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Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial. Jabre et al. Lancet 2009; 374: 293-300. Critically Appraised Topic Chris Hawthorne ST4 Anaesthetics Stirling Royal Infirmary September 2009. Aims.
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Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial. Jabre et al. Lancet 2009; 374: 293-300. Critically Appraised Topic Chris Hawthorne ST4 Anaesthetics Stirling Royal Infirmary September 2009
Aims • Present critical appraisal of a recent Lancet publication of a randomised controlled trial comparing etomidate to ketamine in critically ill patients. • Put results into context of Scottish intensive care practice.
Background • French study. • Structure of French emergency medical services is different to that in the UK. • The emergency medical services are ambulance base stations equipped with mobile intensive care units led by a senior physician. • Etomidate is the sedative-hypnotic drug that is most often used for rapid sequence intubation in this context. • Etomidate can cause reversible adrenal insufficiency and may be associated with increased morbidity in critically ill patients. • A possible alternative to etomidate is ketamine, which is not known to inhibit the adrenal axis.
Methods • Patient Selection – over 18 years old and needing sedation for emergency intubation by emergency medical service. • Randomisation – computerised random number generator. • Treatment Groups • Control – Etomidate 0.3mg/kg with suxamethonium 1mg/kg • Study – Ketamine 2mg/kg with suxamethonium 1mg/kg Patients transferred to 1 of 65 ICUs for ongoing care. Does control group represent best practice? • Blinding – the emergency physician was aware of assignment but ICU staff were masked to treatment assigned.
Methods • End Points • Primary – maximum SOFA (sequential organ failure assessment) score during the first 3 days in the intensive care unit. • Secondary – Δ-SOFA score, 28-day all-cause mortality, days free from ICU and organ support free days. How valid is the SOFA score as a surrogate marker of morbidity to compare the effect of etomidate versus ketamine? • Analysis • Modified intention to treat
Trial Profile • Of 655 randomised patients, only 469 were used for analysis. • Was it appropriate to exclude patients who were discharged early or died before reaching hospital?
Trial Conclusions “Our study shows that one etomidate bolus is not associated with a significant increase in morbidity or mortality compared with ketamine in patients admitted to the intensive care unit.” “In conclusion, our results show that ketamine is a safe and valuable alternative to etomidate for intubation in critically ill patients, particularly in septic patients.”
Applicability • Study relates to rapid sequence intubation performed by emergency medical services – not within ICU. • Patient population is unselected critically ill patients – likely to relate to UK ICU practice. • Etomidate would be unlikely to feature in the control arm of a UK ICU trial.
Bottom Line • Flawed study: • not ‘gold standard’ control group • maximum SOFA score in 72 hours is a questionable primary end point • many patients excluded from analysis • However, from this trial it would seem reasonable to choose ketamine over etomidate for rapid sequence intubation by emergency services – no evidence of harm, avoid adrenal suppression. • Unlikely to significantly influence UK ICU practice.