Faculty Bibliography

OBJECTIVE: Acetaminophen-induced fulminant hepatic failure is associated with acute kidney injury, metabolic acidosis, and fluid and electrolyte imbalances, requiring treatment with renal replacement therapies. Although antidote, acetylcysteine, is potentially extracted by renal replacement therapies, pharmacokinetic data are lacking to guide potential dosing alterations. We aimed to determine the extracorporeal removal of acetylcysteine by various renal replacement therapies. METHODS: Simultaneous urine, plasma and effluent specimens were serially collected to measure acetylcysteine concentrations in up to three stages: before, during and upon termination of renal replacement therapy. Alterations in pharmacokinetics were determined by applying standard pharmacokinetic equations. RESULTS: Over 2 years, 10 critically ill patients in fulminant hepatic failure requiring renal replacement therapy coincident with acetylcysteine were consecutively enrolled. All 10 patients required continuous venovenous hemofiltration (n = 10) and 2 of the 10 also required hemodialysis (n = 2). There was a significant alteration in the pharmacokinetics of acetylcysteine during hemodialysis; the area under the curve (AUC) decreased 41%, the mean extraction ratio was 51%, the mean hemodialytic clearance was 114.01 ml/kg/h, and a mean 166.75 mg/h was recovered in the effluent or 41% of the hourly dose. Alteration in the pharmacokinetics of acetylcysteine during continuous venovenous hemofiltration did not appear to be significant: the AUC decreased 13%, the mean clearance was 31.77 ml/kg/h and a mean 62.12 mg/h was recovered in the effluent or 14% of the hourly dose. CONCLUSIONS: There was no significant extraction of acetylcysteine from continuous venovenous hemofiltration. In contrast, there was significant extracorporeal removal of acetylcysteine during hemodialysis. A reasonable dose adjustment may be to double the IV infusion rate or possibly supplement with oral acetylcysteine during hemodialysis.

The epidemic of prescription opioid-related morbidity and mortality demonstrates the need for a fresh, open, and balanced approach to managing pain while minimizing adverse personal and public health outcomes. Interventions by pharmacists in situations in which prescriptions are felt to be inappropriate have raised the ire of prescribers who feel their professional judgment is being questioned and their time is being usurped from patient care. Pharmacists, however, represent an important check and balance in the opioid analgesic prescribing chain, and prescribers should embrace their involvement and recognize that the time and effort of the pharmacist are directed at improving care of individual patients and keeping a watchful eye on the public health. Pharmacies need to keep a mindful eye toward professional practices of physicians and use noninvasive means, such as database inquiries, prior to directly contacting a prescriber. Collaboration is the most professional approach that can be taken to assure that our joint priority of caring for patients in distress will be accomplished effectively and safely.