A quick inexpensive laboratory method in acute paracetamol poisoning could improve risk assessment, management and resource utilization

Abstract

Objectives:Acute paracetamol poisoning is an emerging problem in Sri Lanka. Management guidelines recommend ingested dose and serum paracetamol concentrations to assess the risk. Our aim was to determine the usefulness of the patient's history of an ingested dose of >150 mg/kg and paracetamol concentration obtained by a simple colorimetric method to assess risk in patients with acute paracetamol poisoning.Materials and Methods:Serum paracetamol concentrations were determined in 100 patients with a history of paracetamol overdose using High Performance Liquid Chromatography (HPLC); (reference method). The results were compared to those obtained with a colorimetric method. The utility of risk assessment by reported dose ingested and colorimetric analysis were compared.Results:The area under the receiver operating characteristic curve for the history of ingested dose was 0.578 and there was no dose cut-off providing useful risk categorization. Both analytical methods had less than 5% intra- and inter-batch variation and were accurate on spiked samples. The time from blood collection to result was six times faster and ten times cheaper for colorimetry (30 minutes, US$2) than for HPLC (180 minutes, US$20). The correlation coefficient between the paracetamol levels by the two methods was 0.85. The agreement on clinical risk categorization on the standard nomogram was also good (Kappa = 0.62, sensitivity 81%, specificity 89%).Conclusions:History of dose ingested alone greatly over-estimated the number of patients who need antidotes and it was a poor predictor of risk. Paracetamol concentrations by colorimetry are rapid and inexpensive. The use of these would greatly improve the assessment of risk and greatly reduce unnecessary expenditure on antidotes.

Sensitivity of dose‐estimations for acute acetaminophen overdose in predicting hepatotoxicity risk using the Rumack‐Matthew Nomogram

“…In addition, even when most practitioners initially decide to start NAC based solely on the estimated ingested dose, the subsequent timely return of serum acetaminophen level will dictate whether such treatment will need to be continued. And in rural and district hospitals where obtaining acetaminophen level is not an option, physicians are forced to base the initiation, and indeed the continuation, of NAC therapy on the estimated ingested dose of 150 mg/kg alone 2,5–7 . Acetaminophen level remains an elusive clinical tool to most physicians in these healthcare facilities, and patients are obligated to being hospitalized and completing the full course of NAC.…”

“…(Table 1) Although they differ in their study populations and methodologies, these studies reflect the reliance of practitioners of toxicology on the dose‐estimate method in instituting early NAC therapy in real‐world practices. Optimization of an appropriate dose‐estimate threshold means initiating treatment in patients with reasonable risks for hepatotoxicity and minimizing the costs incurred by overtreatment with the antidote 7–10 . These diverse sets of data echo the reality that, despite its long‐regarded use in toxicology, there is lacking evidence of sensitivity and specificity of the 150 mg/kg dose‐estimate at predicting hepatotoxicity when using the 150 mg/L treatment line.…”

“…And in rural and district hospitals where obtaining acetaminophen level is not an option, physicians are forced to base the initiation, and indeed the continuation, of NAC therapy on the estimated ingested dose of 150 mg/kg alone. 2,[5][6][7] Acetaminophen level remains an elusive clinical tool to most physicians in these healthcare facilities, and patients are obligated to being hospitalized and completing the full course of NAC.…”

“…8 A study from Sri Lanka finds the dose-estimate of 150 mg/kg has 89% sensitivity against the 200-treatment line reference while having only a 5% specificity. 7 A retrospective study from the UK and Australia finds that the 10-g dose-estimate has an 85% sensitivity when using the 150 mg/L treatment line. 9 (Table 1) Although they differ in their study populations and methodologies, these studies reflect the reliance of practitioners of toxicology on the dose-estimate method in instituting early NAC therapy in real-world practices.…”

CLS, PLS and PCR Methods in Different Sets of Data for Simultaneous Determination of Paracetamol and Orphenadrine Citrate in Their Combined Pharmaceutical Dosage Forms

“…PAR & ORP were determined in their pharmaceutical formulation by using spectrophotometric methods [1][2][3][4][5][6], HPLC methods [7][8][9], TLC and microemulsion HPLC method [10], square wave voltammetric method [11] and capillary electrophoresis method [12]. Several methods have been reported for determination of PAR alone in biological matrix including spectrophotometric methods [13][14][15][16], HPLC methods [17][18][19][20][21], HPTLC method [22], GC method [23] and voltammetric methods [24][25][26]. On the other hand, only chromatographic methods have been reported for determination of ORP alone in biological matrix including HPLC method [27] and GC methods [28][29][30].…”