ABSTRACT
Pulmonary hypertension (PH), defined by a mean pulmonary artery pressure of >20 mm Hg, often presents with non-specific symptoms such as dyspnea and exercise intolerance, making it difficult to diagnose early before the onset of right heart dysfunction. Therefore, exercise testing can be of great utility for clinicians who are evaluating patients with an unclear etiology of exercise intolerance by helping identify the underlying mechanisms of their disease. The presence of PH is associated with adverse clinical outcomes, with distinct differences and patterns in the cardiovascular and ventilatory responses to exercise across various PH phenotypes. We discuss the role of exercise-invasive hemodynamic testing, cardiopulmonary exercise testing, and exercise stress echocardiography modalities across the spectrum of PH.
ABSTRACT
Air emboli are rare and often difficult to diagnose. Transesophageal echocardiography remains the most definitive method of diagnosis, but this is not feasible in emergencies. We present a case of fatal air embolism in the setting of hemodialysis with recent evidence of pulmonary hypertension. The diagnosis was made by visualizing air in the right ventricle using bedside point of care ultrasound (POCUS). While POCUS is not routinely used for the diagnosis of air embolism, its accessibility makes it a powerful yet practical emerging tool for the diagnosis of respiratory and cardiovascular emergencies.
ABSTRACT
Microvascular dysfunction progressing to pulmonary hypertension can be a primary cause of right ventricular failure or a secondary cause because of an underlying systemic illness. Little is known regarding the etiology and epidemiology of coronary microvascular dysfunction in pulmonary hypertension. Despite this limitation, its presence has been described in patients with pulmonary hypertension. This review focuses on the pathogenesis of cardiac and pulmonary microvascular dysfunction in pulmonary hypertension. Additionally, this review provides a contemporary assessment on the diagnosis and treatment of microvascular dysfunction in patients in pulmonary hypertension. This topic is important to raise awareness of microvascular dysfunction in the coronary and pulmonary circulation, so that future studies will investigate its impact on the pulmonary hypertension patient cohort.
ABSTRACT
INTRODUCTION: Acute respiratory distress syndrome (ARDS) management in the intensive care unit (ICU) has attracted strong interest since the start of the COVID-19 pandemic. Our retrospective study aims to describe the outcomes and predictors of mortality of ARDS associated with COVID-19 within one university-based healthcare system. METHODS: We identified 165 patients within our healthcare system during the months of April 2020 through July 2020, who were admitted to our medical ICUs and eligible for our study. Baseline patient characteristics, ICU and hospital course information, ICU interventions, ventilator settings, and hospital complications were collected and analyzed using descriptive statistical techniques. RESULTS: Our cohort had an average age of 64. No significant difference in mortality was identified with male vs. female gender or BMI. Most of the patient cohort was identified as black (68.2%). The overall mortality of our cohort was 38.2%. Hyperlipidemia, coronary artery disease, and chronic obstructive pulmonary disease were all associated with higher mortality. There was a significant difference in mortality between those with higher observed ventilator plateau pressures at 24 hours and higher driving pressures at 24 hours. CONCLUSION: COVID-19-associated ARDS is associated with significant mortality. Physicians should be aware of pre-existing conditions potentially related to worse outcomes so that they receive an appropriate level of care in a timely manner. Ventilator management should focus on maintaining low intra-thoracic pressure changes. Prospective studies are needed to guide COVID-19-associated ARDS management.
ABSTRACT
Proteus syndrome is a rare progressive multisystem disorder characterized by asymmetric, disproportionate overgrowth of bone, skin, and other tissue types. Molecular pathogenesis has been identified as somatic activating mutations of the AKT1 gene. The presentation of Proteus syndrome is exceptionally variable. Respiratory complications include emphysematous lung disease and predisposition to pulmonary emboli, the latter of which is a significant source of mortality. Pulmonary hypertension due to longstanding hypoxic lung disease as well as chronic thromboembolic events has been observed in this population. In contrast, precapillary pulmonary arterial hypertension in the absence of chronic pulmonary emboli and parenchymal lung disease has not been described in the literature on patients with Proteus syndrome. We report such a case in a young patient with Proteus syndrome, reviewing subsequent management and emphasizing the need for a detailed investigation of dyspnea.
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Meticulous risk stratification is essential when considering intubation of a patient with decompensated pulmonary hypertension (dPH). It is paramount to understand both the pathophysiology of dPH (and associated right ventricular failure) and the complications related to a high-risk intubation before attempting the procedure. There are few recommendations in this area and the literature, guiding these recommendations, is limited to expert opinion and very few case reports/case series. This review will discuss the complex pathophysiology of dPH, the complications associated with intubation, the debates surrounding induction agents, and the available options for the intubation procedure, with specific emphasis on the emerging role for awake fiberoptic intubation. All patients should be evaluated for candidacy for veno-arterial extracorporeal membrane oxygen as a bridge to recovery, lung transplantation, or pulmonary endarterectomy prior to intubation. Only an experienced proceduralist who is both comfortable with high-risk intubations and the pathophysiology of dPH should perform these intubations.
Subject(s)
Extracorporeal Membrane Oxygenation , Hypertension, Pulmonary , Airway Management/methods , Endarterectomy , Extracorporeal Membrane Oxygenation/methods , Humans , Intubation, Intratracheal/methodsABSTRACT
Atrial arrhythmias are common during episodes of acute respiratory failure in patients with chronic lung disease-associated pulmonary hypertension. Expert opinion suggests that management of atrial arrhythmias in patients with pulmonary hypertension should aim to restore sinus rhythm. This is clinically challenging in pulmonary hypertension patients with coexisting chronic lung disease, as there is controversy on the use of rhythm control agents; generally, in regard to either their pulmonary toxicity profile or the lack of evidence supporting their use. Rate control methods are largely focused on the use of beta blockers and calcium channel blockers. Concerns regarding their use involve their negative inotropic properties in cor pulmonale, the risk of bronchospasm associated with beta blockers, and the potential for ventilation/perfusion mismatching associated with calcium channel blockers. While digoxin has been associated with promising outcomes during acute right ventricular failure, there is limited evidence to suggest its routine use. Electrical cardioversion is associated with a high failure rate and it frequently requires multiple attempts. Radiofrequency catheter ablation is a more definitive approach, but concerns surrounding mechanical ventilation and sedation limit its applicability in decompensated pulmonary hypertension. Individual approaches are needed to address atrial arrhythmia management during acute episodes of respiratory failure.
ABSTRACT
Interstitial lung disease represents a group of diffuse parenchymal lung diseases with overwhelming morbidity and mortality when complicated by acute respiratory failure. Recently, trials investigating outcomes and their determinants have provided insight into these high mortality rates. Pulmonary hypertension is a known complication of interstitial lung disease and there is high prevalence in idiopathic pulmonary fibrosis, connective tissue disease, and sarcoidosis subtypes. Interstitial lung disease associated pulmonary hypertension has further increased mortality with acute respiratory failure, and there is limited evidence to guide management. This review describes investigations and management of interstitial lung disease associated acute respiratory failure complicated by pulmonary hypertension. Despite the emerging attention on interstitial lung disease associated acute respiratory failure and the influence of pulmonary hypertension, critical care management remains a clinical and ethical challenge.
Subject(s)
Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/therapy , Lung Diseases, Interstitial/complications , Lung Diseases, Interstitial/therapy , Acute Disease , Critical Care , Humans , Hypertension, Pulmonary/epidemiology , Nuclear Respiratory Factors , Prognosis , Pulmonary Fibrosis/epidemiology , Pulmonary Fibrosis/etiology , Pulmonary Fibrosis/therapyABSTRACT
BACKGROUND: Interstitial Lung Disease [ILD] patients requiring Invasive Mechanical Ventilation [IMV] for Acute Respiratory Failure [ARF] are known to have a poor prognosis. Few studies have investigated determinants of outcomes and the utility of trialing Non-Invasive Positive Pressure Ventilation [NIPPV] prior to IMV to see if there are any effect[s] on mortality or morbidity. METHODS: A retrospective study was designed using patients at four different intensive care units within one health care system. The primary objective was to determine if there are differences in outcomes for in-hospital and one-year mortality between patients who undergo NIPPV prior to IMV and those who receive only IMV. A secondary objective was to identify potential determinants of outcomes. RESULTS: Out of 54 ILD patients with ARF treated with IMV, 20 (37.0%) survived until hospital discharge and 10 (18.5%) were alive at one-year. There was no significant mortality difference between patients trialed on NIPPV prior to IMV and those receiving only IMV. Several key determinants of outcomes were identified with higher mortality, including higher ventilatory support, idiopathic pulmonary fibrosis (IPF) subtype, high dose steroids, use of vasopressors, supraventricular tachycardias (SVTs), and higher body mass index. CONCLUSION: Considering that patients trialed on NIPPV prior to IMV were associated with no mortality disadvantage to patients treated with only IMV, trialing patients on NIPPV may identify responders and avoid complications associated with IMV. Increased ventilator support, need of vasopressors, SVTs, and high dose steroids reflect higher mortality and palliative care involvement should be considered as early as possible if a lung transplant is not an option.
Subject(s)
Continuous Renal Replacement Therapy , Extracorporeal Membrane Oxygenation , Heart-Assist Devices , Intra-Aortic Balloon Pumping , Myocardial Infarction/therapy , Percutaneous Coronary Intervention , Shock, Cardiogenic/therapy , Vasoconstrictor Agents/therapeutic use , Cardiac Catheterization , Coronary Angiography , Diagnosis, Differential , Electrocardiography , Fluid Therapy , Heart Failure/diagnosis , Hemodynamics , Humans , Monitoring, Physiologic , Myocardial Infarction/complications , Myocardial Infarction/diagnosis , Noninvasive Ventilation , Oxygen Inhalation Therapy , Respiration, Artificial , Shock, Cardiogenic/diagnosis , Shock, Cardiogenic/epidemiology , Shock, Cardiogenic/etiologyABSTRACT
Insulin-Like Growth Factor 1 (IGF-1) is a neurotrophic polypeptide with crucial roles to play in Central Nervous System (CNS) growth, development and maturation. Following interrogation of the neurobiology underlying several neurodevelopmental disorders and Autism Spectrum Disorders (ASD), both recombinant IGF-1 (mecasermin) and related derivatives, such as (1-3)IGF-1, have emerged as potential therapeutic approaches. Clinical pilot studies and early reports have supported the safety/preliminary efficacy of IGF-1 and related compounds in the treatment of Rett Syndrome, with evidence mounting for its use in Phelan McDermid Syndrome and Fragile X Syndrome. In ASD, clinical trials are ongoing. Here, we review the role of IGF-1 in the molecular etiologies of these conditions in addition to the accumulating evidence from early clinical studies highlighting the possibility of IGF-1 and related compounds as potential treatments for these childhood-onset neurodevelopmental disorders.
ABSTRACT
Insulin-Like Growth Factor 1 (IGF-1) is a phylogenetically ancient neurotrophic hormone with crucial roles to play in CNS development and maturation. Recently, IGF-1 has been shown to have potent effects on cellular neuroplasticity. Neuroplasticty refers to the adaptive changes made by the CNS in the face of changing functional demands and is crucial in processes such as learning and memory. IGF-1, signaling through its glycoprotein receptor (IGF-1R), and canonical signaling pathways such as the PI3K-Akt and Ras-Raf-MAP pathways, has potent effects on cellular neuroplasticity in the CNS. In the present review, the role of IGF-1 in brain development is reviewed, followed by a detailed discussion of the role played by IGF in cellular neuroplasticity in the CNS. Findings from models of perturbed and reparative plasticity detailing the role played by IGF-1 are discussed, followed by the electrophysiological, structural and functional evidence supporting this role. Finally, the post-lesion and post-injury roles played by IGF-1 are briefly evaluated. We discuss the putative neurobiology underlying these changes, reviewing recent evidence and highlighting areas for further research.