Is it safe to order PRN (as needed) lorazepam (Ativan) for a patient with a history of seizures and impaired renal function (on dialysis)?

PRN Lorazepam for Seizure Management in Dialysis Patients

Yes, you can order PRN lorazepam for a dialysis patient with a history of seizures, but you must use reduced dosing (typically 50% reduction), monitor closely for propylene glycol toxicity with repeated doses, and ensure airway management equipment is immediately available.

Key Pharmacokinetic Considerations in Renal Failure

Lorazepam pharmacokinetics are significantly altered in dialysis patients:

• Volume of distribution increases by 75% and terminal half-life increases by 75% in hemodialysis patients compared to normal subjects 1
• Mean total clearance remains relatively unchanged despite renal failure because lorazepam is primarily metabolized by hepatic glucuronidation, not renal excretion 1
• Only 8% of administered IV lorazepam is removed during a 6-hour dialysis session, making supplemental dosing after dialysis unnecessary 1
• The lorazepam glucuronide metabolite accumulates significantly in renal failure (terminal half-life prolonged by 125% in hemodialysis patients), though this inactive metabolite is not clinically concerning 1

Critical Safety Concerns: Propylene Glycol Toxicity

The primary risk with IV lorazepam in dialysis patients is propylene glycol accumulation, not the lorazepam itself:

• IV lorazepam formulations contain propylene glycol as a diluent, which can cause metabolic acidosis and acute kidney injury 2
• Toxicity can occur at total daily doses as low as 1 mg/kg - much lower than previously thought 2
• Serum osmol gap >10-12 mOsm/L can screen for propylene glycol accumulation 2
• This toxicity is easily overlooked because metabolic acidosis and kidney injury are already common in dialysis patients 2

Specific Dosing Recommendations

For a dialysis patient requiring PRN seizure management:

• Start with 50% dose reduction based on the 75% increase in half-life and volume of distribution 1
• For a typical adult, use 1-2 mg IV (rather than the standard 2-4 mg) as initial PRN dose
• Dilute with equal volume of compatible diluent before IV administration 1
• Inject slowly with repeated aspiration to avoid intra-arterial injection 1
• Limit cumulative daily doses to minimize propylene glycol exposure, ideally keeping total daily dose <1 mg/kg 2

Essential Monitoring and Precautions

When using PRN lorazepam in this population:

• Airway management equipment must be immediately available - respiratory depression is the most important risk 1
• Monitor for excessive sedation, which is prolonged in dialysis patients due to increased half-life 1
• Check serum osmol gap if multiple doses are needed or if unexplained metabolic acidosis develops 2
• Patients over 50 years may have more profound and prolonged sedation 1
• No supplemental dosing after dialysis is needed since only 8% is removed during dialysis 1

Alternative Considerations

Given the propylene glycol concerns with repeated IV lorazepam use:

• Consider alternative benzodiazepines (such as midazolam) for prolonged or frequent seizure management in renal insufficiency 2
• For breakthrough seizures, lorazepam remains appropriate as PRN rescue medication with proper precautions
• Seizures in dialysis patients occur in approximately 3-5% of patients and are often related to dialysis disequilibrium, electrolyte shifts, or uremic encephalopathy rather than primary epilepsy 3, 4, 5

Common Pitfalls to Avoid

• Do not use standard dosing - the 75% increase in half-life and volume of distribution necessitates dose reduction 1
• Do not assume propylene glycol toxicity only occurs with high doses - it can occur at 1 mg/kg/day 2
• Do not give supplemental doses after dialysis - minimal drug removal occurs during dialysis 1
• Do not administer without immediately available airway equipment - respiratory depression risk is significant 1
• Do not overlook metabolic acidosis as potential propylene glycol toxicity - it mimics common ICU problems 2