Sudden Deaths: A Failure of Feedback Control

Abstract

AbstractObjective: Recent animal work, reviews, and retrospective analysis have identified oxygen conserving reflexes as potentially implicated in types of sudden death, namely sudden unexpected death in epilepsy (SUDEP) and sudden infant death syndrome (SIDS). Here we present a summary of current thinking on the topic, supported by our primary research results.Methods: We present an abbreviated review of the literature on autonomic instability in sudden death, on the reflexes in question, and on how the two may dangerously interact. Specifically, we explore the functions of the mammalian diving reflex, the laryngeal chemoreflex, and the carotid body. We include current theory on feedback, control, and hyperactivation of these reflexes. We include recent animal work in rats which explores reflex activity during seizure, resulting in sudden deaths. We conclude with potential mechanism and therapies which may be able to stop fatal reflex responses.Results: Significant historical data has suggested autonomic instability is related to SIDS and SUDEP. Autonomic instability can be dangerous when both branches of the autonomic nervous system are strongly co-activated, which occurs during certain oxygen conserving reflexes. Human and animal research has suggested for decades that these reflexes may cause sudden deaths. Mammalian diving reflex and laryngeal chemoreflex responses are stronger in infants, and the reflex strength peaks with SIDS risk. Carotid body resection, a now uncommon procedure, caused significant impairments to reflex and respiratory control in both animals and humans, and resulted in a high sudden death mortality. The carotid body is strongly implicated in mammalian diving reflex control.Conclusions: Recent and historical data suggest oxygen conserving reflexes may be causative of some sudden deaths. These mechanisms appear to coalesce around a strong terminal central apnea, a result of a failure of feedback control. Fatal apnea appears to be controlled by the mammalian diving reflex and the carotid body. Methods of feedback control on these pathways may be able to prevent some sudden deaths.KeywordsSudden unexpected death in epilepsy (SUDEP)Sudden infant death syndrome (SIDS)EpilepsySudden deathMammalian diving reflex (MDR)Laryngeal chemoreflex (LCR)Kainic acidGastroesophageal refluxOxygen conserving reflexCarotid bodyLaryngospasmVagus nerveAutonomic instabilityFeedback controlReflex pathway