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GLUTAMICS: a randomized clinical trial on glutamate infusion in patients operated for acute coronary syndrome
Örebro University, School of Health and Medical Sciences.
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2011 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: Glutamate has been claimed to protect the heart from ischemia and to facilitate metabolic and hemodynamic recovery after ischemia. The GLUTAMICS-trial investigated if intravenous glutamate infusion given in association with surgery for acute coronary syndrome can reduce mortality and prevent or mitigate myocardial injury and postoperative heart failure. Methods: In this investigator-initiated prospective, double-blind study 861 patients undergoing surgery for acute coronary syndrome in three Swedish Hospitals were randomly assigned to intravenous infusion of glutamate (n=428) or saline (n=433) perioperatively. The primary endpoint was a composite of postoperative mortality (30 days), perioperative myocardial infarction and left ventricular heart failure on weaning from cardiopulmonary bypass. Results: Thirty-day mortality was 0.9 % in the glutamate group and 1.2% in the control group. Cardiac mortality was 0.2% in the glutamate group and 0.9% the control group. The incidence of the composite primary end point was 7.2% in the glutamate group and 5.8% in the control group. None of these differences were statistically significant. Regarding secondary end points significantly fewer patients in the glutamate group were hemodynamically unstable at completion of surgery (0.3% v 1.8%; p=0.035) or in need of intra-aortic balloon pump on arrival to the intensive care unit (0.0% v 1.2%; p=0.026). In patients with severe unstable angina (CCS class IV; n=475) the incidence of severe circulatory failure according to prespecified criteria was significantly lower in the glutamate group (2.6% v 6.6%; p=0.036). Conclusions: The primary endpoint did not differ significantly between the groups. Regarding secondary end points there were significant differences compatible with a beneficial effect of glutamate on myocardial recovery. (ClinicalTrials.gov Identifier: NCT00489827)

Place, publisher, year, edition, pages
2011. Vol. 57, no 14, supplement, p. E938-
National Category
Medical and Health Sciences Surgery
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-20140DOI: 10.1016/S0735-1097(11)60938-8OAI: oai:DiVA.org:oru-20140DiVA, id: diva2:450626
Available from: 2011-10-21 Created: 2011-10-21 Last updated: 2017-10-17Bibliographically approved
In thesis
1. Glutamate for metabolic intervention in coronary surgery: with special reference to the GLUTAMICS-trial
Open this publication in new window or tab >>Glutamate for metabolic intervention in coronary surgery: with special reference to the GLUTAMICS-trial
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2011. p. 87
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 58
Keywords
myocardial ischemia, coronary artery bypass, cardiac surgery, acute coronary syndrome, glutamate, metabolic intervention, postoperative heart failure, myocardial recovery
National Category
Medical and Health Sciences Clinical Medicine Surgery
Research subject
Surgery
Identifiers
urn:nbn:se:oru:diva-19757 (URN)978-91-7668-824-3 (ISBN)
Public defence
2011-11-11, Wilandersalen, Universitetssjukhuset, Örebro, 09:00 (Swedish)
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Supervisors
Available from: 2011-10-07 Created: 2011-10-07 Last updated: 2017-10-17Bibliographically approved

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Publisher's full texthttp://content.onlinejacc.org/cgi/reprint/57/14_Suppl_S/E938

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Vidlund, Mårten

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