Increased Dead Space Ventilation and Refractory Hypercapnia in Patients With Coronavirus Disease 2019: A Potential Marker of Thrombosis in the Pulmonary Vasculature

Abstract

Objectives: Mortality rates in intubated coronavirus disease 2019 patients remain markedly elevated. Some patients develop sudden refractory hypercapnia and hypoxemia not explained by worsening pulmonary parenchymal disease. This case series highlights clinical findings and management of coronavirus disease 2019 patients with refractory hypercapnia despite maximal/optimal ventilatory support. Hypercapnia could not be explained by worsening lung disease or other common factors, and thus, a pulmonary vascular etiology was suggested. The pillars of management were targeted to improve pulmonary vascular patency via aggressive anticoagulation and support right ventricular function.

Data sources: Four consecutive patients with confirmed coronavirus disease 2019 infection with sudden hypercapnia and hypoxemia were included.

Data synthesis: There was sequential development of: 1) severe hypercapnia attributable to marked elevation of dead space without radiographic changes; 2) concomitant coagulopathy manifest by an increase in d-dimer levels; 3) progressive shunt with consequent hypoxemia; and 4) right ventricular dysfunction. Management included extracorporeal Co₂ removal, direct thrombin inhibition, pulmonary vasodilators, and inotropic support. Marked improvement in Pao₂ allowed reduction in Fio₂ in all patients, extracorporeal Co₂ removal was discontinued in three patients over the ensuing 3 weeks, and one patient was discharged home.

Conclusions: We speculate that thromboinflammation with pulmonary microvasculature occlusion leads to a sudden increase in dead space and shunt resulting in severe hypercapnia and hypoxemia in coronavirus disease 2019 patients. Early identification of these physiologic and clinical biomarkers could trigger the institution of therapies aiming to reverse the hypercoagulable state and support right ventricular function.

Keywords: blood coagulation disorder; coronavirus disease 2019; hypercapnia; hypoxemia; respiratory dead space; respiratory failure.

Figure 1.

Chest radiographs from each patient at time of admission to the ICU. L = left side of the chest.

Figure 2.

Trends for Paco₂, dead space to tidal volume ratio (Vd/Vt), plasma d-dimer, and intrapulmonary shunt are shown for a representative patient during care in the ICU. Arrows indicate timing of interventions including institution of extracorporeal Co₂ removal (ECCOR), dobutamine, and argatroban.