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Management of Pharmaceutical and Recreational Drug Poisoning

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Management of Pharmaceutical and Recreational Drug Poisoning Mégarbane et al. Ann. Intensive Care (2020) 10:157 https://doi.org/10.1186/s13613-020-00762-9 REVIEW Open Access Management of pharmaceutical and recreational drug poisoning Bruno Mégarbane1* , Mathieu Oberlin2, Jean‑Claude Alvarez3, Frederic Balen4, Sébastien Beaune5, Régis Bédry6, Anthony Chauvin7, Isabelle Claudet8, Vincent Danel9, Guillaume Debaty10, Arnaud Delahaye11, Nicolas Deye12, Jean‑Michel Gaulier13, Francis Grossenbacher14, Philippe Hantson15, Frédéric Jacobs16, Karim Jafal1, Magali Labadie17, Laurence Labat18, Jérôme Langrand19, Frédéric Lapostolle20, Philippe Le Conte21, Maxime Maignan22, Patrick Nisse23, Philippe Sauder24, Christine Tournoud25, Dominique Vodovar19, Sebastian Voicu1, Pierre‑Géraud Claret26 and Charles Cerf27 Abstract Background: Poisoning is one of the leading causes of admission to the emergency department and intensive care unit. A large number of epidemiological changes have occurred over the last years such as the exponential growth of new synthetic psychoactive substances. Major progress has also been made in analytical screening and assays, enabling the clinicians to rapidly obtain a defnite diagnosis. Methods: A committee composed of 30 experts from fve scientifc societies, the Société de Réanimation de Langue Française (SRLF), the Société Française de Médecine d’Urgence (SFMU), the Société de Toxicologie Clinique (STC), the Société Française de Toxicologie Analytique (SFTA) and the Groupe Francophone de Réanimation et d’Urgences Pédiatriques (GFRUP) evaluated eight felds: (1) severity assessment and initial triage; (2) diagnostic approach and role of toxicologi‑ cal analyses; (3) supportive care; (4) decontamination; (5) elimination enhancement; (6) place of antidotes; (7) specif‑ cities related to recreational drug poisoning; and (8) characteristics of cardiotoxicant poisoning. Population, Interven‑ tion, Comparison, and Outcome (PICO) questions were reviewed and updated as needed, and evidence profles were generated. Analysis of the literature and formulation of recommendations were then conducted according to the GRADE® methodology. Results: The SRLF‑SFMU guideline panel provided 41 statements concerning the management of pharmaceutical and recreational drug poisoning. Ethanol and chemical poisoning were excluded from the scope of these recommen‑ dations. After two rounds of discussion and various amendments, a strong consensus was reached for all recommen‑ dations. Six of these recommendations had a high level of evidence (GRADE 1 ) and six had a low level of evidence (GRADE 2 ). Twenty‑nine recommendations were in the form of expert opinion± recommendations due to the low evidences± in the literature. Conclusions: The experts reached a substantial consensus for several strong recommendations for optimal man‑ agement of pharmaceutical and recreational drug poisoning, mainly regarding the conditions and efectiveness of naloxone and N‑acetylcystein as antidotes to treat opioid and acetaminophen poisoning, respectively. Keywords: Guidelines, Poisoning, Intoxication, Pharmaceutical drug, Recreational drug, Antidote *Correspondence: [email protected] Background 1 Department of Medical and Toxicological Critical Care, Federation Poisoning is probably one of the leading causes of admis- of Toxicology, Lariboisière Hospital, AP‑HP, INSERM MURS‑1144, University of Paris, 2 Rue Ambroise Paré, Paris 75010, France sion to emergency departments and intensive care units. Full list of author information is available at the end of the article A large number of radical epidemiological changes have © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat iveco mmons .org/licen ses/by/4.0/. Mégarbane et al. Ann. Intensive Care (2020) 10:157 Page 2 of 30 occurred over the last decade, particularly the US opioid its concentration in the target organ. A toxin is said to overdose crisis and the exponential growth of new syn- be "organ-damaging" when it causes organ damage, the thetic recreational drugs called "new psychoactive sub- severity of which depends on the maximum concentra- stances" (NPS). Major progress has also been made in the tion in this target organ, while the outcome is independ- feld of analytical screening and assay techniques, now ent of plasma concentrations, with a risk of disorders that enabling the physicians in charge of the poisoned patient can persist despite elimination of the toxin. Te guide- to increasingly rapidly obtain a defnite diagnosis. lines also address the four usual aspects of treatment that Te Société de Réanimation de Langue Française need to be considered in any patient, in whom poison- (SRLF) and the Société Française de Médecine d’Urgence ing is confrmed or suspected: supportive care, antidotes (SFMU), with the participation of the Société de Toxicolo- (or specifc treatments), decontamination (i.e. designed gie Clinique (STC), the Société Française de Toxicologie to reduce the bioavailability of the toxin) and elimination Analytique (SFTA) and the Groupe Francophone de Réan- enhancing treatments (i.e. designed to enhance elimi- imation et d’Urgences Pédiatriques (GFRUP) decided nation of the toxin that has already entered the internal to revise the 2005 clinical practice guidelines on acute environment). Te concept of antidote was considered poisoning. Te objective of these guidelines, based on from a restrictive point of view, limited to drugs that analysis of the level of evidence in the literature, was to have been clearly established to act on toxicokinetics or clarify the diagnostic approach, patient triage and thera- toxicodynamics, allowing improvement of the poisoned peutic management. Because of the very wide range of patient’s functional or vital prognosis. toxins potentially involved, it was decided to focus these Finally, these guidelines provided an opportunity to guidelines on pharmaceutical and recreational drug poi- highlight the role of poison control and toxicovigilance soning, excluding ethanol and chemical poisoning. Tese centres and the important role played by expert centres. guidelines were also designed to cover all emergency care Poison control centres are centres that provide informa- settings, from the pre-hospital setting (telephone triage tion about toxic risks to health care professionals and by SAMU emergency services and on-site intervention the general public, as well as telephone assistance in the by a doctor or SMUR mobile emergency and intensive diagnosis, management and treatment of poisoning, care unit) to the hospital emergency department and with an active role in toxicovigilance. Expert centres are intensive care unit. No specifc guidelines for children emergency or intensive care facilities with more extensive were adopted, but any paediatric specifcities of clini- experience of acute toxicology, with access to more rarely cal presentation or management were identifed in each used antidotes and/or able to rapidly display exceptional recommendation. treatments. Of note, extrapolation of these guidelines, Tere is a real risk of exposure to a xenobiotic (or a adapted frst to the French practice, to other countries substance that is foreign to the human body), whether should be adjusted to the local situations such as travel- intentional or accidental, in modern society, which ling times to the hospital when considering the recom- can sometimes lead to serious or even fatal poisoning. mendations on pre-hospital interventions. We will defne "exposure" by contact with a xenobiotic, regardless of the route and "poisoning" by the presence of Methods clinical (somatic and/or mental) manifestations, or labo- Tese guidelines are the result of the work conducted ratory and/or electrocardiographic abnormalities result- by an SRLF and SFMU joint expert committee. Te ing from this exposure. We will defne the "reported dose" expert committee agenda was defned at the beginning of exposure as that reported by the patient during clini- of the study. Te organizing committee initially defned cal interview or that reported by the entourage or frst the questions to be addressed in collaboration with the responders according to the signs observed at the time of coordinators and then appointed experts in charge of discovery of the patient (empty blister packs, for exam- each question. Questions were formulated according to ple) and the "potentially toxic dose" as the dose that can a Patient Intervention Comparison Outcome (PICO) for- theoretically lead to the onset of toxic signs, for exam- mat after the frst expert committee meeting. Review of ple a supratherapeutic dose of a medication. Te guide- the literature and formulation of recommendations were lines have strived to distinguish functional toxins from then conducted according to the Grade of Recommenda- so-called "organ-damaging"
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