The renin–angiotensin system (RAS) has long been described in the field of cardiovascular physiology as the main player in blood pressure homeostasis. However, other effects have since been described, and include proliferation, fibrosis, and inflammation. To illustrate the immunomodulatory properties of the RAS, we chose three distinct fields in which RAS may play a critical role and be the subject of specific treatments. In oncology, RAS hyperactivation has been associated with tumor migration, survival, cell proliferation, and angiogenesis; preliminary data showed promise of the benefit of RAS blockers in patients treated for certain types of cancer. In intensive care medicine, vasoplegic shock has been associated with severe macro- and microcirculatory imbalance. A relative insufficiency in angiotensin II (AngII) was associated to lethal outcomes and synthetic AngII has been suggested as a specific treatment in these cases. Finally, in solid organ transplantation, both AngI and AngII have been associated with increased rejection events, with a regional specificity in the RAS activity. These elements emphasize the complexity of the direct and indirect interactions of RAS with immunomodulatory pathways and warrant further research in the field.

OBJECTIVES The aim of this study was to compare the incidence of permanent pacemaker (PPM) implantation after aortic valve replacement by rapid-deployment bioprosthesis (RDB) and standard valve (Standard). METHODS All patients undergoing aortic valve replacement between 2015 and 2018, in 1 centre, were included. A multivariate analysis on the whole cohort and then a propensity score matching were used to compare the 2 groups. The primary end point was PPM implantation. RESULTS We studied 924 patients (256 RDBs and 668 Standards). Overall, 67 PPM were implanted, 37 (14.5%) in the RDB group and 26 (3.9%) in the Standard group (P < 0.0001, univariate analysis). The multivariate analysis in the unmatched population found 4 independent factors associated with PPM implantation: right bundle branch block with odds ratios (ORs 3.7, 95% CI 2.9–6.7; P < 0.0001), RDB (OR 3.6, 95% CI 2.0–6.2; P < 0.0001), age (OR 1.1, 95% CI 1.0–1.1; P < 0.006) and endocarditis (OR 3.4, 95% CI 1.0–11.0; P < 0.04). In the propensity score-matched RDB group (203 patients per group), 25 patients required PPM implantation versus 3 in the Standard group (12.3% vs 1.5%, P < 0.0001). RDBs also had more postoperative left bundle branch block and new onset of atrial fibrillation (30.2% vs 5.1%, P < 0.0001 and 34.0% vs 24.1%, P = 0.029). RDBs had lower operating times (in min): aortic cross-clamping = 62 (44–76.5) vs 72 (57.5–91.5) and cardiopulmonary bypass = 81 (63–98.5) vs 91 (75–112), P < 0.0001. There was no significant difference in other outcomes. CONCLUSIONS RDBs were associated with reduced operating times, increased risk of atrial fibrillation and PPM implantation as compared with standard aortic valves.

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Introduction The management of pain and anxiety remains a challenge in the intensive care unit. By distracting patients, virtual reality (VR) may have a role in painful procedures. We compared VR vs. an inhaled equimolar mixture of N2O and O2 (Kalinox®) for pain and anxiety management during the removal of chest drains after cardiac surgery. Methods Prospective, non-inferiority, open-label study. Patients were randomized, for Kalinox® or VR session during drain removal. The analgesia/nociception index (ANI) was monitored during the procedure for objective assessment of pain and anxiety. The primary endpoint was the ΔANI (ANImin − ANI0) during the procedure, based on ANIm (average on 4 min). We prespecified VR as non-inferior to Kalinox® with a margin of 3 points. Self-reported pain and anxiety were also analysed using numeric rate scale (NRS). Results 200 patients were included, 99 in the VR group and 101 in the Kalinox® group; 90 patients were analysed in both groups in per-protocol analysis. The median age was 68.0 years [60.0–74.8]. The ΔANI was − 15.1 ± 12.9 in the Kalinox® group and − 15.7 ± 11.6 in the VR group (NS). The mean difference was, therefore, − 0.6 [− 3.6 to 2.4], including the non-inferiority margin of 3. Patients in the VR group had a significantly higher pain NRS scale immediately after the drain removal, 5.0 [3.0–7.0] vs. 3.0 [2.0–6.0], p = 0.009, but no difference 10 min after. NRS of anxiety did not differ between the two groups. Conclusion Based on the ANI, the current study showed that VR did not reach the statistical requirements for a proven non-inferiority vs. Kalinox® in managing pain and anxiety during chest drain removal. Moreover, VR was less effective based on NRS. More studies are needed to determine if VR might have a place in the overall approach to pain and anxiety in intensive care units. Trial registration NCT, NCT03956264. Registered 20 May 2019, https://clinicaltrials.gov/ct2/show/NCT03956264

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is manifested by an acute respiratory distress syndrome (ARDS) with intense inflammation and endothelial dysfunction leading to particularly severe hypoxemia. We hypothesized that an impaired hypoxic pulmonary vasoconstriction aggravates hypoxemia. The objective of the study was to test the effect of two pulmonary vasoactive drugs on patient oxygenation.Methods: Observational, single-center, open-label study in one intensive care unit (ICU) of the Paris area, realized in April 2020. Eligible patients had coronavirus disease 2019 (COVID-19) and moderate to severe ARDS [arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) <200 mmHg] despite conventional protective ventilation. Exclusion criteria included pulmonary artery hypertension defined by a pulmonary artery systolic pressure (PAPs) >45 mmHg. The assessment of oxygenation was based on PaO2/FiO2 at (1) baseline, then after (2) 30 min of inhaled nitric oxide (iNO) 10 ppm alone, then (3) 30 min combination of iNO + almitrine infusion 8 μg/kg/min, then (4) 30 min of almitrine infusion alone.Results: Among 20 patients requiring mechanical ventilation during the study period, 12 met the inclusion criteria. Baseline PaO2/FiO2 was 146 ± 48 mmHg. When iNO was combined with almitrine, PaO2/FiO2 rose to 255 ± 90 mmHg (+80 ± 49%, p = 0.005), also after almitrine alone: 238 ± 98 mmHg (+67 ± 75%, p = 0.02), but not after iNO alone: 185 ± 73 mmHg (+30 ± 5%, p = 0.49). No adverse events related to almitrine infusion or iNO was observed.Conclusion: Combining iNO and infused almitrine improved the short-term oxygenation in patients with COVID-19-related ARDS. This combination may be of interest when first-line therapies fail to restore adequate oxygenation. These findings argue for an impaired pulmonary hypoxic vasoconstriction in these patients.

Introduction: Right ventricular failure (RVF) after cardiac surgery is an important risk factor for morbidity and mortality. Its diagnosis is challenging, and thus, its incidence and predictors are not well-established. We investigated the incidence, complications, and variables associated with clinically relevant post-operative RVF.Methods: We included all patients who underwent cardiac surgery with cardiopulmonary bypass between 2016 and 2019 in a cardiac surgery center with standardized diagnostic and therapeutic management of RVF. RVF was considered only if clinically relevant: associated with hemodynamic instability requiring catecholamine support and inhaled nitric oxide relayed by sildenafil.Results: Overall, 3,826 patients were included, of whom, 110 (2.9%) developed post-operative RVF. Mortality was not different among patients who developed post-operative RVF, compared with the rest of the cohort (1.8 vs. 0.7%, p = 0.17). Using a composite outcome that combined death, reintubation, stroke, and prolonged intensive care unit stay (more than 14 days) yielded an incidence of 6.6%, and RVF was associated with this composite outcome with an odds ratio of 3.6 (2.2–5.8), p < 0.001. In a multivariable model, pre-operative variables independently associated with post-operative RVF were pre-operative atrial fibrillation (AF) {adjusted odds ratio (adjOR) 3.22 [95% confidence interval (95%CI) = 1.94–5.36], p < 0.001}, left ventricle ejection fraction below 50% [adjOR = 2.55 (95%CI = 1.52–4.33), p < 0.001], systolic pulmonary artery pressure above 55 mmHg [adjOR = 8.64 (95%CI = 5.27–14.1); p < 0.001], mitral valve surgery [adjOR = 2.17 CI (95%CI = 1.28–3.66), p = 0.004], and tricuspid valve surgery [adjOR = 10.33 (95%CI = 6.14–17.4), p < 0.001]. In patients who developed post-operative RVF requiring treatment, 32 (29.1%) showed RV dysfunction before surgery.Conclusion: In this cohort study, 2.9% of patients developed clinically significant post-operative RVF. Moreover, RVF was associated with severe adverse outcomes, including death, strokes, reintubation, and prolonged intensive care unit stay.

Background:The effect of prone positioning (PP) on respiratory mechanics remains uncertain in patients with severe acute respiratory distress syndrome (ARDS) requiring venovenous extracorporeal membrane oxygenation (VV-ECMO).Methods:We prospectively analyzed the effects of PP on respiratory mechanics from continuous data with over a thousand time points during 16-h PP sessions in patients with COVID-19 and ARDS under VV-ECMO conditions. The evolution of respiratory mechanical and oxygenation parameters during the PP sessions was evaluated by dividing each PP session into four time quartiles: first quartile: 0–4 h, second quartile: 4–8 h, third quartile: 8–12 h, and fourth quartile: 12–16 h.Results:Overall, 38 PP sessions were performed in 10 patients, with 3 [2–5] PP sessions per patient. Seven (70%) patients were responders to at least one PP session. PP significantly increased the PaO2/FiO2 ratio by 14 ± 21% and compliance by 8 ± 15%, and significantly decreased the oxygenation index by 13 ± 18% and driving pressure by 8 ± 12%. The effects of PP on respiratory mechanics but not on oxygenation persisted after supine repositioning. PP-induced changes in different respiratory mechanical parameters and oxygenation started as early as the first-time quartile, without any difference in PP-induced changes among the different time quartiles. PP-induced changes in driving pressure (−14 ± 14 vs. −6 ± 10%, p = 0.04) and mechanical power (−11 ± 13 vs. −0.1 ± 12%, p = 0.02) were significantly higher in responders (increase in PaO2/FiO2 ratio > 20%) than in non-responder patients.Conclusions:In patients with COVID-19 and severe ARDS, PP under VV-ECMO conditions improved the respiratory mechanical and oxygenation parameters, and the effects of PP on respiratory mechanics persisted after supine repositioning.

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