Using the nociception level index to compare the intraoperative antinociceptive effect of propofol and sevoflurane during clinical and experimental noxious stimulus in patients under general anesthesia.

STUDY: Propofol and sevoflurane are two anesthetic agents widely used to induce and maintain general anesthesia (GA). Their intrinsic antinociceptive properties remain unclear and are still debated. OBJECTIVE: To determine whether propofol presents stronger antinociceptive properties than sevoflurane using intraoperative clinical and experimental noxious stimulations and evaluating postoperative pain outcomes. DESIGN: A prospective randomized monocentric trial. SETTING: Perioperative care. PATIENTS: 60 adult patients with ASA status I to III who underwent elective abdominal laparoscopic surgery under GA were randomized either in propofol or sevoflurane group to induce and maintain GA. INTERVENTIONS: We used clinical and experimental noxious stimulations (intubation, tetanic stimulation) to assess the antinociceptive properties of propofol and sevoflurane in patients under GA and monitored using the NOL index, BIS index, heart rate, and mean arterial blood pressure. MEASUREMENTS: We measured the difference in the NOL index alterations after intubation and tetanic stimulation during either intravenous anesthesia (propofol) or inhaled anesthesia (sevoflurane). We also intraoperatively measured the NOL index and remifentanil consumption and recorded postoperative pain scores and opioid consumption in the post-anesthesia care unit. Intraoperative management was standardized by targeting similar values of depth of anesthesia (BIS index), hemodynamic (HR and MAP), NOL index values (below the threshold of 20), same multimodal analgesia and type of surgery. MAIN RESULTS: We found the antinociceptive properties of propofol and sevoflurane similar. The only minor difference was after tetanic stimulation: the delta NOL was higher in the sevoflurane group (39 ± 13 for the propofol group versus 47 ± 15 for sevoflurane; P = 0.04). Intraoperative and postoperative pain outcomes and opioid consumption were similar between groups. CONCLUSIONS: Despite a precise intraoperative experimental and clinical protocol using the NOL index, propofol does not provide a higher level of antinociception during anesthesia or analgesia after surgery when compared to sevoflurane. Anesthesiologists may prefer propofol over sevoflurane to reduce PONV or anesthesia-related pollution, but not for superior antinociceptive properties.

Early chest tube removal on the 1st postoperative day protocol of an enhanced recovery after cardiac surgery programme is safe.

OBJECTIVES: The aim of this study was to assess the safety of early chest tube removal (CTR) protocol on the 1st postoperative day (POD1) of our Enhanced Recovery After Surgery (ERAS) programme by comparing the risk of postoperative pneumothorax, pleural and pericardial effusion requiring intervention and hospital mortality. METHODS: All consecutive patients undergoing elective coronary revascularization and/or valve surgery between 2015 and 2021 were assessed in terms of their perioperative management pathways: conventional standard of care (control group) versus standardized systematic perioperative ERAS programme including an early CTR on POD1 (ERAS group). A propensity score matching was applied. The primary end-point was a composite of postoperative pneumothorax, pleural and pericardial effusion requiring intervention and hospital mortality. RESULTS: A total of 3153 patients were included. Propensity score analysis resulted in 2 groups well-matched pairs of 1026 patients. CTR on POD1 was significantly increased from 29.5% in the control group to 70.3% in the ERAS group (P < 0.001). The incidence of the primary end-point was 6.4% in the control group and 6.9% in the ERAS group (P = 0.658). Patients in the ERAS group, as compared with control group, had significant lower incidence of bronchopneumonia (9.0% vs 13.5%; P = 0.001) and higher incidence of mechanical ventilation ≤6 h (84.6% vs 65.2%; P < 0.001), length of intensive care unit ≤1 day (61.2% vs 50.8%; P < 0.001) and hospital ≤6 days (67.3% vs.43.2%; P < 0.001). CONCLUSIONS: CTR on POD1 protocol can be safely incorporated into a standardized systematic ERAS programme, enabling early mobilization, and contributing to the improvement of postoperative outcomes. CLINICAL TRIAL REGISTRATION NUMBER: Ethics committee of the French Society of Thoracic and Cardio-Vascular Surgery (CERC-SFCTCV-2022-09-13_23140).

COVID-19 promotes endothelial dysfunction and thrombogenicity: role of proinflammatory cytokines/SGLT2 prooxidant pathway.

BACKGROUND: COVID-19 is associated with an increased risk of cardiovascular complications. Although cytokines have a predominant role in endothelium damage, the precise molecular mechanisms are far from being elucidated. OBJECTIVES: The present study hypothesized that inflammation in patients with COVID-19 contributes to endothelial dysfunction through redox-sensitive SGLT2 overexpression and investigated the protective effect of SGLT2 inhibition by empagliflozin. METHODS: Human plasma samples were collected from patients with acute, subacute, and long COVID-19 (n = 100), patients with non-COVID-19 and cardiovascular risk factors (n = 50), and healthy volunteers (n = 25). Porcine coronary artery endothelial cells (ECs) were incubated with plasma (10%). Protein expression levels were determined using Western blot analyses and immunofluorescence staining, mRNA expression by quantitative reverse transcription-polymerase chain reaction, and the level of oxidative stress by dihydroethidium staining. Platelet adhesion, aggregation, and thrombin generation were determined. RESULTS: Increased plasma levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, monocyte chemoattractant protein-1, and soluble intercellular adhesion molecule-1 were observed in patients with COVID-19. Exposure of ECs to COVID-19 plasma with high cytokines levels induced redox-sensitive upregulation of SGLT2 expression via proinflammatory cytokines IL-1ß, IL-6, and tumor necrosis factor-α which, in turn, fueled endothelial dysfunction, senescence, NF-κB activation, inflammation, platelet adhesion and aggregation, von Willebrand factor secretion, and thrombin generation. The stimulatory effect of COVID-19 plasma was blunted by neutralizing antibodies against proinflammatory cytokines and empagliflozin. CONCLUSION: In patients with COVID-19, proinflammatory cytokines induced a redox-sensitive upregulation of SGLT2 expression in ECs, which in turn promoted endothelial injury, senescence, platelet adhesion, aggregation, and thrombin generation. SGLT2 inhibition with empagliflozin appeared as an attractive strategy to restore vascular homeostasis in COVID-19.

Enhanced recovery after surgery program for patients undergoing isolated elective coronary artery bypass surgery improves postoperative outcomes.

OBJECTIVE: To evaluate the effect of a perioperative systematic standardized enhanced recovery after surgery (ERAS) program for patients undergoing isolated elective coronary artery bypass grafting (CABG) in terms of mortality, hospital morbidities, and length of stay. METHODS: From January 2015 to September 2020, 1101 patients underwent isolated elective CABG. Our standardized systematic ERAS program was implemented in November 2018. Propensity score matching resulted in well-matched pairs of 362 patients receiving standard perioperative care (control group) and 362 patients on the ERAS program (ERAS group). There were no significant intergroup differences in preoperative and operative data except for the normothermia rate, which was significantly greater in the ERAS group (P < .001). The primary outcome was 3-year mortality. The secondary outcomes were hospital morbidities and length of stay. RESULTS: In-hospital and 3-year mortality did not differ between the 2 groups. The ERAS program was associated with a significant relative risk decrease in mechanical ventilation duration (-53.1%, P = .003), length of intensive care unit stay (-28.0%, P = .015), length of hospital stay (-10.5%, P = .046), bronchopneumonia (-51.5%, P < .001), acute respiratory distress syndrome (-50.8%, P = .050), postoperative delirium (-65.4%, P = .011), moderate-to-severe acute kidney injury (-72.0%, P = .009), 24-hour chest tube output (-26.4%, P < .001), and overall red blood cell transfusion rate (-32.4%, P = .005) compared with the control group. CONCLUSIONS: A systematic standardized ERAS program for low-risk patients undergoing isolated elective CABG was associated with a significant improvement in postoperative outcomes, reduction in red blood cell transfusion, shorter lengths of intensive care unit and hospital stays, and comparable long-term mortality.

Evolution of Neuroimaging Findings in Severe COVID-19 Patients with Initial Neurological Impairment: An Observational Study.

BACKGROUND AND OBJECTIVES: Cerebral complications related to the COVID-19 were documented by brain MRIs during the acute phase. The purpose of the present study was to describe the evolution of these neuroimaging findings (MRI and FDG-PET/CT) and describe the neurocognitive outcomes of these patients. METHODS: During the first wave of the COVID-19 outbreak between 1 March and 31 May 2020, 112 consecutive COVID-19 patients with neurologic manifestations underwent a brain MRI at Strasbourg University hospitals. After recovery, during follow-up, of these 112 patients, 31 (initially hospitalized in intensive care units) underwent additional imaging studies (at least one brain MRI). RESULTS: Twenty-three men (74%) and eight women (26%) with a mean age of 61 years (range: 18-79) were included. Leptomeningeal enhancement, diffuse brain microhemorrhages, acute ischemic strokes, suspicion of cerebral vasculitis, and acute inflammatory demyelinating lesions were described on the initial brain MRIs. During follow-up, the evolution of the leptomeningeal enhancement was discordant, and the cerebral microhemorrhages were stable. We observed normalization of the vessel walls in all patients suspected of cerebral vasculitis. Four patients (13%) demonstrated new complications during follow-up (ischemic strokes, hypoglossal neuritis, marked increase in the white matter FLAIR hyperintensities with presumed vascular origin, and one suspected case of cerebral vasculitis). Concerning the grey matter volumetry, we observed a loss of volume of 3.2% during an average period of approximately five months. During follow-up, the more frequent FDG-PET/CT findings were hypometabolism in temporal and insular regions. CONCLUSION: A minority of initially severe COVID-19 patients demonstrated new complications on their brain MRIs during follow-up after recovery.

Impact of COVID-19 and lockdown regarding blood transfusion.

BACKGROUND: The outbreak of a SARS-CoV-2 resulted in a massive afflux of patients in hospital and intensive care units with many challenges. Blood transfusion was one of them regarding both blood banks (safety, collection, and stocks) and consumption (usual care and unknown specific demand of COVID-19 patients). The risk of mismatch was sufficient to plan blood transfusion restrictions if stocks became limited. STUDY DESIGN AND METHODS: Analyses of blood transfusion in a tertiary hospital and blood collection in the referring blood bank between February 24 and May 31, 2020. RESULTS: Withdrawal of elective surgery and non-urgent care and admission of 2291 COVID-19 patients reduced global activity by 33% but transfusion by 17% only. Only 237 (10.3) % of COVID-19 patients required blood transfusion, including 45 (2.0%) with acute bleeding. Lockdown and cancellation of mobile collection resulted in an 11% reduction in blood donation compared to 2019. The ratio of reduction in blood transfusion to blood donation remained positive and stocks were slightly enhanced. DISCUSSION: Reduction of admissions due to SARS-CoV-2 pandemic results only in a moderate decrease of blood transfusion. Incompressible blood transfusions concern urgent surgery, acute bleeding (including some patients with COVID-19, especially under high anticoagulation), or are supportive for chemotherapy-induced aplasia or chronic anemia. Lockdown results in a decrease of blood donation by cancellation of mobile donation but with little impact on a short period by mobilization of usual donors. No mismatch between demand and donation was evidenced and no planned restriction to blood transfusion was necessary.

Prevalence and outcome of heparin-induced thrombocytopenia diagnosed under veno-arterial extracorporeal membrane oxygenation: a retrospective nationwide study.

PURPOSE: Thrombocytopenia is a frequent and serious adverse event in patients treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for refractory cardiogenic shock. Similarly to postcardiac surgery patients, heparin-induced thrombocytopenia (HIT) could represent the causative underlying mechanism. However, the epidemiology as well as related mortality regarding HIT and VA-ECMO remains largely unknown. We aimed to define the prevalence and associated 90-day mortality of HIT diagnosed under VA-ECMO. METHODS: This retrospective study included patients under VA-ECMO from 20 French centers between 2012 and 2016. Selected patients were hospitalized for more than 3 days with high clinical suspicion of HIT and positive anti-PF4/heparin antibodies. Patients were classified according to results of functional tests as having either Confirmed or Excluded HIT. RESULTS: A total of 5797 patients under VA-ECMO were screened; 39/5797 met the inclusion criteria, with HIT confirmed in 21/5797 patients (0.36% [95% CI] [0.21-0.52]). Fourteen of 39 patients (35.9% [20.8-50.9]) with suspected HIT were ultimately excluded because of negative functional assays. Drug-induced thrombocytopenia tended to be more frequent in Excluded HIT at the time of HIT suspicion (p = 0.073). The platelet course was similar between Confirmed and Excluded HIT (p = 0.65). Mortality rate was 33.3% [13.2-53.5] in Confirmed and 50% [23.8-76.2] in Excluded HIT (p = 0.48). CONCLUSIONS: Prevalence of HIT among patients under VA-ECMO is extremely low at 0.36% with an associated mortality rate of 33.3%, which appears to be in the same range as that observed in patients treated with VA-ECMO without HIT. In addition, HIT was ultimately ruled out in one-third of patients with clinical suspicion of HIT and positive anti-PF4/heparin antibodies.