What can cause hypothermia, hypertension, bradycardia, altered mental status, and lactic acidosis?

Metformin-Associated Lactic Acidosis (MALA)

The constellation of hypothermia, hypertension, bradycardia, altered mental status, and lactic acidosis is most characteristically caused by metformin-associated lactic acidosis (MALA), particularly in patients with renal impairment or other predisposing conditions. 1

Primary Diagnosis: Metformin Toxicity

Metformin carries an FDA Black Box Warning specifically for lactic acidosis that can result in death, hypothermia, hypotension (though hypertension can occur initially), and resistant bradyarrhythmias. 1 The key risk factors include:

• Renal impairment with eGFR <30 mL/min 1
• Age ≥65 years 1
• Hypoxic states including acute heart failure 1
• Hepatic impairment 1
• Concomitant use of carbonic anhydrase inhibitors 1
• Excessive alcohol intake 1

Clinical Presentation Pattern

The specific combination you describe follows a recognized pattern:

• Altered mental status progressing from confusion to coma occurs as core temperature drops below 32°C 1
• Bradycardia develops as a direct toxic effect and from hypothermia (typically at 28°C) 1
• Hypertension can occur initially from increased sympathetic tone in mild hypothermia (<36°C) before progressing to hypotension 1
• Lactic acidosis results from metformin's inhibition of gluconeogenesis and mitochondrial dysfunction 1, 2
• Hypothermia represents thermoregulatory failure from the acute illness 3

Immediate Management Algorithm

If MALA is suspected, discontinue metformin immediately and initiate prompt hemodialysis. 1 This is the definitive treatment because:

1. Metformin is dialyzable and kinetic removal is the only effective intervention 2
2. Sodium bicarbonate therapy is of little value and increases lactate production 2
3. The mortality rate approaches 50% without aggressive intervention 1

Temperature Management Priority

Active rewarming must be initiated immediately while addressing the underlying cause. 1 The approach depends on:

• Core temperature measurement via esophageal or bladder probe (rectal lags behind and is unreliable) 1
• Rewarming rate should be controlled at 0.5-1°C per hour to avoid complications 1
• Avoid vasopressors initially as they may worsen outcomes in hypothermic patients with metabolic acidosis 1

Critical Monitoring Requirements

Monitor continuously for:

• Cardiac arrhythmias including ventricular fibrillation risk below 28°C 1
• Electrolyte shifts particularly potassium (initial hyperkalemia followed by hypokalemia) 1
• Coagulopathy as clotting factors lose 10% function per degree below 37°C 1
• Impaired lactate clearance which worsens with hypothermia 1

Alternative Differential Diagnoses

Synthetic Cannabinoid Toxicity (ADB-FUBINACA)

This can present with an identical constellation: mental status depression, bradycardia, autonomic instability, seizures, hypoglycemia, and hypothermia. 4 Consider this in:

• Younger patients without diabetes medication history
• Presence of seizure activity
• Hypoglycemia without diabetic medication use
• History suggesting drug ingestion or body-packing 4

Severe Hypothermia from Other Causes

Primary hypothermia with secondary complications can mimic this presentation 3:

• Metabolic acidosis occurs in all cases of severe hypothermia 3
• Bradyarrhythmias develop in three of six patients with acute thermoregulatory failure 3
• Altered sensorium occurs in five of six patients 3
• Underlying precipitants include pneumonia, heart failure, renal failure, or hypoglycemia 3

Beta-Blocker Toxicity

Esmolol and other beta-blockers can cause bradycardia, hypotension (or paradoxical hypertension in pheochromocytoma), and altered mental status, but typically do not cause the degree of hypothermia or lactic acidosis seen here. 5

Key Diagnostic Pitfalls

Do not assume ST-elevation on ECG represents acute MI in hypothermic patients. 6 Hypothermia causes:

• Diffuse ST elevations mimicking STEMI 6
• J waves (Osborne waves) in leads V3-V6, I, and II 6
• First-degree AV block and sinus bradycardia 6
• These changes completely resolve with rewarming 6

Do not diagnose brain death while core temperature remains below 34°C as hypothermia causes loss of deep tendon reflexes and pupillary responses that mimic brain death. 1

Treatment Sequence

1. Obtain rectal or esophageal temperature immediately (not axillary or bladder which lag by up to 1°C) 1
2. Check serum metformin level, lactate, renal function, and blood gas 1
3. Initiate active rewarming with warmed IV fluids, forced air warming, and consider extracorporeal rewarming if temperature <28°C 1
4. Contact nephrology emergently for hemodialysis if metformin toxicity confirmed 1
5. Correct hypovolemia before considering vasopressors as hypothermia causes cold diuresis 1, 5
6. Maintain serum potassium 4.0-4.5 mmol/L to prevent arrhythmias 1

The combination of prompt hemodialysis and controlled rewarming offers the best chance of survival in MALA, with five of six patients surviving acute thermoregulatory failure when appropriately managed. 3