Glutamate for metabolic intervention in coronary surgery : with special reference to the GLUTAMICS-trial

Myocardial ischemia is a major cause of postoperative heart failure and adverse outcome in coronary artery bypass graft surgery (CABG). Conventional treatment of postoperative heart failure with inotropic drugs may aggravate underlying ischemic injury. Glutamate has been claimed to increase myocardial tolerance to ischemia and promote metabolic and hemodynamic recovery after ischemia. The aim of this work was to investigate if intravenous glutamate infusion given in association with CABG for acute coronary syndrome can reduce mortality and prevent or mitigate myocardial injury and postoperative heart failure. We also wanted to assess neurological safety issues, as a concern with the use of glutamate is that it may act as an excitotoxin under certain conditions.A metabolic strategy for perioperative care was assessed in an observational study on 104 consecutive patients with severe left ventricular dysfunction undergoing CABG. Based on encouraging clinical results, unsurpassed in the literature, the GLUTAMICS-trial was initiated. 861 patients undergoing CABG for acute coronary syndrome were randomly allocated to blinded intravenous infusion of L-glutamicacid solution or saline. The primary endpoint was a composite of postoperative mortality (≤30 days), perioperative myocardial infarction and left ventric ular heart failure in association with weaning from cardiopulmonary bypass. Secondary endpoints included neurological safety issues, degree of myocardial injury,postoperative hemodynamic state, use of circulatory support and cardiac mortality.The event rate was lower than anticipated and the primary endpoint did not differ significantly between the groups. Regarding secondary endpoints there were significant differences compatible with a beneficial effect of glutamate on post-ischemic myocardial recovery. The putative effect of glutamate infusion was seen in more ischemic patients (CCS class IV) and in patients with evident or anticipated LV-failure on weaning from CPB. No evidence for increased incidence of clinical or subclinical neurological injury was found. In conclusion, intravenous glutamate infusion is safe in the dosages employed and could provide a novel and important way of promoting myocardial recovery after ischemic injury

Glutamate for metabolic intervention in coronary surgery : with special reference to the GLUTAMICS-trial

Myocardial ischemia is a major cause of postoperative heart failure and adverse outcome in coronary artery bypass graft surgery (CABG). Conventional treatment of postoperative heart failure with inotropic drugs may aggravate underlying ischemic injury. Glutamate has been claimed to increase myocardial tolerance to ischemia and promote metabolic and hemodynamic recovery after ischemia. The aim of this work was to investigate if intravenous glutamate infusion given in association with CABG for acute coronary syndrome can reduce mortality and prevent or mitigate myocardial injury and postoperative heart failure. We also wanted to assess neurological safety issues, as a concern with the use of glutamate is that it may act as an excitotoxin under certain conditions.A metabolic strategy for perioperative care was assessed in an observational study on 104 consecutive patients with severe left ventricular dysfunction undergoing CABG. Based on encouraging clinical results, unsurpassed in the literature, the GLUTAMICS-trial was initiated. 861 patients undergoing CABG for acute coronary syndrome were randomly allocated to blinded intravenous infusion of L-glutamicacid solution or saline. The primary endpoint was a composite of postoperative mortality (≤30 days), perioperative myocardial infarction and left ventric ular heart failure in association with weaning from cardiopulmonary bypass. Secondary endpoints included neurological safety issues, degree of myocardial injury,postoperative hemodynamic state, use of circulatory support and cardiac mortality.The event rate was lower than anticipated and the primary endpoint did not differ significantly between the groups. Regarding secondary endpoints there were significant differences compatible with a beneficial effect of glutamate on post-ischemic myocardial recovery. The putative effect of glutamate infusion was seen in more ischemic patients (CCS class IV) and in patients with evident or anticipated LV-failure on weaning from CPB. No evidence for increased incidence of clinical or subclinical neurological injury was found. In conclusion, intravenous glutamate infusion is safe in the dosages employed and could provide a novel and important way of promoting myocardial recovery after ischemic injury

http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-54390 A METABOLIC PROTECTIVE STRATEGY COULD IMPROVE LONG-TERM SURVIVAL IN PATIENTS WITH LV- DYSFUNCTION UNDERGOING CABG

A metabolic protective strategy could improve long-term survival in patients with LVdysfunction undergoing CAB

Health-related quality of life after Nuss procedure for pectus excavatum : A cross-sectional study

OBJECTIVES: Pectus excavatum (PE) can cause both physical and psychosocial symptoms and affect patients' health-related quality of life. Previous international studies have shown that the Nuss procedure increases both self-esteem and body image. The aim of the study was to evaluate the health-related quality of life in patients who have undergone the Nuss procedure for PE. METHODS: The study had a cross-sectional multicentre design. All patients (N = 420) who underwent the Nuss procedure for PE in 3 cardiothoracic departments in Sweden from 2000 to 2019 were invited to answer the RAND-36 and Nuss Questionnaire modified for adults. Genders were compared using the Mann-Whitney U-test. Patients were divided into groups based on age at time of surgery (30 years) and analysed by the Kruskal-Wallis H-test with post-hoc analyses. RESULTS: A total of 236 patients returned the questionnaires; 82.2% were males. Men scored significantly better on the modified Nuss Questionnaire total (P = 0.01) and psychosocial (P = 0.02) subscales. Patients who had surgery at 30 years. Patients who had their bar removed had significantly better values on both scales. CONCLUSIONS: Male gender, young age at surgery and bar removal seem to be associated with better health-related quality of life after the Nuss procedure for PE

Effect of glutamate infusion on NT-proBNP after coronary artery bypass grafting in high-risk patients (GLUTAMICS II) : A randomized controlled trial

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 &amp;lt; 0.30 or EuroSCORE II &amp;lt; 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 &amp; PLUSMN; 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 &amp; PLUSMN; 5,396 ng/L versus 6,452 &amp; PLUSMN; 5,215 ng/L; p = 0.086). One patient died &amp; LE;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 &amp; PLUSMN; 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.Funding Agencies|The Swedish Heart-Lung Foundation [20140633]; Region Ostergotland [RO 796412, RO 693091, RO 610951]</p

Post hoc analysis of the glutamics-trial: intravenous glutamate infusion and use of inotropic drugs after cabg

Background: Intravenous glutamate reduced the risk of developing severe circulatory failure after isolated coronary artery bypass graft surgery (CABG) for acute coronary syndrome (ACS) in a double-blind randomised clinical trial (GLUTAMICS-ClinicalTrials. gov Identifier:NCT00489827). Here our aim was to study if glutamate was associated with reduced the use of inotropes. Methods: Post-hoc analysis of 824 patients undergoing isolated CABG for ACS in the GLUTAMICS-trial. ICU-records were retrospectively scrutinised including hourly registration of inotropic drug infusion, dosage and total duration during the operation and postoperatively. Results: ICU-records were found for 171 out of 177 patients who received inotropes perioperatively. Only one fourth of the patients treated with inotropes fulfilled study criteria for postoperative heart failure at weaning from cardiopulmonary bypass (CPB) or later in the ICU. Inotropes were mainly given preemptively to facilitate weaning from CPB or to treat postoperative circulatory instability (bleeding, hypovolaemia). Except for a significantly lower use of epinephrine there were only trends towards lower need of other inotropes overall in the glutamate group. In patients treated with inotropes (glutamate n = 17; placebo n = 13) who fulfilled study criteria for left ventricular failure at weaning from CPB the average duration of inotropic treatment (34 +/- 20 v 80 +/- 77 h; p = 0.014) and the number of inotropes used (1.35 +/- 0.6 v 1.85 +/- 0.7; p = 0.047) were lower in the glutamate group. Conclusions: Intravenous glutamate was associated with a minor influence on inotrope use overall in patients undergoing CABG for ACS whereas a considerable and significant reduction was observed in patients with heart failure at weaning from CPB.Funding Agencies|Swedish Heart-Lung Foundation [20030595]; Capio Research Foundation [2005-1021, 2006-1203]; Linkoping University; Ostergotlands Lans Landsting</p

Translation and psychometric evaluation of the Swedish versions of the Nuss Questionnaire modified for Adults and the Single Step Questionnaire

Background: Pectus excavatum (PE) is the most common congenital chest wall deformity. Most individuals with PE suffer from psychosocial problems, with low self-esteem and poor body image. Correctional surgery for PE is available, the most widely used is the Nuss procedure. The Nuss procedure has previously been reported to improve self-esteem, body image and health-related quality of life (HRQoL). To assess HRQoL among individuals with PE, the Nuss Questionnaire modified for Adults (NQ-mA) and Single Step Questionnaire (SSQ) has been developed. The aim of the current study was to translate and culturally adapt NQ-mA and SSQ to fit a Swedish context, and to evaluate the psychometric properties, and validate the culturally adapted versions. Methods: Individuals who had undergone the Nuss procedure for pectus excavatum were invited to participate in a multicentre study with cross-sectional design. HRQoL was assessed by NQ-mA, SSQ and RAND-36. Psychometric properties for NQ-mA and SSQ were evaluated by content validity index and construct validity (exploratory factor analysis, confirmatory factor analysis, and inter-scale correlations). Known-groups validity, as well as floor and ceiling effects, were evaluated. Internal consistency reliability was examined using Cronbach’s alpha. Results: In total 236 individuals participated in the study. Content validity index for NQ-mA showed satisfactory results, except for two items. Factor analysis for NQ-mA suggested a two-factor model, with exclusion of two items. Subscales correlated adequately with RAND-36’s domains. Known-groups validity for NQ-mA demonstrated high sensitivity for between-group differences. Ceiling effects were present in several items. Cronbach’s alpha for NQ-mA was.89. Confirmatory factor analysis for SSQ resulted in a three-factor model, with exclusion of five items. However, this model was shown to be unstable through further exploratory factor analysis testing, and no further psychometric tests were conducted for SSQ. Conclusion: The 10-item Swedish version of NQ-mA was shown to be valid for research and clinical assessment of HRQoL in individuals with pectus excavatum. The Swedish version of SSQ requires revision of items before further validation can be performed

Utility of NT-proBNP as an objective marker of postoperative heart failure after coronary artery bypass surgery : a prospective observational study

Background: Postoperative heart failure (PHF) is the main cause for mortality after cardiac surgery but unbiased evaluation of PHF is difficult. We investigated the utility of postoperative NT-proBNP as an objective marker of PHF after coronary artery bypass surgery (CABG). Methods: Prospective study on 382 patients undergoing isolated CABG for acute coronary syndrome. NT-proBNP was measured preoperatively, the first (POD1) and third postoperative morning (POD3). A blinded Endpoints Committee used prespecified criteria for PHF. Use of circulatory support was scrutinized. Results: After adjusting for confounders PHF was associated with 1.46 times higher NT-proBNP on POD1 (p = 0.002), 1.54 times higher on POD3 (p &amp;lt; 0.0001). In severe PHF, NT-proBNP was 2.18 times higher on POD1 (p = 0.001) and 1.81 times higher on POD3 (p = 0.019). Postoperative change of NT-proBNP was independently associated with PHF (OR 5.12, 95% CI 1.86-14.10, p = 0.002). The use of inotropes and ICU resources increased with incremental quartiles of postoperative NT-proBNP. Conclusions: Postoperative NT-proBNP can serve as an objective marker of the severity of postoperative myocardial dysfunction. Due to overlap in individuals, NT-proBNP is useful mainly for comparisons at cohort level. As such, it provides a tool for study purposes when an unbiased assessment of prevention or treatment of PHF is desirable.Funding Agencies|Swedish Heart-Lung FoundationSwedish Heart-Lung Foundation [20030595, 20140633]; Region Ostergotland [LIO-443891, LIO693091]; Linkoping University</p