Acta anaesth. scund. 1980, 24, 1-4

Ketamine/Diazepam Infusion Anaesthesia With Special Attention to the Effect on Cerebrospinal Fluid Pressure and Arterial Blood Pressure T. THORSEN AND L. GRAN Department of Anaesthesiology, University Hospital of Bergen, Haukeland Sykehus, Norway

Ketamine/diazepam solution was used as the only anaesthetic in 105 patients selected for neuroradiological examinations. A rapid intravenous injection, 1 ml/kg bodyweight, followed by continuous drip infusion constituted the method used. No important side effects were seen, except psychotomimetic reactions in two cases. Cardiovascular disturbances were absent and no significant intracranial pressure rise occurred in nine patients examined.

Received 9 March, accepted for publication 16 May 1979

The combination of ketamine and diazepam for general anaesthesia has been proposed by several authors, for a wide range of surgical interventions. General agreement exists that the side-effects of ketamine are reduced by combination with diazepam, and that the ketamine dose can thereby be reduced.

The effect of diazepam on the ketamine-induced increase in arterial and intracranial pressures is, how- ever, rather controversial. In such studies the two drugs have been given separately. However, with the method proposed by BURNAP, the drugs are given simultaneously in a drip infusion (BURNAP 1974). Searching for a convenient intravenous method which would avoid gas anaesthesia under certain conditions, this method has been evaluated for 105 patients undergoing neuroradio- logical examinations at our hospital.

MATERIAL AND METHODS The study was carried out on 105 patients, ranging in age from 10 months to 75 years (57 males and 48 females). Air encephalography was performed in 97 patients and cerebral angiography in 8 patients. Premedication was with droperidol 0.1 mg/kg and atropine 0.6 mg. For children less than 20 kg b.w., only atropine 0.02 mg/kg wasgiven. All patients were in good physical health (group I according to the American Anesthetic. Association 1962). Before anaesthesia, none of the patients had signs of increased intracranial pressure.

Anaesthesia was induced with the ketamine/diazepam solution, pre- pared according to BURNAP, as follows: ketamine 500 mg and diazepam 50 mg were added to 500 ml of dextrose 5% in 0.11 % NaC1. A clear solution with pH 5.3 resulted (BURNAP 1974).

For induction, 1 ml of the solution per kg b.w. was injected intravenously. When the patients were asleep, the solution was given as a drip, and the drop rate was titrated according to anaesthetic requirements. Anaesthesia was completed with ketamine/diazepam solution in eight patients breathing air spontaneously. The remaining 97 patients were given succinylcholine, 1 mg/kg intravenously, and were then intubated, ventilated with oxygen, relaxed with pancuro- nium bromide (0.03-0.05 mg/kg) and given additional maintenance doses of the latter as required.

In nine patients who underwent air encephalography, the cerebro- spinal fluid pressure (CSFP) was recorded. With the patients in the right lateral position, a 22-gauge needle was inserted into the subarachnoidal space, care being taken not to lose any spinal fluid. The needle was connected to a transducer (Akers Electronique) filled with saline, and the pressure was recorded ona twin-pen recorder. The arterial blood pressure (BP) was recorded in the same way from an indwelling cannula placed in the left radial artery (Fig. 1).

Recordings were started preoperatively and continued until at least 5 min after the sleep dose had been given.

In three patients, induction was with thiopentone 3 mg/kg, succinylcholine 1 mg/kg was given for intubation, and further relaxation was obtained with pancuronium 0.1 mg/kg. Gas anaesthe- sia was given (02/N20=25%/75%) using intermittent positive pres- sure ventilation (IPPV) with a volume-controlled ventilator (Servo - Siemens). After a period of 20 min, when anaesthesia with stabilized blood-gas values had been obtained, the ordinary induction dose of 1 ml/kg b.w. of ketamine/diazepam solution was rapidly injected intravenously (Fig. 1).

The remaining 96 patients had their pulse and arterial blood pressure conventionally recorded at 5-min intervals.

RESULTS Cerebrospinal f luid pressure CSFP recorded under induction with ketamine/diaz-

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2 T. THORSEN AND L. GRAN

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Table 1 The maximal variations observed in mean arterial blood pressure and mean cerebrospinal fluid pressure during the first 5 min after intravenous injection of ketamine/diazepam solution (1 ml/kg body weight). In patients nos. 7, 8 and 9, a stabilized ventilation had been obtained by relaxation and intermittent positive pressure ventilation. Control=prein,jection readings.

Mean blood pressure (mmHg) CSF pressure (mmHnO) Patient no. Control After ketamine/diazepam Control After ketamine/diazepam

4 1

~~

1 95 90 140 140

2 100 100 100 100

3 90 95 180 150 ~~

4 90 90 160 180

5 90 90 150 200

6 125 110 120 180 ~~

7 117 117 145 130

8 85 85 100 90

9 87 92 174 140

Mean change3zs.e mean 1 .11 f200 -4.44k11 04

epam solution showed small variations. The maximal rise in one patient out of nine was 60 mmHnO (4 mmHg). The results are listed in Table 1. When given to relaxed, ventilated patients under stabilized gas anaes- thesia, the variations were even smaller (patients nos. 7, 8 and 9). Here a tendency to CSFP-decrease was recorded during the first 5 min after the injection.

BP-registration showed that no marked increase occurred compared with the pre-anaesthetic values (Table 1). During air encephalography, the patients were brought into a sitting position. This manoeuvre was well toler- ated, with no special precautions being taken. The total blood pressure and pulse variations are shown in Figures 2 and 3.

rnm He

crn H20

Fig. 1

20

15

10

5

0 1 2 3 4 5 min Blood prersure (BP) and cerebrospinal fluid pressure (CSFP)

under stabilized anaesthesia during injection of ketamine/diazepam solution, 1 ml/kg bodyweight.

The anaesthetic effect was satisfactory in all 105 patients. In three cases salivation was increased during anaesthesia and the early post-anaesthetic period. During the recovery stage, nausea and vomiting occurred in four patients, who had all had air encephalography perfor- med. Only two patients, both alcoholics, showed psychic reactions with screaming and shouting while waking up. No patients were able to recall unpleasant dreams or

ul +J c +J q c 0

KETAMINE/DIAZEPAM INFUSION ANAESTHESIA 3

60 40 20 0 2 0 40 60 fall rise - Pulse

Fig. 3. Maximal pulse variations during anaesthesia with ketamine/ diazepam infusion. An even distribution is found, indicating no influence of the anaesthetic.

hallucinations when examined before they left the recovery room.

The mean duration of anaesthesia was 100 min (f 10 rnin). The mean recovery time measured from when the infusion was stopped until questions were answered was 68 min (Ifr 15 min).

The total dose requirements, including the induction dose, averaged 2.66 ml/kg/h (s.e.m. f0 .38) , equivalent to a 2.6 mg/kg/h dose of ketamine, and to diazepam 0.26 mg/kg/h.

DISCUSSION Ketamine was introduced as an anaesthetic in 1966. Initially it gained high popularity, but this gradually declined, due to its side effects. The psychotomimetic reactions experienced by 30-50 % of the patients during the recovery period could, however, be dramatically reduced by combination with diazepam ( MATTILA & NUMMI 1973).

In 1974, BURNAP proposed simultaneous administra- tion of the two drugs by a drip method as an alternative to inhalation anaesthesia. His method, with some modi- fications, has since been adopted in gastrointestinal surgery (HATANO et al. 1978) and in cardiac surgery (KUMAM et al. 1978).

The cardiovascular effects of ketamine were also shown to be markedly modified by diazepam (ALLEN et

al. 1974). This could be explained by inhibition of the epinephrine response provoked by ketamine ( KUMAR et al. 1978).

Whether or not the ketamine-induced increase of intracranial pressure, which is about 250 mmHnO in man after a dose of ketamine 2 mg/kg b.w. (GARDNER et al. 1971), can be abolished by diazepam is controversial. After pre-treatment with diazepam 0.3 mg/kg b.w., TROP found a marked prevention of pressure rise in 18 adults (TROP 1978). In experimental studies, ALBIN et al. found that diazepam was able to abolish intracranial pressure augmentation in dogs given ketamine (ALBIN et al. 1978).

The aim of this study was to observe the influence on cerebrospinal fluid pressure when the two drugs were given simultaneously, according to the method of BUR- NAP (1974). The results show'that no significant rise occurred after 5 min when the drugs were given simultaneously. The effect on patients with a raised intracranial pressure remains to be determined.

We think that the prolonged recovery time (mean: 68 min) can be accepted when the lack of other side effects, such as psychotomimetic reactions, cardiovascular dis- turbances and intracranial pressure rise, can be avoided. Contraindications to the use of ketamine in epileptic patients (INNES 1973) may also be eliminated by the administration with diazepam. About 20 of our patients were using antiepileptic medication, and none of them showed fits or convulsions during anaesthesia.

Where gas anaesthesia is to be avoided (e.g. in air encephalography), ketamine/diazepam infusion has proved to be a valuable alternative. For mass casualties, anaesthesia under primitive conditions and during transport, intravenous anaesthesia has to be relied upon. Under such circumstances, the ketamine/diazepam infusion could be an alternative method of choice.

REFERENCES ALBIN, M. S., GONZALEZ-ABOLA, E., CHANG, J. L., HELSEL, P. &

BUNEGIN, L. (1978) Attenuation of intracranial hypertension after ketamine by diazepam pretreatment. Vth European Congress of Anaesthesiology, Paris. Paper 389, p. 213.

ALLEN, G. D., BOAS, R. A. & EVERETT, G. G. (1974) Modification of cardiovascular effects of ketamine by diazepam. Anesth. Progr.

BURNAP, R. W. (1974) Ketamine/diazepam solution as general anaesthetic. IVth European Congress of Anaesthesiology, Madrid. Paper 422, p. 177.

GARDNER, A. E., OLSON, B. E. & LICHTIGER, M. (1971) Cerebrospinal fluid-pressure during anaesthesia with ketamine. Anesthesiology 35, 226.

-TWO, S., NISHIWADA, M. & MATSUMIJRA, M.(1978) Ketamine/ diazepam anaesthesia for abdominal surgery. Anaeslhesist 27, 172.

INNES, R. (1973) Ketamine. 7. norske Lageforen. 93, 2425. KUMAR, S. M., KOTHARY, S. P, & ZSIGMOND, E. K. (1978) Plasma

21, 8.

4 T. THORSEN AND L. GRAN

free norepinephrine and epinephrine concentrations following diazepam-ketamine induction. A d a anuesth. scund. 22, 593.

MATTILA, M. A. K & NUMMI, S. (1973) The efFect of diazepam on emergence from ketamine anaesthesia. XIth Congress of the Scandinavian Society of Anaesthesiologists, Reykjavik. Paper 72, p. 85. N-5016 Haukeland Hospital

TROP, D. (1 978) Diazepam in ketamine-induced intracranial pressure increase. Vth European Congress of Anaesthesiology, Paris. Paper 403, p. 221.

Address:

Terje Thorsen, M.D.

Department of Anaesthesiology

Bergen Norway