Maintenance of beta-blockers and cardiac surgery-related outcomes: a prospective propensity-matched multicentre analysis.

BACKGROUND: We investigated the effects of maintaining beta-blockers on the day of surgery on the incidence of atrial fibrillation and postoperative acute kidney injury (AKI) in patients undergoing cardiac surgery. METHODS: We conducted a multicentre prospective observational study with propensity matching on patients treated with beta-blockers. We collected their baseline patient characteristics, comorbidities, and operative and postoperative outcomes. The endpoints were postoperative atrial fibrillation and AKI after cardiac surgery. RESULTS: Of the 1789 included patients, propensity matching led to 583 patients in each group. Maintenance of beta-blockers was not associated with a reduced risk of atrial fibrillation (odds ratio: 0.86 [95% confidence interval 0.66-1.14], P=0.335; 141 patients [24.2%] vs 126 patients [21.6%]). Sensitivity analysis did not demonstrate association between beta-blocker maintenance and atrial fibrillation after cardiac surgery (odds ratio: 0.93 [95% confidence interval: 0.72-1.22], P=0.625). Maintenance of beta-blockers was associated with a higher rate of norepinephrine use (415 [71.2%] vs 465 [79.8%], P=0.0001) and postoperative AKI (124 [21.3%] vs 159 [27.3%], P=0.0127). No statistically significant difference was observed in ICU length of stay. CONCLUSIONS: Maintenance of beta-blockers on the day of surgery was not associated with a reduced incidence of postoperative atrial fibrillation. However, maintenance of beta-blockers was associated with increased usage of vasopressors, potentially contributing to adverse postoperative renal events. CLINICAL TRIAL REGISTRATION: NCT04769752.

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.

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.

Thoracic ultrasound influences physiotherapist's clinical decision-making in respiratory management of critical care patients: a multicentre cohort study.

BACKGROUND: The potential influence of thoracic ultrasound on clinical decision-making by physiotherapists has never been studied. The aim of this study was to assess the impact of thoracic ultrasound on clinical decision-making by physiotherapists for critical care patients. METHODS: This prospective, observational multicentre study was conducted between May 2017 and November 2020 in four intensive care units in France and Australia. All hypoxemic patients consecutively admitted were enrolled. The primary outcome was the net reclassification improvement (NRI), quantifying how well the new model (physiotherapist's clinical decision-making including thoracic ultrasound) reclassifies subjects as compared with an old model (clinical assessment). Secondary outcomes were the factors associated with diagnostic concordance and physiotherapy treatment modification. RESULTS: A total of 151 patients were included in the analysis. The NRI for the modification of physiotherapist's clinical decisions was-40% (95% CI (-56 to -22%), p=0.02). Among the cases in which treatment was changed after ultrasound, 41% of changes were major (n=38). Using a multivariate analysis, the physiotherapist's confidence in their clinical diagnosis was associated with diagnostic concordance (adjusted OR=3.28 95% CI (1.30 to 8.71); p=0.014). Clinical diagnosis involving non-parenchymal conditions and clinical signs reflecting abolished lung ventilation were associated with diagnostic discordance (adjusted OR=0.06 95% CI (0.01 to 0.26), p<0.001; adjusted OR=0.26 95% CI (0.09 to 0.69), p=0.008; respectively). CONCLUSION: Thoracic ultrasound has a high impact on the clinical decision-making process by physiotherapists for critical care patients. TRIAL REGISTRATION NUMBER: NCT02881814; https://clinicaltrials.gov.

Inflammation and oxidative stress markers in type 2 diabetes patients with Advanced Carotid atherosclerosis.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a major global health issue and a significant risk factor for atherosclerosis. Atherosclerosis in T2DM patients has been associated with inflammation, insulin resistance, hyperglycemia, dyslipidemia, and oxidative stress. Identifying molecular features of atherosclerotic plaques in T2DM patients could provide valuable insights into the pathogenesis of the disease. METHODS: The MASCADI (Arachidonic Acid Metabolism in Carotid Stenosis Plaque in Diabetic Patients) study aimed to investigate the increase of 2-arachidonoyl-lysophatidylcholine (2-AA-LPC) in carotid plaques from T2DM and control patients and to explore its association with plaque vulnerability as well as with blood and intra-plaque biomarkers altered during diabetes. RESULTS: In a population of elderly, polymedicated patients with advanced stage of atherosclerosis, we found that T2DM patients had higher systemic inflammation markers, such as high-sensitivity C-reactive protein (hsCRP) and IL-1ß, higher levels of oxysterols, increased triglyceride levels, and decreased HDL levels as compared to control patients. Furthermore, 2-AA-LPC was significantly enriched in plaques from diabetic patients, suggesting its potential role in diabetic atherosclerosis. Interestingly, 2-AA-LPC was not associated with systemic markers related to diabetes, such as hsCRP, triglycerides, or HDL cholesterol. However, it was significantly correlated with the levels of inflammatory markers within the plaques such as lysophospholipids and 25-hydroxycholesterol, strengthening the link between local inflammation, arachidonic acid metabolism and diabetes. CONCLUSION: Our study is in line with a key role for inflammation in the pathogenesis of diabetic atherosclerosis and highlights the involvement of 2-AA-LPC. Further research is needed to better understand the local processes involved in the alteration of plaque composition in T2DM and to identify potential therapeutic targets. TRIAL REGISTRATION: The MASCADI was registered on ClinicalTrials.gov (clinical registration number: NCT03202823).

Prevalence of systemic venous congestion assessed by Venous Excess Ultrasound Grading System (VExUS) and association with acute kidney injury in a general ICU cohort: a prospective multicentric study.

BACKGROUND: The importance of assessing venous congestion in ICU patients is widely acknowledged, but its study is hampered by the lack of a practical evaluation tool. The Venous Excess Ultrasound Grading System (VExUS), based on a semi-quantitative combined ultrasound assessment, has been associated with acute kidney injury (AKI) in cardiac ICU patients. The objectives of this study were to assess the prevalence of congestion using VExUS in general ICU patients, and to evaluate the association between VExUS, AKI and death. METHODS: This prospective, observational study included adult patients within 24 h of ICU admission. VExUS and hemodynamic parameters were measured four times during the ICU stay: within 24 h of ICU admission, after day 1 (between 24 and 48 h), after day 2 (between 48 and 72 h), and last day of ICU stay. The prevalence of AKI during the first week in ICU and 28-day mortality were assessed. RESULTS: Among the 145 patients included, the percentage of patients with a VExUS score of 2 (moderate congestion) and 3 (severe congestion) was 16% and 6%, respectively. The prevalence did not change over the study period. There was no significant association between admission VExUS scores and AKI (p = 0.136) or 28-day mortality (p = 0.594). Admission VExUS ≥ 2 was not associated with AKI (OR 0.499, CI95% 0.21-1.17, p = 0.109) nor 28-day mortality (OR 0.75, CI95% 0.2-2.8, p = 0.669). The results were similar for VExUS scores measured at day 1 and day 2. CONCLUSIONS: In general ICU cohort the prevalence of moderate to severe venous congestion was low. Early assessment of systemic venous congestion using VExUS scores was not associated with the development of AKI or with 28-day mortality.

Combination of serum and peritoneal 1.3-beta-D-glucan can rule out intra-abdominal candidiasis in surgical critically ill patients: a multicenter prospective study.

BACKGROUND: Intra-abdominal candidiasis (IAC) is difficult to predict in critically ill patients with intra-abdominal infection, leading to the overuse of antifungal treatments. Serum and peritoneal 1.3-beta-D-glucan (sBDG and pBDG) have been proposed to confirm or invalidate the diagnosis of IAC, but clinical studies have reported inconsistent results, notably because of heterogeneous populations with a low IAC prevalence. This study aimed to identify a high-risk IAC population and evaluate pBDG and sBDG in diagnosing IAC. METHODS: This prospective multicenter noninterventional French study included consecutive critically ill patients undergoing abdominal surgery for abdominal sepsis. The primary objective was to establish the IAC prevalence. The secondary objective was to explore whether sBDG and pBDG could be used to diagnose IAC. Wako® beta-glucan test (WT, Fujifilm Wako Chemicals Europe, Neuss, Germany) was used for pBDG measurements. WT and Fungitell® beta-D-glucan assay (FA, Associate of Cape Cod, East Falmouth, USA) were used for sBDG measurements. RESULTS: Between 1 January 2020 and 31 December 2022, 199 patients were included. Patients were predominantly male (63%), with a median age of 66 [54-72] years. The IAC prevalence was 44% (87/199). The main IAC type was secondary peritonitis. Septic shock occurred in 63% of cases. After multivariate analysis, a nosocomial origin was associated with more IAC cases (P = 0.0399). The median pBDG level was significantly elevated in IAC (448 [107.5-1578.0] pg/ml) compared to non-IAC patients (133 [16.0-831.0] pg/ml), P = 0.0021. For a pBDG threshold of 45 pg/ml, the negative predictive value in assessing IAC was 82.3%. The median sBDG level with WT (n = 42) at day 1 was higher in IAC (5 [3.0-9.0] pg/ml) than in non-IAC patients (3 [3.0-3.0] pg/ml), P = 0.012. Similarly, median sBDG level with FA (n = 140) at day 1 was higher in IAC (104 [38.0-211.0] pg/ml) than in non-IAC patients (50 [23.0-141.0] pg/ml), P = 0.009. Combining a peritonitis score < 3, sBDG < 3.3 pg/ml (WT) and pBDG < 45 pg/ml (WT) yielded a negative predictive value of 100%. CONCLUSION: In critically ill patients with intra-abdominal infection requiring surgery, the IAC prevalence was 44%. Combining low sBDG and pBDG with a low peritonitis score effectively excluded IAC and could limit unnecessary antifungal agent exposure. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov (ID number 03997929, first registered on June 24, 2019).

Balanced Nonopioid General Anesthesia With Lidocaine Is Associated With Lower Postoperative Complications Compared With Balanced Opioid General Anesthesia With Sufentanil for Cardiac Surgery With Cardiopulmonary Bypass: A Propensity Matched Cohort Study.

BACKGROUND: There are no data on the effect of balanced nonopioid general anesthesia with lidocaine in cardiac surgery with cardiopulmonary bypass. The main study objective was to evaluate the association between nonopioid general balanced anesthesia and the postoperative complications in relation to opioid side effects. METHODS: Patients undergoing cardiac surgery with cardiopulmonary bypass between 2019 and 2021 were identified. After exclusion of patients for heart transplantation, left ventricular assistance device, and off-pump surgery, we classified patients according to an opioid general balanced anesthesia or a nonopioid balanced anesthesia with lidocaine. The primary outcome was a collapsed composite of postoperative complications that comprise respiratory failure and confusion, whereas secondary outcomes were acute renal injury, pneumoniae, death, intensive care unit (ICU), and hospital length of stay. RESULTS: We identified 859 patients exposed to opioid-balanced general anesthesia with lidocaine and 913 patients exposed to nonopioid-balanced general anesthesia. Propensity score matching yielded 772 individuals in each group with balanced baseline covariates. Two hundred thirty-six patients (30.5%) of the nonopioid-balanced general anesthesia versus 186 patients (24.1%) presented postoperative composite complications. The balanced lidocaine nonopioid general anesthesia group was associated with a lower proportion with the postoperative complication composite outcome OR, 0.72 (95% CI, 0.58-0.92; P = .027). The number of patients with acute renal injury, death, and hospital length of stay did not differ between the 2 groups. CONCLUSIONS: A balanced nonopioid general anesthesia protocol with lidocaine was associated with lower odds of postoperative complication composite outcome based on respiratory failure and confusion.

Diuretics depletion improves cardiac output and ventriculo-arterial coupling in congestive ICU patients during hemodynamic de-escalation.

PURPOSE: Congestion was shown to hamper organ perfusion, but the exact timing of diuretic initiation during hemodynamic de-escalation in shock is unclear. The aim of this study was to describe the hemodynamic effects of diuretic initiation in the stabilized shock. METHODS: We performed a monocentric, retrospective analysis, in a cardiovascular medico-surgical ICU. We included consecutive resuscitated adult patients, for whom the clinician decided to introduce loop diuretic treatment for clinical signs of fluid overload. The patients were hemodynamically evaluated at the moment of diuretic introduction and 24 h later. RESULTS: Seventy ICU patients were included in this study, with a median duration of ICU stay before diuretic initiation of 2 [1-3] days. 51(73%) patients were classified as congestive (central venous pressure > 12 mmHg). After treatment, the cardiac index increased towards normal values in the congestive group (2.7 ± 0.8 L min- 1 m- 2 from 2.5 ± 0.8 L min- 1 m- 2, p = 0.042), but not in the non-congestive group (2.7 ± 0.7 L min- 1 m- 2 from baseline 2.7 ± 0.8 L min- 1 m- 2, p = 0.968). A decrease in arterial lactate concentrations was observed in the congestive group (2.1 ± 2 mmol L- 1 vs. 1.3 ± 0.6 mmol L- 1, p < 0.001). The diuretic therapy was associated with an improvement of ventriculo-arterial coupling comparing with baseline values in the congestive group (1.69 ± 1 vs. 1.92 ± 1.5, p = 0.03). The norepinephrine use decreased in congestive patients (p = 0.021), but not in the non-congestive group (p = 0.467). CONCLUSION: The initiation of diuretics in ICU congestive patients with stabilized shock was associated with improvement of cardiac index, ventriculo-arterial coupling, and tissue perfusion parameter. These effects were not observed in non-congestive patients.

Doppler study of portal vein and renal venous velocity predict the appropriate fluid response to diuretic in ICU: a prospective observational echocardiographic evaluation.

BACKGROUND: Fluid overload and venous congestion are associated with morbi-mortality in the ICU (intensive care unit). Administration of diuretics to correct the fluid balance is common, although there is no strong relationship between the consequent fluid loss and clinical improvement. The aim of the study was to evaluate the ability of the portal pulsatility index, the renal venous impedance index, and the VEXUS score (venous ultrasound congestion score) to predict appropriate diuretic-induced fluid depletion. METHODS: The study had a prospective, observational, single-center observational design and was conducted in a university-affiliated medico-surgical ICU. Adult patients for whom the clinician decided to introduce loop diuretic treatment were included. Hemodynamic and ultrasound measurements (including the portal pulsatility index, renal venous impedance index and VEXUS score) were performed at inclusion and 2 hours after the initiation of the diuretics. The patients' characteristics were noted at inclusion, 24 h later, and at ICU discharge. The appropriate diuretic-induced fluid depletion was defined by a congestive score lower than 3 after diuretic fluid depletion. The congestive score included clinical and biological parameters of congestion. RESULTS: Eighty-one patients were included, and 43 (53%) patients presented with clinically significant congestion score at inclusion. Thirty-four patients (42%) had an appropriate response to diuretic-induced fluid depletion. None of the left- and right-sided echocardiographic parameters differed between the two groups. The baseline portal pulsatility index was the best predictor of appropriate response to diuretic-induced fluid depletion (AUC = 0.80, CI95%:0.70-0.92, p = 0.001), followed by the renal venous impedance index (AUC = 0.72, CI95% 0.61-0.84, p = 0.001). The baseline VEXUS score (AUC of 0.66 CI95% 0.53-0.79, p = 0.012) was poorly predictive of appropriate response to diuretic-induced fluid depletion. CONCLUSION: The portal pulsatility index and the renal venous impedance index were predictive of the appropriate response to diuretic-induced fluid depletion in ICU patients. The portal pulsatility index should be evaluated in future randomized studies.

Implementation of a regional multidisciplinary veno-venous extracorporeal membrane oxygenation unit improved survival: a historical cohort study.

PURPOSE: Veno-venous extracorporeal membrane oxygenation (vvECMO) is a highly invasive technique with a high risk of mortality. Based on reports of improved outcomes in high-volume ECMO centers, we established a regional vvECMO unit. The objective of this study was to evaluate how the vvECMO unit affected patient mortality rates. METHODS: This was a historical cohort study of all patients admitted to Dijon University Hospital and supported by vvECMO between January 2011 and June 2021. Patients managed with the vvECMO unit were compared with patients managed with non-vvECMO units. The primary outcome was 90-day mortality. RESULTS: Of 172 patients treated using vvECMO, 69% were men, and the median [interquartile range] age was 59 [48-66] yr. Of the 172 patients, 35 were treated in the vvECMO unit and 137 were treated elsewhere (110/137 before the unit was established and 27/137 after). Ninety-day mortality was lower in patients managed in the vvECMO unit (15/35, 43% vs 92/137, 67%; P = 0.005). Within the vvECMO unit, mortality rates were also lower for the subgroup of patients managed after the specialized unit was established (15/35, 43% vs 20/27, 74%; P = 0.002). After adjusting for baseline severity of illness at vvECMO initiation, the vvECMO unit was independently associated with a lower 90-day mortality rate (hazard ratio, 0.41; 95% confidence interval, 0.21 to 0.80). CONCLUSION: The establishment of a vvECMO unit was associated with reduced 90-day mortality. This improved survival may relate to patient selection, more specialized mechanical ventilation support, and/or improvement of vvECMO care.

RéSUMé: OBJECTIF: L'oxygénation par membrane extracorporelle veino-veineuse (ECMO-VV) est une technique hautement invasive qui s'accompagne d'un risque élevé de mortalité. Sur la base de comptes rendus faisant état d'améliorations des devenirs dans les centers pratiquant un volume important d'ECMO, nous avons mis en place une unité régionale d'ECMO-VV. L'objectif de cette étude était d'évaluer l'impact de l'unité d'ECMO-VV sur les taux de mortalité des patients. MéTHODE: Nous avons réalisé une étude de cohorte historique incluant tous les patients admis au CHU de Dijon et traités par ECMO-VV entre janvier 2011 et juin 2021. Les patients pris en charge par l'unité d'ECMO-VV ont été comparés aux patients pris en charge par d'autres unités. Le critère d'évaluation principal était la mortalité à 90 jours. RéSULTATS: Sur 172 patients traités par ECMO-VV, 69 % étaient des hommes et l'âge médian [écart interquartile] était de 59 [48-66] ans. Sur les 172 patients, 35 ont été traités par l'unité d'ECMO-VV et 137 ont été traités ailleurs (110/137 avant la création de l'unité et 27/137 après). La mortalité à 90 jours était plus faible chez les patients pris en charge par l'unité d'ECMO-VV (15/35, 43 % vs 92/137, 67 %; P = 0,005). Au sein de l'unité d'ECMO-VV, les taux de mortalité étaient également plus faibles pour le sous-groupe de patients pris en charge après la création de l'unité spécialisée (15/35, 43 % vs 20/27, 74 %; P = 0,002). Après ajustement pour tenir compte de la gravité initiale de la maladie à la mise en place de l'ECMO-VV, l'unité d'ECMO-VV était indépendamment associée à un taux de mortalité plus faible à 90 jours (rapport de risque, 0,41; intervalle de confiance à 95 %, 0,21 à 0,80). CONCLUSION: La mise en place d'une unité d'ECMO-VV a été associée à une réduction de la mortalité à 90 jours. Cette amélioration de la survie peut être liée à la sélection des patients, à un soutien par ventilation mécanique plus spécialisé et /ou à l'amélioration des soins d'ECMO-VV.

Increased Weight Gain and Insulin Resistance in HF-Fed PLTP Deficient Mice Is Related to Altered Inflammatory Response and Plasma Transport of Gut-Derived LPS.

Bacterial lipopolysaccharides (LPS, endotoxins) are found in high amounts in the gut lumen. LPS can cross the gut barrier and pass into the blood (endotoxemia), leading to low-grade inflammation, a common scheme in metabolic diseases. Phospholipid transfer protein (PLTP) can transfer circulating LPS to plasma lipoproteins, thereby promoting its detoxification. However, the impact of PLTP on the metabolic fate and biological effects of gut-derived LPS is unknown. This study aimed to investigate the influence of PLTP on low-grade inflammation, obesity and insulin resistance in relationship with LPS intestinal translocation and metabolic endotoxemia. Wild-type (WT) mice were compared with Pltp-deficient mice (Pltp-KO) after a 4-month high-fat (HF) diet or oral administration of labeled LPS. On a HF diet, Pltp-KO mice showed increased weight gain, adiposity, insulin resistance, lipid abnormalities and inflammation, together with a higher exposure to endotoxemia compared to WT mice. After oral administration of LPS, PLTP deficiency led to increased intestinal translocation and decreased association of LPS to lipoproteins, together with an altered catabolism of triglyceride-rich lipoproteins (TRL). Our results show that PLTP, by modulating the intestinal translocation of LPS and plasma processing of TRL-bound LPS, has a major impact on low-grade inflammation and the onset of diet-induced metabolic disorders.

Are adipokines the missing link between obesity, immune response, and outcomes in severe COVID-19?

INTRODUCTION: Obesity is commonly reported in COVID-19 patients and is associated with poorer outcomes. It is suggested that leptin could be the missing link between obesity and severe COVID-19. Our study aimed to unravel the link between adipokines, COVID-19 status, immune response, and outcomes in severe pneumonia. METHODS: In this prospective observational single-center study, 63 immunocompetent patients with severe pneumonia (36 non-COVID-19 and 27 COVID-19) were enrolled, most required intensive care. Clinical and biological characteristics (glucose metabolism, plasma adipokines, and cytokine concentrations) and outcomes were compared. RESULTS: At similar baseline severity, COVID-19 patients required mechanical ventilation for significantly longer than non-COVID-19 patients (p = 0.0049). Plasma concentrations of leptin and adiponectin were respectively positively and negatively correlated with BMI and glucose metabolism (glycemia and insulinemia), but not significantly different between the two groups. Leptin levels were negatively correlated with IL-1ß and IL-6, but the adipokines were not correlated with most other inflammatory mediators, baseline severity (SOFA score), or the duration of mechanical ventilation. CONCLUSION: Adipokine levels were correlated with BMI but not with most inflammatory mediators, severity, or outcomes in severe pneumonia, regardless of the origin. The link between obesity, dysregulated immune response, and life-threatening COVID-19 requires further investigation. CLINICAL TRIAL: ClinicalTrials.gov: NCT03505281.

The dysregulated innate immune response in severe COVID-19 pneumonia that could drive poorer outcome.

BACKGROUND: Although immune modulation is a promising therapeutic avenue in coronavirus disease 2019 (COVID-19), the most relevant targets remain to be found. COVID-19 has peculiar characteristics and outcomes, suggesting a unique immunopathogenesis. METHODS: Thirty-six immunocompetent non-COVID-19 and 27 COVID-19 patients with severe pneumonia were prospectively enrolled in a single center, most requiring intensive care. Clinical and biological characteristics (including T cell phenotype and function and plasma concentrations of 30 cytokines) and outcomes were compared. RESULTS: At similar baseline respiratory severity, COVID-19 patients required mechanical ventilation for significantly longer than non-COVID-19 patients (15 [7-22] vs. 4 (0-15) days; p = 0.0049). COVID-19 patients had lower levels of most classical inflammatory cytokines (G-CSF, CCL20, IL-1ß, IL-2, IL-6, IL-8, IL-15, TNF-α, TGF-ß), but higher plasma concentrations of CXCL10, GM-CSF and CCL5, compared to non-COVID-19 patients. COVID-19 patients displayed similar T-cell exhaustion to non-COVID-19 patients, but with a more unbalanced inflammatory/anti-inflammatory cytokine response (IL-6/IL-10 and TNF-α/IL-10 ratios). Principal component analysis identified two main patterns, with a clear distinction between non-COVID-19 and COVID-19 patients. Multivariate regression analysis confirmed that GM-CSF, CXCL10 and IL-10 levels were independently associated with the duration of mechanical ventilation. CONCLUSION: We identified a unique cytokine response, with higher plasma GM-CSF and CXCL10 in COVID-19 patients that were independently associated with the longer duration of mechanical ventilation. These cytokines could represent the dysregulated immune response in severe COVID-19, as well as promising therapeutic targets. ClinicalTrials.gov: NCT03505281.

Glucagon-like peptide-1 is associated with poor clinical outcome, lipopolysaccharide translocation and inflammation in patients undergoing cardiac surgery with cardiopulmonary bypass.

INTRODUCTION: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with gut barrier dysfunction. Gut barrier dysfunction might be estimated non-invasively by lipopolysaccharide (LPS) plasma concentration. Glucagon-like peptide-1 (GLP-1) is a gut secreted hormone that is a potential marker of mucosal integrity. Our objective was to evaluate GLP-1 as a peri-operative marker of gut barrier dysfunction in patients undergoing cardiac surgery with CPB. METHODS: GLP-1, intestinal fatty acid binding protein (I-FABP) and lipopolysaccharide were assayed: at induction, after CPB and 24 h after admission in the intensive care unit. The primary end-point was peri-operative lipopolysaccharide concentration (LPS concentration at those 3 time points). RESULTS: Seventy-two patients were included in the present analysis. The highest measured post-operative GLP-1 concentration was in the sample taken 24 h after admission to intensive care, which was associated with peri-operative lipopolysaccharide plasma concentration. Patients who had the highest GLP-1 concentrations at 24 h experienced more severe inflammation and worse clinical outcomes. CONCLUSION: Our study supports that GLP-1 is not only a hormone of glucose metabolism but is also secreted when gut barrier is impaired in cardiac surgery with CPB. The GLP-1 levels measured 24 h after admission to the intensive care unit were associated with LPS concentration, inflammation and clinical outcomes.

CXCL10 could drive longer duration of mechanical ventilation during COVID-19 ARDS.

BACKGROUND: COVID-19-related ARDS has unique features when compared with ARDS from other origins, suggesting a distinctive inflammatory pathogenesis. Data regarding the host response within the lung are sparse. The objective is to compare alveolar and systemic inflammation response patterns, mitochondrial alarmin release, and outcomes according to ARDS etiology (i.e., COVID-19 vs. non-COVID-19). METHODS: Bronchoalveolar lavage fluid and plasma were obtained from 7 control, 7 non-COVID-19 ARDS, and 14 COVID-19 ARDS patients. Clinical data, plasma, and epithelial lining fluid (ELF) concentrations of 45 inflammatory mediators and cell-free mitochondrial DNA were measured and compared. RESULTS: COVID-19 ARDS patients required mechanical ventilation (MV) for significantly longer, even after adjustment for potential confounders. There was a trend toward higher concentrations of plasma CCL5, CXCL2, CXCL10, CD40 ligand, IL-10, and GM-CSF, and ELF concentrations of CXCL1, CXCL10, granzyme B, TRAIL, and EGF in the COVID-19 ARDS group compared with the non-COVID-19 ARDS group. Plasma and ELF CXCL10 concentrations were independently associated with the number of ventilator-free days, without correlation between ELF CXCL-10 and viral load. Mitochondrial DNA plasma and ELF concentrations were elevated in all ARDS patients, with no differences between the two groups. ELF concentrations of mitochondrial DNA were correlated with alveolar cell counts, as well as IL-8 and IL-1ß concentrations. CONCLUSION: CXCL10 could be one key mediator involved in the dysregulated immune response. It should be evaluated as a candidate biomarker that may predict the duration of MV in COVID-19 ARDS patients. Targeting the CXCL10-CXCR3 axis could also be considered as a new therapeutic approach. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03955887.

Predicting postoperative complications with the respiratory exchange ratio after high-risk noncardiac surgery: A prospective cohort study.

BACKGROUND: The respiratory exchange ratio (RER), defined as the ratio of CO2 production (VCO2) to O2 consumption (VO2), is reported to be a noninvasive marker of anaerobic metabolism. The intubated, ventilated patient's inspired and expired fractions of O2 and CO2 (FiO2, FeO2, FiCO2 and FeCO2) are monitored in the operating room and can be used to calculate RER. OBJECTIVE: To investigating the ability of the RER to predict postoperative complications. DESIGN: An observational, prospective study. SETTING: Two French university hospitals between March 2017 and September 2018. PATIENTS: A total of 110 patients undergoing noncardiac high-risk surgery. MAIN OUTCOME MEASURES: The RER was calculated as (FeCO2 - FiCO2)/(FiO2 - FeO2) at five time points during the operation. The primary endpoint was at the end of the surgery. The secondary endpoints were systemic oxygenation indices (pCO2 gap, pCO2 gap/arteriovenous difference in O2 ratio, central venous oxygen saturation) and the arterial lactate level at the end of the surgery. Complications were classified according to the European Peri-operative Clinical Outcome definitions. RESULTS: Postoperative complications occurred in 35 patients (34%). The median [interquartile range] RER at the end of surgery was significantly greater in the subgroup with complications, 1.06 [0.84 to 1.35] than in the subgroup without complications, 0.81 [0.75 to 0.91], and correlated significantly with the arterial lactate (r = 0.31, P < 0.001) and VO2 (r = -0.23, P = 0.001). Analysis of the area under the receiver operating characteristic curve for the predictive value of RER for postoperative complications revealed a value of 0.77 [95% confidence interval (CI) 0.69 to 0.88, P = 0.001]. The best cut-off for the RER was 0.94, with a sensitivity of 71% (95% CI 54 to 85) and a specificity of 79% (95% CI 68 to 88). CONCLUSION: As a putative noninvasive marker of tissue hypoperfusion and anaerobic metabolism, the RER can be used to predict complications following high-risk surgery. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03471962.

Agreement between different non-invasive methods of ventricular elastance assessment for the monitoring of ventricular-arterial coupling in intensive care.

Ventricular-arterial coupling is calculated as the arterial elastance to end systolic elastance ratio (EA/Ees). Although the gold standard is invasive pressure volume loop analysis, Chen method is the clinical reference non-invasive method for estimating end systolic elastance (Ees). Several simplified methods calculate Ees from the end systolic pressure to volume ratio (ESP/ESV). The objective of the present study was to determine whether ESP/ESV simplification can be used instead of the Chen formula to measure ventricular-arterial coupling and to monitor changes following therapeutic intervention. In this retrospective, single-center study, 3 non-invasive EA/Ees calculation methods were applied to 86 cardiac ICU patients. The Chen method was used as the reference method. Ees was also calculated according to method 1: Ees1 = 0.9 × SAP/ESV and method 2: Ees2= EA/(1/LVEF) - 1. EA was estimated as 0.9 × SAP/SV (mmHg ml-1). After simplification: EA/Ees1 = EA/Ees2 = (1/LVEF) - 1, with the stroke volume estimated as the product of the aortic velocity-time integral (VTIAo) and the aortic area or as the difference between the end diastolic volume (EDV) and the ESV. All patients received fluid infusion, norepinephrine, or dobutamine. At baseline, the concordance correlation coefficient with EA/EesChen was 0.13 [- 0.07; 0.31] for EA/Ees1 and 0.32 [0.19; 0.44] for EA/Ees2. Bias and limit of agreement were 0.28 [- 0.02; 0.36] and [- 5.8; 2.6] for EA/Ees1 and of 0.44 [0.31; 0.53] and [- 3.2; 2.6] for EA/Ees2. When used to follow variations in EA/Ees following therapeutic interventions, only 65% (for EA/Ees1) and 70% (for EA/Ees2) of measures followed the same trend as EA/EesChen. Our results do not support the use of ESP/ESV based method as substitute for Chen method to measure and assess changes in ventriculo-arterial coupling (EA/Ees) in cardiac intensive care patients. Further investigations are needed to establish the most reliable non-invasive method.

Effect of opioid-free anaesthesia on post-operative period in cardiac surgery: a retrospective matched case-control study.

BACKGROUND: No study has been conducted to demonstrate the feasibility of an opioid-free anesthesia (OFA) protocol in cardiac surgery to improve patient care. The aim of the present study was to evaluate the effect of OFA on post-operative morphine consumption and the post-operative course. METHODS: After retrospectively registering to clinicaltrial.gov (NCT03816592), we performed a retrospective matched cohort study (1:1) on cardiac surgery patients with cardiopulmonary bypass between 2018 and 2019. Patients were divided into two groups: OFA (lidocaine, dexamethasone and ketamine) or opioid anaesthesia (OA) (sufentanil). The main outcome was the total postoperative morphine consumption in the 48 h after surgery. Secondary outcomes were rescue analgesic use, a major adverse event composite endpoint, and ICU and hospital length of stay (LOS). RESULTS: One hundred ten patients were matched (OFA: n = 55; OA: n = 55). On inclusion, demographic and surgical data for the OFA and OA groups were comparable. The total morphine consumption was higher in the OA group than in the OFA group (15 (6-34) vs 5 mg (2-18), p = 0.001). The pain score during the first 48 post-operative hours did not differ between the two groups. Creatinine values did not differ on the first post-operative day (80 (IQR: 66-115) vs 77 mmol/l (IQR: 69-95), p = 0.284). Incidence of the composite endpoint was lower in the OFA group (25 patients (43%) vs 38 patients (68%), p = 0.021). The time to extubation and the ICU stays were shorter in the OFA group (3 (1-5) vs 5 (3-6) hours, p = 0.001 and 2 (1-3) vs 3 (2-5) days, p = 0.037). CONCLUSION: The use of OFA was associated with lower morphine consumption. OFA might be associated with shorter intubation time and ICU stays. Further randomized studies are needed to confirm these results. TRIAL REGISTRATION: This study was retrospectively registered to ct2 (identifier: NCT03816592 ) on January 25, 2019.