Evaluation of Time to Therapeutic Anticoagulation and Associated Outcomes in Critically Ill, Obese Patients With Pulmonary Embolism Receiving Unfractionated Heparin.

BACKGROUND: Delays in time to therapeutic activated partial thromboplastin time (aPTT) have been associated with poor outcomes in patients with acute pulmonary embolism (PE). OBJECTIVE: To investigate the relationship between time to therapeutic anticoagulation and in-hospital mortality in critically ill, obese patients with acute PE. METHODS: This study examined 204 critically ill patients with a body mass index (BMI) ≥30 kg/m2 receiving unfractionated heparin (UFH) for PE treatment. Patients achieving therapeutic anticoagulation within 24 hours of UFH initiation (early) were compared to those in >24 hours (delayed). Additional end points included 30-day mortality, median time to therapeutic aPTT, proportion of therapeutic and supratherapeutic aPTT values, hemodynamic deterioration, thrombolytic therapy after UFH initiation, length of stay, and bleeding. RESULTS: No difference in in-hospital or 30-day all-cause mortality was seen (odds ratio [OR]: 1.33, confidence interval [CI]: 0.647-2.72; OR: 1.003, CI: 0.514-1.96). Patients in the early group had a greater proportion of therapeutic aPTT values (66.7% vs 50%, P < .001) and higher percentage of supratherapeutic aPTT values (20.9% vs 11.3%, P < .001); however, no increase in clinically significant bleeding was evident (15.2% vs 10.9%, P = .366). CONCLUSION: In this population, a shorter time to therapeutic aPTT was not associated with improved survival.

Evaluation of Clinical Outcomes with Phosphodiesterase-5 Inhibitor Therapy for Right Ventricular Dysfunction After Left Ventricular Assist Device Implantation.

Few studies have evaluated the use of phosphodiesterase-5 inhibitors (PDE5-i) for right ventricular (RV) dysfunction after left ventricular assist device (LVAD) implantation. The study purpose was to examine the impact of postoperative inpatient PDE5-i therapy on clinical outcomes in patients with LVADs. This single-center, retrospective cohort study screened 445 LVAD recipients between January 2011 and May 2015 for eligibility. Subjects receiving post-LVAD PDE5-i were compared with those who did not. The primary outcome was the proportion of all-cause hospital readmission at 30 days. Additional outcomes assessed included duration of intravenous inotrope or inhaled epoprostenol therapy, length of stay, duration of mechanical ventilation, overall survival, and improvement in the degree of postoperative RV dysfunction. Comparative analyses were performed before and after propensity score (PS) matching. Three-hundred and eighteen patients were included; 208 received post-LVAD inpatient PDE5-i and 110 patients did not. There was no difference in the rate of readmission at 30 days before or after PS matching. No significant differences were found between groups with regard to inotrope or epoprostenol duration, lengths of stay, duration of mechanical ventilation, overall survival, or improvement in the degree of RV dysfunction after PS matching. In the current study, the use of PDE5-i for adjunctive treatment of post-LVAD RV dysfunction was not associated with improved clinical outcomes.

Outcomes and Predictors of Early Infection after Heart Transplantation.

BACKGROUND: Limited data exist on the incidence and outcome of early infection after orthotopic heart transplantation (OHT). The purpose of this study was to describe characteristics and outcomes of OHT recipients with an early infection and to identify predictors of such infections. METHODS: This retrospective, single-center study included patients greater than 18 years of age who underwent OHT from February 2009 to May 2014 and had an infection within 30 days of transplantation. Patient demographics, clinical variables, and outcomes were collected. Multivariable logistic regression was performed to identify independent predictors of infection. RESULTS: Of the 172 eligible OHT recipients, 51 (29.7%) had an early infection. The median time to diagnosis was five days, with gram-negative organisms being slightly more common (58.2%). No differences in mortality rate, rejection, or re-admission were found between the groups. Longer durations of mechanical ventilation and lengths of stay were found in the infection group (p < 0.001). Patients with an early infection also had a higher incidence of mechanical circulatory support, history of drive-line infection, longer duration of mechanical ventilation, continuous renal replacement therapy (CRRT), and delayed chest closure (p < 0.05 for all). Pre-OHT left-ventricular assist device (adjusted odds ratio [AOR] 2.53; 95% confidence interval [CI] 1.015-6.286; p < 0.046), pre-OHT extracorporeal membrane oxygenation (AOR 14.10; 95% CI 1.38-150.5; p = 0.026) and post-OHT CRRT (AOR 3.98; 95% CI 1.67-9.52; p = 0.002) were found to be independent risk factors for an early infection. A total of 90% of the available susceptibility panels for the gram-negative isolates (26/29) were resistant to the standard peri-operative cephalosporin given. CONCLUSIONS: Prior mechanical circulatory support and the acute need for CRRT may predispose OHT patients to an infection early in the post-operative period. Evaluation of peri-operative antimicrobial prophylaxis, based on an individual center's resistance panels, may be warranted.

Contaminated heparin and outcomes after cardiac surgery: a retrospective propensity-matched cohort study.

BACKGROUND: During 2007 and 2008 it is likely that millions of patients in the US received heparin contaminated (CH) with oversulfated chondroitin sulfate, which was associated with anaphylactoid reactions. We tested the hypothesis that CH was associated with serious morbidity, mortality, intensive care unit (ICU) stay and heparin-induced thrombocytopenia following adult cardiac surgery. METHODS AND FINDINGS: We conducted a single center, retrospective, propensity-matched cohort study during the period of CH and the equivalent time frame in the three preceding or the two following years. Perioperative data were obtained from the institutional record of the Society of Thoracic Surgeons National Database, for which the data collection is prospective, standardized and performed by independent investigators. After matching, logistic regression was performed to evaluate the independent effect of CH on the composite adverse outcome (myocardial infarction, stroke, pneumonia, dialysis, cardiac arrest) and on mortality. Cox regression was used to determine the association between CH and ICU length of stay. The 1∶5 matched groups included 220 patients potentially exposed to CH and 918 controls. There were more adverse outcomes in the exposed cohort (20.9% versus 12.0%; difference  =  8.9%; 95% CI 3.6% to 15.1%, P < 0.001) with an odds ratio for CH of 2.0 (95% CI, 1.4 to 3.0, P < 0.001). In the exposed group there was a non-significant increase in mortality (5.9% versus 3.5%, difference = 2.4%; 95% CI, -0.4 to 3.5%, P  =  0.1), the median ICU stay was longer by 14.1 hours (interquartile range -26.6 to 79.8, S = 3299, P = 0.0004) with an estimated hazard ratio for CH of 1.2 (95% CI, 1.0 to 1.4, P = 0.04). There was no difference in nadir platelet counts between cohorts. CONCLUSIONS: The results from this single center study suggest the possibility that contaminated heparin might have contributed to serious morbidity following cardiac surgery.

The use of eptifibatide for suspected pump thrombus or thrombosis in patients with left ventricular assist devices.

BACKGROUND: Pump thrombosis in patients with left ventricular assist devices (LVADs) continues to present treatment challenges. Anti-coagulation strategies used to treat this complication are empiric and without firm data for guidance. The addition of a platelet glycoprotein IIb/IIIa inhibitor to intravenous anti-coagulation has been suggested by several case series and recent guidelines. The aim of this study was to evaluate our use of eptifibatide for the treatment of suspected pump thrombus/thrombosis. METHODS: This retrospective, single-center cohort study was performed at Barnes-Jewish Hospital. The medical informatics system was queried to identify all LVAD patients who received eptifibatide for suspected pump thrombus/thrombosis from January 1, 2011, through April 30, 2013. RESULTS: A total of 17 patients (16 HeartMate II [Thoratec, Pleasanton, CA], 1 HeartWare [HeartWare International Inc, Framingham, MA]) with 22 separate administration attempts received eptifibatide (dose range, 0.1-2 µg/kg/min) for suspected pump thrombus/thrombosis presenting as one or more of the following findings: elevated lactate dehydrogenase, decreased haptoglobin, elevated plasma free hemoglobin, LVAD dysfunction, or new, persistently high LVAD power. The mean time from device implantation to eptifibatide therapy was 47.34 days (range, 3.88-397.67 days). Of the 22 attempts, 5 (22.7%) resulted in resolution of 1 or more patient-specific indicators of LVAD thrombus/thrombosis. Three patients (17.6%) had resolution of an indicator while also remaining free from continued hemolysis, death, pump exchange, or emergent heart transplant. Bleeding events were common, with 11 patients (64.7%) experiencing bleeding during the infusion. Seven patients (41.2%) died, with intraparenchymal hemorrhage as the cause of death in 2 patients. Pump exchange was performed in 3 patients. CONCLUSIONS: Our limited experience indicates the risk of using eptifibatide outweighs the proposed benefit of salvaging the existing LVAD in the setting of suspected pump thrombus/thrombosis at our institution.

Current strategies for the treatment of complicated intraabdominal infections.

INTRODUCTION: Complicated intraabdominal infections (cIAIs) are a common cause of infection-related morbidity and mortality in hospitalized patients and present many challenges unique from other serious infections. cIAIs are generally polymicrobial in nature; however, controversy exists around the pathogenicity of some of the frequently identified microorganisms. Increasing antibiotic resistance among commonly isolated bacteria poses further challenges for clinicians managing patients with cIAIs. AREAS COVERED: This article highlights the microbiology and recent trends in antibiotic resistance most relevant to cIAIs, provides recommendations for treatment using currently available antimicrobials and introduces antibiotics in development with potential roles in managing cIAIs. EXPERT OPINION: Successful treatment of cIAI requires a combination of timely source control and thorough assessment of patient characteristics to guide selection of an appropriate empiric antimicrobial regimen. Specific considerations that should be made when choosing antibiotics include the origin of infection, presence of risk factors for potentially resistant pathogens and severity of disease. While it is encouraging that agents in development may prove helpful in the treatment of cIAIs with resistant pathogens, further identification of novel antibiotics is needed to address this growing concern. In addition, adherence to the principles of antimicrobial stewardship is needed if current antimicrobial resources are to be preserved for the treatment of cIAIs.

Occurrence and predictors of dexmedetomidine infusion intolerance and failure.

BACKGROUND: Dexmedetomidine, a selective α2 adrenergic receptor agonist, exhibits sedative, analgesic, anxiolytic, and sympatholytic effects, and may aid in controlling agitation in the intensive care unit (ICU). At our hospital (Barnes-Jewish Hospital, St. Louis, MO), dexmedetomidine is commonly used as a sedative in the medical ICU. Predictors of dexmedetomidine intolerance or failure have not yet been defined. OBJECTIVE: Describe the rate of dexmedetomidine infusion intolerance/failure and identify patient predictors of intolerance/failure. METHODS: This retrospective single-center cohort study evaluated 75 mechanically ventilated adults who received dexmedetomidine infusion. Patients were included in the study if they were aged ≥ 18 years; mechanically ventilated for > 24 hours; received dexmedetomidine infusion for ≥ 1 hour following > 24 hours of continuous infusions of midazolam, fentanyl, or propofol; and were admitted to our medical ICU between August 1, 2009 and August 1, 2010. Multivariate logistic regression analysis was performed to identify independent predictors of intolerance/failure. RESULTS: A total of 85 episodes of dexmedetomidine infusion were analyzed (75 total patients). Eighteen episodes (21%) met the criteria for intolerance/failure and 67 episodes (79%) met the criteria for tolerance/success. The median duration of mechanical ventilation, total dexmedetomidine infusion time, and ICU length of stay did not differ between groups. Nonblack race was the only variable independently associated with treatment failure or intolerance in the logistic regression analysis. CONCLUSION: Twenty-one percent of dexmedetomidine infusion episodes met the criteria for intolerance/failure. No predictors of intolerance/failure were found to be clinically significant.

Desirudin: a review of the pharmacology and clinical application for the prevention of deep vein thrombosis.

Direct thrombin inhibitors (DTIs) are an emerging class of anticoagulants in routine clinical practice, although they have been under investigation for quite some time. Desirudin (Iprivask®, Canyon Pharmaceuticals™) is a recombinant hirudin derivative that directly inhibits free and fibrin-bound thrombin. Desirudin was the first DTI approved for deep vein thrombosis (DVT) prophylaxis in Europe (Revasc®) and is the newest injectable DTI commercially available in the USA. Desirudin is one of the few nonheparin subcutaneous drugs that has demonstrable efficacy for DVT prophylaxis. Subcutaneous desirudin has been shown to be more effective than both subcutaneous unfractionated heparin and enoxaparin, with comparable bleeding rates in the prevention of DVT in patients undergoing elective hip replacement. Desirudin also offers the advantage of a fixed dosing regimen while being less immunogenic than unfractionated heparin. However, owing to its pharmacokinetic properties, patients with renal dysfunction require dosing modifications. The favorable profile shown with desirudin thus far will allow its clinical use to grow and will promote further investigation into broadening its clinical applications.