Renal Adverse Effects of Intravenous Lorazepam

Mechanism of Renal Toxicity

• IV lorazepam formulations contain propylene glycol as a diluent, which can accumulate and cause toxicity in critically ill patients 1
• Propylene glycol toxicity manifests primarily as metabolic acidosis and acute kidney injury 2
• These adverse effects may be overlooked in critically ill patients because metabolic acidosis and kidney injury are common in this population 2

Risk Factors for Renal Adverse Effects

• Total daily IV doses as low as 1 mg/kg can cause propylene glycol toxicity 2
• Initially thought to occur only with high doses, but now recognized to occur at much lower doses 2

Pharmacokinetic Considerations

• Lorazepam itself is primarily metabolized by the liver to lorazepam glucuronide 3
• The elimination half-life and duration of clinical effect of lorazepam are increased in patients with renal failure 1

Monitoring for Propylene Glycol Toxicity

• Serum osmol gap can be used as a reliable screening tool for propylene glycol accumulation 2
• An osmol gap greater than 10-12 mOsm/L may help identify patients with significant propylene glycol accumulation 2

Clinical Recommendations

• Consider alternative sedatives in patients with renal insufficiency, especially for prolonged sedation 2
• Be particularly cautious when administering lorazepam to elderly patients, who have decreased benzodiazepine clearance 3

Common Pitfalls

• Failure to recognize that renal adverse effects are primarily due to the propylene glycol diluent rather than lorazepam itself 2
• Overlooking propylene glycol toxicity because metabolic acidosis and renal dysfunction are common in critically ill patients 2
• Assuming that only very high doses of lorazepam cause propylene glycol toxicity, when in fact doses as low as 1 mg/kg/day can be problematic 2