~ u r g e r y . ~Anaesthesia -~ is characterised by stable haemodynamics, after a temporary initial increase in heart rate and systolic arterial pressure. U p to 15% of patients report dreaming. The object of this study was to investigate whether propofol could eliminate the side effects of ketamine. The propofol/ketamine combination resulted in a stable arterial pressure and heart rate during surgery. Slow recovery was observed, but the postoperative behaviour was normal in all patients and no patient reported dreaming during or
27
after the operation. Propofol therefore seems to be effective in eliminating the side effects of a subanaesthetic dose of ketamine in humans. The advantage of using ketamine as the analgesic in combination with propofol for total intravenous anaesthesia is the achievement of stable haemodynamics during surgery. A stable arterial pressure throughout the operative period was observed, compared with the lower blood pressure found in the patients given propofol/fentanyl. The maintenance dose of fentanyl was not sufficient for analgesia in all patients in the propofol/fentanyl group and a dose of2.0 to 2.5 pg/kg/hour might have been more appropriate. However, a higher dose of fentanyl might have depressed the circulation even more. Side effects of the propofol/ketamine combination were the prolonged duration of the action of ketamine, resulting in a slower awakening and recovery, dizziness, and minor confusion directly after surgery. However, all patients judged anaesthesia to be good. We recommend the propofol/ketamine combination for total intravenous anaesthesia when stable haemodynamics are warranted. References 1. REICHDL, SILVAYG. Ketamine. An update on the first twenty-five years of clinical experience. Canadian Journal of Anaesthesia 1989; 36: 186-97.
2. RESTALLJ, TULLYAM, WARD PJ, KIDD AG. Total intravenous anaesthesia for military surgery. A technique using ketamine, midazolam and vecuronium. Anaesthesia
1988; 4 3 46-9. 3. BAILIE R, CRAIG G, RESTALL J. Total intravenous anaesthesia for laparoscopy. Anaesthesia 1989; 44: 60-3. 4. CHAI M, THANGA D, MORGAN E, VILJOEN J. Ketamine-midazolam continuous infusion in cardiac surgical patients. Anaesthesia 1989; 44: 364. 5 . NOETHER GE. Introduction to statistics. Boston: Houghton Mifflin, 1976. 6. AMIOTJF, Bourou PH, PALACCI JH, BALLINERE. Intravenous regional anaesthesia with ketamine. Anaesthesia 1985; 4 0 899-901. I . KITAHATA LM, TAUB A, KOSAKAY. Lamina-specific suppression of dorsal-horn unit activity by ketamine hydrochloride. Anesthesiology 1973; 3 8 4-1 1. 8. SMITHDJ, PEKOEGM, MARTINLL, COALGATE B. The interaction of ketamine with the opiate receptor. Lqe Sciences 1980; 2 6 789-95. 9. MAURSET A, SKOGLUND LA, HUSTVEIT 0, OYEI. Comparison of ketamine and pethidine in experimental and postoperative pain. Pain 1989; 38: 37-41. 10. PEKOEGM, SMITHDJ. The involvement of opiate and monoaminergic neuronal systems in the analgesic effects of ketamine. Pain 1982; 12: 57-73.
