Rationale: The inspiratory rise in transpulmonary pressure during mechanical ventilation increases right ventricular (RV) afterload. One mechanism is that when Palv exceeds left atrial pressure, West zone 1 or 2 (non–zone 3) conditions develop, and Palv becomes the downstream pressure opposing RV ejection. The Vt at which this impact on the right ventricle becomes hemodynamically evident is not well established. Objectives: To determine the magnitude of RV afterload and prevalence of significant non–zone 3 conditions during inspiration across the range of Vt currently prescribed in clinical practice. Methods: In postoperative passively ventilated cardiac surgery patients, we measured right atrial, right ventricle, pulmonary artery, pulmonary artery occlusion pressure, plateau pressure, and esophageal pressure during short periods of controlled ventilation, with Vt increments ranging between 2 and 12 ml/kg predicted body weight (PBW). The inspiratory increase in RV afterload was evaluated hemodynamically and echocardiographically. The prevalence of non–zone 3 conditions was determined using two definitions based on changes in esophageal pressure, pulmonary artery occlusion pressure, and plateau pressure. Measurements and Main Results: Fifty-one patients were studied. There was a linear relationship between Vt, driving pressure, transpulmonary pressure, and the inspiratory increase in the RV isovolumetric contraction pressure. Echocardiographically, increasing Vt was associated with a greater inspiratory increase in markers of afterload and a decrease in stroke volume. Non–zone 3 conditions were present in >50% of subjects at a Vt ⩾ 6 ml/kg PBW. Conclusions: In the Vt range currently prescribed, RV afterload increases with increasing Vt. A mechanical ventilation strategy that limits Vt and driving pressure is cardioprotective.

Acute respiratory distress syndrome (ARDS) remains an important clinical challenge with a mortality rate of 35–45%. It is being increasingly demonstrated that the improvement of outcomes requires a tailored, individualized approach to therapy, guided by a detailed understanding of each patient’s pathophysiology. In patients with ARDS, disturbances in the physiological matching of alveolar ventilation (V) and pulmonary perfusion (Q) (V/Q mismatch) are a hallmark derangement. The perfusion of collapsed or consolidated lung units gives rise to intrapulmonary shunting and arterial hypoxemia, whereas the ventilation of non-perfused lung zones increases physiological dead-space, which potentially necessitates increased ventilation to avoid hypercapnia. Beyond its impact on gas exchange, V/Q mismatch is a predictor of adverse outcomes in patients with ARDS; more recently, its role in ventilation-induced lung injury and worsening lung edema has been described. Innovations in bedside imaging technologies such as electrical impedance tomography readily allow clinicians to determine the regional distributions of V and Q, as well as the adequacy of their matching, providing new insights into the phenotyping, prognostication, and clinical management of patients with ARDS. The purpose of this review is to discuss the pathophysiology, identification, consequences, and treatment of V/Q mismatch in the setting of ARDS, employing experimental data from clinical and preclinical studies as support.

Patient self-inflicted lung injury (P-SILI) is a major challenge for the ICU physician: although spontaneous breathing is associated with physiological benefits, in patients with acute respiratory distress syndrome (ARDS), the risk of uncontrolled inspiratory effort leading to additional injury needs to be assessed to avoid delayed intubation and increased mortality. In the present review, we analyze the available clinical and experimental evidence supporting the existence of lung injury caused by uncontrolled high inspiratory effort, we discuss the pathophysiological mechanisms by which increased effort causes P-SILI, and, finally, we consider the measurements and interpretation of bedside physiological measures of increased drive that should alert the clinician. The data presented in this review could help to recognize injurious respiratory patterns that may trigger P-SILI and to prevent it.

Rationale: Blood flow rate affects mixed venous oxygenation (SvO2) during venovenous extracorporeal membrane oxygenation (ECMO), with possible effects on the pulmonary circulation and the right heart function. Objectives: To describe the physiologic effects of different levels of SvO2 obtained by changing ECMO blood flow in patients with severe acute respiratory distress syndrome receiving ECMO and controlled mechanical ventilation. Methods: Low (SvO2 target, 70–75%), intermediate (SvO2 target, 75–80%), and high (SvO2 target, >80%) ECMO blood flows were applied for 30 minutes in random order in 20 patients. Mechanical ventilation settings were left unchanged. The hemodynamic and pulmonary effects were assessed with pulmonary artery catheter and electrical impedance tomography. Measurements and Main Results: Cardiac output decreased from low to intermediate and to high blood flow/SvO2 (9.2 [6.2–10.9] vs. 8.3 [5.9–9.8] vs. 7.9 [6.5–9.1] L/min; P = 0.014), as well as mean pulmonary artery pressure (34 ± 6 vs. 31 ± 6 vs. 30 ± 5 mm Hg; P < 0.001) and right ventricular stroke work index (14.2 ± 4.4 vs. 12.2 ± 3.6 vs. 11.4 ± 3.2 g × m/beat/m2; P = 0.002). Cardiac output was inversely correlated with mixed venous and arterial Po2 values (R2 = 0.257; P = 0.031; and R2 = 0.324; P = 0.05). Pulmonary artery pressure was correlated with decreasing mixed venous Po2 (R2 = 0.29; P < 0.001) and with increasing cardiac output (R2 = 0.378; P < 0.007). Measures of V̇/Q̇ mismatch did not differ between the three steps. Conclusions: In patients with severe acute respiratory distress syndrome, increased ECMO blood flow rate resulting in higher SvO2 decreases pulmonary artery pressure, cardiac output, and right heart workload.

Right ventricular (RV) dysfunction is a commonly considered cause of low cardiac output in critically ill patients. Its management can be difficult and requires an understanding of how the RV limits cardiac output. We explain that RV stroke output is caught between the passive elastance of the RV walls during diastolic filling and the active elastance produced by the RV in systole. These two elastances limit RV filling and stroke volume and consequently limit left ventricular stroke volume. We emphasize the use of the term “RV limitation” and argue that limitation of RV filling is the primary pathophysiological process by which the RV causes hemodynamic instability. Importantly, RV limitation can be present even when RV function is normal. We use the term “RV dysfunction” to indicate that RV end-systolic elastance is depressed or diastolic elastance is increased. When RV dysfunction is present, RV limitation occurs at lowerpulmonary valve opening pressures and lower stroke volume, but stroke volume and cardiac output still can be maintained until RV filling is limited. We use the term “RV failure” to indicate the condition in which RV output is insufficient for tissue needs. We discuss the physiological underpinnings of these terms and implications for clinical management.