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

Mårten Vidlund, Bashir Tajik, Erik Håkanson, Örjan Friberg, Jonas Holm, Farkas Vanky, Rolf Svedjeholm, Mårten Vidlund, Bashir Tajik, Erik Håkanson, Örjan Friberg, Jonas Holm, Farkas Vanky, Rolf Svedjeholm

Abstract

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.

Keywords: Coronary artery bypass surgery; Epinephrine; Glutamate; Inotropic drugs; Intensive care; Milrinone; Postoperative complications.

Figures

Fig. 1
Fig. 1
Flowchart of patient selection and presentation of results at three different levels

References

    1. Vidlund M, Hakanson E, Friberg O, Juhl-Andersen S, Holm J, Vanky F, Sunnermalm L, Borg JO, Sharma R, Svedjeholm R. GLUTAMICS - a randomized clinical trial on glutamate infusion in 861 patients undergoing surgery for acute coronary syndrome. J Thorac Cardiovasc Surg. 2012;144(4):922–30. doi: 10.1016/j.jtcvs.2012.05.066.
    1. Svedjeholm R, Hakanson E, Szabo Z. Routine SvO2 measurement after CABG surgery with a surgically introduced pulmonary artery catheter. Eur J Cardiothorac Surg. 1999;16(4):450–7. doi: 10.1016/S1010-7940(99)00287-0.
    1. Holm J, Hakanson E, Vanky F, Svedjeholm R. Mixed venous oxygen saturation predicts short- and long-term outcome after coronary artery bypass grafting surgery: a retrospective cohort analysis. Br J Anaesth. 2011;107(3):344–50. doi: 10.1093/bja/aer166.
    1. Svedjeholm R, Vidlund M, Vanhanen I, Hakanson E. A metabolic protective strategy could improve long-term survival in patients with LV-dysfunction undergoing CABG. Scand Cardiovasc J. 2010;44(1):45–58. doi: 10.3109/14017430903531008.
    1. O’Connor GT, Birkmeyer JD, Dacey LJ, Quinton HB, Marrin CA, Birkmeyer NJ, Morton JR, Leavitt BJ, Maloney CT, Hernandez F, et al. Results of a regional study of modes of death associated with coronary artery bypass grafting. Northern New England Cardiovascular Disease Study Group. Ann Thorac Surg. 1998;66(4):1323–8. doi: 10.1016/S0003-4975(98)00762-0.
    1. Vanky F, Hakanson E, Maros T, Svedjeholm R. Different characteristics of postoperative heart failure after surgery for aortic stenosis and coronary disease. Scand Cardiovasc J. 2004;38(3):152–8. doi: 10.1080/14017430410029734.
    1. Vanky FB, Hakanson E, Svedjeholm R. Long-term consequences of postoperative heart failure after surgery for aortic stenosis compared with coronary surgery. Ann Thorac Surg. 2007;83(6):2036–43. doi: 10.1016/j.athoracsur.2007.01.031.
    1. Maganti MD, Rao V, Borger MA, Ivanov J, David TE. Predictors of low cardiac output syndrome after isolated aortic valve surgery. Circulation. 2005;112(9 Suppl):I448–52.
    1. Kirklin JW, Rastelli GC. Low cardiac output after open intracardiac operations. Prog Cardiovasc Dis. 1967;10(2):117–22. doi: 10.1016/0033-0620(67)90003-5.
    1. Gillies M, Bellomo R, Doolan L, Buxton B. Bench-to-bedside review: Inotropic drug therapy after adult cardiac surgery - a systematic literature review. Crit Care. 2005;9(3):266–79. doi: 10.1186/cc3024.
    1. Mebazaa A, Pitsis AA, Rudiger A, Toller W, Longrois D, Ricksten SE, Bobek I, De Hert S, Wieselthaler G, Schirmer U, et al. Clinical review: practical recommendations on the management of perioperative heart failure in cardiac surgery. Crit Care. 2010;14(2):201. doi: 10.1186/cc8153.
    1. Fellahi JL, Parienti JJ, Hanouz JL, Plaud B, Riou B, Ouattara A. Perioperative use of dobutamine in cardiac surgery and adverse cardiac outcome: propensity-adjusted analyses. Anesthesiology. 2008;108(6):979–87. doi: 10.1097/ALN.0b013e318173026f.
    1. Svedjeholm R, Hallhagen S, Ekroth R, Joachimsson PO, Ronquist G. Dopamine and high-dose insulin infusion (glucose-insulin-potassium) after a cardiac operation: effects on myocardial metabolism. Ann Thorac Surg. 1991;51(2):262–70. doi: 10.1016/0003-4975(91)90798-U.
    1. Lazar HL, Buckberg GD, Foglia RP, Manganaro AJ, Maloney JV., Jr Detrimental effects of premature use of inotropic drugs to discontinue cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1981;82(1):18–25.
    1. Hakanson E, Svedjeholm R, Vanhanen I. Physiologic aspects in postoperative cardiac patients. Ann Thorac Surg. 1995;59(2 Suppl):S12–4. doi: 10.1016/0003-4975(94)00902-J.
    1. Maroko PR, Kjekshus JK, Sobel BE, Watanabe T, Covell JW, Ross J, Jr, Braunwald E. Factors influencing infarct size following experimental coronary artery occlusions. Circulation. 1971;43(1):67–82. doi: 10.1161/01.CIR.43.1.67.
    1. Slogoff S, Keats AS. Does perioperative myocardial ischemia lead to postoperative myocardial infarction? Anesthesiology. 1985;62(2):107–14. doi: 10.1097/00000542-198502000-00002.
    1. Aya HD, Cecconi M, Hamilton M, Rhodes A. Goal-directed therapy in cardiac surgery: a systematic review and meta-analysis. Br J Anaesth. 2013;110(4):510–7. doi: 10.1093/bja/aet020.
    1. Giglio M, Dalfino L, Puntillo F, Rubino G, Marucci M, Brienza N. Haemodynamic goal-directed therapy in cardiac and vascular surgery. A systematic review and meta-analysis. Interact Cardiovasc Thorac Surg. 2012;15(5):878–87. doi: 10.1093/icvts/ivs323.
    1. Shahin J, DeVarennes B, Tse CW, Amarica DA, Dial S. The relationship between inotrope exposure, six-hour postoperative physiological variables, hospital mortality and renal dysfunction in patients undergoing cardiac surgery. Crit Care. 2011;15(4):R162. doi: 10.1186/cc10302.
    1. Rau EE, Shine KI, Gervais A, Douglas AM, Amos EC. Enhanced mechanical recovery of anoxic and ischemic myocardium by amino acid perfusion. Am J Physiol. 1979;236(6):H873–9.
    1. Safer B. The metabolic significance of the malate-aspartate cycle in heart. Circ Res. 1975;37(5):527–33. doi: 10.1161/01.RES.37.5.527.
    1. Pisarenko OI. Mechanisms of myocardial protection by amino acids: facts and hypotheses. Clin Exp Pharm Physiol. 1996;23(8):627–33. doi: 10.1111/j.1440-1681.1996.tb01748.x.
    1. Svedjeholm R, Hakanson E, Vanhanen I. Rationale for metabolic support with amino acids and glucose-insulin-potassium (GIK) in cardiac surgery. Ann Thorac Surg. 1995;59(2 Suppl):S15–22. doi: 10.1016/0003-4975(94)00917-V.
    1. Lazar HL, Buckberg GD, Manganaro AJ, Becker H. Myocardial energy replenishment and reversal of ischemic damage by substrate enhancement of secondary blood cardioplegia with amino acids during reperfusion. J Thorac Cardiovasc Surg. 1980;80(3):350–9.
    1. Haas GS, DeBoer LW, O’Keefe DD, Bodenhamer RM, Geffin GA, Drop LJ, Teplick RS, Daggett WM. Reduction of postischemic myocardial dysfunction by substrate repletion during reperfusion. Circulation. 1984;70(3 Pt 2):I65–74.
    1. Engelman RM, Rousou JA, Flack JE, Iyengar J, Kimura Y, Das DK. Reduction of infarct size by systemic amino acid supplementation during reperfusion. J Thorac Cardiovasc Surg. 1991;101(5):855–9.
    1. Pisarenko OI, Lepilin MG, Ivanov VE. Cardiac metabolism and performance during L-glutamic acid infusion in postoperative cardiac failure. Clin Sci. 1986;70(1):7–12. doi: 10.1042/cs0700007.
    1. Svedjeholm R, Vanhanen I, Hakanson E, Joachimsson PO, Jorfeldt L, Nilsson L. Metabolic and hemodynamic effects of intravenous glutamate infusion early after coronary operations. J Thorac Cardiovasc Surg. 1996;112(6):1468–77. doi: 10.1016/S0022-5223(96)70005-3.
    1. Loop FD, Higgins TL, Panda R, Pearce G, Estafanous FG. Myocardial protection during cardiac operations. Decreased morbidity and lower cost with blood cardioplegia and coronary sinus perfusion. J Thorac Cardiovasc Surg. 1992;104(3):608–18.
    1. Svedjeholm R, Hakanson E, Szabo Z, Vanky F. Neurological injury after surgery for ischemic heart disease: risk factors, outcome and role of metabolic interventions. Eur J Cardiothorac Surg. 2001;19(5):611–8. doi: 10.1016/S1010-7940(01)00664-9.
    1. Vidlund M, Holm J, Hakanson E, Friberg O, Sunnermalm L, Vanky F, Svedjeholm R. The S-100B substudy of the GLUTAMICS trial: Glutamate infusion not associated with sustained elevation of plasma S-100B after coronary surgery. Clin Nutr. 2009;21(3):358–64.
    1. Vanhanen I, Svedjeholm R, Hakanson E, Joachimsson PO, Jorfeldt L, Nilsson L, Vanky F. Assessment of myocardial glutamate requirements early after coronary artery bypass surgery. Scand Cardiovasc J. 1998;32(3):145–52. doi: 10.1080/14017439850140102.

Source: PubMed

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