Inhaled treprostinil in pulmonary hypertension associated with COPD: PERFECT study results.

BACKGROUND: Pulmonary hypertension (PH) accompanying COPD (PH-COPD) is associated with worse outcomes than COPD alone. There are currently no approved therapies to treat PH-COPD. The PERFECT study (ClinicalTrials.gov: NCT03496623) evaluated the safety and efficacy of inhaled treprostinil (iTRE) in this patient population. METHODS: Patients with PH-COPD (mean pulmonary arterial pressure ≥30 mmHg and pulmonary vascular resistance ≥4 WU) were enrolled in a multicentre, randomised (1:1), double-blind, placebo-controlled, 12-week, crossover study. A contingent parallel design was also prespecified and implemented, based on a blinded interim analysis of missing data. Patients received treatment with iTRE up to 12 breaths (72 µg) 4 times daily or placebo. The primary efficacy end-point was change in peak 6-min walk distance (6MWD) at week 12. RESULTS: In total, 76 patients were randomised, 64 in the original crossover design and 12 in the contingent parallel design; 66 patients received iTRE and 58 received placebo. The study was terminated early at the recommendation of the data and safety monitoring committee based on the totality of evidence that iTRE increased the risk of serious adverse events and suggestive evidence of an increased risk of mortality. The change in 6MWD was numerically worse with iTRE exposure than with placebo exposure. CONCLUSIONS: The risk-benefit observations associated with iTRE in patients with PH-COPD did not support continuation of the PERFECT study. The results of this study do not support iTRE as a viable treatment option in patients with PH-COPD.

A case of severe cancer-related pulmonary hypertension; An unexpected resolution.

Pulmonary hypertension (PH) in cancer patients can be caused by several mechanisms. It can be a direct cancer effect through pulmonary tumor thrombotic microangiopathy, pulmonary tumor emboli, extrinsic compression, intravascular tumors, or a secondary consequence of therapy, including chemotherapy agents, radiation, and stem cell transplantation. We present the first case of complete resolution of cancer-related PH.

Clinical Characteristics Between Survivors and Nonsurvivors of COVID-19 Patients Requiring Extracorporeal Membrane Oxygenation (ECMO) Support: A Systematic Review and Meta-Analysis.

Background: The use of extracorporeal membrane oxygenation (ECMO) in coronavirus disease 2019 (COVID-19) for refractory respiratory failure, severe cardiac dysfunction, and bridge to lung transplantation has been steadily increasing during the ongoing global pandemic. Objective: Our meta-analysis aims to compare the clinical characteristics between COVID-19 survivors and nonsurvivors requiring ECMO support. Methods: A systematic search of Pubmed, Cochrane, Embase, Scopus, and Web of Science databases was performed between December first, 2019, to June first, 2021. Studies with comparative data of COVID-19 ECMO patients were selected, in which clinical characteristics and complications were assessed. Results: Sixteen cohort studies involving 706 COVID-19 patients requiring ECMO support with pooled mortality rate of 40% were included. Younger age (mean 51 years vs 55 years; P < .001), fewer comorbidities (23% vs 31%; odds ratio [OR] 0.55; P = .02), and less renal replacement therapy (RRT) (21% vs 39%; OR 0.41; P = .007) and vasopressor (76% vs 92%; OR 0.35; P = .008) requirement were demonstrated in COVID-19 survivors requiring ECMO support than nonsurvivors. Survivors also had higher pre-ECMO pH (mean 7.33 vs 7.26; P < .001) than nonsurvivors. No difference was observed in gender, body mass index, duration of mechanical ventilation (MV) before ECMO support initiation, total ECMO support duration, and pre-ECMO parameters of PaO2/FiO2 ratio, tidal volume (mL/kg), positive end-expiratory pressure, and plateau pressure. The rate of bleeding complications was lower in survivors (32% vs 59%; OR 0.36; P = .001) than nonsurvivors, but no difference was observed in thromboembolism and secondary infections. Conclusions: We found advanced age, multiple comorbidities, lower pre-ECMO pH, greater RRT, and vasopressor requirements, and bleeding are predictors of death in COVID-19 patients requiring ECMO support. The duration of MV before ECMO support initiation and total ECMO support duration was similar among survivors and nonsurvivors. Our study results have important clinical implications when considering ECMO support in critically ill COVID-19 patients.

A systematic review and meta-analysis comparing the clinical characteristics and outcomes of COVID-19 and influenza patients on ECMO.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a valuable rescue therapy to treat refractory hypoxemia caused by influenza. The present meta-analysis aimed to compare the clinical characteristics and outcomes of ECMO between COVID-19 and influenza. METHODS: We searched the PubMed, Cochrane Library, SCOPUS, and Web of Science databases from inception to May 1, 2021. The included studies compared the clinical characteristics and outcomes of ECMO between adults with COVID-19 and those with influenza. RESULTS: The study included four retrospective cohorts involving a total of 129 patients with COVID-19 and 140 with influenza who were treated using ECMO. Clinical characteristics were similar between the COVID-19 and influenza groups, including body mass index (BMI), diabetes mellitus, hypertension, and immunocompromised status. A higher proportion of patients with COVID-19 on ECMO were male (75.9% vs. 62.9%; P = 0.04). There was no difference between the groups in terms of illness severity based on sequential organ failure assessment (SOFA) score or serum pH. Patients with COVID-19 had a longer mean duration of mechanical ventilation before ECMO (6.63 vs. 3.38 days; P < 0.01). The pooled mortality rate was 43.8%. The mean ECMO duration (14.13 vs. 12.55 days; P = 0.25) and mortality rate (42.6% vs. 45.0%; P = 0.99) were comparable between the groups. CONCLUSION: Clinical characteristics, ECMO duration, and mortality were comparable between patients with COVID-19 and those with influenza who required ECMO to treat refractory hypoxemia. The duration of mechanical ventilation before ECMO did not influence outcomes. Patients with COVID-19 benefit from ECMO salvage therapy similarly to those with influenza.

Comparing Central Venous Blood Gas to Arterial Blood Gas and Determining Its Utility in Critically Ill Patients: Narrative Review.

Arterial blood gas (ABG) analysis is used in critical care units to determine the degree of oxygenation, adequacy of ventilation, and the presence and severity of acid-base disturbances in the body. However, arterial puncture may result in complications, and the difficulty in acquiring arterial blood may delay care. Central venous blood gas (VBG) is a potentially more accessible alternative to ABG sampling. Current evidence suggests that pH and Pco2 obtained via peripheral VBG correlate well with ABG measurement. Nevertheless, the value of using central VBG to guide clinical decisions or as a surrogate for ABG is unclear. The purpose of this review is to explore the relationship between ABGs and central VBGs in critically ill patients. We performed a MEDLINE search using the following search terms: venous blood gas, arterial blood gas, and central venous blood gas. We excluded studies that did not involve human subjects, and only pH and Pco2 values were reviewed and examined from the studies included. All cited references from included studies were also reviewed to identify relevant literature. We identified 7 studies that met our criteria. In studies of hemodynamically stable patients, the mean difference between arterial and central venous pH and Pco2 was 0.03 units and 4-6.5 mm Hg, respectively. However, in patients with circulatory failure, the difference between central venous and arterial pH/Pco2 was 4-fold greater. We concluded that central VBG parameters of pH and Pco2 are potentially good surrogates for determining arterial pH and Pco2 in a stable patient without severe acid-base disturbances. Furthermore, central VBG can be used as a useful screening tool for arterial hypercapnia. In addition, we derived an adjustment formula for ABG conversion from central VBG: (1) arterial pH = venous pH + 0.05 units and (2) arterial Pco2 = venous Pco2 - 5 mm Hg.

Readdressing the entity of exercise pulmonary arterial hypertension.

Exercise pulmonary hypertension (EPH) indicates an abnormally elevated pulmonary artery pressure (PAP) during exercise. The physiological range of PAP during exercise remains poorly defined and, therefore, a universally accepted definition of EPH remains elusive. Nevertheless, previous data concerning the distribution of PAP in normal populations and more recent retrospective clinical data enhanced our ability to define EPH. EPH can impair exercise capacity and cause dyspnea. The underlying pathophysiology of the arterial form of EPH (EPAH) appears to be similar to that seen in resting pulmonary arterial hypertension (PAH), and EPAH individuals are at risk of developing resting PAH. Patients with collagen vascular disease, especially scleroderma, are at risk for EPAH and its presence indicates a relatively poor prognosis. The prevalence of EPAH in scleroderma may be as high as 50%. The utility of pulmonary vasodilator therapy for EPAH is not well defined; however, a sizable subgroup of EPAH patients will achieve an improvement in symptoms.

Methemoglobinemia Caused by Portable Dialysis in the Critically Ill.

OBJECTIVE: To evaluate the root cause of a series of methemoglobinemia cases in a medical ICU. RESULTS: We report a sentinel case of methemoglobinemia that was associated with dialysis sessions using a portable dialysis unit in our hospital. This led to the identification of four additional patients who developed methemoglobinemia while undergoing portable dialysis. We determined that these episodes were caused by inadequate clearance of chloramine from the tap water used for portable dialysis. Introduction of larger capacity carbon filters into the portable dialysis systems resulted in no further cases of methemoglobinemia at our institution. CONCLUSIONS: Clinicians should be aware of municipal tap water as a potential cause of methemoglobinemia and monitor for excessive levels of oxidants in dialysis water sources. The capacity of the hemodialysis equipment to clear chloramine can vary as a function of external factors. Using a reliable test method to identify chloramines in the water prior to entering the hemodialysis equipment is essential.

Effect of SSRIs and SNRIs on Nocturnal Urinary Frequency.

BACKGROUND: Existing data suggest that selective serotonin uptake inhibitors (SSRIs) may have an impact on urinary frequency. OBJECTIVE: To evaluate the impact of SSRIs and selective noradrenaline reuptake inhibitors (SNRIs) on nocturnal urinary frequency. METHODS: This was a retrospective study comparing nocturnal urinary frequency in individuals on SSRI or SNRI therapy versus no therapy during nocturnal polysomnography in a 14-month period at a sleep center. RESULTS: A total of 316 individuals were studied: 94 in the SSRI/SNRI group and 222 controls. No statistically significant difference was found in nocturnal urinary frequency between those on SSRI/SNRI therapy and the control group (0.40 vs 0.34 bathroom visits/night, P = 0.40). The degree of urinary frequency was higher in sertraline users (0.61 bathroom visits/night) compared with duloxetine users (0.18 visits/night, 2-tailed P = 0.04). A post hoc analysis suggested that the difference between these 2 agents is a class effect (SSRIs vs SNRIs, 2-tailed P = 0.03). The sample size did not allow conclusive comparison of either the SSRI or the SNRI group with the control group. CONCLUSION: SSRI/SNRI agents as a combined group do not appear to have a significant impact on nocturnal urinary frequency. The SSRIs and SNRIs may have an opposite effect on nocturnal frequency.

Interrelationship between sleep-disordered breathing and sarcoidosis.

Sleep-disordered breathing (SDB) has a high prevalence in sarcoidosis. This high prevalence may be the result of increased upper airways resistance from sarcoidosis of the upper respiratory tract, corticosteroid-induced obesity, or parenchymal lung involvement from sarcoidosis. OSA is a form of SDB that is particularly common in patients with sarcoidosis. Sarcoidosis and SDB share many similar symptoms and clinical findings, including fatigue, gas exchange abnormalities, and pulmonary hypertension (PH). Sarcoidosis-associated fatigue is a common entity for which stimulants may be beneficial. Sarcoidosis-associated fatigue is a diagnosis of exclusion that requires an evaluation for the possibility of OSA. Hypercapnia is unusual in a patient with sarcoidosis without severe pulmonary dysfunction and, in this situation, should prompt evaluation for alternative causes of hypercapnia, such as SDB. PH is usually mild when associated with OSA, whereas the severity of sarcoidosis-associated PH is related to the severity of sarcoidosis. PH caused by OSA usually responds to CPAP, whereas sarcoidosis-associated PH commonly requires the use of vasodilators. Management of OSA in sarcoidosis is problematic because corticosteroid treatment of sarcoidosis may worsen OSA. Aggressive efforts should be made to place the patient on the lowest effective dose of corticosteroids, which involves early consideration of corticosteroid-sparing agents. Because of the significant morbidity associated with SDB, early recognition and treatment of SDB in patients with sarcoidosis may improve their overall quality of life.

The role of calcium channel blockers for the treatment of pulmonary arterial hypertension: How much do we actually know and how could they be positioned today?

Calcium channel blockers (CCB) were the first vasodilator agents to gain popular acceptance in the treatment of pulmonary arterial hypertension (PAH). They have been shown to be particularly effective in patients who show a significant immediate hemodynamic response to pulmonary vasodilators ("responders"). The application of CCB is currently restricted to "responders" only. It is believed that no more than 5% of PAH patients will benefit from CCB long term. The response rate of most non-idiopathic forms of PAH is considered to be even lower. The "non-responders" as well as "responders" who fail to benefit from CCB should be treated with newer agents, collectively called "advanced PAH therapy." The basis of this consensus rests on empiric experience gained in the PAH community over the years. However, the cut-points where advanced agents are more effective than CCB and where there is no additional role for CCB remain unknown. In this manuscript, we review the data concerning this issue and postulate a role for CCB in the modern era of pulmonary hypertension therapy.

Clinical aspects of portopulmonary hypertension.

Portopulmonary hypertension (PoPH) is an often neglected form of pulmonary hypertension where pulmonary hypertension occurs in the presence of portal hypertension. PoPH is important to diagnose and treat as it may improve the patient's quality of life and improve the outcome after liver transplantation. In this review, we discuss the clinical aspects of PoPH including its pathophysiology, diagnosis, treatment, and prognosis.

Patient-reported outcome measures for sleep disorders and related problems: clinical and research applications.

Patients with sleep disorders are most concerned with the impact of these diseases on their quality of life. Patient-reported outcome (PRO) measurement tools, which assess aspects of a patient's health status that come directly from the patient, are well suited to evaluate quality of life related to sleep disorders. Although PRO data are subjective, they can be quantified, evaluated for reliability and reproducibility, and used to answer questions of clinical and research importance. This article reviews various PRO measure tools used for sleep disorders in clinical and research settings. These instruments may play a role in screening, diagnosis, and monitoring of various sleep disorders.

Milk-alkali syndrome.

Milk-alkali syndrome (MAS) consists of hypercalcemia, various degrees of renal failure, and metabolic alkalosis due to ingestion of large amounts of calcium and absorbable alkali. This syndrome was first identified after medical treatment of peptic ulcer disease with milk and alkali was widely adopted at the beginning of the 20th century. With the introduction of histamine2 blockers and proton pump inhibitors, the occurrence of MAS became rare; however, a resurgence of MAS has been witnessed because of the wide availability and increasing use of calcium carbonate, mostly for osteoporosis prevention. The aim of this review was to determine the incidence, pathogenesis, histologic findings, diagnosis, and clinical course of MAS. A MEDLINE search was performed with the keyword milk-alkali syndrome using the PubMed search engine. All relevant English language articles were reviewed. The exact pathomechanism of MAS remains uncertain, but a unique interplay between hypercalcemia and alkalosis in the kidneys seems to lead to a self-reinforcing cycle, resulting in the clinical picture of MAS. Treatment is supportive and involves hydration and withdrawal of the offending agents. Physicians and the public need to be aware of the potential adverse effects of ingesting excessive amounts of calcium carbonate.

Diurnal variations in human pulmonary function.

Pulmonary function has circadian modulations. Variations in human pulmonary function during the daytime hours (diurnal variations) remain to be well characterized. Discerning these variations will contribute to better understanding the relationship between biorhythms and lung physiology and to improving clinical management of pulmonary diseases. The aim of this study was to determine the magnitude of pulmonary function variability during the usual daytime hours in a population of patients referred for pulmonary function testing. Diurnal fluctuations of human pulmonary function were examined by studying retrospectively a study population of 4,756 individuals with performed pulmonary function tests. We found the lowest and highest spirometric values in the 12:00-12:59 pm and 3:00-4:59 pm time intervals respectively. The difference in the forced expiratory volume in 1 second (FEV1) between the noon (12:00-12:59 pm) and afternoon (4:00-4:59 pm) intervals was 17.6% (P<0.01). Furthermore, the highest values of diffusing capacity of the lung for carbon monoxide [DLCO] and alveolar volume [Va] were identified in the 8:00-8:59 am time interval. These findings, identifying a model of diurnal variations of pulmonary function in individuals referred for pulmonary function testing, are of interest for better understanding lung physiology and human circadian rhythms and may have clinical value in managing lung disorders.

Legionella micdadei infection presenting as severe secretory diarrhea and a solitary pulmonary mass.

Sixty percent of infections with non-pneumophila species of Legionella are caused by Legionella micdadei. Although diarrhea is a common symptom of legionellosis, including that due to L. micdadei infection, severe, life-threatening diarrhea is rare. We describe a patient with profound secretory diarrhea (secretion rate, up to 8 L/day) that was secondary to culture-proven L. micdadei pneumonia. In addition, a 3-cm pulmonary nodule was detected, which completely resolved after proper treatment for Legionella infection. Resolving pulmonary nodules have been previously reported in association with treatment of L. micdadei infections.