Hyperthermia

Brief H&P

A young male with unknown medical history is brought in by ambulance with altered mental status. EMS reports that the patient was agitated, requiring restraints for transportation. On arrival, the patient is agitated, uncooperative and unable to provide history. Vital signs are notable for tachycardia, tachypnea and hypertension. Physical examination demonstrates diaphoresis and mydriasis, as well as increased muscle tone – particularly in the lower extremities with ankle clonus. A core temperature is obtained and noted to be elevated at 41.5°C. Point-of-care glucose is normal.

Rapid external cooling measures were instituted and several doses of intravenous benzodiazepines were administered with improvement in agitation. Laboratory studies were notable for a modest leukocytosis (WBC 18.4 without immature forms), serum sodium was 135 without osmolar gap, creatine kinase was slightly elevated without renal dysfunction, and thyroid function tests were normal. Toxicology screen was negative. ECG revealed sinus tachycardia but was otherwise normal and non-contrast computed tomography of the head was normal.

After a brief admission in the intensive care unit, the patient’s mental status improved and he reported MDMA use on the evening of presentation, he also described a history of major depression and was taking paroxetine.

Evaluation of Elevated Temperature

The designation of 38°C as “suspicious” for fever dates to 1868 and the analysis of over one million (axillary) temperature measurements by Carl Wunderlich1. Any cutoff is arbitrary and requires recognition of the clinical context and normal daily variations (with nadir in the morning and peak in evening) 2,3. What is clear is that peripheral thermometry (unless demonstrating fever) is unreliable and a core temperature should be sought4.

Thermoregulation

Temperature homeostasis is a balance between heat production and dissipation maintained by the anterior hypothalamus. Heat production is a byproduct of normal metabolic processes and skeletal muscle activity. Conservation, maintenance or dissipation of heat is aided by cutaneous vasodilation, sweating, or behavioral responses.

Fever is caused by endogenous or exogenous pyrogens which alter the homeostatic set-point, inducing thermogenesis and elevating the body temperature. Precipitants of fever are usually infectious, however non-infectious processes (ex. malignancy, tissue ischemia/infarction, auto-immune disease) resulting in inflammation can provoke a similar response 5-7.

There is no explicit temperature distinction to diagnose hyperthermia, instead the physiologic mechanism is different. In hyperthermia, the body’s homeostatic mechanisms are dysfunctional or overwhelmed due to heat exposure, excess production, ineffective dissipation or hypothalamic malfunction 8.

Algorithm for the Evaluation of Hyperthermia 8-15

Algorithm for the Evaluation of Hyperthermia

Implicated Agents in Drug-Induced Hyperthermic Syndromes 9,10

Serotonin Syndrome

Class Examples
SSRI sertraline, fluoxetine, paroxetine
Other anti-depressants trazodone, venlafaxine, lithium
MAOI phenelzine, isocarboxazid
Anti-epileptic drugs valproate
Analgesics meperidine, fentanyl, tramadol
Anti-emetic ondansetron, metoclopramide
Anti-migraine sumatriptan
Antimicrobial linezolid, ritonavir
Illicit substances MDMA, LSD

Neuroleptic Malignant Syndrome (NMS)

Class Examples
Typical anti-psychotic haloperidol, prochlorperazine
Atypical anti-psychotic risperidone, olanzapine, quetiapine, aripiprazole
Anti-dopaminergic metoclopramide, droperidol

References:

  1. Wunderlich CA. Das Verhalten Der Eigenwärme in Krankheiten. 1870.
  2. Mackowiak PA, Wasserman SS, Levine MM. A critical appraisal of 98.6 degrees F, the upper limit of the normal body temperature, and other legacies of Carl Reinhold August Wunderlich. JAMA. 1992;268(12):1578-1580.
  3. Lee-Chiong TL, Stitt JT. Disorders of temperature regulation. Compr Ther. 1995;21(12):697-704.
  4. Niven DJ, Gaudet JE, Laupland KB, Mrklas KJ, Roberts DJ, Stelfox HT. Accuracy of peripheral thermometers for estimating temperature: a systematic review and meta-analysis. Ann Intern Med. 2015;163(10):768-777. doi:10.7326/M15-1150.
  5. Dinarello CA. Infection, fever, and exogenous and endogenous pyrogens: some concepts have changed. J Endotoxin Res. 2004;10(4):201-222. doi:10.1179/096805104225006129.
  6. Greisman LA, Mackowiak PA. Fever: beneficial and detrimental effects of antipyretics. Curr Opin Infect Dis. 2002;15(3):241-245.
  7. Dinarello CA. Thermoregulation and the pathogenesis of fever. Infect Dis Clin North Am. 1996;10(2):433-449.
  8. Simon HB. Hyperthermia. N Engl J Med. 1993;329(7):483-487. doi:10.1056/NEJM199308123290708.
  9. Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120. doi:10.1056/NEJMra041867.
  10. Berman BD. Neuroleptic malignant syndrome: a review for neurohospitalists. Neurohospitalist. 2011;1(1):41-47. doi:10.1177/1941875210386491.
  11. Hayes BD, Martinez JP, Barrueto F. Drug-induced hyperthermic syndromes: part I. Hyperthermia in overdose. Emerg Med Clin North Am. 2013;31(4):1019-1033. doi:10.1016/j.emc.2013.07.004.
  12. Oruch R, Pryme IF, Engelsen BA, Lund A. Neuroleptic malignant syndrome: an easily overlooked neurologic emergency. Neuropsychiatr Dis Treat. 2017;13:161-175. doi:10.2147/NDT.S118438.
  13. Musselman ME, Saely S. Diagnosis and treatment of drug-induced hyperthermia. Am J Health Syst Pharm. 2013;70(1):34-42. doi:10.2146/ajhp110543.
  14. Ahuja N, Cole AJ. Hyperthermia syndromes in psychiatry. Adv psychiatr treat (Print). 2018;15(03):181-191. doi:10.1192/apt.bp.107.005090.
  15. Tomarken JL, Britt BA. Malignant hyperthermia. Ann Emerg Med. 1987;16(11):1253-1265. doi:10.1016/S0196-0644(87)80235-4.

Altitude and Dysbarism

Altitude Illness

  • Risk factors: altitude, rapidity of ascent, sleeping altitude
  • Pathophysiology
    • Hypobaric hypoxia
      • Pulmonary: vasoconstriction  pulmonary hypertension capillary leak
      • Cerebral: vasodilation edema
    • Acclimatization
      • Hyperventilation primary respiratory alkalosis compensatory metabolic acidosis
      • Acetazolamide promotes renal bicarbonate excretion and accelerates acclimatization
  • Management: oxygen and descent

Acute mountain sickness (2000m)

  • Mild cerebral edema
  • Symptoms: headache, nausea/vomiting, fatigue (hangover)
  • Management: acetazolamide 250mg PO BID, dexamethasone 4mg q6h

High-altitude pulmonary edema (HAPE, 3000m)

  • Non-cardiogenic pulmonary edema
  • Symptoms: dyspnea at rest, cough, fever
  • Signs: hypoxia, crackles
  • CXR: patchy infiltrates
  • Management: nifedipine, PDEi (sildenafil), HBO

High-altitude cerebral edema (HACE, 4500m)

  • Cerebral edema
  • Symptoms: ataxia, altered mental status
  • Management: acetazolamide 250mg PO BID, dexamethasone 10mg then 4mg q6h, HBO
  • Gamow bag: portable HBO

Dysbarism (diving pathology)

  • Principles
    • Boyle’s Law: volume = 1/pressure
      • Volume changes greatest near surface
    • Henry’s Law: increased pressure increases proportion of dissolved gas

Barotrauma

  • Localized (descent)
    • Barotitis media
      • Mechanism: unequal pressure between external and middle ear.
      • Symptoms: pain, vertigo if ruptured
    • Barotitis externa
      • EAC edema/hemorrhage
    • Barotitis interna
      • Bleeding/rupture of round window
      • Symptoms: vertigo, tinnitus, hearing loss
      • Management: ENT referral
    • Sinus squeeze: pain and epistaxis
    • Mask squeeze: periorbital petechiae
  • Localized (ascent)
    • Barodontalgia
      • Air trapped in filling
      • Symptoms: pain, fracture
    • Alternobaric vertigo: Unequal ear pressure causing vertigo
    • GI barotrauma: belching, flatulence
  • Pulmonary overpressurization (ascent)
    • Mechanism: rapid ascent without exhalation, focal alveolar rupture leading to pneumomediastinum, rarely pneumothorax
    • CXR: continuous diaphragm sign
    • Symptoms: dysphonia, neck fullness, chest pain
    • Management: supportive
  • Air gas embolism (ascent)
    • Mechanism: similar to POP, air enters pulmonary venous circulation
    • Symptoms: MI, arrest, stroke, seizure within 10 minutes
    • Management: IVF, oxygen, HBO

Dissolved Gas Problems

  • Nitrogen narcosis
    • At >100ft, nitrogen enters nervous system and acts similarly to general anesthetic
    • Symptoms: similar to alcohol intoxication, complications arise from poor judgement
    • Management: ascent
  • Oxygen toxicity
    • Setting: industrial dives, deep
    • Symptoms: seizure, nausea, muscle twitching
  • Decompression sickness
    • Mechanism: nitrogen gas dissolves poorly in solution, with ascent forms bubbles, occurs 1-2 hours after ascent
    • Types
      • Musculoskeletal, integumentary (“bends”)
        • Symptoms: arthralgia, cutis marmorata
      • Neurological
        • Lower spinal cord (thoracic/lumbar/sacral)
          • Symptoms: paraplegia, paresthesia, bladder dysfunction
        • Cerebellum (“staggers”)
          • Symptoms: ataxia
        • Pulmonary (“chokes”)
          • Symptoms: similar to pulmonary embolus
        • Management: IVF, oxygen, HBO

Bites

Mammalian

  • Human: Eikenella corrodens
  • Dog/Cat: Pasteurella multocida

Athropod

  • Hymenoptra (bee, wasp, hornet, ant)
    • Venom: histamine reaction, anaphylaxis
    • Symptoms
      • Local: pain, swelling, pruritus
      • Toxic (<48h): multiple bits, N/V, syncope, HA
      • Anaphylaxis: minutes
      • Delayed (10-14d): serum sickness, fever, arthralgia, malaise
    • Management
      • Remove stinger
      • Wash, ice, anti-histamine, analgesia
  • Brown recluse (violin pattern)
    • Location: Midwest, wood pile
    • Symptoms: initially painless, cytotoxic venom may cause necrosis
    • Management: supportive, Tdap, delayed debridement if necrotic
  • Black widow (red hourglass)
    • Venom: neurotoxic, ACh, NE
    • Symptoms: painful, erythema, muscle contractions (“acute abdomen”), localized diaphoresis from ACh release
    • Management: analgesia, benzodiazepines, antivenom for refractory pain (may cause anaphylaxis)

Snake

  • Crotalid (rattlesnake, copperhead, cottonmouth, collectively “pit vipers”)
    • Venom: cytotoxic, hemorrhagic
    • Symptoms: erythema/edema (ecchymoisis/bullae), nausea/vomiting, metallic taste
    • Labs: DIC
    • Management
      • Immobilization (no tourniquet)
      • Local wound care, Tdap
      • CBC, INR, fibrinogen (q2h)
      • Antivenom (Crofab 4-6 vials): given until symptoms or laboratory abnormalities arrest
      • Compartment syndrome: avoid surgery
  • Elapidae (coral snake, “red on yellow”)
    • Venom: neurotoxic, delayed 10-12h
    • Symptoms: no significant local reaction, bulbar palsies, respiratory depression
    • Management: no antivenom, supportive care, intubation

Cnidaria (jellyfish)

  • Symptoms: local pain, erythema, pruritus
  • Management: 5% acetic acid, alcohol, remove stinger
    • Antivenom for box jellyfish

Stingray

    • Symptoms: local pain, edema
    • Management: Local wound care, Tdap, hot water immersion, antibiotics for Vibrio (cephalexin with doxycycline)

Vibrio vulnificus

  • Symptoms: necrotizing fasciitis, in cirrhotic primary septicemia after ingesting shellfish

Electrical Injuries

 

Physics

  • High-voltage defined as >1,000V
  • Voltage related to injuries current via resistance (V=IR)
  • AC is 3x more lethal than DC
    • Fluctuation at 60Hz causes tetany, maintained grasp on source

Effects

  • Dysrhythmia
    • DC: asystole
    • AC: ventricular fibrillation
    • Delayed dysrhythmia uncommon
  • Burn
  • Tissue ischemia: vascular spasm or thrombosis
  • CNS: AMS, seizure, ICH, neuropathy
  • MSK: posterior shoulder dislocation

Management

  • Asymptomatic: None
  • Mild (i.e. small burn): ECG, UA (rhabdo)
  • High voltage: Labs, CT, admit for observation
  • Pediatrics: oral commissure burn, discharge with plastic surgery follow-up if no LOC, normal ECG, tolerating PO. Risk of delayed labial artery bleeding.

Complications

  • Keraunoparalysis: current travels up and down lower extremities causing transient paresthesia and paralysis.
  • Trauma: TM rupture, other mechanical injuries

 

Heat Emergencies

Overview

  •  Spectrum
    • Cramps
    • Syncope
    • Exhaustion
    • Stroke
  • Physiology of cooling
    • Radiation: body warmer than environment, heat radiates away
    • Evaporation: environment warmer than body, sweat promotes heat exchange, affected by ambient humidity

Heat cramps

  • Mechanism: fluid/electrolyte depletion resulting in muscle cramps
  • Management: IVF, electrolyte repletion, cooling

Heat syncope

  • Mechanism: vasodilation resulting in hypotension
  • Management: IVF, cooling, rule out alternative etiologies

Heat exhaustion

  • Mechanism: similar to heat cramps
  • Symptoms: influenza-like, headache, fatigue, dizziness, nausea, normal mental status distinguishes from heat stroke
  • Findings: temperature <40°C
  • Management: IVF, cooling

Heat stroke

  • Mechanism: similar to heat cramps
  • Symptoms: prodrome of heat exhaustion
  • Signs: AMS, ataxia, seizure
  • Findings: temperature >40°C
  • Mortality: 30-80%
  • Labs: AST/ALT, coagulopathy, DIC, rhabdomyolysis, ATN/AKI
  • CXR: pulmonary edema
  • Types
    • Classical: elderly, dry skin, mild dehydration, increased mortality
    • Exertional: young athlete, diaphoretic, increased morbidity (organ failure)
  • Management
    • Evaporative cooling
    • Ice packs to large vessels
    • GI lavage
    • Liberal intubation
    • Benzodiazepines or thorazine for inappropriate thermogenesis (shivering)
    • Halt cooling at 40°C

Hypothermia

Overview

  • Risk factors
    • Extremes of age
    • Behavioral: psychosis, intoxication
  • Types
    • Chillblains
    • Immersion foot
    • Frostnip
    • Frostbite
    • Generalized

Hypothermia

Chilblains

  • Findings: red/white plaques on extremities
  • Symptoms: pruritus, pain
  • Management: supportive (gentle warming), topical corticosteroids, consider nifedipine

Immersion foot (trench)

  • Mechanism: prolonged immersion in non-freezing water, vasoconstriction leads to ischemia/necrosis
  • Findings: pale, mottled skin, paresthesia
  • Management: supportive, drying and rewarming
  • Complications: gangrene

Frostnip

  • Retrospective distinction from frostbite after rewarming if no tissue loss

Frostbite

  • Mechanism: extracellular then intracellular crystal formation (mechanistically similar to crush injury)
  • Reperfusion: cellular injury triggers cytokine release upon reperfusion, results in microvascular thrombosis and tissue ischemia/necrosis
  • Classification: grades I-II superficial to dermis, grades III-IV involve subcutaneous tissue to bone
  • Management
    • Rapid rewarming (immersion in warm water at 41°C)
    • Tdap
    • Debridement of clear blisters

Generalized

  • Causes
    • Exposure
    • Metabolic (adrenal, thyroid, hypoglycemia)
    • Sepsis
  • Grading
    • Mild (32.2-35°C)
      • Findings: excitation, tachycardia, hypertension, shivering thermogenesis
    • Moderate (30-32.2°C)
      • Findings: ataxia, AMS, bradycardia, hypotension, bradypnea
      • ECG:  Osborn wave
    • Severe (<30°C)
      • Complications
        • Increased risk of arrhythmia (bradycardia, slow atrial fibrillation, ventricular fibrillation, asystole)
        • Irritable myocardium
        • Decreased enzymatic activity
          • Renal: cold diuresis
          • Heme: coagulopathy (hidden on labs as blood rewarmed prior to testing)
          • Metabolic: hyperglycemia as insulin ineffective
      • Management
        • Ventricular fibrillation: attempt one shock, then focus on rewarming if ineffective
        • Goal >30°C

Radiation Exposure

Physics

  • Units
    • Gray (amount of radiation absorbed by body)
    • Sievert (toxicity associated with radiation exposure)
  • Types
    • Alpha: 0.1mm penetration, injury through ingestion
    • Beta: 1cm penetration, injury through skin or ingestion
    • Gamma: deep penetration
  • Factors
    • Time and distance (1/d2)
    • Shielding
    • Radiosensitive cells (rapidly dividing such as hematopoetic, GI)

Injury

  • Localized: epilation or burns, delayed by days
  • Internal (inhaled, ingestion)
    • Radioactive iodine: high dose results in thyroid ablation, low dose increases risk of thyroid malignancy
  • External: managed by removing clothing, soap/water shower
  • Whole body (gamma)
System Dose Time of onset Signs/Symptoms
Hematopoetic 2G 2d Pancytopenia, increased risk of infection
GI 6G Hours Nausea/vomiting, diarrhea, GI bleeding
CV/CNS 10G Minutes Shock, seizure

Key clinical features

  • Multiple affected individuals with nausea/vomiting suggests radiation exposure
  • Rapidity of onset of symptoms suggests increased dose/exposure
  • LD505G
  • Prognosis by lymphocyte count
    • ALC >1000 at 48h suggests good prognosis
    • ALC <300 at 48h suggests poor prognosis

Submersion Injury

Pathophysiology

  • Breath-holding until eventual involuntary gasp which triggers reflexive laryngospasm. Resultant loss of consciousness may cause laryngeal relaxation and aspiration.
  • Fluid aspiration results in decreased surfactant activity and atelectasis. This is complicated by V/Q mismatch and atelectrauma which can lead to ARDS.

Symptoms

  • Progressive respiratory distress
  • AMS: due to cerebral hypoxia
  • Shock: uncommon, consider trauma

Management

  • Albuterol
  • BiPAP
  • Endotracheal intubation
  • ECMO

Disposition

  • Asymptomatic or minor event: observe 2-3 hours
  • Mildly symptomatic: observe 4-6 hours
  • Hypoxia: admit
  • PPV: ICU