ABSTRACT
INTRODUCTION/HYPOTHESIS: Prolonged exposure to opioids through analgosedation may lead to iatrogenic opioid withdrawal syndrome (IWS) once patients are extubated and weaned from sedation. With the lack of validated assessment tools, IWS is likely underdiagnosed in critically ill adult patients. METHODS: This was an IRB-approved, prospective, observational study assessing IWS based on Clinical Opiate Withdrawal Scale (COWS) from October 2019 to November 2020. Patients were included if they were ≥18 years, admitted to the critical care medicine (CCM) service, and received ≥24 hours of continuous opioid infusion. Patients were excluded if they were admitted for drug overdose, intracranial pathology, active COVID-19, transitioned to withdrawal of life support or hospice, remained GCS ≤8 and/or RASS < -2 throughout assessment period, prisoners, pregnant patients, or missing ≥2 assessments. Patients were assessed within 24 hours from opioid cessation and followed for 5 days. The primary outcome was the incidence of at least moderate IWS diagnosis assessed using COWS. Secondary outcomes included the incidence of mild IWS based on COWS, the incidence of IWS diagnosis based on a positive DSM-V score, the correlation between diagnosis of IWS by DSM-V and COWS, and the identification of risk factors for IWS. RESULTS: Ninety-two patients were 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 at least moderate IWS, based on COWS. There was a strong, positive correlation between DSM-V and COWS on the day COWS was the highest (rs(90)=0.64;p< 0.01). The IWSpositive 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. No significant differences were found between the two groups for scheduled or PRN opioids after cessation of the opioid infusion. Logistic regression did not identify any independent predictors for the development of IWS. CONCLUSION: At least 12% of CCM patients who received ≥24 hours of continuous opioid infusions developed IWS. These patients had significantly longer durations, higher cumulative daily and total opioid doses, and higher opioid infusion rates.
ABSTRACT
INTRODUCTION: Remdesivir is a direct-acting nucleoside RNA polymerase inhibitor with activity against the novel SARS-CoV-2 virus used in the treatment of COVID-19 pneumonia. Here we describe a case of suspected remdesivir-induced acute liver failure (ALF) successfully treated with intravenous acetylcysteine. METHODS: A 68-year-old female was identified as COVID-19 positive while in the operating room undergoing multi-vessel cardiac bypass surgery. While previously asymptomatic, she required intensive care unit admission for worsening oxygenation on post-operative day (POD) 2, and remdesivir was initiated. On POD 3, amiodarone was initiated for new onset atrial fibrillation. By POD 4 (remdesivir day 3, amiodarone day 2), the patient developed an AST/ALT of >5000 units/L each, a total bilirubin of 3.1 mg/dL, and an ammonia of 161 umol/L. Remdesivir and amiodarone were discontinued and continuous infusion acetylcysteine was initiated using the 21-hour acetaminophen toxicity protocol of 150 mg/kg over 1 hour, 50 mg/kg over 4 hours, and 100 mg/kg over 16 hours. By the end of the 21-hour infusion, the AST/ ALT had decreased to 1348/1861 units/L. The patient's LFTs and total bilirubin returned to normal within 14 days of discontinuation of remdesivir (POD 18). The patient was discharged home with home health 4 days later (POD 22). RESULTS: Remdesivir has been reported in practice to cause transaminitis up to 5-10 times the upper limit of normal based on early clinical trials, and the Emergency Use Authorization (EUA) issued by the FDA requires ongoing monitoring of ALT throughout therapy. Due to remdesivir only recently being widely used in clinical practice, the incidence of remdesivir-induced ALF is unclear. Amiodarone was unlikely the cause of ALF due to very recent timing of initiation and the rapid resolution of symptoms once discontinued despite the long half-life of amiodarone. While acetylcysteine is FDA approved only for acetaminophen overdose, there are small studies and case reports of its use in nonacetaminophen- induced liver failure. The use of a novel, unapproved therapy through an EUA program may place patients at risk for unexpected adverse events and, in this case, the patient's acute liver failure resolved after treatment with acetylcysteine.