A patient had a recent seizure and creatine kinase was downtrending but is now rising sharply without any new seizures; what is the best management and work‑up for possible rhabdomyolysis?

Management of Rising CK After Seizure Without New Seizures

Immediately discontinue any potentially causative medications (especially statins, supplements like red yeast rice, creatine, or antiepileptics like levetiracetam), initiate aggressive IV fluid resuscitation targeting urine output of 300 mL/hour, and perform comprehensive laboratory workup to identify the underlying cause of ongoing muscle breakdown. 1, 2, 3

Immediate Management Priorities

Discontinue Causative Agents

• Stop all medications that can cause or exacerbate rhabdomyolysis immediately, including:
  • Statins (most common drug cause at 1.6 per 100,000 patient-years) 1
  • Levetiracetam (can cause rhabdomyolysis even after previous tolerance, with CK rising to >47,000 U/L in documented cases) 3
  • Supplements: red yeast rice containing lovastatin, creatine monohydrate, wormwood oil, licorice, and Hydroxycut 1
  • Any interacting drugs, particularly gemfibrozil which carries 10-fold higher rhabdomyolysis risk 1

Aggressive Fluid Resuscitation

• Initiate crystalloid fluid resuscitation now, even with mildly elevated CK, because the rising trend suggests progressive rhabdomyolysis 1
• Use isotonic saline (0.9% NaCl) as first-line fluid 1
• Target urine output of 300 mL/hour for severe cases 2
• For severe rhabdomyolysis (CK >15,000 IU/L), volumes >6L may be required; for moderate cases, 3-6L per day is typical 1
• Early fluid resuscitation is critical—delayed treatment significantly increases acute kidney injury risk 1

Essential Laboratory Workup

Core Diagnostic Tests (Order Immediately)

• Complete electrolyte panel with particular focus on potassium (hyperkalemia can cause life-threatening arrhythmias) 1
• Daily trending of CK, creatinine, and electrolytes until CK is declining and renal function is stable 1
• Urinalysis for myoglobinuria (brown color, cloudiness, positive for blood without RBCs) 1
• Liver function tests (AST, ALT, alkaline phosphatase) to assess transaminitis from muscle enzyme release 1
• Additional muscle enzymes: LDH, aldolase 1
• Arterial blood gas to assess for metabolic acidosis 1
• Coagulation studies to evaluate for disseminated intravascular coagulation 1

Cardiac Assessment

• ECG and cardiac troponin to rule out cardiac involvement in severe rhabdomyolysis 1
• Use total CK, not CK-MB, for rhabdomyolysis diagnosis (CK-MB lacks sensitivity/specificity for this condition) 1

Etiology-Specific Testing (Based on Clinical Context)

For recurrent or unexplained rhabdomyolysis:

• Thyroid function tests (hypothyroidism predisposes to muscle toxicity) 1
• Autoimmune markers (ANA, ASMA, ANCA) if autoimmune myositis suspected 1
• Genetic testing: RYR1 and CACNA1S for malignant hyperthermia susceptibility; CPT2, PYGM, ACADM, AMPD1, VLCAD for metabolic myopathies 1
• Metabolic workup: serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone, 25-hydroxy-vitamin D 1
• Viral studies if viral myositis suspected 1

For medication review:

• Document all over-the-counter medications, herbal supplements, and performance-enhancing products 1
• Screen for recreational drug use (cocaine, methamphetamine, MDMA, ketamine, heroin) 1

Critical Monitoring and Complications

Electrolyte Management

• Monitor potassium closely and correct hyperkalemia emergently (can precipitate cardiac arrhythmias) 1
• Repeated electrolyte measurements, particularly potassium, throughout treatment 1
• Monitor calcium, phosphorus, and magnesium levels 1

Renal Replacement Therapy Indications

Initiate dialysis for: 1

• Life-threatening hyperkalemia unresponsive to medical management
• Volume overload despite diuretic therapy
• Uremic symptoms (nausea, vomiting, pericarditis, encephalopathy)

Compartment Syndrome Surveillance

• Monitor for pain, tension, paresthesia, paresis (early signs) 1
• Late signs (pulselessness, pallor) indicate irreversible damage 1
• Consider fasciotomy when compartment pressure >30 mmHg or differential pressure (diastolic BP – compartment pressure) <30 mmHg 1

Understanding CK Kinetics: Critical Pitfall

CK levels peak 24-120 hours after the inciting event, NOT immediately 1, 4

• At 9 hours post-event, CK is typically still rising and has not reached maximum 1
• The large CK molecule (82 kDa) requires lymphatic clearance, explaining the delay 1
• A rising CK despite no new seizures suggests ongoing muscle breakdown from another cause (medication toxicity, metabolic disorder, autoimmune process) 3, 5
• Impact trauma can elevate CK without true rhabdomyolysis, but given a doubling trend, assume true muscle breakdown until proven otherwise 1

Pain Management Strategy

First-Line Analgesic

• Acetaminophen 500-1000 mg (onset 15-30 minutes, maximum 4-6 grams daily) 1
• Preferred because it avoids nephrotoxic effects in patients already at high AKI risk 1

Agents to Avoid

• All NSAIDs (ibuprofen, ketoprofen, diclofenac, naproxen, mefenamic acid) due to gastrointestinal and renal toxicity 1

Severe Pain Management

• Reserve opioids for severe muscle pain unresponsive to acetaminophen 1
• Oral morphine 20-40 mg for opioid-naive patients (first choice) 1
• If eGFR <30 mL/min, use fentanyl or buprenorphine (safest in renal impairment) 1
• Provide round-the-clock dosing with rescue doses (10-15% of total daily dose) for breakthrough pain 1

Special Considerations for Seizure-Related Rhabdomyolysis

Seizure-induced CK elevation characteristics: 4

• CK levels can exceed 39,000 U/L after seizures
• All patients with significantly elevated CK post-seizure exhibit eGFR <90 mL/min/1.73m²
• Serial assessment of CK, myoglobin, eGFR, and electrolytes is mandatory 4
• Fluid resuscitation, urine alkalinization, and diuretic agents should be administered when CK is significantly elevated 4

However, rising CK without new seizures suggests an alternative or additional etiology beyond the initial seizure 3, 5

Disposition and Follow-Up

• Most patients require hospitalization for aggressive hydration and monitoring 1, 2
• Continue daily CK, creatinine, and electrolyte monitoring until CK is declining and renal function is stable 1
• If persistently elevated CK (idiopathic hyperCKemia) after full evaluation, further investigation including genetic testing is required 1