Cardiac Safety of Clonidine and Quetiapine in Post-Cardiac Surgery Intensive Care Unit Patients.

Background: Clonidine and quetiapine are frequently used medications in the cardiac surgery intensive care unit (ICU). Objective: The purpose of this study is to assess the impact of clonidine compared to quetiapine on cardiac safety outcomes in adult cardiac surgery ICU patients. Methods: This was a single-center, retrospective observational analysis at a tertiary care, academic medical center. Results: One hundred and sixty-one cardiac surgery patients who were administered clonidine or quetiapine during their ICU stay were included between June 2015 and May 2017. The major endpoint of this study was a cardiac safety composite of bradycardia, hypotension, and QTc prolongation. Minor endpoints included ICU and hospital length of stay, and in-hospital mortality. There were 115 patients included in the clonidine arm and 46 patients in the quetiapine arm. There was no difference between groups with regard to the major endpoint (30.43% vs 33.15%; P < .8). There was a shorter ICU and hospital length of stay in the clonidine arm compared to quetiapine P < .0001. All other endpoints were not statistically significant. Conclusion: Patients who received clonidine tended to have undergone less complex procedures, be younger, and have a lower APACHE II score than patients who received quetiapine. The incidence of composite cardiac safety outcomes was not different in clonidine compared to quetiapine in cardiac surgery ICU patients.

Practical approach to clinical controversies in glycemic control for hospitalized surgical patients.

The importance of glycemic management in surgical patient populations stems from an association between hyperglycemia and increased rates of surgical site infections, sepsis, and mortality. Various guidelines provide recommendations regarding target glucose concentrations, but all stress the importance of avoiding hypoglycemia as well. Within the surgical patient population, glycemic targets may vary further depending on the surgical service, such as cardiac surgery, neurosurgery, or reconstructive burn surgery. Glycemic management in critically ill surgical patients is achieved primarily through the use of intravenous insulin infusion protocols. These protocols can include fixed protocols, multiplication factor protocols, and computerized algorithms. In contrast, noncritically ill surgical patients are generally managed through the utilization of subcutaneous insulin with a combination of basal, bolus, and sliding scale insulin. Insulin protocols should be effective at maintaining glucose concentrations within the specified target range with minimal hypoglycemic events. Monitoring glucose concentrations while on either an intravenous or subcutaneous insulin protocol is essential. Point-of-care testing is the primary method for monitoring glucose concentrations in both critically ill and noncritically ill surgical patients and allows for adjustment of the insulin regimen. As patients move between units and to the outpatient setting, ensuring adequate follow-up is essential to maintaining control of hyperglycemia.

Pharmacist driven antibiotic redosing in the emergency department.

STUDY OBJECTIVE: Determine whether an expanded emergency medicine (EM) pharmacist scope of practice reduces the frequency of major delays in subsequent antibiotic administration in patients boarded in the emergency department (ED). METHODS: A pre-post, quasi-experimental study conducted from November 2019-March 2020 at a single-center tertiary academic medical center following the implementation of an expanded EM pharmacist scope of practice. Adult patients were included if they received an initial antibiotic dose in the ED and deemed to be high-risk. Subsequent antibiotic doses were reordered by EM pharmacists for up to 24-h after the initial order pending ED length of stay (LOS). The historical control group consisted of retrospective chart review of cases from the previous year. RESULTS: The study identified that of the 181 participants enrolled, major delays in subsequent antibiotic administration occurred in 13% of the intervention group and 48% of the control group (p < 0.01). When compared to the control group, the intervention group had a significant decrease in the number of delays among antibiotics dosed at 6-h (39% vs 13%) and 8-h (60% vs 8%) intervals. For antibiotics dosed at 12-h intervals, no statistically significant difference was observed between the control and intervention groups respectively (19% vs 5%). A statistically significant lower incidence of in-hospital mortality was observed in the intervention group (3% vs 11%, p = 0.02). In the intervention group, 97% of patients received subsequent antibiotic doses while boarded in the ED, compared to 65% in the control group (<0.01). CONCLUSION: Expanding EM pharmacist scope of practice was associated with a significant reduction in the frequency of major delays in subsequent antibiotic administration as well as a decreased incidence of hospital mortality.

Variation in Fluid and Vasopressor Use in Shock With and Without Physiologic Assessment: A Multicenter Observational Study.

OBJECTIVES: To characterize the association between the use of physiologic assessment (central venous pressure, pulmonary artery occlusion pressure, stroke volume variation, pulse pressure variation, passive leg raise test, and critical care ultrasound) with fluid and vasopressor administration 24 hours after shock onset and with in-hospital mortality. DESIGN: Multicenter prospective cohort study between September 2017 and February 2018. SETTINGS: Thirty-four hospitals in the United States and Jordan. PATIENTS: Consecutive adult patients requiring admission to the ICU with systolic blood pressure less than or equal to 90 mm Hg, mean arterial blood pressure less than or equal to 65 mm Hg, or need for vasopressor. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Of 1,639 patients enrolled, 39% had physiologic assessments. Use of physiologic assessment was not associated with cumulative fluid administered within 24 hours of shock onset, after accounting for baseline characteristics, etiology and location of shock, ICU types, Acute Physiology and Chronic Health Evaluation III, and hospital (beta coefficient, 0.04; 95% CI, -0.07 to 0.15). In multivariate analysis, the use of physiologic assessment was associated with a higher likelihood of vasopressor use (adjusted odds ratio, 1.98; 95% CI, 1.45-2.71) and higher 24-hour cumulative vasopressor dosing as norepinephrine equivalent (beta coefficient, 0.37; 95% CI, 0.19-0.55). The use of vasopressor was associated with increased odds of in-hospital mortality (adjusted odds ratio, 1.88; 95% CI, 1.27-2.78). In-hospital mortality was not associated with the use of physiologic assessment (adjusted odds ratio, 0.86; 95% CI, 0.63-1.18). CONCLUSIONS: The use of physiologic assessment in the 24 hours after shock onset is associated with increased use of vasopressor but not with fluid administration.

Evaluation of Vasopressor Exposure and Mortality in Patients With Septic Shock.

OBJECTIVES: The objectives of this study were to: 1) determine the association between vasopressor dosing intensity during the first 6 hours and first 24 hours after the onset of septic shock and 30-day in-hospital mortality; 2) determine whether the effect of vasopressor dosing intensity varies by fluid resuscitation volume; and 3) determine whether the effect of vasopressor dosing intensity varies by dosing titration pattern. DESIGN: Multicenter prospective cohort study between September 2017 and February 2018. Vasopressor dosing intensity was defined as the total vasopressor dose infused across all vasopressors in norepinephrine equivalents. SETTING: Thirty-three hospital sites in the United States (n = 32) and Jordan (n = 1). PATIENTS: Consecutive adults requiring admission to the ICU with septic shock treated with greater than or equal to 1 vasopressor within 24 hours of shock onset. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Out of 1,639 patients screened, 616 were included. Norepinephrine (93%) was the most common vasopressor. Patients received a median of 3,400 mL (interquartile range, 1,851-5,338 mL) during the 24 hours after shock diagnosis. The median vasopressor dosing intensity during the first 24 hours of shock onset was 8.5 µg/min norepinephrine equivalents (3.4-18.1 µg/min norepinephrine equivalents). In the first 6 hours, increasing vasopressor dosing intensity was associated with increased odds ratio of 30-day in-hospital mortality, with the strength of association dependent on concomitant fluid administration. Over the entire 24 hour period, every 10 µg/min increase in vasopressor dosing intensity was associated with an increased risk of 30-day mortality (adjusted odds ratio, 1.33; 95% CI, 1.16-1.53), and this association did not vary with the amount of fluid administration. Compared to an early high/late low vasopressor dosing strategy, an early low/late high or sustained high vasopressor dosing strategy was associated with higher mortality. CONCLUSIONS: Increasing vasopressor dosing intensity during the first 24 hours after septic shock was associated with increased mortality. This association varied with the amount of early fluid administration and the timing of vasopressor titration.

Evaluation of a Clinical Pharmacist-Led Automated Dispensing Cabinet Stewardship Program at a Tertiary Academic Medical Center.

BACKGROUND: There is little guidance regarding the best methodology or frequency to optimize automated dispensing cabinets. Clinical pharmacists are in the unique position to make decisions regarding automated dispensing cabinet inventory to best serve their specific patient population. OBJECTIVE: The purpose of this evaluation was to determine if automated dispensing cabinet optimization by clinical pharmacists would affect the number of dispenses from central pharmacy, number of stockouts, and inventory cost. METHODS: A retrospective analysis was completed to evaluate the quantity of medications dispensed from a central pharmacy department over 2 separate 2-month periods, with optimization of automated dispensing cabinets occurring in between. The differences in quantity of medications dispensed and redispensed, as well as the number of stockouts and inventory cost on all automated dispensing cabinets, were compared pre- and postintervention. RESULTS: There were 1132 medication additions, 262 medication removals, and 167 medication par level adjustments. Medications dispensed from central pharmacy were decreased by 12% from the preintervention group to the postintervention group. The number of stockouts per cabinet per day also decreased from 0.75 to 0.61 in the pre- and postintervention groups, respectively. The inventory-at-par cost level was decreased by 15%. CONCLUSION AND RELEVANCE: Automated dispensing cabinet optimization by clinical pharmacists led to increased medication availability on inpatient units and decreased the number of dispenses from central pharmacy. Simple yet meaningful interventions can be taken to improve multiple medication distribution metrics simultaneously.

Evaluation of the Effect of Apixaban on INR in the Inpatient Population.

Direct oral anticoagulants (DOACs), particularly direct factor Xa inhibitors, have been associated with prolongation of the prothrombin time and the international normalized ratio (INR). Although DOACs do not require monitoring, elevations in the INR have been reported in in vitro and observational studies. The literature surrounding the extent of elevation and the clinical significance is limited. The objective of this study was to quantify the degree of INR elevation in hospitalized patients receiving apixaban. This was a single-center, retrospective, observational analysis of adult patients who received at least 1 dose of apixaban during their hospital admission and had at least 1 INR sample collected prior to and following administration. The major end point of this study was to characterize the effect of apixaban on the INR by determining the percentage of patients with an INR higher than our laboratory defined normal (defined as INR > 1.1). Minor end point outcomes included the incidence of an INR increase >0.3 from baseline INR and additional patient-specific factors that may influence INR elevation. Seventy-nine patients were included in the analysis. On day 1 of therapy, the median (interquartile range, IQR) INR was 1.4 (1.3:1.6) with 84.5% of patients having an elevated INR. The median (IQR) INR increased to 1.5 (1.4:1.6) and 1.7 (1.5:1.9) on day 4 and day 7, respectively. Of patients whose INR increased by more than 0.3, the median (IQR) change in INR from baseline was 0.5 (0.4:0.6). Apixaban is associated with a notable increase in INR in hospitalized patients, although it is not clear the clinical impact of the increase. Although literature does not support monitoring INR as a marker of apixaban activity, it is important for clinicians to understand the association apixaban has on the INR to avoid inappropriate interpretation of routine coagulation assays.

Review of Nonformulary Medication Approvals in an Academic Medical Center.

BACKGROUND: The Joint Commission requires hospitals to formally review formulary medications at least annually based on new clinical information. Although review of nonformulary medication (NFM) use is not required, frequent and inappropriate use of NFMs has the potential to increase hospital costs, negatively affect quality of care, and increase medication errors. Limited resources may restrict an institution's ability to review NFM use in addition to the required annual formulary review. NFM use at Brigham and Women's Hospital (BWH) was reviewed to provide insight on how to best direct an NFM review that is both effective and efficient. How an NFM review may negatively affect cost, quality of care, and medication errors is also inferred. METHODS: All approved NFM requests between 2009 and 2012 from Brigham and Women's Hospital's computerized provider order entry system were extracted and categorized according to the American Hospital Formulary Service (AHFS) Pharmacologic-Therapeutic Classification System. RESULTS: Of the 15,356,016 new medication orders, there were 223,266 NFM approvals for 433 unique NFMs. NFMs were categorized into 91 AHFS, 14 combination, and 4 "Others" classes. Twenty-five AHFS Classes accounted for approximately the top 90% of all NFM approvals, and the top 2 NFMs in each class accounted for a majority of the NFM approvals. CONCLUSION: Only a few classes of medications and a few medications within each class accounted for most of the NFM use at BWH. Targeting review of the most frequently used NFMs in each class may be a feasible strategy to reviewing NFMs annually that is both effective and efficient in optimizing formulary benefits.

The frequency of inappropriate nonformulary medication alert overrides in the inpatient setting.

BACKGROUND: Experts suggest that formulary alerts at the time of medication order entry are the most effective form of clinical decision support to automate formulary management. OBJECTIVE: Our objectives were to quantify the frequency of inappropriate nonformulary medication (NFM) alert overrides in the inpatient setting and provide insight on how the design of formulary alerts could be improved. METHODS: Alert overrides of the top 11 (n = 206) most-utilized and highest-costing NFMs, from January 1 to December 31, 2012, were randomly selected for appropriateness evaluation. Using an empirically developed appropriateness algorithm, appropriateness of NFM alert overrides was assessed by 2 pharmacists via chart review. Appropriateness agreement of overrides was assessed with a Cohen's kappa. We also assessed which types of NFMs were most likely to be inappropriately overridden, the override reasons that were disproportionately provided in the inappropriate overrides, and the specific reasons the overrides were considered inappropriate. RESULTS: Approximately 17.2% (n = 35.4/206) of NFM alerts were inappropriately overridden. Non-oral NFM alerts were more likely to be inappropriately overridden compared to orals. Alerts overridden with "blank" reasons were more likely to be inappropriate. The failure to first try a formulary alternative was the most common reason for alerts being overridden inappropriately. CONCLUSION: Approximately 1 in 5 NFM alert overrides are overridden inappropriately. Future research should evaluate the impact of mandating a valid override reason and adding a list of formulary alternatives to each NFM alert; we speculate these NFM alert features may decrease the frequency of inappropriate overrides.

Treatment of enterococcal peritonitis with intraperitoneal daptomycin in a vancomycin-allergic patient and a review of the literature.

BACKGROUND: Intraperitoneal (IP) administration of antibiotics is a mainstay of therapy in the treatment of peritoneal dialysis-related peritonitis. The therapeutic options against gram-positive organisms in patients intolerant to vancomycin are limited. METHODS: This case report and review of the literature used a search of PubMed with the terms "daptomycin," "intraperitoneal," and "peritoneal" for 2004 through 7 February 2013 to find relevant publications. RESULTS: In addition to our patient, we identified 6 case reports of IP daptomycin for the treatment of peritonitis. Our patient was treated with a 14-day course of IP daptomycin, with resolution of signs and symptoms of peritonitis. She presented again 7 weeks later with signs and symptoms of peritonitis and was treated with a repeat course of IP daptomycin. Among the 6 patients reported in the literature, 4 received loading doses of daptomycin. Daptomycin 20 mg per liter of dialysate was administered in 4 patients, and the other 2 patients received higher doses based on body weight (milligrams per kilogram). Treatment duration averaged 10 or 14 days. In all 6 cases, clinical cure was reported. CONCLUSIONS: Although limited to case reports, the available literature suggests that IP daptomycin is a viable alternative for peritoneal dialysis-related peritonitis. However, routine use of this agent must be cautioned, because further prospective studies are required.