Bench-to-bedside review: Mechanisms and management of hyperthermia due to toxicity

Abstract

Body temperature can be severely disturbed by drugs capable of altering the balance between heat production and dissipation. If not treated aggressively, these events may become rapidly fatal. Several toxins can induce such non-infection-based temperature disturbances through different underlying mechanisms. The drugs involved in the eruption of these syndromes include sympathomimetics and monoamine oxidase inhibitors, antidopaminergic agents, anticholinergic compounds, serotonergic agents, medicaments with the capability of uncoupling oxidative phosphorylation, inhalation anesthetics, and unspecific agents causing drug fever. Besides centrally disturbed regulation disorders, hyperthermia often results as a consequence of intense skeletal muscle hypermetabolic reaction. This leads mostly to rapidly evolving muscle rigidity, extensive rhabdomyolysis, electrolyte disorders, and renal failure and may be fatal. The goal of treatment is to reduce body core temperature with both symptomatic supportive care, including active cooling, and specific treatment options. IntroductionBody temperature regulation is complex and requires a balance between heat production and dissipation. Hyperthermia occurs when metabolic heat production exceeds heat dissipation. Many exogenously administered drugs are capable of altering the body's ability to maintain a constant temperature.Normal body temperature is approximately 37.0°C, although this varies with the time of day. The Society of Critical Care Medicine has defined fever as a body temperature of ≥38.3°C, which has gained wide acceptance [1]. Adaptive thermogenesis by heat production is controlled through hypothalamic regulation of the sympathetic nervous system [2]. The preoptic nucleus of the anterior hypothalamus responds to core temperature changes and regulates the autonomic nervous system, inducing either cutaneous vasodilatation, which dissipates heat, or vasoconstriction, which conserves heat [3]. Norepinephrine, dopamine and serotonin have all been suggested to play major roles in regulating hypothalamic control of body temperature [4]. Sympathetic nervous system activation contributes to effects on thermogenesis through cutaneous vasoconstriction and nonshivering thermogenesis [5]. Thus, drugs altering the hypothalamic levels of these neurotransmitters are capable of altering body temperature regulation [6]. Activation of the hypothalamic-pituitary-thyroid and the hypothalamic-pituitaryadrenal axes are adjacent mechanisms in regulating body core temperature that can be influenced by drugs that affect them. Nonshivering thermogenesis occurs primarily by uncoupling of oxidative phosphorylation through the activity of a group of mitochondrial proteins known as uncoupling proteins.Uncontrolled hyperthermia is independently associated with increased morbidity and mortality [7]. Hyperthermia may cause rhabdomyolysis, liver failure, disseminated intravasal coagulation and multi-organ failure [8]. It accentuates excitotoxic neurotransmitter release, increases production ...

Dantrolene in the Treatment of Refractory Hyperthermic Conditions in Critical Care: A Multicenter Retrospective Study

“…Several syndromes including malignant hyperthermia (MH), neuroleptic malignant syndrome (NMS), serotonin syndrome, anticholinergic poisoning, heat stroke and sympathomimetic poisoning have been reported to be associated with hyperthermia [1]- [4]. Extreme hyperthermia with temperatures as high as >41˚C have been reported in some syndromes [5] [6].…”

Hyperthermia-induced micronucleus formation in a human keratinocyte cell line

“…Basically all biological structures can be affected by hyper-and hypothermia [2]. Besides experimental hyperthermia treatment in oncology, drug-induced temperature changes can be of clinical relevance [3].…”

Chaleur accablante et santé mentale : vulnérabilité des personnes avec troubles mentaux

“…Le noyau préoptique antérieur de l'hypothalamus régule la température (Cuddy, 2004 ;Eyer et Zilker, 2007 ;Reilly et Kirk, 2007). La dopamine, la norépinephrine, la sérotonine et les récepteurs alphaadrénergiques peuvent être impliqués (Cuddy, 2004).…”

“…La dopamine, la norépinephrine, la sérotonine et les récepteurs alphaadrénergiques peuvent être impliqués (Cuddy, 2004). Les médicaments qui affectent les neurotransmetteurs peuvent donc influencer la thermorégulation (Eyer et Zilker, 2007 ;Reilly et Kirk, 2007), et certains peuvent entraîner de l'hyperthermie maligne, le syndrome neuroleptique malin ou le syndrome de la sérotonine (Reilly et Kirk, 2007). De plus, les médicaments anti-cholinergiques peuvent agir comme inhibiteur de la sudation et mener à la perte des effets refroidissant de l'éva-poration.…”