Tirofiban in Suspected Left Ventricular Assist Device Pump Thrombosis.

Antithrombotic optimization with a glycoprotein IIb/IIIa inhibitor has been used for the treatment of suspected pump thrombosis, but available literature with tirofiban is lacking. This study aims to describe the use of tirofiban for suspected pump thrombosis. This was a single-center cohort study of left ventricular assist device patients who received tirofiban for the treatment of suspected pump thrombosis from January 1, 2016 to July 31, 2017. Tirofiban was initiated at 0.1 µg/kg/min in patients with normal renal function and subsequent dose adjustments for altered renal function or history of bleeding were employed. Success was defined as resolution of lactate dehydrogenase back to patients' known baseline. Fourteen patients were included for 16 total instances of tirofiban use during the time period. Tirofiban was continued for a median of 5 days (range: 0.3-35 days). Successful treatment was achieved in 12 of the 16 tirofiban uses (75%). Seven bleeding events occurred while on therapy, two major and five minor. This study showed a majority of patients achieved success with tirofiban for suspected pump thrombosis. For patients who are not current candidates for pump exchange or transplant, tirofiban may be considered a therapeutic medical management option.

Assessment of hospital emergency medication kit use at a large academic medical center with automated dispensing machine technology.

PURPOSE: Hospital emergency medication kits (HEMKs) are used to provide certain critical medications in emergent situations, despite many technological advancements for patient safety and medication distribution. We sought to evaluate HEMK usage and analyze associated costs to identify and recommend process improvements. METHODS: Mayo Clinic in Rochester, MN, is a large multisite academic medical center with 2 hospital campuses and many ambulatory clinics. All documentation of the approximately 250 HEMKs in circulation was analyzed from January to November 2017. The primary outcome was HEMK use. Secondary outcomes included individual medication usage and associated costs. These data were then used to recommend process improvements. RESULTS: Of 880 HEMKs evaluated, 675 (76.7%) were used, resulting in expiration 23.3% of the time. A total of 1,024 emergency medications were used, most commonly for hypoglycemia. Many of these medications are also available in automated dispensing machines for patient care use. Cost analysis revealed an average annual cost of nearly $200,000 associated with HEMKs. The results of our analysis indicated little added benefit of HEMKs in the setting of automated dispensing machine optimization. Steps for HEMK retirement are described. CONCLUSION: HEMKs offered little added benefit considering technological advancements that have been made in patient safety and medication distribution since their inception. Retirement of HEMKs is anticipated to increase pharmacy operational efficiency by using automated dispensing machine technology and appropriate emergency response protocols to ensure optimal patient care.

Relationship of Ganciclovir Therapeutic Drug Monitoring with Clinical Efficacy and Patient Safety.

The clinical utility of ganciclovir therapeutic drug monitoring (TDM) is unknown. We retrospectively analyzed adult patients treated for cytomegalovirus (CMV) infection with ganciclovir with TDM between 2005 and 2015. The primary outcome was an association between ganciclovir TDM and clinical efficacy endpoints within 30 days, defined by viral load and symptomatology. Secondary outcomes included safety endpoints, evaluated within 7 days of the last administered dose of ganciclovir. Of 175 patients evaluated, 82 patients with CMV infection were included in our analysis with a median (interquartile range) baseline CMV viral load of 5,500 (3,000 to 15,200) copies/ml. The majority achieved undetectable or reduced CMV viral load below the lower limit of quantification (74.4%) with improvement in symptomatology (70.7%) at 30 days. Among patients with detectable CMV viremia at 30 days, the viral load had declined to a median of 1,000 (1,000 to 3,090) copies/ml. We did not observe significant associations between the efficacy outcomes and ganciclovir trough (P = 0.20 and P = 0.20, respectively) or peak concentrations (P = 0.14 and P = 0.14, respectively). Similarly, there was no significant association between ganciclovir trough or peak concentrations and safety endpoints, including leukopenia (P = 0.48 and P = 0.69), neutropenia (P = 0.59 and P = 0.69), thrombocytopenia (P = 0.29 and P = 0.37), anemia (P = 0.51 and P = 0.35), nephrotoxicity (P = 0.41 and P = 0.57), and neurotoxicity (P = 0.22 and P = 0.48). We did not observe any associations between ganciclovir TDM and clinical efficacy or safety endpoints. Routine ganciclovir TDM may be of limited value. Future studies may be warranted to identify specific populations with unpredictable pharmacokinetic and pharmacodynamics profiles in whom ganciclovir TDM may be of benefit.

Nicardipine Reduces Blood Pressure Variability After Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Blood pressure variability (BPV) is an independent predictor for early hematoma expansion, neurologic deterioration, and mortality. There are no studies on the effect of intravenous (IV) antihypertensive drugs on BPV. We sought to determine whether patients have more BPV with certain antihypertensive agents, in particular the effect of IV nicardipine. METHODS: We conducted a single-center, retrospective chart review of individuals diagnosed with spontaneous intracerebral hemorrhage (ICH) receiving labetalol, hydralazine, and/or nicardipine within 24 h of hospital admission to assess the primary endpoint of BPV, defined as the standard deviation of systolic BP, with labetalol and/or hydralazine compared to nicardipine ± labetalol and/or hydralazine. Repeated measures linear regression was performed to compare BPV over 24 h between regimens, and Cox proportional hazards regression was used to compare the time to goal SBP between regimens. RESULTS: Of the 1330 patients screened, 272 were included in our analysis; those included had a mean age of 69 years with 87.9% of Caucasian race. A total of 164 patients received IV bolus antihypertensives alone (labetalol, hydralazine or both), and 108 patients received IV nicardipine with or without additional IV boluses (labetalol, hydralazine, or both). Those who had IV nicardipine had significantly less BPV (p = 0.04) and was more likely to attain an SBP goal < 140 mmHg (p < 0.01). CONCLUSION: Our study suggests patients with ICH who do not receive a nicardipine-based antihypertensive regimen have more BPV, which has been associated with poor clinical outcomes. Prospective, randomized, controlled trials are needed to determine the impact of specific antihypertensive regimens on clinical outcomes.

Sedation Variability Increases Incidence of Delirium in Adult Medical Intensive Care Unit Patients at a Tertiary Academic Medical Center.

BACKGROUND: Variability in sedation may increase the incidence of delirium and mortality, as well as increased intensive care unit (ICU) and hospital lengths of stay (LOS), despite mean Richmond Agitation Sedation Scale (RASS) scores at goal. Coefficient of variation (CV) can be used to represent variability with a higher ratio indicating increased variability. STUDY QUESTION: Do patients with an increased variability in sedation, as evaluated by CV in RASS, have an increased incidence of delirium? METHODS: We conducted a retrospective chart review of adult medical ICU patients requiring mechanical ventilation (MV) for ≥24 hours between January and April 2013. Patients were excluded if intubated at an outside hospital, neuromuscularly blocked, suffering from anoxic brain injury, or had a goal RASS of -4 or -5. Outcomes assessed included the presence of delirium, as evaluated by the Confusion Assessment Method, RASS, CV in RASS, duration of MV, ICU, and hospital LOS, and survival. RESULTS: Of 45 included patients, 32 experienced delirium during their ICU admission and 13 did not. The groups were similar at baseline. There was no difference in mean RASS when comparing the delirium and nondelirium groups (-1.6 ± 1.3 vs. -1.8 ± 0.8, respectively; P = 0.61). Patients with delirium had a greater CV in RASS (0.3 ± 0.135 vs. 0.2 ± 0.105; P = 0.02), a longer MV duration [4 (2-8) vs. 3 (2-3) days; P = 0.045], and a trend toward increased ICU LOS [8 (5-12.25) vs. 4 (3-8) days; P = 0.096], but no difference in hospital LOS [13 (10-25) vs. 18 (9-39) days; P = 0.83] and survival (71.9% vs. 69.2%; P = 1.0). CONCLUSION: Medical ICU patients with delirium had a higher CV in RASS compared with patients without delirium, suggesting that greater variability in sedation may increase the incidence of delirium. Patients with delirium also had a greater duration of MV and a trend toward longer ICU LOS.

International Analysis of LVAD Point-of-Care Versus Plasma INR: A Multicenter Study.

International normalized ratio (INR) measurements manage risks of bleeding and clotting sequelae in the population with left ventricular assist device (LVAD). Studies suggest that point-of-care (POC) INR does not significantly differ from plasma INR (P-INR) values in other patient populations, although this has not been validated in a multicenter LVAD study. We sought to determine whether POC-INR and P-INR values differ significantly in the LVAD population and reviewed patients with permanent LVAD implantation at seven institutions internationally. Our cohort comprised of 279 paired POC-INR and P-INR checks in patients supported on average 630 ± 598 days postimplant with predominately HeartWare, HeartMate II, and HeartMate III devices. The population averaged 57.9 years of age, and there were 86.7% male. We found no statistically significant difference between POC-INR and P-INR values. International normalized ratio accuracy correlated weakly with the time between INR measurements (p < 0.001). When the time difference was less than 4 hours, the difference between INR pairs was significantly lower than measurements greater than 8 hours (p = 0.006). There was no statistically significant difference when comparing paired INR values and time after implant to INR check (p = 0.43), age (p = 0.12), known coagulopathy (p = 0.12), bleeding history (p = 0.22), or thrombosis history (p = 0.34). This is the first large multicenter international study comparing POC-INR and P-INR measurements in patients with LVAD and found no statistically significant difference between either methods, particularly when measured within less than 4 hours of each other.

Risk factors for acute kidney injury associated with the treatment of bacterial endocarditis at a tertiary academic medical center.

BACKGROUND: Acute kidney injury (AKI) is a common complication of endocarditis. OBJECTIVE: To determine risk factors for the development of AKI in patients treated for endocarditis. METHODS: This single centre, retrospective univariate and multivariate analysis to determine risk factors for the development of AKI included patients diagnosed with endocarditis between January 2009 and October 2013. RESULTS: Of 211 included patients, a total of 84 (39.8%) patients developed AKI. We identified multiple independent variables associated with the development of AKI, including: age ≥ 65 years, presence of hardware, chronic kidney disease, AKI on admission, infection with Staphylococcus spp, receipt of nafcillin or oxacillin or aminoglycoside and nafcillin or oxacillin or aminoglycoside and vancomycin, vancomycin trough level ≥ 20.0 mcg/ml, aminoglycoside total daily dose reduction, duration of vancomycin exceeding three days, receipt of loop diuretic or more than three concomitant nephrotoxins and duration of loop diuretic or non-steroidal anti-inflammatory drug therapy exceeding seven days. CONCLUSIONS: In patients treated for endocarditis, multiple risk factors for AKI were identified. Prospective studies are needed to evaluate these variables for causation of AKI in patients treated for endocarditis.

Comparison of an IgG-Specific Enzyme-Linked Immunosorbent Assay Cutoff of 0.4 Versus 0.8 and 1.0 Optical Density Units for Heparin-Induced Thrombocytopenia.

BACKGROUND: Previous studies have demonstrated optimized diagnostic accuracy in utilizing higher antiheparin-platelet factor 4 (PF4) enzyme-linked immunosorbent assay (ELISA) optical density (OD) thresholds for diagnosing heparin-induced thrombocytopenia (HIT). We describe the incidence of positive serotonin release assay (SRA) results, as well as performance characteristics, for antiheparin-PF4 ELISA thresholds ≥0.4, ≥0.8, and ≥1.0 OD units in the diagnosis of HIT at our institution. METHODS: Following institutional review board approval, we conducted a single-center retrospective chart review on adult inpatients with a differential diagnosis of HIT evaluated by both antiheparin-PF4 ELISA and SRA from 2012 to 2014. The major endpoints were to assess incidence of positive SRA results, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy at antiheparin-PF4 ELISA values ≥0.4 OD units when compared to values ≥0.8 and ≥1.0 OD units. Clinical characteristics, including demographics, laboratory values, clinical and safety outcomes, length of stay, and mortality, were collected. RESULTS: A total of 140 patients with 140 antiheparin-PF4 ELISA and SRA values were evaluated, of which 23 patients were SRA positive (16.4%) and 117 patients were SRA negative (83.6%). We identified a sensitivity of 91.3% versus 82.6% and 73.9%, specificity of 61.5% versus 87.2% and 91.5%, PPV of 31.8% versus 55.9% and 63.0%, NPV of 97.3% versus 96.2% and 94.7%, and accuracy of 66.4% versus 86.4% and 88.6% at antiheparin-PF4 ELISA thresholds ≥0.4, ≥0.8, and ≥1.0 OD units, respectively. CONCLUSION: Our study suggests an increased antiheparin-PF4 ELISA threshold of 0.8 or 1.0 OD units enhances specificity, PPV, and accuracy while maintaining NPV with decreased sensitivity.

Evaluation of sedatives, analgesics, and neuromuscular blocking agents in adults receiving extracorporeal membrane oxygenation.

PURPOSE: The objective of this study was to evaluate the use of sedative, analgesic, and neuromuscular blocking agents (NMBAs) in patients undergoing extracorporeal membrane oxygenation (ECMO) support. MATERIALS AND METHODS: This was a 2-year, prospective, observational study of adult intensive care unit patients on ECMO support for more than 48hours. RESULTS: We analyzed 32 patients, including 15 receiving VA (venoarterial) ECMO and 17 VV (venovenous) ECMO. The median daily dose of benzodiazepines (midazolam equivalents) was 24mg, and the median daily dose of opioids (fentanyl equivalents) was 3875 µg. There was a moderate negative correlation between the day of ECMO and the median daily benzodiazepine dose (r=-0.5515) and a very weak negative correlation for the median daily opioid dose (r=-0.0053). On average, patients were sedated to Richmond Agitation Sedation Scale scores between 0 and -1. Continuous infusions of opioids, benzodiazepines, propofol, dexmedetomidine, and NMBAs were administered on 404 (85.1%), 199 (41.9%), 95 (20%), 32 (6.7%), and 60 (12.6%) ECMO days, respectively. Patients in the VA arm received a continuous infusion opioid (96.4% vs 81.6% days; P<.001) and benzodiazepine (58.2% vs 37.0% days; P<.001) more frequently. CONCLUSIONS: Patients received relatively low doses of sedatives and analgesics while at a light level of sedation on average. Patients rarely required neuromuscular blockade.

Treatment of heparin-induced thrombocytopenia before and after the implementation of a hemostatic and antithrombotic stewardship program.

In October 2013, we implemented a hemostatic and antithrombotic (HAT) stewardship program with the primary focus of ensuring appropriate use of intravenous direct thrombin inhibitors (DTI) in patients with heparin-induced thrombocytopenia (HIT). We sought to compare the duration and cost of DTI therapy for the management of HIT before and after implementation of the HAT stewardship program. Following institutional review board approval, we conducted a single center, retrospective chart review of all patients with a suspected diagnosis of HIT as assessed by an anti-heparin-PF4 enzyme-linked immunosorbent assay 6 months pre-HAT and post-HAT implementation. Patients were excluded if they were initiated on a DTI at an outside hospital, had a prior episode of HIT, or received mechanical circulatory support. Clinical characteristics, including demographics, comorbidities, medications, laboratory values, clinical and safety outcomes, length of stay, and mortality, were collected. A total of 592 patients were included; 333 patients were evaluated pre-HAT, while 259 patients were evaluated post-HAT. The mean duration of DTI treatment was significantly decreased in the post-HAT cohort (6.64 vs 5.17 days, p = 0.01), primarily driven by decreased duration of use for patients with suspected HIT (4.07 vs 2.86 days, p = 0.01). The HAT Stewardship program demonstrated a total decrease in annual costs associated with the diagnosis and management of HIT of $248,500. Our results indicate that the implementation of the HAT stewardship program had a significant impact on reducing the duration and costs of DTI therapy and the costs of laboratory evaluations in the management of HIT at our institution.