Ketamine use for endotracheal intubation in severe sepsis and septic shock

Objective. We conducted this study to evaluate the clinical outcomes of patients with severe sepsis and septic shock who were treated with ketamine for endotra-cheal intubation.

Methods. A single-center, retrospective study was carried out to compare the out-comes of patients with severe sepsis and septic shock who received a ketamine or non-ketamine agent for rapid sequence intubation (RSI). We analyzed the sepsis registry for adult patients who presented to the emergency department (ED), met the criteria for severe sepsis or septic shock, and underwent endotracheal intubation between August 2008 and March 2014. The primary outcome was 28-day mortal-ity. We performed a multivariable logistic regression analysis to assess the association between ketamine use for intubation and 28-day mortality.

Results. In all, 170 patients were intubated during the study period. Of the eligible patients, 95 received ketamine and 75 re-ceived a non-ketamine agent. The 28-day mortality of the ketamine group was not significantly different from that of the non-ketamine group (38% vs. 40%, respectively, P=0.78). The unadjusted odds ratio (OR) of ketamine use for 28-day mortality was 0.92 (95% CI: 0.49–1.70, P=0.78). The as-sociation remained insignificant after ad-justing for age, gender, malignancy, initial lactate level on ED admission, time to first antibiotic administration, Acute Physiolo-gy and Chronic Health Evaluation II score on admission day, and propensity score re-garding ketamine use (adjusted OR: 1.09; 95% confidence interval [CI]: 0.49–2.40;P=0.84). Initial serum lactate on ED ad-mission was the only significant predictive factor of 28-day mortality (adjusted OR: 1.23; 95% CI: 1.10–1.38; P<0.01). Conclusions. For patients with severe sep-sis and septic shock who were intubated using RSI, we found no significant differ-ence in 28-day mortality between those who received ketamine as a sedative agent and those who received alternative seda-tives.

sepsis, ketamine, intubation, mortality  

1. Annane D, Vignon P, Renault A, Bollaert PE, Charpentier C, Martin C, et al. Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial. Lancet 2007;370(9588):676-84.

2. Sakles JC, Mosier J, Patanwala AE, Dicken J. Learning curves for direct laryngoscopy and GlideScope(R) video laryngoscopy in an emergency medicine residency. Simul Healthc 2014;9(6):377-83. doi: 10.1097/SIH.0000000000000057.

3. ProCESS Investigators. A Randomized Trial of Protocol-Based Care for Early Septic Shock. N Engl J Med . 2014;370(18):1683-93.

4. Mouncey PR, Osborn TM, Power GS, Harrison DA, Sadique MZ, Grieve RD, et al. Trial of Early, Goal-Directed Resuscitation for Septic Shock. N Engl J Med 2015;372(14):1301-11.

5. Caironi P, Tognoni G, Masson S, Fumagalli R, Pesenti A, Romero M, et al. Albumin Replacement in Patients with Severe Sepsis or Septic Shock. N Engl J Med 2014;370(15):1412-21.

6. Li J, Murphy-Lavoie H, Bugas C, Martinez J, Preston C. Complications of emergency intubation with and without paralysis. Am J Emerg Med 1999;17(2):141-3.

7. Sagarin MJ, Barton ED, Chng YM, Walls RM. Airway management by US and Canadian emergency medicine residents: a multi-center analysis of more than 6,000 endotracheal intubation attempts. Ann Emerg Med. 2005;46(4):328-36.

8. Mohammad Z, Afessa B, Finkielman JD. The incidence of relative adrenal insufficiency in patients with septic shock after the ad-ministration of etomidate. Crit Care 2006;10(4):R105.

9. Pai A, Heining M. Ketamine. Continuing Education in Anaesthesia, Critical Care & Pain. 2007;7(2):59-63.

10. Jabre P, Combes X, Lapostolle F, Dhaouadi M, Ricard-Hibon A, Vivien B, et al. Etomidate versus ketamine for rapid sequence intu-bation in acutely ill patients: a multicentre randomised controlled trial. Lancet 2009;374(9686):293-300.

11. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physi-cians/Society of Critical Care Medicine. Chest 1992;101(6):1644-55.

12. Shin TG, Jo IJ, Choi DJ, Kang MJ, Jeon K, Suh GY, et al. The adverse effect of emergency department crowding on compliance with the resuscitation bundle in the management of severe sepsis and septic shock. Crit Care 2013;17(5):R224.

13. Kang MJ, Shin TG, Jo IJ, Jeon K, Suh GY, Sim MS, et al. Factors influencing compliance with early resuscitation bundle in the man-agement of severe sepsis and septic shock. Shock (Augusta, Ga) 2012;38(5):474-9.

14. Hwang SY, Shin TG, Jo IJ, Jeon K, Suh GY, Lee TR, et al. Association between hemodynamic presentation and outcome in sepsis patients. Shock (Augusta, Ga) 2014;42(3):205-10.

15. Patanwala AE, McKinney CB, Erstad BL, Sakles JC. Retrospective analysis of etomidate versus ketamine for first-pass intubation success in an academic emergency department. Acad Emerg Med 2014;21(1):87-91.

16. Ballow SL, Kaups KL, Anderson S, Chang M. A standardized rapid sequence intubation protocol facilitates airway management in critically injured patients. J Trauma Acute Care Surg 2012;73(6):1401-5.

17. Price B, Arthur AO, Brunko M, Frantz P, Dickson JO, Judge T, et al. Hemodynamic consequences of ketamine vs etomidate for endotracheal intubation in the air medical setting. Am J Emerg Med 2013;31(7):1124-32.

18. Dewhirst E, Frazier WJ, Leder M, Fraser DD, Tobias JD. Cardiac arrest following ketamine administration for rapid sequence in-tubation. J Intensive Care Med 2013;28(6):375-9.

19. Chang Y, Chen TL, Sheu JR, Chen RM. Suppressive effects of ketamine on macrophage functions. Toxicol Appl Pharmacol 2005;204(1):27-35.

20. Wu GJ, Chen TL, Ueng YF, Chen RM. Ketamine inhibits tumor necrosis factor-alpha and interleukin-6 gene expressions in lipopol-ysaccharide-stimulated macrophages through suppression of toll-like receptor 4-mediated c-Jun N-terminal kinase phosphoryla-tion and activator protein-1 activation. Toxicol Appl Pharmacol 2008;228(1):105-13.

21. Roytblat L, Talmor D, Rachinsky M, Greemberg L, Pekar A, Appelbaum A, et al. Ketamine attenuates the interleukin-6 response after cardiopulmonary bypass. Anesth Analg 1998;87(2):266-71.

22. Zilberstein G, Levy R, Rachinsky M, Fisher A, Greemberg L, Shapira Y, et al. Ketamine attenuates neutrophil activation after car-diopulmonary bypass. Anesth Analg 2002;95(3):531-6, table of contents.

23. Shapiro NI, Howell MD, Talmor D, Nathanson LA, Lisbon A, Wolfe RE, et al. Serum lactate as a predictor of mortality in emer-gency department patients with infection. Ann Emerg Med 2005;45(5):524-8.

24. Jones AE, Shapiro NI, Trzeciak S, Arnold RC, Claremont HA, Kline JA. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA . 2010;303(8):739-46.

25. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Intensive Care Med 2013;41(2):580-637.

26. Puskarich MA, Trzeciak S, Shapiro NI, Heffner AC, Kline JA, Jones AE. Outcomes of patients undergoing early sepsis resuscitation for cryptic shock compared with overt shock. Resuscitation 2011;82(10):1289-93.

27. Casserly B, Phillips GS, Schorr C, Dellinger RP, Townsend SR, Osborn TM, et al. Lactate measurements in sepsis-induced tissue hypoperfusion: results from the Surviving Sepsis Campaign database. Crit Care Med 2015;43(3):567-73