Hypokalaemia is a recognized complication of acute acetaminophen overdose. It is unclear whether this might be a pharmacological effect of acetaminophen, or due to association with confounding factors. The present study sought to better characterize the relationship between acetaminophen concentrations and risk of hypokalaemia. A prospective study of patients received N-acetylcysteine treatment within 15 hr of acute acetaminophen ingestion. Serum potassium concentrations were determined before and after N-acetylcysteine. Serum acetaminophen concentrations were used to indicate overall drug exposure by comparison to the Rumack-Matthew nomogram. Hypokalaemia was pre-defined by serum concentrations 156 mmol/l gave 81% sensitivity and 48% specificity. The risk of hypokalaemia after acute acetaminophen overdose depends on the extent of acetaminophen exposure, irrespective of N-acetylcysteine administration and independent of whether vomiting occurred. Acetaminophen appears to cause concentration-dependent hypokalaemia after overdose, and the pharmacological basis requires further consideration.

Acute Acetaminophen Overdose Is Associated with Dose-Dependent Hypokalaemia: A Prospective Study of 331 Patients

Background: Hypokalemia is not an isolated disease but an associated finding in a number of different diseases. It is also a commonly neglected condition among patients with acute acetaminophen overdose. Objectives: This study intended to determine the prevalence of hypokalemia and its clinical correlates in acute psychiatric illness among hypokalemic and normokalemic patients after acetaminophen overdose. Methods: This is a ret- rospective cohort study of hospital admissions for acute acetaminophen overdose conducted over a period of 5 years from 1 January 2004 to 31 December 2008. Demographic data and different types of psychiatric illness were compared between hypokalemic and normokalemic patients. Hypokalemia was predefined by a serum concentration <3.5 mmol/L. Statistical Package for Social Sciences (SPSS) 15 was used for data analysis. Results: Two hundred and eighty patients out of 305 admissions were studied. Hypokalemia was found in 63.6% of patients with a higher prevalence in the presence of psychiatric illness (67.7%). Hypokalemic patients were significantly associated with the presence of major depression (p ¼ .04), adjustment disorder (p < .001), anxiety (p ¼ .01), and suicidal attempts (p ¼ .04). Conclusion: Hypokalemia was common among patients with psychiatric illness and acute acetaminophen overdose.

High prevalence of hypokalemia after acute acetaminophen overdose: Impact of psychiatric illness:

We were interested to read the case report study on two patients who had taken significant paracetamol overdoses presenting within 4 h post-ingestion and developing significant hypokalaemia within 8 h of presentation. Both cases received intravenous NAC treatment. The authors also reported hypokalaemia within 36 h of admission in 254 patients with paracetamol overdose. The potential effect of NAC therapy, acid-base change and stress on hypokalaemia was discussed. The authors recommended that although the possible mechanisms for hypokalaemia after paracetamol overdose are unclear, regular monitoring of serum potassium should be carried out over 36 h post-ingestion. Treatment of any significant hypokalaemia has also been suggested. We have published retrospective and prospective studies studying this phenomenon. 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. No relationship was seen between serum paracetamol or serum bicarbonate and the same trend in potassium was seen in the group with and without NAC treatment. To have a better understanding of the possible mechanism of potassium change after paracetamol overdose we then prospectively studied 41 subjects taking a single paracetamol overdose and presenting within 4–6 h postingestion. We measured serum paracetamol at 4 h, and serum potassium (K) and fractional excretion of K (FeK) at 4–6, 12 and 24 h. There was a significant dose-dependent relationship between serum paracetamol and FeK at 12 h. The FeK had returned to normal by 24 h. Our control group did not show changes in serum K or FeK. Studies on the rat have shown paracetamol overdose causes a significant decrease in renal perfusion and an increase in FeK at 16 h which had normalized by 24 h. Based on our studies and animal study, we concluded that 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. We appreciate the authors’ enthusiasm for treating patients with significant hypokalaemia. However, both our data and animal data show that the renal effect of paracetamol overdose is transient and is resolved by 24 h postingestion. We believe a 36 h monitoring period is unnecessary and potentially wasteful of hospital resources. Interestingly, we did not find evidence that this renal effect of paracetamol was related to its well-recognized nephrotoxicity in our cohort. N Pakravan, J Goddard and D N Bateman NPIS Edinburgh; Department of Renal Medicine, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA, UK Email: n.pakravan@sms.ed.ac.uk DOI: 10.1258/acb.2007.071601

https://journals.sagepub.com/doi/pdf/10.1258/acb.2007.071601

Hypokalaemia following paracetamol overdose.

We present a case of paracetamol overdose in a 34-year-old female with a history of depression and alcoholism. Following treatment with N-acetylcysteine (Parvolex ® ) our patient developed ventricular tachycardia resulting in cardiac arrest from which she was successfully resuscitated. Subsequent ECG demonstrated prolongation of the QTc interval and repeat blood tests revealed a significant fall in serum potassium from 4.2mmol/l on admission to 2.2mmol/l. The possible mechanisms contributing to the development of hypokalaemia after overdose with paracetamol are discussed. The existing literature relating to paracetamol-induced hypokalaemia is briefly reviewed.

Cardiac arrest following paracetamol overdose complicated by hypokalaemia

Poisoning and Laboratory Medicine, by Ian Watson and Alex Proudfoot: ACB Venture Publications.

We report on two teenage girls presenting following significant paracetamol overdoses (>28 g paracetamol). Both presented within 4 h of the overdose and both were treated with N-acetylcysteine, in accordance with the National Poisons Information Service protocol. Within 8 h of presentation both had developed significant hypokalaemia with serum potassium concentrations <3.0 mmol/L and were treated with intravenous potassium chloride. Potassium concentrations returned to within reference limits (>3.5 mmol/L) after commencing potassium chloride supplementation. An audit of potassium concentrations in 254 patients presenting with significant paracetamol overdose (paracetamol >0.5 mmol/L) admitted through four A&E departments in the West of Scotland showed a significant decline in mean serum potassium from 3.9 mmol/L on admission to 3.6 mmol/L (P = <0.001) over the next 36 h. The mechanism for this hypokalaemia in these two individuals is unclear, however regular monitoring of potassium is advocated in such patients during their initial treatment.

Case Report Hypokalaemia following paracetamol overdose in two teenage girls

https://journals.sagepub.com/doi/pdf/10.1258/acb.2007.071602

Donogh Maguire

Papers

Case Report Hypokalaemia following paracetamol overdose in two teenage girls

Author's response to Pakravan et al.: