Jeffrey Gonzales

Relationship of continuous infusion lorazepam to serum propylene glycol concentration in critically ill adults.

Objectives:The primary objective was to evaluate the relationship between high-dose lorazepam and serum propylene glycol concentrations. Secondary objectives were a) to document the occurrence of propylene glycol accumulation associated with continuous high-dose lorazepam infusion; b) to assess the relationship between lorazepam dose, serum propylene glycol concentrations, and propylene glycol accumulation; and c) to assess the relationship between the osmol gap and serum propylene glycol concentrations. Design:Prospective, observational study. Setting:Tertiary care, medical intensive care unit. Patients:Nine critically ill adults receiving high-dose lorazepam (≥10 mg/hr) infusion. Interventions:Cumulative lorazepam dose (mg/kg) and the rate of infusion (mg·kg−1·hr−1) were monitored from initiation of lorazepam infusion until 24 hrs after discontinuation of the high-dose lorazepam infusion. Serum osmolarity was collected at 48 hrs into the high-dose lorazepam infusion and daily thereafter. Serum propylene glycol concentrations were drawn at 48 hrs into the high-dose lorazepam infusion, and the presence of propylene glycol accumulation, as evidenced by a high anion gap (≥15 mmol/L) metabolic acidosis with elevated osmol gap (≥10 mOsm/L), was assessed at that time. Measurements and Main Results:The mean cumulative high-dose lorazepam received and mean high-dose lorazepam infusion rate were 8.1 mg/kg (range, 5.1–11.7) and 0.16 mg·kg−1·hr−1 (range, 0.11–0.22), respectively. A significant correlation between high-dose lorazepam infusion rate and serum propylene glycol concentrations was observed (r2 = .557, p = .021). Osmol gap was the strongest predictor of serum propylene glycol concentrations (r2 = .804, p = .001). Propylene glycol accumulation was observed in six of nine patients at 48 hrs. No significant correlation between duration of lorazepam infusion and serum propylene glycol concentrations was observed (p = .637). Conclusions:Propylene glycol accumulation, as reflected by a hyperosmolar anion gap metabolic acidosis, was observed in critically ill adults receiving continuous high-dose lorazepam infusion for ≥48 hrs. Study findings suggest that in critically ill adults with normal renal function, serum propylene glycol concentrations may be predicted by the high-dose lorazepam infusion rate and osmol gap.

The effects of thermal injury on transcellular permeability and intestinal P-glycoprotein in rats

This study was designed to assess intestinal drug transport via transcellular absorption and intestinal P-glycoprotein content following thermal injury in rats using propranolol as a marker substrate. Male, Sprague Dawley rats (n=30) underwent either a 30% total body surface area full thickness burn or sham treatment. Twenty-four hours later, animals were anesthetized, underwent laparotomy and the proximal jejunum was cannulated. The jejunal segment was perfused with buffer containing [3H] propranolol. Following euthanasia, jejunal tissue was harvested for Western immunoblotting of P-glycoprotein and villin, and immunohistochemical analysis of P-glycoprotein. Dramatic structural changes in jejunal integrity were observed following thermal injury; however, no significant differences in the absorption characteristics of propranolol following thermal injury were observed. Mean effective permeability of propranolol was 5.67+/-1.79 and 5.85+/-1.67cm/sx10(-5) for burn and sham groups, respectively (P>0.05). P-glycoprotein and villin content in the jejunum were significantly decreased in burn animals. The transcellular transport of propranolol is unaffected 24h following thermal injury in rats, despite alterations in intestinal P-glycoprotein content. The decrease in P-glycoprotein and villin content in thermally injured animals may reflect loss of mature enterocytes at the villus tips.

Impact of an Antipsychotic Discontinuation Bundle During Transitions of Care in Critically Ill Patients

Introduction: Delirium affects a large proportion of patients admitted to the intensive care unit (ICU) and is associated with increased morbidity and mortality. Antipsychotics have become frequently used agents for the treatment of delirium; however, they are often continued at transitions of care. This has potential negative short- and long-term health consequences that are preventable. We investigated the antipsychotic tapering bundle’s impact on the rate of antipsychotic continuation at transitions from the medical intensive care unit (MICU). Methods: This was a preretrospective and postretrospective chart review that included adult patients in the MICU initiated on antipsychotic therapy for ICU delirium. A bundled multidisciplinary education program and antipsychotic discontinuation algorithm were implemented in the MICU to provide recommendations for safe and effective use of antipsychotics for ICU delirium and minimize continuation of therapy at transitions of care. Rates of antipsychotic continuation at transition from the MICU were compared between the preintervention and postintervention groups with the χ2 test. Results: A total of 140 patients in the prebundle group and 141 patients in the postbundle group were enrolled. Overall, baseline characteristics were similar. After implementation of the discontinuation bundle, antipsychotic continuation at MICU discharge decreased (27.9% in the prebundle group vs 17.7% in the postbundle group; P < .05). In the multivariate analysis, patients were less likely to be continued on antipsychotic therapy at MICU discharge after implementation of the bundle (odds ratio [OR]: 0.47; 95% confidence interval [CI]: 0.26-0.86). There were also lower rates of overall antipsychotic continuation at hospital discharge (OR: 0.4; 95% CI: 0.18-0.89). Conclusion: This is the first study to demonstrate a reduction in antipsychotic continuation at transition from the MICU after implementation of an antipsychotic discontinuation bundle in ICU patients. We believe this bundle allows for safer transitions of care from the MICU and decreases unnecessary antipsychotic therapy.

410: EXPERIENCES AND PERCEPTIONS OF PROGRAM DIRECTORS AND PRECEPTORS ON THE SCCM CPP SECTION JOURNAL CLUB

Learning Objectives: The SCCM Clinical Pharmacy and Pharmacology (CPP) Section Education Committee has facilitated a monthly journal club webinar since 2007 in which PGY-2 critical care pharmacy residents thoroughly evaluate and present publications relevant to critical care pharmacotherapy. The purpose of this research was to describe resident program directors’ (RPD) and preceptors’ experience and perceptions of the journal club webinar. Methods: An 18-item survey was developed, evaluated for face and content validity by six critical care pharmacists, and administered through an online survey tool to RPDs and preceptors of programs whose residents presented a journal club at any time from 2011-2016. Domains surveyed were demographics, precepting experience, and journal club feedback. Results were summarized using descriptive statistics. Results: Of the 57 RPDs and preceptors from unique programs that had at least one participant in the journal club, 29 (50.9%) responded. Most respondents (n=27; 93.1%) have viewed the journal club for more than two years. RPDs and preceptors felt that participation in the journal club increased their knowledge in the article content (n=13/19; 68.4%) and improved capability to provide verbal feedback (n=10/19; 52.6%). On a 5-point Likert scale (1=strongly disagree, 5=strongly agree), most RPDs and preceptors (n=27) felt participation in the journal club increased their involvement in the CPP Section (median 4, IQR 3-4), and their resident’s future involvement with the journal club (median 5, IQR 4-5), CPP Section (median 4, IQR 3-5), and SCCM (median 4, IQR 4-5). Most RPDs and preceptors (n=24) felt that it was extremely likely they would have future residents participate in the journal club (median 5, IQR 5-5). Conclusions: RPDs and preceptors felt the SCCM CPP Section journal club was beneficial in increasing content knowledge and the ability to provide feedback. Participation increased their resident’s future involvement within SCCM, the CPP Section, and the journal club. Most RPDs and preceptors would have future PGY-2 critical care residents participate in the journal club.

835: IMPACT OF AN ANTIPSYCHOTIC DISCONTINUATION BUNDLE DURING TRANSITIONS OF CARE IN ICU

Learning Objectives: Antipsychotics have become first-line treatment options for ICU delirium despite questionable efficacy. These agents are often continued at transitions of care, potentially increasing the risk of medication-related issues. No studies have evaluated an intervention aimed at decreasing the frequency of continued antipsychotic therapy at transitions of care. The purpose of this study was to determine the effect of an antipsychotic discontinuation bundle on the frequency of patients continued on antipsychotic therapy upon ICU discharge and hospital discharge. Methods: This was a pre and post retrospective study that included adult patients admitted to the MICU who were initiated on antipsychotic therapy for ICU delirium. A bundled multidisciplinary education program and antipsychotic discontinuation algorithm was developed and implemented to provide recommendations for use of antipsychotics and minimize continuation at transitions of care. The education program targeted physicians, nurse practitioners, nurses, and pharmacists. Descriptive and inferential statistics were used. Results: 140 patients in the pre-bundle group and 141 patients in the postbundle group were enrolled. Baseline characteristics were similar. Antipsychotic continuation at MICU discharge decreased, with 27.9% in the pre-bundle group versus 17.7% in the post-bundle group (OR, 0.56; 95% CI, 0.31–0.99; p<0.05). 15.7% of patients in the pre-bundle group were continued on therapy at hospital discharge versus 8.5% of patients in the post-bundle group (p=0.064). After a multivariate analysis adjustment for hospital length of stay, we found that patients were less likely to be continued on antipsychotic therapy at MICU discharge after implementation of the bundle (OR, 0.47; 95% CI, 0.26–0.86). There were also lower rates of overall antipsychotic continuation at hospital discharge (OR, 0.4; 95% CI, 0.18–0.89). Conclusions: In conclusion, this is the first study to demonstrate beneficial effects of an antipsychotic discontinuation bundle on the rate of antipsychotic continuation in ICU patients at transitions of care.

108: THE DEVELOPMENT AND DESCRIPTION OF A PHARMACOTHERAPY RESEARCH NETWORK

Introduction: Over the last decade several critical care clinical trial groups (CCCTG, ANZICS, USCIITG) have been created to foster critical care research. Complex critical care pharmacotherapy issues are often a secondary consideration of these groups. The Critical Care Pharmacotherapy Trials Netwo