Duration of action of atracurium when given by infusion to critically ill children

Abstract

The aim of the study was to investigate the offset time of atracurium when given by continuous infusion on a paediatric intensive care unit and to look for evidence of tolerance. Over a period of 8 months, 20 mechanically ventilated children had a steady-state infusion of atracurium discontinued to enable the assessment of their level of sedation. The offset time of atracurium was assessed by train-of-four (TOF) stimulation of the ulnar nerve. The initial TOF reading was documented as was the time taken to reach a TOF ratio of 0.9. Thirty-five assessments were carried out. The mean offset time of atracurium was 28.7 min (SEM 1.76 min, range 8-56 min). There was no correlation between the dose of atracurium at discontinuation and the offset time of the infusion. The duration of infusion was negatively correlated with the offset time of atracurium, and this effect was most prominent in children who had received infusions for longer than 48 h. When given by continuous infusion, the offset time of atracurium is very variable between individual patients. Infusions administered for longer than 48 h are associated with a significant reduction in the offset time as a result of increasing tolerance.

The effect of induced hypothermia on the duration of action of atracurium when given by infusion to critically ill children

“…Atracurium is broken down primarily by two purely chemical mechanisms; Hofmann degradation (a nonenzymatic base‐catalysed reaction) and nonspecific ester hydrolysis, with elimination T½ of 21 min ( 16). Variations of temperature within the physiological range are not felt to significantly alter the duration of action of atracurium, and this has been borne out by our previous experience in a normothermic group of individuals ( 2).…”

“…The mean offset time of atracurium was 82.0 min (SEM 5.65, range 57–110 min) which is 2.86 times longer than in the normothermic group ( Figure 3); this represents a highly significant difference both statistically and clinically (Mann–Whitney U ‐test: W =630, P < 0.0001). Given our previous findings that duration of infusion is correlated with offset time ( 2), and the suggestion of an apparently greater effect of hypothermia in children than in adults, we went on to match the six hypothermic cases with normothermic cases with similar ages and duration of infusion. There was no statistical difference between these groups in terms of age or duration of infusion ( P =0.7 and P =0.8, respectively) but again there was a significant difference in offset time between the two groups (Mann–Whitney U ‐test; W =21.0, P =0.002).…”

“…Atracurium besylate is the most commonly employed neuromuscular blocking agent on our unit during induced hypothermia. Atracurium is administered according to a protocol previously described ( 2)…”

“…In order to be assessed patients must have had an infusion of atracurium running uninterrupted, and at a constant rate, for at least 8 h. Peripheral nerve stimulation was delivered using train‐of‐four (TOF) stimulation with an uncalibrated accelerometer (TOF‐Guard, Organon‐Teknika NV) to assess adductor pollicis contraction using a standard technique fully described elsewhere ( 2). Baseline TOF results were recorded and the infusion of atracurium discontinued.…”

Continuous‐Infusion Neuromuscular Blocking Agents in Critically Ill Neonates and Children

“…The offset time after discontinuation of atracurium infusion was investigated in 20 children receiving mechanical ventilation (Table 1). 21 Patients were given a bolus dose followed by a continuous infusion. A total of 35 assessments were made among the 20 children by using TOF stimulation of the ulnar nerve.…”