Br. J. clin. Pharmac. (1979), 8, 229S-232S
USE OF LABETALOL DURING HYPOTENSIVE ANAESTHESIA AND IN THE MANAGEMENT OF PHAEOCHROMOCYTOMA LEON KAUFMAN Department of Anaesthesia, University College Hospital Medical School, University Street, London WC1 E 6JJ, UK.
1 The circulatory effects of labetalol have been studied in 88 patients undergoing plastic surgery, 8 patients with carcinoma of the breast, 10 with carcinoma in the head and neck, and in 2 patients with phaeochromocytoma, each anaesthetized twice. 2 The use of labetalol intravenously produced hypotension and a bloodless operating field in patients undergoing plastic surgery and in those undergoing radical surgery for the removal of carcinoma.
3 Two patients with phaeochromocytoma pre-treated with oral labetalol before anaesthesia, had well controlled BPs and heart rates during surgery, although in one instance additional intravenous labetalol was required. 4 Pre-operative preparation of patients with phaeochromocytoma with labetalol seems to be simpler and safer than previous techniques involving drugs with separate a- and fl-adrenoceptorblocking effects.
UNTIL recently controlled hypotension during surgical procedures has been accomplished either by ganglion-blocking drugs or by the use of sodium nitroprusside (SNP). A side-effect of their use is tachycardia, especially in young patients, which can be controlled by propranolol. Thus, with the advent of labetalol, which has non-selective ,B- and aadrenoceptor-blocking properties (Farmer et al., 1972; Richards, 1976), it has been suggested that it might have a place in the production of hypotensive anaesthesia (Scott et al., 1976). In addition, the pre-operative and operative management of patients with phaeochromocytoma require the use of a- and fJ-adrenoceptor-blocking agents, and labetalol has already been used in such patients (Rosei et al., 1976). Thus, the aim of this study was to evaluate the effects of labetalol during anaesthesia and in the management of patients undergoing surgery for phaeochromocytoma. Methods In this study there were 80 patients between the ages of 18 and 44 undergoing the operation of rhinoplasty (70 female, 10 male). In addition, 8 patients underwent other plastic procedures, including 2 for face-lift. There were a further 18 patients, 8 of whom were having surgery for removal of carcinoma of the breast and 10 for carcinoma in the head and neck,
including the orbit, tongue and floor of mouth (block dissection of glands of neck in 2 patients). All the patients were premedicated with papaveretum (10-15 mg intramuscularly) and hyoscine (0.2-0.3 mg intramuscularly) and anaesthesia was induced with thiopentone, suxamethonium and maintained with nitrous oxide, oxygen (50:50) and halothane (0.5-2.0%). Respiration was spontaneous. ECG and heart rate were monitored continuously and BP recorded serially by non-invasive means using a Doppler probe to determine the end-point. The last 50 cases were monitored using the Dinamap automatic non-invasive arterial BP monitor, which displays the systolic, diastolic and mean BPs as well as the heart rate. When the patient's circulatory state was stable, intravenous labetalol 10-25 mg was administered. In some patients supplementary doses of labetalol 10 mg were administered within 5 min of the original dose if the BP had not fallen to the desired maintenance level. The halothane concentration was gradually reduced to 0.5%, although painful stimuli could still cause small peaks in BP which required a temporary deepening of anaesthesia with halothane. The degree of head-up tilt during operation was never greater than 15 degrees. Two patients with phaeochromocytoma, who underwent two procedures each under general anaesthesia, were also treated with labetalol. The patients with phaeochromocytoma are reported as case-histories.
0) Macmillan Journals Ltd
In a- .
+10 min halothane off -
After 01 3 5 inducction
Time after labetalol (min)
Figure 1 Effect of intravenous bolus injection of labetalol 25 in 20 patients anaesthetized with halothane.
Results The effect of intravenous labetalol on systolic BP and heart rate in 20 patients anaesthetized with halothane is shown in Figure 1. Labetalol caused an immediate marked reduction in BP and fall in heart rate. Figure 2 shows the effect of labetalol in a young person having a rhinoplasty who required incremental doses of labetalol to produce the desired hypotensive effect. In contrast, in a 60-yr-old woman undergoing plastic surgery to the face, controlled hypotension was produced after only 10 mg labetalol (Figure 3). In those patients undergoing rhinoplasty, blood loss during surgery was never more than 25 ml and in those more extensive procedures for carcinoma only minimal blood loss was recorded and blood transfusion was never required. The duration of operations was considerably reduced with this hypotensive technique.
mg on mean
systolic BP and
mean heart rate
Anaesthesia was induced with thiopentone and suxamethonium and maintained with nitrous oxide and oxygen and intermittent doses of tubocurarine and fentanyl. The ECG was recorded continuously throughout the operation, as well as pulse rate, BP and central venous pressure. 7.-
200 150io a)
Patients with phaeochromocytoma Case I In a 50-yr-old man a right adrenal tumour had been removed in 1976 but despite this, attacks of hypertension persisted. He was subsequently treated with phenoxybenzamine and propranolol. BP was 160/110 mmHg and urinary VMA excretion was 25 mg per 24 hours. Aortography revealed increased vascularity above the upper pole of the left kidney. The patient was prepared for exploratory surgery by receiving oral labetalol commencing with 300 mg daily and increasing to 1200 mg daily. On the morning of the operation, he was given labetalol 500 mg and hydrocortisone 100 mg. Premedication was with papaveretum 15 mg and hyoscine 0.3 mg.
Time (min) Figure 2 Effect of incremental intravenous injections of labetalol in a young woman (aged 22 yr) having a rhinoplasty.
HYPOTENSIVE ANAESTHESIA & PHAEOCH ROMOCYTOMA -
Tubarine (mg) 10 Labetalol 25mg i.v. Fentanyl (jAg) 200 100 Atropine
oQ E -0E_
* Incision * Stripping off peritoneum * Pressure on tumour * Adrenal removed
a) 100 a) (0 50
Figure 3 Effect of a single low dose (10 mg) of intravenous labetalol in a female (aged 60 yr) undergoing plastic surgery.
During the early part of the operation systolic BP increased to 200 mm Hg attributable to too light a level of anaesthesia. An increase in BP and pulse rate occurred as the adrenal gland was manipulated which was controlled by two intravenous doses of labetalol 25 mg. BP and pulse rate remained stable until the end of the operation when atropine was given (Figure 4). Recovery from anaesthesia was immediate and BP, pulse rate and central venous pressure remained satisfactory during the post-operative period. A recurrence of a malignant tumour necessitated further surgery during which BP and heart rate remained remarkably stable until the end of the operation. After the administration of atropine a marked tachycardia and hypertensive response occurred which was subsequently controlled with intravenous labetalol. Case 2 An obese Greek lady who had a history and biochemical evidence of a phaeochromocytoma was prepared for an arteriogram to localize the site of the tumour with oral labetalol 1000 mg daily. During this procedure BP and pulse rate were remarkably stable and the arteriogram confirmed the presence of a phaeochromocytoma in the adrenal gland (Figure 5). Before surgical removal of the tumour she received oral labetalol; and during surgery pulse rate and BP were reasonably stable except when the tumour was being dissected. Labetalol 50 mg was given in divided
15 10 5
Figure 4 Use of intravenous labetalol in a male patient undergoing surgery for removal of phaeochromocytoma.The effect of atropine is particularly noticeable on heart rate. Arteriogram Phaeochromocytoma 800mg rLabetalol orally E3 Halothane 1 % C1o 5mg i.v. Intubation Dye injectedr
Q- E E
Time (min) Figure 5 Use of intravenous labetalol during an arteriogram in a female (aged 50 yr) already receiving oral labetalol to control a suspected phaeochromocytoma.
doses to bring BP down from 216/141 to 165/135 mm Hg. Despite this increase in BP, pulse rate remained under 60 beats/minute. When the last vessel to the tumour was clamped, BP fell to 60/43 mm Hg which was rapidly corrected by the administration of two units of blood. The hypertensive response had masked the effects of bleeding on BP. Recovery was uneventful.
Discussion Labetalol is unique in causing competitive antagonism at both cx- and fl-adrenoceptor sites. It has been shown to be an antagonist exclusively at postsynaptic a-adrenoceptor sites (Blakeley & Summers 1977). Scott et al., (1976) and Scott et al., (1978) have reported in detail on the circulatory effects of labetalol during halothane anaesthesia. They have shown the effects of 1% halothane causing a drop in mean arterial pressure, cardiac output, heart rate and peripheral resistance, with little effect on the central venous pressure. However, labetalol given in the presence of 3% halothane resulted in marked declines in mean arterial pressure, cardiac output and an increase in central venous pressure. The combination of sympathetic inhibition from labetalol and the effect of 3% halothane was sufficient to depress cardiac output. In this series the maximum concen-
tration of halothane was 2%. However, we have seen a further fall in BP about 20 min after the injection of labetalol, which may be due to a decrease in cardiac output, resulting in a further increase in alveolar halothane concentration. The present study confirms that the technique with labetalol produces a remarkably bloodless operation field except for the initial incision. Here, presumably, the aadrenoceptor-blocking effect has produced skin vasodilatation. The onset of hypotension was rapid, tachycardia did not occur, and no side-effects were seen. Recovery was rapid and patients were in good clinical condition on the day following operation. Although it is too early to estimate the value of labetalol in the management of phaeochromocytoma from only two patients, it does seem to offer advantages over previous experiences with 60 patients in whom phenoxybenzamine and propranolol were used. Labetalol has a more rapid onset compared with phenoxybenzamine and a half-life of only 4 h, which is much less than that of phenoxypenzine. Phentolamine has been found to have a transient action and also to produce a tachycardia. Despite the radiographic evidence of the tumours in both the patients being very vascular, there was very little bleeding during the dissection. Recovery from anaesthesia was very rapid, unlike the experience with phenoxybenzamine. Patients were remarkably well during the recuperative phase after surgery. It is now customary to give labetalol in hypotensive anaesthesia as an infusion until the desired level of BP is reached rather than giving it as a single bolus.
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