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CLINICAL APPROACH TO TOXIN-INDUCED HYPERTHERMIA

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Hyperthermia is defined as an increase in body temperature above normal. It develops when the rate of heat production exceeds the rate of heat dissipation. Body temperature above 40 degrees C can be life threatening.

Specific Substances

    1) Hyperpyrexia
    2) Fever
    3) BODY TEMPERATURE, INCREASED
    4) HYPERTHERMIA
    5) INCREASED BODY TEMPERATURE

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) WITH POISONING/EXPOSURE
    1) Toxin-induced hyperthermia may occur in a variety of settings. Patients with hyperthermia secondary to a toxin commonly present with prolonged agitation, muscle rigidity and/or seizures and may also have manifestations of impaired sweating and dehydration. Environmental heat stress (especially with high humidity) and preexisting medical conditions may also contribute. This management will focus on toxin-hyperthermia when the agent responsible is unknown. Refer to the appropriate individual management when the involved toxin is known or suspected.
    2) ANTICHOLINERGIC - Hyperthermia is common in patients with anticholinergic overdose. Other common manifestations include central anticholinergic effects such as confusion, agitation, delirium, hallucinations and seizures, and peripheral effects such as dry mouth and axillae, mydriasis, sinus tachycardia, and urinary retention. The combination of increased heat production from muscular hyperactivity and decreased heat dissipation from decreased sweating may cause hyperthermia. Severe intoxications may result in body temperatures of 40 to 43 degrees C. The peripheral anticholinergic effects and the absence of muscle rigidity differentiates anticholinergic toxicity from other syndromes, such as neuroleptic malignant syndrome or malignant hyperthermia. For further information regarding the clinical effects of anticholinergic poisoning and subsequent treatment, refer to the ANTICHOLINERGIC POISONING management.
    3) SYMPATHOMIMETIC intoxication (amphetamine, methamphetamine, cocaine, etc) may cause severe hyperthermia (greater than 42 degrees C). Severe agitation, combativeness, tachycardia, hypertension, seizures, and dysrhythmias are characteristic. Rhabdomyolysis, renal failure, hepatic injury and coagulopathy may develop in severe cases.
    4) MONOAMINE OXIDASE INHIBITOR - Early manifestations after overdose include tremor, tachycardia, and agitation which may progress to hypertension, muscle rigidity, hyperthermia. Sever effects include hypotension, seizures, respiratory depression, rhabdomyolysis, cardiac arrest. ONSET: Usually 6-12 hrs, may be delayed 24 hrs.
    5) SALICYLATE - Fever is common but severe hyperthermia is not. Tinnitus, N/V, tachypnea, respiratory alkalosis, metabolic acidosis and lethargy are common. Seizures, coma, acute lung injury and coagulopathy may develop with severe poisoning.
    6) STRYCHNINE - Characterized by the rapid onset of muscle spasms or seizures during which the patient remains awake and lucid. Spasms may be precipitated by stimulation and are extremely painful. In severe cases may cause hyperthermia, metabolic acidosis, rhabdomyolysis, and respiratory failure.
    7) NEUROLEPTIC MALIGNANT SYNDROME - Characterized by fever and autonomic dysfunction (tachycardia and hypo or hypertension), movement disorder (rigidity, tremor, myoclonus) and altered mentation following use of neuroleptic drugs or withdrawal of dopamine agonists in patients with Parkinsonism. See Neuroleptic Malignant Syndrome management for details.
    8) SEROTONIN SYNDROME - Hyperthermia, autonomic dysfunction, cognitive and behavioral abnormalities, and neuromuscular effects (tremor, myoclonus, ataxia, hyperactivity) develop usually with combined use of two or more serotonergic agents or after overdose. See Serotonin Syndrome management for more details.
    0.2.3) VITAL SIGNS
    A) WITH POISONING/EXPOSURE
    1) Hyperthermia has been reported following acute exposure with anticholinergic agents, sympathomimetic psychostimulants, hallucinogenic amphetamines, INH overdose, strychnine, salicylate, theophylline overdose, among others. It is particularly likely in patients with prolonged seizures or increased muscle activity.

Laboratory Monitoring

    A) Monitor core temperature. Continuous monitoring with a rectal, esophageal or bladder probe is essential to assess response to therapy. Hyperthermia of 41 degrees C or more is life-threatening and mandates immediate aggressive cooling and sedation.
    B) Monitor blood pressure frequently. Institute continuous cardiac monitoring and pulse oximetry.
    C) Monitor serum glucose, electrolytes (including calcium, magnesium and phosphorus), renal function, hepatic enzymes, UA, CBC, CPK, INR and PTT. Obtain an ABG in patients with metabolic acidosis or hypoxia.
    D) Obtain an ECG.
    E) Monitor urine output.
    F) A drug screen may help elucidate the cause of hyperthermia in some cases (particularly if drugs of abuse are involved).
    G) Insert a central line or pulmonary artery catheter in patients with persistent hypotension to guide resuscitation.
    H) Obtain a chest radiograph in patients with hypoxia or clinical evidence of pneumonia.
    I) Other studies to rule out other etiologies of fever, such as brain or abdominal CT, urine culture, blood culture, lumbar puncture should be performed as clinically indicated.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) HYPERTHERMIA - Core temperatures of 41 degrees or greater are life threatening. Immediate cooling is the highest priority. Place patient in a cool room and remove the patient's clothing. Sponge patient with tepid to cool water, and use fans to maximize evaporative heat loss. Minimize physical activity. Use benzodiazepines to sedate patients who are agitated; large doses may be necessary. While evaporation provides the greatest heat loss, other modalities that may be employed in addition include a hypothermia blanket, intubation and cool air ventilation, and gastric lavage with ice saline. Immersion in ice water should be reserved for patients not responding to evaporative methods as immersion makes monitoring and resuscitation more difficult. Antipyretics such as acetaminophen or salicylates are not effective in reducing the core temperature.
    B) Insert a large bore intravenous line and administer crystalloid 10 to 20 mL/kg in patients with evidence of dehydration.
    C) Endotracheal intubation and mechanical ventilation should be strongly considered in patients with mental status depression.
    D) Once methods to treat hyperthermia are begun and the temperature is dropping, the administration of activated charcoal should be considered if a recent ingestion is suspected as the cause of hyperthermia.
    E) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    F) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT: 5 to 10 mg IV initially; repeat every 5 to 20 minutes as needed. CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed) or LORAZEPAM (ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist. CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue).
    1) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
    2) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.
    G) REFRACTORY SEIZURES - Consider a continuous infusion of midazolam, propofol or pentobarbital in seizures refractory to benzodiazepines and phenobarbital. If INH intoxication is a possibility, administer pyridoxine 5 g IV.
    H) RHABDOMYOLYSIS: Administer sufficient 0.9% saline (10 to 15 mL/kg/hour) to maintain urine output of at least 1 to 2 mL/kg/hour (or greater than 150 to 300 mL/hr). Monitor input and output, serum electrolytes, CK, and renal function. Diuretics may be necessary to maintain urine output, but should only be considered if urine output is inadequate after volume status is restored. Urinary alkalinization is NOT routinely recommended.
    I) CYPROHEPTADINE - If serotonin syndrome is suspected administer cyproheptadine. Begin with 12 mg orally in adults, repeat in 30 minutes if necessary, followed by 4 to 8 mg every 4 to 6 hours if symptoms persist.

Range Of Toxicity

    A) Because of the numerous agents that may be associated with toxin-induced hyperthermia, a minimum toxic dose cannot be delineated. Coadministration of multiple agents that increase heat production and/or decrease heat loss, environmental heat stress, and underlying medical conditions may combine to increase the propensity to develop hyperthermia. A core body temperature of 41 degrees C or more may produce life threatening effects and should be treated aggressively.

Clinical Effects

Summary Of Exposure

    A) WITH POISONING/EXPOSURE
    1) Toxin-induced hyperthermia may occur in a variety of settings. Patients with hyperthermia secondary to a toxin commonly present with prolonged agitation, muscle rigidity and/or seizures and may also have manifestations of impaired sweating and dehydration. Environmental heat stress (especially with high humidity) and preexisting medical conditions may also contribute. This management will focus on toxin-hyperthermia when the agent responsible is unknown. Refer to the appropriate individual management when the involved toxin is known or suspected.
    2) ANTICHOLINERGIC - Hyperthermia is common in patients with anticholinergic overdose. Other common manifestations include central anticholinergic effects such as confusion, agitation, delirium, hallucinations and seizures, and peripheral effects such as dry mouth and axillae, mydriasis, sinus tachycardia, and urinary retention. The combination of increased heat production from muscular hyperactivity and decreased heat dissipation from decreased sweating may cause hyperthermia. Severe intoxications may result in body temperatures of 40 to 43 degrees C. The peripheral anticholinergic effects and the absence of muscle rigidity differentiates anticholinergic toxicity from other syndromes, such as neuroleptic malignant syndrome or malignant hyperthermia. For further information regarding the clinical effects of anticholinergic poisoning and subsequent treatment, refer to the ANTICHOLINERGIC POISONING management.
    3) SYMPATHOMIMETIC intoxication (amphetamine, methamphetamine, cocaine, etc) may cause severe hyperthermia (greater than 42 degrees C). Severe agitation, combativeness, tachycardia, hypertension, seizures, and dysrhythmias are characteristic. Rhabdomyolysis, renal failure, hepatic injury and coagulopathy may develop in severe cases.
    4) MONOAMINE OXIDASE INHIBITOR - Early manifestations after overdose include tremor, tachycardia, and agitation which may progress to hypertension, muscle rigidity, hyperthermia. Sever effects include hypotension, seizures, respiratory depression, rhabdomyolysis, cardiac arrest. ONSET: Usually 6-12 hrs, may be delayed 24 hrs.
    5) SALICYLATE - Fever is common but severe hyperthermia is not. Tinnitus, N/V, tachypnea, respiratory alkalosis, metabolic acidosis and lethargy are common. Seizures, coma, acute lung injury and coagulopathy may develop with severe poisoning.
    6) STRYCHNINE - Characterized by the rapid onset of muscle spasms or seizures during which the patient remains awake and lucid. Spasms may be precipitated by stimulation and are extremely painful. In severe cases may cause hyperthermia, metabolic acidosis, rhabdomyolysis, and respiratory failure.
    7) NEUROLEPTIC MALIGNANT SYNDROME - Characterized by fever and autonomic dysfunction (tachycardia and hypo or hypertension), movement disorder (rigidity, tremor, myoclonus) and altered mentation following use of neuroleptic drugs or withdrawal of dopamine agonists in patients with Parkinsonism. See Neuroleptic Malignant Syndrome management for details.
    8) SEROTONIN SYNDROME - Hyperthermia, autonomic dysfunction, cognitive and behavioral abnormalities, and neuromuscular effects (tremor, myoclonus, ataxia, hyperactivity) develop usually with combined use of two or more serotonergic agents or after overdose. See Serotonin Syndrome management for more details.

Vital Signs

    3.3.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Hyperthermia has been reported following acute exposure with anticholinergic agents, sympathomimetic psychostimulants, hallucinogenic amphetamines, INH overdose, strychnine, salicylate, theophylline overdose, among others. It is particularly likely in patients with prolonged seizures or increased muscle activity.
    3.3.3) TEMPERATURE
    A) WITH POISONING/EXPOSURE
    1) ANTICHOLINERGIC AGENTS
    a) Hyperthermia, observed with anticholinergic toxicity, is caused by both central and peripheral muscarinic receptor blockade and typically results from the combination of heat production by increased muscle activity and the inability to lose heat through diaphoretic mechanisms. Because children have a more immature thermoregulatory mechanism than adults, they are more likely to develop hyperthermia following anticholinergic intoxication (Halloran & Bernard, 2004; Chan et al, 1997; Di Rosa et al, 1995).
    1) CASE REPORT - A 23-year-old female presented with extreme hyperpyrexia (peak temperature of 41.3 degrees C), as well as pupil dilation, tachycardia, hot and dry skin, and perioral cyanosis after administration of 0.4 mg scopolamine intramuscularly (Torline, 1992).
    2) CASE REPORT (CHILD) - A 6-month-old female developed seizures, hyperpyrexia, pupil dilation, hyperreflexia, and diminished bowel sounds after being given a scopolamine-like compound to control diarrhea. Signs and symptoms resolved 48 hours later following supportive treatment (Banner, 1983).
    b) Hyperthermia has been reported following anticholinergic plant ingestions (Coremans et al, 1994; Hanna et al, 1992; Pereira & Nishioka, 1994; Rauber-Luthy et al, 1999; Isbister et al, 2003) and may be life-threatening, particularly in children in warm climates. About 18.1% of patients exposed to Jimson weed in one study had elevated temperatures (O'Grady et al, 1983).
    c) Hyperthermia has been reported in tricyclic antidepressant overdose, usually in patients with recurrent seizures or increased muscular activity (Hantson et al, 1994; Tribble et al, 1989; Crome & Newman, 1979; Greenblatt et al, 1974; Fouron & Chicoine, 1971; Giles, 1963). Other manifestations include CNS depression, tachycardia, hypotension and widened QRS complexes.
    1) CASE REPORT - A 17-year-old male taking 4.5 mg/kg of desipramine daily for one year had a single episode of hyperthermia following 2 hours of strenuous exercise. His core temperature rose to 108 degrees F (Squires, 1992).
    2) SYMPATHOMIMETIC STIMULANTS
    a) AMPHETAMINE/METHAMPHETAMINE
    1) Severe hyperthermia may develop after amphetamine and methamphetamine use (Wallace & Squires, 2000; Kolecki, 1998; Chan et al, 1994; Katsumata et al, 1993; Ginsberg et al, 1970). Hyperthermia may result from hypothalamic dysfunction, metabolic and muscle hyperactivity, or prolonged seizures.
    a) Severe hyperthermia (greater than 41 degrees C) is associated with a high fatality rate and requires aggressive sedation and cooling (Lan et al, 1998).
    b) CASE REPORT - A rectal temperature of 45 degrees C (113 degrees F) was reported in a young male after ingesting 1 gram ("body stuffing") of methamphetamine during a police altercation, in which the individual fled the scene on foot and was chased, eventually requiring physical restraint (Suchard & Saba, 1999). Following aggressive cooling therapy and supportive care, the patient made a complete recovery.
    c) CASE REPORTS - Twin 3-year-old boys developed increased temperatures of 38 to 39 degrees C approximately 30 minutes after an accidental pemoline ingestion. They were found playing with an empty container which originally contained 59 tablets (Stork & Cantor, 1997).
    b) HALLUCINOGENIC AMPHETAMINES
    1) Hyperthermia occurs in severe cases of hallucinogenic amphetamine intoxication (Watson et al, 1993; Singarajah & Lavies, 1992; Woods & Henry, 1992; Russell et al, 1992; Brown et al, 1986; Ginsberg et al, 1970).
    a) Hyperthermia may be life-threatening and has been contributory to death (James & Dinan, 1998; Iwersen & Schmoldt, 1996; Dar & McBrien, 1996). Core temperatures above 42 degrees C may develop, and indicate a need for aggressive cooling measures and control of agitation (Tehan et al, 1993; Logan et al, 1993; Campkin & Davies, 1992; Henry et al, 1992; Screaton et al, 1992; Chadwick et al, 1991).
    b) INCIDENCE/FATALITY - In a retrospective chart review of 191 cases of 3,4-methylenedioxymethamphetamine (MDMA) exposure, 7 cases developed hyperthermia with 1 death associated with hyperthermia (Rella et al, 2000).
    c) CASE REPORT/MDEA - Core body temperature was 42.5 degrees C in a young man exposed to methylenedioxyethylamphetamine (MDEA) following an ingestion at home. Hyperthermia was believed to be contributory to death (Iwersen & Schmoldt, 1996).
    d) CASE SERIES/PMA - Paramethoxyamphetamine (PMA), a methoxylated phenethylamine derivative that is structurally related to MDMA, produced severe hyperthermia in young adults; of the six cases reported, all resulted in death (Felgate et al, 1998).
    c) COCAINE
    1) HYPERTHERMIA is common and life-threatening and may be due to increased muscular activity, vasoconstriction, and perhaps a direct effect on the hypothalamus (Tanen et al, 2000; Wetli et al, 1996) Ritcxhie & Greene, 1980; (Wetli & Fishbain, 1985; Bauwens et al, 1989). It is often associated with rhabdomyolysis, seizures, and renal failure (Saleem et al, 2001; Lombard et al, 1988) Menashe & Gottleib, 1988; (Merigian & Roberts, 1987; Bauwens et al, 1989; Hoffman et al, 1992; Merigian et al, 1994).
    a) A small randomized double blind study (n=7 healthy, cocaine-naive volunteers) found that low doses of cocaine (2 mg/kg intranasally) augmented the esophageal temperature and impaired vasodilation and sweating in response to heat stress compared with lidocaine used as a control. Cocaine also attenuated the discomfort perceived by the subjects associated with heat stress. The mechanism is not fully understood, but it was speculated that cocaine-induced shifts in the threshold for cutaneous vasodilation and sweating are mediated centrally. In this study, cocaine appeared to impair the perception of heat stress, which may be evidence that cocaine acts centrally to alter thermoregulatory responses (Crandall et al, 2002).
    b) These findings were challenged based on the small experimental dose of cocaine used, which was not considered representative of the psychomotor agitation that is often seen in patients with cocaine toxicity (Schier et al, 2002).
    c) Cocaine potentiates dopaminergic neurotransmission in the basal ganglia, thus participating in the regulation of core body temperature leading to hyperthermia (Callaway & Clark, 1994).
    d) PHENCYCLIDINE
    1) Common manifestations of phencyclidine poisoning include nystagmus (57.4%), hypertension (57%), acute brain syndrome (36.9%), violent/agitated/bizarre behavior (28.8 to 35.4%), tachycardia (30%), and hallucinations/delusions (18.5%) (McCarron et al, 1981b; McCarron et al, 1981a). Other manifestations that develop in 2 to 12% of patients include hyperthermia, mutism/staring, coma, lethargy, generalized rigidity, mydriasis (6.2% in adults), diaphoresis, seizures (3.1% in adults, up to 21% in children), apnea, urinary retention, localized dystonias, bronchospasm, and miosis (2.1% in adults, 75 to 100% in children) (McCarron et al, 1981b; McCarron et al, 1981a)
    3) ISONIAZID
    a) Hyperthermia develops in patients with protracted seizures after INH overdose (Shah et al, 1995). Nausea, vomiting, diarrhea and tachycardia are manifestations of mild poisoning. Severe poisoning is characterized by protracted seizures, coma, severe acidosis, hyperthermia, respiratory depression, tachypnea, rhabdomyolysis, renal failure, abnormal reflexes.
    4) MONOAMINE OXIDASE INHIBITOR
    a) Hyperthermia is common in patients with monoamine oxidase inhibitor overdose (Meredith & Vale, 1985). Other manifestations include tremor, tachycardia, agitation early on which may progress to hypertension and muscle rigidity. In severe cases hypotension, seizures, respiratory depression, rhabdomyolysis may develop.
    5) SALICYLATE
    a) Patients with salicylate poisoning often develop fever but severe hyperthermia is unusual. Other manifestations include nausea and vomiting, abdominal pain, tinnitus, metabolic acidosis, respiratory alkalosis and dehydration. In severe cases coma, seizures, coagulopathy, and acute lung injury may develop.
    6) STRYCHNINE
    a) Hyperthermia may develop after strychnine poisoning in patients with neuromuscular hyperactivity, particularly those with severe or prolonged seizures (Oberpaur et al, 1999; Boyd et al, 1983; Dittrich et al, 1984). Typically patients develop painful muscle spasms or seizures shortly after exposure. Spasms are often precipitated by stimulation. The patient remains awake and lucid despite repetitive spasms. Prolonged seizures may cause metabolic and respiratory acidosis, rhabdomyolysis, and renal failure (Shadnia et al, 2004; Flood, 1999).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) TACHYARRHYTHMIA
    1) WITH POISONING/EXPOSURE
    a) SYMPATHOMIMETIC AGENTS
    1) Most patients with hyperthermia of any etiology will also manifest tachycardia. Tachycardia may be particularly severe in patients with anticholinergic or sympathomimetic overdose (Banner, 1983; Goldfrank et al, 1982).
    2) CASE REPORT - A 21-year-old female presented to the ED with tachycardia (130 bpm), flushing, hypertension (150/85 mmHg), abdominal cramping, and a rectal temperature of 100.9 degrees F approximately 45 minutes after ingesting 140 mcg of clenbuterol hydrochloride. The patient gradually recovered following decontamination with activated charcoal (Cortes-Belen et al, 1998).
    B) HYPERTENSIVE DISORDER
    1) WITH POISONING/EXPOSURE
    a) Mild hypertension is fairly common in patients with anticholinergic poisoning (Banner, 1983; Goldfrank et al, 1982). More severe hypertension may develop after sympathomimetic overdose (Havlik & Nolte, 2000; Van der Woude, 2000; June et al, 2000).
    C) CONDUCTION DISORDER OF THE HEART
    1) WITH POISONING/EXPOSURE
    a) Ventricular dysrhythmias may develop with severe sympathomimetic overdose (Halloran & Bernard, 2004; Chan et al, 1997) and with cocaine overdose, possibly as a result of sodium channel blockade (Lange & Hillis, 2001; Havlik & Nolte, 2000; Merigian et al, 1994; Anon, 1979).
    b) Tachycardia with widened QRS complexes occur with severe tricyclic antidepressant overdose and have been reported less often with severe anticholinergic overdose (Frank & Kierdorf, 2000; Danze & Langdorf, 1991).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) DELIRIUM
    1) WITH POISONING/EXPOSURE
    a) Anticholinergic poisoning frequently causes an agitated delirium, in which the patient is restless and agitated and often appears to be having visual hallucinations (Banner, 1983; Goldfrank et al, 1982).
    B) PSYCHOMOTOR AGITATION
    1) WITH POISONING/EXPOSURE
    a) Patients with sympathomimetic poisoning are often agitated and combative. Many also manifest paranoid delusions. Patients with phencyclidine poisoning may be particularly violent (Halloran & Bernard, 2004; Chan et al, 1997; McCarron et al, 1981a).
    C) SEIZURE
    1) WITH POISONING/EXPOSURE
    a) Any agent that causes prolonged seizures can cause hyperthermia secondary to sustained muscular activity. Recurrent seizures that are resistent to anticonvulsant are typical of INH overdose (Shah et al, 1995; Blowey et al, 1995) and may also occur with theophylline overdose (Shannon, 1997). Strychnine causes repetitive seizures or muscle spasms during which the patient is awake and lucid (Shadnia et al, 2004; Flood, 1999). Seizures may also occur with severe sympathomimetic or anticholinergic overdose (Halloran & Bernard, 2004; Chan et al, 1997; Tehan et al, 1993; Rosenberg et al, 1986).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) HEPATIC NECROSIS
    1) WITH POISONING/EXPOSURE
    a) Hepatic injury is common after severe hyperthermia of any etiology. It may be particularly common in the setting of severe sympathomimetic overdose (Halloran & Bernard, 2004; Chan et al, 1997).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) RETENTION OF URINE
    1) WITH POISONING/EXPOSURE
    a) Urinary retention is a common finding in patients with anticholinergic poisoning (Banner, 1983; Goldfrank et al, 1982)
    B) ACUTE RENAL FAILURE SYNDROME
    1) WITH POISONING/EXPOSURE
    a) SYMPATHOMIMETIC STIMULANTS
    1) Severe agitation or prolonged seizures that result in hyperthermia also commonly cause severe rhabdomyolysis, which may cause acute renal failure. While this may from any overdose causing rhabdomyolysis, it appears to be particularly common with sympathomimetic overdose (Halloran & Bernard, 2004; Chan et al, 1997).
    2) CASE REPORT - A 21-year-old male ingested approximately 2.2 g of amphetamine sulfate in a suicide attempt. One hour after ingestion the patient became agitated, hyperkinetic, and incoherent. Rectal temperature reached 108.4 degrees F with a blood pressure of 160/80 mmHg and a pulse of 168 bpm and regular.
    a) Treatment with gastric lavage, chlorpromazine, pentobarbital, diuretics, and fluids were initiated. Following chlorpromazine therapy, the patient became hypotensive, somnolent, and obtunded. Subsequently, he developed coagulopathy with intramuscular hemorrhages producing entrapment neuropathies and acute renal failure. Hemodialysis was initiated and the patient recovered (Ginsberg et al, 1970).

Acid-Base

    3.11.2) CLINICAL EFFECTS
    A) METABOLIC ACIDOSIS
    1) WITH POISONING/EXPOSURE
    a) Most agents which cause hyperthermia can also cause metabolic acidosis, either from prolonged agitation (stimulants, anticholinergics) or refractory seizures (INH, theophylline, strychnine) (Halloran & Bernard, 2004; Chan et al, 1997).
    b) Salicylates commonly cause mild metabolic acidosis with respiratory alkalosis. Severe acidemia is common with INH overdose(Panganiban et al, 2001).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) DISSEMINATED INTRAVASCULAR COAGULATION
    1) WITH POISONING/EXPOSURE
    a) Severe hyperthermia of any etiology may cause coagulopathy. This appears to be particularly common after sympathomimetic poisoning (Halloran & Bernard, 2004; Chan et al, 1997)

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) DRY SKIN
    1) WITH POISONING/EXPOSURE
    a) ANTICHOLINERGIC AGENTS - Dry, flushed skin with absent axillary sweat is characteristic of anticholinergic poisoning (Banner, 1983; Goldfrank et al, 1982)

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) RHABDOMYOLYSIS
    1) WITH POISONING/EXPOSURE
    a) Any agent that causes hyperthermia secondary to severe agitation or repetitive seizures can cause rhabdomyolysis (Halloran & Bernard, 2004; Chan et al, 1997).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor core temperature. Continuous monitoring with a rectal, esophageal or bladder probe is essential to assess response to therapy. Hyperthermia of 41 degrees C or more is life-threatening and mandates immediate aggressive cooling and sedation.
    B) Monitor blood pressure frequently. Institute continuous cardiac monitoring and pulse oximetry.
    C) Monitor serum glucose, electrolytes (including calcium, magnesium and phosphorus), renal function, hepatic enzymes, UA, CBC, CPK, INR and PTT. Obtain an ABG in patients with metabolic acidosis or hypoxia.
    D) Obtain an ECG.
    E) Monitor urine output.
    F) A drug screen may help elucidate the cause of hyperthermia in some cases (particularly if drugs of abuse are involved).
    G) Insert a central line or pulmonary artery catheter in patients with persistent hypotension to guide resuscitation.
    H) Obtain a chest radiograph in patients with hypoxia or clinical evidence of pneumonia.
    I) Other studies to rule out other etiologies of fever, such as brain or abdominal CT, urine culture, blood culture, lumbar puncture should be performed as clinically indicated.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients with severe hyperthermia and systemic complications (coagulopathy, acidosis, acute renal failure) should be admitted to an intensive care setting.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a nephrologist to discuss hemodialysis if renal function is worsening despite standard supportive measures.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Selected patients with mild hyperthermia without systemic effects may be observed for 6 to 8 hours in the emergency department and discharged if hyperthermia has resolved, other vital signs are normal, and laboratory evaluation is normal.

Monitoring

    A) Monitor core temperature. Continuous monitoring with a rectal, esophageal or bladder probe is essential to assess response to therapy. Hyperthermia of 41 degrees C or more is life-threatening and mandates immediate aggressive cooling and sedation.
    B) Monitor blood pressure frequently. Institute continuous cardiac monitoring and pulse oximetry.
    C) Monitor serum glucose, electrolytes (including calcium, magnesium and phosphorus), renal function, hepatic enzymes, UA, CBC, CPK, INR and PTT. Obtain an ABG in patients with metabolic acidosis or hypoxia.
    D) Obtain an ECG.
    E) Monitor urine output.
    F) A drug screen may help elucidate the cause of hyperthermia in some cases (particularly if drugs of abuse are involved).
    G) Insert a central line or pulmonary artery catheter in patients with persistent hypotension to guide resuscitation.
    H) Obtain a chest radiograph in patients with hypoxia or clinical evidence of pneumonia.
    I) Other studies to rule out other etiologies of fever, such as brain or abdominal CT, urine culture, blood culture, lumbar puncture should be performed as clinically indicated.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) If a recent ingestion is suspected as the cause of hyperthermia administer activated charcoal AFTER methods to treat hyperthermia have been started and the temperature is dropping.
    B) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) MONITORING OF PATIENT
    1) Monitor core temperature; use a continuously reading rectal probe to monitor the response to therapy.
    B) BODY TEMPERATURE ABOVE REFERENCE RANGE
    1) Core temperature of 41 40 degrees C or more is life-threatening and indicates the need for aggressive cooling and sedation.
    2) Place patient in a cool room and remove their clothing.
    3) Sponge patient repeatedly with tepid to cool water, and aim fans to blow air over the patient's skin maximize evaporative heat loss.
    4) Evaporative cooling is generally rapidly effective in lowering temperature. Other methods that may be used in addition include hypothermia blanket, endotracheal intubation with cool air ventilation, and gastric lavage with iced saline.
    5) Immersion in iced water should be reserved for patients not responding to evaporative cooling, as it makes monitoring and resuscitation of the patient more difficult.
    C) INTUBATION
    1) Aggressive airway management is important in any patient with CNS depression. Perform endotracheal intubation and initiate mechanical ventilation as needed.
    D) DEHYDRATION
    1) Most patients with hyperthermia have some degree of dehydration. Insert a large bore intravenous catheter and administer 10 to 20 milliliters per kilogram of intravenous 0.9% saline. Further fluid therapy may be needed and should be guided by patients vital signs, urine output, physical exam, and CVP.
    E) SEDATION
    1) Control agitation and neuromuscular activity as these will contribute to ongoing hyperthermia. Intravenous benzodiazepines are the preferred drugs (Diazepam: Adults: 5 to 10 milligrams IV repeat every 5 to 10 minutes as needed; Children: 0.1 to 0.3 milligram/kilogram IV repeat every 5 to 10 minutes as needed. Lorazepam: Adults: 2 to 4 milligrams IV repeat every 5 to 10 minutes as needed; Children: 0.05 to 0.1 milligram/kilogram IV repeat every 5 to 10 minutes as needed). Phenothiazines, butyrophenones and antihistamines should be avoided as they interfere with heat loss. Minimize the use of physical restraints, as continued struggling with worsen hyperthermia.
    F) SEIZURE
    1) Treat seizures aggressively as continued seizures worsen hyperthermia.
    2) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    3) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    4) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    5) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2010; Chin et al, 2008).
    6) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    7) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
    8) RECURRING SEIZURES
    a) If seizures are not controlled by the above measures, patients will require endotracheal intubation, mechanical ventilation, continuous EEG monitoring, a continuous infusion of an anticonvulsant, and may require neuromuscular paralysis and vasopressor support. Consider continuous infusions of the following agents:
    1) MIDAZOLAM: ADULT DOSE: An initial dose of 0.2 mg/kg slow bolus, at an infusion rate of 2 mg/minute; maintenance doses of 0.05 to 2 mg/kg/hour continuous infusion dosing, titrated to EEG (Brophy et al, 2012). PEDIATRIC DOSE: 0.1 to 0.3 mg/kg followed by a continuous infusion starting at 1 mcg/kg/minute, titrated upwards every 5 minutes as needed (Loddenkemper & Goodkin, 2011).
    2) PROPOFOL: ADULT DOSE: Start at 20 mcg/kg/min with 1 to 2 mg/kg loading dose; maintenance doses of 30 to 200 mcg/kg/minute continuous infusion dosing, titrated to EEG; caution with high doses greater than 80 mcg/kg/minute in adults for extended periods of time (ie, longer than 48 hours) (Brophy et al, 2012); PEDIATRIC DOSE: IV loading dose of up to 2 mg/kg; maintenance doses of 2 to 5 mg/kg/hour may be used in older adolescents; avoid doses of 5 mg/kg/hour over prolonged periods because of propofol infusion syndrome (Loddenkemper & Goodkin, 2011); caution with high doses greater than 65 mcg/kg/min in children for extended periods of time; contraindicated in small children (Brophy et al, 2012).
    3) PENTOBARBITAL: ADULT DOSE: A loading dose of 5 to 15 mg/kg at an infusion rate of 50 mg/minute or lower; may administer additional 5 to 10 mg/kg. Maintenance dose of 0.5 to 5 mg/kg/hour continuous infusion dosing, titrated to EEG (Brophy et al, 2012). PEDIATRIC DOSE: A loading dose of 3 to 15 mg/kg followed by a maintenance dose of 1 to 5 mg/kg/hour (Loddenkemper & Goodkin, 2011).
    4) THIOPENTAL: ADULT DOSE: 2 to 7 mg/kg, at an infusion rate of 50 mg/minute or lower. Maintenance dose of 0.5 to 5 mg/kg/hour continuous infusing dosing, titrated to EEG (Brophy et al, 2012)
    b) Endotracheal intubation, mechanical ventilation, and vasopressors will be required (Brophy et al, 2012) and consultation with a neurologist is strongly advised.
    c) Neuromuscular paralysis (eg, rocuronium bromide, a short-acting nondepolarizing agent) may be required to avoid hyperthermia, severe acidosis, and rhabdomyolysis. If rhabdomyolysis is possible, avoid succinylcholine chloride, because of the risk of hyperkalemic-induced cardiac dysrhythmias. Continuous EEG monitoring is mandatory if neuromuscular paralysis is used (Manno, 2003).
    9) If INH overdose is a possibility in a patient with recurrent seizures or coma and acidosis, administer pyridoxine 5 grams IV.
    G) RHABDOMYOLYSIS
    1) SUMMARY: Early aggressive fluid replacement is the mainstay of therapy and may help prevent renal insufficiency. Diuretics such as mannitol or furosemide may be added if necessary to maintain urine output but only after volume status has been restored as hypovolemia will increase renal tubular damage. Urinary alkalinization is NOT routinely recommended.
    2) Initial treatment should be directed towards controlling acute metabolic disturbances such as hyperkalemia, hyperthermia, and hypovolemia. Control seizures, agitation, and muscle contractions (Erdman & Dart, 2004).
    3) FLUID REPLACEMENT: Early and aggressive fluid replacement is the mainstay of therapy to prevent renal failure. Vigorous fluid replacement with 0.9% saline (10 to 15 mL/kg/hour) is necessary even if there is no evidence of dehydration. Several liters of fluid may be needed within the first 24 hours (Walter & Catenacci, 2008; Camp, 2009; Huerta-Alardin et al, 2005; Criddle, 2003; Polderman, 2004). Hypovolemia, increased insensible losses, and third spacing of fluid commonly increase fluid requirements. Strive to maintain a urine output of at least 1 to 2 mL/kg/hour (or greater than 150 to 300 mL/hour) (Walter & Catenacci, 2008; Camp, 2009; Erdman & Dart, 2004; Criddle, 2003). To maintain a urine output this high, 500 to 1000 mL of fluid per hour may be required (Criddle, 2003). Monitor fluid input and urine output, plus insensible losses. Monitor for evidence of fluid overload and compartment syndrome; monitor serum electrolytes, CK, and renal function tests.
    4) DIURETICS: Diuretics (eg, mannitol or furosemide) may be needed to ensure adequate urine output and to prevent acute renal failure when used in combination with aggressive fluid therapy. Loop diuretics increase tubular flow and decrease deposition of myoglobin. These agents should be used only after volume status has been restored, as hypovolemia will increase renal tubular damage. If the patient is maintaining adequate urine output, loop diuretics are not necessary (Vanholder et al, 2000).
    5) URINARY ALKALINIZATION: Alkalinization of the urine is not routinely recommended, as it has never been documented to reduce nephrotoxicity, and may cause complications such as hypocalcemia and hypokalemia (Walter & Catenacci, 2008; Huerta-Alardin et al, 2005; Brown et al, 2004; Polderman, 2004). Retrospective studies have failed to demonstrate any clinical benefit from the use of urinary alkalinization (Brown et al, 2004; Polderman, 2004; Homsi et al, 1997).
    H) CYPROHEPTADINE
    1) If serotonin syndrome is suspected as the cause of hyperthermia, administer cyproheptadine. A reasonable initial dose in an adult is 12 milligrams orally; repeat in 30 minutes if necessary. Subsequent doses are 4 to 8 milligrams every 4 to 6 hour if needed for persistent symptoms.

Range Of Toxicity

Summary

    A) Because of the numerous agents that may be associated with toxin-induced hyperthermia, a minimum toxic dose cannot be delineated. Coadministration of multiple agents that increase heat production and/or decrease heat loss, environmental heat stress, and underlying medical conditions may combine to increase the propensity to develop hyperthermia. A core body temperature of 41 degrees C or more may produce life threatening effects and should be treated aggressively.

Pharmacology Toxicology

Toxicologic Mechanism

    A) Drug-induced hyperthermia may be due to either increased heat production or interference of heat dissipation.
    B) Increased muscular activity (agitation, rigidity, myoclonus, seizures) results in increased heat production. Drugs and chemicals that uncouple oxidative phosphorylation induce metabolic hyperactivity that increases heat production.
    C) Drugs or conditions that decrease sweating (anticholinergics, phenothiazines, dehydration) and those that cause cutaneous vasoconstriction (sympathomimetics) impair the ability of the body to dissipate heat (Rosenberg et al, 1986).
    D) Other drugs or conditions may impair a patients ability to respond appropriately to increased environmental heat (ethanol, advanced age, poverty, medical or psychiatric illness) placing them at increased risk of environmental heat stroke.

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