Journal of Cardiothoracic and Vascular Anesthesia
Volume 25, Issue 3 , Pages 581-582, June 2011

Reducing Post-Cardiopulmonary Bypass Delirium: More Ketamine or Less Etomidate?

published online 23 August 2010.

Article Outline

 

To the Editor:

We read with great interest the study performed by Hudetz et al1 showing that a single dose of ketamine on induction of anesthesia significantly reduced the incidence of delirium after cardiac surgery with cardiopulmonary bypass (CPB). Randomly assigned patients received either 0.5 mg/kg of ketamine or placebo 1 hour before surgery. Induction was performed using fentanyl and 0.2 to 0.5 mg/kg of etomidate in all patients, followed by a muscle relaxant and inhalation and fentanyl maintenance of anesthesia.

We wonder if a confounding variable in this study was the use of etomidate as the induction agent. Etomidate is widely acknowledged to inhibit adrenal steroidogenesis,2 principally through blockade of the enzyme 11β-hydroxylase in the cortisol production pathway; even a single dose potentially resulting in the development of relative adrenal insufficiency for at least 24 hours after its administration.3, 4, 5, 6, 7

The normal physiologic response to surgery includes cortisol release, perhaps dampening the inflammatory response to surgery and CPB. Postoperative cortisol levels usually are raised sufficiently to inhibit the release of interleukin-1 and interleukin-6 and, in turn, C-reactive protein (CRP).8 Although most drugs and techniques used in anesthesia blunt the stress response to surgery, etomidate causes a prolonged reduction in postoperative cortisol levels, conferring a proinflammatory effect, which may be important in limiting the systemic inflammatory response syndrome (SIRS)/multiorgan dysfunction syndrome (MODS) associated with CPB.9

Using ketamine an hour before surgery may have had a sparing effect on the dose of etomidate required for the induction of anesthesia, reducing the steroid suppressant effect in the ketamine versus the placebo group, and may contribute to the relative differences in the CRPs measured 1 day after surgery; and perhaps also in the development of postoperative delirium, assuming that an inflammatory process is indeed involved in the CPB-associated neurologic injury.

In our hospital, etomidate is rarely (if ever) used now for routine cardiac cases because of this concern. We have found thiopental, propofol, or benzodiazepines to be suitable alternatives. Postoperative delirium is still a problem, however, and we look forward to seeing further work in this area.

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References 

  1. Hudetz JA, Patterson KM, Iqbal Z, et al. Ketamine attenuates delirium after cardiac surgery with cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 2009;23:651–657
  2. Wagner RL, White PF, Kan PB, et al. Inhibition of adrenal steroidogenesis by the anesthetic etomidate. N Eng J Med. 1984;310:1415–1421
  3. Preziosi P, Vacca M. Adrenocortical suppression and other endocrine effects of etomidate. Life Sci. 1988;42:477–489
  4. Lundy JB, Slane ML, Frizzi JD. Acute adrenal insufficiency after a single dose of etomidate. J Intensive Care Med. 2007;22:111–117
  5. Mohammad Z, Afessa B, Finkielman JD, et al. The incidence of relative adrenal insufficiency in patients with septic shock after the administration of etomidate. Crit Care. 2006;10:R105
  6. Annane A. ICU physicians should abandon the use of etomidate!. Intensive Care Medicine. 2005;31:325–326
  7. Malerba G, Romano-Girard F, Cravoisy A, et al. Risk factors of relative adrenocortical deficiency in intensive care patients needing mechanical ventilation. Intensive Care Med. 2005;31:388–392
  8. Desborough JP. The stress response to trauma and surgery. Br J Anaesth. 2000;85:109–117
  9. Khabar KS, elBarbary MA, Khouqeer F. Circulating endotoxin and cytokines after cardiopulmonary bypass: Differential correlation with duration of bypass and systemic inflammatory response/multiple organ dysfunction syndromes. Clin Immunol Immunopathol. 1997;85:97–103

PII: S1053-0770(10)00271-5

doi:10.1053/j.jvca.2010.06.020

Refers to article:

  • Ketamine Attenuates Delirium After Cardiac Surgery With Cardiopulmonary Bypass , 23 February 2009

    Judith A. Hudetz, Kathleen M. Patterson, Zafar Iqbal, Sweeta D. Gandhi, Alison J. Byrne, Anthony G. Hudetz, David C. Warltier, Paul S. Pagel
    Journal of Cardiothoracic and Vascular Anesthesia October 2009 (Vol. 23, Issue 5, Pages 651-657)

Journal of Cardiothoracic and Vascular Anesthesia
Volume 25, Issue 3 , Pages 581-582, June 2011

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