Updated review of postmortem biochemical exploration of hypothermia with a presentation of standard strategy of sampling and analyses

Abstract

Hypothermia is defined as a core body temperature below 35°C and can be caused by environmental exposure, drug intoxication, metabolic or nervous system dysfunction. This lethal pathology with medico-legal implications is complex to diagnose because macroscopic and microscopic lesions observed at the autopsy and the histological analysis are suggestive but not pathognomonic. Postmortem biochemical explorations have been progressively developed through the study of several biomarkers to improve the diagnosis decision cluster. Here, we present an updated review with novel biomarkers (such as catecholamines O-methylated metabolites, thrombomodulin and the cardiac oxyhemoglobin ratio) as well as some propositional interpretative postmortem thresholds and, to the best of our knowledge, for the first time, we present the most adapted strategy of sampling and analyses to identify biomarkers of hypothermia. For our consideration, the most relevant identified biomarkers are urinary catecholamines and their O-methylated metabolites, urinary free cortisol, blood cortisol, as well as blood, vitreous humor and pericardial fluid for ketone bodies and blood free fatty acids. These biomarkers are increased in response either to cold-mediated stress or to bioenergetics ketogenesis crisis and significantly contribute to the diagnosis by exclusion of death by hypothermia.

Cortisol levels after cold exposure are independent of adrenocorticotropic hormone stimulation

“…The half-life of hormones may also differ in the cell culture models and in humans. Furthermore, it is necessary to examine differences between human cortisol and mouse corticosterone and address problems associated with temperature setting in the cell culture model [94].…”

“…Many reports have documented the pathologic changes observed in human affected by hypothermia due to cold exposure, and "classic" morphologic findings supporting a diagnosis of hypothermia have been established [1][2][3][4][5][6][7]. However, as other etiologies of hypothermia include drug abuse, dementia, malnutrition, and infectious disease, only a few studies have specifically examined pathologic findings after cold exposure [8,9], especially from a biochemical perspective, such as the presence and levels of ketone bodies [10][11][12][13]. Furthermore, only a few reports have estimated hormone levels as part of the pathophysiologic findings of cold exposure [14][15][16].…”

Biomarkers of Cerebral Damage in Fatal Hypothermia

“…Hypothermia is a condition characterized by a decrease in body temperature to below 35 degrees and occurs when the loss of heat within an organism is greater than its production (1). Potentially fatal hypothermia develops insidiously and compromises numerous physiological functions, including neuromuscular, cardiovascular, and respiratory functions.…”

Cortisol levels after cold exposure are independent of adrenocorticotropic hormone stimulation

“…The half-life of hormones may also differ in the cell culture models and in humans. Furthermore, it is necessary to examine differences between human cortisol and mouse corticosterone and address problems associated with temperature settings in the cell culture model [61].…”

“…Many reports have documented the pathologic changes observed in humans affected by hypothermia due to cold exposure, and “classic” morphologic findings supporting a diagnosis of hypothermia have been established [1-7]. However, as other etiologies of hypothermia include drug abuse, dementia, malnutrition, and infectious disease, only a few studies have specifically examined pathologic findings after cold exposure [8,9], especially from a biochemical perspective, such as the presence and levels of ketone bodies [10-13]. Furthermore, only a few reports have estimated hormone levels as part of the pathophysiologic findings of cold exposure [14-16].…”