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.

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.

Liberal or Conservative Oxygen Therapy for Acute Respiratory Distress Syndrome.

BACKGROUND: In patients with acute respiratory distress syndrome (ARDS), the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network recommends a target partial pressure of arterial oxygen (Pao2) between 55 and 80 mm Hg. Prospective validation of this range in patients with ARDS is lacking. We hypothesized that targeting the lower limit of this range would improve outcomes in patients with ARDS. METHODS: In this multicenter, randomized trial, we assigned patients with ARDS to receive either conservative oxygen therapy (target Pao2, 55 to 70 mm Hg; oxygen saturation as measured by pulse oximetry [Spo2], 88 to 92%) or liberal oxygen therapy (target Pao2, 90 to 105 mm Hg; Spo2, ≥96%) for 7 days. The same mechanical-ventilation strategies were used in both groups. The primary outcome was death from any cause at 28 days. RESULTS: After the enrollment of 205 patients, the trial was prematurely stopped by the data and safety monitoring board because of safety concerns and a low likelihood of a significant difference between the two groups in the primary outcome. Four patients who did not meet the eligibility criteria were excluded. At day 28, a total of 34 of 99 patients (34.3%) in the conservative-oxygen group and 27 of 102 patients (26.5%) in the liberal-oxygen group had died (difference, 7.8 percentage points; 95% confidence interval [CI], -4.8 to 20.6). At day 90, 44.4% of the patients in the conservative-oxygen group and 30.4% of the patients in the liberal-oxygen group had died (difference, 14.0 percentage points; 95% CI, 0.7 to 27.2). Five mesenteric ischemic events occurred in the conservative-oxygen group. CONCLUSIONS: Among patients with ARDS, early exposure to a conservative-oxygenation strategy with a Pao2 between 55 and 70 mm Hg did not increase survival at 28 days. (Funded by the French Ministry of Health; LOCO2 ClinicalTrials.gov number, NCT02713451.).

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.

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.

Diaphragm function in patients with sepsis and septic shock: A longitudinal ultrasound study.

BACKGROUND: Previous literature on the determinants of diaphragm dysfunction in septic patients is limited. The goal of this study is to assess diaphragm dysfunction in terms of its prevalence and its potential associated factors in septic intensive care unit (ICU) patients. METHODS: This prospective and observational study was conducted between June 2015 and July 2019. Ultrasound measures of diaphragm thickness were performed daily on septic patients. The primary outcome was the prevalence of diaphragm dysfunction at baseline and during the ICU stay. The secondary outcome was the diaphragm thickness. Possible associated factors were prospectively recorded. RESULTS: Fifty patients were enrolled in the study. The prevalence of diaphragm dysfunction was 58%. No diaphragm atrophy was found during the ICU stay. Diaphragm dysfunction was associated with the alteration of consciousness, intra-abdominal sepsis, hypnotics and opioids, and mechanical ventilation. Administration of hypnotics, opioids, and steroids was associated with a decreased diaphragm thickening fraction. Diaphragm dysfunction had no impact on patient outcomes. CONCLUSIONS: Our data reveal a high prevalence of diaphragm dysfunction in septic patients at the onset of sepsis. Administration of hypnotics, opioids, and steroids was associated with the alteration of diaphragm function as well as intra-abdominal sepsis.

The weaning from mechanical ventilation: a comprehensive ultrasound approach.

PURPOSE OF REVIEW: Due to heart, lung and diaphragm interactions during weaning from mechanical ventilation, an ultrasound integrated approach may be useful in the detection of dysfunctions potentially leading to weaning failure. In this review, we will summarize the most recent advances concerning the ultrasound applications relevant to the weaning from mechanical ventilation. RECENT FINDINGS: The role of ultrasonographic examination of heart, lung and diaphragm has been deeply investigated over the years. Most recent findings concern the ability of lung ultrasound in detecting weaning induced pulmonary edema during spontaneous breathing trial. Furthermore, in patients at high risk of cardiac impairments, global and anterolateral lung ultrasound scores have been correlated with weaning and extubation failure, whereas echocardiographic indexes were not. For diaphragmatic ultrasound evaluation, new indexes have been proposed for the evaluation of diaphragm performance during weaning, but further studies are needed to validate these results. SUMMARY: The present review summarizes the potential role of ultrasonography in the weaning process. A multimodal integrated approach allows the clinician to comprehend the pathophysiological processes of weaning failure.

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.

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

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

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.

Quantitative Lung Ultrasound: Technical Aspects and Clinical Applications.

Lung ultrasound is increasingly used in emergency departments, medical wards, and critical care units-adult, pediatric, and neonatal. In vitro and in vivo studies show that the number and type of artifacts visualized change with lung density. This has led to the idea of a quantitative lung ultrasound approach, opening up new prospects for use not only as a diagnostic but also as a monitoring tool. Consequently, the multiple scoring systems proposed in the last few years have different technical approaches and specific clinical indications, adaptable for more or less time-dependent patients. However, multiple scoring systems may generate confusion among physicians aiming at introducing lung ultrasound in their clinical practice. This review describes the various lung ultrasound scoring systems and aims to clarify their use in different settings, focusing on technical aspects, validation with reference techniques, and clinical applications.

Lung Ultrasound Findings in the Postanesthesia Care Unit Are Associated With Outcome After Major Surgery: A Prospective Observational Study in a High-Risk Cohort.

BACKGROUND: Postoperative pulmonary complications are associated with increased morbidity. Identifying patients at higher risk for such complications may allow preemptive treatment. METHODS: Patients with an American Society of Anesthesiologists (ASA) score >1 and who were scheduled for major surgery of >2 hours were enrolled in a single-center prospective study. After extubation, lung ultrasound was performed after a median time of 60 minutes by 2 certified anesthesiologists in the postanesthesia care unit after a standardized tracheal extubation. Postoperative pulmonary complications occurring within 8 postoperative days were recorded. The association between lung ultrasound findings and postoperative pulmonary complications was analyzed using logistic regression models. RESULTS: Among the 327 patients included, 69 (19%) developed postoperative pulmonary complications. The lung ultrasound score was higher in the patients who developed postoperative pulmonary complications (12 [7-18] vs 8 [4-12]; P < .001). The odds ratio for pulmonary complications in patients who had a pleural effusion detected by lung ultrasound was 3.7 (95% confidence interval, 1.2-11.7). The hospital death rate was also higher in patients with pleural effusions (22% vs 1.3%; P < .001). Patients with pulmonary consolidations on lung ultrasound had a higher risk of postoperative mechanical ventilation (17% vs 5.1%; P = .001). In all patients, the area under the curve for predicting postoperative pulmonary complications was 0.64 (95% confidence interval, 0.57-0.71). CONCLUSIONS: When lung ultrasound is performed precociously <2 hours after extubation, detection of immediate postoperative alveolar consolidation and pleural effusion by lung ultrasound is associated with postoperative pulmonary complications and morbi-mortality. Further study is needed to determine the effect of ultrasound-guided intervention for patients at high risk of postoperative pulmonary complications.

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.