Stephen J. Rooney

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 &mgr;mol/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 &mgr;mol/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 &mgr;mol/L or 1.47 to 2.25 mg/dL (mild renal dysfunction group) and 3945 patients with a serum creatinine <130 &mgr;mol/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 &mgr;mol/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.

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 &mgr;g · kg−1 followed by 0.113 &mgr;g · 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.

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 &bgr;-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. Clinical Trial Registration— URL: http://www.controlled-trials.com. Reference number: ISRCTN 05758301.

Glucose-Insulin-Potassium Reduces the Incidence of Low Cardiac Output Episodes After Aortic Valve Replacement for Aortic Stenosis in Patients With Left Ventricular Hypertrophy

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 &bgr;-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. Clinical Trial Registration— URL: http://www.controlled-trials.com. Reference number: ISRCTN 05758301.

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.

S-100β release in hypothermic circulatory arrest and coronary artery surgery

Abstract Background . Aortic surgery utilizing profound hypothermic circulatory arrest (HCA) has a higher incidence of neurological injury than coronary artery bypass grafting (CABG). S-100β is a potential marker of cerebral ischemic injury. The aim of this study is to assess its use in investigating cerebral injury during HCA. Methods . We studied 40 patients (10 CABG, 30 HCA). The mean cardiopulmonary bypass (CPB) times were 72 and 158 minutes, respectively. Mean HCA duration was 27.6 min, with retrograde cerebral perfusion (RCP) used in 18 patients (mean 28.5 minutes, 95% CI 16–25). Perioperative venous blood samples were subjected to S100β assay. Results . S100β levels with HCA (peak: 2.68 μg/L, 95% CI 1.99–3.38 μg/L; calculated area under the curve [AUC]: 1596 μg/L/min, 95% CI 825–2368 μg/L/min) were significantly higher (peak, p = 0.028 and AUC, p = 0.007) than with CABG (peak: 1.16 μg/L, 95% CI 0.25–2.1 μg/L and AUC: 53.4 μg/L/min 95% CI 3.0–103.8). Peak S100β correlated with CPB time in CABG cases ( r = 0.76, p r = 0.46 and 0.21, respectively, p > 0.05) and with RCP ( r = 0.88 and 0.33, respectively, p p = 0.05). Conclusions . S100β release correlates with duration of CPB and HCA. Elevated serum S100 indicates astrocyte death or activation, and suggests blood-brain barrier dysfunction. The continuing release of S100 after the end of operation suggests that HCA may be associated with greater injury than CABG. RCP did not influence S-100β release in this study.

Prediction of thoracic aortic aneurysm expansion: validation of formulae describing growth

BACKGROUND The expansion rate of thoracic aortic aneurysms may be an important and clinically relevant index of the risk of rupture. The aims of this study were to assess the validity of three published exponential equations that predict expansion rate in a separate sample population, and to calculate an expansion rate formula for this cohort of patients. METHODS We studied 88 consecutive patients undergoing serial computed tomographic or magnetic resonance imaging scanning to monitor thoracic aortic aneurysm progression. In interval scans of at least 6 months, we measured minimum coronal aortic diameter at seven set levels and maximal diameter, yielding 780 segment-intervals. RESULTS The linear expansion rate (mean 2.6 mm/year) increased with incremental aortic diameter (aortic diameter < 40 mm: 2.0; 40-49 mm: 2.3; 50-59 mm: 3.6; > or = 60 mm: 5.6 mm/year; p < 0.01). Regression analysis showed close correlation between predicted and sample data, but there were significant differences between observed and expected measurements. The Yale formula underestimated growth by 0.8 mm, while Mt. Sinai and Osaka formulae overestimated actual change by 1.5 and 0.2 mm, respectively. The expansion rate derived from our population was: last diameter = initial diameter x e(0.00367 x time) (r = 0.617). CONCLUSIONS Although formulae derived from one thoracic aortic aneurysm sample population may not extrapolate exactly to others, there is close concordance of results for patient populations in three different continents.

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.

Reproducibility of thoracic aortic diameter measurement using computed tomographic scans.

OBJECTIVES Decisions to recommend elective surgical repair of thoracic aortic aneurysms (TAA) may be based on size or expansion rate, which are used as indices of the risk of rupture. Measurement error may thus affect clinical decision-making. In order to evaluate the reproducibility of aortic diameter measurements of TAA, we assessed departmental inter- and intra-observer variability of measurement of pre-selected computed tomographic scan images of aneurysmal segments of the thoracic aorta. METHODS We compared measurements of minimum aortic diameter made by four observers in 50 pre-selected scans and at different times by two observers using a calliper method and a measurement tool within the scan. Differences in measured dimension were analysed using Wilcoxons signed ranks test and the repeatability assessed using the method of Bland and Altman. RESULTS There were no significant inter-observer differences among three observers but there were significant differences between another observer and two other observers (P < 0.05). No significant intra-observer differences existed. The best intra-observer repeatability was 2.25 while the worst inter-observer repeatability was 4.37. The mean and maximum difference in measurement were +/-0.88 mm and +/-8.0 mm, respectively. Variability of measurement increased with aortic diameter. CONCLUSIONS Calliper measurement of TAA is an acceptable measurement method for surveillance of TAA but appears most accurate with a single observer. Increasing error is seen with increasing diameter which may compound error in estimation of expansion rate. Standardisation of technique is advisable for multiple observers and aortic units should adopt quality assurance protocols to minimise error.

The effect of adhesion molecule blockade on pulmonary reperfusion injury

BACKGROUND Selectins are the molecules involved in the initial adhesion of the activated neutrophil on pulmonary endothelium. We investigated the efficacy of selectin blockade in a selective (monoclonal antibody RMP-1) and nonselective (Fucoidin) manner in pulmonary reperfusion injury. METHODS Groups of six rat lungs were flushed with University of Wisconsin solution then stored at 4 degrees C for 4 hours. They then underwent sanguinous reperfusion for 30 minutes during which functional measures (gas exchange, pulmonary artery pressure, and airway pressure) of lung performance were made. After reperfusion we estimated their capillary filtration coefficient (Kfc units g/cm water/minute/g wet lung tissue) using a gravimetric technique. Four groups were studied: group I had no reperfusion, group II had 30 minutes of reperfusion, group III had infusion of 20 mg/kg Fucoidin before reperfusion, and group IV had infusion of 20 microg/mL RMP-1 before reperfusion. RESULTS Reperfusion injury was found between groups I and II by an increase in capillary filtration coefficient (1.048 +/- 0.316 to 3.063 +/- 0.466, p < 0.01). Groups III and IV had a significantly lower Kfc than group II (0.967 +/- 0.134 and 1.205 +/- 0.164, respectively, p < 0.01). There was no significant functional difference between groups II, III, and IV. CONCLUSIONS Reperfusion-induced hyperpermeability was ameliorated by selective (RMP-1) and nonselective (Fucoidin) selectin blockade.