Prevalence and Risk Factors for Iatrogenic Opioid Withdrawal in Medical Critical Care Patients.

Opioids are the mainstay of pain management and sedation in critically ill patients, which can lead to the development of physiologic tolerance and dependency. The prevalence of iatrogenic opioid withdrawal syndrome (IWS) is reported as 17-32% in the ICU; however, limited evidence exists for the medical ICU patient population. OBJECTIVES: To identify the and risk factors for IWS in adult patients admitted to critical care medicine services who received greater than or equal to 24 hours of continuous opioid infusion therapy. DESIGN SETTING AND PARTICIPANTS: A prospective, observational study was conducted in a tertiary care hospital in adult medical ICU patients. Ninety-two patients who received greater than or equal to 24 hours of continuous opioid infusions were included in the study. MAIN OUTCOMES AND MEASUREMENTS: Patients were assessed daily after opioid infusion discontinuation using the Clinical Opiate Withdrawal Scale (COWS) and the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) opioid withdrawal criteria for a maximum of 5 days. The primary outcome was the prevalence of IWS of moderate severity or greater using COWS. Secondary outcomes included the prevalence of IWS diagnosis of any severity based on COWS, the prevalence of IWS diagnosis based on a positive DSM-V score, and the identification of potential risk factors for developing IWS of any severity. RESULTS: Four hundred forty-seven patients received greater than or equal to 24 hours of continuous opioid therapy. Of these, 385 were excluded, leaving 92 patients included in the final analysis. Except for a higher prevalence of psychiatric history in the IWS-positive group, baseline characteristics were similar. Overall, 11 patients (12%) developed IWS of moderate severity or greater, based on COWS. The IWS-positive group also had longer durations of opioid infusions, higher cumulative opioid infusion doses, higher mean daily doses, and higher infusion rates at any given time. The concomitant use of dexmedetomidine (38.3 vs 15.6%, p = 0.014) and benzodiazepines (63.8 vs 37.8%, p = 0.021) during or after the opioid infusion were significantly higher in the IWS-positive group compared with the IWS-negative group. No significant differences were found between the two groups for scheduled or as needed opioids after cessation of the opioid infusion. Continuous opioid infusions greater than or equal to 72 hours and total daily dose greater than or equal to 1,200 µg were found to be independent predictors for the development of iatrogenic opioid withdrawal via logistic regression. CONCLUSIONS AND RELEVANCE: Approximately one in every eight patients receiving continuous infusion opioid for greater than 24 hours while mechanically ventilated in the medical ICU will develop IWS of moderate severity or greater; this increases to one in three patients diagnosed with DSM-V criteria or any level of IWS severity. Patients receiving opioid infusions greater than or equal to 72 hours, or a total daily fentanyl dose of greater than or equal to 1,200 µg (~ 50 µg/hr) are at a higher risk for developing IWS and should be monitored as part of clinical practice when opioid infusions are discontinued.

Acetylcysteine for the Treatment of Suspected Remdesivir-Associated Acute Liver Failure in COVID-19: A Case Series.

Remdesivir is a direct-acting nucleoside RNA polymerase inhibitor with activity against the novel severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) virus used in the treatment of coronavirus disease 2019 (COVID-19) pneumonia. Here, we present two cases of suspected remdesivir-associated acute liver failure (ALF) in which the liver failure improved after continuous infusion acetylcysteine and withdrawal of remdesivir. Both patients had significant increases in transaminases between day 3 and day 10 of remdesivir therapy accompanied by coagulopathy and encephalopathy. After initiation of continuous infusion acetylcysteine, the transaminases of both patients rapidly improved. Ultimately, one patient fully recovered while the other died of suspected septic shock. Due to its novel nature and only recent widespread use, there are very little data on the risk of ALF from remdesivir. Additionally, the data for the use of acetylcysteine to manage non-acetaminophen-induced ALF are limited. It is important to consider the risk of remdesivir-associated ALF when weighing the risk versus benefits of use, and acetylcysteine may have a role in its management.

Activated prothrombin complex concentrate for warfarin reversal in traumatic intracranial hemorrhage.

BACKGROUND: Patients with traumatic intracranial hemorrhage (TIH) anticoagulated with warfarin are at an increased risk of mortality. Fresh frozen plasma (FFP) and vitamin K have been the standard treatment for warfarin reversal; however, guidelines now recommend the use of prothrombin complex concentrate (PCC) for warfarin reversal in patients with life-threatening bleeding. Our protocol uses one vial (∼1000 units) of activated PCC (aPCC) for warfarin reversal, regardless of the weight or presenting international normalized ratio (INR). The purpose of this study was to determine the safety and efficacy of using fixed, low-dose aPCC for warfarin reversal in patients with TIH. METHODS: This was a retrospective chart review that included patients with an Abbreviated Injury Scale Head score of ≥3, TIH, and initial INR ≥ 1.5 on warfarin. Patients aged <18 years and those with no repeat INR were excluded. The primary outcome was to compare the percentage of patients with INR ≤ 1.4 after receiving aPCC versus FFP within 24 hours. RESULTS: Eighty-nine patients were in the FFP group and 31 patients in the aPCC group. The INR was reversed more effectively in the aPCC group compared with the FFP group (90.3% versus 69.7%, P = 0.029). The median time (hours) to reversal was also significantly shorter in the aPCC group compared with the FFP group (3.75 versus 6.75, P = 0.003). However, there was no difference in mortality (35.5% aPCC versus 22.2% control, P = 0.162) or incidences of thrombosis. CONCLUSION: Fixed, low-dose aPCC is safe and more effective at reversing the effects of warfarin than FFP in patients with TIH.