THE RESPIRATORY EFFECTS OF DIAZEPAM SUPPLEMENTATION OF SPINAL ANAESTHESIA IN ELDERLY MALES

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Br. J. Anaesth. (1974), 46, 439

THE RESPIRATORY EFFECTS OF DIAZEPAM SUPPLEMENTATION OF SPINAL ANAESTHESIA IN ELDERLY MALES C. PEARCE SUMMARY

Elderly patients with impaired cardio-respiratory reserve presenting for lower abdominal, perineal or lower extremity surgery are offered lumbar subarachnoid or epidural analgesia with increasing frequency. As a rule many of these patients express a wish to be asleep during the operative procedure, but to resort to the administration of supplementary general anaesthesia in such cases would defeat the initial purpose of employing conduction techniques. Ideally a supplementary sedative should not possess cardio-respiratory depressant effects; the sleep produced should not be unduly prolonged and recovery should be free from "hangover". In addition, there should be no antagonism of the action of the local analgesic agent and, if possible, there should also be a reduction in unwanted side-effects. Barbiturates reduce the incidence of convulsions associated with local analgesics (Usubiaga et al., 1966) but in a dose adequate to ensure sleep they produce respiratory depression and, in the elderly, recovery is often prolonged. Chlorpromazine has been the subject of conflicting reports. Rink, Wever and Lundberg (1966) found no significant change in mean arterial pressure when the drug was administered orally in a dose of 50 mg 2 hours before spinal anaesthesia, but Moore and Bridenbaugh (1956) reported nine cases of serious acute hypotension with one fatality in patients receiving chlorpromazine shortly before spinal subarachnoid and epidural block. In recent years, the benzodiazepine derivatives, and in particular diazepam, have found increasing C. PEARCE, F.F.A.R.C.S.; Department of Anaesthesiology,

University Hospital, Free University, de Boelelaan 1117, Amsterdam, Netherlands.

usage as premedicant and induction agents (Knight and Burgess, 1968). Among the advantages claimed for diazepam are minimal depression of cardiac function (Dalen et al., 1969) and protection against local anaesthetic seizures (de Jong and Heavner, 1971). One definite disadvantage noted by Stuart Brown and Dundee (1968) was prolonged recovery from sleep as well as "persistence of dizziness for 24 hours in 30% of patients". Pain along the course of the vein during the injection of diazepam has been reported by several authors (McClish, 1966; Hellewell, 1968; Stovner and Endresen, 1966). Indeed, Stovner and Endresen (1966) diluted the drug to 0.2% in 5% dextrose solution in an attempt to reduce this pain. The effects of diazepam on respiration have been the subject of widely differing reports. Stovner and Endresen (1966) reported a 20-30% reduction in respiratory minute volume following 15-30 mg diazepam given by intravenous injection. In all cases premedication was morphine 10 mg with hyoscine 0.4 mg. McClish (1966) stated that respiratory depression was moderate and transitory and never progressed to apnoea; he also suggested, but without providing evidence, that elderly patients were more susceptible in this respect. Hellewell (1968) observed apnoea of short duration in a 72year-old patient and stated in the conclusion of his paper that "The occurrence of apnoea, although rare, indicates that more caution is necessary when using the drug in the aged and in patients premedicated with opiates". The relationship between the dose of diazepam and the development of respiratory depression has given rise to conflicting statements also.

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In 15 elderly male patients undergoing lower abdominal surgery under lumbar subarachnoid or epidural analgesia, Pac02 determinations were performed before and at intervals following the intravenous injection of a sleep dose of diazepam. No statistically or clinically significant changes in Pa0o2 were observed and it was concluded that diazepam in a dose of 0.32 mg/kg, did not produce respiratory depression. Prolonged recovery and postoperative amnesia were observed as possible disadvantages of the use of this technique in elderly patients.

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BRITISH JOURNAL OF ANAESTHESIA

440

MATERIAL

The 15 patients in this study were all male, and all over 65 years of age; their ages, the dose of diazepam given, the operative procedures and analgesic techniques employed are listed in table I. Patients were excluded from the study if there was a specific contraindication to "spinal" analgesia or if the patient refused the technique. METHOD

All patients received nitrazepam 5 mg orally on the evening before operation and diazepam 10 mg i.m. at least 30 minutes before anaesthesia. On arrival in the anaesthetic room, an intravenous infusion of lactated Ringer's solution was set up and Richards' modification of Allen's test (Richards, 1970) was TABLE I. Age, diazepam dose, operation and analgesic technique. Patient No. 1 2 3

73

10

4

70

15

5 6 7 8

66 68 71 77 74 69 69 79

25 35 30 30 35 15

9

10 11 12 13 14

15 Mean SE

Age Diazepam (yr) dose (mg) 81 20 20 70

67 79 69 72.1 1.26

10 10 20 15 20

Operation Inguinal hernia Transurethral resection Removal hip nail Transurethral resection Prostatectomy Prostatectomy Prostatectomy Prostatectomy Prostatectomy Prostatectomy Prostatectomy Prostatectomy Transurethral resection Prostatectomy Inguinal hernia

Analgesic technique

20.7 2.23

SA = subarachnoid; CE = caudal epidural; LE=lumbar epidural.

SA

CE SA SA LE SA SA SA SA SA SA SA CE SA SA

performed on the left hand to determine the adequacy of circulation in the ulnar artery. Puncture of the left radial artery was then carried out under local anaesthesia with 1% lignocaine using a 20-gauge Argyll Medicut cannula which was then advanced 2-3 cm into the artery. This disposable polypropylene cannula has been shown to produce minimal reaction when used for intravenous infusions (Jones and Craig, 1972) and the sharp, short point of the removable inner needle renders arterial puncture a simple procedure. A disposable plastic 3-way tap (Pharmaseal K-75) was then firmly attached to the cannula and, after allowing free flow to clear the deadspace in the system, a 2-ml control sample for gas analysis was collected anaerobically in a heparinized plastic syringe. The system was then flushed with a dilute solution of heparin and the tap closed. Spinal anaesthesia was then induced, and after checking for an adequate extent of analgesia diazepam was injected intravenously in 5-mg increments until sleep was produced. Further 2-ml blood samples were taken 5, 15 and, when possible, 30 min after completing the injection of diazepam. In every case 2 ml were discarded before taking the sample and the system was again flushed with diluted heparin immediately after sampling. PaCO2 was determined with an Eschweiler-type electrode (Combi-test, Godart) immediately following withdrawal of each sample. During the operative procedure humidified oxygen (2-3 l./min) was administered by means of a sponge-tip nasal catheter. RESULTS

The average sleep dose of diazepam in these patients was 20.7 mg (table I). The Pa c02 showed a tendency to increase during the first 15 min after injection with a return towards the control value at 30 min (table II). It is possible that these changes may denote a trend, but in fact they are neither statistically nor clinically significant. No circulatory changes could be attributed to the administration of diazepam, and with one exception all the patients slept through, or remained drowsy during, the operation. Particularly noteworthy was the prolonged recovery observed in all cases. As a rule the patients awakened in the recovery room only to fall asleep again 4—6 hours later. Anterograde amnesia was seen commonly and in a few patients this lasted longer than 24 hours: a norm-

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Catchlove and Kafer (1971) found a 19% increase in PaC02 with 0.14 mg/kg, whereas Cohen, Finn and Steen (1969) found "no significant respiratory depression at dose levels up to 0.266 mg/kg". On account of these varying opinions and the absence of documented studies on the respiratory effects of diazepam in the aged, it was decided to study the influence of a sleep dose of the drug on the arterial carbon dioxide tension in elderly patients undergoing surgery of the lower half of the body under subarachnoid or epidural spinal block.

441

DIAZEPAM SUPPLEMENTATION IN SPINAL ANALGESIA TABLE II. Paco, values in 15 patients before, and at intervals following the intravenous injection of diazepam. Pa M 2 (mm Hg)

Patient No. 1 2 3 4

15min

30min

37

40 42

39

43.5

39 42

43.5 40

43.5 41 42 43 35 39 46 43

37.5 44 39 43

46.5 38 42 50 45

41.5

42.5

32 42 38

33 39 43

Mean

40.4

SD

3.68

37

43.5 39.5

43 48

36.5

46 48 43 42 37 42

37.5

44 38 42 44 42 39 39

41.6

44.5 42.2

4.10

3.74

2.43

40.6

ally alert 71-year-old man complained that he had lost three days of his life. Retrograde amnesia for the induction of local anaesthesia was not observed in these patients. Complaints of a burning sensation, or of actual pain, along the course of the vein were frequent during the injection of diazepam. These symptoms were not related to the speed of injection nor were they modified by changing the rate of the i.v. infusion. DISCUSSION

In the present investigation the intravenous injection of diazepam 0.32 mg/kg in male patients over 65 years of age led to an average increase in PaCo2 of 4.3%. This is considerably lower than the 19% increase observed by Catchlove and Kafer (1971) in a younger age group (average age 40 years) with a dose of 0.14 mg/kg. A possible explanation for this discrepancy may be found in the low mean control PaCo2 of 34 mm Hg in the latter series (Catchlove and Kafer, 1971) whereas their post-drug value of 40.5 mm Hg lies considerably nearer the generally accepted normal value. These patients had received no premedication before an assessment of their baseline values had been made and it is therefore reasonable to expect a moderate increase in ventilation "2 hours before the induction of anaesthesia, with the patient sitting comfortably on a bed", with an indwelling Cournand needle in place, and anticipating operation. The effect of diazepam in these patients is that of satisfactory sedation with normalization of the PaOo2- Th e patients reported in this study all

REFERENCES

Catchlove, R. F. H., and Kafer, E. R. (1971). The effects of diazepam on the ventilatory response to carbon dioxide and on steady state gas exchange. Anesthesiology, 34, 9. Cohen, R., Finn, H., and Steen, S. N. (1969). Effect of diazepam and meperidine, alone and in combination, on respiratory response to carbon dioxide. Anesth. Analg. (Cleve.), 48, 353. Dalen, J. E., Evans, G. L., Banas, J. S. jr, Brooke, H. L., Paraskos, J. A., and Dexter, L. (1969). The hemodynamic and respiratory effects of diazepam. Anesthesiology, 30, 259. Hellewell, J. (1968). Induction of anaesthesia with diazepam; in Diazepam in Anaesthesia, p. 47. Bristol: John Wright. Jones, M. V., and Craig, D. B. (1972). Venous reaction to plastic intravenous cannulae: influence of cannula composition. Can. Anaesth. Soc. J., 19, 491. de Jong, R. H., and Heavner, J. E. (1971). Diazepam prevents local anesthetic seizures. Anesthesiology, 34, 523. Knight, P. F., and Burgess, C. G. (eds.) (1968). Diazepam in Anaesthesia. Bristol: John Wright. McClish, A. (1966). Diazepam as an intravenous induction agent for general anaesthesia. Can. Anaesth. Soc. J., 13, 562. Moore, D. C , and Bridenbaugh, L. D. (1956). Chlorpromazine: a report of one death and eight near fatalities following its use in conjunction with spinal, epidural and celiac plexus block. Surgery, 40, 543. Richards, R. L. (1970). Peripheral Arterial Disease, a physician's approach, p. 47. Edinburgh and London: Livingstone. Rink, R. A., Wever, R. C , and Lundberg, G. D. (1966). Chlorpromazine: effect on mean arterial pressure when used as a premedicant in spinal anesthesia in healthy male patients. Anesth. Analg. (Cleve.), 45, 599. Stovner, J., and Endresen, R. (1966). Intravenous anaesthesia with diazepam. Acta anaesthesiol. Scand. Proc. II (Suppl.) 24, 223. Stuart Brown, S., and Dundee, J. W. (1968). Clinical studies of induction agents. XXV: Diazepam. Br. J. Anaesth., 40, 108. Usubiaga, J. E., Wikinski, J., Ferrero, R., Usubiaga, L. E., and Wikinski, R. (1966). Local anesthetic induced convulsions in man. Anesth. Analg. (Cleve.), 45, 611.

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5

6 7 8 9 10 11 12 13 14 15

Control

5min

received diazepam 10 mg intramuscularly as premedication 1 hour before arterial puncture and the average control Pa 002 of 40.4 mm Hg was almost identical with the post-drug value found by Catchlove and Kafer. The fact that a further larger dose, administered intravenously, produced only a slight increase in PaC02 and that the post-drug value was well within normal limits suggests that diazepam possesses little or no respiratory depressant effect when given in a dosage of 0.32 mg/kg to normallyventilating elderly male patients. The administration of opiates in the premedication should probably be avoided.

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