{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T03:55:27Z","timestamp":1781582127798,"version":"3.54.5"},"reference-count":40,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,24]],"date-time":"2021-10-24T00:00:00Z","timestamp":1635033600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>COVID-19 patients suffering from severe acute respiratory distress syndrome (ARDS) require mechanical ventilation (MV) for respiratory failure. To achieve these ventilatory goals, it has been observed that COVID-19 patients in particular require high regimens and prolonged use of sedatives, analgesics and neuromuscular blocking agents (NMBA). Withdrawal from analgo-sedation may induce a \u201cdrug withdrawal syndrome\u201d (DWS), i.e., clinical symptoms of anxiety, tremor, agitation, hallucinations and vomiting, as a result of adrenergic activation and hyperalgesia. We describe the epidemiology, mechanisms leading to this syndrome and our strategies to prevent and treat it.<\/jats:p>","DOI":"10.3390\/jcm10214917","type":"journal-article","created":{"date-parts":[[2021,10,24]],"date-time":"2021-10-24T22:06:16Z","timestamp":1635113176000},"page":"4917","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["How to Manage Withdrawal of Sedation and Analgesia in Mechanically Ventilated COVID-19 Patients?"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3327-7263","authenticated-orcid":false,"given":"Am\u00e9d\u00e9e","family":"Ego","sequence":"first","affiliation":[{"name":"Department of Intensive Care, Erasme Hospital, Universit\u00e9 Libre de Bruxelles (ULB), 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina","family":"Halenarova","sequence":"additional","affiliation":[{"name":"Department of Intensive Care, Erasme Hospital, Universit\u00e9 Libre de Bruxelles (ULB), 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Creteur","sequence":"additional","affiliation":[{"name":"Department of Intensive Care, Erasme Hospital, Universit\u00e9 Libre de Bruxelles (ULB), 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio Silvio","family":"Taccone","sequence":"additional","affiliation":[{"name":"Department of Intensive Care, Erasme Hospital, Universit\u00e9 Libre de Bruxelles (ULB), 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1186\/s13054-020-03176-y","article-title":"Development of a work of breathing scale and monitoring need of intubation in COVID-19 pneumonia","volume":"24","author":"Apigo","year":"2020","journal-title":"Crit. Care"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1097\/MCC.0000000000000793","article-title":"Ventilation of coronavirus disease 2019 patients","volume":"27","author":"Grasselli","year":"2020","journal-title":"Curr. Opin. Crit. Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1002\/phar.2471","article-title":"Analgesia and Sedation Strategies in Mechanically Ventilated Adults with COVID-19","volume":"40","author":"Adams","year":"2020","journal-title":"Pharmacother. J. Hum. Pharmacol. Drug Ther."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Tapaskar, N., Hidalgo, D.C., Koo, G., Shingada, K., Rao, S., Rodriguez, R., Alcantar, D., Barrera, D.E., Lee, R., and Rameshkumar, N. (2021). Sedation Usage in COVID-19 Acute Respiratory Distress Syndrome: A Multicenter Study. Ann. Pharmacother.","DOI":"10.1177\/10600280211021925"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e198","DOI":"10.1213\/ANE.0000000000005131","article-title":"The Use of Analgesia and Sedation in Mechanically Ventilated Patients with COVID-19 Acute Respiratory Distress Syndrome","volume":"131","author":"Kapp","year":"2020","journal-title":"Anesthesia Analg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2342","DOI":"10.1007\/s00134-020-06307-9","article-title":"Analgesia and sedation in patients with ARDS","volume":"46","author":"Chanques","year":"2020","journal-title":"Intensive Care Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"353","DOI":"10.4037\/aacnacc2019267","article-title":"Opioid and Benzodiazepine Iatrogenic Withdrawal Syndrome in Patients in the Intensive Care Unit","volume":"30","author":"Puntillo","year":"2019","journal-title":"AACN Adv. Crit. Care"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1111\/aas.13818","article-title":"Iatrogenic withdrawal syndrome frequently occurs in paediatric intensive care without algorithm for tapering of analgosedation","volume":"65","author":"Dokken","year":"2021","journal-title":"Acta Anaesthesiol. Scand."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1097\/CCM.0b013e318181600d","article-title":"Withdrawal symptoms in critically ill children after long-term administration of sedatives and\/or analgesics: A first evaluation*","volume":"36","author":"Ista","year":"2008","journal-title":"Crit. Care Med."},{"key":"ref_10","unstructured":"Kamat, P.P., and Berkenbosch, J.W. (2020). Tolerance and Withdrawal in Critically Ill Children. Sedation and Analgesia for the Pediatric Intensivist: A Clinical Guid, Springer International Publishing."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1097\/00003246-199804000-00015","article-title":"Acute withdrawal syndrome related to the administration of analgesic and sedative medications in adult intensive care unit patients","volume":"26","author":"Cammarano","year":"1998","journal-title":"Crit. Care Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1177\/000313480006600409","article-title":"Opioid and benzodiazepine withdrawal syndrome in adult burn patients","volume":"66","author":"Brown","year":"2000","journal-title":"Am. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1007\/s00134-005-2579-3","article-title":"Withdrawal following sufentanil\/propofol and sufentanil\/midazolam. Sedation in surgical ICU patients: Correlation with central nervous parameters and endogenous opioids","volume":"31","author":"Likar","year":"2005","journal-title":"Intensive Care Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s13613-017-0310-5","article-title":"Opioid-associated iatrogenic withdrawal in critically ill adult patients: A multicenter pro-spective observational study","volume":"7","author":"Wang","year":"2017","journal-title":"Ann. Intensive Care"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1186\/cc6149","article-title":"Delirium in the intensive care unit","volume":"12","author":"Girard","year":"2008","journal-title":"Crit. Care"},{"key":"ref_16","first-page":"160","article-title":"ICU delirium\u2015A diagnostic and therapeutic challenge in the intensive care unit","volume":"50","author":"Kotfis","year":"2018","journal-title":"Anestezjol. Intensywna Ter."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"20f02686","DOI":"10.4088\/PCC.20f02686","article-title":"Weaning from Exogenous Sedation in the Era of COVID-19 Infection: Recommendations for Sedation and Its Discontinuation","volume":"22","author":"Jiang","year":"2020","journal-title":"Prim. Care Companion CNS Disord."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e0035","DOI":"10.1097\/CCE.0000000000000035","article-title":"Incidence of Dexmedetomidine Withdrawal in Adult Critically Ill Patients: A Pilot Study","volume":"1","author":"Bouajram","year":"2019","journal-title":"Crit. Care Explor."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1056\/NEJMra020617","article-title":"Management of Drug and Alcohol Withdrawal","volume":"348","author":"Kosten","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1097\/CCM.0b013e3181e7c73e","article-title":"Validity and reliability of an intuitive conscious sedation scoring tool: The nursing instrument for the communication of sedation*","volume":"38","author":"Mirski","year":"2010","journal-title":"Crit. Care Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Witenko, C.J., Littlefield, A.J., Abedian, S., An, A., Barie, P.S., and Berger, K. (2021). The Safety of Continuous Infusion Propofol in Mechanically Ventilated Adults with Coronavirus Disease 2019. Ann. Pharmacother., 10600280211017316.","DOI":"10.1177\/10600280211043188"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1007\/s00134-020-05942-6","article-title":"Respiratory drive in the acute respiratory distress syndrome: Pathophysiology, monitoring, and therapeutic interventions","volume":"46","author":"Spinelli","year":"2020","journal-title":"Intensive Care Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1177\/0885066615587868","article-title":"Low-Dose Ketamine in Chronic Critical Illness","volume":"31","author":"Moitra","year":"2015","journal-title":"J. Intensive Care Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Chen, K., Lu, Z., Xin, Y.C., Cai, Y., Chen, Y., and Pan, S.M. (2012). Alpha-2 agonists for long-term sedation during mechanical ventilation in critically ill patients. Cochrane Database Syst. Rev.","DOI":"10.1002\/14651858.CD010269"},{"key":"ref_25","first-page":"CD002024","article-title":"Alpha\u2082-adrenergic agonists for the management of opioid withdrawal","volume":"2016","author":"Gowing","year":"2016","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1053\/bean.2000.0081","article-title":"Pharmacokinetics and interaction pharmacodynamics of dexmedetomidine in humans","volume":"14","author":"Karol","year":"2000","journal-title":"Best Pract. Res. Clin. Anaesthesiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e0245","DOI":"10.1097\/CCE.0000000000000245","article-title":"Effects of a Clonidine Taper on Dexmedetomidine Use and Withdrawal in Adult Critically Ill Patients\u2014A Pilot Study","volume":"2","author":"Bhatt","year":"2020","journal-title":"Crit. Care Explor."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1177\/0960327112454896","article-title":"Two cases of acute dexmedetomidine withdrawal syndrome following prolonged infusion in the intensive care unit: Report of cases and review of the literature","volume":"32","author":"Kukoyi","year":"2013","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1016\/S0140-6736(20)30852-7","article-title":"New directions in the treatment of opioid withdrawal","volume":"395","author":"Srivastava","year":"2020","journal-title":"Lancet"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Gowing, L., Ali, R., and White, J.M. (2009). Buprenorphine for the management of opioid withdrawal. Cochrane Database Syst. Rev., CD002025.","DOI":"10.1002\/14651858.CD002025.pub4"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"187","DOI":"10.3109\/00952990.2011.653426","article-title":"Opioid Detoxification and Naltrexone Induction Strategies: Recommendations for Clinical Practice","volume":"38","author":"Sigmon","year":"2012","journal-title":"Am. J. Drug Alcohol Abus."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1046\/j.1460-9592.2003.01153.x","article-title":"Methadone dosage for prevention of opioid withdrawal in children","volume":"13","author":"Siddappa","year":"2003","journal-title":"Pediatr. Anesthesia"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1056\/NEJMra1800222","article-title":"Opioid Tolerance in Critical Illness","volume":"380","author":"Martyn","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1093\/bja\/aep392","article-title":"Opioid-induced hyperalgesia: A clinical challenge","volume":"104","author":"Colvin","year":"2010","journal-title":"Br. J. Anaesth."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.pharma.2009.07.001","article-title":"Benzodiazepine dependence: Focus on withdrawal syndrome","volume":"67","author":"Authier","year":"2009","journal-title":"Ann. Pharm. Fr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1111\/apa.14327","article-title":"Oral lorazepam can be substituted for intravenous midazolam when weaning paediatric intensive care patients off sedation","volume":"107","author":"Ista","year":"2018","journal-title":"Acta Paediatr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1159\/000362953","article-title":"Repeated administration of ketamine can induce hippocampal neurodegeneration and long-term cognitive impairment via the ROS\/HIF-1\u03b1 pathway in developing rats","volume":"33","author":"Yan","year":"2014","journal-title":"Cell Physiol. Biochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e0353","DOI":"10.1097\/CCE.0000000000000353","article-title":"ABCDEF Bundle and Supportive ICU Practices for Patients with Coronavirus Disease 2019 Infection: An International Point Prevalence Study","volume":"3","author":"Liu","year":"2021","journal-title":"Crit. Care Explor."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1503\/cmaj.1041064","article-title":"Modern antipsychotic drugs: A critical overview","volume":"172","author":"Gardner","year":"2005","journal-title":"Can. Med. Assoc. J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1176\/appi.psy.43.3.171","article-title":"The Role of Atypical Antipsychotics in the Treatment of Delirium","volume":"43","author":"Schwartz","year":"2002","journal-title":"J. Psychosom. Res."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/21\/4917\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:22:31Z","timestamp":1760167351000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/21\/4917"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,24]]},"references-count":40,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["jcm10214917"],"URL":"https:\/\/doi.org\/10.3390\/jcm10214917","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,24]]}}}