Impact of Pharmacists to Improve Patient Care in the Critically Ill: A Large Multicenter Analysis Using Meaningful Metrics With the Medication Regimen Complexity-ICU (MRC-ICU) Score.

OBJECTIVES: Despite the established role of the critical care pharmacist on the ICU multiprofessional team, critical care pharmacist workloads are likely not optimized in the ICU. Medication regimen complexity (as measured by the Medication Regimen Complexity-ICU [MRC-ICU] scoring tool) has been proposed as a potential metric to optimize critical care pharmacist workload but has lacked robust external validation. The purpose of this study was to test the hypothesis that MRC-ICU is related to both patient outcomes and pharmacist interventions in a diverse ICU population. DESIGN: This was a multicenter, observational cohort study. SETTING: Twenty-eight ICUs in the United States. PATIENTS: Adult ICU patients. INTERVENTIONS: Critical care pharmacist interventions (quantity and type) on the medication regimens of critically ill patients over a 4-week period were prospectively captured. MRC-ICU and patient outcomes (i.e., mortality and length of stay [LOS]) were recorded retrospectively. MEASUREMENTS AND MAIN RESULTS: A total of 3,908 patients at 28 centers were included. Following analysis of variance, MRC-ICU was significantly associated with mortality (odds ratio, 1.09; 95% CI, 1.08-1.11; p < 0.01), ICU LOS (ß coefficient, 0.41; 95% CI, 00.37-0.45; p < 0.01), total pharmacist interventions (ß coefficient, 0.07; 95% CI, 0.04-0.09; p < 0.01), and a composite intensity score of pharmacist interventions (ß coefficient, 0.19; 95% CI, 0.11-0.28; p < 0.01). In multivariable regression analysis, increased patient: pharmacist ratio (indicating more patients per clinician) was significantly associated with increased ICU LOS (ß coefficient, 0.02; 0.00-0.04; p = 0.02) and reduced quantity (ß coefficient, -0.03; 95% CI, -0.04 to -0.02; p < 0.01) and intensity of interventions (ß coefficient, -0.05; 95% CI, -0.09 to -0.01). CONCLUSIONS: Increased medication regimen complexity, defined by the MRC-ICU, is associated with increased mortality, LOS, intervention quantity, and intervention intensity. Further, these results suggest that increased pharmacist workload is associated with decreased care provided and worsened patient outcomes, which warrants further exploration into staffing models and patient outcomes.

Front-Loaded Versus Low-Intermittent Phenobarbital Dosing for Benzodiazepine-Resistant Severe Alcohol Withdrawal Syndrome.

INTRODUCTION: Phenobarbital is frequently used to manage severe alcohol withdrawal. The purpose of this study was to compare the incidence of mechanical ventilation in patients with benzodiazepine-resistant alcohol withdrawal between front-loaded and low-intermittent phenobarbital dosing strategies. METHODS: In this retrospective before-after study, we analyzed patients that received phenobarbital for severe alcohol withdrawal syndrome in a tertiary medical ICU. Patients received low-intermittent phenobarbital doses (260 mg intravenous push × 1 followed by 130 mg intravenous push every 15 min as needed) from January  2013 to July 2015, and front-loaded phenobarbital doses (10 mg/kg intravenous infusion over 30 min) from July 2015 to January 2017. RESULTS: In total, 87 patients met inclusion criteria for this study: 41 received low-intermittent phenobarbital and 46 received front-loaded phenobarbital). The incidence of mechanical ventilation was 13 (28%) in the front-loaded dosing group vs. 26 (63%) in the low-intermittent dosing group (odds ratio 4.4 [95% CI 1.8-10.9]). The cumulative dose of phenobarbital administered and serum phenobarbital levels were similar between both groups, although the front-loaded group had significantly lower benzodiazepine requirements than the low-intermittent group (median 86 mg [IQR 24-197] vs. 228 mg [115-298], P < 0.01) and reduced need for any continuous sedative infusion (OR 7.7 [95% CI 1.6-27], P < 0.01). There was no difference in respiratory failure or hypotension. CONCLUSIONS: Front-loaded phenobarbital dosing, when compared to low-intermittent phenobarbital dosing, for benzodiazepine-resistant alcohol withdrawal was associated with significantly lower mechanical ventilation incidence and continuous sedative use.

Adjunctive Use of Ketamine for Benzodiazepine-Resistant Severe Alcohol Withdrawal: a Retrospective Evaluation.

INTRODUCTION: Benzodiazepine (BZD)-resistant alcohol withdrawal remains a challenge for most institutions due to limited evidence with available agents. One published study currently exists utilizing the N-methyl-D-aspartate antagonist, ketamine, for alcohol withdrawal. OBJECTIVE: The purpose of our study was to evaluate the effect of adjunctive ketamine continuous infusion on symptom control and lorazepam infusion requirements for BZD-resistant alcohol withdrawal patients in the intensive care unit. METHODS: A retrospective review was conducted of patients receiving ketamine adjunctively with a lorazepam infusion for severe alcohol withdrawal between August 2012 and August 2014. Outcomes included time to symptom control, lorazepam infusion requirements, ketamine initial and maximum daily infusion rates, and adverse effects of ketamine. RESULTS: Thirty patients were included in the analysis. Mean time to initiation of ketamine after the initiation of a lorazepam infusion was 41.4 h. All patients achieved initial symptom control within 1 h of ketamine initiation. Median initial ketamine infusion rate was 0.75 mg/kg/h and the average maximum daily rate was 1.6 mg/kg/h. Significant decreases in lorazepam infusion rates from baseline were observed at 24 h (- 4 mg/h; p = 0.01) after ketamine initiation. No patients experienced documented CNS adverse effects. Two patients experienced hypertension and no patients experienced tachycardia related to ketamine. CONCLUSION: Adjunctive ketamine could provide symptom control for BZD-refractory patients and may potentially reduce lorazepam infusion requirements. Future studies to determine optimal dosing, timing of initiation, and place in therapy for BZD-resistant alcohol withdrawal are needed. The mechanism of action via the NMDA receptor with ketamine may provide benefit for BZD-resistant alcohol withdrawal.

Correlation Between Partial Pressure of Arterial Carbon Dioxide and End Tidal Carbon Dioxide in Patients with Severe Alcohol Withdrawal.

BACKGROUND: Respiratory depression is a common adverse effect of benzodiazepine administration to patients with severe alcoholic withdrawal. This study was conducted to assess the value of end tidal carbon dioxide (ETCO2) levels compared to partial pressure of arterial carbon dioxide (PaCO2) levels in monitoring respiratory depression secondary to benzodiazepine treatment in patients with severe alcohol withdrawal. METHODS: We retrospectively analyzed 36 patients admitted to the intensive care unit for severe alcohol withdrawal who had been administered sedative agents. RESULTS: We observed a statistically significant correlation between PaCO2 and ETCO2 at time 1 (r=0.74, P<0.01) and time 3 (r=0.52, P=0.02) but not at time 2 (r=0.22, P=0.31). CONCLUSION: Our study confirms a positive correlation between PaCO2 and ETCO2 levels in patients experiencing severe alcohol withdrawal.

Addition of vasopressin to norepinephrine as independent predictor of mortality in patients with refractory septic shock: an observational study.

OBJECTIVE: To identify predictors of 28-day mortality among patients with refractory septic shock treated with norepinephrine with or without vasopressin. DESIGN: Prospective observational cohort study. SETTING: A 1,200-bed academic medical center. PATIENTS: One hundred thirty-seven patients with septic shock treated with norepinephrine with or without vasopressin. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The 28-day mortality rate was 37.2% (n = 51). By multivariate analysis, significant predictors of death were norepinephrine plus vasopressin administration (adjusted odds ratio [AOR], 13.96; 95% confidence interval [CI] 6.47, 30.08; p = 0.001), lack of goal-directed fluid administration during initial resuscitation (AOR 15.82; 95% CI 6.16, 40.61; p = 0.003), inappropriate initial antimicrobial therapy (AOR 8.95; 95% CI 2.93, 27.33; p = 0.05), and higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (AOR 1.14; 95% CI 1.07, 1.21; p = 0.033). Patients who received norepinephrine plus vasopressin (n = 68) had a significantly higher mortality rate than patients managed with norepinephrine alone (n = 69) 28 days after the initiation of vasopressors (54.4% vs. 20.3%; p < 0.001). This finding was confirmed in patients matched optimally across treatment groups. CONCLUSIONS: Our study found an association between the use of norepinephrine plus vasopressin and 28-day mortality in refractory septic shock. In view of its known mechanism of action, vasopressin contributed to this excess mortality. Further recommendations regarding the use of vasopressin await the results of large randomized trials evaluating its efficacy and safety for septic shock.