Evaluation of Clinical Outcomes Associated With Phenobarbital With Taper Compared to No Taper for the Management of Alcohol Withdrawal Syndrome.

BACKGROUND: Phenobarbital (PHB) has been shown to be an effective treatment of alcohol withdrawal syndrome (AWS), with multiple dosing strategies used (e.g., single-dose and symptom-triggered). Studies have often used tapered doses, typically following a front-loaded dose, despite PHB's long half-life which should lead to an ability to auto-taper. OBJECTIVE: The purpose of this study was to compare clinical outcomes associated with two PHB dosing strategies (taper [T], no taper [NT]) for AWS. METHODS: This retrospective cohort study compared adult patients admitted to the ICU from October 2017 to May 2019 who received an initial loading dose of PHB for AWS. The use of PHB was at the discretion of the clinician per our institutional guidelines. Prior to November 2018, patients were prescribed a PHB taper, while after this period, the taper was no longer recommended. The primary outcome was the proportion of patients requiring rescue PHB or adjunctive medications for AWS. Secondary outcomes included number of adjunctive agents used, prevalence of severe manifestations of AWS, ICU and hospital lengths of stay, and incidence of potentially significant drug interactions. RESULTS: A total of 172 patients were included (T: n = 81, NT: n = 91). Baseline characteristics were similar between groups, including history of severe AWS and cumulative benzodiazepine dose pre-PHB. There was no difference in the primary outcome between groups (T: 70.4% vs NT: 59.3%, P = 0.152). The median number of adjunctive agents per patient, severe manifestations, and ICU and hospital length of stay did not differ between groups. Twenty-five patients (14.5%) had potentially significant drug interactions. CONCLUSION AND RELEVANCE: The use of a PHB loading dose without a taper may be comparable to a taper strategy on clinical outcomes. Prospective studies are needed to further delineate the optimal dose of PHB for AWS.

Perceptions of a virtual interview process for pharmacy residents during the COVID-19 pandemic: A multisite survey of residency candidates, preceptors, and residency program directors.

PURPOSE: To describe the perceptions of residency candidates, residency practitioners (current residents and preceptors), and residency program directors (RPDs) regarding a virtual interview process for pharmacy residency programs across multiple institutions. METHODS: In May 2021, an anonymous web-based questionnaire characterizing perceptions of the virtual interview process used during the coronavirus disease 2019 (COVID-19) pandemic was distributed to residency candidates, residency practitioners, and RPDs across 13 institutions. Quantitative responses measured on a 5-point Likert scale were summarized with descriptive statistics, and open-ended questions were analyzed using thematic qualitative methods. RESULTS: 236 residency candidates and 253 residency practitioners/RPDs completed the questionnaire, yielding response rates of 27.8% (236 of 848), and 38.1% (253 of 663), respectively. Overall, both groups perceived the virtual interview format positively. When asked whether virtual interviews should replace in-person interviews moving forward, 60.0% (18 of 30) of RPDs indicated they agreed or strongly agreed, whereas only 30.5% (61 of 200) of current preceptors/residents and 28.7% (66 of 230) of residency candidates agreed or strongly agreed. Thematic analysis of qualitative responses revealed that while virtual interviews were easier logistically, the lack of in-person interactions was a common concern for many stakeholders. Lastly, the majority (65.0%) of residency candidates reported greater than $1,000 in savings with virtual interviews. CONCLUSION: Virtual interviews offered logistical and financial benefits. The majority of RPDs were in favor of offering virtual interviews to replace in-person interviews, whereas the majority of residency candidates and practitioners preferred on-site interviews. As restrictions persist with the ongoing pandemic, our results provide insight into best practices for virtual pharmacy residency interviews.

A Systematic Mixed-Studies Review of Hope Experiences in Parents of Children With Cancer.

BACKGROUND: Hope is negatively associated with parental psychosocial distress and psychological maladjustment as well as an important aspect of emotional well-being and coping for adults with cancer and their caregivers. Yet, little is known about hope experiences of parents of children with cancer. OBJECTIVE: The aim of this study was to comprehensively describe hope experiences in parents of children with cancer using a systematic mixed-studies review. INTERVENTION/METHODS: Psych INFO, PubMed, Academic Search Premier, and CINAHL databases were used to retrieve articles published in English between January 2005 and October 2019. Using the systematic mixed-studies review convergent design, qualitative and quantitative data were collected and extracted followed by qualitative synthesis. Seventeen articles met the inclusion criteria. Exclusion criteria were systematic reviews, nonresearch articles, case reports, and abstracts. RESULTS: Hope is a fundamental source of strength and inner guidance for parents. Findings suggest that hope is negatively correlated with parental psychological distress symptoms and coping dysfunctions. Religiosity, spirituality, and adequate provider-parent communication may strengthen hope in parents. CONCLUSION: Parental hope may help minimize psychological distress and maladjustment after a child's cancer diagnosis. Open communication channels between providers and parents are critical in preserving hope. An understanding of religiosity, spirituality, optimism, and sociodemographic variables may inform parental psychosocial interventions. IMPLICATIONS FOR PRACTICE: Early identification of parents with psychological distress is critical as they may struggle more in the absence of hope. Targeted psychosocial interventions may help parents of children with cancer cope better. Ongoing assessments of spiritual needs may be important in sustaining hope.

A Retrospective Comparison of the Effectiveness and Safety of Intravenous Olanzapine Versus Intravenous Haloperidol for Agitation in Adult Intensive Care Unit Patients.

OBJECTIVE: Intravenous (IV) olanzapine could be an alternative to first-generation antipsychotics for the management of agitation in intensive care unit (ICU) patients. We compared the effectiveness and safety of IV olanzapine to IV haloperidol for agitation management in adult patients in the ICU at a tertiary academic medical center. METHODS: A retrospective cohort study was conducted. The primary outcome was the proportion of patients who achieved a Richmond Agitation Sedation Scale (RASS) score of < +1 within 4 hours of IV olanzapine or IV haloperidol administration. Secondary outcomes included the proportion of patients who required rescue medications for agitation within 4 hours of initial IV olanzapine or IV haloperidol administration, incidence of adverse events and ICU length of stay. RESULTS: In the 192 patient analytic cohort, there was no difference in the proportion of patients who achieved a RASS score of < +1 within 4 hours of receiving IV olanzapine or IV haloperidol (49% vs. 42%, p = 0.31). Patients in the IV haloperidol group were more likely to receive rescue medications (28% vs 55%, p < 0.01). There was no difference in the incidence of respiratory events or hypotension between IV olanzapine and IV haloperidol. Patients in the IV olanzapine group experienced more bradycardia (11% vs. 3%, p = 0.04) and somnolence (9% vs. 1%, p = 0.02) compared to the IV haloperidol group. Patients in the IV olanzapine group had a longer median ICU length of stay (7.5 days vs. 5 days, p = 0.04). CONCLUSION: In this retrospective cohort study, there was no difference in the effectiveness of IV olanzapine compared to IV haloperidol for the management of agitation. IV olanzapine was associated with an increased incidence of bradycardia and somnolence.

Conventional versus restricted anti-Xa-guided heparin protocol in adult patients undergoing extracorporeal membrane oxygenation.

OBJECTIVE: The optimal intensity of anticoagulation for adult patients supported with extracorporeal membrane oxygenation (ECMO) remains uncertain. The objective of this study was to evaluate the effectiveness and safety of two anticoagulation protocols using conventional (0.3-0.7 IU/ml) versus restricted (0.2-0.5 IU/ml) anti-factor Xa (anti-Xa) targets for the management of unfractionated heparin (UFH) in adult ECMO patients. METHODS: This retrospective before-after cohort study compared two groups of ECMO patients who received UFH for at least 24-h from March 2016 to May 2019. The primary outcome was the composite rate of major bleeding or thrombotic events per ECMO day. Secondary outcomes included the mean amount of blood products transfused per ECMO day, the proportion of patients who were within the target anti-Xa at 24-h, the time to achieve target anti-Xa, and the number of heparin infusion adjustments to reach target anti-Xa. RESULTS: Forty-one patients were included in this analysis (conventional, n = 25; restricted, n = 16). There was no difference in the composite rate of major bleeding or thrombotic events per ECMO day (p = .090). The restricted group had lower rates of packed red blood cells (pRBC) transfusion per ECMO day (mean 1 ± 1 vs 3 ± 2 units, p = .003) and required fewer heparin infusion adjustments to reach the target (p = .007). There was no difference between the groups in the number of patients who achieved target anti-Xa at 24-h (p = .940). CONCLUSION: In adult ECMO patients, anticoagulation with a restricted anti-Xa target was associated with lower pRBC transfusions and did not provoke an excess of thrombotic events.

Major Publications in the Critical Care Pharmacotherapy Literature: 2020.

OBJECTIVES: To summarize selected meta-analyses and trials related to critical care pharmacotherapy published in 2020. DATA SOURCES: The Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update group screened 36 journals monthly for impactful publications. STUDY SELECTION: The group reviewed a total of 119 articles during 2020 according to relevance for practice. DATA EXTRACTION: Articles were selected with consensus and importance to clinical practice from those included in the monthly Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update. The group reviewed articles according to Grading of Recommendations, Assessment, Development, and Evaluations criteria. Articles with a 1A grade were selected. DATA SYNTHESIS: Several trials were summarized, including two meta-analyses and five original research trials. Original research trials evaluating vitamin C, hydrocortisone, and thiamine versus hydrocortisone in sepsis, the use of nonsedation strategies, dexmedetomidine in cardiac surgery, remdesivir for severe acute respiratory syndrome coronavirus 2, and thrombectomy in acute ischemic stroke. Two meta-analyses determining the impact of norepinephrine initiation in patients with septic shock and the use of corticosteroids in severe acute respiratory syndrome coronavirus 2 was included. CONCLUSIONS: This clinical review provides summary and perspectives of clinical practice impact on influential critical care pharmacotherapy publications in 2020.

Safety and Effectiveness of an Accelerated Intravenous Iron Administration Protocol in Hospitalized Patients With Heart Failure.

BACKGROUND: The ACC/AHA heart failure (HF) guidelines include a class IIb recommendation for intravenous (IV) iron replacement in patients with iron deficiency and New York Heart Association class II or III to improve functional status and quality of life. Several studies have addressed the use of IV iron formulations such as ferric carboxymaltose or iron sucrose in HF population; however, few studies focused on sodium ferric gluconate complex (SFGC). OBJECTIVES: To assess the safety and effectiveness of an IV SFGC administration protocol in patients hospitalized with HF. METHODS: A retrospective cohort study was conducted. We included patients admitted to the HF service from September 2017 to March 2018. The primary outcome was the frequency of adverse reactions. The secondary outcome was the odds of HF readmissions between the 2 groups (IV SFGC vs. control). RESULTS: Of the 123 patients, 70 received IV iron (SFGC group) and 53 did not receive IV iron (control group). Five (7%) patients of the 70 in the SFGC group experienced adverse events, which included hypotension (n = 2, 2.8%), fever (n = 2, 2.8%) and myalgia (n = 2, 2.8%). Nine (12.8%) and 18 (25.7%) were readmitted within 30 days and 6 months respectively. In the control arm, 5 (9.4%) and 14 (26.4%) were admitted within 30 days and 6 months respectively. The odds of HF readmission at 30 days [OR 1.4 (95% CI: 0.45, 4.5)] and at 6 months [OR 0.96 (95% CI: 0.43, 2.2)] were similar in those who did not receive IV iron compared to those who received IV iron. CONCLUSIONS: Sodium ferric gluconate complex given at an accelerated dosing schedule appears to provide a more efficient means to prescribe IV iron in the inpatient setting and is safe with a low frequency of hypotension, fevers, and myalgias.

Weight-Based Dosing Versus a Fixed-Dose Regimen of 4-Factor Prothrombin Complex Concentrate in Obese Patients Requiring Vitamin K Antagonist Reversal.

INTRODUCTION: Despite an increase in the use of fixed-dose protocols of 4-factor prothrombin complex concentrate (4F-PCC) for the reversal of vitamin K antagonists (VKAs), there remains a paucity of data in obese patients. In this study, we aimed to compare the proportion of patients attaining international normalized ratio (INR) goals using a weight-based dosing strategy versus a fixed-dose regimen of 4F-PCC. METHODS: This was a retrospective study conducted in patients 18 years of age or older, weighing ≥ 100 kg, who received either a weight-based dose or fixed dose of 4F-PCC (2000 units) for the reversal of VKA, and had a documented baseline and post-treatment INR. The primary outcome was the proportion of patients achieving an INR of < 2 for all indications of warfarin reversal, except in patients with intracranial hemorrhage, where the goal was an INR of < 1.5. RESULTS: A total of 44 patients met the inclusion criteria; 25 patients in the weight-based dosing group and 19 patients in the fixed-dose group. The median baseline INR was similar in both groups (weight-based dosing group 3.2 [interquartile range {IQR} 2.8-3.7] vs fixed-dose group 3.0 [IQR 2.7-4.9], p = 1). The median post-treatment INR was significantly lower in the weight-based dosing group compared to the fixed-dose group (1.3 [IQR 1.2-1.5] vs 1.6 [IQR 1.5-1.9], p < 0.01). However, there was no significant difference in the primary outcome between both groups (weight-based dosing strategy 84% vs fixed dose strategy 90%, p = 0.68). CONCLUSION: Our findings suggest that a fixed-dose regimen of 2000 units in obese patients weighing ≥ 100 kg is adequate to achieve these INR goals.

An Integrative Review of Factors Associated With Symptom Burden at the End of Life in Children With Cancer.

Children with cancer experience multiple symptoms at end of life (EOL) that impair their health-related quality of life. Using the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, this integrative literature review comprehensively summarized symptom experiences of children with cancer at EOL. The Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed, and Academic Premier were searched between January 2007 to September 2019 for articles published in English using the MeSH terms: symptom burden or distress AND children with cancer or pediatric cancer or cancer children or oncology and pediatrics AND EOL care or palliative care or death or dying or terminally ill. The inclusion criteria were the following: (a) study designs [randomized controlled trials, nonexperimental, secondary analysis (if aims were distinct from primary studies) and qualitative]; (b) participants <18 years old (died of cancer, had no realistic chance of cure, or had advanced cancer); and (c) focused on symptom experiences/burden at EOL. Exclusion criteria were nonresearch articles, systematic reviews, case studies, reports, and studies that focused on cancer survivors and/or those receiving curative therapies. Twenty-seven articles met inclusion criteria. The most prevalent symptoms-pain, fatigue, dyspnea, and loss of appetitewere associated with impairments in health-related quality of life. Children with brain tumors experienced higher symptom burden compared to those with hematologic/solid malignancies. Children who received cancer-directed therapies experienced disproportionate symptoms and were more likely to die in the intensive care unit compared with those who did not receive cancer-directed therapies. Most common location of death was home. This integrative review indicated that children with cancer were polysymptomatic at EOL. Strategies facilitating effective symptom management at EOL are needed.

Delayed Cardiotoxicity From a Massive Nortriptyline Overdose Requiring Prolonged Treatment.

PURPOSE: A case of a nortriptyline overdose complicated by delayed ventricular arrhythmias necessitating prolonged sodium bicarbonate infusion is presented, along with a review of tricyclic antidepressant (TCA) toxicology and key concepts for massive overdose management. SUMMARY: A 61-year-old man presented after an intentional nortriptyline overdose with a possible consumption of up to 2500 mg of nortriptyline. Electrocardiogram on presentation demonstrated QRS widening to 240 milliseconds. Despite treatment with a sodium bicarbonate infusion and further narrowing of his QRS interval, his course was complicated by repeated episodes of wide complex tachycardia. Given these episodes, an elevated quantitative serum nortriptyline level of 468 µg/L on hospital day 6 and persistently positive TCA urine screens, the patient was continued on a sodium bicarbonate infusion until hospital day 14. Based on our patient's quantitative serum nortriptyline levels, we calculated an elimination half-life of 184 hours, 6 days post ingestion as compared to the reported half-life of nortriptyline of 14 to 51 hours. CONCLUSION: This case demonstrates that at toxic levels of ingestion, routine TCA pharmacokinetics may be unreliable due to delayed absorption, enterohepatic recirculation, large volume of distribution, and saturable kinetics. Therefore, in these cases, pharmacokinetic values derived from routine dosing should not be used to make clinical decisions (such as timing of discontinuation of sodium bicarbonate infusion). We found that urine TCA screens provided similar information to quantitative nortriptyline levels and can be used to guide therapy along the QRS duration.

Intraoperative Unfractionated Heparin Unresponsiveness during Endovascular Repair of a Ruptured Abdominal Aortic Aneurysm following Administration of Andexanet Alfa for the Reversal of Rivaroxaban.

The authors describe a case of unfractionated heparin (UFH) unresponsiveness in the operating room secondary to reversal of rivaroxaban with coagulation factor Xa (recombinant) inactivated-zhzo (andexanet alfa). A 70-year-old man with a known 4.5- to 5.0-cm abdominal aortic aneurysm and atrial fibrillation managed with rivaroxaban presented with severe right-sided flank pain radiating to the left side of his abdomen. Computed tomography-angiography on arrival demonstrated a left retroperitoneal hematoma and a suspected ruptured abdominal aortic aneurysm. He received andexanet alfa to reverse rivaroxaban prior to an emergent endovascular aneurysm repair. During surgery, he received a total of 14,000 units (167 units/kg) of UFH with minimal changes in activated clotting time (132-144 sec; baseline 135 sec [reference range 74-137 sec]). This case highlights the potential complications of using UFH anticoagulation following reversal of factor Xa inhibitors with andexanet alfa and underscores the importance of peri-procedural anticoagulation planning. For patients who require intra-operative anticoagulation, providers should consider anticoagulation reversal with prothrombin complex concentrate instead of andexanet alfa or administration of a parenteral direct thrombin inhibitor, such as argatroban or bivalirudin during the surgical procedure.