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.

Implementation of Pharmacy Executive Quality and Safety Walkrounds at a Tertiary Academic Medical Center.

Background: Executive Quality and Safety WalkRounds (EWRs) is a tool that engages department leadership in discussion with the front-line employees to solicit feedback to improve quality and safety. The purpose of this study was to evaluate the impact of the implementation of pharmacy department specific EWRs on quality and safety at a tertiary academic medical center. Method: This was a single-center, retrospective analysis conducted at Brigham and Women's Hospital between November 2016 and November 2019. This study aimed to analyze the implementation of EWRs conducted every other month throughout various service areas and satellites of the pharmacy department. Data evaluated included the number of EWRs conducted, the specific areas visited, the total number of action items recommended by the staff, along with the total number of action items that were completed or remained in process. Results: During the study period, 17 visits were completed in 12 different BWH pharmacy sub-departments. A total of 98 operational, technological, and environmental action items were recommended by staff to improve quality and safety. Of the 98 action items documented, 95 (96.9%) were completed by time of our analysis. Conclusion: Pharmacy department EWRs are an important and systematic process of communication between the pharmacy leadership and frontline staff. Pharmacy department EWRs have resulted in safety and quality improvements at different levels in the pharmacy department. The EWRs program at the pharmacy department was effective in identifying and completing safety initiatives to improve the safety culture of the department.

Low Efficacy of Medication Shortage Clinical Decision Support Alerts.

OBJECTIVE: We examined clinical decision support (CDS) alerts designed specifically for medication shortages to characterize and assess provider behavior in response to these short-term clinical situations. MATERIALS AND METHODS: We conducted a retrospective analysis of the usage of medication shortage alerts (MSAs) that included at least one alternative medication suggestion and were active for 60 or more days during the 2-year study period, January 1, 2018 to December 31, 2019, in a large health care system. We characterized ordering provider behavior in response to inpatient MSAs. We then developed a linear regression model to predict provider response to alerts using the characteristics of the ordering provider and alert frequency groupings. RESULTS: During the study period, there were 67 MSAs in use that focused on 42 distinct medications in shortage. The MSAs suggested an average of 3.9 alternative medications. Adjusting for the different alerts, fellows (p = 0.004), residents (p = 0.03), and physician assistants (p = 0.02) were less likely to accept alerts on average compared with attending physicians. Further, female ordering clinicians (p < 0.001) were more likely to accept alerts on average compared with male ordering clinicians. CONCLUSION: Our findings demonstrate that providers tended to reject MSAs, even those who were sometimes flexible about their responses. The low overall acceptance rate supports the theory that alerts appearing at the time of order entry may have limited value, as they may be presented too late in the decision-making process. Though MSAs are designed to be attention-grabbing and higher impact than traditional CDS, our findings suggest that providers rarely change their clinical decisions when presented with these alerts.

Management of a parenteral opioid shortage using ASHP guidelines.

PURPOSE: Management of an acute shortage of parenteral opioid products at a large hospital through prescribing interventions and other guideline-recommended actions is described. SUMMARY: In early 2018, many hospitals were faced with a shortage of parenteral opioids that was predicted to last an entire year. The American Society of Health-System Pharmacists (ASHP) has published guidelines on managing drug product shortages. This article describes the application of these guidelines to manage the parenteral opioid shortage and the impact on opioid dispensing that occurred in 2018. Our approach paralleled that recommended in the ASHP guidelines. Daily dispensing reports generated from automated dispensing cabinets and from the electronic health record were used to capture dispenses of opioid medications. Opioid prescribing and utilization data were converted to morphine milligram equivalents (MME) to allow clinical leaders and hospital administrators to quickly evaluate opioid inventories and consumption. Action steps included utilization of substitute opioid therapies and conversion of opioid patient-controlled analgesia (PCA) and opioid infusions to intravenous bolus dose administration. Parenteral opioid supplies were successfully rationed so that surgical and elective procedures were not canceled or delayed. During the shortage, opioid dispensing decreased in the inpatient care areas from approximately 2.0 million MME to 1.4 million MME and in the operating rooms from 0.56 MME to 0.29 million MME. The combination of electronic health record alerts, increased utilization of intravenous acetaminophen and liposomal bupivacaine, and pharmacist interventions resulted in a 67% decline in PCA use and a 65% decline in opioid infusions. CONCLUSION: A multidisciplinary response is necessary for effective management of drug shortages through implementation of strategies and practices for notifying clinicians of shortages and identifying optimal alternative therapies.

Single Center Experience with Robot Technologies for Sterile Compounding: A Retrospective Review.

The compounding of sterile medication admixtures is a labor-intensive process and subject to potential human error. The addition of robotic devices and workflow technology may mitigate some of the challenges of compounding sterile product admixtures, especially for those associated with antineoplastic and hazardous medications. This article discusses the single-center experiences from October 2009 through August 2017 with various sterile compounding robotic technologies. The robotic devices included Intellifill  i.v., Cytocare, i.v.Station, i.v.Station ONCO, and i.v.Soft Assist. The objective of this analysis was to describe the experience with robotic technology and workflow devices in compounding sterile medication admixtures. The number of prepared doses for each device was tracked, and each device had a tool to validate the dose accuracy via specific gravity measurement. Nonhazardous preparations with a dose variation of > (+/- 10%) were considered failures. For hazardous medications, variation of > (+/- 5%) was considered a failure. Doses that were prepared manually were also analyzed. The Intellifill i.v. robot was used to compound more than 1,000,000 admixtures (75% of all compounded  products). The i.v.Station, Cytocare, i.v.Station  ONCO, and i.v.Soft Assist robots compounded 14%, 7%,  3%, and 0.7% of the total chemotherapy doses required. Identified barriers to optimal performance included device (hardware) and software failures as well as shortages with specific fluid and drug containers. The qualitative analysis was done for 36 drugs that were prepared using i.v.Station and i.v.Station ONCO. The passing rate was estimated to be 95%. Barriers to use the device included lack of the appropriate medication container, diluent supplies issues, and software failure. Robotic devices and workflow technology for compounding sterile medication admixtures were unable to produce all routine parenteral doses required daily.

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.

Longer hospitalization of patients with positive blood cultures receiving total parenteral nutrition.

BACKGROUND: Total parenteral nutrition (TPN) via central venous catheters has improved nutrient delivery to patients unable to receive nutrition enterally, but its administration can be complicated by bacteremia and fungemia. METHODS: At a large tertiary-care academic medical center, 245 patients with concurrent positive blood cultures, among 1,716 adult patients who received TPN over a period of three consecutive years, were divided into those in whom parenteral nutrition was continued and those in whom it was stopped after the occurrence of a positive blood culture. To determine whether continuation of TPN after a positive blood culture was associated with a statistically significantly longer hospitalization than with its discontinuation after a positive blood culture, we performed a logistic regression analysis with step-wise selection, with parenteral nutrition status as the dependent variable and type of venous access, type of pathogen responsible for a positive blood culture, recurrence of a positive blood culture, respiratory failure, shock, and length of stay as covariates. RESULTS: The prevalence of positive blood cultures was 14% among all hospitalized patients given parenteral nutrition. Parenteral nutrition was continued in 60% of the patients. Baseline co-morbid and laboratory parameters were comparable in the group of patients in whom TPN was continued and the group in which it was stopped except that the white blood cell count (WBC) was lower in the former group (9.1±6.6 mm(3) vs. 12±12.1 mm(3), p=0.015). Both groups received an average of 30 kcal/kg and 1.4 g protein/kg via TPN. There was no difference in the two groups in total calories, lipids, protein, or glutamine-base received before the occurrence of a positive blood culture (p=0.86, p=0.51, p=0.79, and p=0.42, respectively). The hospital stay of the group in which TPN was continued after a positive blood culture was statistically significantly longer than that of the group in which it was discontinued (44.6±32.3 d vs. 28.2±18.5 d, p<0.001). This difference remained significant in the multivariable logistic regression analysis. CONCLUSION: Continuation of TPN after a positive blood culture was associated with statistically significantly longer hospitalization before and after adjustment for co-morbid conditions.

Safety of compounded calcium chloride admixtures for peripheral intravenous administration in the setting of a calcium gluconate shortage.

Calcium gluconate is preferred over calcium chloride for intravenous (IV) repletion of calcium deficiencies in the inpatient setting. In the setting of a national shortage of IV calcium gluconate, our institution implemented a compounded calcium chloride admixture for IV administration. The objective of this analysis is to evaluate the peripheral infusion site safety of compounded IV calcium chloride admixtures in adult inpatients. A total of 222 patients, encompassing 224 inpatient admissions, from April to June 2011 were retrospectively reviewed. Sterile preparations of calcium chloride in 5% dextrose (600 mg/250 mL and 300 mg/100 mL) were used during the study time period. Adverse infusion site reactions were assessed using an institutional infiltration and phlebitis grading system. A total of 333 doses were administered peripherally. In all, 4 (1.8%) patients experienced a moderate to severe infusion site reaction, with 3 due to phlebitis and 1 due to infiltration. Naranjo Nomogram for Adverse Drug Reaction Assessment classified all 4 reactions to have a possible link to calcium chloride administration. Peripheral administration of compounded calcium chloride admixtures in 5% dextrose is associated with a low incidence of IV infusion site reactions and can be considered as an alternative in the event of a calcium gluconate shortage.

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).

Impact of robotic antineoplastic preparation on safety, workflow, and costs.

PURPOSE: Antineoplastic preparation presents unique safety concerns and consumes significant pharmacy staff time and costs. Robotic antineoplastic and adjuvant medication compounding may provide incremental safety and efficiency advantages compared with standard pharmacy practices. METHODS: We conducted a direct observation trial in an academic medical center pharmacy to compare the effects of usual/manual antineoplastic and adjuvant drug preparation (baseline period) with robotic preparation (intervention period). The primary outcomes were serious medication errors and staff safety events with the potential for harm of patients and staff, respectively. Secondary outcomes included medication accuracy determined by gravimetric techniques, medication preparation time, and the costs of both ancillary materials used during drug preparation and personnel time. RESULTS: Among 1,421 and 972 observed medication preparations, we found nine (0.7%) and seven (0.7%) serious medication errors (P = .8) and 73 (5.1%) and 28 (2.9%) staff safety events (P = .007) in the baseline and intervention periods, respectively. Drugs failed accuracy measurements in 12.5% (23 of 184) and 0.9% (one of 110) of preparations in the baseline and intervention periods, respectively (P < .001). Mean drug preparation time increased by 47% when using the robot (P = .009). Labor costs were similar in both study periods, although the ancillary material costs decreased by 56% in the intervention period (P < .001). CONCLUSION: Although robotically prepared antineoplastic and adjuvant medications did not reduce serious medication errors, both staff safety and accuracy of medication preparation were improved significantly. Future studies are necessary to address the overall cost effectiveness of these robotic implementations.