Abstract

TOPIC IMPORTANCE Critical care clinicians are likely to see an increasing number of patients admitted to the intensive care unit (ICU) who are receiving FDA-approved medications for opioid use disorder (MOUD) given the well-documented benefits of these agents. Oral methadone, multiple formulations of buprenorphine, and extended-release naltrexone are the three types of MOUD most likely to be encountered by ICU clinicians; however, these formulations vary with respect to formulations, pharmacokinetics, and adverse effects. REVIEW FINDINGS No published clinical practice guidelines or consensus statements are available to guide decision making in patients admitted to the ICU setting who were receiving MOUD prior to admission. Additionally, there are no randomized trials and limited observational studies evaluating issues related to MOUD use in the ICU. Therefore, ICU clinicians caring for patients admitted on MOUD must base their decision making on data extrapolation from pharmacokinetic, pharmacologic, and clinical studies performed in non-ICU settings.

Abstract

The opioid epidemic has resulted in increased opioid‐related critical care admissions, presenting challenges in acute pain management. Limited guidance exists in the management of critically ill patients with opioid use disorder (OUD). This narrative review provides the intensive care unit clinician with guidance and treatment options, including nonopioid analgesia, for patients receiving medications for OUD and for patients actively misusing opioids. Verification and continuation of the patient's outpatient medications for OUD regimen, specifically buprenorphine and methadone formulations; assessment of pain and opioid withdrawal; and treatment of acute pain with nonopioid analgesia, nonpharmacologic strategies, and short‐acting opioids as needed, are all essential to adequate management of acute pain in patients with OUD. A multidisciplinary approach to treatment and discharge planning in patients with OUD may be beneficial to engage patients with OUD early in their hospital stay to prevent withdrawal, stabilize their OUD, and reduce the risk of unplanned discharge and other associated morbidity.

Abstract

OBJECTIVES: To describe practice patterns surrounding the use of medications to treat opioid use disorder (MOUD) in critically ill patients. DESIGN: Retrospective, multicenter, observational study using the Premier AI Healthcare Database. SETTING: The study was conducted in U.S. ICUs. PATIENTS: Adult (≥ 18 yr old) patients with a history of opioid use disorder (OUD) admitted to an ICU between 2016 and 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 108,189 ICU patients (658 hospitals) with a history of OUD, 20,508 patients (19.0%) received MOUD. Of patients receiving MOUD, 13,745 (67.0%) received methadone, 2,950 (14.4%) received buprenorphine, and 4,227 (20.6%) received buprenorphine/naloxone. MOUD use occurred in 37.9% of patients who received invasive mechanical ventilation. The median day of MOUD initiation was hospital day 2 (interquartile range [IQR] 1–3) and the median duration of MOUD use was 4 days (IQR 2–8). MOUD use per hospital was highly variable (median 16.0%; IQR 10–24; range, 0–70.0%); admitting hospital explained 8.9% of variation in MOUD use. A primary admitting diagnosis of unintentional poisoning (aOR 0.41; 95% CI, 0.38–0.45), presence of an additional substance use disorder (aOR 0.66; 95% CI, 0.64–0.68), and factors indicating greater severity of illness were associated with reduced odds of receiving MOUD in the ICU. CONCLUSIONS: In a large multicenter, retrospective study, there was large variation in the use of MOUD among ICU patients with a history of OUD. These results inform future studies seeking to optimize the approach to MOUD use during critical illness.

Abstract

OBJECTIVES Buprenorphine (BUP), a partial mu-opioid receptor (MOR) agonist, is an effective analgesic and is standard-of-care for treating opioid use disorder (OUD). Transitioning from full MOR agonists to stable BUP dosing can be challenging as some patients experience BUP-precipitated opioid withdrawal (BPOW) due to its ability to displace full MOR agonists. To improve patient tolerability low-dose BUP initiation protocols deliver small, progressively escalating BUP doses, allowing gradual displacement of other opioids and replacement with BUP. We describe a case series using a novel intravenous BUP "micro-infusion" protocol for rapid medication transition with no patients meeting the operational criteria for BPOW. METHODS A retrospective case series of patients who received an 8-hour 1200 mcg BUP infusion (150 mcg/hr) and one (or more) sublingual BUP doses after medical or nonmedical full MOR agonist administration. Variables included demographic characteristics, presence of OUD, opioid medications, BUP continuation/prescription fill rates, and evidence of BPOW based on Clinical Opiate Withdrawal Scale (COWS) scores. RESULTS Of 23 patients included, 8 presented with current OUD (34.8%) and 15 were treated with full MOR agonists for analgesia (65.2%) before BUP micro-infusion. There were no instances of BPOW. Among the 8 patients with OUD, 5 (62.5%) continued sublingual BUP and filled their prescription for BUP upon discharge. CONCLUSIONS Overall, the 8-hour intravenous 1200 mcg BUP micro-infusion protocol was well-tolerated with no clinically apparent cases of BPOW and similar rates of continued sublingual BUP treatment post-discharge among patients with OUD compared with other low-dose BUP initiation protocols.

Abstract

Introduction Following prolonged opioid and/or hypnotic exposure, iatrogenic withdrawal syndrome (IWS) can develop in critically ill patients due to improper cessation of these drugs. While IWS is well-documented in pediatric and neonatal intensive care unit (ICU), research on adult ICU patients remains scarce. This scoping review aimed to map existing evidence on IWS in critically ill adults, focusing on diagnosis, epidemiology, risk factors, complications, clinical effects, treatment, and prevention. Methods A literature search across PubMed, Scopus, and Web of Science included studies from 1990 to 2024 with prospective, retrospective, or randomized controlled trial designs. Out of 3105 retrieved titles, 29 studies met inclusion criteria. Results Most studies addressed diagnosis (83%) and epidemiology (79%), with IWS definitions largely adapted from chronic drug users. Incidence varied from 13.6 to 49.5%. Several studies identified risk factors, primarily therapy-related, but only some performed robust statistical analyses. Complications and clinical effects were discussed in 12 studies but results on ICU and hospital outcomes were inconsistent. Physiological studies linked IWS to sympathetic overactivity and central nervous system excitability. Only 20% of studies examined treatment or prevention, with randomized trials assessing substitution therapy. Most strategies did not significantly alter IWS incidence, though clonidine showed potential benefits. Discussion This review highlights critical knowledge gaps and the lack of consensus or guidelines for IWS in adult ICU patients, emphasizing the need for further research.

Abstract

The number of patients maintained on buprenorphine is steadily increasing. To date, no study has reported buprenorphine management practices for these patients during critical illness, nor its relationship with supplemental full‐agonist opioid administration during their hospital stay. In this single‐center retrospective study, we have explored the incidence of buprenorphine continuation during critical illness among patients receiving buprenorphine for the treatment of opioid use disorder. Additionally, we investigated the relationship between nonbuprenorphine opioid exposure and buprenorphine administration during the intensive care unit (ICU) and post‐ICU phases of care. Our study included adults maintained on buprenorphine for opioid use disorder admitted to the ICU between December 1, 2014, and May 31, 2019. Nonbuprenorphine, full agonist opioid doses were converted to fentanyl equivalents (FEs). Fifty‐one (44%) patients received buprenorphine during the ICU phase of care, with an average dose of 8 (8–12) mg/day. During the post‐ICU phase of care, 68 (62%) received buprenorphine, with an average dose of 10 (7–14) mg/day. Lack of mechanical ventilation and acetaminophen use were also associated with buprenorphine use. Full agonist opioid use was more frequent on days when buprenorphine was not given (odds ratio [OR], 6.2 [95% CI, 2.3–16.4]; P < .001). Additionally, the average cumulative dose of opioids given on nonbuprenorphine administration days was significantly higher both in the ICU (OR, 1803 [95% CI, 1271–2553] vs OR, 327 [95% CI, 152–708] FEs/day; P < 0.001) and after ICU discharge (OR, 1476 [95% CI, 962–2265] vs OR, 238 [95% CI, 150‐377] FEs/day; P < .001). Given these findings, buprenorphine continuation during critical illness should be considered, as it is associated with significantly decreased full agonist opioid use.

Abstract

As the opioid public health crisis evolves to include fentanyl and other potent synthetic opioids, more patients are admitted to the hospital with serious complications of drug use and frequently require higher levels of care, including intensive care unit (ICU) admission, for acute and chronic conditions related to opioid use disorder (OUD). This patient population poses a unique challenge when managing sedation and ensuring adequate ventilation while intubated given their high opioid requirements. Starting a patient on medications such as buprenorphine may be difficult for inpatient providers unfamiliar with its use, which may lead to undertreatment of patients with OUD, prolonged mechanical ventilation and length of stay. We developed a 7-day buprenorphine low dose overlap initiation (LDOI) schedule for patients with OUD admitted to the ICU (Table 1). Buprenorphine tablets were split by pharmacists and placed into pre-made blister packs as a kit to be loaded into the automated medication dispensing machine for nursing to administer daily. An internal quality review validated the appropriate dosing of split-dose tablets. To simplify order entry and increase prescriber comfort with this new protocol, we generated an order set within our electronic health record software with prebuilt buprenorphine titration orders. This protocol was implemented alongside patient and healthcare team education and counseling on the LDOI process, with follow-up offered to all patients upon discharge. Here we report a series of 6 ICU patients started on buprenorphine using the LDOI schedule with split buprenorphine tablets. None of the 6 patients experienced precipitated withdrawal upon buprenorphine initiation using the LDOI schedule, and 5/6 patients were successfully extubated during the buprenorphine initiation. Four of six patients had a decrease in daily morphine milligram equivalents, with 3 patients transitioning to buprenorphine alone. Initiating buprenorphine via LDOI was found to be successful in the development of a protocol for critically ill patients with OUD. We examined LDOI of buprenorphine in intubated ICU patients and found no events of acute precipitated withdrawal. This protocol can be used as a guide for other institutions seeking to start critically ill patients on medication treatment for OUD during ICU admission.

Abstract

ABSTRACT Purpose: Pain may pose significant challenges in the intensive care unit, especially in mechanically ventilated patients. Methadone has recently emerged as an alternative option for eliciting acute analgesia. In this systematic review, we evaluated the use of methadone in mechanically ventilated patients in the intensive care unit. Source: We searched MEDLINE, EMBASE, Wiley's Cochrane Library, CINAHL, PubMed (non-MEDLINE), Scopus, and LILACS databases from inception to January 24th, 2025. Eligible studies included randomized controlled trials and observational studies that compared the use of methadone to the standard of care or to other analgosedation strategies in mechanically ventilated patients in the intensive care unit. The primary outcome was the duration of mechanical ventilation. The secondary outcomes included opioid-associated adverse effects and scores regarding pain, agitation, and delirium. Principal findings: The search strategy yielded 3,523 studies. A total of 773 patients were included across the 12 studies (including 7 abstracts and 5 manuscripts). Patient populations included patients with trauma, those with burns, those at high risk for fentanyl abstinence syndrome, those with opioid use disorder, those with opioid withdrawal symptoms, and those who had received fentanyl for 72 hours prior to weaning. Overall, compared with the group that did not receive methadone, the methadone group was associated with more ventilator-free days, shorter weaning times, and a greater probability of successful weaning on day 5. Most of the studies exhibited high risks of bias; moreover, the overall quality of the evidence was low. Conclusion: Few studies have evaluated the use of methadone in mechanically ventilated patients. Based on the low-quality evidence, methadone may be associated with improved patient-centered outcomes. Further research is warranted with respect to this topic.