Effect of acute paracetamol overdose on changes in serum and urine electrolytes

Abstract

What is already known about this subject • Paracetamol causes renal failure in overdose. Experimental studies have shown that paracetamol can inhibit COX II systemically in a manner similar to selective COX‐II inhibitors. • In overdose nonsteroidal anti‐inflammatory drugs such as ibuprofen, cause dose‐dependent increase in urinary potassium excretion (FeK) and sodium retention, probably due to vasoconstriction. What this study adds • Paracetamol overdose is associated with dose‐related hypokalaemia and kaliuresis of short duration (<24 h), suggesting a specific renal effect of paracetamol in overdose. • This effect seems likely to be via cyclo‐oxygenase inhibition and may be separate from the nephrotoxic effects of paracetamol. Aims To investigate the effects of acute paracetamol overdose on renal function, serum and urine electrolyte excretion in man. Methods Two studies were performed in patients admitted with paracetamol overdose: a retrospective study examining changes in serum electrolytes, and a prospective study evaluating changes in serum and urine electrolytes. A control group with SSRI overdose was included in the prospective study. Results There was a significant dose‐dependent relationship between admission (4 h) paracetamol concentration and fall in serum potassium in the retrospective study (P < 0.01) and a significant positive relationship between serum paracetamol at 4 h and fractional excretion of potassium at 12 h postingestion (P < 0.01) in the prospective study. No changes were seen in the control group. No cases developed renal failure. Conclusions Paracetamol overdose is associated with dose‐related hypokalaemia, and kaliuresis of short duration (<24 h), suggesting a specific renal effect of paracetamol in overdose perhaps via cyclo‐oxygenase inhibition. This effect seems distinct from any nephrotoxic effect of paracetamol.

Acetaminophen Toxicity and 5-Oxoproline (Pyroglutamic Acid)

“…The best characterized of these disorders is hepatic toxicity produced by an acute acetaminophen overdose (1)(2)(3). Acute acetaminophen poisoning can also produce renal injuries that reduce glomerular filtration and cause renal tubule damage characterized by potassium and/or phosphate wasting (4)(5)(6)(7). The pathogenic mechanisms responsible for these acute renal disorders may parallel those responsible for hepatic injury but they are less well characterized.…”

Renal injury at first presentation as a predictor for poor outcome in severe paracetamol poisoning referred to a liver transplant unit

“…Referral K in the group with mild dysfunction was significantly lower than that in severe renal dysfunction (p<0.0001) k Worst PT in normal group was significantly lower than mild (p<0.05), moderate (p<0.0001) ,or severe renal dysfunction (p<0.05) m Patients with moderate and severe renal dysfunction stayed longer in the intensive care unit (ITU) than those with normal renal function (p<0.0001and p<0.01, respectively) n Mortality in the group with normal renal function was significantly lower those with mild, moderate and severe renal dysfunction (p<0.0001). Those with mild renal dysfunction had lower mortality than those with moderate or severe renal dysfunction (p <0.05) renal failure, paracetamol ingestion is associated with dosedependent changes in electrolyte transport, suggesting a direct pharmacological action of paracetamol on renal tubular function [17,18]. Risk factors, such as glutathione depletion in the kidney, concomitant ingestion of nephrotoxic substances, dehydration at presentation, chronic excessive overdose of paracetamol and pre-existing liver and renal insufficiency may all increase the risk of renal injury after paracetamol overdose [19].…”

Author's response to Pakravan et al.

“…2 The authors have sought to extrapolate evidence gathered in an animal model, which certainly points towards a renal perfusion hypothesis as the cause of the hypokalaemia. Conclusive proof has however not yet been established that this model can be extrapolated into a human population.…”

“…2 In our retrospective study, in 155 subjects who had taken single paracetamol overdoses and presented within 4 -6 h post-ingestion serum potassium change between admission to hospital (4 -6 h postingestion) and 24 h post-ingestion was studied. We showed a dose-dependent relationship between fall in serum potassium and serum paracetamol at presentation.…”