Should sodium valproate (valproic acid) and quetiapine (Seroquel) be discontinued in a patient with traumatic rhabdomyolysis and impaired renal function?

Should Sodium Valproate and Quetiapine Be Discontinued in Traumatic Rhabdomyolysis?

Yes, both sodium valproate and quetiapine should be immediately discontinued in a patient with traumatic rhabdomyolysis, as these medications can directly worsen muscle breakdown and increase the risk of acute kidney injury and death.

Immediate Medication Management

Discontinue both agents immediately upon diagnosis of rhabdomyolysis. The evidence strongly supports stopping all medications that can exacerbate rhabdomyolysis 1, 2. This is not optional—continuation of these drugs in the setting of active rhabdomyolysis significantly increases morbidity and mortality risk.

Specific Evidence for Each Drug

Quetiapine:

• Quetiapine has been directly implicated in causing severe rhabdomyolysis, particularly through 5-hydroxytryptamine 2a serotonergic receptor inhibition 3
• A documented case showed severe rhabdomyolysis induced by quetiapine that resolved only after drug discontinuation 3
• Neuroleptic agents like quetiapine can trigger neuroleptic malignant syndrome (NMS), characterized by fever, muscle rigidity, and progression to rhabdomyolysis with acute renal failure 4
• Discontinuation of neuroleptic medication is imperative in drug-induced rhabdomyolysis 4

Sodium Valproate:

• Valproic acid can trigger acute rhabdomyolysis with renal failure, particularly in patients with underlying metabolic vulnerabilities 5
• Valproic acid toxicity is amplified in the setting of renal dysfunction and hypoalbuminemia—both common in rhabdomyolysis patients—leading to increased unbound (active) drug levels even when total plasma levels appear therapeutic 6
• The combination of trauma-induced rhabdomyolysis with impaired renal function creates a perfect storm for valproic acid toxicity 6

Critical Pathophysiologic Considerations

The decision to discontinue these medications is based on three key mechanisms:

1. Direct muscle toxicity: Both drugs can independently cause or worsen rhabdomyolysis through serotonergic mechanisms (quetiapine) and metabolic interference (valproate) 4, 3, 5

2. Renal dysfunction amplification: Traumatic rhabdomyolysis causes acute kidney injury, which dramatically increases the toxicity of both medications through reduced clearance and altered protein binding 6

3. Additive nephrotoxicity: Continuing these drugs while the kidneys are already injured from myoglobin deposition compounds the risk of progression to dialysis-requiring renal failure 4, 7

Management Algorithm After Discontinuation

Once both medications are stopped, proceed with standard rhabdomyolysis management:

Immediate actions (within first hour):

• Start aggressive IV fluid resuscitation with 0.9% normal saline at 1000 mL/hour 2
• Insert bladder catheter to monitor hourly urine output 8
• Check CK, creatinine, potassium, calcium, and phosphorus immediately 1

Target parameters:

• Urine output ≥300 mL/hour (not the standard 0.5 mL/kg/hour used in general AKI) 8
• Monitor electrolytes every 6-12 hours in severe cases 8
• Avoid potassium-containing fluids like Lactated Ringer's 8

Fluid volume requirements:

• For severe rhabdomyolysis (CK >15,000 IU/L): >6L per day 1
• For moderate cases: 3-6L per day 1

Common Pitfalls to Avoid

Do not wait for psychiatric consultation before stopping these medications. The immediate threat to life from rhabdomyolysis and acute kidney injury far outweighs any short-term psychiatric destabilization 4. Psychiatric symptoms can be managed with alternative agents once the patient is medically stable.

Do not rely on "therapeutic" total valproic acid levels. In the setting of hypoalbuminemia and renal dysfunction (both present in rhabdomyolysis), the unbound fraction rises dramatically, causing toxicity even with normal total levels 6.

Do not use NSAIDs for pain management. These are nephrotoxic and contraindicated in rhabdomyolysis 1. Use acetaminophen 500-1000 mg as first-line, with opioids (fentanyl or buprenorphine if GFR <30) reserved for severe pain 1.

Monitoring for Complications

After discontinuation, monitor specifically for:

• Life-threatening hyperkalemia requiring emergent treatment 1, 2
• Compartment syndrome (fasciotomy if pressure >30 mmHg) 1
• Need for dialysis (indications: refractory hyperkalemia, severe acidosis, fluid overload, persistently elevated CK after 4 days) 2

The CK will continue to rise for 24-120 hours after the initial trauma, so do not be falsely reassured by current levels 1. Repeat measurements are essential.