The Effect of Concomitant Sirolimus and Propofol Therapy on Triglyceride Concentrations in Critically Ill Patients.

BACKGROUND: Sirolimus and propofol are both independently associated with the development of hypertriglyceridemia (HTG) during therapy. To date, there are no published reports describing synergistic or additive drug interaction resulting in HTG with concomitant use of these medications. STUDY QUESTION: To identify the occurrence of HTG in patients receiving concomitant sirolimus and propofol infusion therapy. METHODS: Adult patients receiving sirolimus and a continuous propofol infusion for at least 12 hours from January 2005 to August 2009 were retrospectively evaluated. Data included Acute Physiology and Chronic Health Evaluation II score, weight, length of propofol therapy, and baseline triglyceride (TG) concentrations. The major outcome was incidence of HTG (TGs ≥500 mg/dL). Minor outcomes included the change in TG concentration from therapy initiation and manifestations of propofol-related infusion syndrome (PRIS). RESULTS: Sixteen patients were included in the analysis, with 8 (50%) of the patients developing HTG. The patients in this case series had the following mean values: Acute Physiology and Chronic Health Evaluation II score of 20.2 ± 5.3, weight of 76.3 ± 21.2 kg, and baseline TG concentrations of 181.3 ± 89.7 mg/dL. Indications for sirolimus therapy included hematopoietic stem-cell transplantation (n = 15) and heart transplantation (n = 1). Mean length of propofol infusion was 99.8 ± 88.5 hours. The mean TG concentration during infusion was 515.6 ± 468.1 mg/dL. Fourteen (87.5%) patients had an increase of ≥100 mg/dL, 12 (75%) patients had an increase of ≥200 mg/dL, and 6 (37.5%) patients had an increase of ≥300 mg/dL in TG concentrations during therapy. Eleven patients developed one manifestation of PRIS, excluding HTG, and one patient had more than 2 new onset PRIS manifestations during propofol therapy. CONCLUSIONS: Coadministration of propofol and sirolimus can potentially result in HTG, which may warrant more frequent monitoring. Further analysis is needed to examine the mechanism and clinical impact of this interaction.

Intravenous Immune Globulin Stewardship Program at a Tertiary Academic Medical Center.

BACKGROUND: In October 2010, a pharmacist-driven stewardship program was implemented at the Brigham and Women's Hospital to ensure continued adherence to the prescribing guideline, focusing on indications for intravenous immune globulin (IVIG) use and dosing per ideal body weight. OBJECTIVE: The primary objective was to describe an IVIG stewardship program at a tertiary academic medical center. METHODS: This was a prospective, observational study from January 2013 through December 2014. All patients ordered to receive IVIG during the defined study period were included. The intervention assessed describes a pharmacist-driven IVIG stewardship program for medication approval. The primary end point was guideline compliance based on indication, dose, dosing weight, and frequency. Secondary end points included the number of patients receiving IVIG, indications, orders discontinued as a result of guideline nonadherence, and total amount dispensed. RESULTS: A total of 418 patients were identified during the study time frame. The top indications were: hypogammaglobulinemia in bone marrow transplantation and hematological malignancy (50.7%), acute solid organ rejection (11.8%), and immune thrombocytopenia with bleeding (10.1%). In all, 12 patients (2.9%) received IVIG for an indication nonadherent with the IVIG prescribing guideline; 9 patients (2.2%) and 2 patients (0.5%), respectively, received a different dose or frequency per the prescribed indication; and 12 orders (2.9%) for indications nonadherent to the guideline were discontinued. A total of 26 033 g of IVIG were dispensed during the study period. CONCLUSIONS: An IVIG stewardship program, including an institution-specific prescribing guideline and a pharmacist-driven stewardship program, may ensure guideline compliance for appropriateness of indication and dose at an academic medical center.

Pharmacy Response to the Boston Marathon Bombings at a Tertiary Academic Medical Center.

OBJECTIVE: Effective crisis response requires multidisciplinary communication and rapid action. Our goals are to highlight the experience of a pharmacy department's response to the 2013 Boston Marathon bombing, to discuss the role of the pharmacist in a crisis response, and to identify potential learning opportunities for a future mass casualty event. CASE SUMMARY: Our initial response targeted 3 general areas: staffing, supplies, and communication. Pharmacist and technician staffing was increased throughout the hospital, with a 6-fold increase of pharmacists to the emergency department (ED). To ensure adequate supplies were available, inventory on the ED automatic dispensing cabinets (ADC) was assessed for vaccines, antibiotics, and vasoactive medications. ED pharmacists prepared emergent intravenous medications in the ED while the sterile products room bolstered our supply of intravenous medications for patients in the ED and operating room. Overall, there was a 33% increase in the number of ADC transactions, with pharmacists representing 28% of all ADC transactions. To optimize communication, we formulated a comprehensive plan for the timely dissemination of information to the entire pharmacy staff. DISCUSSION: A mass casualty event is a rare occasion, and it is vital for the pharmacy department to respond rapidly with little notification. CONCLUSION: The role of a pharmacist is unique and can most effectively triage drug information and medication distribution, especially during times of high demand and high stress.

Non-Sterile to Sterile Compounding: An Unconventional Response During the COVID-19 Pandemic.

The drug supply chain has suffered many interruptions over the past decade. The COVID-19 pandemic exacerbated an already fragile infrastructure for supplying critical medications to hospitals and health-systems. The purpose of this paper is to provide insight to the history, thought-processes, and response to critical medication shortages during the COVID-19 pandemic, with a focus on hydromorphone infusions and the action steps taken to engage in non-sterile to sterile (NSTS) compounding. Over a period of 6 weeks, we compounded 1,613 NSTS hydromorphone infusion bags. All lots were cleared for sterility, particulate, potency, and endotoxin testing by an outside FDA registered laboratory. We did not have any safety reports filed specific to the NSTS compounded hydromorphone infusion bags. Over a period of 15 weeks, 715 infusions were consumed. The drug supply chain suffers frequent interruptions and critical shortages, particularly in times of a natural disaster or a global pandemic. Non-sterile to sterile compounding is often associated with risks of inaccuracies, impurities, and contamination. There are instances in which non-sterile to sterile compounding is appropriate and should be considered in times of drug shortages to support the care of hospitalized patients.

Evaluation of Cost, Workflow, and Safety of Implementing a Vial Transfer Device for Ready-to-Mix Drugs at an Academic Medical Center.

OBJECTIVE: To evaluate the cost, workflow, and safety of implementing a vial transfer device system. METHODS: In this retrospective analysis, pharmacy systems and electronic health record reports identified high-volume and high-cost medications prepared by a Vial2Bag® (V2B) system from July 2017 to June 2018. The major outcome was the extrapolated yearly cost avoidance (EYCA) from utilization of a V2B system, calculated by subtracting total costs of the V2B system from total cost of ready-to-use products and locally compounded sterile products. Secondary outcomes included a workflow and safety analysis. RESULTS: Implementing a V2B system led to a total EYCA of $2 295 261. A total of 283 209 potential V2B units were available for dispensing from automated dispensing systems and 41 082 yearly sterile product room units were avoided. A 0.02% safety report incidence per V2B administration was calculated at our institution. CONCLUSION: Use of a V2B system resulted in a substantial cost avoidance compared to purchasing commercial products and preparing locally compounded sterile products. The V2B system appears to be a safe addition to further optimize workflow but may require further investigation in prospective analyses.

Utilization of an Integrated Electronic Health Record in the Emergency Department to Increase Prospective Medication Order Review by Pharmacists.

PURPOSE:: The objective of this study is to evaluate the impact of an integrated medical record system on prospective medication order verification by pharmacists in the emergency department (ED) of a level I trauma center. METHODS:: This was a single-center retrospective analysis comparing medication orders verified by a pharmacist during a 7-day period in 2013 (phase I) versus 2015 (phase II). Outcome measures include the percentage of medication orders reviewed by a pharmacist prior to administration and time from order entry to each of the following: pharmacist review, medication procurement from an automated dispensing cabinet (ADC), and medication administration. RESULTS:: In total, 5450 medication orders were included in the study. The percentage of medication orders reviewed by a pharmacist prior to administration increased from 51.8% to 94% in phase I versus phase II, respectively ( P < .001). Median time from order entry to pharmacist verification decreased from 13 to 4 minutes in phase I versus phase II, respectively ( P < .001). Time from order entry to ADC dispense increased from a median of 9 minutes in phase I to 15 minutes in phase II ( P < .001). Time from order entry to nursing administration increased from a median time of 15 minutes in phase I to 23 minutes in phase II ( P < .001). CONCLUSION:: Implementation of prospective pharmacist order verification in the ED increased the percentage of medications reviewed by a pharmacist prior to administration and improved pharmacist efficiency in the medication verification process. This increase in pharmacist review was associated with a marginal increase in time to medication procurement and administration.

Evaluation of glucose management during therapeutic hypothermia at a Tertiary Academic Medical Center.

STUDY AIM: Alterations in metabolic function during therapeutic hypothermia (TH) decrease responsiveness to insulin and increase the risk of hyperglycemia. Glycemic control is associated with improved outcomes in selected patients; however, glycemic management strategies during TH are not defined. The objective of this analysis was to evaluate the glycemic metrics and IV insulin administration in critically ill patients during the cooling and rewarming phases of TH. METHODS: Data from 37 patients who received at least 6h of therapeutic hypothermia for cardiac arrest between January 2007 and January 2010 were retrospectively evaluated, 14 (37.8%) of whom had diabetes. RESULTS: The mean blood glucose was 9.16±3.22mmol/L and 6.54±2.45mmol/L; p<0.01 during cooling and rewarming, respectively. Twelve (32.4%) patients experienced at least one hypoglycemic event, defined as a blood glucose <4mmol/L. Nineteen (51.4%) patients experienced at least one hyperglycemic event, defined as a blood glucose >11.11mmol/L and 15 (40.5%) patients received IV insulin therapy. Patients on IV insulin had a higher incidence of diabetes (9 vs. 5; p<0.05), higher admission blood glucose (13.89±6.13 vs. 11.03±4.65mmol/L; p=0.11), and a higher incidence of hyperglycemia (14 vs. 2; p<0.01) and hypoglycemia (8 vs. 4; p<0.05). Of the patients on IV insulin, mean insulin requirements during cooling and rewarming were 15.2±16.1 and 7±12.5units/h, respectively. CONCLUSION: TH is commonly associated with hyperglycemia, hypoglycemia, and the use of IV insulin therapy. Further research is needed to determine optimal glycemic management strategies to prevent hyper- and hypoglycemia in patients during the different phases of TH.

Evaluation of the maximum beyond-use-date stability of regular human insulin extemporaneously prepared in 0.9% sodium chloride in a polyvinyl chloride bag.

BACKGROUND: Regular human insulin 100 units added to a sufficient quantity of 0.9% sodium chloride, to yield a total volume of 100 mL within a polyvinylchloride bag, is accepted to be stable for 24 hours due to physical denaturation and chemical modification. The objective of this study was to evaluate the extended stability of such extemporaneously prepared regular human insulin, stored under refrigeration, to the maximum beyond-use-date allowed by United States Pharmacopeia chapter 797. METHODS: At time "0" three admixtures of regular human insulin were prepared by withdrawing 1 mL of regular human insulin with a concentration of 100 units/mL and adding it to a sufficient quantity of 0.9% sodium chloride for injection in a polyvinylchloride bag to yield a total volume of 100 mL. The three admixtures were stored under refrigeration (2°C-8°C [36°F-46°F]), and one sample of each admixture was withdrawn and tested in duplicate at 0, 6, 24, 48, 72, 144, 168, 192, 216, 240, 312, and 336 hours. Utilizing high performance liquid chromatography, each sample underwent immediate testing. The time points were stable if the mean concentration of the samples exceeded 90% of the equilibrium concentration at 6 hours. RESULTS: The equilibrium concentration was 0.89 units/mL. Time points were stable if the mean concentration was at least 0.80 units/mL. All time points retained at least 90% of the equilibrium concentration, with the exception of hour 168 (0.79 ± 0.03 units/mL). At 192 hours the mean concentration was 0.88 ± 0.03 units/mL. At 336 hours the mean concentration was 0.91 ± 0.02 units/mL. CONCLUSION: Based on these results, regular human insulin 100 units added to 0.9% sodium chloride for injection in a polyvinylchloride bag to yield a total volume of 100 mL is stable for up to 336 hours when stored at 2°C-8°C (36°F-46°F).