Improving the management of the paracetamol poisoned patient
Bibliographic record
Abstract
We read with interest the article by Pettie et al. [[1]Pettie J. Caparrotta T.M. Hunter R.W. et al.Safety and efficacy of the SNAP 12-hour acetylcysteine regimen for the treatment of paracetamol overdose.EClinicalMedicine. 2019; https://doi.org/10.1016/j.eclinm.2019.04.005Summary Full Text Full Text PDF PubMed Scopus (31) Google Scholar] and commend the group for aiming to improve the management of paracetamol overdose. We note a high proportion of (25.9%, n = 294) RIE patients in the 12-h SNAP protocol group did not have a 20-h blood concentration, largely as the result of self-discharge (n = 164) or medical decision (n = 118). Of these, six had elevated and rising ALT activity after 10 h of acetylcysteine including presumably one with a 10-h ALT of 961 U/L. It is reassuring to see a low rate of hepatotoxicity and coagulopathy (and zero deaths in Scotland), presumably attributable to excluding those presenting with hepatotoxicity. However, with imbalanced loss to follow up by 20 h, low event rates, and by modeling only the highest measured ALT (rather than rise from baseline [2Bateman D.N. Dear J. Thanacoody H.K. et al.Reduction of adverse effects from intravenous acetylcysteine treatment for paracetamol poisoning: a randomised controlled trial.Lancet. 2014; 383: 697-704Summary Full Text Full Text PDF PubMed Scopus (145) Google Scholar, 3Wong A. McNulty R. Taylor D.M. et al.The NACSTOP trial: a multi-center, cluster-controlled trial of early cessation of acetylcysteine in acetaminophen overdose.Hepatology. 2019; 69: 774-784Crossref PubMed Scopus (20) Google Scholar]), a subtler efficacy signal may have been masked. One strategy that may help prevent early discharge, in patients with signs of early liver injury, is to treat all patients requiring acetylcysteine with a 2-bag 20-h regimen [4Wong A. Isbister G.K. McNulty R. et al.Efficacy of a 2 bag acetylcysteine regimen to treat paracetamol overdose (2NAC study). Abstracts from the “39th International Congress of European Association of Poison Centres and Clinical Toxicologists (EAPCCT) 21-24th May 2019,” Naples, Italy.Clin Toxicol. 2019; https://doi.org/10.1080/15563650.2019.1598646Crossref Google Scholar, 5Wong A. Sivilotti M.L. Mcnulty R. Gunja N. Graudins A. Accuracy of the paracetamol-aminotransferase product to predict hepatotoxicity in paracetamol overdose treated with a 2 bag acetylcysteine regimen.Clin Tox. 2018; 56: 182-188Crossref PubMed Scopus (7) Google Scholar], only ceasing the infusion for patients at low risk of developing hepatotoxicity (i.e. ALT <40 U/L and a low paracetamol concentration) after 12-h of treatment [[3]Wong A. McNulty R. Taylor D.M. et al.The NACSTOP trial: a multi-center, cluster-controlled trial of early cessation of acetylcysteine in acetaminophen overdose.Hepatology. 2019; 69: 774-784Crossref PubMed Scopus (20) Google Scholar]. It should also be acknowledged that the SNAP studies were performed under the supervision of specialist toxicology units. Wider adoption at other hospitals needs to be monitored to ensure safety and efficacy. We look forward to further studies optimizing the dose and duration of acetylcysteine treatment to improve treatment of the paracetamol poisoned patient.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".