Oral or intravenous antidote for paracetamol overdose

Abstract

A short cut review was carried out to establish whether there was any evidence to decide between oral or intravenous antidote in paracetamol (acetaminophen) poisoning. Altogether 330 papers were found using the reported search, of which two presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. A clinical bottom line is stated. Clinical scenarioA 23 year old woman attends an emergency department having taken sixty 500 mg paracetamol tablets. Her four hour paracetamol levels are above the treatment line. She does not want to be treated with intravenous therapy. You wonder whether oral antidote is as effective. Search outcomeAltogether 330 papers were identified, of which two were directly relevant to the question (table 1). Comment(s)Perry's study used historical controls although the demographic characteristics of the two groups were remarkably similar. It was not included in Buckley's meta-analysis because the patients were not recruited sequentially and it was unclear whether the patients were treated solely at the study centre (possible variations in other treatment modalities could act as confounding factors).There have been no RCTs in this area. A meta-analysis of observational studies has failed to show a difference in efficacy between the oral and intravenous routes. However, these studies do not address other factors that may influence the choice of route, which include: activated charcoal adsorbs antidote and therefore precludes its use; the IV regimen is shorter than the oral (24 hours and 52 hours respectively); the IV route is safer with patients with altered levels of consciousness (for example due to coingestants) who may subsequently lose their airway protective reflexes.c CLINICAL BOTTOM LINE The IV route is the treatment of choice for paracetamol poisoning, but the oral route has a similar efficacy and is a suitable alternative if IV access is difficult (for example IV drug abusers) or refused by the patient. Best evidence topic reports (BETs) summarise the evidence pertaining to particular clinical questions. They are not systematic reviews, but rather contain the best (highest level) evidence that can be practically obtained by busy practising clinicians. The search strategies used to find the best evidence are reported in detail in order to allow clinicians to update searches whenever necessary. The BETs published below were first reported at the Critical Appraisal Journal Club at the Manchester Royal Infirmary. 1 Each BET has been constructed in the four stages that have been described elsewhere.2 The BETs shown here together with those published previously and those currently under construction can be seen at http://www.bestbets.org.3 Six BETs are included in this issue of the journal.

Take-home naloxone programs for suspected opioid overdose in community settings: a scoping umbrella review

“… Effectiveness of naloxone and take-home naloxone (THN) for opioid overdose reversal 3 2006 – Brooker_2019 [ 52 ] Short cut/rapid review To explore the experience in administering naloxone in a home or community setting by community and lay users, community service staff, police and other non-healthcare professionals, as well as allied health professional. Provision, feasibility and acceptability of naloxone distribution 11 2019 – Clarke_2002 [ 53 ] Short cut/rapid review To establish whether patients with no recurrence of symptoms one hour after receiving naloxone for an opioid overdose can safely be discharged. Overdose response after naloxone administration 5 2000 – Ishiyama_2013 [ 54 ] Short cut/rapid review To establish whether nebulised naloxone is a safe and effective alternative to intravenous naloxone in reversing opioid toxicity.…”

“…None of the primary articles compared outcomes between people transported and not transported to hospital [ 30 ]. Three more non-systematic review articles evaluated evidence related to the need for observation after treatment with naloxone [ 65 , 73 , 74 ]. A fourth evidence review examined the effectiveness of giving chest compression and/or rescue breaths after naloxone administration [ 66 ].…”

Simple Reversed-Phase HPLC Method with Spectrophotometric Detection for Measuring Acetaminophen-Protein Adducts in Rat Liver Samples

“…dose, 30 min before a treatment with APAP. While NAC is the most widely accepted antidote for cases of APAP overdose [ 14 , 15 ], TAU has shown prophylactic and therapeutic effects in APAP-induced hepatic injury, apoptosis, and necrosis [ 13 ]. In the absence of an antidote, a discernible peak with a retention time ( ∼ 22.5 min) comparable with that of an authentic sample of APAP-Cys, and yielding an area equivalent to 19 μ g/g of liver sample, was observed at 6 hr after a treatment with APAP.…”

Take-Home Naloxone Programs for Suspected Opioid Overdose in Community Settings: A Scoping Umbrella Review

“…None of the primary articles compared outcomes between people transported and not transported to hospital (51). Three more non-systematic review articles evaluated evidence related to the need for observation after treatment with naloxone (63)(64)(65). A fourth evidence review examined the effectiveness of giving chest compression and/or rescue breaths after naloxone administration (66).…”