Etomidate in cardiac surgery - a met analysis

Etomidate is a cardio stable induction agent

1. Etomidate in Cardiac Surgery: A Meta-analysis Dr Gayathri G

2. ETOMIDATE The first report on etomidate was published in 1965 I ntroduced into clinical practice in 1972 The enthusiasm among clinicians for etomidate was tempered in the 1980s by reports that the drug can cause temporary inhibition of steroid synthesis after single doses and infusions.

3. The unique properties of etomidate include He modynamic stability M inimal respiratory depression C erebral protection F avorable toxicity profile P harmacokinetics enabling rapid recovery after either a single dose or a continuous infusion

4. Pharmacokinetics Etomidate is an imidazole derivative E tomidate is metabolized in the liver primarily by ester hydrolysis to metabolites 2% of drug excreted unchanged, the remaining part being excreted as metabolites by the kidney 75% protein bound

5. Pharmacodynamics Etomidate reduces CBF by 34% and CMRO2 by 45% without altering MAP CPP is maintained or increased B eneficial net increase in the cerebral oxygen supply-to-demand ratio. Etomidate has less effect on ventilation than other agents Lack of effect on sympathetic NS and baroreceptors – hemodynamic stability No analgesic efficacy

6. Endocrine effects Dose dependent reversible inhibition of 11 beta hydroxylase – decreased cortisol levels, mineralocorticoid production, increased intermediates Concentration required for adrenal cortical suppression is lower than that for hypnosis

7. Dose Induction – 0.2-0.6 mg/kg IV

8. Side effects PONV P ain on injection M yoclonic movement H iccups. Adrenal insufficiency

9. JCVA MAY 2013

10. M eta-analysis aimed to systematically review the effects of etomidate (ETM) during anesthetic induction on patients undergoing cardiac surgery. Primary outcomes included hemodynamic profiles and stress responses. Secondary outcomes included morbidity, mortality, and postoperative recovery

11. Study quality & risk bias 18 randomized trials 3 triple blinded trials 2 double blinded trials Other 3 – not mentioned Bias – 5 trials high risk, 11 trials unclear risk and 2 low risk

12. Measurements and Main Results Hemodynamics during induction Myoclonus during induction Cortisol levels and adrenal function Catecholamines and postop hemodynamic support Mortality, morbidity and postop recovery

13. Hemodynamics during induction Comparable before anaesthetic induction PCWP higher in ETM grp After induction, ETM patients had lower HR, higher PCWP and higher CI Immediately after induction, ETM patients had higher SBP, MAP, DBP, lower CVP and SVR 4 trials had impaired LVEF, 14 had normal LVEF Meta analysis showed ETM group had less requirement of vasopressor and more NTG use during induction Incidences of new onset MI and arrhythmia were comparable

14. Myoclonus during induction 5 trials - 323 patients had myoclonus Similar to control group

15. Cortisol levels and adrenal function 7 trials reported cortisol levels 5 trials reported V shaped trend curve Intergroup comparison – lower cortisol conc in ETM group intraop and after 24 hrs postop Single dose ETM lowered cortisol levels transiently (30 min after induction to <24 hrs) Metaanalysis – ETM group had higher incidence of transient adrenal insuffiency

16. Catecholamines and postop hemodynamic support Metaanalysis – endogenous concentration of both NA and ADR were similar in both groups preop, post induction, post intubation and intraop ETM exposure was not associated with increased inotrope/vasopressor requirement postop

17. Mortality, morbidity and postop recovery Neither mortality nor morbidity was associated with ETM, except incidence of adrenal insufficiency Comparable MV Days and length of postop ICU stay

18. Conclusion Single dose ETM administered during induction could be associated with more stable hemodynamics, with transient lower cortisol levels and higher adrenal insuffiency incidence but not worse outcomes in cardiac surgical patients

19. Anesthesiology March 2014

20. Anesthesiology March 2014 R etrospectively examined the association between etomidate exposure during anesthetic induction and postoperative outcomes in patients undergoing cardiac surgery Postoperative outcomes of interest were severe hypotension, mechanical ventilation hours, hospital length of stay and in-hospital mortality T here was no evidence to suggest that etomidate exposure was associated with severe hypotension, longer mechanical ventilation hours, longer length of hospital stay or in-hospital mortality.

21. EJA February 2016

22. EJA February 2016 They tested the hypotheses that single-dose etomidate increases cumulative vasopressor requirement, time to extubation and length of stay in the ICU CABG patients were allocated randomly to receive either etomidate with placebo, propofol with placebo or etomidate with hydrocortisone MVS patients received either etomidate or propofol Main outcome measures: Cumulative vasopressor requirements, incidence of adrenocortical insufficiency, length of time to extubation and length of stay in ICU

23. EJA February 2016 Cumulative vasopressor requirements 24 h after induction did not differ between treatments in patients who underwent CABG, whereas more noradrenaline was used in MVS patients following propofol induction The incidence of relative adrenocortical insufficiency was higher after etomidate alone than propofol The time to extubation, length of stay in ICU and 30-day mortality did not differ among treatments. Within low and high-risk subgroups, no differences in vasopressor use or outcomes were found.

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