Author's response to Pakravan et al.

Abstract

We were interested to read the case report study 1 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.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. 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 3 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 4 in our cohort.