Hospital Pharmacy

Background: The COVID-19 pandemic has shown how fragile our healthcare supply chain is with product delays, drug shortages, and labor shortages being exacerbated in recent years. Objective: This article reviews current threats to the healthcare supply chain that impact patient safety and highlights potential solutions for the future. Method: A review of the literature was conducted, and important up-to-date resources associated with drug shortages and supply chain were analyzed to build foundational knowledge. Potential supply chain threats and solutions were then explored through further literature analyses. Conclusions: The information provided in this article helps to brief pharmacy leaders on current supply chain issues and solutions that can be integrated throughout the healthcare supply chain in the future.

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are available online to subscribers. Monographs can be customized to meet the needs of a facility. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, contact Wolters Kluwer customer service at 866-397-3433.

A 14-year-old boy with movement disorder and epilepsy developed status dystonicus leading to rhabdomyolysis and subsequent acute kidney injury requiring continuous renal replacement therapy (CRRT). He was given multiple intravenous sedatives and analgesics to control his dystonia and dyskinesia. 8 days after admission, his condition had improved and a trial termination of CRRT was carried out. The sedatives and analgesics were switched to oral diazepam, morphine, clonidine, and chloral hydrate. However, his renal function did not recover fully. There was rising trend of serum creatinine level with evolving hyperphosphatemia and metabolic acidosis. He also gradually developed hypoventilation, hypercapnia and pinpoint pupils after weaning CRRT. The clinical impression was over-sedation resulting in hypoventilation and respiratory failure, contributed by the deteriorating renal function. Non-invasive ventilatory support was then started and CRRT was resumed. His condition improved over the next 24 hours. Dexmedetomidine infusion was used during CRRT and he slowly required stepping up of sedatives again. A separate set of dosage for all his oral sedative agents was prepared for his subsequent CRRT weaning challenge and no more over-sedative episode was then encountered. Our case illustrated that patients at recovery phase of AKI are susceptible to medication overdose, especially during the period of CRRT weaning. Sedatives and analgesics including morphine and benzodiazepines should be used with caution during this period and alternatives may need to be considered. Advanced planning of medication dosage adjustment is advised to reduce the risk of medication overdose.

Background:Thousands of patients die every year from opioid overdose. Naloxone is a lifesaving medication FDA approved for opioid overdose reversal. Many patients may present to the emergency department (ED) and require naloxone administration. The purpose of this study was to evaluate parenteral naloxone usage in the ED. It assessed parenteral naloxone indication of use and the patient population requiring its administration in order to support the need of a take home naloxone distribution program. Methods: This study was a retrospective, randomized, single center, chart review that took place at a community hospital ED. A computerized report was generated to identify all patients 18 years of age or older who were administered naloxone in the ED from June 2020 to June 2021. The charts of 100 patients randomly selected from the generated report were reviewed to collect the following information: gender, age, indication for use, dosing, drug being reversed, risk factors for overdose, ED revisits within 1 year. Results: Out of the 100 patients randomly reviewed, 55 (55%) patients were administered parenteral naloxone for overdose indication. Eighteen (32%) of overdose patients revisited the hospital within 1 year for overdose. Thirty-six (65%) of patients administered naloxone for overdose had history of substance abuse with 45 (82%) being under the age of 65 years. Conclusion: These results support the need for a take home naloxone distribution program to be implemented for patients at risk for opioid overdose or individuals at risk of witnessing a drug overdose.

Purpose:In addition to opioid abuse and dependency, opioid use can lead to opioid related adverse drug events (ORADEs). ORADEs are associated with increased length of stay, cost of care, 30-day readmission rate, and inpatient mortality. The addition of scheduled non-opioid analgesic medications has shown to be effective in reducing opioid utilization in post-surgical and trauma populations, but evidence in entire hospital patient populations is limited. The objective of this study was to determine the effects of a multimodal analgesia order set on opioid utilization and adverse drug events in adult hospitalized patients. Methods: This retrospective pre/post implementation analysis was conducted at 3 community hospitals and a level II trauma center between January 2016 and December 2019. Patients included were 18 years of age or older, admitted for greater than 24 hours, and had at least one opioid ordered during hospital admission. The primary outcome of this analysis was the average oral morphine milligram equivalents (MME) used on days 1 through 5 of hospitalization. Secondary outcomes included the percentage of hospitalized patients with an opioid ordered for analgesia who received a scheduled non-opioid analgesic medication, the average number of ORADEs recorded in nursing assessments on hospitalization days 1 through 5, length of stay, and mortality. Multimodal analgesic medications included acetaminophen, gabapentinoids, non-steroidal anti-inflammatory drugs, muscle relaxants, and transdermal lidocaine. Results: The pre- and post-groups included 86 535 patients and 85 194 patients, respectively. The average oral MMEs used on days 1 through 5 were lower in the post-group (P < .0001). Utilization of multimodal analgesia as measured by the percentage of patients with 1 or more scheduled multimodal analgesia agent ordered increased from 33% to 49% at the end of the analysis. Conclusion: Utilization of a multimodal analgesia order set was associated with a decrease in opioid use and an increase in multimodal analgesia use in an entire hospital adult population.

Background: New-onset insomnia and other sleep disturbances occur more frequently in the inpatient setting due to a variety of physical and psychological factors. Studies have found that non-pharmacologic interventions can be effective in treating insomnia in the inpatient setting, particularly in the ICU, to prevent adverse outcomes, but further research is needed to identify optimal pharmacologic interventions. Objective: To compare treatment outcomes of patients initiated on melatonin and trazodone to treat new-onset insomnia in non-ICU hospitalized patients based on the need for an additional sleep aid therapy during hospitalization and to compare the rate of adverse events of each agent. Methods: A retrospective chart review was conducted for adult patients admitted to a non-ICU general medicine or surgical floor at a community teaching hospital between July 1, 2020 and June 30, 2021. Patients were included if they were initiated on scheduled melatonin or trazodone for the treatment of new onset insomnia during their hospitalization. Patients were excluded if they had a previous diagnosis of insomnia, were prescribed 2 sleep aids simultaneously, or if their admission medication reconciliation included pharmacologic treatment for insomnia. Clinical data collected included non-pharmacologic interventions, sleep aid dose, number of doses of sleep aid administered, and total number of nights an additional sleep aid was needed. The primary outcome was the percentage of patients needing additional therapy defined as, administering an additional sleep aid between 2100-0600 or utilizing more than 1 sleep aid agent during hospitalization compared between melatonin and trazodone. Secondary outcomes of this study included the rate of adverse events such as difficulty awakening, daytime sleepiness, serotonin syndrome, falls, and development of in hospital delirium. Results: Of 158 included patients, 132 received melatonin and 26 received trazodone. Male sex (53.8% [melatonin] vs. 53.8% [trazodone]; P = 1), hospital length of stay (7.7 vs 7.7 days; P = .68), and administration of drugs that could cause insomnia (34.1% vs 23.1%vs; P = .27) were similar between sleep aids. Percentage of patients needing an additional sleep aid during hospitalization (19.7% vs 34.6%; P = .09), and patients prescribed a sleep aid at discharge (39.4% vs 46.2%; P = .52) were similar between sleep aids, respectively. Rates of adverse events were similar between sleep aids. Conclusions: There was no significant difference between the 2 agents in terms of the primary outcome, even though a higher rate of patients treated with trazodone for new-onset insomnia during hospitalization required an additional sleep aid compared to those treated with melatonin. No difference in adverse events was observed.

Background: Enoxaparin is commonly used for venous thromboembolism (VTE) prophylaxis in hospitalized patients. Published literature exists for dose adjustment in higher body weights and renal dysfunction, but sparse literature on optimal dosing of prophylactic enoxaparin in underweight patients exists. Objective: To determine if there is a difference in adverse outcomes or effectiveness if enoxaparin VTE prophylaxis dosing is reduced to 30 mg subcutaneously once daily from standard dosing in underweight medically ill patients. Methods: This study was a retrospective chart review of a total of 171 patients, with 190 individual courses of enoxaparin included. Patients were ≥18 years of age, weighed ≤50 kg, and were given at least 2 days of consecutive therapy. Patients were excluded if they were taking anticoagulation upon admission, had a creatinine clearance <30 mL/min, were admitted to the ICU or a trauma or surgical service, or presented with bleeding or thrombosis. The Padua score and a modified score from the IMPROVE trial were used to evaluate baseline thrombotic risk and bleeding risk, respectively. Bleeding events were classified using the Bleeding Academic Research Consortium criteria. Results: No difference was seen in baseline risk of bleeding or thrombosis when comparing the reduced and standard dosing groups. No differences were observed with rates of bleeding, thrombotic events, mortality, or 30-day readmission. Conclusion: Both reduced and standard dosing strategies appeared effective for VTE prophylaxis, but neither showed superiority in reducing bleeding events. Additional larger studies are needed to evaluate safety and effectiveness of reduced dose of enoxaparin in this patient population.

Purpose:Evaluate the stability of isoproterenol hydrochloride injection in 0.9% sodium chloride in polyvinyl chloride bags for up to 90 days. Methods: Dilutions of isoproterenol hydrochloride injection to a concentration of 4 μg/mL were performed under aseptic conditions. The bags were stored in amber ultraviolet light blocking bags at room temperature (23°C-25°C) or under refrigeration (3°C-5°C). Three samples of each preparation and storage environment were analyzed on days 0, 2, 14, 30, 45, 60, and 90. Physical stability was performed by visual examination. The pH was assessed at baseline, each analysis day, and upon final degradation evaluation. Sterility of the samples was not assessed. Chemical stability of isoproterenol hydrochloride was evaluated using liquid chromatography with tandem mass spectrometry. Samples were considered stable if there was <10% degradation of the initial concentration. Results: Isoproterenol hydrochloride diluted to 4 μg/mL with 0.9% sodium chloride injection was physically stable throughout the study. No precipitation was observed. At days 2, 14, 30, 45, 60, and 90 all bags diluted to 4 μg/mL had <10% degradation when stored under refrigeration (3°C-5°C) or stored at room temperature (23°C-25°C). Conclusion: Isoproterenol hydrochloride diluted to a concentration of 4 μg/mL with 0.9% sodium chloride for injection in ultraviolet light blocking bags was stable for 90 days at room temperature and under refrigeration.

Purpose: Medications that require prior authorization can complicate the discharge planning process. This study implemented and evaluated a process for identifying and completing prior authorizations during the inpatient setting prior to patient discharge. Methods: A patient identification tool was developed within the electronic health record to alert the patient care resource manager of inpatient orders for targeted medications that frequently require prior authorization with the potential to delay discharge. A workflow process using the identification tool and flowsheet documentation was developed to prompt the initiation of a prior authorization, if necessary. Following hospital-wide implementation, descriptive data for a 2-month period was collected. Results: The tool detected 1353 medications for 1096 patient encounters over the 2-month period. The most frequent medications identified included apixaban (28.1%), enoxaparin (14.4%), sacubitril/valsartan (6.4%), and darbepoetin (6.4%). For the medications identified, there were 93 medications documented in the flowsheet data for 91 unique patient encounters. Of the 93 medications documented, 30% did not require prior authorization, 29% had prior authorization started, 10% were for patients discharged to a facility, 3% were for home medications, 3% were medications discontinued at discharge, 1% had prior authorization denied, and 24% had missing data. The most frequent medications documented in the flowsheet included apixaban (12%), enoxaparin (10%), and rifaximin (20%). Of the 28 prior authorizations processed, 2 led to a referral to the Medication Assistance Program. Conclusion: The implementation of an identification tool and documentation process can help improve PA workflow and discharge care coordination.

Background: Sugammadex is approved for postoperative recovery from rocuronium neuromuscular blockade with train-of-four (TOF) guided dosing. Data for non-perioperative sugammadex efficacy and dosing are limited when TOF is not available and reversal is not immediate. Objective: This study evaluated the efficacy, safety, and dose of sugammadex when administered in the emergency department (ED) or intensive care unit (ICU) for delayed rocuronium reversal when TOF guidance was not consistently available. Methods: This single-center, retrospective cohort study included patients over a 6-year period who received sugammadex in the ED or ICU at least 30 minutes after rocuronium administration for rapid sequence intubation (RSI). Patients who received sugammadex for intra-operative neuromuscular blockade reversal were excluded. Efficacy was defined as successful reversal documented in progress notes, TOF assessment, or improvement in Glasgow Coma Scale (GCS). Dose was evaluated in patients with successful reversal by correlating sugammadex and rocuronium dose with reversal time after paralysis. Results: Thirty-four patients were included with 19 (55.9%) patients receiving sugammadex in the ED. Sugammadex indication was acute neurologic assessment in 31 (91.1%) patients. Twenty-nine patients (85.2%) had successful reversal documented. The remaining 5 patients had fatal neurologic injuries with GCS 3 limiting non-TOF efficacy assessment. The median (IQR) sugammadex dose was 3.4 (2.5-4.1) mg/kg administered 89 (56.3-158) minutes after rocuronium. No correlation was identified between sugammadex dose, rocuronium dose, and administration time. No adverse events were noted. Conclusion: This pilot investigation demonstrated safe and effective rocuronium reversal with sugammadex 3 to 4 mg/kg administered in the non-operative setting 1 to 2 hours after RSI. Larger, prospective studies are necessary to determine the safety in patients outside of the operating room when TOF is not available.

Background: Direct oral anticoagulants (DOACs) are increasingly prescribed for the treatment of venous thromboembolism (VTE). However, little is known regarding pharmacists’ practice patterns and preferences in clinical areas of contention, such as initiation dosing, obesity, and renal impairment. Objective: To determine pharmacist trends in practice regarding DOACs for the treatment of VTE overall and within areas of clinical controversy. Methods: An electronic survey was distributed to pharmacists in the United States through national and state pharmacy organizations. Responses were collected for 30 days. Results: One hundred fifty-three complete responses were submitted. The majority of pharmacists preferred apixaban (90.2%) for the oral treatment of venous thromboembolism. When initiating apixaban or rivaroxaban for a new VTE, 76% and 64% of pharmacists surveyed, respectively, state the duration of the initiation dose phases are reduced if the patient received parenteral anticoagulation. Fifty-eight percent of pharmacists used body mass index to evaluate the appropriateness of DOACs in obese patients whereas 42% used total body weight. Preference for rivaroxaban (31.4%) was higher in this population compared to the global population (10%). Apixaban was preferred for patients with renal impairment (92.2%). However, as creatinine clearance as calculated by the Cockcroft-Gault equation (CrCl) reduced to ≤15 milliliters/minute (mL/min), preference for warfarin increased (36%). Conclusion: This national survey of pharmacists demonstrated an overall preference for apixaban and significant variability in practice patterns regarding DOACs for patients with new VTE, patients with obesity, and patients with renal impairment. Further research is warranted to evaluate the efficacy and safety of DOAC initiation dosing phase modifications. Prospective evaluations of DOACs in obese and renal dysfunction populations would confirm the safety and efficacy of DOACs in these populations.

Background. Vasopressin is frequently utilized for a variety of shock states in critically ill patients. Short stability (≤24 hours) after intravenous admixture with current manufacturer labeling requires just in time preparation and may lead to delays in therapy and increased medication waste. We aimed to evaluate vasopressin stability in 0.9% sodium chloride stored in polyvinyl chloride bags and polypropylene syringes for up to 90 days. Additionally, we evaluated the impact of extended stability on the time to administration and cost savings from reduced medical waste at an academic medical center. Methods. Dilutions of vasopressin to concentrations of 0.4 and 1.0 unit/mL were performed under aseptic conditions. The bags and syringes were stored at room temperature (23°C-25°C) or under refrigeration (3°C-5°C). Three samples of each preparation and storage environment were analyzed on days 0, 2, 14, 30, 45, 60, and 90. Physical stability was performed by visual examination. The pH was assessed at each point and upon final degradation evaluation. Sterility of the samples was not assessed. Chemical stability of vasopressin was evaluated using liquid chromatography with tandem mass spectrometry. Samples were considered stable if there was <10% degradation of the initial concentration. Results. Vasopressin diluted to 0.4 and 1.0 unit/mL with 0.9% sodium chloride injection was physically stable throughout the study. No precipitation was observed. At days 2, 14, 30, 45, 60, and 90 all bags and syringes diluted to 0.4 units/mL had <10% degradation. Vasopressin diluted to 1 unit/mL and stored under refrigeration had <10% degradation at all measured days, but when stored under room temperature was found to have >10% degradation at day 30. Implementation of a batching process resulted in reduced waste ($185 300) and improved time to administration (26 vs 4 minutes). Conclusion. Vasopressin diluted to a concentration of 0.4 units/mL with 0.9% sodium chloride injection is stable for 90 days at room temperature and under refrigeration. When diluted to 1.0 unit/mL with 0.9% sodium chloride injection it is stable for 90 days under refrigeration. Use of extended stability and sterility testing to batch prepare infusions may lead to improved time to administration and cost savings from reduced medication waste.

Purpose: Assess the impact of electronic health record interventions on patient access to post-hospital discharge prescriptions. Methods: Five interventions were implemented in the electronic health record to improve patient access to prescriptions after discharge from hospital: electronic prior authorization, alternative medication suggestions, order sets, mail order pharmacy alerts, and medication interchange instructions. This was a retrospective cohort study of patient responses from discharges during 6 months before the first intervention implementation and 6 months after the last intervention implementation documented in the electronic health record and a transition-in-care platform. Primary endpoint was the proportion of discharges with patient-reported issues that would have been prevented by the studied interventions out of number of discharges with at least one prescription, analyzed using Chi-squared test (level of significance .05). Results: Discharges with patient-reported issues that would have been prevented by the studied interventions decreased from 1.68 to 1.07 out of 1000 discharges with prescriptions (P < .001). Conclusion: Interventions in the electronic health record reduced barriers faced by patients to picking up prescriptions post-discharge from hospital, potentially leading to improved patient satisfaction and improved health outcomes. Important factors to consider for electronic health record intervention implementation are workflow development and intrusiveness of clinical decision support. Multiple targeted electronic health record interventions can improve patients’ access to prescriptions after discharge from hospital.