Treatment of Rhabdomyolysis with Acetaminophen History
If rhabdomyolysis occurs in the context of acetaminophen use, immediately assess for acetaminophen toxicity and initiate N-acetylcysteine (NAC) if indicated, while simultaneously treating the rhabdomyolysis with aggressive IV fluid resuscitation. 1, 2
Immediate Assessment for Acetaminophen Toxicity
Critical first step: Obtain acetaminophen level, AST, ALT, INR, and creatinine immediately to determine if acetaminophen is contributing to the clinical picture, as rhabdomyolysis can occur as an extra-hepatic manifestation of acetaminophen poisoning. 3
- Acetaminophen overdose can cause rhabdomyolysis as a direct toxic effect, along with metabolic acidosis, shock, renal insufficiency, and hepatotoxicity. 3
- Very high aminotransferases (AST/ALT >3,500 IU/L) are highly correlated with acetaminophen poisoning and should prompt immediate NAC treatment even without clear overdose history. 1
- Acute renal failure occurs in less than 2% of all acetaminophen poisonings but in 10% of severely poisoned patients, manifesting as acute tubular necrosis. 4
NAC Administration Decision Algorithm
Start NAC immediately without waiting for laboratory confirmation if: 1, 2
- Acetaminophen level plots above the "possible toxicity" line on the Rumack-Matthew nomogram (for acute ingestions 4-24 hours post-ingestion). 1
- Time of ingestion is unknown and acetaminophen level is detectable. 1
- Any elevation in AST or ALT above normal with suspected acetaminophen exposure. 1
- Clinical evidence of acetaminophen toxicity (rhabdomyolysis, metabolic acidosis, shock, renal insufficiency). 3
- Presentation >8 hours after known ingestion—do not delay for laboratory results. 1
- Loading dose: 150 mg/kg in 5% dextrose over 15 minutes. 1
- Second dose: 50 mg/kg over 4 hours. 1
- Third dose: 100 mg/kg over 16 hours (total 21-hour protocol). 1
Concurrent Rhabdomyolysis Management
Early and aggressive IV fluid resuscitation is the cornerstone of rhabdomyolysis treatment and must be initiated immediately. 5, 6
- Administer crystalloid solution (0.9% normal saline or lactated Ringer's) at 200-1000 mL/hr initially, targeting urine output of 200-300 mL/hr. 5, 6
- Monitor creatine kinase (CK) levels—diagnosis confirmed when CK >1000 U/L or at least 5x upper limit of normal. 5
- Check serum myoglobin, urinalysis for myoglobinuria, and complete metabolic panel including creatinine and electrolytes. 5
- Calculate McMahon score on admission—score ≥6 predicts acute kidney injury requiring renal replacement therapy. 5
Fluid management considerations: 5, 6
- Continue aggressive hydration until CK levels are declining and urine output is adequate. 5
- There is no established benefit of routine bicarbonate infusion or mannitol despite common practice. 6
- Monitor for and treat hyperkalemia, hypocalcemia, and hyperphosphatemia with standard medical management. 5, 6
Critical Pitfalls and Monitoring
Do not assume acetaminophen is irrelevant just because the patient took "therapeutic doses": 7
- Severe hepatotoxicity has been documented with doses as low as 4-5 g/day in patients with risk factors like chronic alcohol use. 7
- Therapeutic doses of 4 g/day for 14 days caused ALT elevations >3x normal in 31-41% of healthy adults. 7
- Repeated supratherapeutic ingestions (≥6 grams per day for ≥48 hours) are potentially toxic. 7
Monitor for evolving multi-organ failure: 3
- Acetaminophen toxicity with rhabdomyolysis can progress to pancytopenia, pancreatitis, hepatorenal failure, and death despite initial improvement. 3
- Continue NAC beyond 21 hours if transaminases are rising, coagulopathy develops, or renal function deteriorates. 1
- If hepatotoxicity develops (AST/ALT >1000 IU/L), continue NAC until transaminases are declining and INR normalizes—this reduces mortality from 80% to 52%. 1
Assess for compartment syndrome as an additional complication of rhabdomyolysis requiring urgent surgical intervention. 6