Background: Prone positioning in combination with the application of low tidal volume and adequate positive end-expiratory pressure (PEEP) improves survival in patients with moderate to severe acute respiratory distress syndrome (ARDS). However, the effects of PEEP on end-expiratory transpulmonary pressure (Ptp_exp) during prone positioning require clarification. For this purpose, the effects of three different PEEP titration strategies on Ptp_exp, respiratory mechanics, mechanical power, gas exchange, and hemodynamics were evaluated comparing supine and prone positioning. Methods: In forty consecutive patients with moderate to severe ARDS protective ventilation with PEEP titrated according to three different titration strategies was evaluated during supine and prone positioning: (A) ARDS Network recommendations (PEEP_ARDSNetwork), (B) the lowest static elastance of the respiratory system (PEEP_Estat,RS), and (C) targeting a positive Ptp_exp (PEEP_Ptpexp). The primary endpoint was to analyze whether Ptp_exp differed significantly according to PEEP titration strategy during supine and prone positioning. Results: Ptp_exp increased progressively with prone positioning compared with supine positioning as well as with PEEP_Estat,RS and PEEP_Ptpexp compared with PEEP_ARDSNetwork (positioning effect p < 0.001, PEEP strategy effect p < 0.001). PEEP was lower during prone positioning with PEEP_Estat,RS and PEEP_Ptpexp (positioning effect p < 0.001, PEEP strategy effect p < 0.001). During supine positioning, mechanical power increased progressively with PEEP_Estat,RS and PEEP_Ptpexp compared with PEEP_ARDSNetwork, and prone positioning attenuated this effect (positioning effect p < 0.001, PEEP strategy effect p < 0.001). Prone compared with supine positioning significantly improved oxygenation (positioning effect p < 0.001, PEEP strategy effect p < 0.001) while hemodynamics remained stable in both positions. Conclusions: Prone positioning increased transpulmonary pressures while improving oxygenation and hemodynamics in patients with moderate to severe ARDS when PEEP was titrated according to the ARDS Network lower PEEP table. This PEEP titration strategy minimized parameters associated with ventilator-induced lung injury induction, such as transpulmonary driving pressure and mechanical power. We propose that a lower PEEP strategy (PEEP_ARDSNetwork) in combination with prone positioning may be part of a lung protective ventilation strategy in patients with moderate to severe ARDS. Trial registration: German Clinical Trials Register (DRKS00017449). Registered June 27, 2019. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00017449

Background: Even an ultraprotective ventilation strategy in severe acute respiratory distress syndrome (ARDS) patients treated with extracorporeal membrane oxygenation (ECMO) might induce ventilator-induced lung injury and apneic ventilation with the sole application of positive end-expiratory pressure may, therefore, be an alternative ventilation strategy. We, therefore, compared the effects of ultraprotective ventilation with apneic ventilation on oxygenation, oxygen delivery, respiratory system mechanics, hemodynamics, strain, air distribution and recruitment of the lung parenchyma in ARDS patients with ECMO. Methods: In a prospective, monocentric physiological study, 24 patients with severe ARDS managed with ECMO were ventilated using ultraprotective ventilation (tidal volume 3 ml/kg of predicted body weight) with a fraction of inspired oxygen (FiO₂) of 21%, 50% and 90%. Patients were then treated with apneic ventilation with analogous FiO₂. The primary endpoint was the effect of the ventilation strategy on oxygenation and oxygen delivery. The secondary endpoints were mechanical power, stress, regional air distribution, lung recruitment and the resulting strain, evaluated by chest computed tomography, associated with the application of PEEP (apneic ventilation) and/or low V_T (ultraprotective ventilation). Results: Protective ventilation, compared to apneic ventilation, improved oxygenation (arterial partial pressure of oxygen, p < 0.001 with FiO₂ of 50% and 90%) and reduced cardiac output. Both ventilation strategies preserved oxygen delivery independent of the FiO₂. Protective ventilation increased driving pressure, stress, strain, mechanical power, as well as induced additional recruitment in the non-dependent lung compared to apneic ventilation. Conclusions: In patients with severe ARDS managed with ECMO, ultraprotective ventilation compared to apneic ventilation improved oxygenation, but increased stress, strain, and mechanical power. Apneic ventilation might be considered as one of the options in the initial phase of ECMO treatment in severe ARDS patients to facilitate lung rest and prevent ventilator-induced lung injury. Trial registration: German Clinical Trials Register (DRKS00013967). Registered 02/09/2018. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00013967.

Background: Procollagen peptides have been associated with lung fibroproliferation and poor outcomes in patients with acute respiratory distress syndrome (ARDS). Therefore, serum procollagen concentrations might have prognostic value in ARDS patients treated with extracorporeal membrane oxygenation (ECMO). Methods: In a prospective cohort study, serum N-terminal procollagen I-peptide (PINP) and N-terminal procollagen III-peptide (PIIINP) concentrations in twenty-three consecutive patients with severe ARDS treated with ECMO were measured at the time of ECMO initiation and during the course of treatment. The predictive value of PINP and PIIINP at the time of ECMO initiation was tested with a univariable logistic regression and a receiver operating characteristic (ROC) curve analysis. Results: Thirteen patients survived to intensive care unit (ICU) discharge. Non-survivors had higher serum PINP and PIIINP concentrations at all points in time during the course of treatment. Serum PIIINP at the day of ECMO initiation showed an odds ratio of 1.37 (95% CI 1.10–1.89, p = 0.017) with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.87 (95% CI 0.69–1.00, p = 0.0029) for death during the course of treatment. Conclusions: PINP and PIIINP concentrations differ between survivors and non-survivors in ARDS treated with ECMO. This exploratory hypothesis generating study suggests an association between PIIINP serum concentrations at ECMO initiation and an unfavorable clinical outcome.

Background: This study evaluated the effects of veno-arterial (V-A) and veno-venoarterial (V-VA) ECMO in a porcine model of septic endotoxemia-induced acute pulmonary arterial hypertension (PAH). Our hypotheses were as follows: (1) V-VA ECMO lowers pulmonary vascular resistance (PVR) by delivering oxygenated blood to the pulmonary circulation, and (2) both V-A and V-VA ECMO improve perfusion to vital organs while simultaneously unloading the right ventricle (RV). Methods: Acute PAH was induced with Salmonella abortus equi lipopolysaccharide (LPS) in 34 pigs. Animals were randomized to either a control group without ECMO or to two groups receiving V-A or V-VA ECMO. Results: All animals developed PAH after one hour of LPS infusion: mean pulmonary artery pressure (PAP) increased significantly from 26 (24–30) mmHg to 40 (34–46) mmHg (p < 0.0001), and PVR increased from 314 (221–390) to 787 (549–1073) (p < 0.0001). Neither V-A nor V-VA ECMO significantly reduced PVR compared to controls. RV end-diastolic area increased in the control group [6.1 (4.3–8.6) cm vs. 8.5 (7.8–9.7) cm, p = 0.2], but not in the V-A [4.7 (3.3–7.6) cm] and V-VA [4.3 (2.5–8.3) cm] ECMO groups. Blood flow in the cranial mesenteric artery and celiac trunk did not differ significantly with or without ECMO. Conclusions: Elevating pulmonary artery oxygen tension through V-A or V-VA ECMO did not reduce PVR or PAP. However, both ECMO configurations effectively unloaded the RV and maintained perfusion to abdominal organs.