The Role of Histamine in the Cardiovascular Effects of Atracurium

Abstract

We have investigated the effect of a bolus injection of atracurium 0.6 mg kg-1 on the cardiovascular system in 16 patients undergoing aortocoronary bypass surgery. H1- and H2-receptor antagonists were administered to eight patients before the neuromuscular blocker. A standard anaesthetic was used comprising fentanyl, flunitrazepam, etomidate and enflurane. After administration of atracurium, haemodynamic changes and plasma histamine concentrations were measured at frequent intervals. In the first group, who received only atracurium, a brief but marked decrease in SVR and MAP occurred, accompanied by an increase in Cl, together with a marked increase in plasma concentration of histamine. In the second group, who received H1- and H2-receptor block, there was no decrease in MAP and only a small increase in plasma histamine concentration. However, there were significant changes in SVR and Cl similar to those in atracurium group.

Persistent hypotension resolved by neostigmine administration in a dog in which atracurium was used

“…The IV administration of laudanosine (10 μg/kg) did not change HR and MAP in anaesthetised dogs 6 ; however, laudanosine plasma concentration > 6 μg/ml, reached after 30 minutes of a constant rate infusion of laudanosine at 15.7 mg/kg/h induced hypotension, decreased HR and increased EEG frequency and amplitude in anaesthetised dogs 9 . These effects might be caused by a direct inhibitory action of laudanosine on nicotinic α 3 β 4 receptors within autonomic ganglia, blocking post‐ganglionic sympathetic fibres and causing hypotension and decreasing HR 5, 18 . In our opinion, it is unlikely that at the dose used (0.3 mg/kg) atracurium would have produced such a high laudanosine concentration (>6 μg/ml) associated with cardiovascular changes in anaesthetised dogs 9 …”

“…Atracurium is considered an NMB with limited cardiovascular effects in dogs 1–4 . Atracurium is also administered in human patients undergoing cardio‐thoracic surgery for aorto‐coronary bypass 5 . In those patients, a temporary and self‐resolving hypotension caused by a reduction of systemic vascular resistances was recorded within 2 minutes after its IV administration at the dose of 0.6 mg/kg, and it was correlated with an increase in plasmatic histamine concentration 5 .…”

“…Atracurium is also administered in human patients undergoing cardio‐thoracic surgery for aorto‐coronary bypass 5 . In those patients, a temporary and self‐resolving hypotension caused by a reduction of systemic vascular resistances was recorded within 2 minutes after its IV administration at the dose of 0.6 mg/kg, and it was correlated with an increase in plasmatic histamine concentration 5 . In another study, the administration of the same atracurium dose did not change HR or MAP, while histamine concentration significantly increased in only one of six human patients.…”

“…Its peculiar metabolism – ester hydrolysis and Hofmann elimination – makes atracurium's pharmacokinetic predictable even in the presence of hepatic and kidney failure. Atracurium is relatively free of cardiovascular effects in dogs 1,2,4 ; however, its administration has been associated with transient hypotension possible related to histamine release in humans 5–8 . No hypotension was recorded after intravenous (IV) injection of 0.1–0.6 mg/kg of atracurium in healthy dogs 1,2,4 .…”

Rapid tracheal intubation with atracurium: the timing principle

“…Adt et al found that despite Hi and H2 receptor antagonist preventing histamine release and hy-potension, there was still a decrease in systemic vascular resistance and increase in cardiac index in patients given atracurium. 26 Other manifestations of histamine release include flushing and bronchospasm. The incidence of flushing in our series was similar to that obtained by other authors at comparable doses 22 and was dose related.…”