Critically Appraised Topic Chris Hawthorne ST4 Anaesthetics Stirling Royal Infirmary

1. 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

2. 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.

3. 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.

4. SOFA Score

5. 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.

6. 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

7. 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?

8. Results

9. Results

10. Results

11. 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.”

12. 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.

13. 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.