Clinical Effectiveness of Transversus Abdominis Plane (TAP) Block versus Local Anesthesia Wound Infiltration for Postoperative Pain Relief After Laparoscopic Appendicectomy in Children: A Study Protocol for a Multicenter Double-Blind Randomized Controlled Phase III Trial.

Purpose: Postoperative pain relief after laparoscopic appendicectomy is a key determinant of early rehabilitation in children. Recent guidelines recommend performing either a transversus abdominis plane (TAP) block or local anesthesia (LA) wound infiltration as part of multimodal postoperative analgesia after appendectomy. To date, the clinical effectiveness of TAP block versus LA wound infiltration has never been compared. The hypothesis of this study is that the TAP block may provide a greater opioid-sparing effect after laparoscopic appendicectomy in children than LA wound infiltration. Study Design and Methods: We designed a multicenter double-blind randomized controlled phase III trial and aim to include 110 children who undergo laparoscopic appendicectomy. Children are randomized to receive either TAP block (TAP group) or LA wound infiltration (infiltration group). Multimodal analgesia is standardized in the two groups using the same protocol, which includes the stepwise prescription of paracetamol, phloroglucinol, ketoprofene, and nalbuphine according to the hetero-evaluation of pain performed by the nurses who were blinded to the treatment allocated using the validated FLACC scale. The primary outcome is the total dose of nalbuphine administered within 24 hours after surgery. Discussion: No study has specifically compared the clinical effectiveness of TAP block versus LA wound infiltration for postoperative pain relief after laparoscopic appendectomy in children. This paper describes the protocol for a randomized trial that addresses this issue. The results of this trial will be useful for editing guidelines with a higher level of evidence on this topic.

Oxygenation management during veno-arterial ECMO support for cardiogenic shock: a multicentric retrospective cohort study.

BACKGOUND: Hyperoxemia is common and associated with poor outcome during veno-arterial extracorporeal membrane oxygenation (VA ECMO) support for cardiogenic shock. However, little is known about practical daily management of oxygenation. Then, we aim to describe sweep gas oxygen fraction (FSO2), postoxygenator oxygen partial pressure (PPOSTO2), inspired oxygen fraction (FIO2), and right radial arterial oxygen partial pressure (PaO2) between day 1 and day 7 of peripheral VA ECMO support. We also aim to evaluate the association between oxygenation parameters and outcome. In this retrospective multicentric study, each participating center had to report data on the last 10 eligible patients for whom the ICU stay was terminated. Patients with extracorporeal cardiopulmonary resuscitation were excluded. Primary endpoint was individual mean FSO2 during the seven first days of ECMO support (FSO2 mean (day 1-7)). RESULTS: Between August 2019 and March 2022, 139 patients were enrolled in 14 ECMO centers in France, and one in Switzerland. Among them, the median value for FSO2 mean (day 1-7) was 70 [57; 79] % but varied according to center case volume. Compared to high volume centers, centers with less than 30 VA-ECMO runs per year were more likely to maintain FSO2 ≥ 70% (OR 5.04, CI 95% [1.39; 20.4], p = 0.017). Median value for right radial PaO2 mean (day 1-7) was 114 [92; 145] mmHg, and decreased from 125 [86; 207] mmHg at day 1, to 97 [81; 133] mmHg at day 3 (p < 0.01). Severe hyperoxemia (i.e. right radial PaO2 ≥ 300 mmHg) occurred in 16 patients (12%). PPOSTO2, a surrogate of the lower body oxygenation, was measured in only 39 patients (28%) among four centers. The median value of PPOSTO2 mean (day 1-7) value was 198 [169; 231] mmHg. By multivariate analysis, age (OR 1.07, CI95% [1.03-1.11], p < 0.001), FSO2 mean (day 1-3)(OR 1.03 [1.00-1.06], p = 0.039), and right radial PaO2 mean (day 1-3) (OR 1.03, CI95% [1.00-1.02], p = 0.023) were associated with in-ICU mortality. CONCLUSION: In a multicentric cohort of cardiogenic shock supported by VA ECMO, the median value for FSO2 mean (day 1-7) was 70 [57; 79] %. PPOSTO2 monitoring was infrequent and revealed significant hyperoxemia. Higher FSO2 mean (day 1-3) and right radial PaO2 mean (day 1-3) were independently associated with in-ICU mortality.

Prospective randomized double-blind study to evaluate the superiority of Vasopressin versus Norepinephrine in the management of the patient at renal risk undergoing cardiac surgery with cardiopulmonary bypass (NOVACC trial).

BACKGROUND: Cardiac surgery-associated acute kidney injury (CS-AKI) affects up to 30% of patients, increasing morbidity and healthcare costs. This condition results from complex factors like ischemia-reperfusion injury and renal hemodynamic changes, often exacerbated by surgical procedures. Norepinephrine, commonly used in cardiac surgeries, may heighten the risk of CS-AKI. In contrast, vasopressin, a noncatecholaminergic agent, shows potential in preserving renal function by favorably affecting renal hemodynamic. Preliminary findings, suggest vasopressin could reduce the incidence of CS-AKI compared to norepinephrine. Additionally, vasopressin is linked to a lower incidence of postoperative atrial fibrillation, another factor contributing to longer hospital stays and higher costs. This study hypothesizes that vasopressin could effectively reduce CS-AKI occurrence and severity by optimizing renal perfusion during cardiac surgeries. STUDY DESIGN: The NOVACC trial (NCT05568160) is a multicenter, randomized, double blinded superiority-controlled trial testing the superiority of vasopressin over norepinephrine in patients scheduled for cardiac surgery with cardiopulmonary bypass (CPB). The primary composite end point is the occurrence of acute kidney injury and death. The secondary end points are neurological, cardiologic, digestive, and vasopressor related complications at day 7, day 30, day 90, hospital and intensive care unit lengths of stay, medico-economic costs at day 90. CONCLUSION: The NOVACC trial will assess the effectiveness of vasopressin in cardiac surgery with CPB in reducing acute kidney injury, mortality, and medical costs. CLINICAL TRIAL REGISTRATION: NCT05568160.

Pulsatile Femoral Vein Doppler Pattern is a Parameter of Venous Congestion in ICU Patients.

OBJECTIVES: The aim of this study was to evaluate if the presence of a pulsatile femoral vein pattern is an indicator of venous congestion in the intensive care unit (ICU). DESIGN: Retrospective observational study. SETTING: Three medico-surgical university-affiliated ICUs. PARTICIPANTS: Adult patients who had an ultrasound evaluation at several time points during their ICU stay: at baseline (within 24 hours of admission to ICU), daily during their ICU stay, and within 24 hours before ICU discharge. INTERVENTIONS: At each time point, the hemodynamic, respiratory, and cardiac ultrasound parameters were recorded. The common femoral vein was studied with pulsed-wave Doppler at the level of the femoral trigonum, with high frequency (5-13 MHz) linear array vascular probe and venous vascular mode, in supine patients. MEASUREMENTS AND MAIN RESULTS: One hundred eight patients who underwent 400 ultrasound evaluations (3.7 ± 1 ultrasound evaluations per patient) during their ICU stay were included. Seventy-nine of 108 patients (73%) had a pulsatile femoral vein pattern at least at 1 time point. The multivariable mixed effects logistic regression model demonstrated an association among pulsatile femoral vein pattern, body mass index (OR: 0.91[95% CI 0.85-0.96], p = 0.002), inferior vena cava mean diameter (OR: 2.35 [95% CI 1.18-4.66], p = 0.014), portal vein pulsatility (OR: 2.3 [95% CI 1.2-4.4], p = 0.012), and congestive renal vein flow pattern (OR: 4.02 [95% CI 2.01-8.03], p < 0.001). The results were confirmed by principal component analysis. CONCLUSION: In the ICU, a pulsatile femoral vein pattern is associated with parameters of venous congestion, independently of the patient's volume status, and ventilatory treatment. These results suggest the femoral vein Doppler pulsatility as a parameter of congestion in ICU patients.

Exploring congestion endotypes and their distinct clinical outcomes among ICU patients: A post-hoc analysis.

BACKGROUND: In the intensive care unit (ICU) patients, fluid overload and congestion are associated with worse outcomes. Because of the heterogeneity of ICU patients, we hypothesized that there may exist different endotypes of congestion. The aim of this study was to identify endotypes of congestion and their association with outcomes. METHODS: We conducted an unsupervised hierarchical clustering analysis on 145 patients admitted to ICU to identify endotypes. We measured several parameters related to clinical context, volume status, filling pressure, and venous congestion. These parameters included NT-proBNP, central venous pressure (CVP), the mitral E/e' ratio, the systolic/diastolic ratio of hepatic veins' flow velocity, the mean diameter of the inferior vena cava (IVC) and its variations, stroke volume changes following passive leg raising, the portal vein pulsatility index, and the venous renal impedance index. RESULTS: Three distinct endotypes were identified: (1) "hemodynamic congestion" endotype (n = 75) with moderate alterations of ventricular function, increased CVP and left filling pressure values, and moderate fluid overload; (2) "volume overload congestion" endotype (n = 50); with normal cardiac function and filling pressure despite high positive fluid balance (fluid overload); (3) "systemic congestion" endotype (n = 20) with severe alterations of left and right ventricular functions, increased CVP and left ventricular filling pressure values. These endotypes vary significantly in ICU admission reasons, acute kidney injury rates, mortality, and length of ICU/hospital stay. CONCLUSIONS: Our analysis revealed three unique congestion endotypes in ICU patients, each with distinct pathophysiological features and outcomes. These endotypes are identifiable through key ultrasonographic characteristics at the bedside. CLINICAL TRIAL GOV: NCT04680728.

Healthcare-associated infections in patients with severe COVID-19 supported with extracorporeal membrane oxygenation: a nationwide cohort study.

BACKGROUND: Both critically ill patients with coronavirus disease 2019 (COVID-19) and patients receiving extracorporeal membrane oxygenation (ECMO) support exhibit a high incidence of healthcare-associated infections (HAI). However, data on incidence, microbiology, resistance patterns, and the impact of HAI on outcomes in patients receiving ECMO for severe COVID-19 remain limited. We aimed to report HAI incidence and microbiology in patients receiving ECMO for severe COVID-19 and to evaluate the impact of ECMO-associated infections (ECMO-AI) on in-hospital mortality. METHODS: For this study, we analyzed data from 701 patients included in the ECMOSARS registry which included COVID-19 patients supported by ECMO in France. RESULTS: Among 602 analyzed patients for whom HAI and hospital mortality data were available, 214 (36%) had ECMO-AI, resulting in an incidence rate of 27 ECMO-AI per 1000 ECMO days at risk. Of these, 154 patients had bloodstream infection (BSI) and 117 patients had ventilator-associated pneumonia (VAP). The responsible microorganisms were Enterobacteriaceae (34% for BSI and 48% for VAP), Enterococcus species (25% and 6%, respectively) and non-fermenting Gram-negative bacilli (13% and 20%, respectively). Fungal infections were also observed (10% for BSI and 3% for VAP), as were multidrug-resistant organisms (21% and 15%, respectively). Using a Cox multistate model, ECMO-AI were not found associated with hospital death (HR = 1.00 95% CI [0.79-1.26], p = 0.986). CONCLUSIONS: In a nationwide cohort of COVID-19 patients receiving ECMO support, we observed a high incidence of ECMO-AI. ECMO-AI were not found associated with hospital death. Trial registration number NCT04397588 (May 21, 2020).

Should the Vasoactive Inotropic Score be a Determinant for Early Initiation of VA ECMO in Postcardiotomy Cardiogenic Shock?

OBJECTIVES: The authors investigated the role of early venoarterial extracorporeal membrane oxygenation (VA ECMO) implantation in patients with postcardiotomy cardiogenic shock (PCS) on mortality and morbidity when integrating vasoactive-inotropic score (VIS) and type of catecholamine support. DESIGN: A retrospective, multicenter, observational study with propensity-weight matching. SETTING: Four university-affiliated intensive care units. PARTICIPANTS: Patients with PCS in the operating room. INTERVENTIONS: Early VA ECMO support. MEASUREMENTS AND MAIN RESULTS: Of 2,742 patients screened during the study period, 424 (16%) patients were treated with inotropic drugs, and 75 (3%) patients were supported by VA ECMO in the operating room. Patients supported by VA ECMO had a higher use of vasopressor and inotropic drugs, with a higher VIS score. After propensity matching (integrating VIS and catecholamines type), mortality (56% v 20%, p < 0.001) and morbidity (cardiac, renal, transfusion) were higher in patients supported by VA ECMO than in a matched control group. CONCLUSIONS: When matching integrated the pre-ECMO VIS and the type of catecholamines, VA ECMO remained associated with high mortality and morbidity, suggesting that VIS alone should not be used as a main determinant of VA ECMO implantation.

Mean systemic filling pressure and venous return to assess the effects of passive leg raising and volume expansion in acute circulatory failure patients: a posthoc analysis of a multi-centre prospective study.

BACKGROUND: The main aim of the study was to investigate the behaviours of the mean systemic filling pressure (Pmsf), calculated by the mathematical method, and its derived variables of venous return after volume expansion (VE) and passive leg raising (PLR), with analysis according to fluid and PLR responsiveness. METHODS: This was a post-hoc analysis of a multicentre prospective study. We included 202 mechanically ventilated patients with acute circulatory failure. Pmsf, dVR (difference between Pmsf and central venous pressure [CVP]), and resistance to venous return (RVR) were calculated before/after PLR and before/after VE. Fluid- and PLR-responsiveness were defined according to the increase in cardiac index (CI) >15% after VE and >10% after PLR, respectively. RESULTS: Pmsf increased significantly after VE and PLR in both fluid and PLR-responder and non-responder groups. In fluid-responder patients, the increase in dVR was significantly higher than in non-responder group (1.5 [IQR:1.0-2.0] vs. 0.3 [IQR:-0.1-0.6] mmHg, p < 0.001) because of the larger increase in CVP relative to Pmsf in the non-responder group. The same findings were observed after PLR. RVR significantly decreased only in the fluid-responder and PLR-responder groups after VE and PLR. CONCLUSIONS: Venous return, derived from the mathematical model, increased in preload-dependent patients after VE and PLR because of the larger increases in Pmsf relative to CVP and the decreases in RVR. In preload-independent patients, VR did not change because of the larger rise in CVP compared to Pmsf after VE and PLR. These findings agree with the physiological model of circulation described by Guyton.

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.

COVID-19 and the Concept of Thrombo-Inflammation: Review of the Relationship between Immune Response, Endothelium and Coagulation.

COVID-19, caused by the SARS-CoV-2 virus, has revealed a complex interplay between inflammation and coagulation, leading to the emergence of the concept of thrombo-inflammation. This concept recognizes that COVID-19 is not solely a respiratory illness, but a systemic disease with significant vascular and hematological components. COVID-19 is associated with an unusual prothrombotic state, with intense endothelial activation leading to vasculopathy, cytokine storm, complement system activation and a hypercoagulability state (the activation of platelets and the coagulation cascade, impaired fibrinolysis). The aim of this review is to discuss the different pathological pathways described in COVID-19 that lead to thromboembolic events. Widespread vaccination and post-COVID-19 immunization allows control over the severity of this pandemic. A better understanding of the pathophysiology of COVID-19 can improve the management of frail patients who are hospitalized in intensive care units.

Protocol Study for the Evaluation of Non-Opioid Balanced General Anaesthesia in Cardiac Surgery with Cardiopulmonary Bypass: A Randomised, Controlled, Multicentric Superiority Trial (OFACAR Study).

Opioid-free anaesthesia (OFA) is general anaesthesia based on the use of several non-opioid molecules that aim to have an analgesic effect, decrease the sympathetic response, decrease hormonal stress, and decrease the inflammatory response during surgery. Although this approach to anaesthesia is regularly used in clinical practice, it remains a novel approach. The literature on this anaesthesia modality finds a number of positive effects on cardiac, respiratory, and cognitive function but no randomised study evaluated these effects during cardiac surgery where there is a high incidence of postoperative complications. The main aim of the study is to compare OFA vs. standard balanced opioid general anaesthesia on the incidence of postoperative complications and the length of stay in intensive care and hospital. OFACAR is a multicentric, randomised, controlled, superiority, single-blind, two parallel-arm clinical trial in patients undergoing cardiac surgery with cardiopulmonary bypass. We compared a balanced general anaesthesia without opioids (OFA group) vs. a balanced opioid general anaesthesia with sufentanil (control group). One hundred and sixty patients will be enrolled in each treatment group. The primary endpoint is a composite one which corresponds to the occurrence of at least one of the postoperative complications, defined according to European standards within 30 days after surgery. Recruitment started in September 2019, and data collection is expected to end in November 2024.

Rotational Thromboelastometry Coagulation Parameters (ROTEM®) May be Discriminative for Active Inflammatory Bowel Disease: A Prospective Observational Study.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is associated with increased risk of thromboembolic events. The rotational thromboelastometry (ROTEM®) is a validated integrative assessment of coagulation, but it has never been studied in IBD patients. METHODS: We performed a monocentric prospective observational study in a national tertiary center. Adult IBD patients underwent ROTEM® analysis on admission to our IBD Department. Parameters evaluated with ROTEM® tests (INTEM, EXTEM and FIBTEM) were clotting time (CT), the time of clot formation (CFT), clot firmness amplitude after 5 and 10 minutes (A5 and A10) and maximum clot firmness (MCF). ROC curves were performed in order to evaluate the ability of ROTEM® to predict active IBD. RESULTS: Several ROTEM® parameters were significantly associated with active IBD compared to patients in remission, towards a hypercoagulable status for patients with active disease: CT, CFT, A5, A10, MCF. ROC analysis demonstrated that parameters related to clot robustness showed a very good prediction ability of active IBD (AUC >0.8): A5, A10, MCF in INTEM (p<0.001), in EXTEM (p<0.001) and MCF in FIBTEM (p<0.001). ROTEM® parameters showed high correlations with inflammation markers as C-reactive protein (CRP) and faecal calprotectin (FC). CONCLUSIONS: Our study showed that ROTEM® parameters are modified in patients with active IBD, being correlating with inflammation markers and demonstrating a high prediction ability of active IBD. Future research is needed to validate ROTEM® as a method to discriminate patterns of active IBD and to guide anticoagulant therapy in patients with active IBD.

Oesophageal-pericardial and atrio-oesophageal fistula complicating a pulmonary vein isolation procedure.

A 66-year-old man with a history of catheter ablation for atrial fibrillation presented with purulent cardiac tamponade, revealing an atrio-oesophageal fistula. He underwent successful endoscopic management. A few days later, the patient fell into a sudden coma due to multiple cerebral air embolisms, resulting from a fistula between the esophagus and the right superior pulmonary vein.

Effect of norepinephrine on the vascular waterfall and tissue perfusion in vasoplegic hypotensive patients: a prospective, observational, applied physiology study in cardiac surgery.

BACKGROUND: Norepinephrine is a commonly used drug for treating vasoplegic acute circulatory failure in ICU. The prediction of norepinephrine macro- and micro-circulatory response is complicated by its uneven receptors' distribution between the arterial and the venous structures, and by the presence of a physiological vascular waterfall (VW) that disconnects the arterial and the venous circulation in two pressure systems. The objectives of this study were to describe the VW in patients with arterial hypotension due to vasodilatory circulatory shock, and its behavior according to its response to norepinephrine infusion. METHODS: A prospective, observational, bi-centric study has included adult patients, for whom the physician decided to initiate norepinephrine during the six first hours following admission to the ICU after cardiac surgery, and unresponsive to a fluid challenge. The mean systemic pressure (MSP) and the critical closing pressure (CCP) were measured at inclusion and after norepinephrine infusion. RESULTS: Thirty patients were included. Norepinephrine increased arterial pressure and total peripheral resistances in all cohort. The cohort was dichotomized as VW responders (patients with a change of VW over the least significant change (≥ 93% increase in VW)), and as VW non-responders. In 19 (63%) of the 30 patients, VW increased from 3.47 [- 14.43;7.71] mmHg to 43.6 [25.8;48.1] mmHg, p < 0.001) with norepinephrine infusion, being classified as VW responders. The VW responders improved cardiac index (from 1.8 (0.6) L min-1 m-2 to 2.2 (0.5) L min-1 m-2, p = 0.002), capillary refill time (from to 4.2 (1.1) s to 3.1 (1) s, p = 0.006), and pCO2 gap (from 9 [7;10] mmHg to 6 [4;8] mmHg, p = 0.04). No baseline parameters were able to predict the VW response to norepinephrine. In comparison, VW non-responders did not significantly change the VW (from 5 [-5;16] mmHg to -2 [-12;15] mmHg, p = 0.17), cardiac index (from 1.6 (0.3) L min-1 m-2 to 1.8 (0.4) L min-1 m-2, p = 0.09) and capillary refill time (from 4.1 (1) s to 3.7 (1.4), p = 0.44). CONCLUSIONS: In post-cardiac surgery patients with vasoplegic arterial hypotension, the vascular waterfall is low. Norepinephrine did not systematically restore the vascular waterfall. Increase of the vascular waterfall was associated with an improvement of laboratory and clinical parameters of tissue perfusion.