Management of Pregabalin Toxicity in Acute Renal Failure with Heart Failure Exacerbation
Immediately discontinue pregabalin and initiate urgent hemodialysis if the patient exhibits significant neurological symptoms (myoclonus, encephalopathy, reduced consciousness), as pregabalin is highly dialyzable with approximately 50% clearance in 4 hours and hemodialysis clearance of 88.8 mL/min has been shown to achieve rapid symptom resolution. 1, 2
Immediate Assessment and Discontinuation
Stop pregabalin immediately upon recognition of toxicity, regardless of whether symptoms have already developed, as pregabalin clearance is directly proportional to creatinine clearance (56-58% reduction with declining renal function) 3, 4
Assess for classic pregabalin toxicity manifestations: myoclonus (limbs and head), encephalopathy, reduced consciousness, confusional state, agitation, depression/anxiety, and restlessness 1, 5
Obtain serum pregabalin level if available, though toxicity can occur even within therapeutic range (3.42 μg/ml) in acute renal failure, suggesting a threshold phenomenon rather than strict dose-dependent toxicity 5
Check serum creatinine, estimated GFR, electrolytes (particularly potassium), and volume status to guide both renal replacement therapy decisions and heart failure management 6
Hemodialysis Decision Algorithm
Initiate emergent hemodialysis if:
- Significant neurological symptoms are present (myoclonus, encephalopathy, coma) 2
- Patient requires mechanical ventilation due to neurological depression 7
- Creatinine clearance <30 mL/min with symptomatic toxicity 3
Consider hemodialysis even with mild symptoms if:
- Patient is already on chronic hemodialysis (standard 4-hour session removes ~50% of pregabalin) 1, 2
- Acute renal failure is severe (creatinine >451 μmol/L or >5.1 mg/dL) with preserved urine output but inadequate drug clearance 5
Supportive care alone may be sufficient if:
- Symptoms are mild and patient is protecting airway 7
- Renal function is expected to recover rapidly (within 24-48 hours) 5
- No life-threatening complications (seizures, heart block, severe respiratory depression) are present 1
Supportive Care During Management
Maintain airway protection: Intubate and mechanically ventilate if Glasgow Coma Scale <8 or inability to protect airway 7
Monitor vital signs continuously and observe for seizures and heart block, which have been reported in pregabalin overdose 1
Do NOT use gastric lavage or activated charcoal if presentation is delayed, as pregabalin is rapidly absorbed (time to peak concentration ~1 hour) 4
There is no specific antidote for pregabalin toxicity 1
Heart Failure Management Considerations
Continue guideline-directed medical therapy (GDMT) for heart failure unless specific contraindications exist:
Maintain beta-blockers throughout acute management unless patient develops cardiogenic shock (systolic BP <85 mmHg) or severe bradycardia (<50 bpm) 6
Continue ACE inhibitors/ARBs at reduced dose (50% reduction) during acute phase unless potassium >5.5 mmol/L or creatinine >221 μmol/L (>2.5 mg/dL) 6, 8, 9
Reduce or temporarily stop ACE inhibitors/ARBs if potassium rises to 5.5-6.0 mmol/L; stop completely if potassium >6.0 mmol/L or creatinine >310 μmol/L (>3.5 mg/dL) 6, 8
Continue diuresis aggressively if patient remains congested, accepting creatinine increases up to 50% above baseline or 266 μmol/L (3 mg/dL), whichever is smaller 9
Diuretic Management in Concurrent Acute Renal Failure
Use IV loop diuretics at 2-2.5 times the total daily oral maintenance dose for congestion, as thiazide diuretics are ineffective with eGFR <30 mL/min 9
Do NOT use thiazide diuretics in this setting, as they are contraindicated with severe renal dysfunction 6, 9
For diuretic resistance, add sequential nephron blockade with acetazolamide 500 mg IV daily or metolazone 2.5-5 mg orally 9
Monitor daily weights, fluid intake/output, blood pressure, serum creatinine, and electrolytes during acute phase 9
Monitoring During Recovery
Check renal function and electrolytes at 1 and 4 weeks after resolution, then at 8 and 12 weeks 6
Pregabalin terminal elimination half-life increases from 6.3 hours in normal renal function to 11.5 hours or longer in acute renal failure 4, 5
Symptoms typically resolve within 24 hours for myoclonus and 48 hours for encephalopathy with supportive care or hemodialysis 5, 2
Critical Pitfalls to Avoid
Never restart pregabalin at previous dose in patients with acute renal failure; if restarted after renal recovery, reduce daily dose by 50% for CLcr 30-60 mL/min, and by an additional 50% for each 50% decrease in CLcr below 30 mL/min 3
Do NOT discontinue beta-blockers or ACE inhibitors/ARBs prematurely during acute decompensation unless specific contraindications exist, as clinical deterioration is likely 6, 9
Avoid adding mineralocorticoid receptor antagonists (spironolactone) during acute phase with hyperkalemia and renal dysfunction, as this increases risk of life-threatening hyperkalemia 8, 9
Do NOT delay hemodialysis in symptomatic patients awaiting spontaneous recovery, as pregabalin's pharmacokinetic properties (low molecular weight 159.23 Da, low volume of distribution 0.5 L/kg, no protein binding) make it highly amenable to dialytic removal 2