Fibrin Derived from Patients with Chronic Thromboembolic Pulmonary Hypertension Is Resistant to Lysis

Rationale: Although acute pulmonary embolism is epidemiologically associated with chronic thromboembolic pulmonary hypertension, the factors responsible for resistance to thrombolysis and a shift toward vascular remodeling within the pulmonary arteries of patients with chronic thromboembolic pulmonary hypertension are unknown

Bosentan as a bridge to pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension

OBJECTIVES: In proximal chronic thromboembolic pulmonary hypertension, pulmonary endarterectomy is the treatment of first choice. In general, medical treatment before pulmonary endarterectomy is not indicated. However, selected "high-risk" patients might benefit by optimization of pulmonary hemodynamics. Moreover, in patients whose surgery is delayed owing to limited medical resources, pretreatment may prevent clinical deterioration. The primary objective of this study was to determine whether the dual endothelin-1 antagonist bosentan improves pulmonary hemodynamics and functional capacity in patients with proximal chronic thromboembolic pulmonary hypertension waiting for pulmonary endarterectomy. METHODS: We used an investigator-initiated, randomized, controlled single-blind study. Patients were randomized to receive bosentan (n = 13) or no bosentan (n = 12) for 16 weeks, next to "best standard of care." The primary end point was change in total pulmonary resistance. Secondary end points included changes in 6-minute walk distance, mean pulmonary artery pressure, and cardiac index. RESULTS: After 16 weeks, the mean differences in change from baseline between the groups were as follows: total pulmonary resistance 299 dynes . s . cm(-5) (P = .004), 6-minute walk distance 33 m (P = .014), mean pulmonary artery pressure 11 mm Hg (P = .005), and cardiac index 0.3 L . min(-1) . m(-2) (P = .08). Treatment with bosentan was safe. After pulmonary endarterectomy, 4 patients died (no-bosentan group: n = 3); the short-term in-hospital postoperative clinical course was similar in both groups of patients. CONCLUSIONS: Patients with proximal chronic thromboembolic pulmonary hypertension may benefit hemodynamically and clinically from treatment with bosentan before pulmonary endarterectomy. Individual factors predictive of a beneficial response and whether this influences either morbidity or mortality associated with pulmonary endarterectomy remain to be establishe

Unexpected intensive care transfer of admitted patients with severe sepsis.

BackgroundPatients with severe sepsis generally respond well to initial therapy administered in the emergency department (ED), but a subset later decompensate and require unexpected transfer to the intensive care unit (ICU). This study aimed to identify clinical factors that can predict patients at increased risk for delayed transfer to the ICU and the association of delayed ICU transfer with mortality.MethodsThis is a nested case-control study in a prospectively collected registry of patients with severe sepsis and septic shock at two EDs. Cases had severe sepsis and unexpected ICU transfer within 48 h of admission from the ED; controls had severe sepsis but remained in a non-ICU level of care. Univariate and multivariate regression analyses were used to identify predictors of unexpected transfer to the ICU, which was the primary outcome. Differences in mortality between these two groups as well as a cohort of patients directly admitted to the ICU were also calculated.ResultsOf the 914 patients in our registry, 358 patients with severe sepsis were admitted from the ED to non-ICU level of care; 84 (23.5%) had unexpected ICU transfer within 48 h. Demographics and baseline co-morbidity burden were similar for patients requiring versus not requiring delayed ICU transfer. In unadjusted analysis, lactate ≥4 mmol/L and infection site were significantly associated with unexpected ICU upgrade. In forward selection multivariate logistic regression analysis, lactate ≥4 mmol/L (OR 2.0, 95% CI 1.03, 3.73; p = 0.041) and night (5 PM to 7 AM) admission (OR 1.9, 95% CI 1.07, 3.33; p = 0.029) were independent predictors of unexpected ICU transfer. Mortality of patients who were not upgraded to the ICU was 8.0%. Patients with unexpected ICU upgrade had similar mortality (25.0%) to those patients with severe sepsis/septic shock (24.6%) who were initially admitted to the ICU, despite less severe indices of illness at presentation.ConclusionsSerum lactate ≥4 mmol/L and nighttime admissions are associated with unexpected ICU transfer in patients with severe sepsis. Mortality among patients with delayed ICU upgrade was similar to that for patients initially admitted directly to the ICU