This study was undertaken to investigate the neuromuscular blocking profile and cardiovascular effects of Org 9487, a new aminosteroidal, non-depolarizing, neuromuscular blocking agent structurally related to vecuronium, in anaesthetized animals and in isolated muscle preparations. In in vitro functional assays of neuromuscular blocking activity, Org 9487 was between eight and 15 times less potent than vecuronium. In cats and monkeys the potency of Org 9487 was approximately one-seventh and one-twentieth, respectively, that of vecuronium. In both species, Org 9487 induced rapidly developing (onset times between 1.5 min and 1.9 min) neuromuscular paralysis, which was shorter-lasting than that of vecuronium and similar in time course to suxamethonium. The vagal: neuromuscular blocking dose ratio for Org 9487 was 3 and ganglion block was seen only at approximately 20 times the neuromuscular blocking dose. There was no evidence in the rat that Org 9487, administered at doses up to 3mg kg−1, inhibited noradrenaline re uptake. In anaesthetized dogs, Org 9487 (3 × 90% blocking dose) induced only relatively small and transient haemodynamic effects. The administration of clinically relevant doses of neostigmine or pyridostigmine shortened the time–course profile of Org 9487, even when administered during profound neuromuscular block. In animals, Org 9487 is a low potency, nondepolarizing neuromuscular blocking agent with a time course profile similar to that of suxamethonium. Although Org 9487 is less selective than vecuronium for the neuromuscular junction, it is unlikely to produce prohibitive cardiovascular side effects in man.

The present report describes a case of cardiac arrest and subsequent death as a result of hyperkalaemia following the use of suxamethonium in a 23-year-old Malawian woman. Five days after the onset of the symptoms of meningitis, the patient aspirated stomach contents and needed endotracheal intubation. Forty seconds after injection of suxamethonium, bradycardia and cardiac arrest occurred. Attempts to resuscitate the patient were not successful. The serum level of potassium was observed to be 8.4 mequiv L−1. Apart from the reduction in the patient's level of consciousness, there were no signs of motor neurone damage or of any of the other known predisposing conditions for hyperkalaemia following the administration of suxamethonium. It is postulated that her death was caused by hypersensitivity to suxamethonium, associated with her 5-day immobilization.

A double-blind and randomized study design was used to investigate 100 healthy children, aged 1–5 years. Intubating conditions and cardiovascular changes duraning deep halothane anaesthesia, defined as an endtidal concentration of 2%, were compared with those changes during 1% halothane and suxamethonium relaxation. Intubating conditions were graded according to the ease of laryngoscopy, vocal cord position, coughing and jaw relaxation. In each group 96% of the children demonstrated acceptable intubating conditions. Jaw relaxation was worse in the 1% halothane/-suxamethonium group (P < 0.01). When anaesthesia with 2% or 1% halothane was compared there was a more pronounced decrease in systolic blood pressure (18 vs. 8%, (P < 0.001). Junctional rhythm occured more frequently during deep halothane anaesthesia (46 vs.18%, (P < 0.01). Intravenously (i.v.) administered atropine attenuated blood pressure depression significantly and reinstituted sinus rhythm in most cases.

The changes in heart rate and arterial blood pressure following the administration of suxamethonium in healthy children (mean age 3.8 ± 0.3 years) during inhalational induction with either sevoflurane (n = 22) or halothane (n = 19) were studied. Heart rate 60 s following suxamethonium administration increased significantly in the sevoflurane but not in the halothane group. In the halothane group, four children required intravenous (i.v.) atropine as a result of bradycardia. None of the children in the sevoflurane group developed bradycardia following suxamethonium (P < 0.05). Values of oxygenation, ventilation and age corrected minimal alveolar concentration were comparable at all measurement times. The haemodynamic response to the administration of suxamethonium in children anaesthetized with sevoflurane seems to reflect the stimulation of the autonomic ganglia by suxamethonium whereas this positive chronotropic effect is attenuated or reversed by halothane.

Eleven adult patients with severe head injuries caused by blunt trauma, (Glasgow Coma Score of eight or less after resuscitation), were studied while being mechanically ventilated and sedated in the intensive care unit (ICU). In a double blind randomized cross over trial each patient received a bolus of suxamethonium (1 mg kg−1) or an equal volume of saline(0.02 mL kg−1) before planned physiotherapy. Intracranial pressure (ICP) and mean arterial pressure(MAP) were measured continuously for 10 min after each injection. There were no significant changes in intracranial pressure or cerebral perfusion pressure(CPP) following the administration of suxamethonium or saline. Suxamethonium appears to be a safe drug to use on sedated persons with severe head injuries following blunt trauma.

Prolongation of the QT interval may produce potentially hazardous arrhythmias. The effects of midazolam or propofol, followed by suxamethonium on the QT interval have been investigated. Thirty patients, ASA I or II, without cardiovascular disease, electrolyte abnormalities or receiving any medication were studied. All patients were premedicated with midazolam 0.08 mg kg−1 i.m., 30–60 min prior to surgery. Anaesthesia was induced with either midazolam 0.4 mg kg−1 i.v., (15 patients) or propofol 1 mg kg−1 i.v. bolus, followed by a continuous infusion (15 patients). ECG, heart rate and arterial pressure were measured before induction of anaesthesia and at 1 and 3 min after the bolus of midazolam or propofol. Further recordings were obtained at 1 and 3 min after a bolus of suxamethonium 1.5 mg kg−1 i.v. and also immediately after tracheal intubation and 1 min later. Neither midazolam nor propofol had any significant effect on QTc interval. Prolongation of QTc was observed in both groups after suxamethonium and this was further prolonged following intubation. Heart rate and arterial pressure were also increased significantly in both groups following intubation.

The effect of the duration of stabilization of control responses on the onset and duration of clinical relaxation of suxamethonium 1 mg kg−1 and rocuronium 0.6 mg kg−1 were investigated in 90 patients. The control responses were allowed to stabilize for 1, 5, 10, 15 or 20 min prior to administration of rocuronium and for 1, 5, 10 or 15 min prior to suxamethonium. The mean onset time for rocuronium decreased from 150 to 46 s as the duration of stabilization increased from 1 to 20 min (P < 0.001) although the maximal effect was observed within the first 5 min. The average duration of clinical relaxation also increased from 25 to 40 min (P < 0.001). No effect was observed for either variable in the case of suxamethonium.