Hyperthermia Syndromes
1) Malignant Hyperthermia
2) Neuroleptic Malignant Syndrome
3) Sympathomimetic Poioning
4) Anticholinergic Poisoning
5) Serotonin Syndrome
Thermal Homeostasis
Production
BMR 1 - 1.5 Kcal/kg/hr
Increase production 10 - 20 times if muscular exertion, stress
Elimination
radiation
convection
conduction
evaporation
these mechanisms of elimination are decreased in hot, humid environments
Thermoregulatory control
central control center in pre-optic area of anterior hypothalamus
peripheral temperature sensors
Mechanisms of Drug-Induced Hyperthermia
- Increased heat production via increased metabolism
Beta stimulation
Increased physical activity
Agitation, restlessness
Physical restraints
Seizures
Anticholinergics impair sweating
Altered central thermoregulation
Decreased central dopaminergic activity (neuroleptics)
Increased central serotonergic activity (SSRI's)
Consequences of Hyperthermia
Mortality directly proportional to temperature elevation with cocaine or amphetamines
Heat cramps or heat exhaustion if mild
Heat stroke (elevated temp with neurologic dysfunction) has 10% mortality
Rhabdomyolysis with renal failure
Coagulopathy
Acute hepatic failure, heart failure
General Treatment
ABC's
Check chemstrip
Sedate to decrease heat production if agitated
benzodiazepines most reliable, may require large doses
barbituates and propafol as second line
avoid haldol as this in itself can alter central thermoregulation
Intravenous crystalloids to replace volume losses
Cooling
ice water immersion not practical
cooling blanket
ice packs on groins, axillae
tepid water mist on skin plus fan to increase evaporative losses
Continuous monitoring of rectal or bladder temperature
No role for antipyretics
Malignant Hyperthermia
- Triad of hyperthermia, muscle rigidity, and metabolic acidosis
- Occurs in genetically susceptible individuals (both autosomal dominant and recessive inheritance patterns)
- Triggered by general anaesthetics (volatile gases, succinylcholine)
- Hypermetabolic state induced in skeletal muscle
- Mortality decreased from 90% to 7 % with appropriate treatment
- Muscle biopsies can be used to test for susceptibility
- Disordered calcium regulation in skeletal muscle fibres may play a role in the pathophysiology of MH. There is decreased ability to retain and regulate calcium in the sarcoplasmic reticulum.
Increased intacellular calcium may lead to excessive and prolonged muscle contraction with resulting excessive heat production
Increased calcium also uncouples oxidative phosphorylation
MH is resistant to neuromuscular blockers
Dantrolene is a direct skeletal muscle relaxant which blocks calcium release from the sarcoplasmic reticulum
Dose is 2 mg/kg iv q5min until resolution
Procainamide has similar action to dantrolene and is the drug of choice for MH associated dysrhythmias
Neuroleptic Malignant Syndrome
an idiosyncratic reaction to certain medications characterized by muscle rididity, hyperthermia, autonomic instability, and altered mental status
mortality rate 10%
since many non-neuroleptic medications can cause NMS, some have proposed that the name be changed to "drug-induced central hyperthermic syndrome"
Pathophysiology most likely includes on acute alterations and reduction of central dopaminergic activity
Many drugs that induce NMS can antagonize dopamine receptors (D2) or lower synaptic dopamine concentrations
NMS has been described in Parkinson's patients when their dopamine agonist meds are acutely withdrawn
Idiosyncratic - not related to dose or duration
Dopamine blocakade in hypothalamus alters central thermoregulation
Dopamine hypoactivity in basal ganglia leads to muscle hyperrigidity with resultant increased heat production
Dopamine blockade in central mesolimbic regions could explain altered mental status
Dopamine blockade at level of spinal cord could result in dysautonomia and altered sympathetic tone
The hyperthermia results from heat generated by excessive muscle acivity which may be augmented by altered central thermoregulation
Diagnostic Criterea
treatment of neuroleptics within 7 days (4 weeks with depot meds)
hyperthermia greater than 38 C
Muscle rigidity
Exclusion of other drug-induced, systemic, or neuropsychiatric illnesses
And five of the following ; altered mental status, tachycardia, hypotension, tachypnea or hypoxia, diaphoresis, tremor, incontinance, elevated CPK or myoglobinuria, metabolic acidosis, leukocytosis
Clinical manifestations
Hyperthermia (38 - 42 C) - may be delayed
Muscle rigidity
Autonomic instability
Differential Diagnosis
Lethal catatonia -
Serotonin syndrome
Dystonic syndromes - respond rapidly to anticholinergics
Malignant Hyperthermia
Treatment
Remove/discontinue offending drug
Respiratory support, IV rehydration, Monitoring, and basic supportive care
Aggressive standard therapy to lower temperature
Bromocriptine - increases central dopamine activity
Dantrolene or neuromuscular blockers to directly relax muscle rigidity