Michael G. Liebl

Recombinant Factor VIIa Treatment of Severe Bleeding in Cardiac Surgery Patients: A Retrospective Analysis of Dosing, Efficacy, and Safety Outcomes

OBJECTIVE To describe rFVIIa dosing and clinical outcomes in cardiovascular surgery patients with refractory bleeding. DESIGN Retrospective chart review of patients receiving rFVIIa from January 1, 2004 to September 30, 2005, in the cardiovascular surgery setting. SETTING Tertiary care, private teaching hospital. PARTICIPANTS Ninety-three patients who received rFVIIa after cardiovascular surgery for the management of refractory bleeding. INTERVENTIONS None. MEASURES AND MAIN RESULTS Patients received an average of 7.6 +/- 6.8 units of red blood cells (RBCs) before rFVIIa dosing (mean dose, 56.2 +/- 26.5 microg/kg). Median and 25th and 75th quartile blood product consumption was significantly reduced 6 hours after rFVIIa versus 6 hours before (RBCs, -3 units, [-1, -7]; cryoprecipitate, -7.5 units [0, -20]; platelet, -3 units [-1, -4]; fresh frozen plasma, -4 units [-2, -7]). Repeated rFVIIa dosing occurred in 10% of patients, with 8 (8.6%) and 2 (2.25%) patients receiving second and third doses, respectively. Subgroup analysis of each rFVIIa dosing quartile >30 microg/kg showed a significant reduction in RBCs; however, no significant differences were found in the magnitude of RBC reduction or percent of patients requiring massive transfusion among the quartiles. No adverse thrombotic episodes were noted, and the observed mortality (22.6%) was not attributed to rFVIIa therapy. CONCLUSIONS rFVIIa effectively reduces blood product use in cardiovascular surgery patients having massive blood loss. Although the optimal dose of rFVIIa for use in cardiovascular surgery remains undetermined, these data provide evidence that dosing regimens using <90 microg/kg are effective in this population and may provide guidance for centers establishing standardized protocols for rFVIIa use in cardiovascular surgery patients.

Evaluation of the activated clotting time and activated partial thromboplastin time for the monitoring of heparin in adult extracorporeal membrane oxygenation patients

Introduction: Historically, the activated clotting time (ACT) has been the preferred monitoring test of the heparin effect in extracorporeal membrane oxygenation (ECMO) patients. However, few adult studies have evaluated its correlation to the heparin dose or other monitoring tests, such as the activated partial thromboplastin time (aPTT). This retrospective study sought to evaluate the correlation between the heparin dose and these monitoring tests. Methods: Patients administered a heparin drip during ECMO were included in this study. The primary endpoints were the correlation between heparin dose and ACT or aPTT and the relationship between paired ACT and aPTT samples. Results: Forty-six patients met the criteria for study inclusion. A better correlation was observed for heparin dose and aPTT (Pearson product-moment correlation coefficient (r) = 0.43 – 0.54) versus ACT (r = 0.11 – 0.14). Among the paired sample data, ACT values did not differ significantly between Groups two (aPTT 60 – 75 seconds) and three (aPTT >75 seconds). Conclusion: The heparin dose correlated better with aPTT relative to ACT and, thus, may be considered a more effective tool for the dosing of heparin in adult ECMO patients. Paired ACT and aPTT sample data suggested a poor relationship between these two anticoagulant monitoring tests.

Health care system vulnerabilities: Understanding the root causes of patient harm

Adverse drug events (ADEs) are any injuries resulting from the use of a drug and can be broken down into two categories: adverse drug reactions (ADRs) and medication errors. ADRs are any undesirable experiences associated with the use of a medicine in a patient, whereas medication errors are defined

Alternative Monitoring of Argatroban Using Plasma-Diluted Thrombin Time

OBJECTIVE To report a case of heparin-induced thrombocytopenia (HIT) in a patient with concurrent liver dysfunction and a prolonged baseline activated partial thromboplastin time (aPTT) in whom argatroban therapy was monitored with aPTT and a novel plasma-diluted thrombin assay. CASE SUMMARY An 80-year-old man with HIT and liver dysfunction was treated with argatroban, which was initiated at a dose of 0.5 μg/kg/min and gradually decreased to 0.09 μg/kg/min. The patient had a mildly prolonged aPTT at baseline (37.5 seconds). He was concurrently monitored with aPTT, per institution protocol, and plasma-diluted thrombin time. Plasma-diluted thrombin times were consistently lower than aPTTs, but mirrored the trend of the aPTTs. Eleven hours after argatroban was stopped, the aPTT remained elevated (53.9 seconds), while the plasma-diluted thrombin time returned to normal range (26.4 seconds). The patients therapy was transitioned to warfarin and he had a hospital course with no thrombotic or bleeding complications. DISCUSSION Plasma-diluted thrombin time is a novel laboratory test consisting of 1 part patient plasma diluted with 3 parts normal plasma. Plasma-diluted thrombin time has been shown to blunt the sensitivity of the thrombin time and may be more accurate for drug monitoring. A MEDLINE search revealed 2 studies using the plasma-diluted thrombin time assay. The first study compared aPTT and plasma-diluted thrombin times in blood samples mixed with argatroban, bivalirudin, or lepirudin at 3 different concentrations. Blood samples contained lupus inhibitors, vitamin k deficiency, or normal baseline aPTTs. The aPTT overestimated drug concentrations in all samples with lupus anticoagulant and vitamin k deficiency, while the plasma-diluted thrombin time correctly estimated drug concentrations in nearly all samples. The second study looked at monitoring dabigatran with plasma-diluted thrombin time and found a linear relationship between the plasma-diluted thrombin time and the dabigatran dose-response curve. CONCLUSIONS Plasma-diluted thrombin time may be an alternative for direct thrombin inhibitor monitoring in patients with elevated aPTT values at baseline. Further randomized control trials are needed to determine its applicability in clinical practice.

Enteral Administration of Naloxone for Treatment of Opioid-Associated Intragastric Feeding Intolerance

Intragastric enteral feeding intolerance, common in the intensive care setting, is attributed to many causes. Opioid antagonists such as naloxone may have a role in reversing the intolerance when it is associated with intravenous opioid infusions. A 38‐year‐old woman hospitalized for acute respiratory distress syndrome was supported with low tidal volume mechanical ventilation. She required lorazepam and morphine administered by continuous intravenous infusion to achieve ventilator synchrony and pain control. While receiving these therapies, the patient developed persistent intolerance to intragastric feeding. Intravenous metoclopramide and laxatives did not decrease gastric volume residuals, and insertion of a jejunal tube was deemed unsafe due to worsening of her respiratory status. Total parenteral nutrition was begun to meet her caloric needs, but she experienced repeated catheter‐related bloodstream infections. Naloxone 2 mg by gastric tube every 8 hours for 8 days was started; the dosage then was increased to 4 mg every 8 hours. Tube feeding was restarted, which provided the patient with more than 90% of her daily caloric needs and allowed for discontinuation of parenteral nutrition. With this dosage of naloxone, tolerance to intragastric feeding was maintained until the patients death due to refractory respiratory failure. Enterally administered naloxone is an effective, noninvasive means of reversing intolerance to intragastric feeding associated with opioids.

Validity and Reliability of a Systematic Database Search Strategy to Identify Publications Resulting From Pharmacy Residency Research Projects

Purpose: This study aims to develop a systematic search strategy and test its validity and reliability in terms of identifying projects published in peer-reviewed journals as reported by residency graduates through an online survey. Methods: This study was a prospective blind comparison to a reference standard. Pharmacy residency projects conducted at the study institution between 2001 and 2012 were included. A step-wise, systematic procedure containing up to 8 search strategies in PubMed and EMBASE for each project was created using the names of authors and abstract keywords. In order to further maximize sensitivity, complex phrases with multiple variations were truncated to the root word. Validity was assessed by obtaining information on publications from an online survey deployed to residency graduates. Results: The search strategy identified 13 publications (93% sensitivity, 100% specificity, and 99% accuracy). Both methods identified a similar proportion achieving publication (19.7% search strategy vs 21.2% survey, P = 1.00). Reliability of the search strategy was affirmed by the perfect agreement between 2 investigators (k = 1.00). Conclusion: This systematic search strategy demonstrated a high sensitivity, specificity, and accuracy for identifying publications resulting from pharmacy residency projects using information available in residency conference abstracts.

Impact of a pharmacotherapy alerting system on medication errors.

PURPOSE An evaluation of a rules-based pharmacotherapy alerting system configured to identify improperly verified new medication orders in an inpatient setting is described. METHODS A retrospective pre-post cohort study was conducted to assess order-verification alerts and pharmacy interventions at a 900-bed hospital before and after implementation of a commercial pharmacotherapy alerting system. In the preintervention phase of the study, the pharmacotherapy alerting system was used on a limited basis, with clinical pharmacists responding to all alerts and the resulting data used to refine the trigger rules; for the intervention phase, the pharmacotherapy alerting system was programmed to alert only on order-verification errors involving four medications (darbepoetin, filgrastim, fondaparinux, and warfarin). In the event of alerts, a pharmacy response team provided nearly real-time feedback to the order-verification pharmacist, mainly via e-mail or paging. RESULTS From the preintervention period to the intervention period, there was a 36% decrease in the frequency of order-verification alerts (p = 0.035), and the average number of alerts per day declined from 1.0 to 0.6, suggesting that the pharmacotherapy alerting system and associated oversight mechanisms were effective in enabling pharmacy staff to prevent future errors at the order-verification step before such errors could result in patient harm. The review team spent an average of 10.2 minutes carrying out interventions in response to alerts during the intervention phase. CONCLUSION Incorporation of a real-time pharmacotherapy alerting system with an oversight response process reduced the number of pharmacotherapy alerts and facilitated interception and prevention of adverse drug events.

Association between health literacy and 30-day healthcare use after hospital discharge in the heart failure population

Background: Low health literacy increases the risk for hospital readmissions. Despite this, the measurement and use of health literacy to guide discharge counseling and planning in heart failure patients is not commonly performed. A short 3‐Question Brief Health Literacy Screen (BHLS) is available and takes less than three minutes to complete, but has never been evaluated to help determine whether health literacy affects healthcare use after discharge in patients with heart failure. Objective: The purpose of this study was to assess 30‐day readmissions and emergency department visits based on health literacy evaluated by the BHLS in an acute care heart failure population. Methods: This was a prospective observational cohort study conducted at a large quaternary health system. Hospitalized patients with a diagnosis of heart failure were assessed for health literacy using the BHLS. Unplanned healthcare use after discharge including 30‐day, all‐cause ED visits and hospital readmissions was assessed using univariate and logistic regression models. Results: Two hundred and sixty four patients aged 66.6 ± 14.3 (mean ± SD) years met inclusion/exclusion criteria of whom 175 (66.3%) had a BHLS score >9 (adequate health literacy) and 89 (33.7%) had a BHLS score ≤9 (low health literacy). Predictors of low health literacy included older age (p = 0.019), lower education level (p < 0.001) and unemployed (p = 0.048). After controlling for potential confounders, low health literacy was independently associated with 30‐day healthcare use after hospital discharge (OR:1.80; 95% CI: 1.04–3.11; p = 0.035). Conclusion: Using a short, 3‐question validated survey instrument, it was demonstrated that low health literacy was associated with increased 30‐day unplanned healthcare use after discharge in this heart failure population. These results provide a clinically useful, easily incorporated tool that could identify high‐risk patients at need for clinical interventions. Highlights:This prospective observational cohort study assessed 30‐day readmissions and emergency department visits based on health literacy evaluated by a short, 3‐question validated survey instrument (BHLS) in an acute care heart failure population.Two hundred and sixty four patients met inclusion/exclusion criteria of whom 175 (66.3%) had adequate health literacy and 89 (33.7%) had low health literacy.After controlling for potential confounders, low health literacy was independently associated with 30‐day healthcare use after hospital discharge (OR:1.80; 95% CI: 1.04–3.11; p = 0.035).These results provide a clinically useful, easily incorporated tool that could identify high‐risk patients at need for clinical interventions.

Multicomponent Interventions Reduce High-Risk Medications for Delirium in Hospitalized Older Adults: Reducing high-risk medications in older adults

Delirium threatens the functional independence and cognitive capacity of patients. Medications, especially those with strong anticholinergic effects, have been implicated as a preventable cause of delirium. We evaluated the effect of multicomponent interventions aimed at reducing the use of 9 target medications in hospitalized older adults at risk of delirium. This continuous quality improvement program was undertaken at a tertiary care facility and 4 community hospitals in a hospital system. We included 21, 541 hospital admissions with patients aged 70 and older on acute care medical or surgical units from the preintervention (2012) period, and 27,764 from the postintervention (2015) period. Implemented interventions include formulary and policy changes, technology‐assisted medication review, age‐conditional order set modifications, best practice alerts, and education. The proportion of hospital admissions with individuals receiving at least 1 target medication declined from 45.6% to 31.3% (relative reduction (RR)=31.4%) from before to after the intervention, meaning that target medication exposure was avoided in approximately 4,000 older adults. The greatest effect was observed for zolpidem (11.2% to 5.3%, RR=52.6%) and diphenhydramine (12.9% to 7.1%, RR=45%). Furthermore, the mean number of doses administered during all hospital admissions was reduced for 7 of 9 medications. Multicomponent interventions implemented in our hospital system were effective at reducing exposure to target medications in hospitalized older adults at risk of delirium. These systematic changes applied throughout the medication use process are sustained today.

Prevalence of Cognitive Impairment Among Elderly Patients Upon Hospital Admission Using Mini-Cog™ Assessments Performed by Advanced Pharmacy Practice Experience Students

Background: Older adults with cognitive impairment may have difficulty understanding and complying with medical or medication instructions provided during hospitalization which may adversely impact patient outcomes. Objective: To evaluate the prevalence of cognitive impairment among patients aged 65 years and older within 24 hours of hospital admission using Mini-Cog™ assessments performed by advanced pharmacy practice experience (APPE) students. Methods: Students on APPE rotations were trained to perform Mini-Cog™ assessments during routine medication education sessions from February 2017 to April 2017. The primary end point was the prevalence of cognitive impairment indicated by a Mini-Cog™ score of ≤3. Secondary end points were the average number of observed Mini-Cog™ practice assessments required for APPE students to meet competency requirements, caregiver identification, and 30-day hospital readmissions. Results: Twelve APPE students completed the training program after an average of 4.4 (standard deviation [SD] = 1.0) graded Mini-Cog™ assessments. Of the 1159 admissions screened, 273 were included in the analysis. The prevalence of cognitive impairment was 55% (n = 149, 95% confidence interval [CI]: 48%-61%). A caregiver was identified for 41% (n = 113, 95% CI: 35%-47%) of patients, and 79 patients had a caregiver present at bedside during the visit. Hospital readmission within 30 days of discharge was 15% (n = 41, 95% CI: 11%-20%). Conclusion: Cognitive impairment could substantially impair a patient’s ability to comprehend education provided during hospitalization. Pharmacy students can feasibly perform Mini-Cog™ assessments to evaluate cognitive function, thereby allowing them to tailor education content and involve caregivers when necessary.