Determining brain death after therapeutic hypothermia on nonpulsatile continuous-flow mechanical circulatory support devices.

Goswami et al1 described 2 cases of determining brain death (BD) after therapeutic hypothermia (TH) in patients supported on nonpulsatile continuous-flow (NPCF) systemic circulation and extracorporal membrane oxygenation. We comment on TH, sedatives, and NPCF as confounders for reversible inhibition of the central nervous system (CNS) and BD findings. Goswami et al1 performed BD examination at 24 to 48 hours after discontinuing TH and sedatives. TH has unpredictable effects on the pharmacokinetics and pharmacodynamics of drugs acting on the central -aminobutyric acid (GABA) reeptors (eg, benzodiazepines, barbiturates, propofol, and aclofen). These drugs potentiate the GABA inhibitory effects n neurotransmission and depress the CNS-producing reversble neurologic findings. Reversible BD findings have been eported several days after discontinuing TH and sedatives.2-4 Brainstem reflexes returned 96 hours after discontinuing propofol, which could not be predicted from the kinetics of drug clearance.4 Baclofen induced a brain-death-like syndrome that as reversed after 5 to 7 days, which exceeded the recomended waiting time of 5 times the drug’s half-life.5 Plasma learance of the drug might not exclude persistent inhibitory ABA action on the CNS because the drug concentration in rain tissue is not routinely measured. Goswami et al1 performed 2 BD examinations at a 6-hour nterval.1 The optimal timing of the second BD examination after TH is unknown. Joffe et al2 reviewed 12 cases of adult and ediatric cases with BD findings that reversed between 12 ours to several days after the first BD examination.2 Confounding factors were not recognized before the first BD examination (eg, sedatives and TH) and could explain reversible brain death findings in these cases.2,4,6,7 Delaying the second BD examination for several days could eliminate the residual pharmacologic CNS inhibition and reversibility of neurologic findings.2-4 Goswami et al1 reduced the sweep gas flow on extracorporal membrane oxygenation raising acutely the arterial carbon dioxide concentration.1 Inducing acute arterial hypercapnia can have detrimental effects on cerebral perfusion and worsen pre-existing acute neurologic injuries.8,9 Performing the apnea est soon after rewarming to normothermia can result in a alse-positive test and abolish any favorable neurologic outome of TH. Furthermore, the hypercapnic hyperoxic apnea est does not verify irreversible cessation of the medullary espiratory rhythm centers.8 Goswami et al1 determined BD according to the 2010 American Academy of Neurology (AAN) guideline.1 The authors claimed that BD determination complied with the Uniform Determination of Death Act of “irreversible cessation of all functions of the whole brain and the brainstem.”1 However, the AAN assigned the evidence level “U” (ie, insufficient or conflicting data) to several critical elements in BD determination.10 2