Antidote removal during haemodialysis for massive acetaminophen overdose

Abstract

Context. Haemodialysis is sometimes used for patients with massive acetaminophen overdose when signs of “mitochondrial paralysis” (lactic acidosis, altered mental status, hypothermia and hyperglycaemia) are present. The role of haemodialysis is debated, in part because the evidence base is weak and the endogenous clearance of acetaminophen is high. There is also concern because the antidote acetylcysteine is also dialyzable. We prospectively measured serum acetylcysteine concentrations during haemodialysis in three such cases. Case details. Three adults each presented comatose and acidemic 10 to ˜ 18 h after ingesting > 1000mg/kg of acetaminophen. Two were hypothermic and hyperglycaemic. Serum lactate concentrations ranged from 7 mM to 12.5 mM. All three were intubated, and initial acetaminophen concentrations were as high as 5980 μM (900 μg/mL). An intravenous loading dose of 150 mg/kg acetylcysteine was initiated between 10.8 and ˜ 18 h post ingestion, and additional doses were empirically administered during haemodialysis to compensate for possible antidote removal. A single run of 3–4 h of haemodialysis removed 10–20 g of acetaminophen (48–80% of remaining body burden), reduced serum acetaminophen concentrations by 56–84% (total clearance 3.4–7.8 mL/kg/min), accelerated native acetaminophen clearance (mean elimination half-life 580 min pre-dialysis, 120 min during and 340 min post-dialysis) and corrected acidemia. Extraction ratios of acetylcysteine across the dialysis circuit ranged from 73% to 87% (dialysance 3.0 to 5.3 mL/kg/min). All three patients recovered fully, and none developed coagulopathy or other signs of liver failure. Discussion. When massive acetaminophen ingestion is accompanied by coma and lactic acidosis, emergency haemodialysis can result in rapid biochemical improvement. As expected, haemodialysis more than doubles the clearance of both acetaminophen and acetylcysteine. Because acetylcysteine dosing is largely empirical, we recommend doubling the dose during haemodialysis, with an additional half-load when dialysis exceeds 6 h.

Keywords:

• Acetaminophen
• N-acetylcysteine
• Haemodialysis
• Mitochondria

Acknowledgments

We are indebted to Dr. Murray Cutler for use of laboratory space and for preparing the solutions used in the acetylcysteine assay. We are also indebted to the other physicians and healthcare providers that cared for these patients at the Kingston General and Oshawa General Hospitals.

Declaration of interest

The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.Supported by a Doctoral Research Award from the Pediatric Oncology Group of Ontario and the Canadian Institutes of Health Research (LNH).