Br. J. clin. Pharmac. (1979), 8, 223S-227S
USE OF LABETALOL DURING HALOTHANE ANAESTHESIA D.H.P. COPE Department of Anaesthesia, Middlesex Hospital, Mortimer Street, London Wl N 8AA, UK
1 The drugs that are available to attain controlled hypotension during anaesthesia are not entirely satisfactory. 2 Problems in controlling hypotension are encountered in the young, the anxious, patients with a tachycardia, and in those for whom halothane is contra-indicated. 3 Labetalol has been investigated as an adjunct to controlled hypotension in 150 major surgical procedures. Anaesthetic technique, labetalol dosage and results are discussed. 4 Labetalol in patients under halothane anaesthesia resulted in a rapid attainment of hypotension which was easily controlled, and quickly and permanently reversed by the intravenous administration of atropine sulphate. It was especially useful in patients in whom problems with other techniques can be anticipated. 5 Controlled hypotension with labetalol was also used in patients with ischaemic heart disease with good cardiovascular control and without any untoward effects.
Controlled hypotension during anaesthesia with intravenous agents has been practised for almost 30 years, with a wide variety of drugs and techniques. The introduction of halothane (Raventos, 1956) greatly facilitated the attainment of controlled hypotension, and its use with d-tubocurarine is now a widely practised technique. In those patients in whom adequate hypotension cannot be produced with an acceptable concentration of halothane the ganglion blockers, hexamethonium bromide or trimetaphan, may be used additionally to gain the desired level of hypotension. These drugs, however, are not entirely satisfactory, as tachyphylaxis and/or undesirable tachycardia often occur. Propranolol has been used .to combat the increase in heart rate, but it is at the expense of an appreciable fall in cardiac output (Hellewell & Potts, 1956). Furthermore, hexamethomium has a fairly prolonged action, so that if the operation proceeds faster than expected the arterial systolic BP may not readily be elevated to a 'bleeding level' of 100 mm Hg before wound closure. Sodium nitroprusside has been used as an alternative (Taylor et al., 1970), but it too may produce a tachycardia (Wildsmith et al., 1973). It can also cause a metabolic acidosis (Macrae & Owen, 1974) from which there have been fatalities (Jack, 1974). The continuous monitoring of the infusion rate and arterial BP impose such demands on the singlehanded anaesthetist that an intra-arterial recording device is desirable, itself not without hazard.
It was considered that labetalol with its combined a- and /3-adrenoceptor-blocking properties might be a useful drug for attaining hypotension during anaesthesia. The cardiovascular responses following labetalol in a small series of patients breathing spontaneously under halothane anaesthesia have already been investigated (Scott et al., 1976). They found that when labetalol was administered intravenously to patients during 1% halothane anaesthesia, mean arterial BP was rapidly reduced, the heart rate slowed, and there was a consequent small reduction in cardiac output; the central venous pressure was unchanged. When the inspired halothane was increased to 3% there was a further reduction in arterial BP, heart rate, cardiac output, and stroke volume, and there was an increase in central nervous pressure. It was concluded that the increased halothane concentration caused a considerable degree of direct myocardial depression. The depressant effect of 3% halothane was greater in patients receiving labetalol, probably because the counteracting adrenergic stimulation from the hypercapnia of deep anaesthesia had been blocked. In another study using controlled respiration in which the pCO2 was unchanged the effects of 1% halothane were more marked than in patients breathing spontaneously (Scott et al., 1978). The fall in cardiac output, however, was only 12% compared with 18% in the spontaneously breathing group. The / 2 Macmillan Journals Ltd 1979
combination of labetalol, controlled respiration and 3% halothane produced such a degree of cardiac depression that made further investigation unjustifiable. A synergistic effect between halothane and labetalol was apparent such that arterial pressure could be readily altered by adjusting the halothane concentration. It was decided, therefore, to investigate the use of labetalol as an adjunct to hypotensive anaesthesia with particular regard to the problems created by special problem patients, such as young patients with high sympathetic drive, the anxious patient, and those in whom halothane is contraindicated. This study describes the use of labetalol in 150 patients mostly in the problem categories or in those in whom systolic BP could not be controlled with high and cardio depressant doses of halothane.
Age 0-9 10-19 20-29 30-39 40-49 50-59 60-69 70-79 80-89 Figure 1 Age distribution of 150 patients. Average age 41 years. Range 9-86 years.
Methods One hundred and fifty patients (age range 9-86 yrs; average 41 yr) were studied (Figure 1). The type of surgical operations performed on these patients are shown in Table 1. As premedication all patients received an intramuscular injection of pethidine or an opiate, plus hyoscine or promethazine or perphenazine 1 h before surgery. Anaesthesia was induced with sodium thiopentone 2.5% and in most cases intubation was performed under suxamethonium relaxation. The
halothane concentration was increased up to 2% and as soon as there was evidence of muscle tone returning d-tubocurarine 30 mg was given intravenously. Patients were ventilated manually with 3 litres of nitrous oxide and 1.5 litres oxygen, or a Manley, ventilator was used with a 10 litre gas flow. The patient was then transferred to the operating table and appropriately postured for the operation.
Table 1 Types of operations (n = 1 50)
Type of surgery Hip
Spinal Other orthopaedic Nasal
Total hip replacement Plate and graft femoral shaft Hindquarter amputation Spinal fusion Laminectomy for PID Cervical fusion Putti-Platt operation Elbow replacement Sacral growths Excision naso-pharyngeal angioma Rhinoplasty
34 7 5 15 13 2 9 1 3 1 4
Hypophysectomy Maxillectomy Tympano myringo-plasty Re-exploration mastoid Stapedectomy Parotidectomy Parathyroidectomy Thyroidectomy Block dissection Laryngectomy Radical mastectomy Major abdominal
5 6 3 4 8 4 3 2
DURING HALOTHANE ANAESTHESIA
Arterial BP measurements were made using a von Recklinghausen oscillotonometer. Our aim was to maintain systolic arterial BP between 70 and 80 mm Hg. If it seemed that a patient would require more than 1% halothane to achieve this level then it was decided to administer labetalol. The initial dose of labetalol was assessed by the apparent resistance of the patient's sympathetic tone, and by the level of the pulse rate. The average for this first dose of labetalol was 20 mg. If, after 5 min, the systolic BP had not fallen to the required level, and the pulse rate was still greater than 60 beats/min, further increments of 5-10 mg were given until the desired level had been attained. The halothane concentration was reduced to 1% when the initial dose of labetalol was given to avoid a profound fall in arterial BP. In most cases the above regimen produced a systolic BP between 60-80 mm Hg, and these pressures could be accurately controlled by adjusting the halothane concentration or by altering the pressure in the reservoir bag. As most of our surgeons preferred the systolic BP to be over 100 mm Hg before closure, this was accomplished by decreasing the halothane concentration and/or by the intravenous administration of atropine sulphate 0.6 mg. At the end of the operation a further 0.6 mg atropine with 2.5 neostigmine were given to reestablish spontaneous respiration.
Thiopentone 450mg 1330 Suxamethonium 75mg Tubocurarine 30mg Labetalol (mg)
a) 'a 01) Co
0.6 0.6 Atropine (mg) 2.5 Prostigmin (mg)
150 140 130 120 110 100 90 80 70 60 50
Figure 2 Tubocurarine and 3% halothane have minimal hypotensive effect in a young (31-yr-old), apprehensive man (spinal fusion; blood loss 95 ml). Labetalol rapidly induces hypotension and a decrease in pulse rate. Readily reversed at end of operation by atropine sulphate.
Effective hypotension was readily obtained using the combination of labetalol and halothane. In those patients receiving halothane in concentrations of 2% or more without adequate hypotension being achieved, the administration of labetalol enabled the maintenance concentration of halothane to be reduced to 1% or less. In a total of 50 patients, 46 of whom received halothane anaesthesia and in 4 of whom did not, several doses (up to 4) of labetalol were used (Table 2). The usual first dose in this group was 20 mg and subsequent doses averaged approximately 9 mg. In the patients for whom halothane was contraindicated, a higher average dose (27.5 mg) was used
140 130 120 X
Table 2 Labetalol dose increments in 50 patients, 46 of whom were anaesthetized with halothane Dose of labetalol (mg) No of patients 50 40 24 11
1st 2nd 3rd 4th
Mean 20.1 9.6 8.0 8.9
Range 5.30 2.5.15 2.5.15 2.5.15
Halothene % 2 O 1
Figure 3 Revision clearance of mastoid cavity in 12-yr-old patient. At 'A', sudden 350 ml blood loss from large emissary vein produced marked hypotension but pulse rate unchanged; beta blockade is reversed with atropine sulphate, and arterial BP increases and is maintained over subsequent 3.5 hours.
Suxamethonium (75mg Tubocararine (30mg)
1630 1100 1130 1200
0830 000 0930 1000 Pethidine (25mg)
0.3 0.6 Atropine (mg) 2.5 Prostigmin (mg)
X. 130 m 120 o
c CD a)
80 70 ~0 60 50
Figure 4 Total hip replacement, age 55 yr. Severe angina at 50 m; aoccasional angina at rest. Shows severe painful stimulus breaking through a-blockade but no change in fl-blockade. Systolic BP returns to previous level with 25 mg pethidine. Reversal of both a- and fl-blockade with atropine sulphate 0.3 mg before wound closure.
with subsequent increments of 10 mg. The maximum dose administered was 75 mg. Examples of three different types of patient illustrate details of the technique. In figure 2 changes in BP and pulse rate in response to changes in labetalol and halothane dosages are shown. The patient was 31 yr old undergoing a spinal fusion. Despite halothane 3% there was no reduction in systolic BP, the pulse rate being 90 beats/minute. Intravenous doses of labetalol 25 mg and subsequently 10 mg reduced systolic BP markedly and pulse rate modestly. In a 12-yr-old patient undergoing a mastoid clearance procedure a sudden blood loss caused a further reduction in BP but the onset of tachycardia was delayed (Figure 3) until atropine sulphate 0.6 mg had been administered. In this patient rapid fluid replacement then restored BP and pulse rate to near normal. In a 55-yr-old man with angina pectoris who underwent a total hip replacement, systolic BP was satisfactorily maintained until sudden painful stimuli provoked an increase (Figure 4). The administration of pethidine 25 mg quickly restored the desired level of hypotension. Fifteen other patients with ischaemic heart disease also received labetalol without any untoward effects. Continuous ECG monitoring revealed no adverse changes in any of these ischaemic hearts, and there were no post-operative sequelae (Cope & Crawford, 1979). Reversal of the hypotension in all cases was
readily achieved by the intravenous administration of atropine sulphate 0.6 mg, systolic BP rapidly returning to a near normal level. The average increase in systolic BP was 17 mm Hg (range 10-35 mm Hg) which usually occurred within 10 min of atropine administration. This was also associated with an increase in average heart rate of 23 beats/minute. All patients were closely observed over the following 24 h, and in no instance did there occur a post-operative residual block.
Discussion Clinical experience with labetalol in controlled hypotension seems to be an advance in the safety of this technique. Tachyphylaxis and tachycardia, encountered with other techniques, were not encountered and there seemed to be minimal cardiac depression occurring with the doses used. The action of labetalol in patients anaesthetized with halothane is readily controllable, and rapidly and permanently reversible. It is especially helpful in those cases where difficulty with other techniques is encountered. Sixteen patients with ischaemic heart disease also received labetalol without any abnormal ECG changes during anaesthesia and with no complications after operation. It is recommended that the initial dose of labetalol in adults should be 20 mg in those patients already
DURING HALOTHANE ANAESTHESIA
receiving halothane, and that the concentration of the latter should not exceed 1%. Further increments of labetalol 5-10 mg may be given if necessary to attain the desired systolic arterial BP. In patients not
receiving halothane, an initial dose of labetalol 30 mg may be given with 5-10 mg increments if necessary until the required systolic arterial BP is reached.
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