Phenobarbital versus benzodiazepines for alcohol withdrawal management: A retrospective comparison

INTRODUCTION: Benzodiazepine (BZD)-based regimens are first-line therapy for alcohol withdrawal syndrome (AWS). Phenobarbital (PHB) is an alternative treatment but with limited guidance for use. We evaluated the efficacy and safety of PHB compared to BZD for AWS. METHODS: This was a single-center retrospective cohort study. Adult patients were included if they received BZD symptom-triggered protocol or PHB monotherapy for management of AWS and excluded if they received both therapies, were COVID positive, or died within 48 hours of hospital admission. Data collection started on December 31, 2020 and data were collected in reverse chronological order until target sample size was attained. Primary endpoint evaluated was development of AWS-related complications. Secondary endpoints included need for adjunct therapy, duration of mechanical ventilation, hospital and ICU length of stay (LOS), and hospital mortality. Safety endpoints included incidence of hypotension, bradycardia, and significant respiratory depression. RESULTS: 100 patients out of 164 screened patients were included, with 50 patients in PHB and 50 patients in BZD cohorts. Baseline characteristics were similar, except more patients in PHB cohort had history of alcohol dependence (82% vs. 56%, p< 0.001). Majority of BZD patients were in medical ICU while PHB patients were in surgical ICU. Baseline median MINDS scores were similar [PHB, 10 (5-16) vs. BZD, 11 (5-15), p=0.99]. Median (IQR) phenobarbital loading dose given was 14.8 (12.8-15.9) mg/kg followed by maintenance dose 356 (259-389) mg with a duration of 5 (3-5) days. Total lorazepam-equivalent dose given was 19.3 (5.0-44.0) mg with a duration of 4 (3-5) days. There was no significant difference in the primary endpoint [4 (8%) vs. 4(8%), p=1.00]. MINDS score post therapy initiation was significantly higher in BZD cohort [5 (1-14) vs. 15 (8-19), p< 0.001]. Patients who received PHB therapy had significantly shorter ICU LOS in days [3 (1-7) vs. 5 (2-6), p< 0.001] but no difference in hospital LOS [PHB, 8 (5-13) vs. BZD, 7 (5-12), p=0.37]. There were no significant differences in other secondary and safety endpoints. CONCLUSION: In this study there was no difference in efficacy or safety of PHB in management of AWS compared to BZD. Larger studies to confirm PHB as first-line AWS therapy are warranted.

Use of cimetidine to reduce dapsoneinduced toxicity in a non-g6pddeficient transplant recipient

INTRODUCTION: Dapsone is a commonly used alternative for the prevention of Pneumocystis jirovecii pneumonia (PJP) in immunocompromised patients. However, its use is limited by its significant dose-dependent hematologic adverse effects such as dapsone-induced methemoglobinemia by inhibiting cytochrome 3A4 preventing dapsone's metabolism to its toxic hydroxylamine metabolite. We report a case of dapsone-induced methemoglobinemia in a kidney transplant recipient where oral cimetidine was trialed to reduce dapsone toxicity. METHODS: A 37-year-old woman presented to the emergency department (ED) with a complaint of exertional shortness of breath. Her past medical history was significant for a prior living-related kidney transplant secondary to cystinosis and recent PJP treated with atovaquone. She was initiated on dapsone for PJP prophylaxis five days prior (previous G6PD level was 20.7 U/g Hgb). Dapsone doses were initiated at 25 mg PO daily and uptitrated to 100 mg PO daily over the course of treatment. Upon arrival to the ED, the patient's oxygen (O2) saturation was 88% on room air. She was transitioned to high-flow nasal cannula and her O2 saturation remained between 83-85%. She was noted to have cyanotic fingernails upon physical examination. Her CT chest without contrast and V/Q scan were without abnormalities. Her COVID-19 PCR was negative. Her methemoglobin level was unable to be obtained. Her initial dapsone serum level was 1.4 mcg/mL. The patient was transferred to intensive care. As the patient remained refractory to O2 in the next 24 hours, it was decided to initiate cimetidine 400 mg PO three times daily. Within 24 hours of starting therapy, the patient's O2 saturation improved to 92-95% and her dapsone level downtrended to 0.88 mcg/mL. Her O2 continued to be weaned until she was stable for transfer to the floor. RESULTS: Dapsone-induced methemoglobinemia is rarely reported in non-deficient G6PD patients. Cimetidine may be an option in patients to reduce dapsone concentrations decreasing the length and degree of toxicity. Providers should closely monitor patients for dapsone toxicity despite G6PD testing as onset can occur as early as a few days after initiation.

Adapting clinical pharmacy staffing models during the COVID-19 pandemic: Lessons learned and considerations for future disaster planning

Introduction: In response to the COVID-19 pandemic, healthcare institutions faced challenges that required operational agility to facilitate provision of optimal patient care. Research Question or Hypothesis: This research was performed to elucidate how pharmacy departments adapted their staffing models and the impact on frontline staff satisfaction. Study Design: Critical care pharmacists in ACCP and ASHP list-serves were electronically invited to participate in a 28-question survey in April/May 2020. Methods: Likert-like questions used a 1-5 (strongly agree to strongly disagree) scale, and responses were compared based on degree of satisfaction with pharmacy leadership strategies implemented. Practice model changes were compared before and during COVID-19. Multivariate logistic regression was used to assess the effects of independent variables on the primary outcome, satisfaction with pharmacy leadership response. Results: Respondents (N = 168) representing 40 United States participated. Forty percent of respondents experienced a surge, 68% experienced a staffing model change, and the majority (64.9%) were satisfied overall with their pharmacy leadership's response to the COVID-19 pandemic. Both specialists (50% vs. 21%, P = 0.013) and unit-based generalists (65% vs. 35%, P < 0.001) decreased rounding in the unit. Disagreement with “Satisfied with leadership efforts to protect staff (limiting in-person meetings, changing code response)” decreased the odds of satisfaction by 96% [Odds Ratio (OR) 0.043 (95% CI 0.005-0.336), P = 0.003). Disagreement with “Satisfied with voice of front-line staff” was associated with an 84% reduction in satisfaction [OR 0.165 (95% CI 0.049- 0.549), P = 0.003]. Eliminating inperson rounds associated with a 95% decrease in satisfaction with pharmacy leadership [OR 0.053 (95% CI 0.007-0.392), P = 0.004]. Disagreement with “I believe I am at increased risk of getting COVID-19 due to departmental staffing decisions (as compared to ICU peers in other institutions)” increased satisfaction [OR 3.8, 95% confidence interval (CI) 1.06-13.91]. Conclusion: Frontline staff perceptions can inform practice model changes to improve employee satisfaction while providing safe, reliable, and responsible patient care.