Opioid-free anaesthesia with dexmedetomidine and lidocaine versus remifentanil-based anaesthesia in cardiac surgery: study protocol of a French randomised, multicentre and single-blinded OFACS trial.

INTRODUCTION: Intraoperative opioids have been used for decades to reduce negative responses to nociception. However, opioids may have several, and sometimes serious, adverse effects. Cardiac surgery exposes patients to a high risk of postoperative complications, some of which are common to those caused by opioids: acute respiratory failure, postoperative cognitive dysfunction, postoperative ileus (POI) or death. An opioid-free anaesthesia (OFA) strategy, based on the use of dexmedetomidine and lidocaine, may limit these adverse effects, but no randomised trials on this issue have been published in cardiac surgery.We hypothesised that OFA versus opioid-based anaesthesia (OBA) may reduce the incidence of major opioid-related complications after cardiac surgery. METHODS AND ANALYSIS: Multicentre, randomised, parallel and single-blinded clinical trial in four cardiac surgical centres in France, including 268 patients scheduled for coronary artery bypass grafting under cardiac bypass, with or without aortic valve replacement. Patients will be randomised to either a control OBA protocol using remifentanil or an OFA protocol using dexmedetomidine/lidocaine. The primary composite endpoint is the occurrence of at least one of the following: (1) postoperative cognitive disorder evaluated by the Confusion Assessment Method for the Intensive Care Unit test, (2) POI, (3) acute respiratory distress or (4) death within the first 48 postoperative hours. Secondary endpoints are postoperative pain, morphine consumption, nausea-vomiting, shock, acute kidney injury, atrioventricular block, pneumonia and length of hospital stay. ETHICS AND DISSEMINATION: This trial has been approved by an independent ethics committee (Comité de Protection des Personnes Ouest III-Angers on 23 February 2021). Results will be submitted in international journals for peer reviewing. TRIAL REGISTRATION NUMBER: NCT04940689, EudraCT 2020-002126-90.

Management and outcomes of pregnant women with cardiovascular diseases in a cardio-obstetric team.

BACKGROUND: Cardiovascular diseases (CVDs) are currently the leading cause of maternal death in Western countries. Although multidisciplinary cardio-obstetric teams are recommended to improve the management of pregnant women with CVD, data supporting this approach are scarce. AIMS: To describe the characteristics and outcomes of pregnant patients with CVD managed within the cardio-obstetric programme of a tertiary centre. METHODS: We included every pregnant patient with history of CVD managed by our cardio-obstetric team between June 2017 and December 2019, and collected all major cardiovascular events (death, heart failure, acute coronary syndromes, stroke, endocarditis and aortic dissection) that occurred during pregnancy, peripartum and the following year. RESULTS: We included 209 consecutive pregnancies in 202 patients. CVDs were predominantly valvular heart diseases (37.8%), rhythm disorders (26.8%), and adult congenital heart diseases (22.5%). Altogether, 47.4% were classified modified World Health Organization (mWHO)>II, 66.5% had CARdiac disease in PREGnancy score (CARPREG II)≥2 and 80 pregnancies (38.3%) were delivered by caesarean section. Major cardiovascular events occurred in 16 pregnancies (7.7%, 95% confidence interval [CI] 4.5-12.2) during pregnancy and in three others (1.5%, 95% CI 0.3-4.1) during 1-year follow-up. Most events (63.1%) occurred in the 16.3% of patients with unknown CVD before pregnancy. CONCLUSIONS: The management of pregnant patients with CVD within a cardio-obstetric team seems encouraging as we found a relatively low rate of cardiovascular events compared to the high-risk profile of our population. However, most of the remaining events occurred in patients without cardiac monitoring before pregnancy.

V stenting technique with covered stents for the management of ostial circumflex perforation: Good or bad idea?

We report the case of a redo Ross surgery complicated by an ostial left circumflex occlusion requiring emergent percutaneous coronary intervention. The latter was complicated by coronary perforation treated by two covered stents with V-stenting technique. After immediate success, the clinical course was marked by acute stent thrombosis requiring emergent coronary bypass. Learning objectives: Ostial left circumflex perforation is a rare and potentially fatal complication that is challenging to manage. V stenting technique with two covered stents could be used as a life-saving procedure, but is associated with a high thrombotic risk.

Definitions of major bleeding for predicting mortality in critically ill adult patients who survived 24 hours while supported with peripheral veno-arterial extracorporeal membrane oxygenation for cardiogenic shock: a comparative historical cohort study.

PURPOSE: The severity of bleeding events is heterogeneously defined during peripheral veno-arterial extracorporeal membrane oxygenation (pVA-ECMO). We studied three bleeding definitions in pVA-ECMO: the Extracorporeal Life Support Organization (ELSO)-serious bleeding, the Bleeding Academic Research Consortium (BARC), and the universal definition of postoperative bleeding (UPDB) classifications. METHODS: We included consecutive adult patients supported by pVA-ECMO for refractory cardiogenic shock admitted to Lille academic hospitals between January 2013 and December 2019. We assessed the association of bleeding definitions with the primary endpoint of 28-day all-cause mortality with the use of multivariate models accounting for time-dependent and competing variables. We compared models' performances using the Harrell's C-Index and the Akaike information criteria. RESULTS: Twenty-eight-day mortality occurred in 128/308 (42%) 308 patients. The ELSO-serious bleeding (hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.09 to 2.56) and BARC ≥ type 2 (HR, 1.55; 95% CI, 1.01 to 2.37) were associated with 28-day mortality (Harrell's C-index, 0.69; 95% CI, 0.63 to 0.74 for both). Predictors of ELSO-serious bleeding were postcardiotomy, body mass index, baseline platelets count, fibrinogen, and hemoglobin levels. CONCLUSION: Extracorporeal Life Support Organization-serious bleeding and BARC ≥ type 2 are relevant definitions of major bleeding regarding their association with mortality in critically ill patients who survived the first 24 hr while supported with pVA-ECMO for cardiogenic shock. STUDY REGISTRATION: CERAR (IRB 00010254-2022-050, Paris, France); first submitted on 18 April 2022.

RéSUMé: OBJECTIF: La gravité des événements hémorragiques est définie de manière hétérogène pendant une oxygénation par membrane extracorporelle veino-artérielle périphérique (ECMO-VA périphérique). Nous avons étudié trois définitions du saignement sous ECMO-VA périphérique : les classifications des saignements graves selon l'Extracorporeal Life Support Organization (ELSO), celles du Bleeding Academic Research Consortium (BARC) et la définition universelle du saignement postopératoire (UPDB). MéTHODE: Nous avons inclus des patient·es adultes pris·es en charge de manière consécutive par ECMO-VA périphérique à la suite d'un choc cardiogénique réfractaire et admis·es dans les centres hospitaliers universitaires de Lille entre janvier 2013 et décembre 2019. Nous avons évalué l'association des définitions du saignement avec le critère d'évaluation principal de mortalité toutes causes confondues à 28 jours à l'aide de modèles multivariés tenant compte des variables dépendantes du temps et concurrentes. Nous avons comparé les performances des modèles à l'aide de l'indice C de Harrell et du critère d'information d'Akaike. RéSULTATS: La mortalité à 28 jours est survenue chez 128/308 (42 %) patient·es. Le saignement grave selon l'ELSO (rapport de risque [RR], 1,67; intervalle de confiance [IC] à 95 %, 1,09 à 2,56) et une classification BARC ≥ type 2 (RR, 1,55; IC 95 %, 1,01 à 2,37) étaient associés à une mortalité à 28 jours (indice C de Harrell, 0,69; IC 95 %, 0,63 à 0,74 pour les deux). Les prédicteurs d'hémorragie grave selon l'ELSO étaient la postcardiotomie, l'indice de masse corporelle, la numération plaquettaire initiale, le taux de fibrinogène et les taux d'hémoglobine. CONCLUSION: Les définitions du saignement grave de l'Extracorporeal Life Support Organization et une classification BARC ≥ type 2 sont des définitions pertinentes des saignements majeurs en ce qui touche à leur association avec la mortalité chez les personnes gravement malades qui ont survécu aux premières 24 heures alors qu'elles étaient prises en charge par ECMO-VA périphérique à la suite d'un choc cardiogénique. ENREGISTREMENT DE L'éTUDE: CERAR (IRB 00010254-2022-050, Paris, France); soumis pour la première fois le 18 avril 2022.

Determinants of postoperative complications in high-risk noncardiac surgery patients optimized with hemodynamic treatment strategies: A post-hoc analysis of a randomized multicenter clinical trial.

STUDY OBJECTIVE: This post-hoc analysis of a randomized controlled trial was undertaken to establish the determinants of postoperative complications and acute kidney injury in high-risk noncardiac surgery patients supported with hemodynamic treatment strategies. DESIGN: We conducted a post-hoc analysis of patients enrolled in the OPtimization Hemodynamic Individualized by the respiratory QUotiEnt (OPHIQUE) trial. SETTING: Operating rooms in four university medical centers and one non-university hospital from December 26, 2018, to September 9, 2021. PATIENTS: We enrolled 350 patients with a high risk of postoperative complications undergoing high-risk noncardiac surgery lasting 2 h or longer under general anesthesia. INTERVENTIONS: All patients were treated according to hemodynamic treatment strategies which included cardiac output optimization by titration of fluid challenge and targeted systolic blood pressure to remain within ±10% of the reference value. MEASUREMENTS: We assessed the association between pre-operative and intra-operative exposure of interest with a composite primary outcome of major complications or death within seven days following surgery using a multivariable logistic regression model. We also assessed the association between these exposures of interest and acute kidney injury. MAIN RESULTS: The data of 341 patients were analyzed. In multivariate analysis, the factors independently associated with the primary outcome were age (OR = 1.04 (1.01-1.06), P = 0.002), preoperative hemoglobin concentration (OR = 0.85 (0.75-0.96), P = 0.012), non-vascular surgery (OR = 0.30 (0.17-0.53), P < 0.0001), and intraoperative surgical complications (OR = 2.08 (1.02-4.24), P = 0.046). The factors independently associated with postoperative acute kidney injury were age (OR = 1.04 (1.01-1.08), P = 0.008), preoperative creatinine concentration (OR = 1.01 (1.00-1.01), P = 0.049), non-vascular surgery (OR = 0.36 (0.20-0.66), P = 0.001), and intraoperative surgical complications (OR = 3.36 (1.50-7.55), P = 0.031). CONCLUSIONS: Surgical complications, a lower preoperative hemoglobin concentration, age, and vascular surgery were associated with postoperative complications in a high-risk noncardiac surgery population supported with hemodynamic treatment strategies.

Shear Forces Induced Platelet Clearance Is a New Mechanism of Thrombocytopenia.

BACKGROUND: Thrombocytopenia has been consistently described in patients with extracorporeal membrane oxygenation (ECMO) and associated with poor outcome. However, the prevalence and underlying mechanisms remain largely unknown, and a device-related role of ECMO in thrombocytopenia has been hypothesized. This study aims to investigate the mechanisms underlying thrombocytopenia in ECMO patients. METHODS: In a prospective cohort of 107 ECMO patients, we investigated platelet count, functions, and glycoprotein shedding. In an ex vivo mock circulatory ECMO loop, we assessed platelet responses and VWF (von Willebrand factor)-GP Ibα (glycoprotein Ibα) interactions at low- and high-flow rates, in the presence or absence of red blood cells. The clearance of human platelets subjected or not to ex vivo perfusion was studied using an in vivo transfusion model in NOD/SCID (nonobese diabetic/severe combined Immunodeficient) mice. RESULTS: In ECMO patients, we observed a time-dependent decrease in platelet count starting 1 hour after device onset, with a mean drop of 7%, 35%, and 41% at 1, 24, and 48 hours post-ECMO initiation (P=0.00013, P<0.0001, and P<0.0001, respectively), regardless of the type of ECMO. This drop in platelet count was associated with a decrease in platelet GP Ibα expression (before: 47.8±9.1 versus 24 hours post-ECMO: 42.3±8.9 mean fluorescence intensity; P=0.002) and an increase in soluble GP Ibα plasma levels (before: 5.6±3.3 versus 24 hours post-ECMO: 10.8±4.1 µg/mL; P<0.0001). GP Ibα shedding was also observed ex vivo and was unaffected by (1) red blood cells, (2) the coagulation potential, (3) an antibody blocking VWF-GP Ibα interaction, (4) an antibody limiting VWF degradation, and (5) supraphysiological VWF plasma concentrations. In contrast, GP Ibα shedding was dependent on rheological conditions, with a 2.8-fold increase at high- versus low-flow rates. Platelets perfused at high-flow rates before being transfused to immunodeficient mice were eliminated faster in vivo with an accelerated clearance of GP Ibα-negative versus GP Ibα-positive platelets. CONCLUSIONS: ECMO-associated shear forces induce GP Ibα shedding and thrombocytopenia due to faster clearance of GP Ibα-negative platelets. Inhibiting GP Ibα shedding could represent an approach to reduce thrombocytopenia during ECMO.

Comparison of landiolol and amiodarone for the treatment of new-onset atrial fibrillation after cardiac surgery (FAAC) trial: study protocol for a randomized controlled trial.

BACKGROUND: Postoperative atrial fibrillation (PoAF) after cardiac surgery has a high incidence of 30%, but its management is controversial. Two strategies are recommended without evidence of a superiority of one against the other: rate control with beta-blocker or rhythm control with amiodarone. Landiolol is a new-generation beta-blocker with fast onset and short half-life. One retrospective, single-center study compared landiolol to amiodarone for PoAF after cardiac surgery with a better hemodynamic stability and a higher rate of reduction to sinus rhythm with landiolol, justifying the need for a multicenter randomized controlled trial. Our aim is to compare landiolol to amiodarone in the setting of PoAF after cardiac surgery with the hypothesis of a higher rate of reduction to sinus rhythm with landiolol during the 48 h after the first episode of POAF. METHODS: The FAAC trial is a multicenter single-blind two parallel-arm randomized study, which planned to include 350 patients with a first episode of PoAF following cardiac surgery. The duration of the study is 2 years. The patients are randomized in two arms: a landiolol group and an amiodarone group. Randomization (Ennov Clinical®) is performed by the anesthesiologist in charge of the patient if PoAF is persistent for at least 30 min after correction of hypovolemia, dyskalemia, and absence of pericardial effusion on a transthoracic echocardiography done at bedside. Our hypothesis is an increase of the percentage of patients in sinus rhythm from 70 to 85% with landiolol in less than 48 h after onset of PoAF (alpha risk = 5%, power = 90%, bilateral test). DISCUSSION: The FAAC trial was approved by the Ethics Committee of EST III with approval number 19.05.08. The FAAC trial is the first randomized controlled trial comparing landiolol to amiodarone for PoAF after cardiac surgery. In case of higher rate of reduction with landiolol, this beta-blocker could be the drug of choice used in this context as to reduce the need for anticoagulant therapy and reduce the risk of complications of anticoagulant therapy for patients with a first episode of postoperative atrial fibrillation after cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT04223739. Registered on January 10, 2020.

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.

Respiratory Exchange Ratio guided management in high-risk noncardiac surgery: The OPHIQUE multicentre randomised controlled trial.

BACKGROUND: There is a need to develop non-invasive markers to identify the occurrence of anaerobic metabolism in high-risk surgery. Our objective was to demonstrate that a goal-directed therapy algorithm incorporating the respiratory exchange ratio (ratio between CO2 production and O2 consumption) can reduce postoperative complications. METHODS: We conducted a randomized, multicenter, controlled clinical trial in four university medical centers and one non-university hospital from December 26, 2018, to September 9, 2021. 350 patients with a high risk of postoperative complications undergoing high-risk noncardiac surgery lasting 2 h or longer under general anesthesia were enrolled. The control group was treated according to current hemodynamic guidelines. The interventional group was treated according to an algorithm based on the measurement of the respiratory exchange ratio. The primary outcome was a composite of major complications or death within seven days of surgery. The secondary outcomes were the length of hospital stay, 30-day mortality, and the total intraoperative volume of fluids administered. RESULTS: The primary outcome occurred for 78 patients (45.6%) in the interventional group and 83 patients (48.8%) in the control group (relative risk: 0.93, 95% confidence interval [CI]: 0.75-1.17; p = 0.55). There were no clinically relevant differences between the two groups for secondary outcomes. CONCLUSIONS: In high-risk surgery, a goal-directed therapy algorithm integrating the measurement of the respiratory-exchange ratio did not reduce a composite outcome of major postoperative complications or death within seven days after surgery compared to routine care. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03852147.

David Procedure: A 21-year Experience With 300 Patients.

BACKGROUND: Valve-sparing aortic root replacement with the David procedure is an alternative to the Bentall procedure in patients with aortic root aneurysm. The aim of this study was to describe our long-term experience with this technique and the predictive factors of late failure. METHODS: Between January 1998 and August 2019, 300 consecutive patients underwent a David procedure. Clinical and echocardiographic early- and long-term outcomes were analyzed. Median follow-up was 7.0 years (range, 4.1-11.5), with 98.3% complete. RESULTS: Early mortality was 1%. No early valve-related reoperations occurred. There were 9 cardiac-related deaths and 22 reinterventions (19 valve-related). All patients survived reoperation. In 3 patients reintervention consisted of transcatheter aortic valve implantation. Overall survival rates were 95.3% (95% confidence interval [CI], 92.0-97.2), 91.1% (95% CI, 86.5-94.2), and 82.9% (95% CI, 75.3-88.4) at 5, 10, and 15 years, respectively. Freedom from postoperative aortic insufficiency (AI) grade ≥ 2 was 84.8% (95% CI, 79.9-88.6) and 74.3% (95% CI, 67.4-79.9) at 5 and 10 years, respectively. Freedom from reintervention for aortic valve disease was 97.1% (95% CI, 94.2-98.5), 92.9% (95% CI, 88.2-95.7), and 92.5% (95% CI, 87.1-95.7) at 5, 10, and 15 years, respectively. Preoperative AI ≥ 2 (hazard ratio, 1.782; 95% CI, 1.352-2.350) and a ventriculoaortic junction ≥ 29 mm (hazard ratio, 3.379; 95% CI, 1.726-6.616) were predictive factors for postoperative AI ≥ 2 in a multivariate analysis (P < .001). CONCLUSIONS: Preoperative AI ≥ 2 and a ventriculoaortic junction ≥ 29 mm were identified as risk factors for late postoperative AI ≥ 2.

Development and usage of an anesthesia data warehouse: lessons learnt from a 10-year project.

This paper describes the development and implementation of an anesthesia data warehouse in the Lille University Hospital. We share the lessons learned from a ten-year project and provide guidance for the implementation of such a project. Our clinical data warehouse is mainly fed with data collected by the anesthesia information management system and hospital discharge reports. The data warehouse stores historical and accurate data with an accuracy level of the day for administrative data, and of the second for monitoring data. Datamarts complete the architecture and provide secondary computed data and indicators, in order to execute queries faster and easily. Between 2010 and 2021, 636 784 anesthesia records were integrated for 353 152 patients. We reported the main concerns and barriers during the development of this project and we provided 8 tips to handle them. We have implemented our data warehouse into the OMOP common data model as a complementary downstream data model. The next step of the project will be to disseminate the use of the OMOP data model for anesthesia and critical care, and drive the trend towards federated learning to enhance collaborations and multicenter studies.

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.

Association between acute kidney injury and norepinephrine use following cardiac surgery: a retrospective propensity score-weighted analysis.

BACKGROUND: Excess exposure to norepinephrine can compromise microcirculation and organ function. We aimed to assess the association between norepinephrine exposure and acute kidney injury (AKI) and intensive care unit (ICU) mortality after cardiac surgery. METHODS: This retrospective observational study included adult patients who underwent cardiac surgery under cardiopulmonary bypass from January 1, 2008, to December 31, 2017, at the Amiens University Hospital in France. The primary exposure variable was postoperative norepinephrine during the ICU stay and the primary endpoint was the presence of AKI. The secondary endpoint was in-ICU mortality. As the cohort was nonrandom, inverse probability weighting (IPW) derived from propensity scores was used to reduce imbalances in the pre- and intra-operative characteristics. RESULTS: Among a population of 5053 patients, 1605 (32%) were exposed to norepinephrine following cardiac surgery. Before weighting, the prevalence of AKI was 25% and ICU mortality 10% for patients exposed to norepinephrine. Exposure to norepinephrine was estimated to be significantly associated with AKI by a factor of 1.95 (95% confidence interval, 1.63-2.34%; P < 0.001) in the IPW cohort and with in-ICU mortality by a factor of 1.54 (95% confidence interval, 1.19-1.99%; P < 0.001). CONCLUSION: Norepinephrine was associated with AKI and in-ICU mortality following cardiac surgery. While these results discourage norepinephrine use for vasoplegic syndrome in cardiac surgery, prospective investigations are needed to substantiate findings and to suggest alternative strategies for organ protection.

Hybrid closure of ventricular septal defect and implantation of systemic right ventricular assist device.

A 50-year-old female patient was readmitted with refractory systemic right ventricular failure. The patient underwent a Mustard procedure during childhood for transposition of the great arteries. A significant residual ventricular septal defect was present, which represents a major risk factor of death following ventricular assist device. We describe the combination of ventricular assist device implantation preceded by hybrid closure of ventricular septal defect.

Thrombus formation during ECMO: Insights from a detailed histological analysis of thrombus composition.

OBJECTIVES: Intra-device thrombosis remains one of the most common complications during extracorporeal membrane oxygenation (ECMO). Despite anticoagulation, approximately 35% of patients develop thrombi in the membrane oxygenator, pump heads, or tubing. The aim of this study was to describe the molecular and cellular features of ECMO thrombi and to study the main drivers of thrombus formation at different sites in the ECMO circuits. APPROACH AND RESULTS: Thrombi (n = 85) were collected immediately after veno-arterial-(VA)-ECMO circuit removal from 25 patients: 23 thrombi from the pump, 25 from the oxygenator, and 37 from the tubing. Quantitative histological analysis was performed for the amount of red blood cells (RBCs), platelets, fibrin, von Willebrand factor (VWF), leukocytes, and citrullinated histone H3 (H3Cit). ECMO thrombi consist of a heterogenous composition with fibrin and VWF being the major thrombus components. A clustering analysis of the four major histological parameters identified two typical thrombus types: RBC-rich and RBC-poor/fibrin-rich thrombi with no significant differences in VWF and platelet content. Thrombus composition was not associated with the thrombus location, except for higher amounts of H3Cit that were found in pump and oxygenator thrombi compared to tubing samples. We observed higher blood leukocyte count and lactate dehydrogenase levels in patients with fibrin-rich thrombi. CONCLUSION: We found that thrombus composition is heterogenous, independent of their location, consisting of two types: RBC-rich and a fibrin-rich types. We also found that NETs play a minor role. These findings are important to improve current anticoagulation strategies in ECMO.

Portal Vein Pulsatility Index as a Potential Risk of Venous Congestion Assessed by Magnetic Resonance Imaging: A Prospective Study on Healthy Volunteers.

High values of the portal vein pulsatility index (PI) have been associated with adverse outcomes in perioperative or critically ill patients. However, data on dynamic changes of PI related to fluid infusion are scarce. We aimed to determine if dynamic changes in PI are associated with the fluid challenge (FC). To address this challenge, we conducted a prospective single-center study. The population study included healthy subjects. FC consisted in the administration of 500 ml of Ringer lactate infusion over 5 min. The portal blood flow and PI were assessed by magnetic resonance imaging. The responsiveness to FC was defined as an increase in the cardiac stroke volume of at least 10% as assessed by echocardiography. We included 24 healthy volunteers. A total of fourteen (58%) subjects were responders, and 10 (42%) were non-responders. In the responder group, FC induced a significant increase in portal blood flow from 881 (762-1,001) at the baseline to 1,010 (778-1,106) ml min-1 (p = 0.005), whilst PI remained stable (from 31 [25-41] to 35 (25-42) %; p = 0.12). In the non-responder group, portal blood flow remained stable after FC (from 1,042 to 1,034 ml min-1; p = 0.084), whereas PI significantly increased from 32 (22-40) to 48% *(25-85) after FC (p = 0.027). PI was negatively correlated to portal blood flow (Rho coefficient = -0.611; p = 0.002). To conclude, PI might be a sensitive marker of early congestion in healthy subjects that did not respond to FC. This finding requires further validation in clinical settings with a larger sample size.

End-tidal Carbon Dioxide for Diagnosing Anaphylaxis in Patients with Severe Postinduction Hypotension.

BACKGROUND: Perioperative hypersensitivity reactions may be difficult to diagnose during general anesthesia. Postinduction hypotension is the most common sign but is not specific. It was recently suggested that low end-tidal carbon dioxide (ETco2) might be a marker of anaphylaxis (Ring and Messmer grades III to IV immediate hypersensitivity reactions) in hypotensive patients under mechanical ventilation. To test this hypothesis, the authors compared ETco2 in patients with a diagnosis of anaphylaxis and in patients with severe hypotension from any other cause after the induction of anesthesia. METHODS: This was a retrospective single-center case-control study in which two groups were formed from an anesthesia data warehouse. The anaphylaxis group was formed on the basis of tryptase/histamine assay data and allergy workup data recorded over the period 2010 to 2018. The control (hypotension) group consisted of all patients having experienced severe hypotension (mean arterial pressure less than 50 mmHg for 5 min or longer) with a cause other than anaphylaxis after anesthesia induction in 2017. RESULTS: The anaphylaxis and hypotension groups comprised 49 patients (grade III: n = 38; grade IV: n = 11) and 555 patients, respectively. The minimum ETco2 value was significantly lower in the anaphylaxis group (median [interquartile range]: 17 [12 to 23] mmHg) than in the hypotension group (32 [29 to 34] mmHg; P < 0.001). The area under the receiver operating characteristic curve (95% CI) for ETco2 was 0.95 (0.91 to 0.99). The sensitivity and specificity (95% CI) for the optimal cutoff value were 0.92 (0.82 to 0.98) and 0.94 (0.92 to 0.99), respectively. In multivariable analysis, minimum ETco2 was associated with anaphylaxis after adjusting for confounders and competing predictors, including arterial pressure, heart rate, and peak airway pressure (odds ratio [95% CI] for ETco2: 0.51 [0.38 to 0.68]; P < 0.001). CONCLUSIONS: In case of severe hypotension after anesthesia induction, a low ETco2 contributes to the diagnosis of anaphylaxis, in addition to the classical signs of perioperative immediate hypersensitivity.