Salbutamol induced hypokalaemia: the effect of theophylline alone and in combination with adrenaline.

Abstract

1 We have previously shown that salbutamol induced hypokalaemia, like adrenaline induced hypokalaemia, is the result of stimulation of a membrane bound 132-adrenoreceptor linked to Na+/K+ ATPase. We have also demonstrated that adrenaline induced hypokalaemia is potentiated by therapeutic concentrations of theophylline. 2 In a single-blind study of 14 normal volunteers, we infused salbutamol in doses used in clinical practice and examined the effects of the addition of theophylline alone or combined with (-)-adrenaline on plasma potassium levels, heart rate and blood pressure. The combinations studied were (i) salbutamol + vehicle control adrenaline infusion + placebo theophylline; (ii) salbutamol + vehicle control adrenaline infusion + theophylline; (iii) salbutamol + adrenaline + theophylline. 3 In a randomised, balanced placebo controlled design oral slow release theophylline or placebo was given for 9 days. Subjects were studied twice on the active limb (days 7 and 9) and once on the placebo limb (day 9) and the procedure was identical on each of the 3 study days except for the solutions administered. 4 Theophylline increased salbutamol induced hypokalaemia and in some individuals profound hypokalaemia (< 2.5 mmol 1-1) was observed with these relatively low doses of salbutamol and theophylline. Adrenaline did not further increase the magnitude of the fall in potassium observed. Combining theophylline with salbutamol increased the tachycardia resulting from the salbutamol infusion. Salbutamol infusion caused a fall in diastolic and rise in systolic blood pressure on all 3 study days and this was not altered by either theophylline or adrenaline alone or together. 5 We conclude that theophylline significantly increases salbutamol induced hypokalaemia and tachycardia and that the addition of adrenaline does not further increase hypokalaemia. Intensive bronchodilator therapy with these two agents in acutely ill, hypoxic patients with asthma or chronic obstructive lung disease may increase the risk of serious cardiac arrhythmias secondary to hypokalaemia.

Systemic beta‐adrenoceptor responses to salbutamol given by metered‐ dose inhaler alone and with pear shaped spacer attachment: comparison of electrocardiographic, hypokalaemic and haemodynamic effects.

“…The arrhythmogenic potential of hypokalaemia is well documented and may predispose to ventricular arrhythmias in patients with ischaemic heart disease (Stewart et al, 1985;Nordrehaug et al, 1985). The hypokalaemic response to salbutamol could be augmented and become clinically relevant in patients with airflow obstruction, who may be taking theophyllines (Whyte et al, 1988) and corticosteroids, or by diuretics (Struthers et al, 1983) for cor pulmonale or coexisting hypertension. The changes in blood pressure although significant were small, and not of clinical relevance.…”

Skeletal muscle magnesium and potassium in asthmatics treated with oral beta 2-agonists

“…It is well-known that β 2 -agonist treatment can reduce serum potassium [6,7], which has been feared to contribute to arrhythmias in fatal asthma [8,9]. The hypokalaemia can be further enhanced by concomitant theophylline treatment [10] and by diuretics [11].…”

The dose-related hyper-and-hypokalaemic effects of salbutamol and its arrhythmogenic potential

“…Although no difference could be found in effect between 10 and 100 fig kg-' salbutamol, both differed significantly from the 500;Lg kg-' dose. A similar biphasic response has been reported for adrenaline (Todd & Vick, 1971;Vick et al, 1972) but only a hypokalaemic effect has been reported for salbutamol (Smith et al, 1984;Whyte et al, 1987;1988) perhaps because the blood samples were taken after the occurrence of the earlier hyperkalaemia. The present results show that the hyperkalaemic effect occurs within 3 min after salbutamol administration.…”

“…thmias were seen (Smith et al, 1984;Whyte et al, 1987;Bremner et al, 1992;Clapham & Hamilton, 1992). In another study hypokalaemia was reported after 2 h and only one subject had premature supraventricular beats (Whyte et al, 1988). In contrast ventricular ectopic beats were reported in asthmatics who were on long-term (12 months) salbutamol therapy but no hypokalaemia was seen .…”

“…The first response was shown to be a combined a-adrenoceptor and P-adrenoceptor effect and the second response a P-adrenoceptor effect. The hypokalaemic effect of the P2-adrenoceptor agonist, salbutamol, was reported in normal volunteers within 30, 60 and 120 min of administration respectively (Smith et al, 1984;Whyte et al, 1987;1988), within 15 min in cats (Clapham & Hamilton, 1992), and within 15 min in asthmatics (Bremner et al, 1992). However, no hypokalaemia was reported in asthmatics on long-term treatment (12 months) .…”