What is the likely diagnosis for a patient with intracranial hemorrhage (ICH), rhabdomyolysis, and severe acute kidney injury (AKI)?

Likely Diagnosis: Sympathomimetic Toxidrome or Drug-Induced Syndrome

The combination of intracranial hemorrhage, rhabdomyolysis, and severe acute kidney injury in a single patient strongly suggests a sympathomimetic drug toxicity (such as cocaine, amphetamines, or synthetic cathinones) or serotonin syndrome as the unifying diagnosis. This triad represents a cascade where the primary insult causes hypertensive crisis leading to ICH, muscle breakdown causing rhabdomyolysis, and subsequent myoglobin-induced nephrotoxicity resulting in AKI 1, 2.

Clinical Reasoning

Why This Triad Points to Drug Toxicity

• Sympathomimetic drugs cause severe hypertension that can precipitate spontaneous ICH, particularly in younger patients without traditional vascular risk factors 3
• These agents directly cause rhabdomyolysis through multiple mechanisms: hyperthermia, agitation, seizures, vasoconstriction, and direct muscle toxicity 4, 2
• Rhabdomyolysis leads to AKI through myoglobin-induced tubular injury, though CPK may occasionally be normal despite severe disease 1, 2

Key Diagnostic Features to Assess

History (from patient, family, or EMS):

• Recent drug use (cocaine, methamphetamine, MDMA, synthetic cathinones/"bath salts") 3
• Prescription medications causing serotonin syndrome (SSRIs, MAOIs, tramadol, linezolid)
• Preceding agitation, seizures, or hyperthermia
• Time of symptom onset and activities at onset 3

Physical Examination Findings:

• Severe hypertension (systolic BP >220 mmHg suggests ICH) 3
• Hyperthermia (core temperature >38.5°C)
• Muscle rigidity, tremor, or hyperreflexia
• Altered mental status or coma (GCS score) 3
• Signs of increased intracranial pressure 3

Laboratory Evaluation:

• Urine toxicology screen for amphetamines, cocaine, synthetic cathinones 3
• CPK levels (though may be normal in early or severe rhabdomyolysis) 1
• Myoglobin in urine (positive blood on dipstick without RBCs on microscopy) 1
• Serum creatinine and electrolytes (hyperkalemia, hyperphosphatemia, hypocalcemia) 3
• Coagulation studies (PT/PTT/INR, platelet count) 3
• Troponin (elevated in 15-20% of ICH patients, associated with worse outcomes) 3

Neuroimaging:

• Immediate non-contrast CT head to confirm ICH location and volume 3
• CT angiography to exclude underlying vascular malformation (aneurysm, AVM) and assess for "spot sign" predicting hematoma expansion 3
• Lobar hemorrhage in younger patients without hypertension suggests secondary causes 3

Alternative Diagnoses to Consider

Other Causes of This Triad

Thrombotic thrombocytopenic purpura (TTP):

• Presents with neurological symptoms, renal failure, and can cause ICH
• Look for thrombocytopenia, microangiopathic hemolytic anemia, fever
• Requires urgent plasma exchange

Hypertensive emergency with posterior reversible encephalopathy syndrome (PRES):

• Severe hypertension causing ICH and AKI
• May have seizures leading to rhabdomyolysis
• Check for underlying causes (eclampsia, renal disease, immunosuppressants)

Cerebral venous sinus thrombosis:

• Can present with ICH and systemic complications
• Requires CT/MR venography if suspected 3

Critical Management Priorities

Immediate Actions

Blood pressure management:

• Target systolic BP <140 mmHg for ICH (safe target per guidelines) 3
• Monitor BP every 15 minutes until stable 3
• Labetalol is first-line unless contraindicated 3

Rhabdomyolysis treatment:

• Aggressive IV fluid resuscitation (target urine output 200-300 mL/hour initially) 4, 2
• Monitor for compartment syndrome
• Correct electrolyte abnormalities (hyperkalemia, hypocalcemia) 4

AKI management:

• Avoid nephrotoxic agents (NSAIDs, aminoglycosides, contrast if possible) 5
• Consider early renal replacement therapy if severe hyperkalemia, volume overload, or uremia 5, 2
• Continuous RRT preferred over intermittent hemodialysis in ICH patients for hemodynamic stability 5

Common Pitfalls

• Do not rely solely on CPK levels to diagnose or exclude rhabdomyolysis—myoglobin casts on urinalysis or kidney biopsy may be present with normal CPK 1
• Avoid mannitol for ICP management if possible, as infusion rates ≥1.34 g/kg/day significantly increase AKI risk 6
• Do not delay CT angiography due to AKI concerns—the diagnostic benefit outweighs contrast nephropathy risk in this setting 3
• Recognize that AKI worsens ICH outcomes through metabolic derangements and inflammatory changes that prolong brain injury 5

Prognosis

• ICH carries 25-50% mortality at 30 days 3
• AKI in neurocritical care patients (occurring in ~20% of ABI cases) significantly worsens outcomes 5
• Hematoma expansion occurs in 28-38% within first 3 hours and predicts poor outcomes 3
• GCS score and ICH volume are strongest predictors of mortality 3