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Purpose To determine the feasibility of conducting a multicenter ICU RCT of AFS compared to either protocol-directed sedation (PDS) or both PDS and daily sedation interruption (DSI) in North America. Materials and methods This single-center RCT compared AFS [fentanyl (bolus ± infusions) to reach CPOT ≤2; if RASS ≥1, CPOT ≤2 and additional fentanyl failed to reach RASS goal (−2 to 0), low-dose propofol (up to 6 h) was given] with either PDS or both PDS and DSI daily in adults mechanically ventilated (MV) ≥48 h. Relevant feasibility, safety, and clinical outcomes were defined and evaluated. Results 90 of 160 eligible patients were enrolled [AFS = 27; PDS = 28; PDS + DSI = 31]; rate = 3/month. Time from intubation to randomization was 17.5 ± 11.6 h. Study days fully adherent to the study intervention [AFS = 95%; PDS = 99%; PDS + DSI = 96%] and time spent in the first 48 h after randomization without pain (CPOT ≤2)[AFS = 82%; PDS = 78%; PDS + DSI = 77%] and at goal RASS[AFS = 88%; PDS = 83%; PDS + DSI = 95%] were high and similar. Nurse-perceived [median (IQR)] study workload (10-point VAS) was higher with AFS [4(2–6)] than PDS [1(1–3)] or PDS + DSI [2(1–5)]; p = .002). Unplanned extubation was rare (AFS = 1; PDS = 0; PDS + DSI = 1). Days [median (IQR)] free of MV in the 28d after intubation [AFS 24(23,26); PDS 24(20,26); PDS + DSI 24(21,26)] was not different (p = .62). Conclusion A multicenter RCT evaluating AFS is feasible to conduct in North America.

Background: This paper describes a series of integrative courses intentionally designed to prepare students for Advanced Pharmacy Practice Experiences (APPEs) in a block system curriculum. Innovation: Three integration blocks are interspersed throughout the didactic curriculum to serve as checkpoints to ensure competency as students progress in the curriculum, rather than waiting until the end to determine competency. Complex patient case discussions and a series of high-stakes assessments are used to reinforce and evaluate cumulative retention of knowledge, skills, and attitudes. Findings: Class of 2022 exam results showed that in the cohort of students who failed the high-stakes comprehensive knowledge assessment (CKA) and pharmacy calculations exams during the first integration block (IB), failure rates decreased in subsequent IBs, indicating early detection of knowledge deficiencies and either exam performance improvement in each IB or failure to progress to the next IB. A survey of the same cohort indicated that the final integration block prior to advanced pharmacy practice experiences (APPEs) helped improve confidence in applying key knowledge and skills into practice. Conclusion: The series of integration blocks designed and implemented at WesternU provides opportunities to reinforce knowledge and skills while requiring students to demonstrate maintenance of core competency as they progress through the curriculum.

The COVID-19 pandemic poses a multitude of unprecedented challenges to the healthcare system and broader public policy arena. Comprehensive guidelines and recommendations have been slow to develop as each community and medical institution face unique challenges due to a dissimilarity in demographics and resources. We seek to describe the experience at our institution to highlight challenges that others may encounter with an emphasis on the value that specialized pharmacists can provide at various levels of the healthcare system.

Although numerous studies have shown that anticoagulation of nonvalvular atrial fibrillation (AF) significantly decreases the risk of stroke, anticoagulating critically ill patients in the intensive care unit (ICU) poses many challenges and the benefits have not been determined.To assess the safety and efficacy of anticoagulation in AF patients with sepsis. Ascertaining the incidence of complications associated with anticoagulation therapy, such as bleeding, can optimize patient care.This was a retrospective observational study to assess the incidence of stroke and anticoagulation-related complications (eg, bleeding, heparin-induced thrombocytopenia) in AF patients with severe sepsis. This study was undertaken in a surgical/medical ICU of a teaching, community-based hospital. A total of 115 patients with AF who were admitted with a diagnosis of sepsis were included in the study.Among 115 patients (mean age 81 ± 9.5 years and CHADS2 [congestive heart failure, hypertension, age75 years, diabetes mellitus, stroke] score 3.17 ± 1.20), 80 (69.6%) did not receive anticoagulation treatment during their hospitalization and none of these patients developed a stroke. Anticoagulation-related complications occurred more often in the group who received anticoagulation (8.6% [3/35] vs 0%, P = .008). In the anticoagulated group, a majority of the patients were within therapeutic range less than 50% of the time during their ICU stay. There was no statistically significant difference in survival rates during their hospitalization (66.2% [53/80] for the non-anticoagulated group vs 74.3% [26/35] in the anticoagulated group, P = .392).Administration of anticoagulation for elderly patients with a CHADS2 score at 2 or more in the setting of sepsis can be associated with an increased risk of anticoagulation-related complications (eg, bleeding, heparin-induced thrombocytopenia). Managing and targeting a therapeutic goal with warfarin therapy in critically ill patients with sepsis is challenging. Further studies are necessary to provide appropriate recommendations in this setting.

Evaluate recent clinical studies involving the use of dexmedetomidine (DEX) infusion for the treatment of delirium in the intensive care unit (ICU).A literature search was conducted to identify peer-reviewed articles in MEDLINE (1966-June 2016) using the terms sedation, analgesic, dexmedetomidine, delirium, and critically ill adult patients.Two studies in the ICU setting reported the potential benefits of DEX for managing agitation during weaning from mechanical ventilation. One pilot study and a clinical trial reported the use of DEX in the treatment of ICU delirium.Further studies are required to evaluate the use of DEX treatment in critically ill patients presenting with delirium.

To determine an appropriate empiric oral sirolimus dose adjustment when given concurrently with posaconazole oral suspension in patients who undergo hematopoietic stem cell transplant (HSCT).Retrospective cohort study.Comprehensive cancer center in the United States.Seventy five allogeneic HSCT patients who received posaconazole oral suspension and oral sirolimus concurrently between 2009 and 2011.Sirolimus concentrations were recorded at baseline and for up to 28 days after posaconazole initiation. The sirolimus concentration/dose (C/D) ratio was determined for each sirolimus concentration obtained. Following analysis of patient data and based on the initial empiric sirolimus dose reduction, patients were stratified into two groups: ≥50% sirolimus dose reduction (Group 1) and50% sirolimus dose reduction (Group 2). The mean sirolimus C/D ratio was 2.29 ng/mL/mg prior to posaconzole initiation. Coadministration of posaconazole and sirolimus resulted in an increase in the steady state sirolimus C/D ratio to 6.24 ng/mL/mg, which occurred approximately 17-20 days after initiation of posaconazole. The mean maximum sirolimus concentration was significantly higher in Group 2 compared to Group 1 (12.64 ng/mL vs. 9.24 ng/mL, p=0.001). Significantly more patients in Group 2 than Group 1 experienced at least one sirolimus concentration15 ng/mL (27% vs. 2.6%, p=0.003).Coadministration of posaconazole oral suspension with oral sirolimus increases the sirolimus C/D ratio by approximately 2.7-fold in HSCT patients. An initial empiric oral sirolimus dose reduction between 50% and 65% may be recommended for most clinically stable patients with close sirolimus concentration monitoring for at least 3 weeks following posaconazole initiation.

Recent meta-analysis has demonstrated that nesiritide may worsen renal function (RF) in patients with acute decompensated heart failure (ADHF). A nesiritide utilization evaluation (NUE) performed in our institution reflected that belief of RF preservation was one reason leading to nesiritide overuse. This study examined the effect of nesiritide on RF in patients evaluated in this NUE.Nesiritide patient records from October 1, 2003 to March 31, 2004 were reviewed (n = 162). Pertinent demographics, laboratory and medication utilization data were obtained.Changes in creatinine clearance (CrCl) and percentage of patients demonstrating worsening RF (decrease in CrClor = 25%) during diuretics therapy before nesiritide initiation and during nesiritide initiation and during nesiritide therapy were compared using Wilcoxon Signed-Ranks test and Chi-Square respectively.Overall, the addition of nesiritide to IV furosemide did not clinically change RF as compared to the use of IV furosemide alone (% change in CrCl: 0 vs. -2.13 mL/min, p = 0.023), although the difference was statistically significant. When categorized into different RF, there is no different in CrCl changes between the nesiritide group and the IV furosemide alone group. There is also no difference in terms of number of patients experiencingor = 25% reduction in CrCl overall. Changes in RF were also not correlated to dose or duration of therapy.Nesiritide did not demonstrate significant impact in RF. Larger studies that examine RF in a more systematic and controlled manner and relate changes in RF to clinical outcomes are necessary to further elucidate the risk versus benefit profile of nesiritide.

Summary Background and objectives: Nesiritide is a new vasodilator approved for decompensated heart failure (DHF). Compared with nitroglycerin, nesiritide improves haemodynamics and symptoms in the first 3 h of therapy. However, nesiritide is more expensive than nitroglycerin (US$380–1500 daily vs. US$2–5 daily). Since its approval in the US in late 2001, nesiritide use has increased dramatically in our institution. Nesiritide has become a focus of our multidisciplinary drug utilization initiative, aimed at performing a nesiritide utilization evaluation (NUE) and developing a nesiritide usage guideline. Methods: Medical records of patients who received nesiritide from 1 October 2003 to 31 March 2004 were reviewed. Nesiritide utilization pattern was presented to the initiative group for guideline development. Results: A total of 162 records were reviewed. A 22·6% of inappropriate usage was reported. The most significant inappropriate usage was in patients who received the agent for precardiac valvular surgery optimization, followed by those for diuresis in non-cardiac-related fluid overload states. The median duration of nesiritide therapy was 6 days (range 1–94). The median length of stay (LOS) in our institution was 14 days (National statistics DHF LOS: 5·3 days). Eliminating inappropriate nesiritide usage can lead to a potential of US$141 886 savings per year. Conclusion: Based on the results, a 48-h nesiritide restriction policy was implemented. Usage beyond 48 h requires Heart Failure Service approval. Future NUE will evaluate the effectiveness of this policy. The overall management of DHF also needs to be evaluated to improve efficiency of care.

BACKGROUND Identifying risk factors for unplanned extubation in patients receiving mechanical ventilation can help guide prevention strategies. OBJECTIVE To assess the risk of unplanned extubation with different sedation strategies. METHODS A 36-month quality improvement study in a 33-bed intensive care unit at a tertiary-care center. RESULTS A total of 92 unplanned extubations occurred (7.5 events/1000 days of mechanical ventilation): patients who were receiving continuous sedation protocol with daily interruption of sedatives had 1.5 events/1000 ventilator days, patients receiving the intermittent sedation protocol had 5.0 events/1000 days, and patients with no sedation protocol had 16 events/1000 days (P < .05). Median duration of mechanical ventilation before unplanned extubation was 2 days. Most unplanned extubations (94%) were deliberate, and 53% occurred in patients scheduled for weaning. Most unplanned extubations in the continuous sedation protocol group (71%) occurred during weaning, in comparison to the intermittent sedation protocol (54%) and no sedation protocol groups (48%, P< .05). The highest incidences of agitation were in patients receiving the intermittent sedation protocol as compared with the other 2 groups (77% vs 50% vs 49%, P < .05). Overall, 73% of patients who had an unplanned extubation did not require reintubation; those who did were older (mean age: 68 vs 53 years, P = .01) and were male (80% vs 20%, P= .02). Reintubation was unrelated to the time of unplanned extubation. CONCLUSION Strategies of no sedation or intermittent sedation are both associated with higher rates of unplanned extubation when compared to a strategy of continuous sedation with daily interruption of sedatives. Sedation strategies that allow agitation may increase the risk of unplanned extubation.