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

Abstract

1 The hypokalaemic effect of salbutamol after more than 30 min of administration has been well described. A hyper-and-hypokalaemic effect for adrenaline has been reported, but no such hyperkalaemic effect for salbutamol. 2 The possible hyper-and-hypokalaemic effects of salbutamol with the concomitant potential for pro-arrhythmia were assessed in the baboon (Papio ursinus). 3 Male and femal baboons were anaesthetized with ketamine (15 mg kg-') and maintained with 6% pentobarbitone as spontaneously breathing animals. Six baboons in each group received either 10, 100 or 500 jg kg-' salbutamol i.v. Lead II of the ECG and femoral i.a. blood pressure were recorded continuously for 10 min. Arterial blood samples were collected at 0 min and then after 3 and 10 min of salbutamol administration. 4 All the animals developed sinus tachycardia (above 200 beatsmin-') within 30s of each dose of salbutamol administration and the high heart rate persisted throughout the experiment. All the animals were hyperkalaemic after 3 min and hypokalaemic after O min for each dose of salbutamol. Left ventricular conduction defects were seen in 3 animals during the hyperkalaemic phase. No arrhythmia was seen during the hypokalaemic phase. 5 Salbutamol has a transient hyperkalaemic and a more prolonged hypokalaemic effect in the baboon. The hypokalaemia could not be associated with arrhythmia although conduction defects were associated with the hyperkalaemia. 6 Since salbutamol is used as a bronchodilator in asthmatic patients and to treat acute hyperkalaemia, it is suggested that caution should be exercised when using salbutamol in high doses to treat acute asthma especially during the first few minutes of administration. The finding of hyperkalaemia with salbutamol questions its use in the treatment of hyperkalaemia.

Pathogenesis and therapy of non-oliguric hyperkalaemia of the premature infant

“…In the baboon, serum K + increased significantly within 3 min after an iv bolus of salbutamol (10, 100 or 500 lg/kg) accompanied by ventricular conduction defects [18]. Starting from a moderately elevated baseline serum K + a paradoxical increase in serum K + was observed in uraemic adults within 2 min after salbutamol inhalation (1200 lg through a spacer device within 2 min) [41].…”

Nichtoligurische Hyperkaliämie Frühgeborener - Ergebnisse einer nationalen Umfrage zur Inzidenz und zur Therapie mit Salbutamol -

“…Es existieren keine kontrollierten Studien zur Therapie der nichtoligurischen Hyperkaliämie Frühgeborener mit Salbutamol. Im Tierversuch und bei urämischen Erwachsenen wurden in den ersten Minuten der Salbutamolgabe paradoxe Anstiege der Serum-[K + ] von bis zu 0,7 mmol/l beobachtet [22,23] Aus den Ergebnissen unserer Umfrage kann nicht geschlossen werden, dass Unterschiede in der lokalen Inzidenz der Hyperkaliämie auf Unterschieden in den Behandlungskonzepten für Frühgeborene bezüglich Flüssigkeits-und Glukosezufuhr beruhen.…”

“…Unter den insgesamt 17 Patienten befanden sich höchstens 4 Frühgeborene mit den Charakteristika der nichtoligurischen Hyperkaliämie[18,20].Die Häufigkeit initialer paradoxer Anstiege der Serum-[K + ] unter Salbutamolinfusion konnte durch unsere Umfrage nicht geklärt werden. Initiale paradoxe Anstiege der Serum-[K + ] sind in den ersten Minuten der Salbutamoltherapie zu erwarten[22,23]. Die erste Bestimmung der Serum-[K + ] erfolgte in den Kliniken jedoch in der Regel erst 1 Stunde nach Beginn der Salbutamolinfusion.…”

“…Da in keinem Fall die Serum-[K + ] während der Salbutamolinfusion bestimmt worden war, bleibt unklar ob es sich dabei um salbutamolinduzierte Anstiege, um Therapieversagen oder um Wiederanstiege gehandelt hat.Die Inzidenz von Herzrhythmusstörungen unter Salbutamolinfusion war nicht Gegenstand unserer Umfrage. Die Mitteilung zweier Fälle von Herzrhythmusstörungen unter Salbutamolinfusion belegt jedoch das Vorkommen dieser im Tierversuch beobachteten[22], möglicherweise lebensbedrohlichen Nebenwirkung auch bei Frühgeborenen.…”

Experimental hyperkalaemia in rabbits: Effects of salbutamol and norepinephrine treatments on blood biochemistry and electrocardiography

“…On the other hand, it has been known for some years that the β 2 -stimulatory drug SAL may be an effective agent to treat HK in humans by inducing a shift of K + into the intracellular compartment (Lens et al, 1989;Murdoch et al, 1991). However, few studies have been conducted in laboratory animals to investigate the effects of SAL on experimentally induced HK (Du Plooy, 1994;Mahmoudian and Damankeshideh, 1996). The present study showed that SAL decreased the serum K + level in rabbits with experimental HK, which is consistent with the findings of our previously published work (Bal et al, 2002) and with the references given above.…”