Reversal of rocuronium-induced neuromuscular block by the selective relaxant binding agent sugammadex: a dose-finding and safety study.

BACKGROUND: Sugammadex (Org 25969) forms a complex with steroidal neuromuscular blocking agents, thereby reversing neuromuscular block. This study investigated the dose-response relation, safety, and pharmacokinetics of sugammadex to reverse rocuronium-induced block. METHODS: Twenty-seven male surgical patients aged 18-64 yr were randomly assigned to receive placebo or sugammadex (0.5, 1.0, 2.0, 3.0, or 4.0 mg/kg) for reversal of 0.6 mg/kg rocuronium-induced neuromuscular block. Anesthesia was induced and maintained using intravenous fentanyl and propofol. Neuromuscular function was assessed using acceleromyography. Sugammadex or placebo was administered at reappearance of T2 of the train-of-four. The primary efficacy variable was the time required for recovery to a train-of-four ratio of 0.9. RESULTS: Sugammadex decreased median recovery time in a dose-dependent manner from 21.0 min in the placebo group to 1.1 min in the group receiving 4.0 mg/kg sugammadex. Doses of sugammadex of 2.0 mg/kg or greater reversed rocuronium-induced neuromuscular block within 3 min. A median of 59-77% of sugammadex was excreted unchanged in the urine within 16 h, mostly in the first 8 h. Sugammadex increased the proportion of the rocuronium dose excreted unchanged in the urine (from a median of 19% in the placebo group to 53% in the 4.0-mg/kg group within 16 h). Sugammadex was safe and well tolerated. No evidence of recurarization was observed in any patient. CONCLUSION: At doses of 2.0 mg/kg or greater, sugammadex safely reversed 0.6 mg/kg rocuronium-induced neuromuscular block in a dose-dependent manner. Sugammadex enhanced renal excretion of rocuronium and was excreted unchanged by the kidneys.

A three year population based survey of paediatric mechanical ventilation in east Denmark.

BACKGROUND: East Denmark has a population of 396,000 children 0-14 years and a yearly birth rate of 30,000, but at present no paediatric intensive care unit (PICU). OBJECTIVE: To perform a population based survey of paediatric mechanical ventilation with the purpose of providing the background for discussions for or against centralization of paediatric intensive care. METHODS: Case records of children 0-14 years treated with mechanical ventilation from January 1996 to December 1998 were retrospectively reviewed and the following data were obtained: Whether or not the child was settled in East Denmark, date of admission, gender, age, underlying chronic condition(s), acute condition(s) leading to mechanical ventilation, duration of positive pressure ventilation, duration of endotracheal intubation, length of stay in ICU, and outcome. Children undergoing mechanical ventilation because of neonatal problems, cardiac surgery or neurosurgery were excluded. RESULTS: Data were obtained from 197 children of which 123 were boys (p < 0.001 for boys vs girls). Median age at admission to ICU was 30 months. Boys were younger than girls (median age 22 vs 41 months, p = 0.01), but as determined by mortality, duration of positive pressure ventilation, intubation and stay in ICU there were no differences between boys and girls with respect to disease course (p > 0.28). Totally, 86 (44%) had at least one underlying chronic condition. The incidence of disease leading to mechanical ventilation in children in East Denmark was estimated to 1.6/10,000/year. An average of 1.1 child was intubated each day. Taking into account the seasonal variation two beds would be required to give coverage for 85% of ICU days needed for paediatric mechanical ventilation while three beds would cover 98%. Children admitted to referral hospital RH more often had underlying chronic conditions and had more severe courses of disease than children admitted to other hospitals (p < 0.001). Mortality did not differ (p = 0.66). CONCLUSION: The number of children requiring mechanical ventilation in East Denmark is too low to provide the background for establishing an independent PICU. However, since paediatric intensive care is a rare and complicated event further centralization of children undergoing mechanical ventilation in East Denmark should be considered.