Pulmonary Thrombosis and Thromboembolism in COVID-19.

COVID-19, the disease responsible for the devastating pandemic that began at the end of 2019, has been associated with a significantly increased risk of pulmonary thrombosis, even in patients receiving prophylactic anticoagulation. The predilection for thrombosis in COVID-19 may be driven by at least two distinct, but interrelated, processes: a hypercoagulable state responsible for large-vessel thrombosis and thromboembolism and direct vascular and endothelial injury responsible for in situ microvascular thrombosis. The presence of pulmonary thrombosis may explain why hypoxemia is out of proportion to impairment in lung compliance in some patients with COVID-19 pneumonia. Because pulmonary embolism (PE) and COVID-19 pneumonia share many signs and symptoms, diagnosing PE in patients with COVID-19 can be challenging. Given the high mortality and morbidity associated with severe COVID-19 and the concern that aspects of the disease may be driven by thrombosis, many hospital systems have instituted aggressive anticoagulation protocols above standard VTE prophylaxis. In this review, the epidemiologic and pathophysiologic features, diagnosis, and treatment of COVID-19 pulmonary thrombosis and thromboembolism are discussed.

Cardiac index is associated with oxygenation in COVID-19 acute respiratory distress syndrome.

Eleven participants with COVID-19 acute respiratory distress syndrome requiring mechanical ventilation underwent pulmonary artery catheterization for clinical indications. Clinical interventions or events concurrent with hemodynamic were recorded. Increased cardiac index was associated with worse hypoxemia. Modulation of cardiac index may improve hypoxemia in patients with COVID-19 acute respiratory distress syndrome.

COVID-19 critical illness pathophysiology driven by diffuse pulmonary thrombi and pulmonary endothelial dysfunction responsive to thrombolysis.

Patients with severe COVID-19 disease have been characterized as having the acute respiratory distress syndrome (ARDS). Critically ill COVID-19 patients have relatively well-preserved lung mechanics despite severe gas exchange abnormalities, a feature not consistent with classical ARDS but more consistent with pulmonary vascular disease. Many patients with severe COVID-19 also demonstrate markedly abnormal coagulation, with elevated d-dimers and higher rates of venous thromboembolism. We present four cases of patients with severe COVID-19 pneumonia with severe respiratory failure and shock, with evidence of markedly elevated dead-space ventilation who received tPA. All showed post treatment immediate improvements in gas exchange and/or hemodynamics. We suspect that severe COVID-19 pneumonia causes respiratory failure via pulmonary microthrombi and endothelial dysfunction. Treatment for COVID-19 pneumonia may warrant anticoagulation for milder cases and thrombolysis for more severe disease.

COVID-19 Critical Illness Pathophysiology Driven by Diffuse Pulmonary Thrombi and Pulmonary Endothelial Dysfunction Responsive to Thrombolysis.

Patients with severe COVID-19 disease have been characterized as having the acute respiratory distress syndrome (ARDS). Critically ill COVID-19 patients have relatively well-preserved lung mechanics despite severe gas exchange abnormalities, a feature not consistent with classical ARDS but more consistent with pulmonary vascular disease. Patients with severe COVID-19 also demonstrate markedly abnormal coagulation, with elevated D-dimers and higher rates of venous thromboembolism. We present five cases of patients with severe COVID-19 pneumonia with severe respiratory failure and shock, with evidence of markedly elevated dead-space ventilation who received tPA. All showed post treatment immediate improvements in gas exchange and/or hemodynamics. We suspect that severe COVID-19 pneumonia causes respiratory failure via pulmonary microthrombi and endothelial dysfunction. Treatment for COVID-19 pneumonia may warrant anticoagulation for milder cases and thrombolysis for more severe disease.

Biomarkers and Right Ventricular Dysfunction.

Right ventricular failure is common in critically ill patients, as it frequently results from pulmonary embolism or pulmonary hypertension, and can complicate sepsis and the acute respiratory distress syndrome. Right ventricular dysfunction can be challenging to manage and is associated with poor outcomes in this wide array of disease. Laboratory biomarkers are rapid, noninvasive, accurate, and widely available and thus are useful in the diagnosis and management of right ventricular dysfunction in the critically ill patient. This article discusses the pathophysiology of right ventricular failure and reviews the applications of commonly used biomarkers in right ventricular dysfunction in critical care.

Pulmonary artery stiffness in chronic obstructive pulmonary disease (COPD) and emphysema: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study.

PURPOSE: Chronic obstructive pulmonary disease (COPD) and particularly emphysema are characterized by stiffness of the aorta, due in part to accelerated elastin degradation in the lungs and aorta. Stiffness of the pulmonary arteries (PAs) may also be increased in COPD and emphysema, but data are lacking. We assessed PA stiffness using MRI in patients with COPD and related these measurements to COPD severity and percent emphysema. MATERIALS AND METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study recruited 290 participants, age 50-79 years with 10 or more packyears and free of clinical cardiovascular disease. COPD severity were defined on postbronchodilator spirometry by ATS/ERS criteria. Percent emphysema was defined as the percentage of regions of the lung < -950 Hounsfield units on full-lung computed tomography (CT). PA stain was defined by the percent change in cross-sectional PA area between systole and diastole on MRI. Blood flow across the tricuspid and mitral valves was assessed by phase-contrast MRI for determination of the ventricular diastolic dysfunction (E/A ratio). RESULTS: PA strain was reduced in COPD compared with controls (P = 0.002) and was inversely correlated with COPD severity (P = 0.004). PA strain was inversely associated to percent emphysema (P = 0.01). PA strain was also markedly correlated with right ventricular diastolic dysfunction measured by E/A ratios in the fully adjusted mix models (P = 0.02). CONCLUSION: PA strain is reduced in COPD, related in part to percent emphysema on CT scan, which may have implications for pulmonary small vessel flow and right ventricular function. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:262-271.

Successful Treatment of Refractory Massive Pulmonary Embolism with Repeated Administration of Systemic Thrombolysis.

BACKGROUND: We report a case series of two patients in the intensive care unit with massive pulmonary embolism and obstructive shock who had resolution of shock after repeated administration of alteplase. CASE SUMMARIES: Both patients were initially dosed 10 mg of alteplase followed by infusion of 90 mg over 2 hours, but remained in obstructive shock requiring significant inotropic and vasopressor support. Both patients were deemed poor candidates for embolectomy. The first patient received repeated doses reaching an accumulative dose of 200 mg alteplase over 15 hours. The second patient received an accumulative dose of 250 mg alteplase over 36 hours. Both patients had resolution of shock within 24 hours of repeated administration of alteplase, but also experienced significant drops in hemoglobin, which were supported with transfusions. They were transferred out of the intensive care unit after resolution of obstructive shock and hemorrhage. The first patient died one week after transfer from the intensive care unit due to invasive candidiasis and septic shock. The second patient was weaned from the ventilator and discharged home. CONCLUSION: Patients with obstructive shock secondary to massive pulmonary embolism despite a one-time dose of alteplase and poor candidacy for embolectomy may benefit from repeated doses of alteplase. Due to the short half-life, repeated administration of thrombolytic may be appropriate for younger patients without absolute contraindications to thrombolysis, but future studies are needed to identify the optimal patient population.

Pulmonary hyperinflation due to gas trapping and pulmonary artery size: The MESA COPD Study.

BACKGROUND: Pulmonary hypertension is associated with increased morbidity and mortality in chronic obstructive pulmonary disease (COPD). Since pulmonary artery (PA) size increases in pulmonary hypertension, we measured PA cross-sectional area using magnetic resonance imaging (MRI) to test the hypothesis that pulmonary hyperinflation due to gas trapping is associated with PA cross-sectional area in COPD. METHODS: The MESA COPD Study recruited participants with COPD and controls from two population-based cohort studies ages 50-79 years with 10 or more pack-years and free of clinical cardiovascular disease. Body plethysmography was performed according to standard criteria. Cardiac MRI was performed at functional residual capacity to measure the cross-sectional area of the main PA. Percent emphysema was defined as the percentage of lung voxels less than -950 Hounsfield units as assessed via x-ray computed tomography. Analyses were adjusted for age, gender, height, weight, race-ethnicity, the forced expiratory volume in one second, smoking status, pack-years, lung function, oxygen saturation, blood pressure, left ventricular ejection fraction and percent emphysema. RESULTS: Among 106 participants, mean residual volume was 1.98±0.71 L and the mean PA cross-sectional area was 7.23±1.72 cm2. A one standard deviation increase in residual volume was independently associated with an increase in main PA cross-sectional area of 0.55 cm2 (95% CI 0.18 to 0.92; p = 0.003). In contrast, there was no evidence for an association with percent emphysema or total lung capacity. CONCLUSION: Increased residual volume was associated with a larger PA in COPD, suggesting that gas trapping may contribute to pulmonary hypertension in COPD.

Ombitasvir-Paritaprevir-Ritonavir-Dasabuvir (Viekira Pak)-Induced Lactic Acidosis.

OBJECTIVE: To report a case series of three patients with hepatitis C virus infection who all presented with severe type B lactic acidosis shortly after starting treatment with ombitasvir-paritaprevir-ritonavir-dasabuvir. DESIGN: Case series. SETTING: ICU. PATIENTS: Three patients, all who had HCV cirrhosis with mild hepatic impairment (Child-Pugh A) and had started taking ombitasvir-paritaprevir-ritonavir-dasabuvir within the preceding 2 weeks, presented with similar nonspecific symptoms of lethargy, fatigue, and nausea. All had elevated lactate levels at admission without evidence of hypovolemia, cardiogenic failure, or vasodilatory shock. INTERVENTIONS: All patients were given appropriate supportive intensive care for what was initially suspected to be sepsis, including a minimum of 30 mL/kg of IV fluids, infectious workup including blood cultures, broad-spectrum antibiotics, and mechanical ventilatory support. The first patient received continuous veno-venous hemofiltration. The second patient received hemodialysis. The third patient was initially started on hemodialysis despite high norepinephrine requirements and ultimately transitioned to continuous veno-venous hemofiltration. MEASUREMENTS AND MAIN RESULTS: The first patient died despite maximal intensive care. The second patient improved immediately upon starting hemodialysis and was extubated within 48 hours and discharged home. The third patient eventually became hypotensive and was treated with repeated sessions of renal replacement therapy. He ultimately was extubated and discharged home. The infectious workup was negative for all three patients, and antibiotics were discontinued after 2 days in the second and third patients. CONCLUSIONS: Ombitasvir-paritaprevir-ritonavir-dasabuvir may cause type B lactic acidosis. Further study is warranted to identify risk factors and elucidate the mechanisms of excessive lactate production.

Cor pulmonale parvus in chronic obstructive pulmonary disease and emphysema: the MESA COPD study.

BACKGROUND: The classic cardiovascular complication of chronic obstructive pulmonary disease (COPD) is cor pulmonale or right ventricular (RV) enlargement. Most studies of cor pulmonale were conducted decades ago. OBJECTIVES: This study sought to examine RV changes in contemporary COPD and emphysema using cardiac magnetic resonance (CMR) imaging. METHODS: We performed a case-control study nested predominantly in 2 general population studies of 310 participants with COPD and control subjects 50 to 79 years of age with ≥10 pack-years of smoking who were free of clinical cardiovascular disease. RV volumes and mass were assessed using magnetic resonance imaging. COPD and COPD severity were defined according to standard spirometric criteria. The percentage of emphysema was defined as the percentage of lung regions <-950 Hounsfield units on full-lung computed tomography; emphysema subtypes were scored by radiologists. Results were adjusted for age, race/ethnicity, sex, height, weight, smoking status, pack-years, systemic hypertension, and sleep apnea. RESULTS: Right ventricular end-diastolic volume (RVEDV) was reduced in COPD compared with control subjects (-7.8 ml; 95% confidence interval: -15.0 to -0.5 ml; p = 0.04). Increasing severity of COPD was associated with lower RVEDV (p = 0.004) and lower RV stroke volume (p < 0.001). RV mass and ejection fraction were similar between the groups. A greater percentage of emphysema also was associated with lower RVEDV (p = 0.005) and stroke volume (p < 0.001), as was the presence of centrilobular and paraseptal emphysema. CONCLUSIONS: RV volumes are lower without significant alterations in RV mass and ejection fraction in contemporary COPD, and this reduction is related to the greater percentage of emphysema on computed tomography.

World Health Organization Group III pulmonary hypertension.

Pulmonary hypertension in the setting of parenchymal lung disease and conditions associated with chronic hypoxemia is commonly encountered in clinical practice and may adversely affect patients' function and mortality. Diagnosis of this subgroup of pulmonary hypertension has evolved but still requires right heart catheterization for confirmation. The primary treatment goal is optimization of the underlying parenchymal lung or hypoxemia-associated condition prior to consideration of pharmacologic therapy. Limited published experience with pulmonary hypertension-specific medications for treatment of WHO Group 3 pulmonary hypertension suggests symptomatic and functional benefit in selected individuals. The potential for worsening ventilation-perfusion matching must be considered in these cases, however, since there is a paucity of data regarding the optimal approach to treatment selection. Ongoing medication trials and further investigation of mechanisms of hypoxic pulmonary vasoconstriction provide hope for these patients who in the past often had only lung transplantation as a potential treatment option.

Pulmonary hypertension in the intensive care unit.

Pulmonary hypertension, a condition that can lead to right ventricular failure and hemodynamic collapse, can be very challenging to manage in critically ill patients who require the intensive care unit. Because of the underlying structure of the right ventricle, significant increases in right ventricular afterload initiate a vicious cycle of degenerating right ventricular function, giving rise to right ventricular failure and cardiogenic shock. In patients with pulmonary hypertension, inciting factors such as sepsis and arrhythmias can exacerbate this process. Important management principles include close monitoring of hemodynamics with both noninvasive and invasive modalities, optimization of right ventricular preload, maintenance of systemic blood pressure, enhancement of right ventricular contractility, reduction of right ventricular afterload, and reversal of identifiable inciting factors. The goal of this review is to discuss these key concepts in managing this difficult patient population.