Ketamine's Hemodynamic Effects - Michael Plewa, MD
Post-intubation hypotension is not uncommon
with all RSI sedation medications [1,2] due to loss of sympathetic tone, positive-pressure ventilation, and reduction in venous return, especially in volume-depleted patients. Post-intubation hypotension is concerning since it has been associated with increased mortality [3,4].
Ketamine in a standard dose of 2 mg/kg [5] is considered a safe agent for RSI in critically ill patients [2,5,6], and ketamine has been shown to result in less hypotension than etomidate [7], midazolam, or propofol [8,9]. Ketamine may maintain hemodynamic stability in some patients by several mechanisms [10], including catecholamine release from direct sympathomimetic stimulation, increased norepinephrine concentrations due to inhibition of neuronal reuptake, and adrenocortical stimulation and increased serum cortisol. For these reasons, ketamine is often recommended for patients with hemodynamic compromise.
In catecholamine-depleted patients, however, ketamine may result in hypotension [11,12,13]. Ketamine has direct negative inotropic effects [14,15] on myocardial tissue and left ventricular stroke work index [13]. Miller et al. noted in their prospective observational cohort of out-of-hospital air ambulance RSI cases, patients getting ketamine with high shock index > 0.9 (N=31) were more likely to become hypotensive (26% vs 2%) than those with normal/low shock index (N=81) [12]. In a small cohort of 12 critically ill patients, Waxman et al. noted 50% had decreased ventricular contractility and one-third had decreased cardiac output or mean arterial pressure with ketamine [13]. Upchurch et al. found a longer duration of vasopressor use in ketamine sedated cases in comparison to etomidate, although there were no significant differences in hospital mortality[16].
Some suggest that ketamine, as with other RSI medications, should be dosed based on ideal rather than actual body weight [11,17], and that the dose be decreased in half to 0.5-1 mg/kg in hypotensive patients [11,18,19]. Lyon et al. showed that RSI with 3 mcg/kg fentanyl, 2 mg/kg ketamine and 1 mg/kg rocuronium provided better laryngoscopic views and higher first-pass intubation success than etomidate and suxamethonium in pre-hospital trauma patients [19]. A lower dose of ketamine 1 mg/kg (and fentanyl 1 mcg/kg) was used in hemodynamic compromise. They noted a higher risk of a transient drop in blood pressure greater than 20% (6% vs 1%) in the fentanyl, ketamine, rocuronium group (however, not a statistically significant difference between fentanyl/ketamine/rocuronium and etomidate/suxamethonium groups), but with only one patient hypotensive < 90 mm Hg in each group.
Clinical Bottom Line: While ketamine is hemodynamically neutral, and sometimes HD-supportive, it can cause hypotension in catecholamine-depleted patients, especially in patients with high shock indices. Dosing based on ideal rather than actual body weight and half-dosing in hypotensive patients can potentially lead to fewer adverse events.
References:
Green R, Hutton B, Lorette J, Bleskie D, McIntyre L, Fergusson D. Incidence of postintubation hemodynamic instability associated with emergent intubations performed outside the operating room: a systematic review. CJEM. 2014 Jan;16(1):69-79.
Smischney N.J., Demirci O., Diedrich D.A. Incidence of and risk factors for post-intubation hypotension in the critically ill. Med Sci Monit. 2016;22:346–355.
Green RS, Butler MB, Erdogan M. Increased mortality in trauma patients who develop postintubation hypotension. J Trauma Acute Care Surg. 2017 Oct;83(4):569-574. PMID: 28930950
Heffner AC, Swords D, Kline JA, et al. The frequency and significance of postinbutaion hypotension during emergency airway management. J Crit Care, 2012; 27:417. E9-13.
Jabre P, Combes X, Lapostelle F, et al. Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial. Lancet, 2009; 374:293-300.
Morris C, Perris A, Klein J, Mahoney P. Anaesthesia in haemodynamically compromised emergency patients: does ketamine represent the best choice of induction agent? Anaesthesia, 2009; 64:532-539.
Van Berkel MA, Exline MC, Cape KM, et al. Increased incidence of clinical hypotension with etomidate compared to ketamine for intubation in septic patients: a propensity matched analysis. J Crit Care, 2017; 38:209-14.
Zuin M, Rigatelli G, Dell’Avvocata F, et al. Ketamine and midazolam differently impact post-intubation hemodynamic profile when used as induction agents during emergency airway management in hemodynamically stable patients with ST elevation myocardial infarction. Heart Vessels, 2018; 33:213-25.
Ishimaru T, Goto T, Takihashi J, et al. Association of ketamine use with lower risks of post-intubation hypotension in hemodynamically-unstable patients in the emergency department.
Lippmann M, Appel PL, Mok, MS, et al. Sequential cardiorespiratory patterns of anesthetic induction with ketamine in critically ill patients. Crit Care Med, 1983; 11:730-734. (septic hypovolemic surgery patients, ketamine did not consistently increase HR or BP)
Merelman AH, Perlmutter MC, Strayer RJ. Alternatives to rapid sequence intubation: contemporary airway management with ketamine. West J Emerg Med, 2019; 20:466-471.
Miller M, Kruit N, Heldreich C, et al. Hemodynamic Response After Rapid Sequence Induction With Ketamine in Out-of-Hospital Patients at Risk of Shock as Defined by the Shock Index. Ann Emerg Med, 2016, 68(2): 181-188.
Waxman K, Shoemaker WC, Lippmann M. Cardiovascular effects of anesthetic induction with ketamine. Anesth Analg, 1980; 59:355-258.
Pagel PS, Kampine JP, Schmeling WT, et al. Ketamine depresses myocardial contractility as evaluated by the preload recruitable stroke work relationship in chronically instrumented dogs with autonomic nervous blockade. Anesthesiology, 1992; 76:564-572.
Gelissen HP, Epema AH, Henning RH, et al. Inotropic effects of propofol, thiopental, midazolam, etomidate, and ketamine on isolated human atrial muscle. Anesthesiology, 1996; 84:397-403.
Upchurch CP, Grijalva CG, Russ S, et al. Comparison of etomidate and ketamine for induction during rapid sequence intubation of adult trauma patients. Ann Emerg Med, 2017; 69:24-33.
Brunette DD. Resuscitation of the morbidly obese patient. Am J Emerg Med, 2004; 22:40-7.
Leeuwenburg T. Airway management of the critically ill patient: modifications of traditional rapid sequence induction and intubation. Crit Care Horizons, 2015; 1:1-10.
Lyon RM, Perkins ZB, Chatterjee D, Lockey DJ, Russell MQ. Significant modification of traditional rapid sequence induction improves safety and effectiveness of pre-hospital trauma anaesthesia. Critical Care, 2015; 19:134.
Dr. Michael Plewa is an attending emergency physician at Mercy St. Vincent Medical Center and is the Research Director of the EM residency program. He has authored numerous peer-reviewed articles on a variety of topics in the field of emergency medicine.
Post edited by: Shyam Murali, MD