Convalescent Plasma for Covid-19-Induced ARDS in Mechanically Ventilated Patients.

BACKGROUND: Passive immunization with plasma collected from convalescent patients has been regularly used to treat coronavirus disease 2019 (Covid-19). Minimal data are available regarding the use of convalescent plasma in patients with Covid-19-induced acute respiratory distress syndrome (ARDS). METHODS: In this open-label trial, we randomly assigned adult patients with Covid-19-induced ARDS who had been receiving invasive mechanical ventilation for less than 5 days in a 1:1 ratio to receive either convalescent plasma with a neutralizing antibody titer of at least 1:320 or standard care alone. Randomization was stratified according to the time from tracheal intubation to inclusion. The primary outcome was death by day 28. RESULTS: A total of 475 patients underwent randomization from September 2020 through March 2022. Overall, 237 patients were assigned to receive convalescent plasma and 238 to receive standard care. Owing to a shortage of convalescent plasma, a neutralizing antibody titer of 1:160 was administered to 17.7% of the patients in the convalescent-plasma group. Glucocorticoids were administered to 466 patients (98.1%). At day 28, mortality was 35.4% in the convalescent-plasma group and 45.0% in the standard-care group (P = 0.03). In a prespecified analysis, this effect was observed mainly in patients who underwent randomization 48 hours or less after the initiation of invasive mechanical ventilation. Serious adverse events did not differ substantially between the two groups. CONCLUSIONS: The administration of plasma collected from convalescent donors with a neutralizing antibody titer of at least 1:160 to patients with Covid-19-induced ARDS within 5 days after the initiation of invasive mechanical ventilation significantly reduced mortality at day 28. This effect was mainly observed in patients who underwent randomization 48 hours or less after ventilation initiation. (Funded by the Belgian Health Care Knowledge Center; ClinicalTrials.gov number, NCT04558476.).

Protamine titration to optimize heparin antagonization after cardiopulmonary bypass.

OBJECTIVES: To optimize protamine titration for heparin antagonization after weaning from cardiopulmonary bypass (CPB). DESIGN: A prospective, observational trial. SETTING: Single-center, non-university teaching hospital. PARTICIPANTS: Forty patients presenting for elective on-pump coronary artery bypass grafting with or without single valve surgery. INTERVENTIONS: At the end of CPB, the residual amount of heparin in the patient was estimated using a Bull-curve. The total protamine dose was calculated as 1 unit of protamine for 1 unit of heparin. Protamine was administered as 5 aliquots containing 20% of the total protamine dose each, with 2-min intervals. MEASUREMENTS AND MAIN RESULTS: Activated Clotting Time (ACT) values were measured 2 min after administration of each aliquot. ROTEM(®)-analysis was performed after the full dose of protamine had been administered. After 60% of the total protamine dose had been administered, ACT values were normalized in 86.5% of patients. After the complete dose of protamine had been administered, 61.1% of patients displayed signs of protamine overdose on ROTEM(®)-analysis. CONCLUSIONS: In patients who present for on-pump coronary artery bypass grafting with or without single valve surgery, a 0.6-to-1 ratio of protamine-to-heparin to antagonize heparin may be sufficient and beneficial for patients.

Immunological sub-phenotypes and response to convalescent plasma in COVID-19 induced ARDS: a secondary analysis of the CONFIDENT trial.

BACKGROUND: Convalescent plasma (CP) reduced the mortality in COVID-19 induced ARDS (C-ARDS) patients treated in the CONFIDENT trial. As patients are immunologically heterogeneous, we hypothesized that clusters may differ in their treatment responses to CP. METHODS: We measured 20 cytokines, chemokines and cell adhesion markers using a multiplex technique at the time of inclusion in the CONFIDENT trial in patients of centers having accepted to participate in this secondary study. We performed descriptive statistics, unsupervised hierarchical cluster analysis, and examined the association between the clusters and CP effect on day-28 mortality. RESULTS: Of the 475 patients included in CONFIDENT, 391 (82%) were sampled, and 196/391 (50.1%) had been assigned to CP. We identified four sub-phenotypes representing 89 (22.8%), 178 (45.5%), 38 (9.7%), and 86 (22.0%) patients. The most contributing biomarkers in the principal component analysis were IL-1ß, IL-12p70, IL-6, IFN-α, IL-17A, IFN-γ, IL-13, TFN-α, total IgG, and CXCL10. Sub-phenotype-1 displayed a lower immune response, sub-phenotype-2 a higher adaptive response, sub-phenotype-3 the highest innate antiviral, pro and anti-inflammatory response, and adhesion molecule activation, and sub-phenotype-4 a higher pro and anti-inflammatory response, migration protein and adhesion molecule activation. Sub-phenotype-2 and sub-phenotype-4 had higher severity at the time of inclusion. The effect of CP treatment on mortality appeared higher than standard care in each sub-phenotype, without heterogeneity between sub-phenotypes (p = 0.97). CONCLUSION: In patients with C-ARDS, we identified 4 sub-phenotypes based on their immune response. These sub-phenotypes were associated with different clinical profiles. The response to CP was similar across the 4 sub-phenotypes. TRIAL REGISTRATION: Ethics Committee of the University Hospital of Liège CE 2020/239. CLINICALTRIALS: gov NCT04558476. Registered 2020-09-11, https://www. CLINICALTRIALS: gov/study/NCT04558476 .

The association between increasing fluid balance, acute kidney injury and mortality in patients with sepsis and septic shock: A retrospective single center audit.

PURPOSE: To determine whether a positive fluid balance is associated with AKI and mortality in sepsis and septic shock patients. METHODS: A retrospective chart review of 482 patients treated for sepsis or septic shock. Patients were stratified according to quartiles of cumulative fluid balance on days 1 and 3. Logistic models were built to explore the association between fluid balance, AKI, and ICU mortality. RESULTS: During the first days of ICU admission, fluid input did not differ between survivors and non-survivors, yet a significant difference in output resulted in a more positive fluid balance in non-survivors on day 1 (37.24 ± 31.98 ml/kg vs. 24.97 ± 23.76 ml/kg, p < 0.001) and day 3 (83.33 ± 70.86 ml/kg vs. 62.20 ± 45.90 ml/kg, P = 0.005). Using a logistic regression model, a positive fluid balance on day three was independently associated with higher ICU mortality (odds ratio 1.007 for every one ml/kg, P = 0038) and AKIN stage III (odds ratio 1.006 for every one ml/kg, p = 0.031). CONCLUSION: In patients with sepsis and septic shock, a more positive fluid balance is associated with an increased incidence of acute kidney injury and death after correction for possible confounders.

Intraoperative changes in regional wall motion: can postoperative coronary artery bypass graft failure be predicted?

OBJECTIVE: To evaluate the accuracy of new intraoperative regional wall motions abnormalities (RWMAs) detected by transesophageal echocardiography (TEE) to predict early postoperative coronary artery graft failure. DESIGN: A retrospective study. SETTING: A tertiary care university hospital. PATIENTS: Five thousand nine hundred ninety-eight patients who underwent coronary artery bypass graft (CABG) surgery. INTERVENTIONS: An evaluation of RWMAs recorded with intraoperative TEE before and after cardiopulmonary bypass (CPB) in patients who had coronary angiography for suspected postoperative myocardial ischemia based on electrocardiogram (ECG), CK-MB, troponin T, hemodynamic compromise, low cardiac output, and malignant ventricular arrhythmia. Sensitivity, specificity, positive and negative predictive values, odds ratio, 95% confidence interval, and chi-square analysis were used. MEASUREMENTS AND MAIN RESULTS: Thirty-nine patients (0.7%) underwent early coronary angiography for the suspicion of early graft dysfunction. Of the 32 patients with diagnosed early graft dysfunction, 5 patients (15.6%) had shown new intraoperative RWMAs as detected by TEE, 21 patients (65.6%) had no new RWMAs, no report was available in 5 patients (15.6%), and 1 examination (3.1%) was excluded because of poor imaging quality. The sensitivity of TEE to predict graft failure was 15.6%, the specificity was 57.1%, and the positive predictive and negative values were 62.5% and 12.9%, respectively. The odds ratio and 95% confidence interval was 0.1190 (0.0099-1.4257) when TEE was positive compared with coronary angiography. No association was found between new RWMAs detected with TEE and graft failure as documented with coronary angiography (p = 0.106). CONCLUSIONS: In this retrospective study, RWMAs detected with TEE were of limited value to predict early postoperative CABG failure.

Desflurane Consumption During Automated Closed-circuit Delivery is Higher Than When a Conventional Anesthesia Machine is Used With a Simple Vaporizer-O2-N2O Fresh Gas Flow Sequence.

BACKGROUND: The Zeus® (Dräger, Lübeck, Germany), an automated closed-circuit anesthesia machine, uses high fresh gas flows (FGF) to wash-in the circuit and the lungs, and intermittently flushes the system to remove unwanted N2. We hypothesized this could increase desflurane consumption to such an extent that agent consumption might become higher than with a conventional anesthesia machine (Anesthesia Delivery Unit [ADU®], GE, Helsinki, Finland) used with a previously derived desflurane-O2-N2O administration schedule that allows early FGF reduction. METHODS: Thirty-four ASA PS I or II patients undergoing plastic, urologic, or gynecologic surgery received desflurane in O2/N2O. In the ADU group (n = 24), an initial 3 min high FGF of O2 and N2O (2 and 4 L.min-1, respectively) was used, followed by 0.3 L.min-1 O2 + 0.4 L.min-1 N2O. The desflurane vaporizer setting (FD) was 6.5% for the first 15 min, and 5.5% during the next 25 min. In the Zeus group (n = 10), the Zeus® was used in automated closed circuit anesthesia mode with a selected end-expired (FA) desflurane target of 4.6%, and O2/N2O as the carrier gases with a target inspired O2% of 30%. Desflurane FA and consumption during the first 40 min were compared using repeated measures one-way ANOVA. RESULTS: Age and weight did not differ between the groups (P > 0.05), but patients in the Zeus group were taller (P = 0.04). In the Zeus group, the desflurane FA was lower during the first 3 min (P < 0.05), identical at 4 min (P > 0.05), and slightly higher after 4 min (P < 0.05). Desflurane consumption was higher in the Zeus group at all times, a difference that persisted after correcting for the small difference in FA between the two groups. CONCLUSION: Agent consumption with an automated closed-circuit anesthesia machine is higher than with a conventional anesthesia machine when the latter is used with a specific vaporizer-FGF sequence. Agent consumption during automated delivery might be further reduced by optimizing the algorithm(s) that manages the initial FGF or by tolerating some N2 in the circuit to minimize the need for intermittent flushing.

Development and performance of a two-step desflurane-O(2)/N(2)O fresh gas flow sequence.

STUDY OBJECTIVE: To determine if the previously described single-step O(2)/N(2)O fresh gas flow (FGF) sequence could be combined with a simple desflurane vaporizer (F(D)) sequence to maintain the end-expired desflurane (F(A)des) at 4.5% with the anesthesia delivery unit machine (ADU Anesthesia Machine(R); General Electric, Helsinki, Finland). DESIGN: Prospective randomized clinical study. SETTING: Onze Lieve Vrouw Hospital, Aalst, Belgium, a large teaching hospital. PATIENTS: 42 ASA physical status I and II patients requiring general endotracheal anesthesia and controlled mechanical ventilation. INTERVENTIONS: In 18 patients undergoing general anesthesia with controlled mechanical ventilation, F(D) was determined to maintain F(A)des at 4.5% with O(2)/N(2)O FGF of two and 4 L per minute for three minutes and 0.3 and 0.4 L per minute thereafter. Using the same FGF sequence, we prospectively tested the F(D) schedule that approached this observed F(D) pattern with the fewest possible adjustments in another 24 patients. MAIN RESULTS: F(D) of 6.5% for 15 minutes followed by 5.5% thereafter approximated the observed F(D) course well. When it was prospectively tested, the median (25th, 75th percentiles) performance error was -1% (-5.1%, 5.2%); absolute performance error, 7.1% (3.9%, 9.5%); divergence, -6.6% per hour (23.1%, 3.1%/h); and wobble, 2.2% (1.8%, 3.2%). Because F(A)des increased above 4.9%, F(D) was decreased in 5 patients after 23 minutes (0.5% decrement once or twice); in two patients, F(D) was temporarily increased. In one patient, FGF was temporarily increased because the bellows volume became insufficient. CONCLUSIONS: One O(2)/N(2)O rotameter FGF setting change from 6 to 0.7 L per minute after three minutes and one desflurane F(D) change from 6.5% to 5.5% after 15 minutes maintained anesthetic gas concentrations within predictable and clinically acceptable limits during the first 20 minutes.