The rare vaccine-induced immune thrombotic thrombocytopenia that may follow adenovirus-based Covid-19 vaccination resembles heparin-induced thrombocytopenia, but rapid assays for anti-PF4 antibodies ...used to diagnose HIT may be negative in patients with VITT. The PF4–serotonin release assay appears to detect the IgG antibodies to PF4–PVS that mediate this condition.
Endothelial activation and dysfunction play a key role in the pathogenesis of sepsis. During septic shock, endothelial dysfunction is involved in microcirculation impairment and organ dysfunction. ...Reactive oxygen species (ROS) and reactive nitrogen species (RNS) have several potentially important effects on endothelial function and are implicated in physiological regulation and disease pathophysiology. The imbalance between the production of ROS and their effective removal by non-enzymatic and enzymatic antioxidants systems could induce endothelial dysfunction with alterations of vascular tone, increases in cell adhesion properties (leukocytes and platelet adhesion), increase in vascular wall permeability and a pro-coagulant state. Increasing evidence supports the idea that the principal cause of EC dysfunction during sepsis is cell injury. ROS and RNS contribute to mitochondrial dysfunction by a range of mechanisms and induce both necrotic and apoptotic cell death. Understanding the mechanisms underlying the generation of ROS and RNS in endothelial cells and the causes of endothelial dysfunction in sepsis may help provide therapeutic strategies to tackle endothelial dysfunction and microcirculatory failure in sepsis.
IMPORTANCE: After severe traumatic brain injury, induction of prophylactic hypothermia has been suggested to be neuroprotective and improve long-term neurologic outcomes. OBJECTIVE: To determine the ...effectiveness of early prophylactic hypothermia compared with normothermic management of patients after severe traumatic brain injury. DESIGN, SETTING, AND PARTICIPANTS: The Prophylactic Hypothermia Trial to Lessen Traumatic Brain Injury–Randomized Clinical Trial (POLAR-RCT) was a multicenter randomized trial in 6 countries that recruited 511 patients both out-of-hospital and in emergency departments after severe traumatic brain injury. The first patient was enrolled on December 5, 2010, and the last on November 10, 2017. The final date of follow-up was May 15, 2018. INTERVENTIONS: There were 266 patients randomized to the prophylactic hypothermia group and 245 to normothermic management. Prophylactic hypothermia targeted the early induction of hypothermia (33°C-35°C) for at least 72 hours and up to 7 days if intracranial pressures were elevated, followed by gradual rewarming. Normothermia targeted 37°C, using surface-cooling wraps when required. Temperature was managed in both groups for 7 days. All other care was at the discretion of the treating physician. MAIN OUTCOMES AND MEASURES: The primary outcome was favorable neurologic outcomes or independent living (Glasgow Outcome Scale–Extended score, 5-8 scale range, 1-8) obtained by blinded assessors 6 months after injury. RESULTS: Among 511 patients who were randomized, 500 provided ongoing consent (mean age, 34.5 years SD, 13.4; 402 men 80.2%) and 466 completed the primary outcome evaluation. Hypothermia was initiated rapidly after injury (median, 1.8 hours IQR, 1.0-2.7 hours) and rewarming occurred slowly (median, 22.5 hours IQR, 16-27 hours). Favorable outcomes (Glasgow Outcome Scale–Extended score, 5-8) at 6 months occurred in 117 patients (48.8%) in the hypothermia group and 111 (49.1%) in the normothermia group (risk difference, 0.4% 95% CI, –9.4% to 8.7%; relative risk with hypothermia, 0.99 95% CI, 0.82-1.19; P = .94). In the hypothermia and normothermia groups, the rates of pneumonia were 55.0% vs 51.3%, respectively, and rates of increased intracranial bleeding were 18.1% vs 15.4%, respectively. CONCLUSIONS AND RELEVANCE: Among patients with severe traumatic brain injury, early prophylactic hypothermia compared with normothermia did not improve neurologic outcomes at 6 months. These findings do not support the use of early prophylactic hypothermia for patients with severe traumatic brain injury. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00987688; Anzctr.org.au Identifier: ACTRN12609000764235
Despite numerous studies, controversies about the best intraoperative FiO2 remain. In 2016, the World Health Organization (WHO) recommended that adult patients undergoing general anaesthesia should ...be ventilated intraoperatively with an 80% FiO2 to reduce surgical site infection (SSI). However, several data suggest that hyperoxia could have adverse effects. In order to determine the potential effect of FiO2 on SSI, we included in this systematic review 23 studies (among which 21 randomised controlled trials RCT) published between 1999 and 2020, comparing intraoperative high versus low FiO2. Results were heterogeneous but most recent studies on one hand, and the largest RCTs on the other hand, reported no difference on the incidence of SSI regarding intraoperative FiO2 during general anaesthesia. There was also no difference in the incidence of SSI depending of intraoperative FiO2 in patients receiving regional anaesthesia. The review on secondary endpoints (respiratory and cardiovascular adverse events, postoperative nausea and vomiting, postoperative length-of-stay and mortality) also failed to support the use of high FiO2. On the opposite, some data from follow-up analyses and registry studies suggested a possible negative effect of high intraoperative FiO2 on long-term outcomes. In conclusion, the systematic administration of a high intraoperative FiO2 in order to decrease SSI or improve other perioperative outcomes seems unjustified in the light of the evidence currently available in the literature.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Purpose
To estimate the prevalence, risk factors, prophylactic treatment and impact on mortality for venous thromboembolism (VTE) in patients with moderate to severe traumatic brain injury (TBI) ...treated in the intensive care unit.
Methods
A post hoc analysis of the erythropoietin in traumatic brain injury (EPO-TBI) trial that included twice-weekly lower limb ultrasound screening. Venous thrombotic events were defined as ultrasound-proven proximal deep venous thrombosis (DVT) or clinically detected pulmonary embolism (PE). Results are reported as events, percentages or medians and interquartile range (IQR). Cox regression analysis was used to calculate adjusted hazard ratios (HR) with 95% confidence intervals (CI) for time to VTE and death.
Results
Of 603 patients, 119 (19.7%) developed VTE, mostly comprising DVT (102 patients, 16.9%) with a smaller number of PE events (24 patients, 4.0%). Median time to DVT diagnosis was 6 days (IQR 2–11) and to PE diagnosis 6.5 days (IQR 2–16.5). Mechanical prophylaxis (MP) was used in 91% of patients on day 1, 97% of patients on day 3 and 98% of patients on day 7. Pharmacological prophylaxis was given in 5% of patients on day 1, 30% of patients on day 3 and 57% of patients on day 7. Factors associated with time to VTE were age (HR per year 1.02, 95% CI 1.01–1.03), patient weight (HR per kg 1.01, 95% CI 1–1.02) and TBI severity according to the International Mission for Prognosis and Analysis of Clinical Trials risk of poor outcome (HR per 10% increase 1.12, 95% CI 1.01–1.25). The development of VTE was not associated with mortality (HR 0.92, 95% CI 0.51–1.65).
Conclusions
Despite mechanical and pharmacological prophylaxis, VTE occurs in one out of every five patients with TBI treated in the ICU. Higher age, greater weight and greater severity of TBI increase the risk. The development of VTE was not associated with excess mortality.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
IMPORTANCE: It is not known if use of colloid solutions containing hydroxyethyl starch (HES) to correct for intravascular deficits in high-risk surgical patients is either effective or safe. ...OBJECTIVE: To evaluate the effect of HES 130/0.4 compared with 0.9% saline for intravascular volume expansion on mortality and postoperative complications after major abdominal surgery. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, double-blind, parallel-group, randomized clinical trial of 775 adult patients at increased risk of postoperative kidney injury undergoing major abdominal surgery at 20 university hospitals in France from February 2016 to July 2018; final follow-up was in October 2018. INTERVENTIONS: Patients were randomized to receive fluid containing either 6% HES 130/0.4 diluted in 0.9% saline (n = 389) or 0.9% saline alone (n = 386) in 250-mL boluses using an individualized hemodynamic algorithm during surgery and for up to 24 hours on the first postoperative day, defined as ending at 7:59 am the following day. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of death or major postoperative complications at 14 days after surgery. Secondary outcomes included predefined postoperative complications within 14 days after surgery, durations of intensive care unit and hospital stays, and all-cause mortality at postoperative days 28 and 90. RESULTS: Among 826 patients enrolled (mean age, 68 SD, 7 years; 91 women 12%), 775 (94%) completed the trial. The primary outcome occurred in 139 of 389 patients (36%) in the HES group and 125 of 386 patients (32%) in the saline group (difference, 3.3% 95% CI, −3.3% to 10.0%; relative risk, 1.10 95% CI, 0.91-1.34; P = .33). Among 12 prespecified secondary outcomes reported, 11 showed no significant difference, but a statistically significant difference was found in median volume of study fluid administered on day 1: 1250 mL (interquartile range, 750-2000 mL) in the HES group and 1500 mL (interquartile range, 750-2150 mL) in the saline group (median difference, 250 mL 95% CI, 83-417 mL; P = .006). At 28 days after surgery, 4.1% and 2.3% of patients had died in the HES and saline groups, respectively (difference, 1.8% 95% CI, −0.7% to 4.3%; relative risk, 1.76 95% CI, 0.79-3.94; P = .17). CONCLUSIONS AND RELEVANCE: Among patients at risk of postoperative kidney injury undergoing major abdominal surgery, use of HES for volume replacement therapy compared with 0.9% saline resulted in no significant difference in a composite outcome of death or major postoperative complications within 14 days after surgery. These findings do not support the use of HES for volume replacement therapy in such patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02502773
IMPORTANCE: Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford–AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & ...Johnson). OBJECTIVE: To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine–induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination. EXPOSURES: Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria. MAIN OUTCOMES AND MEASURES: Clinical characteristics and mortality rate. RESULTS: Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later. CONCLUSIONS AND RELEVANCE: In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination.
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