The effect of a selenium-based anti-inflammatory strategy on postoperative functional recovery in high-risk cardiac surgery patients - A nested sub-study of the sustain CSX trial.

AIM: The cardiac surgery-related ischemia-reperfusion-related oxidative stress triggers the release of cytotoxic reactive oxygen and nitrogen species, contributing to organ failure and ultimately influencing patients' short- and long-term outcomes. Selenium is an essential co-factor for various antioxidant enzymes, thereby contributing to the patients' endogenous antioxidant and anti-inflammatory defense mechanisms. Given these selenium's pleiotropic functions, we investigated the effect of a high-dose selenium-based anti-inflammatory perioperative strategy on functional recovery after cardiac surgery. MATERIALS AND METHODS: This prospective study constituted a nested sub-study of the SUSTAIN CSX trial, a double-blinded, randomized, placebo-controlled multicenter trial to investigate the impact of high-dose selenium supplementation on high-risk cardiac surgery patients' postoperative recovery. Functional recovery was assessed by 6-min walk distance, Short Form-36 (SF-36) and Barthel Index questionnaires. KEY FINDINGS: 174 patients were included in this sub-study. The mean age (SD) was 67.3 (8.9) years, and 78.7 % of the patients were male. The mean (SD) predicted 30-day mortality by the European System for Cardiac Operative Risk Evaluation II score was 12.6 % (9.4 %). There was no difference at hospital discharge and after three months in the 6-min walk distance between the selenium and placebo groups (131 m [IQR: not performed - 269] vs. 160 m [IQR: not performed - 252], p = 0.80 and 400 m [IQR: 299-461] vs. 375 m [IQR: 65-441], p = 0.48). The SF-36 and Barthel Index assessments also revealed no clinically meaningful differences between the selenium and placebo groups. SIGNIFICANCE: A perioperative anti-inflammatory strategy with high-dose selenium supplementation did not improve functional recovery in high-risk cardiac surgery patients.

Association between body mass index and difficult intubation with a double lumen tube: A retrospective cohort study.

STUDY OBJECTIVE: Obesity, defined by the World Health Organization as body mass index (BMI) ≥ 30.0 kg/m2, is associated with adverse outcomes and challenges during surgery. Difficulties during endotracheal intubation, occur in 3-8% of procedures and are among the principal causes of anesthetic-related morbidity and mortality. Endotracheal intubation can be challenging in obese patients due to an array of anatomic and physiologic factors. Double lumen tubes (DLTs), the most commonly used airway technique to facilitate anatomic isolation of the lungs for one lung ventilation. However, DLTs can be difficult to properly position and are also more likely to cause airway injuries and bleeding when compared to conventional single lumen tubes. We investigated the association between BMI and difficult tracheal DLT intubation. DESIGN: Retrospective cohort study. SETTING: Operating room. PATIENTS: We analyzed electronic records of adults having cardiac and thoracic surgery requiring general anesthesia and endotracheal intubation with DLT at the Cleveland Clinic between 2008 and 2021. MEASUREMENTS: BMI, preoperative airway abnormalities and difficult intubation, defined as more than one intubation attempt, was assessed using multivariable logistic regression. MAIN RESULTS: Among 8641 analyzed anesthetics requiring DLT, 1459 (17%) were difficult intubations. After adjusting for confounders, each 5 kg/m2 increase in BMI was associated with a marginal increase of difficult intubation, odds ratio (OR) 1.06 (95% Confidence Interval [CI]: 1.002, 1.11; P = 0.040). Difficult intubation was not associated with airway abnormalities, estimated OR 0.85 (95% CI: 0.62, 1.17; P = 0.321). There was no interaction between known airway abnormalities and BMI (P = 0.894). CONCLUSIONS: Difficult intubations with DLT remain common, but BMI is a weak predictor thereof. For example, an increase in BMI from 20 to 40 kg/m2 corresponds to an increase in average absolute risk for difficult intubation from 16 to 19%, which probably is not clinically meaningful.

Fumarate is a terminal electron acceptor in the mammalian electron transport chain.

For electrons to continuously enter and flow through the mitochondrial electron transport chain (ETC), they must ultimately land on a terminal electron acceptor (TEA), which is known to be oxygen in mammals. Paradoxically, we find that complex I and dihydroorotate dehydrogenase (DHODH) can still deposit electrons into the ETC when oxygen reduction is impeded. Cells lacking oxygen reduction accumulate ubiquinol, driving the succinate dehydrogenase (SDH) complex in reverse to enable electron deposition onto fumarate. Upon inhibition of oxygen reduction, fumarate reduction sustains DHODH and complex I activities. Mouse tissues display varying capacities to use fumarate as a TEA, most of which net reverse the SDH complex under hypoxia. Thus, we delineate a circuit of electron flow in the mammalian ETC that maintains mitochondrial functions under oxygen limitation.