naloxone and Critical-Illness

The rapid rise in the opioid epidemic has had a deleterious impact across the United States. This increase has drawn the attention of the critical care community not only because of the surge in acute opioid overdose-related admissions, but also due to the increase in the number of opioid-dependent and opioid-tolerant patients being treated in the intensive care unit (ICU). Opioid-related issues relevant to the critical care physician include direct care of patients with opioid overdoses, the provision of sufficient analgesia to patients with opioid dependence and tolerance, and the task of preventing long-term opioid dependence in patients who survive ICU care. This review identifies the challenges facing the ICU physician working with patients presenting with opioid-related complications, discusses current solutions, and suggests future areas of research and heightened ICU clinician attention.

Topics: Analgesics, Non-Narcotic; Analgesics, Opioid; Anesthesia, Conduction; Comorbidity; Complementary Therapies; Critical Care; Critical Illness; Drug Overdose; Drug Tolerance; Humans; Intensive Care Units; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Pain Management

Sedating critically ill patients often involves prolonged opioid infusions causing opioid tolerance. Naloxone has been hypothesized to limit opioid tolerance by decreasing adenylate cyclase/cyclic adenosine monophosphate activation. The study purpose was to investigate the effect of low-dose naloxone on the maximum cumulative daily fentanyl dose in critically ill children.. We conducted a double-blinded, randomized, placebo-control trial from December 2002 through July 2004 in a university PICU. We enrolled 82 children age 1 day to 18 years requiring mechanical ventilation and fentanyl infusions anticipated to last for >4 days were eligible for enrollment. Those receiving additional oral analgesia or sedation, having a history of drug dependence or withdrawal, or having significant neurologic, renal, or hepatic disease were excluded. In addition to fentanyl infusions, patients received low-dose naloxone or placebo infusions. Medications were adjusted using the Modified Motor Activity Assessment Scale. Withdrawal was monitored using the Modified Narcotic Withdrawal Scale. Intervention was a low-dose naloxone infusion (0.25 microg/kg per hour) and the main outcome variable was the maximum cumulative daily fentanyl dose (micrograms per kilogram per day).. There was no difference in the maximum cumulative daily fentanyl dose between patients treated with naloxone (N = 37) or those receiving placebo (N = 35). Adjustment for the starting fentanyl dose also failed to reveal group differences. Total fentanyl dose received throughout the study in the naloxone group (360 microg/kg) versus placebo (223 microg/kg) was not statistically different. Placebo patients trended toward fewer rescue midazolam boluses (10.7 vs 17.8), lower total midazolam dose (11.6 mg/kg vs 23.9 mg/kg), and fewer rescue fentanyl boluses (18.5 vs 23.9).. We conclude that administration of low-dose naloxone (0.25 microg/kg per hour) does not decrease fentanyl requirements in critically ill, mechanically ventilated children.

Topics: Adolescent; Analgesics, Opioid; Child; Child, Preschool; Conscious Sedation; Critical Illness; Double-Blind Method; Female; Fentanyl; Humans; Hypnotics and Sedatives; Infant; Infant, Newborn; Infusions, Intravenous; Intensive Care Units, Pediatric; Male; Midazolam; Naloxone; Narcotic Antagonists; Respiration, Artificial; Substance Withdrawal Syndrome

Opioid-induced constipation (OIC) may occur in up to 81% of critically ill patients and can lead to many complications. Opioid antagonists are a reasonable approach and may be used for managing OIC.. The purpose of this study was to assess the efficacy of enteral naloxone (NLX) versus subcutaneous methylnaltrexone (MNTX) for the management of OIC in critically ill patients.. A retrospective analysis was conducted on adult patients who received NLX or MNTX and a continuous opioid infusion for at least 48 hours. The primary end point was time to resolution of constipation, defined as hours to first bowel movement (BM) after the first dose of an opioid antagonist. Reversal of analgesia was assessed by comparing the total number of morphine milligram equivalents (MME) 24 hours preopioid and postopioid antagonist administration. Univariate and multivariate analyses were conducted to assess treatment response within 48 hours.. The time to first BM was shorter with enteral NLX. Both NLX and MNTX appear to be effective for the management of OIC without causing reversal of analgesia. Future controlled, prospective trials comparing these agents are warranted.

Topics: Adult; Analgesics, Opioid; Constipation; Critical Illness; Humans; Naloxone; Naltrexone; Narcotic Antagonists; Opioid-Induced Constipation; Pain; Prospective Studies; Quaternary Ammonium Compounds; Retrospective Studies

Buprenorphine/naloxone has been shown to be an effective treatment of opioid use disorder. According to the Canadian National clinical practice guideline on the management of opioid use disorders, given the superior safety profile of buprenorphine/naloxone and its potential for flexible take-home dosing in comparison to other opioid agonist medication it is strongly recommended to initiate opioid agonist treatment with buprenorphine/naloxone as the preferred first-line treatment when possible. Due to its pharmacological properties induction can be challenging, requiring the cessation of all opioids for a certain amount of time to avoid the risk of precipitated withdrawal symptoms. For this reason, buprenorphine/naloxone is not initiated for the treatment of opioid use disorder in critically ill patients where continuous infusion of opioids are required for maintenance of sedation resulting in a missed opportunity for first line treatment of that patient's opioid use disorder.. We present a case of a 29-year-old female with opioid use disorder admitted for infective endocarditis and septic shock requiring intubation for hypoxic respiratory failure secondary to bilateral lung septic emboli with a high opioid debt requiring higher than typical doses of fentanyl and dexmedetomidine infusions to maintain sedation with clinical objective sign of inadequate treatment of her pain and opioid withdrawal. She was successfully started on buprenorphine/naloxone using a rapid micro-induction technique that did not cause precipitated withdrawal or require cessation of her fentanyl infusion.. This case illustrates a new method for starting buprenorphine/naloxone in a critically ill intubated patient, where buprenorphine/naloxone was never a consideration in this specific patient population.. This method can be used to minimize barriers to opioid agonist therapy in intubated patients.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Canada; Critical Illness; Female; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders

Opioid associated admissions to the Intensive Care Unit (ICU) are increasing, but how institutions manage the care of these patients is unknown. We studied the availability of protocols and guidelines in Intensive Care Units (ICUs) for the management of the critically ill patient with opioid use disorder.. A survey was sent to a random sampling of ICU clinicians at acute care hospitals in the United States.. Of the 300 hospitals contacted, 118 agreed to participate and 58 submitted surveys (49%, 58/118 response rate). While a majority of ICUs has a guideline to titrate sedative analgesics, only 7% reported a guideline that addresses the sedation needs of patients with opioid use disorder. Only one respondent identified a guideline for the continuation of medication-assisted treatment such as methadone. Most respondents did not have, or were unaware of, a guideline to manage opioid withdrawal or to prevent over-reversal with naloxone. Outpatient resources were offered to patients by 36% of institutions, while even fewer reported the use of a dedicated addiction care team.. Few institutional guidelines exist to provide clinicians with the tools necessary to prevent harm and promote recovery for this growing and vulnerable ICU population.

Topics: Analgesics, Opioid; Buprenorphine; Critical Care; Critical Illness; Hospitalization; Hospitals; Humans; Hypnotics and Sedatives; Intensive Care Units; Methadone; Naloxone; Opioid-Related Disorders; Outpatients; Practice Guidelines as Topic; Surveys and Questionnaires; United States

To develop novel therapies that prevent opioid tolerance in critically ill children we examined the effects of low-dose naloxone infusions on patients' needs for analgesia or sedation.. Matched case-control study in a pediatric intensive care unit at a university children's hospital.. We compared 14 pediatric ICU patients receiving low-dose naloxone and opioid infusions with 12 matched controls receiving opioid infusions.. Opioid analgesia and sedative requirements were assessed as morphine- and midazolam-equivalent doses, respectively. No differences were observed between groups in opioid doses at baseline or during naloxone, but in the postnaloxone period opioid doses tended to be lower in the naloxone group. Compared to baseline the naloxone group required more opioids during naloxone but fewer opioids after naloxone. Total sedative doses were comparable at baseline in both groups, with no differences in the postnaloxone period. The naloxone group required less sedation after naloxone but sedation doses were unchanged in controls. The two groups did not differ in pain scores, sedation scores, or opioid side effects.. Naloxone did not reduce the need for opioid during the infusion period but tended to reduce opioid requirements in the postnaloxone period without additional need for sedation. Randomized clinical trials may examine the effects of low-dose naloxone on opioid tolerance and side effects in pediatric ICU patients requiring prolonged opioid analgesia.

Topics: Analgesia; Analgesics, Opioid; Case-Control Studies; Child; Conscious Sedation; Critical Care; Critical Illness; Drug Tolerance; Female; Humans; Male; Naloxone; Narcotic Antagonists; Retrospective Studies

Topics: Analgesia; Anesthesia, Intravenous; Critical Illness; Drug Synergism; Humans; Naloxone; Pain, Postoperative; Pentazocine