What causes hyperthermia in a patient with severe hyponatremia?

Hyperthermia in Severe Hyponatremia: Causes and Clinical Approach

In a patient with critically low sodium, hyperthermia is most commonly caused by infection (pneumonia, UTI, sepsis), but drug-induced hyperthermia—particularly neuroleptic malignant syndrome or serotonin syndrome—must be urgently excluded, as these require immediate discontinuation of the offending agent and specific treatment. 1, 2, 3

Primary Causes to Investigate

Infectious Etiologies (Most Common)

• Infection is the most frequent precipitating factor for both hyperthermia and hyponatremia in hospitalized patients, with pneumonia, urinary tract infection, and sepsis being the leading causes 1
• Patients can be normothermic or even hypothermic despite infection due to peripheral vasodilation, and hypothermia when present is a poor prognostic sign 1
• Approximately one-third of patients admitted with acute illness will be hyperthermic (temperature >37.6°C) within the first hours, and hyperthermia is associated with poor neurological outcomes due to increased metabolic demands 1

Drug-Induced Hyperthermia Syndromes (Critical to Exclude)

• Neuroleptic malignant syndrome (NMS) should be suspected if the patient is on antipsychotics like haloperidol, with a lag time averaging 21 days but possible at any point 2, 3
• NMS presents with hyperthermia, muscle rigidity, altered mental status, and autonomic dysfunction, requiring immediate discontinuation of the offending agent 2, 3
• Serotonin syndrome occurs with serotonergic medications (SSRIs, MAOIs), presenting with hyperthermia, agitation, hyperreflexia, and clonus 3
• Malignant hyperthermia is triggered by volatile anesthetics or succinylcholine in susceptible patients, with the earliest sign being increased end-tidal CO2 before temperature elevation 1, 4
• The timing of malignant hyperthermia reactions is highly variable, becoming apparent within 10 minutes to several hours after exposure to triggering agents 1, 4

Hyponatremia-Related Complications

• Exercise-associated hyponatremia with exertional heat illness can present with both hyperthermia and hyponatremia from overhydration during physical activity 5
• Severe hyponatremia itself causes altered mental status, seizures, and coma, which may be mistaken for heat-related illness 5
• The combination of hyponatremia and hyperthermia significantly increases mortality risk, with sodium levels <130 mmol/L linked to a 60-fold increase in fatality 6

Diagnostic Algorithm

Immediate Assessment Steps

1. Obtain medication history to identify potential causative agents (antipsychotics, serotonergic drugs, anesthetics) 2, 3
2. Perform infectious workup including complete blood count, urinalysis, chest X-ray, blood cultures, and urine cultures 1
3. Check creatine kinase to assess for rhabdomyolysis from drug-induced hyperthermia or severe hyponatremia 1, 2
4. Assess volume status through physical examination (orthostatic hypotension, dry mucous membranes, skin turgor, edema, ascites) to guide hyponatremia management 6, 7

Distinguishing Features by Syndrome

• NMS: Muscle rigidity, elevated CK, autonomic instability, history of antipsychotic use 2, 3
• Serotonin syndrome: Hyperreflexia, clonus, agitation, recent serotonergic medication changes 3
• Malignant hyperthermia: Increased end-tidal CO2, tachycardia, muscle rigidity, recent anesthesia exposure 1, 4
• Infection: Localizing symptoms, elevated white blood cell count, positive cultures 1

Management Priorities

For Drug-Induced Hyperthermia

• Immediately discontinue the suspected offending agent—this is the definitive treatment for drug-induced hyperthermia 2, 3
• For NMS, consider benzodiazepines for agitation and muscle activity, and manage hyperthermia with external cooling measures 2
• For malignant hyperthermia, eliminate triggering agents, administer dantrolene sodium, commence active body cooling, and increase minute ventilation 2-3 times normal 4
• Treat dehydration and elevated creatine kinase with IV fluids to prevent renal failure from rhabdomyolysis 2

For Infection-Related Hyperthermia

• Initiate appropriate antimicrobial therapy based on suspected source 1
• Implement measures to achieve normothermia, including both pharmacological (acetaminophen, ibuprofen) and mechanical interventions 1
• Hyperthermia increases metabolic demands and worsens neurological outcomes, making temperature control essential 1

Concurrent Hyponatremia Management

• For severe symptomatic hyponatremia (seizures, altered mental status), administer 3% hypertonic saline with a target correction of 6 mmol/L over 6 hours, but total correction must not exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 6, 7, 8
• Treatment approach depends on volume status: hypovolemic hyponatremia requires isotonic saline, euvolemic hyponatremia requires fluid restriction, and hypervolemic hyponatremia requires fluid restriction with management of underlying condition 6, 7, 8
• Monitor serum sodium every 2 hours during initial correction for severe symptoms 6

Critical Pitfalls to Avoid

• Do not assume fever is always infectious in origin when a patient is on haloperidol or other antipsychotics—consider drug-induced causes early 2
• Do not continue haloperidol or other suspected causative agents if drug-induced hyperthermia is suspected—discontinuation is the definitive treatment 2, 3
• Do not correct chronic hyponatremia faster than 8 mmol/L in 24 hours—overcorrection risks osmotic demyelination syndrome, which can cause parkinsonism, quadriparesis, or death 6, 7
• Do not delay treatment of severely symptomatic hyponatremia while pursuing a diagnosis—this is a medical emergency requiring immediate hypertonic saline 7, 8
• Do not overlook the possibility of exercise-associated hyponatremia in patients with recent physical exertion—symptoms can mimic heat exhaustion or heat stroke 5