Pulmonary arterial hypertension (PAH), the first category of pulmonary hypertension, is a chronic and progressive disorder characterised by angioproliferative vasculopathy in the pulmonary arterioles, leading to endothelial and smooth muscle proliferation and dysfunction, inflammation and thrombosis. These changes increase pulmonary vascular resistance and subsequent pulmonary arterial pressure, causing right ventricular failure which leads to eventual death if untreated. The management of PAH has advanced rapidly in recent years due to improved understanding of the condition’s pathophysiology, specifically the nitric oxide, prostacyclin-thromboxane and endothelin-1 pathways. Five classes of drugs targeting these pathways are now available: phosphodiesterase-5 inhibitors, soluble guanylate cyclase stimulators, prostacyclin analogues, prostacyclin receptor agonists and endothelin receptor antagonists. These developments have led to substantial improvements in mortality rate in recent decades. Recently, long-term studies have demonstrated sustained progression-free survival and have created a new paradigm of initial combination therapy. Despite these targeted therapies, PAH is still associated with significant morbidity and mortality. As such, further research into broadening our understanding of PAH pathophysiology is underway with potential of increasing the repertoire of drugs available.
BackgroundThis cohort study compared the prognostic significance of strong ion gap (SIG) with other acid-base markers in the critically ill.MethodsThe relationships between SIG, lactate, anion gap (AG), anion gap albumin-corrected (AG-corrected), base excess or strong ion difference-effective (SIDe), all obtained within the first hour of intensive care unit (ICU) admission, and the hospital mortality of 6878 patients were analysed. The prognostic significance of each acid-base marker, both alone and in combination with the Admission Mortality Prediction Model (MPM0 III) predicted mortality, were assessed by the area under the receiver operating characteristic curve (AUROC).ResultsOf the 6878 patients included in the study, 924 patients (13.4 %) died after ICU admission. Except for plasma chloride concentrations, all acid-base markers were significantly different between the survivors and non-survivors. SIG (with lactate: AUROC 0.631, confidence interval [CI] 0.611–0.652; without lactate: AUROC 0.521, 95 % CI 0.500–0.542) only had a modest ability to predict hospital mortality, and this was no better than using lactate concentration alone (AUROC 0.701, 95 % 0.682–0.721). Adding AG-corrected or SIG to a combination of lactate and MPM0 III predicted risks also did not substantially improve the latter’s ability to differentiate between survivors and non-survivors. Arterial lactate concentrations explained about 11 % of the variability in the observed mortality, and it was more important than SIG (0.6 %) and SIDe (0.9 %) in predicting hospital mortality after adjusting for MPM0 III predicted risks. Lactate remained as the strongest predictor for mortality in a sensitivity multivariate analysis, allowing for non-linearity of all acid-base markers.ConclusionsThe prognostic significance of SIG was modest and inferior to arterial lactate concentration for the critically ill. Lactate concentration should always be considered regardless whether physiological, base excess or physical-chemical approach is used to interpret acid-base disturbances in critically ill patients.
Indwelling pleural catheters (IPCs) are effective management options for malignant pleural effusion. Symptomatic fluid loculation is a recognized complication of IPC use and is usually managed with intrapleural instillation of fibrinolytic drugs, such as tissue plasminogen activator (tPA). A previous multicentre observational study showed significant heterogeneity among centres in their dosing regimen for tPA (from 2 to 20 mg) in treating symptomatic loculations. Potential pleural bleeding, especially in high‐risk patients, often deters clinicians from initiating intrapleural fibrinolytic therapy. Lower doses of tPA may reduce bleeding risks. This case report describes the successful use of 0.5 mg (the lowest reported dose) of tPA in a patient with significant bleeding risks whose IPC was complicated by symptomatic loculation.
Background:Community-acquired pneumonia (CAP) is a major global disease. Parapneumonic effusions often complicate CAP and range from uninfected (simple) to infected (complicated) parapneumonic effusions and empyema (pus). CAP patients who have a pleural effusion at presentation are more likely to require hospitalization, have a longer length of stay and higher mortality than those without an effusion. Conventional management of pleural infection, with antibiotics and chest tube drainage, fails in about 30% of cases. Several randomized controlled trials (RCT) have evaluated the use of corticosteroids in CAP and demonstrated some potential benefits. Importantly, steroid use in pneumonia has an acceptable safety profile with no adverse impact on mortality. A RCT focused on pediatric patients with pneumonia and a parapneumonic effusion demonstrated shorter time to recovery. The effects of corticosteroid use on clinical outcomes in adults with parapneumonic effusions have not been tested. We hypothesize that parapneumonic effusions develop from an exaggerated pleural inflammatory response. Treatment with systemic steroids may dampen the inflammation and lead to improved clinical outcomes. The steroid therapy and outcome of parapneumonic pleural effusions (STOPPE) trial will assess the efficacy and safety of systemic corticosteroid as an adjunct therapy in adult patients with CAP and pleural effusions.Methods:STOPPE is a pilot multicenter, double-blinded, placebo-controlled RCT that will randomize 80 patients with parapneumonic effusions (2:1) to intravenous dexamethasone or placebo, administered twice daily for 48 hours. This exploratory study will capture a wide range of clinically relevant endpoints which have been used in clinical trials of pneumonia and/or pleural infection; including, but not limited to: time to clinical stability, inflammatory markers, quality of life, length of hospital stay, proportion of patients requiring escalation of care (thoracostomy or thoracoscopy), and mortality. Safety will be assessed by monitoring for the incidence of adverse events during the study.Discussion:STOPPE is the first trial to assess the efficacy and safety profile of systemic corticosteroids in adults with CAP and pleural effusions. This will inform future studies on feasibility and appropriate trial endpoints.Trial registration:ACTRN12618000947202Protocol version:version 3.00/26.07.18
Background Cough is a common symptom in interstitial lung disease (ILD), often leading to treatment dissatisfaction for patients and physicians. Aim To identify the prevalence and subjective adequacy of control of cough in patients with ILD. Methods A cross‐sectional study of patients with ILD attending a tertiary ILD clinic in Perth was undertaken using a pre‐designed questionnaire that patients were invited to complete when attending clinic. Cough severity and impact on quality of life were assessed using a visual analogue scale and the validated Leicester cough questionnaire. Participants were asked to list triggers of their cough and strategies or medications trialled to control cough. Results Of 164 respondents, 118 (72%) had cough, with prevalence common in all ILD subtypes. A lower forced vital capacity (FVC) was found in the cough group versus non‐cough group (74.6 ± 18.7 vs 87.0 ± 15.9, P‐value < 0.0001). Common reported triggers were lung irritants, exertion and doing routine daily activities. Avoidance of triggers was a common strategy to control cough. A high prevalence of non‐ILD causes of cough was recorded in both groups. A variety of medications had been trialled, including anti‐fibrotics, immunosuppression drugs, inhalers and proton pump inhibitors, with moderate benefit reported by 18% of participants. Conclusions Cough is prevalent in ILD but is not adequately suppressed. Cough has a significant impact on quality of life, leading patients to adopt their own strategies to control their cough. More research is needed to understand cough mechanisms in ILD and the interplay of other potential co‐pathologies.
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