Efficacy, safety and pharmacokinetics of sugammadex 4 mg kg-1 for reversal of deep neuromuscular blockade in patients with severe renal impairment.

BACKGROUND: This study evaluated efficacy and safety of sugammadex 4 mg kg(-1) for deep neuromuscular blockade (NMB) reversal in patients with severe renal impairment (creatinine clearance [CLCR] <30 ml min(-1)) vs those with normal renal function (CLCR ≥80 ml min(-1)). METHODS: Sugammadex 4 mg kg(-1) was administered at 1-2 post-tetanic counts for reversal of rocuronium NMB. Primary efficacy variable was time from sugammadex to recovery to train-of-four (T4/T1) ratio 0.9. Equivalence between groups was demonstrated if two-sided 95% CI for difference in recovery times was within -1 to +1 min interval. Pharmacokinetics of rocuronium and overall safety were assessed. RESULTS: The intent-to-treat group comprised 67 patients (renal n=35; control n=32). Median (95% CI) time from sugammadex to recovery to T4/T1 ratio 0.9 was 3.1 (2.4-4.6) and 1.9 (1.6-2.8) min for renal patients vs controls. Estimated median (95% CI) difference between groups was 1.3 (0.6-2.4) min; thus equivalence bounds were not met. One control patient experienced acceleromyography-determined NMB recurrence, possibly as a result of premature sugammadex (4 mg kg(-1)) administration, with no clinical evidence of NMB recurrence observed. Rocuronium, encapsulated by Sugammadex, was detectable in plasma at day 7 in 6 patients. Bioanalytical data for sugammadex were collected but could not be used for pharmacokinetics. CONCLUSIONS: Sugammadex 4 mg kg(-1) provided rapid reversal of deep rocuronium-induced NMB in renal and control patients. However, considering the prolonged sugammadex-rocuronium complex exposure in patients with severe renal impairment, current safety experience is insufficient to support recommended use of sugammadex in this population. CLINICAL TRIAL REGISTRATION: NCT00702715.

Triage Revised Trauma Score change between first assessment and arrival at the hospital to predict mortality.

OBJECTIVE: To assess among seriously injured accident victims whether change of the Triage Revised Trauma Score (T-RTS) between first assessment and arrival at the hospital independently predicts mortality. DESIGN: Prospective cohort study. METHODS: The study analysed data on 507 trauma patients with multiple injuries and with a Hospital Trauma Index-Injury Severity Score (HTI-ISS) of 16 or higher, who were presented directly by ambulance services to the Accident & Emergency Department of the University Medical Centre Utrecht (the Netherlands) in 1999 and 2000. RESULTS: Compared to non-intubated patients whose T-RTS remained unchanged (reference category), the mortality risk was 3.1 times higher [95% confidence interval (CI): 1.5-6.3, p = 0.001] for patients with deteriorating T-RTS, 2.9 times higher (95% CI: 1.3-6.5, p < 0.001) for patients who had an initially good T-RTS but were nevertheless intubated and 5.7 times higher (95% CI: 3.6-9.0, p < 0.001) for patients who had an initially poor T-RTS and were intubated. These associations were independent of factors that could be assumed to have a direct effect on T-RTS, that is intravenous therapy, oxygen administration and being attended to by a mobile medical team at the scene of the accident. Along with T-RTS change, more advanced age was associated with a higher mortality risk. CONCLUSION: Intubation and a deteriorating T-RTS between the time of the accident and patient's arrival at the hospital are powerful independent predictors of mortality after hospitalisation. Together with advanced age, a deteriorating T-RTS should be the main aspect guiding the preclinical procedures.

[Background and consequences of injuries missed when diagnosing severely injured accident victims in prehospital care in patients transported by ambulance to the University Medical Centre in Utrecht, 1999-2000]. / Achtergronden en gevolgen van het missen van letsels in de ambulancezorg bij ernstig gewonde ongevalspatiënten die vervoerd werden naar het Universitair Medisch Centrum Utrecht, 1999-2000.

OBJECTIVE: To determine the background and consequences of failing to diagnose injuries in prehospital care. DESIGN: Prospective cohort study. METHOD: Data were collected from 507 trauma patients with multiple injuries, and a Hospital trauma index-injury severity score of 16 or higher, who were delivered by the emergency ambulance service to the emergency department of the University Medical Centre Utrecht, the Netherlands, in 1999-2000. RESULTS: The percentage of missed injuries varied from 9-55. For every additional year of age the risk of missing thoracic injuries was 2% higher. The risk of missing head injuries was 84% lower in people with a Triage revised trauma score (T-RTS) < 11. Initially missing an injury had no consequences for duration of stay in the ICU except in those patients with injuries to the lower extremities. A difference in quality of life was only reported for patients in whom injuries ofthe ribs, shoulder or clavicle had been missed. For every year of age, there was a 2% greater risk of dying within 1.5 years. A T-RTS < 11 resulted in a 5.6-fold greater risk of death. Failing to diagnose an injury did not in itself increase the risk of death. CONCLUSION: Frequently missing an injury prior to hospitalization did not result in a poorer chance of survival or lesser quality of life. The risk of dying was mainly related to a higher age and a poorer general condition at the scene of the accident. According to these findings there is no reason to adapt the current policy with regard to initial care and transport of trauma patients.