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.

Insulin Glargine in Critically ill Patients: Once/Day versus Twice/Day Dosing.

OBJECTIVE: Twice/day dosing of insulin glargine has been used to treat hyperglycemia in clinical practice; however, data supporting its use in the critically ill population are lacking. This study was designed to evaluate the safety and efficacy of twice/day insulin glargine in critically ill patients. METHODS: A retrospective study was conducted in adult patients admitted to the intensive care units between February 2013 and June 2017 who received insulin glargine twice/day or 40 units or more once/day for 48 hours or longer. Post cardiovascular surgery patients were excluded. Data were collected for up to 14 patient-days. The efficacy outcomes included the incidence of hyperglycemia (blood glucose [BG] above 180 mg/dl), predose hyperglycemia rate (BG above 180 mg/dl within 4 hrs before the dose), and BG variability (standard deviation). The safety outcome was assessed by the development of hypoglycemia (BG below 70 mg/dl). RESULTS: A total of 58 patients (twice/day = 23; once/day = 35) were included in the analysis. Demographics were similar between the groups including history of diabetes mellitus, baseline hemoglobin A1C , and home insulin use. No difference was observed between the twice/day and once/day groups in the mean BG (153 vs 154 mg/dl, p=0.95, respectively), and BG variability (46 vs 44 mg/dl, p=0.29, respectively). Although the overall incidence of hyperglycemia was similar between twice/day and once/day groups (96% vs 97%, p=1.00, respectively), the twice/day group had a significantly lower predose hyperglycemia rate (twice/day 0.27 vs once/day 0.43, p=0.02). Additionally, the twice/day group did not experience an increased incidence of hypoglycemia (twice/day 23% vs once/day 34%, p=0.57) or hypoglycemia without having anything by mouth (twice/day 0% vs once/day 9%, p=0.27). CONCLUSIONS: This is the first study demonstrating that twice/day insulin glargine reduced the rate of predose hyperglycemia without increasing the risk of hypoglycemia in critically ill patients. A large randomized study is needed to confirm the safety and efficacy of twice/day glargine in the critically ill.

Comparison of Lurasidone Versus Quetiapine for the Treatment of Delirium in Critically Ill Patients.

OBJECTIVE: To evaluate the efficacy and safety of lurasidone compared with quetiapine for treatment of delirium in critically ill patients. DESIGN: Prospective, observational cohort study. SETTING: Single-center community teaching hospital. PATIENTS: Forty adult intensive care unit (ICU) patients with delirium (Confusion Assessment Method in the ICU positive), tolerating enteral nutrition, and without active alcohol withdrawal or prior use of atypical antipsychotics. INTERVENTIONS: Patients were treated at the discretion of the prescriber with either lurasidone or quetiapine for delirium. Dose escalation and/or discontinuation were determined at the discretion of individual providers. RESULTS: Baseline characteristics differed with a higher severity of illness in patients in the quetiapine group (n = 20) and a higher baseline QTc interval in the lurasidone group (n = 20). No significant difference was seen in the time to delirium resolution (3.2 vs 3.4 days), average daily haloperidol requirements (5.7 vs 6.9 mg), hospital length of stay (LOS; 23.6 vs 27.9 days), or ICU LOS (12.1 vs 14.2 days). Lurasidone was associated with fewer ventilator support days (4.0 [interquartile range, IQR: 2.3-6.8] days vs 7 [IQR: 4.0-9.8; P = .0295] days) but also a fewer number of delirium-free days (0 [IQR: 0-1.0] days vs 2 [IQR: 0-3.0; P = .0231] days). Additionally, no difference was seen for ICU mortality (20% vs 20%), percentage of time oversedated (2.8% vs 2.7%), or incidence of QTc prolongation (10.0% vs 10.0%). CONCLUSIONS: Lurasidone for the treatment of delirium in critically ill patients did not differ in the time to delirium resolution when compared to quetiapine. Additionally, the incidence of QTc prolongation between agents does not appear to be different. Future randomized trials should evaluate dose escalation schemes and a larger proportion of patients to evaluate differences in mortality, efficacy, and life-threatening arrhythmias associated with atypical antipsychotic use.