A Retrospective Study of Dexamethasone, Remdesivir, and Baricitinib in Severe COVID-19.

Purpose: RECOVERY, ACTT-1, and ACTT-2 trials have demonstrated that utilization of dexamethasone, remdesivir, or a combination of remdesivir with baricitinib leads to mortality benefit and faster time to recovery, respectively. However, no studies have investigated the benefit of triple therapy of dexamethasone, remdesivir, and baricitinib. We investigate the benefits of triple therapy compared to dual therapy of dexamethasone with remdesivir in patients with severe COVID-19 on HFNC. Materials and Methods: A retrospective data analysis was performed on patients with severe COVID-19 requiring HFNC and evaluated for hospital discharge status, requirement of mechanical ventilation, length of stay, and days on HFNC. Results: Among 191 patients with severe COVID-19, 81 patients received dexamethasone, remdesivir, and baricitinib. Patients receiving triple therapy had a significant survival benefit (HR 0.52; P=0.042). Treatment with triple therapy vs. dual therapy also trended towards less requirement of mechanical ventilation (OR 0.66; P=0.26). There was no significant change in length of stay (mean 13.74 vs. 13.31; P=0.74) or days on HFNC (mean 8.95 vs. 7.28 days, P=0.16). Conclusions: The use of dexamethasone, remdesivir, and baricitinib in patients with severe COVID-19 requiring HFNC was associated with a significant survival benefit in comparison to dual therapy of dexamethasone with remdesivir.

Implementation and evaluation of a virtual learning advanced pharmacy practice experience.

BACKGROUND AND PURPOSE: The novel severe acute respiratory syndrome coronavirus 2 restricted student involvement in direct patient care. Virtual learning is an effective education strategy in pharmacy curriculums. This study aimed to evaluate student perceptions of virtual learning advanced pharmacy practice experiences (APPE) utilizing an electronic 12-question survey. EDUCATIONAL ACTIVITY AND SETTING: Virtual learning was developed and implemented, and students were surveyed at the end of the APPE. The survey was comprised of one open-ended and 11 Likert scale questions. It assessed implementation and use of virtual learning in place of a standard on-site APPE. FINDINGS: Responses were attained from 19 students. Questions regarding resources provided and virtual learning enabling autonomous, independent learning had the highest percent of strong agreement. No responses indicated strong disagreement. Three questions solicited >10% response rate of somewhat disagree, 16% associated with virtual learning helping the student become a better member of the healthcare team after graduation. Open-ended responses acknowledged appreciation of the virtual APPE and presented material. One in six students commented on the ability to apply the learned information to direct patient care. Feedback was delivered on consideration for increased utility of patient care-orientated applications to facilitate simulation of real-life patient cases. SUMMARY: Students who completed the virtual APPE were satisfied overall. Virtual teaching modalities may be incorporated into APPEs, particularly when direct patient care access is limited, but should not be used to completely replace the experience gained during direct patient care.

COVID-19 pneumonia: What APRNs should know.

ABSTRACT: COVID-19-associated pneumonia is a complex acute care diagnosis that requires careful evaluation and management. This article includes pertinent recommendations for management of acutely ill patients with COVID-19 pneumonia.

Descriptive analysis of the unwarranted continuation of antipsychotics for the management of ICU delirium during transitions of care: A multicenter evaluation across New Jersey.

PURPOSE: Nearly half of intensive care unit (ICU) patients will develop delirium. Antipsychotics are used routinely for the management of ICU delirium despite limited reliable data supporting this approach. The unwarranted continuation of antipsychotics initiated for ICU delirium is an emerging transitions of care concern, especially considering the adverse event profile of these agents. We sought to evaluate the magnitude of this issue across 6 centers in New Jersey and describe risk factors for continuation. METHODS: This multicenter, retrospective study examined adult ICU patients who developed ICU delirium from June 2016 to June 2018. Patients were included in the study if they received at least 3 doses of antipsychotics while in the ICU with presence of either a clinical diagnosis of delirium or a positive Confusion Assessment Method score. Patients were excluded if they were on an antipsychotic before ICU admission. RESULTS: Of the 300 patients included and initiated on antipsychotics for ICU delirium, 157 (52.3%) were continued on therapy upon transfer from the ICU to another level of inpatient care. The number of patients continued on newly initiated antipsychotics further increased to 183 (61%) upon discharge from the hospital. CONCLUSION: The continuation of antipsychotics for the management of delirium during transitions of care was a common practice across ICUs in New Jersey. Several risk factors for continuation of antipsychotics were identified. Efforts to reduce unnecessary continuation of antipsychotics at transitions of care are warranted.

Impact of a Nurse-Driven Opioid Titration Protocol on Quality of Orders at End of Life.

At our community teaching hospital, orders for end of life often lacked instructions to titrate opioids based on evidence-based principles and failed to address nonpain symptoms. An order set and a nursing-driven opioid titration protocol were implemented in August 2016 after extensive education. The purpose of this retrospective preintervention and postintervention study was to evaluate the impact of this intervention on the quality of end-of-life orders. We evaluated 69 patients with terminal illness receiving morphine infusions. After implementation, more morphine infusion orders included an as-needed bolus dose with an objective indication and appropriate instructions on when and how to titrate the infusion compared with before the intervention (94.6% vs 18.8%, P < .0001). Morphine infusion orders were also significantly more likely to include a maximum dose (P = .041) and an initial bolus dose (P < .0001). In addition, prescribers were more likely to order additional medications to manage nausea/vomiting, constipation, anxiety, or pain using a nonopioid (P < .05 for all). In this study, implementation of a standardized opioid titration protocol and symptom management order set led to an improvement in the quality of morphine infusion orders for pain management at the end of life and increased the use of medications to manage nonpain symptoms in dying patients.

Integrating high fidelity patient simulation into a skills-based doctor of pharmacy curriculum: A literature review with focus on the bedrock pilot course.

INTRODUCTION: Simulation-based teaching is an effective instructional strategy gaining momentum in pharmacy education but remains variable across programs. This is the first known report depicting the development of a multifaceted, integrated simulation program during concurrent initiation of a new skills-based pharmacy curriculum. METHODS: A significant infrastructure expansion created simulation areas whose availability corresponded with the initiation of a new skills-based curriculum. Integration of simulation occurred with existing personnel resources using area pilots. Pilots developed operational and educational design standards spanning the pre-simulation, simulation, and debriefing phases. The value of high-fidelity simulation pilots detailed here was assessed through both student survey and successful transference of tools to other courses. RESULTS: The pilots developed core operational and educational design standards, super-user faculty groups, and created an operational director position, essential for simulation promulgation throughout the curriculum. In the high-fidelity patient simulation pilot, operational elements included mannequin and equipment procedures, best practices for faculty and confederate engagement, and formulary development. Educational design standards addressed objective development, session flow, team roles, and debriefing. A grading rubric template aligned goals and assessed outcomes. All elements were structured into a planning worksheet. Student survey reflected the perceived value of this pilot. CONCLUSIONS: Operational support, integration coordination, and perceived value are all essential elements for successful curricular integration of simulation in a pharmacy curriculum. The pilots created the operational and educational structure establishing standards and defining required resources to sustain success. These pilots allowed for rapid curricular proliferation of simulation across the first and third professional years.

Esmolol Use in Dual Axis Defibrillation Resistant Ventricular Fibrillation.

Cardiac arrest in an event of acute myocardial infarction most commonly results in life-threatening ventricular tachycardia or ventricular fibrillation (VF). Patients who remain in VF despite optimal epinephrine, amiodarone, and three or more attempts at 200 joules of biphasic current defibrillation are known to be in an electrical storm. Here, we describe a case of defibrillation refractory VF responding to intravenous esmolol resulting in a successful return of spontaneous circulation. Learning objective. This case reinforces the growing body of evidence supporting esmolol as a novel treatment approach for refractory VF before the cessation of resuscitative efforts.

Cerebellar Haemorrhage Leading to Sudden Cardiac Arrest.

INTRODUCTION: Intracranial haemorrhage (ICH) is a known, but a rare cause of out of hospital cardiac arrest (OHCA). It results in the development of non-shockable rhythms such as asystole or pulseless electrical activity (PEA). CASE REPORT: A 77- years old male had an OHCA without any prodrome. An emergency medical services (EMS) team responded to an emergency call and intubated the patient at the site before transporting him to the Acute Care Hospital, New Brunswick, New Jersey, USA. On admission, a non-contrast computed tomography scan of the head revealed a large cerebellar haemorrhage. Non-traumatic ICH is a rare cause of OHCA. Although subarachnoid haemorrhage causing cardiac arrest has been described in the literature, cerebellar haemorrhage leading to cardiac arrest is rare. The mechanism by which ICH patients develop cardiac arrest is likely explained by a massive catecholamine surge leading to cardiac stunning. CONCLUSION: A non-shockable rhythm in the seting of a sudden cardiac arrest should raise alarms for a primary non-cardiac ethology, especially a primary cerebrovascular event. The absence of brainstem reflexes increases the likelihood of an intracranial process.

Prospective Observational Evaluation of Sedation and Pain Management Guideline Adherence Across New Jersey Intensive Care Units.

BACKGROUND: The practice guidelines for the management of pain, agitation, and delirium (PAD) from the Society of Critical Care Medicine shifted from primarily focusing on the treatment of anxiety in 2002 to the treatment of pain in 2013. OBJECTIVE: This prospective, observational, multicenter study aimed to assess the degree of practice adherence to the PAD guidelines for ventilated patients in New Jersey intensive care units (ICUs). METHODS: Pharmacist investigators at 8 centers designated 4 days at least 10 days apart to evaluate all patients on mechanical ventilation. The primary outcomes included adherence to 4 guideline recommendations: treatment of pain before sedation, use of nonnarcotic analgesic medications, use of nonbenzodiazepine sedative medications, and use of goal-directed sedation. RESULTS: Of 138 patients evaluated, 50% had a primary medical diagnosis (as opposed to surgical, cardiac, or neurological diagnosis), and the median Sequential Organ Failure Assessment (SOFA) score was 7. Pain was treated prior to administration of sedatives in 55.4% of subjects, with fentanyl being the primary analgesic used. In addition, 19% received no analgesia, and 11.5% received nonopioid analgesia. Sedative agents were administered to 87 subjects (48 nonbenzodiazepine and 39 benzodiazepine). Of those receiving benzodiazepines, 22 received intermittent bolus regimens and 16 received continuous infusions, of which 5 were for another indication besides sedation. Validated scales measuring the degree of sedation were completed at least once in 56 (81.6%) patients receiving sedatives. CONCLUSIONS: Current sedation practices suggest that integration of evidence-based PAD guidelines across New Jersey adult ICUs is inconsistent despite pharmacist involvement.

Significant Bradycardia in Critically Ill Patients Receiving Dexmedetomidine and Fentanyl.

PURPOSE: To report a case series of three patients who developed significant bradycardia while receiving the combination of dexmedetomidine and fentanyl for sedation and analgesia. MATERIALS AND METHODS: This is a case series of patients obtained from a mixed medical, surgical, and cardiac ICU in a community teaching hospital. Three intubated patients receiving fentanyl and dexmedetomidine infusion developed sudden bradycardia requiring intervention. In all three cases, adjustments to therapy were required. RESULTS: All three patients experienced significant bradycardia, with a heart rate less than 50 bpm, and one patient briefly developed asystole. In Case 1, the fentanyl infusion rate was reduced by 67% and the dexmedetomidine infusion rate was reduced by 25%. In Case 2, the sedation was changed to midazolam, and in Case 3, both fentanyl and dexmedetomidine were discontinued. In all three cases, there were no further incidences of significant bradycardia following intervention. CONCLUSIONS: Fentanyl used in combination with dexmedetomidine can result in clinically significant bradycardia. Further study is warranted to identify risk factors and elucidate the mechanisms that result in life-threatening bradycardia.

Efficacy of Intravenous Chlorothiazide for Refractory Acute Decompensated Heart Failure Unresponsive to Adjunct Metolazone.

STUDY OBJECTIVE: To assess the efficacy of intravenous chlorothiazide in patients with acute decompensated heart failure (ADHF) who were determined to be loop diuretic resistant and refractory to metolazone. DESIGN: Retrospective cohort study with patients serving as their own controls. SETTING: Large, academic, tertiary care hospital. PATIENTS: Forty-five patients with ADHF who had an inadequate response to high-dose loop diuretics and then received at least one dose of oral metolazone 5 mg or greater (metolazone index dose) followed by at least one dose of intravenous chlorothiazide 500 mg (chlorothiazide index dose) if the response to metolazone was considered inadequate, according to the institutional protocol, between February 4, 2013, and February 28, 2015, were included. If multiple doses of metolazone were administered, the last dose given before the chlorothiazide index dose was considered the index dose; the metolazone index dose had to have been administered more than 2 hours before the chlorothiazide index dose. MEASUREMENTS AND MAIN RESULTS: Data for a total of 90 diuretic doses (45 metolazone, 45 chlorothiazide) were included in the analysis. The median dose of loop diuretic in intravenous furosemide equivalents given over the 24-hour period before the metolazone index dose was 400 mg. The average length of stay was 34.7 days, and in-hospital mortality was 35.6% (16/45 patients). The primary end point of a net-negative urine output of 500 ml or greater during the 12 hours after the index dose occurred in 42.2% (19/45 patients) and 35.5% (16/45 patients) for the chlorothiazide and metolazone doses, respectively (p=0.581). The median 12-hour urine output following administration of metolazone was 810 ml (interquartile range [IQR] 866 ml) versus 1075 ml (IQR 940 ml) following administration of chlorothiazide (p=0.363). Compared with metolazone, the chlorothiazide doses did not result in an increase in urine output of at least 500 ml during the 12 hours following the dose relative to the 12 hours before the dose (31.1% vs 22.2%, p=0.754). No significant difference in achievement of net-negative urine output of 500 ml or greater during the 12 hours following the chlorothiazide or metolazone dose was noted (42.2% for chlorothiazide vs 35.5% for metolazone, p=0.581). CONCLUSION: The addition of intravenous chlorothiazide did not result in improved diuresis in patients with ADHF determined to be refractory to loop diuretics and adjunctive oral metolazone.

Direct Thrombin Inhibitor Resistance and Possible Mechanisms.

Objective: To report 3 cases in which doses of bivalirudin higher than commonly used in clinical practice were required in order to achieve therapeutic anticoagulation as monitored by the activated partial thromboplastin time (aPTT). Case Summary: The medical records of 3 patients who required large doses of bivalirudin to remain therapeutic were thoroughly reviewed. In all 3 patients, bivalirudin was initiated at a rate appropriate for the patients' renal function and titrated using a nurse-driven protocol with recommended dose adjustments based on aPTT. Indications for bivalirudin were anticoagulation in intra-aortic balloon pump, treatment of deep vein thrombosis, and heparin-induced thrombocytopenia with thrombosis. Target aPTT was achieved between 25.5 and 134 hours after initiation despite appropriate titration intervals per protocol. Discussion: Bivalirudin is a direct thrombin inhibitor frequently used off-label for the medical management of heparin-induced thrombocytopenia. It typically exhibits predictable, dose-dependent anticoagulation. Heparin-induced thrombocytopenia was suspected in 2 of the 3 cases and confirmed in 1. In all 3 patients, target aPTT was initially achieved with doses between 0.456 and 1.0 mg/kg/h after a median of 30.7 hours; up to 1.8 mg/kg/h was required to maintain therapeutic aPTT. In 2 of the cases, the international normalized ratio also increased unexpectedly upon achievement of therapeutic aPTT values. Conclusion: Direct thrombin inhibitors may be subject to resistance mechanisms similar to those previously described in patients receiving heparin. The anticoagulation status of these patients remains unknown.