Background: Myocardial injury after noncardiac surgery (MINS) was defined as prognostically relevant myocardial injury due to ischemia that occurs during or within 30 days after noncardiac surgery. The study’s four objectives were to determine the diagnostic criteria, characteristics, predictors, and 30-day outcomes of MINS. Methods: In this international, prospective cohort study of 15,065 patients aged 45 yr or older who underwent in-patient noncardiac surgery, troponin T was measured during the first 3 postoperative days. Patients with a troponin T level of 0.04 ng/ml or greater (elevated “abnormal” laboratory threshold) were assessed for ischemic features (i.e., ischemic symptoms and electrocardiography findings). Patients adjudicated as having a nonischemic troponin elevation (e.g., sepsis) were excluded. To establish diagnostic criteria for MINS, the authors used Cox regression analyses in which the dependent variable was 30-day mortality (260 deaths) and independent variables included preoperative variables, perioperative complications, and potential MINS diagnostic criteria. Results: An elevated troponin after noncardiac surgery, irrespective of the presence of an ischemic feature, independently predicted 30-day mortality. Therefore, the authors’ diagnostic criterion for MINS was a peak troponin T level of 0.03 ng/ml or greater judged due to myocardial ischemia. MINS was an independent predictor of 30-day mortality (adjusted hazard ratio, 3.87; 95% CI, 2.96–5.08) and had the highest population-attributable risk (34.0%, 95% CI, 26.6–41.5) of the perioperative complications. Twelve hundred patients (8.0%) suffered MINS, and 58.2% of these patients would not have fulfilled the universal definition of myocardial infarction. Only 15.8% of patients with MINS experienced an ischemic symptom. Conclusion: Among adults undergoing noncardiac surgery, MINS is common and associated with substantial mortality.

Indirect measures of cardiac vagal activity are strongly associated with exercise capacity, yet a causal relationship has not been established. Here we show that in rats, genetic silencing of the largest population of brainstem vagal preganglionic neurons residing in the brainstem’s dorsal vagal motor nucleus dramatically impairs exercise capacity, while optogenetic recruitment of the same neuronal population enhances cardiac contractility and prolongs exercise endurance. These data provide direct experimental evidence that parasympathetic vagal drive generated by a defined CNS circuit determines the ability to exercise. Decreased activity and/or gradual loss of the identified neuronal cell group provides a neurophysiological basis for the progressive decline of exercise capacity with aging and in diverse disease states.

Perioperative lymphopenia has been linked with an increased risk of postoperative infectious complications, but the mechanisms remain unclear. We tested the hypothesis that bioenergetic dysfunction is an important mechanism underlying lymphopenia, impaired functionality and infectious complications. In two cohorts of patients (61–82 years old) undergoing orthopaedic joint replacement (n=417 and 328, respectively), we confirmed prospectively that preoperative lymphopenia (≤1.3 x 10⁹·l⁻¹; <20% white cell count; prevalence 15–18%) was associated with infectious complications (relative risk 1.5 (95% confidence interval 1.1–2.0); P=0.008) and prolonged hospital stay. Lymphocyte respirometry, mitochondrial bioenergetics and function were assessed (n=93 patients). Postoperative lymphocytes showed a median 43% fall (range: 26–65%; P=0.029; n=13 patients) in spare respiratory capacity, the extra capacity available to produce energy in response to stress. This was accompanied by reduced glycolytic capacity. A similar hypometabolic phenotype was observed in lymphocytes sampled preoperatively from chronically lymphopenic patients (n=21). This hypometabolic phenotype was associated with functional lymphocyte impairment including reduced T-cell proliferation, lower intracellular cytokine production and excess apoptosis induced by a range of common stressors. Glucocorticoids, which are ubiquitously elevated for a prolonged period postoperatively, generated increased levels of mitochondrial reactive oxygen species, activated caspase-1 and mature interleukin (IL)-1β in human lymphocytes, suggesting inflammasome activation. mRNA transcription of the NLRP1 inflammasome was increased in lymphocytes postoperatively. Genetic ablation of the murine NLRP3 inflammasome failed to prevent glucocorticoid-induced lymphocyte apoptosis and caspase-1 activity, but increased NLRP1 protein expression. Our findings suggest that the hypometabolic phenotype observed in chronically lymphopenic patients and/or acquired postoperatively increases the risk of postoperative infection through glucocorticoid activation of caspase-1 via the NLRP1 inflammasome.

Indirect calorimetry (IC) is the gold-standard for determining measured resting energy expenditure (mREE) in critical illness. When IC is not available, predicted resting energy expenditure (pREE) equations are commonly utilized, which often inaccurately predict metabolic demands leading to over- or under-feeding. This study aims to longitudinally assess mREE via IC in critically ill patients with SARS-CoV-2 (COVID-19) infection throughout the entirety of, often prolonged, intensive care unit (ICU) stays and compare mREE to commonly utilized pREE equations. This single-center prospective cohort study of 38 mechanically ventilated COVID-19 patients from April 1, 2020 to February 1, 2021. The Q-NRG® Metabolic Monitor was used to obtain IC data. The Harris-Benedict (HB), Mifflin St-Jeor (MSJ), Penn State University (PSU), and weight-based equations from the American Society of Parenteral and Enteral Nutrition – Society of Critical Care Medicine (ASPEN-SCCM) Clinical Guidelines were utilized to assess the accuracy of common pREE equations and their ability to predict hypo/hypermetabolism in COVID-19 ICU patients. The IC measures collected revealed a relatively normometabolic or minimally hypermetabolic mREE at 21.3 kcal/kg/d or 110% of predicted by the HB equation over the first week of mechanical ventilation (MV). This progressed to significant and uniquely prolonged hypermetabolism over successive weeks to 28.1 kcal/kg/d or 143% of HB predicted by MV week 3, with hypermetabolism persisting to MV week 7. Obese individuals displayed a more truncated response with significantly lower mREE versus non-obese patients in MV week 1 (19.5 ± 1.0 kcal/kg/d vs 25.1 ± 1.8 kcal/kg/d, respectively; p < 0.01), with little change in weeks 2–3 (19.5 ± 1.5 kcal/kg/d vs 28.0 ± 2.0 kcal/kg/d; p < 0.01). Both ASPEN-SCCM upper range and PSU pREE equations provided close approximations of mREE yet, like all pREE equations, occasionally over- and under-predicted energy needs and typically did not predict late hypermetabolism. Study results show a truly unique metabolic response in COVID-19 ICU patients, characterized by significant and prolonged, progressive hypermetabolism peaking at 3 weeks’ post-intubation, persisting for up to 7 weeks in ICU. This pattern was more clearly demonstrated in non-obese versus obese patients. This response is unique and distinct from any previously described model of ICU stress response in its prolonged hypermetabolic nature. This data reaffirms the need for routine, longitudinal IC measures to provide accurate energy targets in COVID-19 ICU patients. The PSU and ASPEN-SCCM equations appear to yield the most reasonable estimation to IC-derived mREE in COVID-19 ICU patients, yet still often over-/under-predict energy needs. These findings provide a practical guide for caloric prescription in COVID-19 ICU patients in the absence of IC.