{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:17:48Z","timestamp":1787962668604,"version":"build-2784847793"},"reference-count":76,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"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>Opioids play a central role in pain management and sedation in Intensive Care Units (ICUs), where critically ill patients frequently experience moderate-to-severe pain due to illness and invasive procedures or devices. Uncontrolled pain exacerbates stress responses, contributing to clinical deterioration and adverse outcomes. Although analgesics and sedatives can mitigate these effects, their use must be carefully individualized to avoid complications such as delirium, prolonged mechanical ventilation, and increased mortality. Evidence now shows that excessive or poorly controlled analgosedation can prolong ICU length of stay and delay recovery. Current guidelines recommend opioids as first-line agents for severe acute pain in the ICU, preferably within a multimodal analgesia framework to optimize pain control while minimizing adverse effects. Opioids are also essential for improving tolerance to invasive and noninvasive mechanical ventilation. Modern ICU practice emphasizes an analgesia-first or \u201canalgosedation\u201d strategy, prioritizing pain control with intravenous opioids before adding sedatives. This approach aims to achieve light sedation, reduce ventilator days, and improve overall outcomes. Commonly used opioids include fentanyl, morphine, hydromorphone, sufentanil, and remifentanil, with short-acting agents favored when rapid titration is required. Our narrative review aims to evaluate the clinical impact of opioid use in critically ill patients, including post-ICU outcomes, and to explore the role of opioid stewardship in optimizing patient care.<\/jats:p>","DOI":"10.3390\/jcm15031039","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T15:04:46Z","timestamp":1769612686000},"page":"1039","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Strategies for a Rational Use of Opioids in Critical Care Settings"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0560-786X","authenticated-orcid":false,"given":"Giovanni","family":"Misseri","sequence":"first","affiliation":[{"name":"Department of Anaesthesia and Intensive Care, Fondazione Istituto \u201cG.Giglio\u201d Cefal\u00f9, 90015 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2156-0088","authenticated-orcid":false,"given":"Matteo","family":"Piattoli","sequence":"additional","affiliation":[{"name":"School of Medicine, Saint Camillus International University of Health and Medical Sciences \u201cUniCamillus\u201d, 00131 Rome, Italy"},{"name":"Umberto I Policlinico di Roma, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Mirasola","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia, San Giovanni di Dio Hospital, 92100 Agrigento, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Guarrera","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia and Intensive Care, Fondazione Istituto \u201cG.Giglio\u201d Cefal\u00f9, 90015 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Evangelista","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia and Intensive Care, Fondazione Istituto \u201cG.Giglio\u201d Cefal\u00f9, 90015 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5271-1810","authenticated-orcid":false,"given":"Giuseppe","family":"Cuttone","sequence":"additional","affiliation":[{"name":"Anesthesia and Intensive Care Unit, \u2018Abele Ajello\u2019 Hospital, ASP Trapani, 91026 Mazara del Vallo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2156-7554","authenticated-orcid":false,"given":"Luigi","family":"La Via","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Medical Surgical Specialties, University of Catania, 95124 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesare","family":"Gregoretti","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia and Intensive Care, Fondazione Istituto \u201cG.Giglio\u201d Cefal\u00f9, 90015 Palermo, Italy"},{"name":"School of Medicine, Saint Camillus International University of Health and Medical Sciences \u201cUniCamillus\u201d, 00131 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e079789","DOI":"10.1136\/bmj-2024-079789","article-title":"Management of pain and sedation in the intensive care unit","volume":"387","author":"Boncyk","year":"2024","journal-title":"BMJ"},{"key":"ref_2","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_3","doi-asserted-by":"crossref","first-page":"e825","DOI":"10.1097\/CCM.0000000000003299","article-title":"Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation\/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU","volume":"46","author":"Devlin","year":"2018","journal-title":"Crit. Care Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1007\/s00134-016-4297-4","article-title":"Comfort and patient-centred care without excessive sedation: The eCASH concept","volume":"42","author":"Vincent","year":"2016","journal-title":"Intensive Care Med."},{"key":"ref_5","unstructured":"The American College of Surgeon (2025, December 08). Best Practices Guidelines for Acute Pain Management in Trauma Patients. American College of Surgeons, ACS Trauma Quality Program. 2020. Available online: https:\/\/www.facs.org\/media\/exob3dwk\/acute_pain_guidelines.pdf."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"155080","DOI":"10.1016\/j.jcrc.2025.155080","article-title":"Analgosedation practice during noninvasive respiratory supports: Results from an Italian survey","volume":"88","author":"Spinazzola","year":"2025","journal-title":"J. Crit. Care"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1213\/ANE.0000000000001393","article-title":"Impact of an Analgesia-Based Sedation Protocol on Mechanically Ventilated Patients in a Medical Intensive Care Unit","volume":"123","author":"Faust","year":"2016","journal-title":"Anesth. Analg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1056\/NEJMra1208705","article-title":"Sedation and delirium in the intensive care unit","volume":"370","author":"Reade","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s40262-023-01213-x","article-title":"Pharmacokinetic Alterations Associated with Critical Illness","volume":"62","author":"Dresser","year":"2023","journal-title":"Clin. Pharmacokinet."},{"key":"ref_10","first-page":"323","article-title":"Pharmacokinetics of Opioid Infusions in the Adult Intensive Care Unit Setting\u2014A Systematic Review","volume":"64","author":"Rinfret","year":"2025","journal-title":"Clin. Pharmacokinet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1016\/j.clinthera.2018.07.021","article-title":"Altered Pharmacokinetics in Prolonged Infusions of Sedatives and Analgesics Among Adult Critically Ill Patients: A Systematic Review","volume":"40","author":"Tse","year":"2018","journal-title":"Clin. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"R204","DOI":"10.1186\/cc8212","article-title":"The incidence of sub-optimal sedation in the ICU: A systematic review","volume":"13","author":"Jackson","year":"2009","journal-title":"Crit. Care"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1097\/01.CCM.0000218416.62457.56","article-title":"Impact of systematic evaluation of pain and agitation in an intensive care unit","volume":"34","author":"Chanques","year":"2006","journal-title":"Crit. Care Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1097\/00000542-199203000-00003","article-title":"Context-sensitive half-time in multicompartment pharmacokinetic models for intravenous anesthetic drugs","volume":"76","author":"Hughes","year":"1992","journal-title":"Anesthesiology"},{"key":"ref_15","first-page":"76","article-title":"Pharmacokinetics of drug infusions","volume":"4","author":"Hill","year":"2004","journal-title":"Contin. Educ. Anaesth. Crit. Care Pain"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1097\/CCM.0000000000001347","article-title":"Population Pharmacokinetics of Fentanyl in the Critically Ill","volume":"44","author":"Choi","year":"2016","journal-title":"Crit. Care Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0749-0704(05)70039-7","article-title":"Pharmacokinetic considerations","volume":"15","author":"Volles","year":"1999","journal-title":"Crit. Care Clin."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1007\/s00134-003-1920-y","article-title":"Pharmacokinetics of long-term sufentanil infusion for sedation in ICU patients","volume":"29","author":"Ethuin","year":"2003","journal-title":"Intensive Care Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1093\/bja\/aeu160","article-title":"Influence of intensive care treatment on the protein binding of sufentanil and hydromorphone during pain therapy in postoperative cardiac surgery patients","volume":"113","author":"Saari","year":"2014","journal-title":"Br. J. Anaesth."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/S0140-6736(85)91448-5","article-title":"Renal failure and the use of morphine in intensive care","volume":"1","author":"Ball","year":"1985","journal-title":"Lancet"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/bja\/aeh086","article-title":"Pharmacokinetics of remifentanil and its major metabolite, remifentanil acid, in ICU patients with renal impairment","volume":"92","author":"Pitsiu","year":"2004","journal-title":"Br. J. Anaesth."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.pain.2010.08.039","article-title":"The measurement of pain in intensive care unit: Comparison of 5 self-report intensity scales","volume":"151","author":"Chanques","year":"2010","journal-title":"Pain"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1164\/rccm.2107138","article-title":"The Richmond Agitation-Sedation Scale: Validity and reliability in adult intensive care unit patients","volume":"166","author":"Sessler","year":"2002","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1097\/00003246-199907000-00022","article-title":"Prospective evaluation of the Sedation-Agitation Scale for adult critically ill patients","volume":"27","author":"Riker","year":"1999","journal-title":"Crit. Care Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e312","DOI":"10.1016\/j.bja.2019.03.024","article-title":"Objective monitoring of nociception: A review of current commercial solutions","volume":"123","author":"Ledowski","year":"2019","journal-title":"Br. J. Anaesth."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1097\/EJA.0000000000000304","article-title":"Monitoring heart rate variability to assess experimentally induced pain using the analgesia nociception index: A randomised volunteer study","volume":"33","author":"Jess","year":"2016","journal-title":"Eur. J. Anaesthesiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1111\/j.1365-2044.2008.05834.x","article-title":"Monitoring of sympathetic tone to assess postoperative pain: Skin conductance vs surgical stress index","volume":"64","author":"Ledowski","year":"2009","journal-title":"Anaesthesia"},{"key":"ref_28","first-page":"57972","article-title":"Objective Nociceptive Assessment in Ventilated ICU Patients: A Feasibility Study Using Pupillometry and the Nociceptive Flexion Reflex","volume":"137","author":"Wildemeersch","year":"2018","journal-title":"J. Vis. Exp."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1111\/aas.12359","article-title":"Monitoring hypnotic effect and nociception with two EEG-derived indices, qCON and qNOX, during general anaesthesia","volume":"58","author":"Jensen","year":"2014","journal-title":"Acta Anaesthesiol. Scand."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1097\/ALN.0000000000001130","article-title":"Preliminary Intraoperative Validation of the Nociception Level Index: A Noninvasive Nociception Monitor","volume":"125","author":"Edry","year":"2016","journal-title":"Anesthesiology"},{"key":"ref_31","unstructured":"(2025, November 29). Opioid Stewardship. Institute for Safe Medicine Practices Canada Website. Available online: https:\/\/www.ismp-canada.org\/opioid_stewardship\/."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Garnett, M.F., and Mini\u00f1o, A.M. (2024). Drug Overdose Deaths in the United States, 2003\u20132023, NCHS Data Brief, no 522.","DOI":"10.15620\/cdc\/170565"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1177\/25160435241265792","article-title":"Making healthcare safer IV: Marking a quarter century of patient safety improvement","volume":"29","author":"Rosen","year":"2024","journal-title":"J. Patient Saf. Risk Manag."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1002\/jac5.1052","article-title":"Implications of the opioid epidemic for critical care practice","volume":"2","author":"Erstad","year":"2019","journal-title":"J. Am. Coll. Clin. Pharm."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1016\/j.jamcollsurg.2017.10.012","article-title":"Guideline for Discharge Opioid Prescriptions after Inpatient General Surgical Procedures","volume":"226","author":"Hill","year":"2018","journal-title":"J. Am. Coll. Surg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1001\/jamainternmed.2016.3298","article-title":"Incidence of and Risk Factors for Chronic Opioid Use Among Opioid-Naive Patients in the Postoperative Period","volume":"176","author":"Sun","year":"2016","journal-title":"JAMA Intern. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1111\/jgs.12329","article-title":"Inappropriate medication prescriptions in elderly adults surviving an intensive care unit hospitalization","volume":"61","author":"Morandi","year":"2013","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e2417292","DOI":"10.1001\/jamanetworkopen.2024.17292","article-title":"Intravenous Opioid Administration During Mechanical Ventilation and Use After Hospital Discharge","volume":"7","author":"Myers","year":"2024","journal-title":"JAMA Netw. Open"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1080\/15360288.2020.1765066","article-title":"Opioid Stewardship: Building on Antibiotic Stewardship Principles","volume":"34","author":"Uritsky","year":"2020","journal-title":"J. Pain Palliat. Care Pharmacother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1186\/s13054-025-05716-w","article-title":"New persistent opioid use among ICU survivors after discharge: Incidence, predictors, and nationwide cohort analysis","volume":"29","author":"Oh","year":"2025","journal-title":"Crit. Care"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1097\/CCM.0000000000004896","article-title":"Opioid Use After Intensive Care: A Nationwide Cohort Study","volume":"49","author":"Eriksson","year":"2021","journal-title":"Crit. Care Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jss.2021.05.052","article-title":"Impact of a Multimodal Analgesia Protocol on Inpatient and Outpatient Opioid Use in Acute Trauma","volume":"268","author":"Singer","year":"2021","journal-title":"J. Surg. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"105","DOI":"10.2146\/ajhp161021","article-title":"Minimizing opioid use after acute major trauma","volume":"75","author":"Oyler","year":"2018","journal-title":"Am. J. Health-Syst. Pharm."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1053\/j.jvca.2023.03.001","article-title":"Single-Center Retrospective Comparison of Opioid-Based and Multimodal Analgesic Regimens in Adult Cardiac Surgery","volume":"37","author":"Eisenbraun","year":"2023","journal-title":"J. Cardiothorac. Vasc. Anesth."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.jtcvs.2023.11.035","article-title":"The impact of multimodal analgesia in coronary artery bypass graft surgery-a population-based analysis","volume":"169","author":"Cozowicz","year":"2025","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2280","DOI":"10.1016\/S0140-6736(22)00582-7","article-title":"Opioid versus opioid-free analgesia after surgical discharge: A systematic review and meta-analysis of randomised trials","volume":"399","author":"Fiore","year":"2022","journal-title":"Lancet"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Stamenkovic, D.M., Laycock, H., Karanikolas, M., Ladjevic, N.G., Neskovic, V., and Bantel, C. (2019). Chronic Pain and Chronic Opioid Use After Intensive Care Discharge\u2014Is It Time to Change Practice?. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00023"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1177\/0310057X211070008","article-title":"The complications of opioid use during and post-intensive care admission: A narrative review","volume":"50","author":"Moran","year":"2022","journal-title":"Anaesth. Intensive Care"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1213\/ANE.0000000000004018","article-title":"American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Perioperative Management of Patients on Preoperative Opioid Therapy","volume":"129","author":"Edwards","year":"2019","journal-title":"Anesth. Analg."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Graham, L.A., Illarmo, S., Wren, S.M., Mudumbai, S.C., and Odden, M.C. (2025). Optimal Multimodal Analgesia Combinations to Reduce Pain and Opioid Use Following Non-Cardiac Surgery: An Instrumental Variable Analysis. Reg. Anesth. Pain Med., Available online: https:\/\/rapm.bmj.com\/content\/early\/2025\/07\/17\/rapm-2025-106720.","DOI":"10.1136\/rapm-2025-106720"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e090396","DOI":"10.1136\/bmjopen-2024-090396","article-title":"Effect of a multimodal analgesia strategy on remifentanil daily consumption in mechanically ventilated adult ICU patients: Study protocol for a randomised, placebo-controlled, double-blind, parallel-group clinical trial","volume":"15","author":"Widehem","year":"2025","journal-title":"BMJ Open"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"101240","DOI":"10.1016\/j.aucc.2025.101240","article-title":"Opioid administration and weaning practices in mechanically ventilated adult intensive care unit patients: A retrospective analysis","volume":"38","author":"Helliwell","year":"2025","journal-title":"Aust. Crit. Care"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1007\/s11916-024-01319-2","article-title":"A Review of Leveraging Artificial Intelligence to Predict Persistent Postoperative Opioid Use and Opioid Use Disorder and its Ethical Considerations","volume":"29","author":"Gabriel","year":"2025","journal-title":"Curr. Pain Headache Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1038\/s41591-025-03603-z","article-title":"Clinical implementation of AI-based screening for risk for opioid use disorder in hospitalized adults","volume":"31","author":"Afshar","year":"2025","journal-title":"Nat. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1001\/jamapsychiatry.2025.0424","article-title":"Automating the Addiction Behaviors Checklist for Problematic Opioid Use Identification","volume":"82","author":"Chatham","year":"2025","journal-title":"JAMA Psychiatry"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"155263","DOI":"10.1016\/j.jcrc.2025.155263","article-title":"From promise to practice: A roadmap for artificial intelligence in critical care","volume":"91","author":"Agard","year":"2025","journal-title":"J. Crit. Care"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1186\/s13054-025-05532-2","article-title":"Implementing Artificial Intelligence in Critical Care Medicine: A consensus of 22","volume":"29","author":"Cecconi","year":"2025","journal-title":"Crit. Care"},{"key":"ref_58","first-page":"29768675241298918","article-title":"Artificial Intelligence for Mechanical Ventilation: A Transformative Shift in Critical Care","volume":"19","author":"Misseri","year":"2024","journal-title":"Ther. Adv. Pulm. Crit. Care Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"R156","DOI":"10.1186\/cc13995","article-title":"Early sedation and clinical outcomes of mechanically ventilated patients: A prospective multicenter cohort study","volume":"18","author":"Tanaka","year":"2014","journal-title":"Crit. Care"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1097\/CCM.0b013e3182a645bd","article-title":"Delirium in the ICU and subsequent long-term disability among survivors of mechanical ventilation","volume":"42","author":"Brummel","year":"2014","journal-title":"Crit. Care Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/S2213-2600(14)70051-7","article-title":"Depression, post-traumatic stress disorder, and functional disability in survivors of critical illness in the BRAIN-ICU study: A longitudinal cohort study","volume":"2","author":"Jackson","year":"2014","journal-title":"Lancet Respir. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1186\/cc2398","article-title":"Remifentanil versus fentanyl for analgesia based sedation to provide patient comfort in the intensive care unit: A randomized, double-blind controlled trial [ISRCTN43755713]","volume":"8","author":"Muellejans","year":"2004","journal-title":"Crit. Care"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1164\/rccm.201306-1174OC","article-title":"Determinants of procedural pain intensity in the intensive care unit. The Europain\u00ae study","volume":"189","author":"Puntillo","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1007\/s00134-018-5344-0","article-title":"Pain distress: The negative emotion associated with procedures in ICU patients","volume":"44","author":"Puntillo","year":"2018","journal-title":"Intensive Care Med."},{"key":"ref_65","first-page":"451","article-title":"Off-pump coronary artery bypass grafting\u2014Excellent results in a group of selected high-risk patients","volume":"42","author":"Bittner","year":"2001","journal-title":"J. Cardiovasc. Surg."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e1208","DOI":"10.1542\/peds.2009-0489","article-title":"Tolerance and withdrawal from prolonged opioid use in critically ill children","volume":"125","author":"Anand","year":"2010","journal-title":"Pediatrics"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1056\/NEJM200005183422002","article-title":"Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation","volume":"342","author":"Kress","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"591","DOI":"10.2217\/pmt-2016-0002","article-title":"Pain management in critically ill patients: A review of multimodal treatment options","volume":"6","author":"Kohler","year":"2016","journal-title":"Pain Manag."},{"key":"ref_69","first-page":"562","article-title":"Review and critique of opioid rotation practices and associated risks of toxicity","volume":"13","author":"Webster","year":"2012","journal-title":"Pain Med. Malden Mass"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1097\/00000542-200512000-00024","article-title":"Sleep, anesthesiology, and the neurobiology of arousal state control","volume":"103","author":"Lydic","year":"2005","journal-title":"Anesthesiology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1097\/CCM.0B013E3181643F29","article-title":"Sleep and recovery from critical illness and injury: A review of theory, current practice, and future directions","volume":"36","author":"Friese","year":"2008","journal-title":"Crit. Care Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"33","DOI":"10.5664\/jcsm.26742","article-title":"The effect of opioids on sleep architecture","volume":"3","author":"Dimsdale","year":"2007","journal-title":"J. Clin. Sleep Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/BF00420997","article-title":"Human sleep during chronic morphine intoxication","volume":"44","author":"Kay","year":"1975","journal-title":"Psychopharmacologia"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1186\/s13054-025-05634-x","article-title":"Post-intensive care unit clinics: Models and implementation\u2014A systematic review","volume":"29","author":"Chatterjee","year":"2025","journal-title":"Crit. Care"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Pascual, J.L., and Gaulton, T.G. (2021). Opioid Use in Critical Care: A Practical Guide, Springer Nature.","DOI":"10.1007\/978-3-030-77399-1"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1164\/rccm.202109-2112ED","article-title":"New Insights into the Comparative Effectiveness of Fentanyl and Morphine Infusions in ICU Patients","volume":"204","author":"Young","year":"2021","journal-title":"Am. J. Respir. Crit. Care Med."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/3\/1039\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T15:30:18Z","timestamp":1769614218000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/3\/1039"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,28]]},"references-count":76,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["jcm15031039"],"URL":"https:\/\/doi.org\/10.3390\/jcm15031039","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,28]]}}}