Perioperative individualized hemodynamic optimization according to baseline mean arterial pressure in cardiac surgery patients: Rationale and design of the OPTIPAM randomized trial.

BACKGROUND: Postoperative morbidity and mortality after cardiac surgery with cardiopulmonary bypass (CPB) remain high despite recent advances in both anesthesia and perioperative management. Among modifiable risk factors for postoperative complications, optimal arterial pressure during and after surgery has been under debate for years. Recent data suggest that optimizing arterial pressure to the baseline of the patient may improve outcomes. We hypothesize that optimizing the mean arterial pressure (MAP) to the baseline MAP of the patient during cardiac surgery with CPB and during the first 24 hours postoperatively may improve outcomes. STUDY DESIGN: The OPTIPAM trial (NCT05403697) will be a multicenter, randomized, open-label controlled trial testing the superiority of optimized MAP management as compared with a MAP of 65 mm Hg or more during both the intraoperative and postoperative periods in 1,100 patients scheduled for cardiac surgery with CPB. The primary composite end point is the occurrence of acute kidney injury, neurological complications including stroke or postoperative delirium, and death. The secondary end points are hospital and intensive care unit lengths of stay, Day 7 and Day 90 mortality, postoperative cognitive dysfunction on Day 7 and Day 90, and quality of life at Day 7 and Day 90. Two interim analyses will assess the safety of the intervention. CONCLUSION: The OPTIPAM trial will assess the effectiveness of an individualized target of mean arterial pressure in cardiac surgery with CPB in reducing postoperative morbidity. CLINICAL TRIAL REGISTRATION: NCT05403697.

Early hyperoxia and 28-day mortality in patients on venoarterial ECMO support for refractory cardiogenic shock: a bicenter retrospective propensity score-weighted analysis.

BACKGROUND: The mortality rate for a patient with a refractory cardiogenic shock on venoarterial (VA) extracorporeal membrane oxygenation (ECMO) remains high, and hyperoxia might worsen this prognosis. The objective of the present study was to evaluate the association between hyperoxia and 28-day mortality in this setting. METHODS: We conducted a retrospective bicenter study in two French academic centers. The study population comprised adult patients admitted for refractory cardiogenic shock. The following arterial partial pressure of oxygen (PaO2) variables were recorded for 48 h following admission: the absolute peak PaO2 (the single highest value measured during the 48 h), the mean daily peak PaO2 (the mean of each day's peak values), the overall mean PaO2 (the mean of all values over 48 h), and the severity of hyperoxia (mild: PaO2 < 200 mmHg, moderate: PaO2 = 200-299 mmHg, severe: PaO2 ≥ 300 mmHg). The main outcome was the 28-day all-cause mortality. Inverse probability weighting (IPW) derived from propensity scores was used to reduce imbalances in baseline characteristics. RESULTS: From January 2013 to January 2020, 430 patients were included and assessed. The 28-day mortality rate was 43%. The mean daily peak, absolute peak, and overall mean PaO2 values were significantly higher in non-survivors than in survivors. In a multivariate logistic regression analysis, the mean daily peak PaO2, absolute peak PaO2, and overall mean PaO2 were independent predictors of 28-day mortality (adjusted odds ratio [95% confidence interval per 10 mmHg increment: 2.65 [1.79-6.07], 2.36 [1.67-4.82], and 2.85 [1.12-7.37], respectively). After IPW, high level of oxygen remained significantly associated with 28-day mortality (OR = 1.41 [1.01-2.08]; P = 0.041). CONCLUSIONS: High oxygen levels were associated with 28-day mortality in patients on VA-ECMO support for refractory cardiogenic shock. Our results confirm the need for large randomized controlled trials on this topic.

Passive leg raising-induced changes in pulse pressure variation to assess fluid responsiveness in mechanically ventilated patients: a multicentre prospective observational study.

BACKGROUND: Passive leg raising-induced changes in cardiac index can be used to predict fluid responsiveness. We investigated whether passive leg raising-induced changes in pulse pressure variation (ΔPPVPLR) can also predict fluid responsiveness in mechanically ventilated patients. METHODS: In this multicentre prospective observational study, we included 270 critically ill patients on mechanical ventilation in whom volume expansion was indicated because of acute circulatory failure. We did not include patients with cardiac arrythmias. Cardiac index and PPV were measured before/during a passive leg raising test and before/after volume expansion. A volume expansion-induced increase in cardiac index of >15% defined fluid responsiveness. To investigate whether ΔPPVPLR can predict fluid responsiveness, we determined areas under the receiver operating characteristic curves (AUROCs) and grey zones for relative and absolute ΔPPVPLR. RESULTS: Of the 270 patients, 238 (88%) were on controlled mechanical ventilation with no spontaneous breathing activity and 32 (12%) were on pressure support ventilation. The median tidal volume was 7.1 (inter-quartile range [IQR], 6.6-7.6) ml kg-1 ideal body weight. One hundred sixty-four patients (61%) were fluid responders. Relative and absolute ΔPPVPLR predicted fluid responsiveness with an AUROC of 0.92 (95% confidence interval [95% CI], 0.88-0.95; P<0.001) each. The grey zone for relative and absolute ΔPPVPLR included 4.8% and 22.6% of patients, respectively. These results were not affected by ventilatory mode and baseline characteristics (type of shock, centre, vasoactive treatment). CONCLUSIONS: Passive leg raising-induced changes in pulse pressure variation accurately predict fluid responsiveness with a small grey zone in critically ill patients on mechanical ventilation. CLINICAL TRIAL REGISTRATION: NCT03225378.

Pure SARS-CoV-2 related AVDS (Acute Vascular Distress Syndrome).

BACKGROUND: SARS-CoV-2 virus which targets the pulmonary vasculature is supposed to induce an intrapulmonary right to left shunt with an increased pulmonary blood flow. Such vascular injury is difficult to observe because it is hidden by the concomitant lung injury. We report here what may be, to the best of our knowledge, the first case of a pure Covid-19 related Acute Vascular Distress Syndrome (AVDS). CASE PRESENTATION: A 43-year-old physician, tested positive for Covid-19, was addressed to the emergency unit for severe dyspnoea and dizziness. Explorations were non informative with only a doubt regarding a sub-segmental pulmonary embolism (no ground-glass lesions or consolidations related to Covid-19 disease). Dyspnoea persisted despite anticoagulation therapy and normal pulmonary function tests. Contrast-enhanced transthoracic echocardiography was performed which revealed a moderate late right-to-left shunt. CONCLUSIONS: This case report highlights the crucial importance of the vascular component of the viral disease. The intrapulmonary shunt induced by Covid-19 which remains unrecognized because generally hidden by the concomitant lung injury, can persist for a long time. Contrast-enhanced transthoracic echocardiography is the most appropriate test to propose in case of persistent dyspnoea in Covid-19 patients.

Central venous-to-arterial CO2 difference is a poor tool to predict adverse outcomes after cardiac surgery: a retrospective study.

PURPOSE: The venous-to-arterial carbon dioxide partial pressure difference (CO2 gap) has been reported to be a sensitive indicator of cardiac output adequacy. We aimed to assess whether the CO2 gap can predict postoperative adverse outcomes after cardiac surgery. METHODS: A retrospective study was conducted of 5,151 patients from our departmental database who underwent cardiac surgery from 1 January 2008 to 31 December 2018. Lactate level (mmol·L-1), central venous oxygen saturation (ScVO2) (%), and the venous-to-arterial carbon dioxide difference (CO2 gap) were measured at intensive care unit (ICU) admission and on days 1 and 2 after cardiac surgery. The following postoperative adverse outcomes were collected: ICU mortality, hemopericardium or tamponade, resuscitated cardiac arrest, acute kidney injury, major bleeding, acute hepatic failure, mesenteric ischemia, and pneumonia. The primary outcome was the presence of at least one postoperative adverse outcome. Logistic regression was used to assess the association between ScVO2, lactate, and the CO2 gap with adverse outcomes. Their diagnostic performance was compared using a receiver operating characteristic (ROC) curve. RESULTS: There were 1,933 patients (38%) with an adverse outcome. Cardiopulmonary bypass (CPB) parameters were similar between groups. The CO2 gap was slightly higher for the "adverse outcomes" group than for the "no adverse outcomes" group. Arterial lactate at admission, day 1, and day 2 was also slightly higher in patients with adverse outcomes. Central venous oxygen saturation was not significantly different between patients with and without adverse outcomes. The area under the ROC curve to predict outcomes after CPB for the CO2 gap at admission, day 1, and day 2 were 0.52, 0.55, and 0.53, respectively. CONCLUSION: After cardiac surgery with CPB, the CO2 gap at ICU admission, day 1, and day 2 was associated with postoperative adverse outcomes but showed poor diagnostic performance.

RéSUMé: OBJECTIF: La différence de pression partielle de dioxyde de carbone veineux versus artériel (gradient de CO2) a été rapportée comme étant un indicateur sensible d'un débit cardiaque adéquat. Nous avons tenté d'évaluer si le gradient de CO2 pouvait prédire les devenirs postopératoires défavorables après une chirurgie cardiaque. MéTHODE: Une étude rétrospective a été réalisée en se basant sur les dossiers de 5151 patients issus de notre base de données départementale ayant subi une chirurgie cardiaque entre le 1er janvier 2008 et le 31 décembre 2018. Les taux de lactate (mmol·L−1), la saturation en oxygène veineux central (ScVO2) (%), et la différence de dioxyde de carbone veineux versus artériel (gradient de CO2) ont été mesurés lors de l'admission en réanimation (ICU) et aux jours 1 et 2 après la chirurgie cardiaque. Les complications postopératoires suivantes ont été colligées : mortalité en réanimation, hémopéricarde ou tamponnade, arrêt cardiaque récupéré, insuffisance rénale aiguë, saignements majeurs, insuffisance hépatique aiguë, ischémie mésentérique et pneumonie. Le critère d'évaluation principal était la présence d'au moins une complication postopératoire. La régression logistique a été utilisée pour évaluer l'association entre ScVO2, taux de lactate et gradient de CO2 et les complications. Leur performance diagnostique a été comparée à l'aide d'une courbe ROC (receiver operating characteristic). RéSULTATS: Des complications sont survenues chez 1933 patients (38 %). Les paramètres de circulation extracorporelle (CEC) étaient semblables entre les groupes. Le gradient de CO2 était légèrement plus élevé dans le groupe « complications ¼ que dans le groupe « pas de complication ¼. Les taux de lactate artériels à l'admission, au jour 1 et au jour 2 étaient également légèrement plus élevés chez les patients ayant subi des complications. La différence de saturation en oxygène veineux central n'était pas significative entre les patients avec ou sans complications. L'aire sous la courbe ROC pour prédire les devenirs après la CEC pour le gradient de CO2 à l'admission, au jour 1 et au jour 2 était de 0,52, 0,55 et 0,53, respectivement. CONCLUSION: Après une chirurgie cardiaque avec CEC, le gradient de CO2 à l'admission en réanimation, au jour 1 et au jour 2 était associé aux complications postopératoires, mais sa performance diagnostique était médiocre.

Usefulness of Right Ventricular Longitudinal Shortening Fraction to Detect Right Ventricular Dysfunction in Acute Cor Pulmonale Related to COVID-19.

OBJECTIVE: To compare two-dimensional-speckle tracking echocardiographic parameters (2D-STE) and classic echocardiographic parameters of right ventricular (RV) systolic function in patients with coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (CARDS) complicated or not by acute cor pulmonale (ACP). DESIGN: Prospective, between March 1, 2020 and April 15, 2020. SETTING: Intensive care unit of Amiens University Hospital (France). PARTICIPANTS: Adult patients with moderate-to-severe CARDS under mechanical ventilation for fewer than 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Tricuspid annular displacement (TAD) parameters (TAD-septal, TAD-lateral, and RV longitudinal shortening fraction [RV-LSF]), RV global longitudinal strain (RV-GLS), and RV free wall longitudinal strain (RVFWLS) were measured using transesophageal echocardiography with a dedicated software and compared with classic RV systolic parameters (RV-FAC, S' wave, and tricuspid annular plane systolic excursion [TAPSE]). RV systolic dysfunction was defined as RV-FAC <35%. Twenty-nine consecutive patients with moderate-to-severe CARDS were included. ACP was diagnosed in 12 patients (41%). 2D-STE parameters were markedly altered in the ACP group, and no significant difference was found between patients with and without ACP for classic RV parameters (RV-FAC, S' wave, and TAPSE). In the ACP group, RV-LSF (17% [14%-22%]) had the best correlation with RV-FAC (r = 0.79, p < 0.001 v r = 0.27, p = 0.39 for RVGLS and r = 0.28, p = 0.39 for RVFWLS). A RV-LSF cut-off value of 17% had a sensitivity of 80% and a specificity of 86% to identify RV systolic dysfunction. CONCLUSIONS: Classic RV function parameters were not altered by ACP in patients with CARDS, contrary to 2D-STE parameters. RV-LSF seems to be a valuable parameter to detect early RV systolic dysfunction in CARDS patients with ACP.

Aortic root dilatation in PFO-related cryptogenic stroke: A propensity score-matched analysis.

BACKGROUND: Dilatation of the ascending aorta has an important role in the anatomical conformation of interatrial septum (IAS) especially when a patent foramen ovale (PFO) is present. The aim of the study was to investigate the relationship between ascending aortic dilation and PFO-related cryptogenic stroke in a cohort of cryptogenic strokes. METHODS: It is a retrospective, single-center echocardiographic study assessing aortic root dilatation in 315 consecutive patients with cryptogenic stroke between January 2011 and January 2019. Aortic root dilatation was defined by a diameter of the Valsalva sinuses of the proximal aorta >40 mm. Predictive factors of PFO were assessed by a multivariate analysis. Propensity score matching was applied to account for clinical differences. RESULTS: Of the 315 patients, 68 (22%) had an aortic root dilatation and 167 (53%) had a PFO. In the aortic root dilation group, PFO was more often diagnosed (n = 47/68 [69%], vs n = 120/247 [49%], P = .004). In the PFO group with aortic dilatation, IAS was more mobile (n = 37/47[79%] vs n = 69/120[57%], P < .012) and smaller (2.3 ± 0.5 vs 2.5 ± 0.5 mm, P < .009). On multivariate analysis, aortic root dilatation (OR: 2.6; 95% CI [1.2-5.6]; P = .001) and IAS hypermobility (OR: 5.2 95% CI [2.7-10]; P = .001) were associated with PFO. After propensity matching, aortic root dilatation remained strongly associated with PFO (n = 34/107 [32%] vs 15/107[14%], P = .002). CONCLUSION: Aortic root dilation and IAS hypermobility were strongly associated with PFO-related cryptogenic stroke.

An urgent open surgical approach for left ventricle venting during peripheral veno-arterial extracorporeal membrane oxygenation for refractory cardiac arrest: case report.

The objective of the study is to describe an emergency procedure for left ventricle venting during veno-arterial extracorporeal life support for refractory cardiac arrest. Veno-arterial extracorporeal membrane oxygenation is widely used in refractory cardiac arrest but is characterized by an increase in left ventricle afterload, which may impair cardiac contractility improvement. Different left ventricle venting techniques are available. We report the use of a surgical approach with sternotomy for left ventricle venting in a 21-year-old patient who was placed under veno-arterial extracorporeal membrane oxygenation for refractory cardiac arrest with severe pulmonary edema, respiratory failure, and left ventricle stasis. A 21-year-old woman was admitted for laparoscopic sleeve gastrectomy. In the recovery room, she developed a refractory circulatory shock. Transthoracic echocardiography revealed a dilated cardiomyopathy with severe left ventricle systolic dysfunction (left ventricle ejection fraction at 20%). Coronary angiogram was normal. On day 2, she underwent laparotomy for sepsis and she presented cardiac arrest secondary to ventricular tachycardia. We proceeded to peripheral veno-arterial extracorporeal membrane oxygenation as the cardiac arrest was refractory. A miniaturized veno-arterial extracorporeal membrane oxygenation system was implanted into the right femoral vessels onsite .The low flow duration was 40 minutes. Veno-arterial extracorporeal membrane oxygenation blood flow was set to 3 L min-1, resulting in a closed aortic valve and a massive pulmonary edema. Transesophageal echocardiography showed left ventricular ejection fraction at 5% without aortic valve opening. We first implanted an intra-aortic balloon pump without clinical improvement. Transesophageal echocardiography revealed massive thrombus formation into the aortic root. We decided to perform an open surgical approach for left ventricle unload using a transmitral cannula (22 Fr) via the right superior pulmonary vein connected to the inflow tube of the veno-arterial extracorporeal membrane oxygenation with Y connection. Transesophageal echocardiography showed a full opening of aortic valve and elimination of valve aortic thrombus. Chest radiography showed a significant decrease of pulmonary congestion. We were able to withdraw extracorporeal life support organization on day 10 and discharged on day 54. Clinical explorations reveal a fulminant rocuronium-related hypersensitivity myocarditis. This salvage surgical technique using a modified central veno-arterial extracorporeal membrane oxygenation cannulation technique has efficiently decreased blood stasis and permitted rapid recovery.

Time course of fluid responsiveness in sepsis: the fluid challenge revisiting (FCREV) study.

BACKGROUND: Fluid challenge (FC) is one of the most common practices in Intensive Care Unit (ICU). The present study aimed to evaluate whether echocardiographic assessment of the response to FC at the end of the infusion or 20 min later could affect the results of the FC. METHODS: This is a prospective, observational, multicenter study including all ICU patients in septic shock requiring a FC of 500 mL crystalloids over 10 min. Fluid responsiveness was defined as a > 15% increase in stroke volume (SV) assessed by velocity-time integral (VTI) measurements at baseline (T0), at the end of FC (T10), then 10 (T20) and 20 min (T30) after the end of FC. RESULTS: From May 20, 2014, to January 7, 2016, a total of 143 patients were enrolled in 11 French ICUs (mean age 64 ± 14 years, median IGS II 53 [43-63], median SOFA score 10 [8-12]). Among the 76/143 (53%) patient responders to FC at T10, 37 patients were transient responders (TR), i.e., became non-responders (NR) at T30 (49%, 95%CI = [37-60]), and 39 (51%, 95%CI = [38-62]) patients were persistent responders (PR), i.e., remained responders at T30. Among the 67 NR at T10, 4 became responders at T30, (6%, 95%CI = [1.9-15.3]). In the subgroup analysis, no statistical difference in hemodynamic and echocardiographic parameters was found between groups. CONCLUSIONS: This study shows that 51.3% of initial responders have a persistent response to fluid 30 min after the beginning of fluid infusion and only 41.3% have a transient response highlighting that fluid responsiveness is time dependent. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02116413 . Registered on April 16, 2014.

Antifungal Prevention of Systemic Candidiasis in Immunocompetent ICU Adults: Systematic Review and Meta-Analysis of Clinical Trials.

OBJECTIVES: The aim of this study was to identify the impact of antifungal prevention in critically ill immunocompetent adult patients on mortality and subsequent infection. DATA SOURCES: A systematic review and meta-analysis of randomized controlled trials comparing any antifungal use versus placebo to prevent candidiasis in ICU patients were performed. STUDY SELECTION: Searches were performed on PubMed, Embase, Scopus, main conference proceedings, and ClinicalTrials.gov, as well as reference lists. DATA EXTRACTION: The primary outcomes were mortality and invasive candidiasis. The secondary outcome was the rate of Candida albicans and nonalbicans strains after treatment. A random effect model was used, and sensitivity analysis was performed for both outcomes. Results are expressed as risk ratios and their 95% CIs. DATA SYNTHESIS: Nineteen trials (10 with fluconazole, four with ketoconazole, one with itraconazole, three with micafungin, and one with caspofungin) including 2,792 patients were identified. No individual trial showed a decreased mortality rate. Combined analysis showed that preventive antifungal did not decrease mortality (risk ratio, 0.88; 95% CI, 0.74-1.04; p = 0.14) but significantly decreased secondary fungal infections by 50% (risk ratio, 0.49; 95% CI, 0.35-0.68; p = 0.0001). No shift across nonalbicans strains was observed during treatment (risk ratio, 0.62; 95% CI, 0.19-1.97; p = 0.42). However, publication biases preclude any definite conclusions for prevention of infection. CONCLUSIONS: Antifungal prevention of systemic candidiasis in immunocompetent critically ill adults did not reduce mortality and may have decreased secondary fungal infection rates. However, significant publication bias was present.