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Total Suppression of Cerebral Activity by Thiopental Mimicking Propofol Infusion Syndrome: A Fatal Common Pathway?

Augoustides, John G. MD; Culp, Kymberley E. MD; Ochroch, Andrew E. MD; Milas, Bonnie L. MD

doi: 10.1213/01.ANE.0000156682.59859.F3
Letters to the Editor: Letters & Announcements

Department of Anesthesia (Cardiothoracic Section), Hospital of the University of Pennsylvania, Philadelphia, PA,

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In Response:

Enting et al. are to be congratulated for their report of a possible “thiopental infusion syndrome” with similar clinical characteristics to the syndrome we recently reported (1). Unfortunately, their patient succumbed to multisystem organ failure. In our case of cardiogenic shock associated with large-dose propofol infusion, the patient survived after institution of extracorporeal circulation and termination of the propofol infusion (1). This syndrome has not been reported in association with thiopental.

As these authors noted, the propofol infusion syndrome has been extensively reviewed in children and adults (2–14). Although the associations of this syndrome have been described, the exact pathogenesis remains to be determined. There is the possibility that this syndrome may be attributable not only to propofol but also to pentothal. Indeed, this syndrome has been described previously in the setting of status epilepticus (15,16). The possibility exists that this syndrome in status epilepticus may be attributable in part to the sedative anticonvulsant regimen. Decell et al. (16) postulate that the hepatic failure in this syndrome may be partly attributable to altered free radical metabolism as a result of the anticonvulsant regimen.

This clinical scenario raises questions such as the following:

  1. Is status epilepticus perhaps unrelated to the development of this syndrome? Is this syndrome more related to the pharmacokinetics of the anticonvulsant regimen (drug choice, total/peak drug dose, duration of infusion)?
  2. What about pharmacodynamic considerations? Why do only a fraction of patients managed in this pharmacologic fashion develop this syndrome? Is there a pharmacologic predisposition that might be predictable pharmacogenomically? Are there genetic polymorphisms that predict for the development of this syndrome?
  3. Is this syndrome related to a drug-related toxic cellular effect in susceptible patients? Could this cellular toxicity be localized to one or more cellular organelles? Are the mitochondria (17–18) part or all of the explanation?
  4. How do various drugs (propofol, thiopental) trigger this syndrome at the cellular level in susceptible patients?
  5. Clearly, our understanding of this clinical syndrome is evolving with respect to etiologic agents, pathogenesis, risk factors, diagnosis, and management. Doctors Enting, Ligtenberg, Aarts, and Zijlstra have advanced our understanding in focusing our attention beyond propofol as the only etiologic agent.

John G. Augoustides, MD

Kymberley E. Culp, MD

Andrew E. Ochroch, MD

Bonnie L. Milas, MD

Department of Anesthesia (Cardiothoracic Section)

Hospital of the University of Pennsylvania

Philadelphia, PA

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© 2005 International Anesthesia Research Society