Objective: Glutamate has been claimed to protect the heart from ischemia and to facilitate metabolic and hemodynamic recovery after ischemia. The GLUTAmate for Metabolic Intervention in Coronary Surgery trial investigated whether an intravenous glutamate infusion given in association with surgery for acute coronary syndrome could reduce mortality and prevent or mitigate myocardial injury and postoperative heart failure.Methods: In the present prospective, triple-center, double-blind study, 861 patients undergoing surgery for acute coronary syndrome were randomly assigned to an intravenous infusion of glutamate (n ¼ 428) or saline (n ¼ 433) perioperatively.Results: The incidence of the primary endpoint-a composite of 30-day mortality, perioperative myocardial infarction, and left ventricular heart failure at weaning from cardiopulmonary bypass-was 7.3% versus 5.8% (P ¼ .41) in the glutamate and control groups, respectively. Patients with left ventricular failure at weaning from cardiopulmonary bypass had a shorter median intensive care unit stay (25 vs 92 hours; P ¼ .02) if they were treated with glutamate. In patients with unstable angina (Canadian Cardiovascular Society class IV) undergoing isolated coronary artery bypass grafting (n ¼ 458), the incidence of severe circulatory failure according to the prespecified criteria was significantly lower in the glutamate group (1.3% vs 6.9%; P ¼ .004). On multivariate analysis, glutamate infusion was associated with a reduced risk of developing severe circulatory failure (odds ratio, 0.17; 95% confidence interval, 0.04-0.72; P ¼ .02). A relative risk reduction exceeding 50% for developing severe circulatory failure was seen in most risk groups undergoing isolated coronary artery bypass grafting, with those with diabetes a notable exception. Conclusions:The primary endpoint did not differ significantly between the groups. The secondary outcomes and post hoc analyses warrant additional studies with regard to the potential beneficial effect of glutamate on postischemic myocardial recovery.

Objectives Patients undergoing lung cancer surgery are routinely offered physiotherapy. Despite its routine use, effects on postoperative physical recovery have yet not been demonstrated. The aim of this study was to investigate whether physiotherapy could improve postoperative in-hospital physical activity level and physical capacity. Design Single-blind randomized controlled trial. Setting Thoracic surgery department at a University Hospital. Participants Patients undergoing elective thoracic surgery (n = 94) for confirmed or suspected lung cancer were assessed during hospital stay. Intervention Daily physiotherapy, consisting of mobilization, ambulation, shoulder exercises and breathing exercises. The control group received no physiotherapy treatment. Outcomes In-hospital physical activity assessed with the Actigraph GT3X+ accelerometer, six-minute walk test, spirometry and dyspnea scores. Results The treatment group reached significantly more accelerometer counts (2010 (1508) vs 1629 (1146), mean difference 495 [95% CI 44 to 1109]), and steps per hour (49 (47) vs 37 (34), mean difference 14 [95% CI 3 to 30]), compared to the control group, during the first three postoperative days. No significant differences in six-minute walk test (percent of preoperative 71% vs 79%, P = 0.13), spirometry (FEV1 percent of preoperative 69% vs 69%, P = 0.83) or dyspnoea (M-MRC 2 vs 2, P = 0.74) between the groups were found. Conclusions Patients receiving in-hospital physiotherapy showed increased level of physical activity during the first days after lung cancer surgery, compared to an untreated control group. However, no effects on the six-minute walk test or spirometric values were found. The clinical importance of an increased physical activity level during the early postoperative period needs to be further evaluated.Clinical Trial Registration number: NCT01961700.

Background. Lung cancer is the most frequently diagnosed cancer and one of the leading causes of cancer deaths. Surgery is the primary approach for curative treatment. Postoperative complications are common, and physiotherapy is often routinely provided for their prevention and treatment, even though the evidence is limited. The aim of this study was to examine the effect of in-hospital physiotherapy on postoperative physical capacity, physical activity, and lung function among patients undergoing lung cancer surgery. Methods. A total of 107 patients undergoing elective thoracic surgery were included in a single-blinded randomized controlled trial, and randomized to a study group, receiving in-hospital physiotherapy treatment, or a control group, not receiving in-hospital physiotherapy treatment. The patients were assessed preoperatively and 3 months after surgery. The in-hospital physiotherapy treatment consisted of early mobilization, ambulation, breathing exercises, and thoracic range of motion exercises. Physical capacity was assessed with the 6-minute walk test. Level of physical activity was objectively assessed with an accelerometer and subjectively assessed with the International Physical Activity Questionnaire Modified for the Elderly. Results. Physical capacity for the whole sample was significantly decreased 3 months postoperatively compared with preoperative values ( P = .047). There were no statistically significant differences between the groups regarding physical capacity, physical activity, spirometric values, or dyspnea. However, patients in the study group increased their level of self-reported physical activity from preoperatively to 3 months postoperatively, while the patients in the control group did not. Conclusions. No difference in physical capacity, physical activity, or lung function was found 3 months postoperatively in lung cancer surgery patients receiving in-hospital physiotherapy compared with control patients.

NCT00489827.

Background Animal and human data suggest that glutamate can enhance recovery of myocardial metabolism and function after ischemia. N-terminal pro-brain natriuretic peptide (NT-proBNP) reflects myocardial dysfunction after coronary artery bypass surgery (CABG). We investigated whether glutamate infusion can reduce rises of NT-proBNP in moderate- to high-risk patients after CABG. Methods and findings A prospective, randomized, double-blind study enrolled patients from November 15, 2015 to September 30, 2020, with a 30-day follow-up at 4 academic cardiac surgery centers in Sweden. Patients underwent CABG ± valve procedure and had left ventricular ejection fraction ≤0.30 or EuroSCORE II ≥3.0. Intravenous infusion of 0.125 M L-glutamic acid or saline at 1.65 mL/kg/h started 10 to 20 minutes before releasing the aortic cross-clamp, then continued for another 150 minutes. Patients, staff, and investigators were blinded to the treatment. The primary endpoint was the difference between preoperative and day-3 postoperative NT-proBNP levels. Analysis was intention to treat. We studied 303 patients (age 74 ± 7 years; females 26%, diabetes 47%), 148 receiving glutamate group and 155 controls. There was no significant difference in the primary endpoint associated with glutamate administration (5,390 ± 5,396 ng/L versus 6,452 ± 5,215 ng/L; p = 0.086). One patient died ≤30 days in the glutamate group compared to 6 controls (0.7% versus 3.9%; p = 0.12). No adverse events linked to glutamate were observed. A significant interaction between glutamate and diabetes was found (p = 0.03). Among patients without diabetes the primary endpoint (mean 4,503 ± 4,846 ng/L versus 6,824 ± 5,671 ng/L; p = 0.007), and the incidence of acute kidney injury (11% versus 29%; p = 0.005) was reduced in the glutamate group. These associations remained significant after adjusting for differences in baseline data. The main limitations of the study are: (i) it relies on a surrogate marker for heart failure; and (ii) the proportion of patients with diabetes had almost doubled compared to the cohort used for the sample size estimation. Conclusions Infusion of glutamate did not significantly reduce postoperative rises of NT-proBNP. Diverging results in patients with and without diabetes agree with previous observations and suggest that the concept of enhancing postischemic myocardial recovery with glutamate merits further evaluation. Trial registration ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02592824. European Union Drug Regulating Authorities Clinical Trials Database (Eudra CT number 2011-006241-15).