7. Niedermeyer E: The EEG signal: Polarity and field determination, Electro- encephalography: Basic Principles, Clinical Applications and Related Fields, 2nd edition. Edited by Niedermeyer E, Lopes da Silva F. Baltimore, Urban and Schwar- zenberg, 1987, pp 79 – 83 8. Bruder N, Velly L, Rey M: A low voltage EEG signal may give low bispectral index values (letter). Anesth Analg 2004; 98:873 9. McGonigal A, Bartolomei F, Re ´gis J, Guye M, Gavaret M, Tre ´buchon-Da Fonseca A, Dufour H, Figarella-Branger D, Girard N, Pe ´ragut JC, Chauvel P: Stereoelectroencephalography in presurgical assessment of MRI-negative epi- lepsy. Brain 2007; 130:3169–83 (Accepted for publication January 3, 2008.) Anesthesiology 2008; 108:965 Copyright © 2008, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. Anticholinesterase Drugs and the Transplanted Heart To the Editor:—I perused with interest the report by Dr. Sawasdi- wipachai et al. 1 detailing bradycardia followed by cardiac arrest in an infant cardiac transplant recipient after intravenous administration of neostigmine– glycopyrrolate. The authors speculate that rejection of the conducting system may have contributed to this response that is considered to be unusual because of the low likelihood of parasympa- thetic reinnervation. Asystole preceded by bradycardia after neostig- mine– glycopyrrolate administration has been described in three adult transplant patients, 2,3 and neostigmine has been shown to produce an atropine-sensitive dose-dependent bradycardia in recent (6 months) and remote (6 months) adult cardiac transplants. 4 Contrary to the authors’ assertion, rejection in these patients was neither confirmed nor refuted. The observation that remote cardiac transplants may demonstrate greater bradycardic responses to neostigmine compared with recent transplants may be explained by weak, variable parasym- pathetic reinnervation and/or by a denervation supersensitivity to the cholinergic agonist effect of neostimine. 4 The influence of rejection on these responses is an intriguing confounding variable that remains to be determined. Regardless of the underlying mechanisms mediating the bradycardia in cardiac transplant patients after anticholinesterase administration, it is clear that caution should be exercised when reversing neuromuscular block even when a muscarinic antagonist is coadministered with the anticholinesterase. To avoid a potentially catastrophic response to neostigmine, the authors suggest avoidance of neuromuscular block if possible, or use of short-acting drugs if paralysis is required. They speculate that this problem may be circum- vented by the use of new reversal agents such as sugammadex. An- other possibility not considered is reversal of neuromuscular block with edrophonium (and of course a muscarinic antagonist!). While edrophonium, too, produces bradycardia in cardiac transplant recipi- ents, the decrease in heart rate is smaller in magnitude and much more consistent compared with neostigmine. 5 Steven B. Backman, M.D.C.M., Ph.D., F.R.C.P.C., Royal Victoria Hospital, McGill University Health Centre, Montreal, Quebec, Canada. steven.backman@muhc.mcgill.ca References 1. Sawasdiwipachai P, Laussen P, McGowan FX, Smoot L, Casta A: Cardiac arrest after neuromuscular blockade reversal in a heart transplant infant. ANES- THESIOLOGY 2007; 107:663–5 2. Bjerke RJ, Mantione MP: Asystole after intravenous neostigmine in a heart transplant recipient. Can J Anesth 2001; 48:305–7 3. Beebe DS, Shumway SJ, Maddock R: Sinus arrest after intravenous neostig- mine in two heart transplant recipients. Anesth Analg 1994; 78:779–82 4. Backman SB, Fox GS, Stein RD, Ralley FE: Neostigmine decreases heart rate in heart transplant patients. Can J Anaesth 1996; 43:373–8 5. Backman SB, Stein RD, Fox GS, Polosa C: Heart rate changes in cardiac transplant patients and in the denervated cat heart after edrophonium. Can J Anaesth 1997; 44:247–54 (Accepted for publication January 30, 2008.) Anesthesiology 2008; 108:965 Copyright © 2008, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. In Reply:—We appreciate Dr. Backman’s thoughtful comments about our article, 1 including discussion of data from his studies in humans and denervated feline hearts, which suggest that edropho- nium may be more predictable and (consistent with its pharmacol- ogy) cause less bradycardia than neostigmine in transplant recipi- ents. He is also correct in noting that denervation hypersensitivity (as well as variable parasympathetic reinnervation) may underlie the bradycardiac effects of neostigmine in some of these patients, although the data that specifically support this mechanism in trans- plant recipients are in our minds relatively modest and indirect. 2,3 We did want to use our case to heighten awareness of the phenom- enon of acute humoral rejection. Although humoral mechanisms have been recognized for some time as an important and patholog- ically distinct form of rejection, potentially useful diagnostic meth- ods and distinct therapies are a more recent development. We also thought this case would be useful to stimulate speculation about the potential interaction of humoral rejection and its consequences with drugs used during an anesthetic; this includes not only anti- cholinergics and anticholinesterases, but also agents that alter myo- cardial contractility. Prasert Sawasdiwipachai, M.D., Peter C. Laussen, M.B.B.S., Leslie Smoot, M.D., Francis X. McGowan, Jr., M.D., Alfonso Casta, M.D.* *Children’s Hospital Boston and Harvard Medical School, Boston, Massachusetts. alfonso.casta@childrens.harvard.edu References 1. Sawasdiwipachai P, Laussen PC, McGowan FX, Smoot L, Casta A: Cardiac arrest after neuromuscular blockade reversal in a heart transplant infant. ANESTHESIOLOGY 2007; 107:663–5 2. Backman SB, Stein RD, Fox GS, Polosa C: Heart rate changes in cardiac transplant patients and in the denervated cat heart after edrophonium. Can J Anaesth 1997; 44:247–54 3. Backman SB, Stein RD, Blank DW, Collier B, Polosa C: Different properties of the bradycardia produced by neostigmine and edrophonium in the cat. Can J Anaesth 1996; 43:731–40 (Accepted for publication January 30, 2008.) 965 CORRESPONDENCE Anesthesiology, V 108, No 5, May 2008 Downloaded from anesthesiology.pubs.asahq.org by guest on 05/27/2020