Glucose-insulin-potassium reduces the incidence of low cardiac output episodes after aortic valve replacement for aortic stenosis in patients with left ventricular hypertrophy: results from the Hypertrophy, Insulin, Glucose, and Electrolytes (HINGE) trial.

BACKGROUND: Patients undergoing aortic valve replacement for critical aortic stenosis often have significant left ventricular hypertrophy. Left ventricular hypertrophy has been identified as an independent predictor of poor outcome after aortic valve replacement as a result of a combination of maladaptive myocardial changes and inadequate myocardial protection at the time of surgery. Glucose-insulin-potassium (GIK) is a potentially useful adjunct to myocardial protection. This study was designed to evaluate the effects of GIK infusion in patients undergoing aortic valve replacement surgery. METHODS AND RESULTS: Patients undergoing aortic valve replacement for aortic stenosis with evidence of left ventricular hypertrophy were randomly assigned to GIK or placebo. The trial was double-blind and conducted at a single center. The primary outcome was the incidence of low cardiac output syndrome. Left ventricular biopsies were analyzed to assess changes in 5' adenosine monophosphate-activated protein kinase (AMPK), Akt phosphorylation, and protein O-linked ß-N-acetylglucosamination (O-GlcNAcylation). Over a 4-year period, 217 patients were randomized (107 control, 110 GIK). GIK treatment was associated with a significant reduction in the incidence of low cardiac output state (odds ratio, 0.22; 95% confidence interval, 0.10 to 0.47; P=0.0001) and a significant reduction in inotrope use 6 to 12 hours postoperatively (odds ratio, 0.30; 95% confidence interval, 0.15 to 0.60; P=0.0007). These changes were associated with a substantial increase in AMPK and Akt phosphorylation and a significant increase in the O-GlcNAcylation of selected protein bands. CONCLUSIONS: Perioperative treatment with GIK was associated with a significant reduction in the incidence of low cardiac output state and the need for inotropic support. This benefit was associated with increased signaling protein phosphorylation and O-GlcNAcylation. Multicenter studies and late follow-up will determine whether routine use of GIK improves patient prognosis.

Deep sternal wound infection requiring revision surgery: impact on mid-term survival following cardiac surgery.

OBJECTIVE: To assess the impact of deep sternal wound infection on in-hospital mortality and mid-term survival following adult cardiac surgery. METHODS: Prospectively collected data on 4586 consecutive patients who underwent a cardiac surgical procedure via a median sternotomy from 1st January 2001 to 31st December 2005 were analysed. Patients with a deep sternal wound infection (DSWI) were identified in accordance with the Centres for Disease Control and Prevention guidelines. Nineteen variables (patient-related, operative and postoperative) were analysed. Logistic regression analysis was used to calculate a propensity score for each patient. Late survival data were obtained from the UK Central Cardiac Audit Database. Mean follow-up of DSWI patients was 2.28 years. RESULTS: DSWI requiring revision surgery developed in 1.65% (76/4586) patients. Stepwise multivariable logistic regression analysis identified age, diabetes, a smoking history and ventilation time as independent predictors of a DSWI. DSWI patients were more likely to develop renal failure, require reventilation and a tracheostomy postoperatively. Treatment included vacuum assisted closure therapy in 81.5% (62/76) patients and sternectomy with musculocutaneous flap reconstruction in 35.5% (27/76) patients. In-hospital mortality was 9.2% (7/76) in DSWI patients and 3.7% (167/4510) in non-DSWI patients (OR 1.300 (0.434-3.894) p=0.639). Survival with Cox regression analysis with mean propensity score (co-variate) showed freedom from all-cause mortality in DSWI at 1, 2, 3 and 4 years was 91%, 89%, 84% and 79%, respectively compared with 95%, 93%, 90% and 86%, respectively for patients without DSWI ((p=0.082) HR 1.59 95% CI (0.94-2.68)). CONCLUSION: DSWI is not an independent predictor of a higher in-hospital mortality or reduced mid-term survival following cardiac surgery in this population.

Mild renal dysfunction predicts in-hospital mortality and post-discharge survival following cardiac surgery.

OBJECTIVES: To assess the impact of preoperative renal dysfunction on in-hospital mortality and late survival outcome following adult cardiac surgery. METHODS: Prospectively collected data were analysed on 7621 consecutive patients not requiring preoperative renal-replacement therapy, who underwent CABG, valve surgery or combined procedures from 1/1/98 to 1/12/06. Preoperative estimated glomerular filtration rate was calculated using Cockcroft-Gault formula. Patients were classified in the four chronic kidney disease (CKD) stage classes defined by the National Kidney Foundation Disease Outcome Quality Initiative Advisory Board. Late survival data were obtained from the UK Central Cardiac Audit Database. RESULTS: There were 243 in-hospital deaths (3.2%). There was a stepwise increase in operative mortality with each CKD class independent of the type of surgery. Multivariate analysis confirmed CKD class to be an independent predictor of in-hospital mortality (class 2 OR 1.45, 95% CI 1.1-2.35, p=0.001; class 3 OR 2.8, 95% CI 1.68-4.46, p=0.0001; class 4 OR 7.5, 95% CI 3.76-15.2, p=0.0001). The median follow-up after surgery was 42 months (IQR 18-74) and there were 728 late deaths. Survival analysis using a Cox regression model confirmed CKD class to be an independent predictor of late survival (class 2 HR 1.2, 95% CI 1.1-1.6, p=0.0001; class 3 HR 1.95, 95% CI 1.6-2.4, p=0.0001; and class 4 HR 3.2, 95% CI 2.2-4.6, p=0.0001). Ninety-eight percent (7517/7621) of patients had a preoperative creatinine <200 micromol/l, which is not included as a risk factor in most risk stratification systems. CONCLUSIONS: Mild renal dysfunction is an important independent predictor of in-hospital and late mortality in adult patients undergoing cardiac surgery.

Glucose-insulin-potassium and tri-iodothyronine individually improve hemodynamic performance and are associated with reduced troponin I release after on-pump coronary artery bypass grafting.

BACKGROUND: Both glucose-insulin-potassium (GIK) and tri-iodothyronine (T3) may improve cardiovascular performance after coronary artery surgery (CABG) but their effects have not been directly compared and the effects of combined treatment are unknown. METHODS AND RESULTS: In 2 consecutive randomized double-blind placebo-controlled trials, in patients undergoing first time isolated on-pump CABG between January 2000 and September 2004, 440 patients were recruited and randomized to either placebo (5% dextrose) (n=160), GIK (40% dextrose, K+ 100 mmol.L(-1), insulin 70 u.L(-1)) (0.75 mL.kg(-1) h(-1)) (n=157), T3 (0.8 microg.kg(-1) followed by 0.113 microg.kg(-1) h(-1)) (n=63) or GIK+T3 (n=60). GIK/placebo therapy was administered from start of operation until 6 hours after removal of aortic cross-clamp (AXC) and T3/placebo was administered for a 6-hour period from removal of AXC. Serial hemodynamic measurements were taken up to 12 hours after removal of AXC and troponin I (cTnI) levels were assayed to 72 hours. Cardiac index (CI) was significantly increased in both the GIK and GIK/T3 group in the first 6 hours compared with placebo (P<0.001 for both) and T3 therapy (P=0.009 and 0.029, respectively). T3 therapy increased CI versus placebo between 6 and 12 hours after AXC removal (P=0.01) but combination therapy did not. Release of cTnI was lower in all treatment groups at 6 and 12 hours after removal of AXC. CONCLUSIONS: Treatment with GIK, T3, and GIK/T3 improves hemodynamic performance and results in reduced cTnI release in patients undergoing on-pump CABG surgery. Combination therapy does not provide added hemodynamic effect.

Relation between mild renal dysfunction and outcomes after coronary artery bypass grafting.

BACKGROUND: Risk stratification algorithms for coronary artery bypass grafting (CABG) do not include a weighting for preoperative mild renal impairment defined as a serum creatinine 130 to 199 micromol/L (1.47 to 2.25 mg/dL), which may impact mortality and morbidity after CABG. METHODS AND RESULTS: We reviewed prospectively collected data between 1997 and 2004 on 4403 consecutive patients undergoing first-time isolated CABG with a preoperative serum creatinine <200 micromol/L (2.26 mg/dL)] in a single institution. The in-hospital mortality was 2.5% (112 of 4403), the need for new dialysis/hemofiltration was 1.3% (57 of 4403), and the stroke rate was 2.5% (108 of 4403). There were 458 patients with a serum creatinine 130 to 199 micromol/L or 1.47 to 2.25 mg/dL (mild renal dysfunction group) and 3945 patients with a serum creatinine <130 micromol/L (<1.47 mg/dL). Operative mortality was higher in the mild renal dysfunction group (2.1% versus 6.1%; P<0.001) and increased with increasing preoperative serum creatinine level. New dialysis/hemofiltration (0.8%versus 5.2%; P<0.001) and postoperative stroke (2.2% versus 5.0%; P<0.01) were also more common in the patients with mild renal impairment. Multivariate analysis adjusting for known risk factors confirmed preoperative mild renal impairment (creatinine 130 to 199 micromol/L or 1.47 to 2.25 mg/dL; odd ratio, 1.91; 95% CI, 1.18 to 3.03; P=0.007) or glomerular filtration rate estimates <60 mL/min per 1.73 m2, derived using the Cockroft-Gault formula, (odds ratio, 1.98; 95% CI, 1.16 to 3.48; P=0.015) as independent predictors of in-hospital mortality. Preoperative mild renal dysfunction adversely affected the 3-year survival probability after CABG (93% versus 81%; P<0.001). CONCLUSIONS: Mild renal dysfunction is an important predictor of outcome in terms of in-hospital mortality, morbidity, and midterm survival in patients undergoing CABG.

Patient-prosthesis mismatch does not affect survival following aortic valve replacement.

OBJECTIVE: Patient-prosthesis mismatch (PPM) has been reported to increase perioperative mortality and reduce postoperative survival in patients undergoing aortic valve replacement (AVR). We analysed the effect of PPM at values predicting severe mismatch on survival following AVR in our unit. METHODS: Prospectively collected data on 1481 consecutive patients who had undergone AVR with or without coronary artery revascularisation between 1997 and 2005 were analysed. Projected in vitro valve effective orifice area (EOA) and geometric prosthesis internal orifice area (GOA) were evaluated and values were indexed to body surface area (cm(2)m(-2)). PPM was defined as EOAi<0.6 and/or GOAi<1.1. Long-term survival data were obtained from the National Institute of Statistics. RESULTS: One thousand four hundred and eighteen patients were identified. 67/1418 (4.7%) patients had GOAi<1.1; 122/1418 (8.6%) had EOAi<0.6 and 38 (2.6%) patients exhibited both forms of mismatch. One thousand two hundred and sixty-seven patients (89%) demonstrated no mismatch (reference group). There were 75 in-hospital deaths (overall mortality 5.3%) with no significant difference between the mismatch and the reference groups. Survival data were available for up to 8 years (median 36 months, IQR 6-60 months). There were 160 late deaths (13/143 PPM group vs 147/1198 reference group). The 5-year survival estimate was similar for both groups (83% PPM group; 81% reference group; p=0.47). Cox-hazard analysis identified advanced age as the only predictor of reduced survival (age>80, RR 2.13, 95% CI 1.38-4.586, p=0.004). CONCLUSIONS: Severe patient-prosthesis mismatch was predicted in 4-10% of patients undergoing AVR but this did not affect in-hospital mortality or mid-term survival.

Racial and Gender Influences on Pass Rates for the UK and Ireland Specialty Board Examinations.

INTRODUCTION: We explored effects of gender, ethnic origin, first language, and training status on scores in the Intercollegiate Specialty Board examinations in the UK and Ireland across the computer-marked written section and in the face-to-face oral and clinical section. METHODS: Demographic characteristics and examination results from 9987 attempts across 177 sittings from 2009 to 2013 were analyzed in an analysis of variance by training status, gender, ethnic origin, first language, and section (computer-marked multiple-choice examination vs face-to-face oral and clinical examination). RESULTS: We found increasing alignment between examiner and candidate characteristics during this period, with a 50% increase in examiners of Asian ethnic origin and a 60% increase in examiners whose first language is not English. The strongest factor in the analysis of variance was training status (F[2, 9818] = 27.67, p < 0.001), with candidates in training significantly outperforming others. Within "core candidates" (first attempt, in training), we found significant main effects for ethnic origin (F[5, 4809] = 2.36, p = 0.04), and first language (F[2, 4809] = 5.29, p = 0.003), but no interaction effects between these factors and section (both F < 1, p > 0.05). CONCLUSIONS: Training status was the most important factor in candidates' results. Although the analysis showed significant effects of ethnic origin and first language within "core candidates," these differences were statistically indistinguishable between the 2 sections of the examination, suggesting that the differential attainment by these factors cannot be attributed to examiner bias in a face-to-face examination.

Multicentre double-blind randomized controlled trial of perhexiline as a metabolic modulator to augment myocardial protection in patients with left ventricular hypertrophy undergoing cardiac surgery.

OBJECTIVES: Patients undergoing cardiac surgery require adequate myocardial protection. Manipulating myocardial metabolism may improve the extent of myocardial protection. Perhexiline has been shown to be an effective anti-anginal agent due to its metabolic modulation properties by inhibiting the uptake of free fatty acids into the mitochondrion, and thereby promoting a more efficient carbohydrate-driven myocardial metabolism. Metabolic modulation may augment myocardial protection, particularly in patients with left ventricular hypertrophy (LVH) known to have a deranged metabolic state and are at risk of poor postoperative outcomes. This study aimed to evaluate the role of perhexiline as an adjunct in myocardial protection in patients with LVH secondary to aortic stenosis (AS), undergoing an aortic valve replacement (AVR). METHODS: In a multicentre double-blind randomized controlled trial of patients with AS undergoing AVR ± coronary artery bypass graft surgery, patients were randomized to preoperative oral therapy with either perhexiline or placebo. The primary end point was incidence of inotrope use to improve haemodynamic performance due to a low cardiac output state during the first 6 h of reperfusion, judged by a blinded end points committee. Secondary outcome measures included haemodynamic measurements, electrocardiographic and biochemical markers of new myocardial injury and clinical safety outcome measures. RESULTS: The trial was halted early on the advice of the Data Safety and Monitoring Board. Sixty-two patients were randomized to perhexiline and 65 to placebo. Of these, 112 (54 perhexiline and 48 placebo) patients received the intervention, remained in the trial at the time of the operation and were analysed. Of 110 patients who achieved the primary end point, 30 patients (16 perhexiline and 14 placebo) had inotropes started appropriately; there was no difference in the incidence of inotrope usage OR of 1.65 [confidence interval (CI): 0.67-4.06] P = 0.28. There was no difference in myocardial injury as evidenced by electrocardiogram odds ratio (OR) of 0.36 (CI: 0.07-1.97) P = 0.24 or postoperative troponin release. Gross secondary outcome measures were comparable between the groups. CONCLUSIONS: Perhexiline as a metabolic modulator to enhance standard myocardial protection does not provide an additional benefit in haemodynamic performance or attenuate myocardial injury in the hypertrophied heart secondary to AS. The role of perhexiline in cardiac surgery is limited.

The effect of perhexiline on myocardial protection during coronary artery surgery: a two-centre, randomized, double-blind, placebo-controlled trial.

OBJECTIVES: Perhexiline is thought to modulate metabolism by inhibiting mitochondrial carnitine palmitoyltransferase-1, reducing fatty acid uptake and increasing carbohydrate utilization. This study assessed whether preoperative perhexiline improves markers of myocardial protection in patients undergoing coronary artery bypass graft surgery and analysed its effect on the myocardial metabolome. METHODS: In a prospective, randomized, double-blind, placebo-controlled trial, patients at two centres were randomized to receive either oral perhexiline or placebo for at least 5 days prior to surgery. The primary outcome was a low cardiac output episode in the first 6 h. All pre-specified analyses were conducted according to the intention-to-treat principle with a statistical power of 90% to detect a relative risk of 0.5 and a conventional one-sided α-value of 0.025. A subset of pre-ischaemic left ventricular biopsies was analysed using mass spectrometry-based metabolomics. RESULTS: Over a 3-year period, 286 patients were randomized, received the intervention and were included in the analysis. The incidence rate of a low cardiac output episode in the perhexiline arm was 36.7% (51/139) vs 34.7% (51/147) in the control arm [odds ratio (OR) 0.92, 95% confidence interval (CI) 0.56-1.50, P = 0.74]. Perhexiline was associated with a reduction in the cardiac index at 6 h [difference in means 0.19, 95% CI 0.07-0.31, P = 0.001] and an increase in inotropic support in the first 12 h (OR 0.55, 95% CI 0.34-0.89, P = 0.015). There were no significant differences in myocardial injury with troponin-T or electrocardiogram, reoperation, renal dysfunction or length of stay. No difference in the preischaemic left ventricular metabolism was identified between groups on metabolomics analysis. CONCLUSIONS: Preoperative perhexiline does not improve myocardial protection in patients undergoing coronary surgery and in fact reduced perioperative cardiac output, increasing the need for inotropic support. Perhexiline has no significant effect on the mass spectrometry-visible polar myocardial metabolome in vivo in humans, supporting the suggestion that it acts via a pathway that is independent of myocardial carnitine palmitoyltransferase inhibition and may explain the lack of clinical benefit observed following surgery. CLINICALTRIALSGOV ID: NCT00845364.

Subtle changes in renal function are associated with differences in late survival following adult cardiac surgery.

OBJECTIVES: To determine the predictors of post-operative renal function following adult cardiac surgery, and to assess the influence of this on late survival. METHODS: Prospectively collected data were analysed on 8032 patients who underwent coronary artery bypass grafting, valve surgery or combined procedures from 1 January 1998 until 31 December 2008, who did not require preoperative renal replacement therapy. The estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease formula accounting for ethnicity pre-operatively, post-operatively on the fourth post-operative day, and the post-operative nadir based upon the peak post-operative creatinine within 30 days of surgery. Late survival data were obtained from the UK Central Cardiac Audit Database (CCAD). Appropriate frailty analyses were conducted in R and model fit was compared using Aikaike's Information Criterion. Initial analysis intended to determine predictors of post-operative renal function including pre-operative eGFR, EuroSCORE and surgical procedure including the operative procedure and bypass time. Further analysis examined its influence on late survival. RESULTS: Median follow-up was 72 months (IQR 48-105) during which there were 904 late deaths. The most powerful predictor of the day 4 eGFR was the pre-operative eGFR but other factors contributed including increasing EuroSCORE and bypass time. The pre-operative eGFR was shown to be a strong and independent predictor of late outcome (P = 0.0001, HR 0.497 95%CI 0.434-564); however, model fit was significantly improved using the day 4 eGFR (P = 0.0001, HR 0.43 95%CI 0.385-0.482). No specific change in individual renal function was identified as a predictor of adverse late survival, and neither the pre-operative nor day 4 eGFR was predictive of the nadir of renal function. CONCLUSIONS: Subtle early changes in renal function at the time of surgery are powerful predictors of adverse late outcome and can be predicted by pre-operative renal function.

Contemporary outcomes of urgent coronary artery bypass graft surgery following non-ST elevation myocardial infarction: urgent coronary artery bypass graft surgery consistently outperforms Global Registry of Acute Coronary Events predicted survival.

OBJECTIVES: The Global Registry of Acute Coronary Events (GRACE) registry reported that the in-hospital risk of death from non-ST elevation myocardial infarction (NSTEMI) is 5%, with an 11% mortality by 6 months. Prospective Registry of Acute Ischaemic Syndromes in the UK demonstrated that the overall risk of death from NSTEMI over 4 years is 25%. In GRACE, while 28% of patients received percutaneous intervention, only 10% received coronary artery bypass graft (CABG). Results of urgent CABG surgery following NSTEMI are difficult to interpret as these often include patients who have had STEMIs and urgent surgery. With increasing multidisciplinary assessment of patients with acute coronary syndromes (ACS), accurate data collection on the outcome of such patients could inform correct revascularization strategy. METHODS: Three hundred and forty-two consecutive patients who had undergone urgent CABG from April 2004 to April 2009 at a single institution were identified. The GRACE predicted mortality was calculated from hospital records and patients categorized into three groups based upon their predicted risk. Late survival data were obtained from the UK Office of National Statistics. RESULTS: The GRACE score could be calculated in 270 patients with a confirmed diagnosis of NSTEMI. Of the 304 probable patients with NSTEMI, there were 5 in-hospital deaths (1.6%). Survival at 6 months was higher than GRACE predicted mortality in all groups. At 6 months the predicted versus observed mortality in the low-risk group was 4 versus 2% (P = 0.05), in the medium-risk group it was 12.5 versus 1.9% (P = 0.0001) and in the high-risk group it was 25 versus 20% (P = 0.45). CONCLUSIONS: In-hospital CABG performed after NSTEMI is associated with a low-mortality risk and survival significantly better than that predicted by the GRACE score.

Which troponometric best predicts midterm outcome after coronary artery bypass graft surgery?

BACKGROUND: Various troponin I measurements (troponometrics) have been used as surrogate markers of patient outcome after coronary artery bypass grafting (CABG). Our aim was to define the postoperative troponometric best able to predict in-hospital and late mortality. METHODS: In 440 patients (seen from January 2000 to September 2004) undergoing isolated on-pump CABG with standardized anesthesia, perfusion, cardioplegia, and postoperative care, we followed all-cause mortality (census June 2009, 100% complete). Subjects underwent troponin I (cardiac troponin I [cTnI]) estimation at baseline and 6, 12, 24, 48, and 72 hours postoperatively, and individual time-point cTnI (T6, T12, T24, T48, T72), peak cTnI (Cmax), increase in cTnI between 6 and 12 hours (T↑6-12) and 6 and 24 hours (T↑6-24), cumulative area under the curve cTnI (CAUC24, CAUC48, and CAUC72), and cTnI≥13 ng·mL(-1) at any time point were each analyzed using univariate and multivariable Cox models to identify the probability of in-hospital and late death. Logistic EuroSCOREs and calculated creatinine clearance (CrCl) were also included. The Akaike information criterion (AIC) was used to determine goodness of fit. RESULTS: There were 62 of 440 deaths after a median (interquartile range) follow-up period of 7.0 (5.7 to 8.1) years. Univariate Cox analysis demonstrated T12, T24, T48, T72, T↑6-12, T↑6-24, standardized CAUC24, CAUC48, and CAUC72 each to be predictors of midterm mortality. On Cox multivariable analysis in models incorporating both logistic EuroSCOREs and CrCl, both T72 (hazard ratio [HR], 95% confidence interval [CI], 1.10 [1.06 to 1.14]; p<0.001) and CAUC72 (1.45 [1.26 to 1.62], p<0.001) were identified as independent predictors of mortality. Of these, CAUC72 was superior based on the lowest AIC. CONCLUSIONS: In myocardial protection studies, serial troponin I data should be collected until 72 hours postoperatively to calculate CAUC72, as this troponometric best predicts midterm mortality.

Renal tumours with cavo-atrial extension: surgical management and outcome.

Surgery is the most effective treatment for the management of patients with renal cell carcinoma (RCC) and involvement of inferior vena cava (IVC). Data were accrued for 68 consecutive patients, who underwent surgical resection for RCC with IVC extension and required cardiothoracic surgical input from May 1993 to May 2005. The mean age of patients was 60.7 years (range 25-84, S.D. 11.6 years), 49 of these were males. The majority required application of vascular clamp at the junction of IVC with right atrium (RA), however, 21 patients required cardiopulmonary bypass (CPB) (29-193 min, mean 131 min). Hypothermic circulatory arrest (HCA) (12-42 min, mean 26 min) was used in 17 patients. The 30-day mortality was 6% (four patients) with no death in the elective CPB group. At a mean follow-up of 31 months, the overall two- and five-year survival rates were 50% and 37%, respectively. Cox regression revealed presence of metastasis (Odds ratio (OR) 3.1, 95% CI 1.2-8.2) and age >70 years (OR 2.9, 95% CI 1.3-6.3) adversely affected the long-term outcome. The management of RCC with IVC involvement is evolving for this complex group of patients. A multidisciplinary approach in selected patients is associated with good short- and long-term results.

Bleeding in cardiac surgery: the use of aprotinin does not affect survival.

OBJECTIVE: The antifibrinolytic drug aprotinin has been the most widely used agent to reduce bleeding and its complications in cardiac surgery. Several randomized trials and meta-analyses have demonstrated it to be effective and safe. However, 2 recent reports from a single database have implicated the use of aprotinin as a risk for postoperative complications and reduced long-term survival. METHODS: In this single-institution observational study involving 7836 consecutive patients (1998-2006), we assessed the safety of using aprotinin in risk reduction strategy for postoperative bleeding. RESULTS: Aprotinin was used in 44% of patients. Multivariate analysis identified aprotinin use in risk reduction for reoperation for bleeding (odds ratio, 0.51; 95% confidence interval, 0.36-0.72; P = .001) and need for blood transfusion postoperatively (odds ratio, 0.67; 95% confidence interval, 0.57-0.79; P = .0002). The use of aprotinin did not affect in-hospital mortality (odds ratio, 1.03; 95% confidence interval, 0.71-1.49; P = 0.73), intermediate-term survival (median follow-up, 3.4 years; range, 0-8.9 years; hazard ratio, 1.09; 95% confidence interval, 0.93-1.28; P = .30), incidence of postoperative hemodialysis (odds ratio, 1.16; 95% confidence interval, 0.73-1.85; P = .49), and incidence of postoperative renal dysfunction (odds ratio, 0.78; 95% confidence interval, 0.59-1.03; P = .07). CONCLUSION: This study demonstrates that aprotinin is effective in reducing bleeding after cardiac surgery, is safe, and does not affect short- or medium-term survival.

Improved myocardial protection during coronary artery surgery with glucose-insulin-potassium: a randomized controlled trial.

OBJECTIVE: We sought to assess the role of glucose-insulin-potassium in providing myocardial protection in nondiabetic patients undergoing coronary artery surgery with cardiopulmonary bypass. METHODS: A prospective, randomized, double-blind, placebo-controlled trial was conducted at a single-center university hospital performing adult cardiac surgery. Two hundred eighty nondiabetic adult patients undergoing first-time elective or urgent isolated multivessel coronary artery bypass grafting were prospectively randomized to receive glucose-insulin-potassium infusion or placebo (dextrose 5%) before, during, and for 6 hours after surgical intervention. Anesthetic, cardiopulmonary bypass, myocardial protection, and surgical techniques were standardized. The primary end point was postreperfusion cardiac index. Secondary end points were systemic vascular resistance index, the incidence of low cardiac output episodes, inotrope and vasoconstrictor use, and biochemical-electrocardiographic evidence of myocardial injury. The incidence of dysrhythmias and infections requiring treatment was recorded prospectively. RESULTS: The glucose-insulin-potassium group experienced higher cardiac indices (P < .001) throughout infusion and reduced vascular resistance (P < .001). The incidence of low cardiac output episodes was 15.9% (22/138) in the glucose-insulin-potassium group and 27.5% (39/142) in the placebo group (P = .021). Inotropes were required in 18.8% (26/138) of the glucose-insulin-potassium group and 40.8% (58/142) of the placebo group (P < .001). Fewer patients in the glucose-insulin-potassium group (12.3% [16/133]) versus those in the placebo group (23.4% [32/137]) had significant myocardial injury (P = .017). Noncardiac morbidity was not different. CONCLUSION: Glucose-insulin-potassium therapy improves early postoperative cardiovascular performance, reduces inotrope requirement, and might reduce myocardial injury. These potential benefits are not at the expense of increased noncardiac morbidity.