Evaluation of cut-off values in acute paracetamol overdose following the United Kingdom guidelines

Background The United Kingdom guideline for acute paracetamol overdose has recommended the use of ‘100-treatment line’. Emergency medical centers in some developing countries lack the resources for timely reporting of paracetamol concentrations, hence treatment depends on reported dose. This study aimed to examine whether using an reported dose is safe to predict concentration above the 100-line. Methods Data were retrieved from two emergency medical centers retrospectively, between 2010 and 2017. The inclusion criteria were single acute paracetamol overdose, presentation within 15 h, and age ≥ 14 years. Multiple linear regression was performed to determine the effect of ingested dose on paracetamol concentration. Subgroups were created based on ingested dose, rate of concentration above 100-line were investigated. Results One hundred and seventy-two patients were enrolled in the primary analysis; median dose was 133.3 mg/kg and 46 (37.8%) had concentration above 100-line in the first test. Only dose per weight was moderately correlated with the first concentration (R2 = 0.410, p < 0.001). In the ≤200 mg/kg ingestion group, 18 patients showed concentration above 100-line and 8 showed acute liver injury. The cut-off value of 150 mg/kg showed 82.6% sensitivity and 73.8% specificity to predict concentration above 100-line. Conclusion Where paracetamol concentration is not available and activated charcoal is readily used, following United Kingdom guideline, it is safe to use an ingested dose of > 150 mg/kg as the cut-off value for N-acetylcysteine treatment with risk stratification for hepatotoxicity if the patient is ≥14 years and visit the ED within 15 h after an acute paracetamol overdose.

Large paracetamol overdose -- higher dose NAC is required - CON

Paracetamol overdose is common in developed countries but less than 10% involve large ingestions exceeding 30g or 500mg/kg. High dose acetylcysteine (NAC) has been proposed in patients taking large paracetamol overdoses based on reports of hepatotoxicity despite early initiation of NAC treatment with the commonly used 300 mg/kg intravenous acetylcysteine regimen. The evidence from cohorts of patients treated with the standard NAC regimen after large paracetamol overdoses shows that it is effective in most patients. Small studies in patients whose paracetamol concentration are above the 300mg/L nomogram line show that modification of the standard NAC regimen to provide a total of 400-500 mg/kg NAC over 21-22h may reduce the risk of hepatotoxicity (peak ALT>1000 IU/L) but the impact on development of hepatic failure, liver transplantation and mortality with this approach is presently unknown. Better risk stratification of patients taking paracetamol overdose may allow higher dose NAC and adjunctive treatments such as CYP2E1 inhibition and extracorporeal removal of paracetamol to be targeted to those patients at the highest risk of hepatotoxicity after a large paracetamol overdose.

Extra Virgin Olive Oil Protects the Testis and Blood from the Toxicity of Paracetamol (Overdose) in Adult Male Rats

Extra virgin olive oil (EVOO) is important in people’s daily diets. Paracetamol is a widely used analgesic and antipyretic drug. The aim of this study is to investigate the protective effect of EVOO against hematotoxicity and testicular toxicity induced by paracetamol overdose in rats. Forty rats were divided into four groups. Group 1 rats were given water (control), Group 2 rats were given oral EVOO daily (2 mL/kg b.wt.), Group 3 rats were given oral paracetamol daily (650 mg/kg b.wt.), and Group 4 rats were given paracetamol and EVOO daily. After 15 days, blood and testis samples were collected for biochemical, histological, and ultrastructural studies. The results show that paracetamol decreased the PCV, Hb, and RBC counts relative to the control, and significantly increased the WBC counts and stab cells in Group 3. A significant decrease in blood testosterone was found in Group 3 compared to the control, while a significant increase in testosterone levels was observed in Group 4 compared to Group 3. Light and electron microscopy showed disorganized seminiferous tubules in Group 3. The testis in Group 4 appeared in normal shape. In conclusion, the results indicate that EVOO protects the testis and blood from paracetamol toxicity and may also increase fertility in male rats.