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.

A metabolic protective strategy could improve long-term survival in patients with LV-dysfunction undergoing CABG.

OBJECTIVE: Adverse outcome after CABG is closely related to postoperative heart failure precipitated by ischemia and myocardial infarction. Restrictive use of inotropes is therefore desirable. Patients with preoperative left ventricular dysfunction are a high-risk group in this respect. To reduce myocardial oxygen expenditure we evolved a metabolic strategy for perioperative care. DESIGN: Observational study on 104 consecutive patients with severe left ventricular dysfunction undergoing CABG. The metabolic strategy implied physiological measures to minimize myocardial oxygen expenditure including restrictive use of inotropes and specific measures such as extended CPB and metabolic support to facilitate myocardial recovery. Hemodynamic state was primarily assessed by mixed venous oxygen saturation (SvO(2)). Follow-up averaged 9.7+/-1.4 years. RESULTS: LVEF was 0.30+/-0.05 (range 0.20-0.37) and 3.5+/-1.3 vessels were bypassed. Inotropes were used in 6.7% for weaning from CPB. Increase of s-creatinine by > or =50% compared to preoperative values was observed in 2.9%. Logistic EuroSCORE was 8.3% whereas observed 30-day mortality was 1.0%. Crude 5-year survival was 89.4%. CONCLUSIONS: The metabolic strategy allowed restrictive use of inotropes and was associated with encouraging long-term survival. Renal function was well preserved suggesting that SvO(2) served as an adequate marker of circulation. Randomized trials with metabolic support are warranted.

Does glutamate influence myocardial and peripheral tissue metabolism after aortic valve replacement for aortic stenosis?

BACKGROUND & AIMS: Glutamate plays an important role for myocardial metabolism in association with ischaemia. Patients with coronary artery disease characteristically demonstrate increased uptake of glutamate. Improved recovery of myocardial metabolism and haemodynamic state after coronary surgery has been reported in patients treated with glutamate infusion. However, the effect of glutamate has not been studied after other cardiac surgical procedures. In addition, the effects of glutamate on peripheral tissue metabolism remain to be described. METHODS: Twenty patients undergoing surgery for aortic stenosis were studied after randomisation to blinded infusion of glutamate or saline during 1h immediately after skin closure. Myocardial and leg tissue metabolism were assessed with organ balance techniques. RESULTS: Postoperative glutamate infusion induced a marked increase in myocardial and leg tissue uptake of glutamate. This was associated with a significant uptake of lactate in the heart. The negative arterial-venous differences of amino acids and free fatty acids across the leg were significantly smaller in the glutamate group. Haemodynamic state remained stable and did not differ between groups. CONCLUSION: The heart and peripheral tissues consumed the exogenously administered glutamate after surgery for aortic stenosis. Potentially favourable effects of glutamate on myocardial and peripheral tissue metabolism are suggested.

Early postoperative outcome and medium-term survival in 540 diabetic and 2239 nondiabetic patients undergoing coronary artery bypass grafting.

BACKGROUND: An increasing proportion of patients undergoing coronary artery bypass grafting (CABG) are diabetics. Patient characteristics, early postoperative outcome, and midterm survival in diabetic patients after CABG were investigated. METHODS: A total of 2779 consecutive patients undergoing isolated CABG during 1995 to 1999 were studied, 19.4% of whom had diabetes mellitus. Demographic and peri-procedural data were registered prospectively in a computerized institutional database. RESULTS: The diabetic group was younger and included a higher proportion of women, and patients with hypertension, triple-vessel disease, and unstable angina. They required a higher number of bypasses, and longer cross-clamp and cardiopulmonary bypass times. Intensive care unit and hospital stays were prolonged and the need for inotropic agents, hemotransfusions, and dialysis was higher in the diabetic group. Renal failure, stroke (4.3% versus 1.7%), mediastinitis, and wound infections were more frequently encountered. Thirty-day mortality was 2.6% versus 1.6% (p = 0.15). Cumulative 5-year survival was 84.4% versus 91.3% (p < 0.001). CONCLUSIONS: Short-term mortality was acceptable in diabetic patients after CABG but they had increased postoperative morbidity in comparison with nondiabetic patients, particularly with regard to renal function, cerebral complications, and infections. Midterm survival was impaired in diabetic patients mainly because of a less favorable outcome in patients treated with insulin.

Preoperative NT-proBNP independently predicts outcome in patients with acute coronary syndrome undergoing CABG.

OBJECTIVES: The predictive value of preoperative N-terminal pro-B-type natriuretic peptide (NT-proBNP) was evaluated in patients with acute coronary syndrome undergoing coronary artery bypass grafting (CABG). DESIGN: As a substudy to a clinical trial 383 patients with acute coronary syndrome undergoing CABG were studied. 17 patients had a concomitant procedure. NT-proBNP was measured immediately preoperatively and evaluated with regard to in-hospital mortality, and severe circulatory failure postoperatively according to prespecified criteria. Follow-up was 3.2 ± 0.9 years. RESULTS: In patients with isolated CABG, receiver operating characteristics (ROC) analysis showed an area under the curve (AUC) of 0.82 for in-hospital mortality and 0.87 for severe circulatory failure respectively with a best cut-off for preoperative NT-proBNP of 1028 ng/L. This cut-off level independently predicted severe circulatory failure. Patients with NT-proBNP < 1028 ng/L had significantly better long-term survival (p = 0.004). Preoperative NT-proBNP was higher in patients with concomitant procedure than isolated CABG (2146 ± 1858 v 887 ± 1635 ng/L; p = 0.0005). In patients with concomitant procedure ROC analysis showed an AUC of 0.93 for severe circulatory failure with a best cut-off for preoperative NT-proBNP of 3145 ng/L. CONCLUSIONS: Preoperative NT-proBNP predicted in-hospital mortality, severe circulatory failure postoperatively and long-term survival in patients undergoing surgery for acute coronary syndrome but a higher threshold was found in patients having concomitant procedures.

GLUTAMICS--a randomized clinical trial on glutamate infusion in 861 patients undergoing surgery for acute coronary syndrome.

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 = 428) or saline (n = 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 = .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 = .02) if they were treated with glutamate. In patients with unstable angina (Canadian Cardiovascular Society class IV) undergoing isolated coronary artery bypass grafting (n = 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 = .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 = .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.

The S-100B substudy of the GLUTAMICS trial: glutamate infusion not associated with sustained elevation of plasma S-100B after coronary surgery.

BACKGROUND & AIMS: Concerns have been raised about potential neurological injury related to exogenous glutamate. In cardiac surgery glutamate has been administered as a putative cardioprotective agent by cardioplegia or intravenous infusion. In the GLUTAMICS trial, in addition to surveillance of clinical neurological injuries, a prespecified subgroup was analyzed with regard to postoperative S-100B levels to detect potential subclinical neurological injury related to glutamate infusion. METHODS: Sixty-nine patients operated on for unstable coronary syndrome were randomized to intravenous infusion of glutamate (n=35) or saline (n=34) perioperatively. Plasma levels of S-100B were obtained on the third postoperative day. RESULTS: S-100B in the glutamate group and the control group were 0.079+/-0.034microg/L and 0.090+/-0.042microg/L respectively (p=0.245). There were no patients with stroke or mortality. Three patients in the control group and two in the glutamate group had postoperative confusion. These patients had significantly elevated S-100B compared with those without confusion (0.132+/-0.047vs 0.081+/-0.036microg/L; p=0.003). Overall, 21 patients had S-100B above reference level (> or =0.10microg/L) and these patients had significantly more calcifications in the ascending aorta on epiaortic scanning. CONCLUSIONS: Intravenous glutamate infusion during surgery for unstable coronary artery disease did not initiate a sustained elevation of plasma S-100B. Thus, no evidence for subclinical neurological injury related to glutamate infusion was found. In contrast, postoperative elevation of plasma S-100B was linked to calcification of the ascending aorta and postoperative confusion.

Long-term consequences of postoperative heart failure after surgery for aortic stenosis compared with coronary surgery.

BACKGROUND: Although postoperative heart failure is a major determinant of operative mortality in cardiac surgery it has received little attention in the literature, and long-term consequences remain to be addressed. Therefore, the impact of postoperative heart failure on long-term survival in relation to other risk factors was studied. METHODS: All patients undergoing aortic valve replacement (AVR) for aortic stenosis from 1995 through 2000 in the southeast region of Sweden (n = 398) were compared with a cohort, matched for age and sex, undergoing coronary artery bypass grafting (CABG [n = 398]). Risk factors for 5-year mortality were analyzed. RESULTS: Forty-five AVR and 47 CABG patients required treatment for postoperative heart failure. Thirty-day, 1-year, and 5-year mortality in patients with and without postoperative heart failure after AVR were 6.7% versus 1.4% (p = 0.05), 8.9% versus 4.0% (p = 0.13), and 42.2% versus 14.2% (p < 0.0001) respectively. Corresponding results in the CABG group were 21.3% versus 1.1% (p < 0.0001), 25.5% versus 3.1% (p < 0.0001), and 36.2% versus 11.1% (p = 0.0015). Postoperative heart failure, preoperative renal dysfunction, procedure-associated stroke, body mass index less than 19 kg/m2, older age, preoperative atrial fibrillation, and preoperative anemia turned out as independent risk factors for 5-year mortality after AVR. In the CABG group, postoperative heart failure, diabetes mellitus, older age, and procedure-associated stroke emerged as independent risk factor for 5-year mortality. CONCLUSIONS: Postoperative heart failure was associated with high early mortality after CABG whereas the grave consequences of postoperative heart failure after AVR for aortic stenosis became evident only with time.

Risk factors for postoperative heart failure in patients operated on for aortic stenosis.

BACKGROUND: Risk factors for postoperative heart failure (PHF) have not been specifically studied in valve surgery although it has been acknowledged that patient variables may have a more profound influence on postoperative outcome than valve-related factors. METHODS: All patients undergoing isolated aortic valve replacement for aortic stenosis from January 1995 to December 2000 in the southeast region of Sweden were studied (n = 398). Forty-five patients with aortic valve replacement required treatment for PHF. Univariate and multivariate logistic regression analysis was carried out to identify risk factors for PHF. RESULTS: Thirty-day mortality was 6.7% versus 1.4% for patients with and without PHF, respectively (p = 0.05). With regard to clinical presentation of aortic stenosis, angina was associated with reduced risk, whereas history of congestive heart failure increased the risk for PHF. Five preoperative (hypertension, history of congestive heart failure, severe systolic left ventricular dysfunction, pulmonary hypertension, preoperative hemodynamic instability) and two intraoperative (aortic cross-clamp time, intraoperative myocardial infarction) variables were identified as independent risk factors for PHF. Patient-prosthesis mismatch did not influence the risk of PHF significantly. CONCLUSIONS: Postoperative heart failure was associated with a marked increase in postoperative mortality and morbidity. Risk factors for PHF were variables indicating preexisting myocardial dysfunction, increased right or left ventricular afterload, and intraoperative myocardial injury. Our results highlight issues concerning cross-clamp time and myocardial protection, particularly for patients with preoperatively compromised myocardial function. Asymptomatic patients with significant aortic stenosis should be considered for surgery before substantial echocardiographic evidence of left ventricular dysfunction or increased pulmonary artery pressure develops.

Myocardial uptake and release of substrates in patients operated for unstable angina: impact of glutamate infusion.

OBJECTIVE: To study cardiac uptake and release of substrates and the influence of intravenous glutamate in patients operated for unstable angina requiring intravenous nitrates. DESIGN: Nineteen patients were randomized to blinded infusion of glutamate or saline. Arterial-coronary sinus differences of substrates were measured before cardiopulmonary bypass (CPB) and during early reperfusion. RESULTS: Before CPB the only major substrates that were extracted by the heart in the saline group were free fatty acids (FFAs). During reperfusion uptake of glucose and glutamate was found but FFAs remained the major substrate extracted by the heart. Initially transient low oxygen extraction and lactate release were found. Conversion to lactate uptake was not observed. Glutamate infusion was associated with an uptake of glutamate and in contrast to the control group there was also uptake of lactate before CPB and at the end of the study period. CONCLUSION: The metabolic situation before CPB with a reliance on myocardial FFA uptake is less than ideal with regard to ischemia. Early reperfusion was characterized by dynamic changes and a shift towards myocardial glucose uptake but FFAs remained the major substrate extracted. The qualitative findings associated with glutamate infusion agree with previous animal and human studies but have to be interpreted cautiously due to lack of flow measurements

Different characteristics of postoperative heart failure after surgery for aortic stenosis and coronary disease.

OBJECTIVE: Postoperative heart failure (PHF) remains a major determinant of outcome after cardiac surgery. However, possible differences in characteristics of PHF after valve surgery and coronary surgery (CABG) have received little attention. Therefore, this issue was studied in patients undergoing aortic valve replacement (AVR) and CABG, respectively. DESIGN: Three hundred and ninety-eight patients undergoing isolated AVR for aortic stenosis were compared with 398 patients, matched for age and sex, undergoing on-pump isolated CABG. Forty-five AVR and 47 CABG patients required treatment for PHF and these were studied in detail. RESULTS: The AVR group had longer aortic cross-clamp time and higher rate of isolated right ventricular heart failure postoperatively. Myocardial ischemia during induction and perioperative myocardial infarction were more common in the CABG group. One-year mortality was 8.9% in the AVR group vs 25.5% in the CABG group (p = 0.05). CONCLUSIONS: The incidence of PHF was similar in both groups but different characteristics were found. Isolated right ventricular failure and PHF precipitated by septicemia were more common in AVR patients. PHF was more clearly associated with myocardial ischemia and infarction in CABG patients, which could explain their less favorable survival.

Post-infarct left ventricular free wall rupture and ventricular septal defect managed by pericardial aspiration during transport to referral hospital.

Although left ventricular free wall rupture is a comparatively common cause of death in acute myocardial infarction survival is infrequently reported. However, even in cases where surgical expertise is not immediately available the condition can be temporarily controlled by judicious pericardial aspiration and blood transfusion until definitive repair can be undertaken. Here we report the successful management of a patient sustaining combined left ventricular free wall rupture and ventricular septal rupture in a community hospital 130 km from the referral center.