Bethany Tellor

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.

Inadequate Source Control and Inappropriate Antibiotics are Key Determinants of Mortality in Patients with Intra-Abdominal Sepsis and Associated Bacteremia

BACKGROUND Patients with intra-abdominal sepsis and associated bacteremia have a high mortality rate. However, outcomes studies in this population are limited, in part because of the small numbers of such patients. The objective of this study was to describe characteristics of critically ill patients with secondary blood stream infection (BSI) of intra-abdominal origin and identify predictors of mortality. METHODS This retrospective, single-center study evaluated patients admitted between January 2005 and January 2011 with bacteremia because of an intra-abdominal source. Patients were included if they met criteria for severe sepsis based on International Classification of Diseases, 9th Revision (ICD 9) codes for acute organ dysfunction, had a positive blood culture, had at least one ICD 9 code indicative of an intra-abdominal process, and had a confirmed or clinically suspected intra-abdominal infection (IAI) within 72 h of the blood culture. Chart review was performed to confirm the presence of these criteria and also the absence of any other potential source of bacteremia. Data were collected on patient demographics, BSI source, source control procedure details, microorganisms isolated, and antibiotics administered. Multivariable logistic regression analysis was performed to identify independent predictors of mortality. RESULTS Three hundred six patients with BSI were identified, of which 108 episodes were deemed to be of intra-abdominal origin. Gram-negative organisms comprised 43% of blood isolates, followed by gram-positives (33%), anaerobes (14%), and yeast (9%). Appropriate antimicrobial therapy was administered in 71% of patients. The overall mortality rate was 27.8%. As compared with survivors, non-survivors were older, more likely to have underlying COPD or asthma, and have renal or metabolic failure (p<0.05 for all). Among non-survivors, adequate source control was obtained less frequently (64% vs. 91%, p=0.002) and median time to appropriate antibiotics was longer (23 h vs. 4 h, p=0.004). Logistic regression analysis revealed inadequate source control (p=0.002) and inappropriate antibiotics (p=0.016) to be independently associated with mortality. CONCLUSIONS Critically ill patients with a BSI of abdominal origin are at high risk for mortality. Failure to achieve adequate source control and administration of inappropriate antibiotics were independent predictors of mortality. Thus, these represent potential opportunities to impact outcomes in patients with complicated IAI.

Occurrence and predictors of dexmedetomidine infusion intolerance and failure.

Abstract 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.

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.

Ketamine infusion for patients receiving extracorporeal membrane oxygenation support: a case series

The use of ketamine infusion for sedation/analgesia in patients receiving extracorporeal membrane oxygenation (ECMO) therapy has not been described. The aims of this retrospective cohort study were to explore whether ketamine infusion for patients requiring ECMO therapy was associated with altered RASS scores, decreased concurrent sedative or opioid use, or with changes in vasopressor requirements. All patients on ECMO who received ketamine infusions in addition to sedative and/or opioid infusions between December 2013 and October 2014 at Barnes-Jewish Hospital in St. Louis were retrospectively identified. Patient characteristics and process of care data were collected. A total of 26 ECMO patients receiving ketamine infusion were identified. The median (inter quartile range [range]) age was 40 years (30-52 [25-66]) with 62% male. The median starting infusion rate of ketamine was 50 mg/hr (30-50 [6-150]) and it was continued for a median duration of 9 days (4-14 [0.2-21]). Prior to ketamine, 14/26 patients were receiving vasopressor infusions to maintain hemodynamic stability. Ketamine initiation was associated with a decrease in vasopressor requirement in 11/26 patients within two hours, and 0/26 required an increase (p<0.001). All patients were receiving sedative and/or opioid infusions at the time of ketamine initiation; 9/26 had a decrease in these infusions within two hours of ketamine initiation, and 1/26 had an increase (p=0.02; odds ratio for decrease to increase = 9; 95% CI, 1.14 to 71.04). The median (IQR[range]) RASS score 24 hours before ketamine initiation was -4 (-3 to -5, [0 to -5]) and after ketamine was -4 (-3 to -4 [-1 to -5]) ( P = 0.614). Ketamine infusion can be used as an adjunctive sedative agent in patients receiving ECMO and may decrease concurrent sedative and/or opioid infusions without altering RASS scores. The hemodynamic effects of ketamine may provide the benefit of decreasing vasopressor requirements.

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.

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.