Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study.

BACKGROUND: Macitentan is beneficial for long-term treatment of pulmonary arterial hypertension. The microvasculopathy of chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension are similar. METHODS: The phase 2, double-blind, randomised, placebo-controlled MERIT-1 trial assessed macitentan in 80 patients with CTEPH adjudicated as inoperable. Patients identified as WHO functional class II-IV with a pulmonary vascular resistance (PVR) of at least 400 dyn·s/cm5 and a walk distance of 150-450 m in 6 min were randomly assigned (1:1), via an interactive voice/web response system, to receive oral macitentan (10 mg once a day) or placebo. Treatment with phosphodiesterase type-5 inhibitors and oral or inhaled prostanoids was permitted for WHO functional class III/IV patients. The primary endpoint was resting PVR at week 16, expressed as percentage of PVR measured at baseline. Analyses were done in all patients who were randomly assigned to treatment; safety analyses were done in all patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT02021292. FINDINGS: Between April 3, 2014, and March 17, 2016, we screened 186 patients for eligibility at 48 hospitals across 20 countries. Of these, 80 patients in 36 hospitals were randomly assigned to treatment (40 patients to macitentan, 40 patients to placebo). At week 16, geometric mean PVR decreased to 71·5% of baseline in the macitentan group and to 87·6% in the placebo group (geometric means ratio 0·81, 95% CI 0·70-0·95, p=0·0098). The most common adverse events in the macitentan group were peripheral oedema (9 [23%] of 40 patients) and decreased haemoglobin (6 [15%]). INTERPRETATION: In MERIT-1, macitentan significantly improved PVR in patients with inoperable CTEPH and was well tolerated. FUNDING: Actelion Pharmaceuticals Ltd.

Distal vessel pulmonary thromboendarterectomy: Results from a single institution.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is primarily managed by pulmonary thromboendarterectomy (PTE). As advanced surgical techniques permit resection at the segmental and subsegmental level, PTE can now be curative for CTEPH mostly involving the distal pulmonary arteries. METHODS: Between January 2017 and June 2021, consecutive patients undergoing PTE were categorized according to the most proximal level of chronic thrombus resection: Level I (main pulmonary artery), Level II (lobar), Level III (segmental) and Level IV (subsegmental). Proximal disease patients (any Level I or II) were compared to distal disease (Level III or IV bilaterally) patients. Demographics, medical history, preoperative pulmonary hemodynamics, and immediate postoperative outcomes were obtained for each group. RESULTS: During the study period, 794 patients underwent PTE, 563 with proximal disease and 231 with distal disease. Patients with distal disease more frequently had a history of an indwelling intravenous device, splenectomy, upper extremity thrombosis or use thyroid replacement and less often had prior lower extremity thrombosis or hypercoagulable state. Despite more use of PAH-targeted medications in the distal disease group (63.2% vs 50.1%, p < 0.001), preoperative hemodynamics were similar. Both patient groups exhibited significant improvements in pulmonary hemodynamics postoperatively with comparable in-hospital mortality rates. Compared to proximal disease, a lower percentage of patients with distal disease showed residual pulmonary hypertension (3.1% vs 6.9%, p = 0.039) and airway hemorrhage (3.0% vs 6.6%, p = 0.047) postoperatively. CONCLUSIONS: Thromboendarterectomy for distal (segmental and subsegmental) CTEPH is technically feasible and may result in favorable pulmonary hemodynamic outcomes, without increased mortality or morbidity.

Evaluation of Routine Coronary Angiography Before Pulmonary Thromboendarterectomy.

BACKGROUND: At the University of California, San Diego, routine coronary angiography has generally been performed in men 40 years of age and older and women 45 years of age and older before pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension (CTEPH). The prevalence of significant coronary artery disease (CAD) in this population has not been evaluated, however, and the optimal screening strategy has not been established. This study sought to evaluate whether the current approach may be better optimized on the basis of cardiac risk factors. METHODS: This study included 462 consecutive patients with CTEPH who were undergoing preoperative coronary angiography for pulmonary thromboendarterectomy. Baseline demographic and medical information was recorded. Major cardiac risk factors included: diabetes, hypertension, hyperlipidemia, body mass index 25 kg/m2 or greater, tobacco use, and family history of CAD. Charts were then reviewed for presence of significant CAD and revascularization. RESULTS: Significant CAD was found in 13.4% of patients who underwent routine preoperative coronary angiography; it was present in only 5% of patients younger than 50 years of age, compared with 16% of patients 50 years old and older. No patient younger than 50 years of age without cardiac risk factors was found to have significant CAD. Furthermore, in patients younger than 50 years of age, significant CAD was found only among those with 3 or more major risk factors. CONCLUSIONS: In patients younger than 50 years of age with CTEPH, the prevalence of significant CAD was low. Omitting preoperative coronary angiography in this subset of patients is reasonable when no coronary risk factors are present. Preoperative coronary angiography is warranted in individuals 50 years of age and older, as well as in those younger than 50 years who have significant risk factors for CAD.

Chronic Thromboembolic Pulmonary Hypertension: JACC Focus Seminar.

Chronic thromboembolic pulmonary hypertension (CTEPH) is the result of pulmonary arterial obstruction by organized thrombotic material stemming from incompletely resolved acute pulmonary embolism. The exact incidence of CTEPH is unknown but appears to approximate 2.3% among survivors of acute pulmonary embolism. Although ventilation/perfusion scintigraphy has been supplanted by computed tomographic pulmonary angiography in the diagnostic approach to acute pulmonary embolism, it has a major role in the evaluation of patients with suspected CTEPH, the presence of mismatched segmental defects being consistent with the diagnosis. Diagnostic confirmation of CTEPH is provided by digital subtraction pulmonary angiography, preferably performed at a center familiar with the procedure and its interpretation. Operability assessment is then undertaken to determine if the patient is a candidate for potentially curative pulmonary endarterectomy surgery. When pulmonary endarterectomy is not an option, pulmonary arterial hypertension-targeted pharmacotherapy and balloon pulmonary angioplasty represent potential therapeutic alternatives.

Evaluating vancomycin and piperacillin-tazobactam in ED patients with severe sepsis and septic shock.

STUDY OBJECTIVE: To determine the frequency and cause of inadequate initial antibiotic therapy with vancomycin and piperacillin-tazobactam in patients with severe sepsis and septic shock in the emergency department (ED), characterize its impact on patient outcomes, and identify patients who would benefit from an alternative initial empiric regimen. METHODS: Retrospective cohort study conducted between 2012 and 2015 in which 342 patients with culture-positive severe sepsis or septic shock who received initial vancomycin and piperacillin-tazobactam were reviewed to determine appropriateness of antimicrobial therapy, risk factors for inappropriate use, and outcome data. Univariate and multivariate regression analyses were determined to identify associations between inappropriate antibiotic use and outcomes and to identify risk factors that may predict which patients would benefit from an alternative initial regimen. RESULTS: Vancomycin and piperacillin-tazobactam were inappropriate for 24% of patients with severe sepsis or septic shock, largely due to non-susceptible infections, particularly ESBL organisms and Clostridium difficile. Risk factors included multiple sources of infection (OR 4.383), admission from a skilled nursing facility (OR 3.763), a history of chronic obstructive pulmonary disease (COPD) (OR 3.175), intra-abdominal infection (OR 2.890), and immunosuppression (OR 1.930). We did not find a mortality impact. CONCLUSION: Vancomycin and piperacillin-tazobactam were an inappropriate antibiotic combination for approximately 24% of patients with either severe sepsis or septic shock in the ED. Patients with known COPD, residence at a skilled nursing facility, a history concerning for Clostridium difficile, and immunosuppression would benefit from an alternative regimen. Future prospective studies are needed to validate these findings.

Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study.

BACKGROUND: Macitentan is beneficial for long-term treatment of pulmonary arterial hypertension. The microvasculopathy of chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension are similar. METHODS: The phase 2, double-blind, randomised, placebo-controlled MERIT-1 trial assessed macitentan in 80 patients with CTEPH adjudicated as inoperable. Patients identified as WHO functional class II-IV with a pulmonary vascular resistance (PVR) of at least 400 dyn·s/cm5 and a walk distance of 150-450 m in 6 min were randomly assigned (1:1), via an interactive voice/web response system, to receive oral macitentan (10 mg once a day) or placebo. Treatment with phosphodiesterase type-5 inhibitors and oral or inhaled prostanoids was permitted for WHO functional class III/IV patients. The primary endpoint was resting PVR at week 16, expressed as percentage of PVR measured at baseline. Analyses were done in all patients who were randomly assigned to treatment; safety analyses were done in all patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT02021292. FINDINGS: Between April 3, 2014, and March 17, 2016, we screened 186 patients for eligibility at 48 hospitals across 20 countries. Of these, 80 patients in 36 hospitals were randomly assigned to treatment (40 patients to macitentan, 40 patients to placebo). At week 16, geometric mean PVR decreased to 73·0% of baseline in the macitentan group and to 87·2% in the placebo group (geometric means ratio 0·84, 95% CI 0·70-0·99, p=0·041). The most common adverse events in the macitentan group were peripheral oedema (9 [23%] of 40 patients) and decreased haemoglobin (6 [15%]). INTERPRETATION: In MERIT-1, macitentan significantly improved PVR in patients with inoperable CTEPH and was well tolerated. FUNDING: Actelion Pharmaceuticals Ltd.

Unexpected intensive care transfer of admitted patients with severe sepsis.

BACKGROUND: Patients 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. METHODS: This 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. RESULTS: Of 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. CONCLUSIONS: Serum 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.

Chronic Thromboembolic Pulmonary Hypertension. Epidemiology and Risk Factors.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of pulmonary embolism. As for most rare diseases, epidemiologic data are scarce, but recent registries suggest an incidence of at least 5 per million inhabitants per year. A history of massive or recurrent acute pulmonary embolism is observed in most patients with CTEPH, but the proportion of patients who develop CTEPH after acute pulmonary embolism is a matter of debate, further complicated by the possible misdiagnosis of CTEPH as acute pulmonary embolism. A complete resolution of thrombi is usually not achieved after acute pulmonary embolism, and the clinical relevance of a "postpulmonary embolism syndrome" with persistent perfusion defects and exercise intolerance is discussed. Risk factors most consistently associated with CTEPH are circulating anti-phospholipid antibodies or lupus anticoagulant, increased factor VIII, non-O blood groups, and chronic inflammatory diseases. There is no female predominance, and it is a disease of older age. Survival in the absence of specific surgical or medical treatment is poor and depends on the hemodynamic severity.

Efficacy of a Low-Tidal Volume Ventilation Strategy to Prevent Reperfusion Lung Injury after Pulmonary Thromboendarterectomy.

RATIONALE: Reperfusion lung injury is a postoperative complication of pulmonary thromboendarterectomy that can significantly affect morbidity and mortality. Studies in other postoperative patient populations have demonstrated a reduction in acute lung injury with the use of a low-tidal volume (Vt) ventilation strategy. Whether this approach benefits patients undergoing thromboendarterectomy is unknown. OBJECTIVES: We sought to determine if low-Vt ventilation reduces reperfusion lung injury in patients with chronic thromboembolic pulmonary hypertension undergoing thromboendarterectomy. METHODS: Patients undergoing thromboendarterectomy at one center were randomized to receive either low (6 ml/kg predicted body weight) or usual care Vts (10 ml/kg) from the initiation of mechanical ventilation in the operating room through Postoperative Day 3. The primary endpoint was the onset of reperfusion lung injury. Secondary outcomes included severity of hypoxemia, days on mechanical ventilation, and intensive care unit and hospital lengths of stay. MEASUREMENTS AND MAIN RESULTS: A total of 128 patients were enrolled and included in the analysis; 63 were randomized to the low-Vt group and 65 were randomized to the usual care group. There was no statistically significant difference in the incidence of reperfusion lung injury between groups (32%, n=20 in the low-Vt group vs. 23%, n=15 in the usual care group; P=0.367). Although differences were noted in plateau pressures (17.9 cm H2O vs. 20.1 cm H2O, P<0.001) and peak inspiratory pressures (20.4 cm H2O vs. 23.0 cm H2O, P<0.001) between the low-Vt and usual care groups, respectively, mean airway pressures, PaO2/FiO2, days on mechanical ventilation, and ICU and hospital lengths of stay were all similar between groups. CONCLUSIONS: In patients with chronic thromboembolic pulmonary hypertension undergoing pulmonary thromboendarterectomy, intra- and postoperative ventilation using low Vts (6 mg/kg) compared with usual care Vts (10 mg/kg) does not reduce the incidence of reperfusion lung injury or improve clinical outcomes. Clinical trial registered with www.clinicaltrials.gov (NCT00747045).

Prevalence of coronary artery-pulmonary artery collaterals in patients with chronic thromboembolic pulmonary hypertension.

This study sought to determine the prevalence of coronary artery-pulmonary artery collaterals in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and to correlate their presence with the degree of clot burden. CTEPH is a treatable cause of severe pulmonary hypertension and right heart failure. Bronchopulmonary collateral vessels have been used as a supplementary diagnostic and prognostic tool for this disease. Coronary artery-pulmonary artery collaterals in this population have not been described. The coronary angiograms of 300 consecutive patients with CTEPH evaluated for pulmonary thromboendarterectomy (PTE) between January 1, 2007, and May 1, 2014, were examined. Of these patients, 259 (50% male; mean age, 58.3 ± 10.6 years) had cineangiographic images deemed adequate to definitively assess for the presence of coronary artery-pulmonary artery collaterals and were included in the final analyses. Pulmonary angiogram reports were reviewed for extent of pulmonary artery obstruction. The coronary angiograms of 259 age- and sex-matched control patients were also examined. Among 259 CTEPH patients with definitive imaging, 34 coronary artery-pulmonary artery collaterals were found in 28 patients (10.8%), versus 1 coronary artery-pulmonary artery collateral among control subjects (0.4%; P < 0.001). Compared with CTEPH patients without collaterals, patients with collaterals had a significantly higher prevalence of total occlusion of their right or left main pulmonary artery (P < 0.001) or lobar arteries (P < 0.001). In conclusion, the prevalence of coronary artery-pulmonary artery collaterals in CTEPH patients undergoing coronary angiography for possible PTE is approximately 11%. These vessels are associated with more severe pulmonary artery occlusion.

Impact of nurse-initiated ED sepsis protocol on compliance with sepsis bundles, time to initial antibiotic administration, and in-hospital mortality.

INTRODUCTION: Emergency nurses play a key role in the initial triage and care of patients with potentially life-threatening illnesses. The aims of this study were to (1) evaluate the impact of a nurse-initiated ED sepsis protocol on time to initial antibiotic administration, (2) ascertain compliance with 3-hour Surviving Sepsis Campaign (SSC) targets, and (3) identify predictors of in-hospital sepsis mortality. METHODS: A retrospective chart review investigated all adult patients-admitted through either of 2 academic tertiary medical center emergency departments-who were discharged with a diagnosis of severe sepsis or septic shock (N = 195). Pre- and post-protocol implementation data examined both compliance with 3-hour SSC bundle targets and patient outcomes. Multivariate logistic regression analysis identified predictors of in-hospital mortality. RESULTS: Serum lactate measurement (83.9% vs 98.7%, P = .003) and median time to initial antibiotic administration (135 minutes vs 108 minutes, P = .021) improved significantly after protocol implementation. However, one quarter of antibiotic administration times still exceeded the 3-hour target. Significant predictors of in-hospital mortality were respiratory dysfunction, central nervous system dysfunction, urinary tract infection, vasopressor administration, and patient body weight (P < .05). There were no in-hospital mortality rate differences between the pre- and post-protocol implementation groups. DISCUSSION: Compliance with serum lactate measurement and blood culture collection goals approached 100% in the post-protocol group. However, compliance with medical interventions requiring multiple health care-provider involvement (ie, antibiotic and fluid administration) remained suboptimal. Efforts focused on multidisciplinary bundle elements are necessary to achieve full compliance with SSC targets.

Baseline body mass index does not significantly affect outcomes after pulmonary thromboendarterectomy.

BACKGROUND: Obesity is a common comorbidity of patients with chronic thromboembolic pulmonary hypertension referred for pulmonary thromboendarterectomy, yet the effect of obesity on pulmonary thromboendarterectomy outcomes has not been well described. METHODS: We conducted a retrospective cohort study in which 476 consecutive operations over a 3.5-year period were examined to determine the effects of obesity on outcomes. Patients were grouped into four categories based on body mass index (BMI): less than 22 kg/m2, 22 to 30 kg/m2, 30 to 40 kg/m2, and more than 40 kg/m2. RESULTS: There were important differences in baseline pulmonary hemodynamics, with obese patients having significantly lower pulmonary vascular resistances than nonobese patients. All patients achieved a significant reduction in pulmonary vascular resistance, although the improvement was greatest in the lower BMI groups. The overall in-hospital mortality was 0.8%, and there were no differences in risk among BMI groups. Among the BMI groups, there were no differences in incidence of postoperative complications, including atrial fibrillation (overall 24.8%), reperfusion lung injury (overall 23.1%), and surgical site infection (overall 4.4%) or in median lengths of stay (including ventilator days, intensive care unit days, and postoperative length of stay). CONCLUSIONS: Pulmonary thromboendarterectomy outcomes have continued to improve, and this surgery can safely be completed in obese patients, previously deemed to be at high risk for poor outcomes.

Evaluation of patients with chronic thromboembolic pulmonary hypertension for pulmonary endarterectomy.

Pulmonary hypertension as a result of chronic thromboembolic disease (CTEPH) is potentially curable with pulmonary endarterectomy surgery. Consequently, correctly diagnosing patients with this type of pulmonary hypertension and evaluating these patients with the goal of establishing their candidacy for surgical intervention is of utmost importance. And as advancements in surgical techniques have allowed successful resection of segmental-level chronic thromboembolic disease, the number of CTEPH patients that are deemed suitable surgical candidates has expanded, making it even more important that the evaluation be conducted with greater precision. This article will review a diagnostic approach to patients with suspected chronic thromboembolic disease with an emphasis on the criteria considered in selecting patients for pulmonary endarterectomy surgery.

Pulmonary endarterectomy: recent changes in a single institution's experience of more than 2,700 patients.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a known sequela of acute pulmonary embolic disease and yet remains underdiagnosed. Although nonsurgical options for patients with CTEPH have become increasingly available, including pulmonary artery hypertensive medical therapy, surgical endarterectomy provides the most appropriate intervention as a potential cure for this debilitating disorder. This article summarizes the most recent outcomes of pulmonary endarterectomy at a single institution over the past 12 years, with emphasis on the surgical approach to segmental-level chronic thromboembolic disease. METHODS: More than 2,700 pulmonary endarterectomy operations have been performed at the University of California, San Diego Medical Center. Because of recent changes in the patient population and in surgical results, 1,500 patients with symptomatic chronic thromboembolic disease who underwent pulmonary endarterectomy between March 1999 and December 2010 were analyzed. The outcomes for the more recent 500 patients, compared with the previous 1,000 were studied. RESULTS: In-hospital mortality for the cohort of 1,000 patients (group 1) was 5.2% compared with 2.2% for the last 500 operations (group 2) (p < 0.01). There was no mortality in the last 260 consecutive patients undergoing isolated pulmonary endarterectomy. More patients presented with segmental type III disease in the more recent 500 patients (21.4% versus 13.1%; p < 0.001). Between the 2 patient groups, there was a comparable decline in pulmonary vascular resistance (PVR) (group 1: 861.2 ± 446.2 to 94.8 ± 204.2 dynes/sec/cm(-5); group 2: 719.0 ± 383.2 to 253.4 ± 148.6 dynes/sec/cm(-5)) and mean pulmonary artery (PA) pressures (group 1: 46.1 ± 11.4 to 28.7 ± 10.1 mm Hg; group 2: 45.5 ± 11.6 to 26.0 ± 8.4 mm Hg) after endarterectomy. CONCLUSIONS: Despite a patient population with more distal disease, results continue to improve. Pulmonary endarterectomy for patients with CTEPH results in significant pulmonary hemodynamic improvement, with favorable outcomes achievable even in patients with distal segmental-level chronic thromboembolic disease.

Efficacy of methylprednisolone in preventing lung injury following pulmonary thromboendarterectomy.

BACKGROUND: We sought to determine the efficacy and safety of perioperative treatment with methylprednisolone on the development of lung injury after pulmonary thromboendarterectomy. METHODS: This was a randomized, prospective, double-blind, placebo-controlled study of 98 adult patients with chronic thromboembolic pulmonary hypertension who were undergoing pulmonary thromboendarterectomy at a single institution. The patients received either placebo (n = 47) or methylprednisolone (n = 51) (30 mg/kg in the cardiopulmonary bypass prime, 500 mg IV bolus following the final circulatory arrest, and 250 mg IV bolus 36 h after surgery). The primary end point was the presence of lung injury as determined by two independent, blinded physicians using prospectively defined criteria. The secondary end points included ventilator-free, ICU-free, and hospital-free days and selected levels of cytokines in the blood and in BAL fluid. RESULTS: The incidence of lung injury was similar in both treatment groups (45% placebo, 41% steroid; P = .72). There were no statistical differences in the secondary clinical end points between treatment groups. Treatment with methylprednisolone, compared with placebo, was associated with a statistically significant reduction in plasma IL-6 and IL-8, a significant increase in plasma IL-10, and a significant reduction in postoperative IL-1ra and IL-6, but not IL-8 in BAL fluid obtained 1 day after surgery. CONCLUSIONS: Perioperative methylprednisolone does not reduce the incidence of lung injury following pulmonary thromboendarterectomy surgery despite having an antiinflammatory effect on plasma and lavage cytokine levels.

Diagnostic approach to deep venous thrombosis and pulmonary embolism in the critical care setting.

Considerable progress has been made during the last 30 years in the prevention, diagnosis, and therapy of venous thromboembolism. This article discusses the epidemiology, pathophysiology, and clinical presentation of the disease as well as the diagnostic uncertainty that exists in the critical care setting. Diagnostic approaches for deep venous thrombosis and pulmonary embolism are considered, including clinical prediction rules, D-dimer, contrast venography, duplex ultrasonography, computed tomographic angiography and venography, magnetic resonance imaging, ventilation­perfusion scanning, chest radiograph, arterial blood gases, electrocardiography, and echocardiography.

Chronic thromboembolic pulmonary hypertension.

Over the past 4 decades, chronic thromboembolic pulmonary hypertension has evolved from an autopsy curiosity to a potentially correctable form of pulmonary hypertension. Advances in surgical techniques along with the introduction of pulmonary hypertension disease-modifying therapies provide a therapeutic option for the majority of patients afflicted with the disease. Approximately 5,000 thromboendarterectomy procedures have now been performed worldwide with mortality rates reported by established programs experienced in the management of this disease process falling to a range of 4 to 7%. A mortality rate of 1.3% has been reported in patients at low risk based on their preoperative hemodynamic profile. After a successful pulmonary thromboendarterectomy, substantial improvement and often normalization can be achieved in right ventricular function, gas exchange, exercise capacity, and quality of life. For patients not candidates for thromboendarterectomy, or for those with persistent post-thromboendarterectomy pulmonary hypertension, disease-modifying medical therapies have been demonstrated to stabilize and improve pulmonary hemodynamics, albeit not to the same extent as primary thromboendarterectomy. The current review focuses on the diagnostic approach to chronic thromboembolic pulmonary hypertension and the available surgical and medical therapeutic options. Additional research is necessary to more accurately predict postoperative hemodynamic outcome and to define the optimal therapeutic approach, especially in patients with involvement of the distal vasculature.

Chronic thromboembolic pulmonary hypertension in pediatric patients.

OBJECTIVE: Chronic thromboembolic pulmonary hypertension is a rare form of pulmonary hypertension that can lead to progressive right heart failure and death. Pulmonary thromboendarterectomy surgery is the treatment of choice resulting in significant improvements in functional status, cardiopulmonary hemodynamics, and survival. This study reports the largest case series of pediatric patients with chronic thromboembolic pulmonary hypertension who underwent pulmonary thromboendarterectomy surgery at one institution. PATIENT AND METHODS: The University of California, San Diego, chronic thromboembolic pulmonary hypertension database identified patients 18 years or younger at the time of pulmonary thromboendarterectomy surgery (n = 17). Medical charts were reviewed for hemodynamics, thromboembolic risk factors, and postoperative outcomes. RESULTS: Pulmonary thromboendarterectomy surgery in pediatric patients resulted in improved functional status and significantly improved cardiopulmonary hemodynamics: mean arterial pressure decreased from 45.5 mm Hg ± 20.7 to 27.3 ± 13.0 mm Hg (P = .00073), pulmonary vascular resistance decreased from 929 ± dynes · s · cm(-5) to 299 ± 307 dynes · s · cm(-5) (P = .0012), and cardiac output improved from 3.8 ± 1.1 L/min to 5.6 ± 1.6 L/min (P = .0061). There were no deaths during surgery or 30 days after surgery, and long-term survival (5+ years) was achieved in 87.5%. As compared to adults with chronic thromboembolic pulmonary hypertension, there was a higher rate of rethrombosis in pediatric patients (38% vs 1%-4%). CONCLUSIONS: This study demonstrates that pulmonary thromboendarterectomy surgery in pediatric patients with chronic thromboembolic pulmonary hypertension is well tolerated with improved postoperative hemodynamics, functional status, minimal postoperative complications, and low perioperative mortality, similar to that reported for adults with chronic thromboembolic pulmonary hypertension, with the notable exception being a higher rate of rethrombosis in pediatric patients.

Defining urine output criterion for acute kidney injury in critically ill patients.

BACKGROUND: The widespread use of RIFLE and AKIN classification systems for acute kidney injury (AKI) diagnosis and staging has established the association between AKI severity and adverse outcomes. However, as a result of the difficulties in measuring and recording the urine output every hour, a few prospective studies have validated the urine output criterion as stated in these classification systems. We assessed hourly urine output in ICU patients using an automated and accurate device to determine if changes in urine flow and volume could be a sensitive marker of AKI. Additionally, we assessed various definitions of oliguria to determine whether measurement of urine output using a fixed 6-h interval that matches nurses' shifts would be equivalent to the current standard for AKI diagnosis and staging. METHODS: Hourly urine output was recorded continuously using a digital monitor in a medical ICU. Serum creatinine measurements were done at least once per 24 h. We assessed changes in urine output by four different definitions of oliguria. Patients with no AKI by either criterion were compared with patients diagnosed exclusively by the urine output criterion, exclusively by serum creatinine criterion and by both criteria. RESULTS: Fifty-five percent of patients had an episode of oliguria during the ICU stay. There was no significant difference assessing urine output every hour or the total urine volume in a 6-h period for the detection of episodes of oliguria. Twenty-one patients (28%) were diagnosed as AKI using the serum creatinine criterion, whereas additional 24 (32%) were identified by the urine output criterion. CONCLUSIONS: Episodes of oliguria occur frequently in ICU patients and identify a higher percentage of AKI patients compared to serum creatinine criterion. Alterations in urine flow may be a sensitive marker of renal dysfunction and need to be validated in larger cohorts.