The role of the central nervous system in heatstroke: Reversible profound depression of cerebral activity in a primate model

Background: The neurological manifestations of heatstroke victims vary. The exact sequence of the central nervous system (CNS) changes during lethal hyperthermia has only been partially explored, and the data covering the post-resuscitation CNS changes, which in most cases lead to secondary cardiac arrest, are insufficient. Hypothesis: Following heating of the organism to cardiopulmonary arrest, successful resuscitation may be achieved by standard cardiopulonary resusitation (CPR), plus glucose and surface cooling. There is a characteristic sequence of neurological responses to hyperthermia preceding cardiopulmonary arrest, and questionable reversibility following successful resuscitation. Methods: We exposed 12 pigtail monkeys under light anesthesia to total body hyperthermia (cerebral T = 42°C) until cardiac arrest. We monitored EEG, mean arterial pressure (MAP), intracranial pressure (ICP), epidural temperatures, PaO₂, PaO₂, serum sodium, osmolality, blood glucose, pupillary diameter, light response, corneal reflex, extremity movement, and seizures. Results: During hyperthermia EEG frequency decreased and amplitude increased, followed by burst suppression pattern of the EEG. Then during severe hypoglycemia, EEG seizure activity and isoelectric EEG occurred when MAP and cerebral perfusion pressure (CPP) decreased while ICP was almost unchanged. Pupils were first responsive to light and became gradually unresponsive with maximal dilation, correlating with low CPP. After temporarily successful cardiopulmonary resuscitation (restoration of spontaneous circulation), normal EEG tracing and reversibility of the unresponsive pupils were observed. As shock led to secondary rearrest, deterioration with depression of all cerebral functions was documented. Some147 min after restoration of spontaneous circulation, brains were macroscopically (and microscopically) normal in six of the eight monkeys. Conclusions: The acute cerebral derangements during and after lethal hyperthermia are reversible. The cause of death is probably not CNS damage, but systemic hemodynamic deterioration.