Acute pulmonary embolism represents a major complication of venous thromboembolism that is associated with high morbidity and mortality. Guidelines recommend the rapid initiation of anticoagulation and consideration of thrombolytic therapy in select patients, including those with hypotension or at high risk of developing hypotension. Evaluation for thrombolytic therapy should only be considered after assessment of contraindications and risk for major bleeding. The objective of this perspective article is to evaluate the bleeding risk associated with systemic thrombolytic therapy in the management of acute pulmonary embolism and discuss strategies to minimize this risk. Risk stratification of acute pulmonary embolism will be discussed to identify patient populations that warrant specific consideration of risk for major bleeding with thrombolytic therapy. In addition, the incidence, patient-specific risk factors, and pharmacologic characteristics, including concurrent anticoagulation and thrombolytic therapy, will be evaluated in the context of risk for major hemorrhage. Finally, supporting evidence for strategies to minimize risk of hemorrhage, including evaluation of contraindications, weight adjusted dosing, infusion strategy and catheter-directed thrombolytic administration will be evaluated. Despite published guidelines and review articles, select aspects to thrombolytic therapy for the management of pulmonary embolism remain controversial and under recognized, including risk of major hemorrhage. When making decisions about the role of thrombolytic therapy in pulmonary embolism, clinicians must be knowledgeable about the associated risks of thrombolytic therapy and individually evaluate patient risk factors prior to determining appropriate candidacy for thrombolytic therapy. For patients considered to be at high risk of major bleeding, strategies to minimize risk should be considered, including weight-adjusted doses and catheter directed therapy. Additional research is needed specific to the acute pulmonary embolism setting to validate risk factors and strategies to minimize major hemorrhage.

Background. Trials have shown that novel oral anticoagulants may decrease length of stay versus warfarin. A comparison of length of stay in the treatment of pulmonary embolism (PE) has not been performed outside post hoc analysis of a large clinical trial. Objective. To evaluate if rivaroxaban decreases length of stay compared to warfarin plus enoxaparin in the treatment of PE. Methods. This was a multicenter, retrospective, observational cohort study. Patients were identified based on discharge diagnosis of PE and were excluded if they received anticoagulants prior to admission and had additional indications for anticoagulation or reduced creatinine clearance. The primary endpoint was length of stay. Secondary endpoints included time from initial dose of oral anticoagulant to discharge and length of stay comparison between subgroups. Results. Inclusion criterion was met by 158 patients (82 warfarin, 76 rivaroxaban). The median length of stay was 4.5 days (interquartile range [IQR], 2.7, 5.9) in the warfarin group and 1.8 days (IQR, 1.2, 3.7) in the rivaroxaban group (P < 0.001). Time interval from first dose of oral anticoagulant to discharge was shorter with rivaroxaban (P < 0.001). Conclusions. Patients given rivaroxaban had decreased length of stay versus those given warfarin plus enoxaparin for the treatment of PE.

Thromboelastography (TEG) with platelet mapping has been proposed as an assay to detect the presence of antiplatelet agents (APA), yet no study has evaluated TEG markers of platelet dysfunction in acute trauma patients stratified by the use of preinjury APA. We hypothesized that patients on preinjury APA would demonstrate prolonged TEG markers of platelet dysfunction compared with those not on preinjury APA. This retrospective review evaluated all trauma patients admitted to a Level I trauma center from February 2011 to April 2013 who received a TEG within the first 24 hours of admission. Patients were classified as receiving preinjury APA or no APA if their documented medications included either aspirin or adenosine diphosphate (ADP) antagonists, including clopidogrel, prasugrel, and ticagrelor. A total of 129 patients were included (APA, n = 35; no APA n = 94) in the study. The time from admission to the first TEG was similar (APA 175 ± 289 minutes versus no APA 216 ± 321 minutes, P = 0.5). There was no significant difference in TEG markers of platelet dysfunction, including per cent ADP inhibition (APA 61.7 ± 25.8% versus no APA 62.3 ± 28.8%; P = 0.91) or per cent arachidonic acid inhibition (APA 58.2 ± 31% versus no APA 53.8 ± 34%; P = 0.54). Both groups had similar proportion of severe platelet dysfunction, defined as ADP inhibition greater than 70 per cent (APA 40% versus no APA 40%; P = 0.8) and arachidonic acid inhibition greater than 70 per cent (APA 40% versus no APA 39%; P = 0.89). In conclusion, platelet dysfunction after major trauma is common. Therefore, TEG alone should not be used to evaluate for the presence of APA due to apparent lack of specificity.

ObjectivesHypoalbuminemia occurs in 25% to 76% of patients hospitalized for acute heart failure (HF) and is associated with increased mortality. Hypoalbuminemia may predispose patients to intravascular volume depletion, hypotension, and acute worsening of renal function; however, its association with treatment outcomes during hospitalization is unknown.MethodsThis retrospective cohort study involved 414 adult patients hospitalized for HF requiring intravenous diuretics. Temporal changes in serum albumin and the association of hypoalbuminemia with urine output, renal function changes, blood pressure, use of intravenous vasoactive drugs, and short-term outcomes were assessed.ResultsSerum albumin decreased in most patients (72%) during hospitalization. Hypoalbuminemia was present in 29% and 50% of patients based on the mean admission and nadir serum albumin level, respectively. Hypoalbuminemia as assessed by the nadir albumin level was associated with an increased risk of acute worsening of renal function. A nadir albumin level of <3.0 g/dL remained significantly associated in the multivariate analyses.ConclusionsSerum albumin commonly decreases during hospitalization for acute HF. Hypoalbuminemia assessed using the nadir level during hospitalization, not the admission level, was associated with an increased risk of acute worsening of renal function. The timing of serum albumin measurement may influence its utility as a biomarker.

Sepsis is a common intensive care unit event occurring in approximately 750 000 patients annually, with a case mortality rate approaching 50%. Sepsis is characterized by a chaotic and excessive release of inflammatory cytokines and procoagulants including tumor necrosis factor, interleukin (IL)-1, IL-6, IL-8, platelet-activating factor, and tissue factor. Efforts to inhibit individual cytokines in order to modify poor outcomes have been generally disappointing, suggesting the need to target multiple inflammatory mediators to obtain clinical benefit. Statins lower lipids by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which in turn inhibits the rate-limiting step in cholesterol biosynthesis. In addition to lowering total cholesterol, statins have pleiotropic effects on inflammation and immunity. Instead of impacting a single entity in the sepsis syndrome, statins may have positive effects on multiple inflammatory, immunomodulating, and coagulation targets involved in the development of infection and sepsis. There have been a number of institutional- and population-based studies that have evaluated the impact of statins in patients with infection and sepsis. Most of these studies, but not all, have demonstrated a number of positive outcomes in patients with statins, including reduction in mortality. Based on these data, statins are a promising therapy in the management of patients with sepsis and warrant larger and more rigorous clinical trials.

When commencing a patient on aripiprazole the possibility of emergence of problem gambling and other impulse-control deficits should be monitored, even in those with no history of similar behaviours and even on a low dose.

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OBJECTIVES: Evidence suggests palivizumab may be beneficial for respiratory syncytial virus (RSV) infection in pediatric patients, although it is only approved by the US Food and Drug Administration for RSV prophylaxis. The objective of this study is to compare outcomes among pediatric patients with RSV infection who received intravenous palivizumab and standard of care versus standard of care alone. METHODS: This is a retrospective, single-center cohort study conducted between November 2003 and October 2013. Pediatric patients with active RSV infection treated with intravenous (IV) palivizumab after initiation of mechanical ventilation were matched 1:1 to a control selected from ventilated patients who received standard of care. The primary end point evaluated the duration of mechanical ventilation between groups. Secondary end points included hospital length of stay, intensive care unit length of stay, duration of respiratory support over baseline, time to RSV microbiologic cure, duration of antibiotic therapy, and in-hospital mortality. RESULTS: A total of 22 patients with a median age of 3 months were included in the study. Patients in the treatment group received a median of 2 doses of IV palivizumab, with a mean dose of 14.2 mg/kg. All patients received bronchodilators and corticosteroids, with the exception of 1 patient in the control group, and only 1 treatment group patient received IV ribavirin. Duration of mechanical ventilation was longer in the treatment group (18.9 ± 9.5 vs. 14.3 ± 9.3 days; p = 0.26). No statistically significant differences were observed between groups for any of the secondary end points. CONCLUSIONS: Pediatric patients who received IV palivizumab in addition to standard of care for treatment of RSV infection following initiation of mechanical ventilation experienced similar outcomes to those who received standard of care alone. Further studies are necessary to evaluate the potential benefit of IV palivizumab in addition to current standard of care.