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A Multicenter, Randomized, Controlled Phase IIb Trial of Avoidance of Hyperoxemia during Cardiopulmonary Bypass.
McGuinness, SP, Parke, RL, Drummond, K, Willcox, T, Bailey, M, Kruger, C, Baker, M, Cowdrey, KA, Gilder, E, McCarthy, L, et al
Anesthesiology. 2016;(3):465-73
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Abstract
BACKGROUND Cardiac surgery utilizing cardiopulmonary bypass (CPB) is one of the most common forms of major surgery. Cardiac surgery-associated multiorgan dysfunction (CSA-MOD) is well recognized and includes acute kidney injury (AKI), hepatic impairment, myocardial damage, and postoperative neurologic deficit. Pathophysiology of CSA-MOD involves numerous injurious pathways linked to the use of CPB including oxidative stress and formation of reactive iron species. During cardiac surgery with CPB, arterial return blood is oxygenated to supranormal levels. This study aimed to determine whether the avoidance of arterial hyperoxemia decreased oxidative stress and reduced the severity of the multiorgan dysfunction in patients undergoing cardiac surgery utilizing CPB. METHODS The study was a multicenter, open-label, parallel-group, randomized controlled study of the avoidance of arterial hyperoxemia versus usual care in patients undergoing cardiac surgery involving CPB. Primary outcome was the incidence and severity of AKI. Secondary outcomes included serum biomarkers for CSA-MOD, duration of mechanical ventilation, and length of intensive care and hospital stay. RESULTS A total of 298 patients were randomized and analyzed at two hospitals in New Zealand and Australia. Mean PaO2 was significantly different between groups during CPB. There was no difference in the development of AKI (intervention arm 72.0% vs. usual care 66.2%; difference, -5.8% [95% CI, -16.1 to 4.7%]; P = 0.28), other markers of organ damage, or intensive care unit and hospital length of stay. CONCLUSIONS Avoiding modest hyperoxemia during CPB failed to demonstrate any difference in AKI, markers of organ damage, or length of stay.
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Plasma acetate, gluconate and interleukin-6 profiles during and after cardiopulmonary bypass: a comparison of Plasma-Lyte 148 with a bicarbonate-balanced solution.
Davies, PG, Venkatesh, B, Morgan, TJ, Presneill, JJ, Kruger, PS, Thomas, BJ, Roberts, MS, Mundy, J
Critical care (London, England). 2011;(1):R21
Abstract
INTRODUCTION As even small concentrations of acetate in the plasma result in pro-inflammatory and cardiotoxic effects, it has been removed from renal replacement fluids. However, Plasma-Lyte 148 (Plasma-Lyte), an electrolyte replacement solution containing acetate plus gluconate is a common circuit prime for cardio-pulmonary bypass (CPB). No published data exist on the peak plasma acetate and gluconate concentrations resulting from the use of Plasma-Lyte 148 during CPB. METHODS Thirty adult patients were systematically allocated 1:1 to CPB prime with either bicarbonate-balanced fluid (24 mmol/L bicarbonate) or Plasma-Lyte 148. Arterial blood acetate, gluconate and interleukin-6 (IL-6) levels were measured immediately before CPB (T1), three minutes after CPB commencement (T2), immediately before CPB separation (T3), and four hours post separation (T4). RESULTS Acetate concentrations (normal 0.04 to 0.07 mmol/L) became markedly elevated at T2, where the Plasma-Lyte group (median 3.69, range (2.46 to 8.55)) exceeded the bicarbonate group (0.16 (0.02 to 3.49), P < 0.0005). At T3, levels had declined but the differential pattern remained apparent (Plasma-Lyte 0.35 (0.00 to 1.84) versus bicarbonate 0.17 (0.00 to 0.81)). Normal circulating acetate concentrations were not restored until T4. Similar gluconate concentration profiles and inter-group differences were seen, with a slower T3 decay. IL-6 increased across CPB, peaking at T4, with no clear difference between groups. CONCLUSIONS Use of acetate containing prime solutions result in supraphysiological plasma concentrations of acetate. The use of acetate-free prime fluid in CPB significantly reduced but did not eliminate large acetate surges in cardiac surgical patients. Complete elimination of acetate surges would require the use of acetate free bolus fluids and cardioplegia solutions. TRIAL REGISTRATION Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000267055.
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Microemboli from cardiopulmonary bypass are associated with a serum marker of brain injury.
Groom, RC, Quinn, RD, Lennon, P, Welch, J, Kramer, RS, Ross, CS, Beaulieu, PA, Brown, JR, Malenka, DJ, O'Connor, GT, et al
The journal of extra-corporeal technology. 2010;(1):40-4
Abstract
An increasing number of reports surrounding neurologic injury in the setting of cardiac surgery has focused on utilizing biomarkers as intermediate outcomes. Previous research has associated cerebral microemboli and neurobehavioral deficits with biomarkers. A leading source of cerebral microemboli is the cardiopulmonary bypass (CPB) circuit. This present study seeks to identify a relationship between microemboli leaving the CPB circuit and a biomarker of neurologic injury. We enrolled 71 patients undergoing coronary artery bypass grafting at a single institution from October 14, 2004 through December 5, 2007. Microemboli were monitored using Power-M-Mode Doppler in the inflow and outflow of the CPB circuit. Blood was sampled before and within 48 hours after surgery. Neurologic injury was measured using S100beta (microg/L). Significant differences in post-operative S100beta relative to microemboli leaving the circuit were tested with analysis of variance and Kruskal-Wallis. Most patients had increased serum levels of S100beta (mean .25 microg/L, median .15 microg/L) following surgery. Terciles of microemboli measured in the outflow (indexed to the duration of time spent on CPB) were associated with elevated levels of S100beta (p = .03). Microemboli leaving the CPB circuit were associated with increases in postoperative S100beta levels. Efforts aimed at reducing microembolic load leaving the CPB circuit should be adopted to reduce brain injury.
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Arterio-jugular differences in serum S-100beta proteins in patients receiving selective cerebral perfusion.
Kunihara, T, Shiiya, N, Bin, L, Yasuda, K
Surgery today. 2006;(1):6-11
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Abstract
PURPOSE The early increase in serum S100beta after cardiopulmonary bypass (CPB) seems to be derived from an extracerebral source. To exclude contamination, we investigated the arterio-jugular differences in S100beta levels in patients receiving selective cerebral perfusion (SCP). We also evaluated the brain-protective effect of SCP by comparing the arterial S100beta levels with those in patients undergoing coronary artery bypass grafting (CABG). METHODS We measured arterial and jugular venous levels of S100beta in ten patients undergoing aortic arch repair with SCP for up to 12 h postoperatively (SCP group). We also measured arterial levels of S100beta in nine patients undergoing CABG (CPB group). RESULTS There was no incidence of hospital death or stroke. The arterial levels of S100beta in both groups were comparable and peaked just after the conclusion of CPB. The arterial and jugular venous levels of S100beta were almost equivalent. The arterio-jugular differences in S100beta levels were negligible, even in our SCP-group patient with postoperative delirium, who had a peak value three times higher than the other patients. CONCLUSIONS The arterio-jugular differences in S100beta did not clarify the origin of their increase. Thus, measuring the jugular venous levels of S100beta in patients without postoperative clinical neurological deterioration would be of little benefit. However, SCP seems to protect the brain against S100beta release as effectively as conventional CPB.
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Ginsenosides compound (shen-fu) attenuates gastrointestinal injury and inhibits inflammatory response after cardiopulmonary bypass in patients with congenital heart disease.
Xia, ZY, Liu, XY, Zhan, LY, He, YH, Luo, T, Xia, Z
The Journal of thoracic and cardiovascular surgery. 2005;(2):258-64
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OBJECTIVE This study was undertaken to demonstrate that gastrointestinal mucosal injury occurs during cardiopulmonary bypass in children, increasing systemic inflammatory responses, and to determine whether shen-fu injection (the major components of which are ginsenosides compound, extract of Panax ginseng shown to have antioxidant properties) could attenuate gastrointestinal mucosal injury and subsequent inflammatory responses. METHODS Twenty-four children undergoing heart surgery for congenital heart defects were randomly assigned to groups C (placebo control, n = 12) and G (1.35 mg/kg ginsenosides compound intravenously before and throughout the course of cardiopulmonary bypass, n = 12). Central venous blood samples were taken before cardiopulmonary bypass and at 60 and 120 minutes after aortic declamping (reperfusion). Gastric intramucosal pH was measured by perioperative tonometry. Plasma lipid peroxidation product malondialdehyde, myocardium-specific creatine kinase isoenzyme MB activity, diamine oxidase, lipopolysaccharide, and interleukin 6 were all measured. RESULTS Significant decrease in gastric intramucosal pH and increase in plasma diamine oxidase were seen during reperfusion in group C, accompanied by increases in plasma levels of malondialdehyde, lipopolysaccharide, interleukin 6, and creatine kinase isoenzyme MB (P < .01 vs before cardiopulmonary bypass). Shen-fu injection significantly attenuated these changes (P < .05). Consequently, fewer patients in group G (2/12) than in group C (7/12) needed postoperative inotropic support. Postoperative intensive care unit stay was shorter in group G than in group C. A tight positive correlation was seen between diamine oxidase and interleukin 6 at 60 minutes after aortic declamping and between diamine oxidase and lipopolysaccharide at 120 minutes after aortic declamping (r = 0.79, P < .0001). CONCLUSION Ginsenosides compound may attenuate gastrointestinal injury and inhibit inflammatory response after cardiopulmonary bypass in patients with congenital heart disease.
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Effect of dexamethasone on perioperative renal function impairment during cardiac surgery with cardiopulmonary bypass.
Loef, BG, Henning, RH, Epema, AH, Rietman, GW, van Oeveren, W, Navis, GJ, Ebels, T
British journal of anaesthesia. 2004;(6):793-8
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BACKGROUND In cardiac surgery with cardiopulmonary bypass (CPB), corticosteroids are administered to attenuate the physiological changes caused by the systemic inflammatory response. The effects of corticosteroids on CPB-associated renal damage have not been documented. The purpose of this study was to evaluate the effects of dexamethasone on perioperative renal dysfunction in patients undergoing cardiac surgery with CPB. METHODS Renal damage was prospectively studied in 20 patients without concomitant morbidity undergoing coronary artery surgery with CPB. Patients were randomized in a double-blind fashion to receive dexamethasone or placebo. Markers of glomerular function (creatinine clearance) and damage (microalbuminuria), and markers of tubular function (fractional excretion of sodium and free water clearance) and damage (N-acetyl-beta-D glucosaminidase (NAG)) were evaluated in addition to plasma and urinary glucose levels. Plasma and urinary specimens were obtained at the following time periods: (1) baseline, during the 12 h before surgery; (2) skin incision before heparinization; (3) from heparinization until the end of CPB; (4) during the 2 h following weaning from CPB; (5) in the intensive care unit from 2 to 6 h after weaning of CBP; (6) and from 36 to 60 h after weaning of CPB. RESULTS CPB was associated with an increase in markers in the placebo group, which returned to baseline during the second postoperative day, demonstrating a transient impairment of glomerular and tubular renal function. Similar patterns were observed in patients treated with dexamethasone. While postoperative glycosuria was significantly higher in the dexamethasone-treated group, no other differences between groups were observed. CONCLUSION Dexamethasone administration before CPB has no protective effect on perioperative renal dysfunction in low-risk cardiac surgical patients.
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Cardioprotective properties of sevoflurane in patients undergoing coronary surgery with cardiopulmonary bypass are related to the modalities of its administration.
De Hert, SG, Van der Linden, PJ, Cromheecke, S, Meeus, R, Nelis, A, Van Reeth, V, ten Broecke, PW, De Blier, IG, Stockman, BA, Rodrigus, IE
Anesthesiology. 2004;(2):299-310
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BACKGROUND Experimental studies have related the cardioprotective effects of sevoflurane both to preconditioning properties and to beneficial effects during reperfusion. In clinical studies, the cardioprotective effects of volatile agents seem more important when administered throughout the procedure than when used only in the preconditioning period. The authors hypothesized that the cardioprotective effects of sevoflurane observed in patients undergoing coronary surgery with cardiopulmonary bypass are related to timing and duration of its administration. METHODS Elective coronary surgery patients were randomly assigned to four different anesthetic protocols (n = 50 each). In a first group, patients received a propofol based intravenous regimen (propofol group). In a second group, propofol was replaced by sevoflurane from sternotomy until the start of cardiopulmonary bypass (SEVO pre group). In a third group, propofol was replaced by sevoflurane after completion of the coronary anastomoses (SEVO post group). In a fourth group, propofol was administered until sternotomy and then replaced by sevoflurane for the remaining of the operation (SEVO all group). Postoperative concentrations of cardiac troponin I were followed during 48 h. Cardiac function was assessed perioperatively and during 24 h postoperatively. RESULTS Postoperative troponin I concentrations in the SEVO all group were lower than in the propofol group. Stroke volume decreased transiently after cardiopulmonary bypass in the propofol group but remained unchanged throughout in the SEVO all group. In the SEVO pre and SEVO post groups, stroke volume also decreased after cardiopulmonary bypass but returned earlier to baseline values than in the propofol group. Duration of stay in the intensive care unit was lower in the SEVO all group than in the propofol group. CONCLUSION In patients undergoing coronary artery surgery with cardiopulmonary bypass, the cardioprotective effects of sevoflurane were clinically most apparent when it was administered throughout the operation.
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Supplemental nitric oxide and its effect on myocardial injury and function in patients undergoing cardiac surgery with extracorporeal circulation.
Gianetti, J, Del Sarto, P, Bevilacqua, S, Vassalle, C, De Filippis, R, Kacila, M, Farneti, PA, Clerico, A, Glauber, M, Biagini, A
The Journal of thoracic and cardiovascular surgery. 2004;(1):44-50
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BACKGROUND Cardiopulmonary bypass induces a systemic inflammatory response that may contribute to clinical morbidity. Gaseous nitric oxide at relatively low concentrations may elicit peripheral anti-inflammatory effects in addition to a reduction of pulmonary resistances. We examined the effects of 20 ppm of inhaled nitric oxide administered for 8 hours during and after cardiopulmonary bypass. METHODS AND RESULTS Twenty-nine consecutive patients undergoing aortic valve replacement combined with aortocoronary bypass were randomly allocated to either 20 ppm of inhaled nitric oxide (n = 14) or no additional inhalatory treatment (n = 15). Blood samples for total creatine kinase, creatine kinase MB fraction, and troponin I measurements were collected at 4, 12, 24, and 48 hours postsurgery. In addition, we collected perioperative blood samples for measurements of circulating nitric oxide by-products and brain natriuretic peptide. Soluble P-selectin was analyzed in blood samples withdrawn from the coronary sinus before and after aortic clamping. The area under the curve of creatine kinase MB fraction (P =.03), total creatine kinase (P =.04), and troponin I (P =.04) levels were significantly decreased in the nitric oxide-treated patients. Moreover, in the same group we observed blunted P-selectin and brain natriuretic peptide release (P =.01 and P =.02, respectively). Nitric oxide inhalation consistently enhanced nitric oxide metabolite levels (P =.01). CONCLUSIONS Nitric oxide, when administered as a gas at low concentration, is able to blunt the release of markers of myocardial injury and to antagonize the left ventricular subclinical dysfunction during and immediately after cardiopulmonary bypass. The organ protection could be mediated, at least in part, by its anti-inflammatory properties.
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N-acetylcysteine prevents reactive oxygen species-mediated myocardial stress in patients undergoing cardiac surgery: results of a randomized, double-blind, placebo-controlled clinical trial.
Tossios, P, Bloch, W, Huebner, A, Raji, MR, Dodos, F, Klass, O, Suedkamp, M, Kasper, SM, Hellmich, M, Mehlhorn, U
The Journal of thoracic and cardiovascular surgery. 2003;(5):1513-20
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OBJECTIVE Reactive oxygen species have been shown to contribute to myocardial stress in patients undergoing cardiac surgery, as demonstrated by myocardial 8-iso-prostaglandin-F(2)alpha and nitrotyrosine formation. We hypothesized that the reactive oxygen species scavenger N-acetylcysteine attenuates reactive oxygen species-mediated myocardial stress in patients undergoing cardiac surgery. METHODS Forty patients undergoing coronary artery surgery (mean age +/- SD, 66 +/- 9 years; 9 women and 31 men) were randomized to receive either N-acetylcysteine (100 mg/kg into cardiopulmonary bypass prime followed by infusion at 20 mg.kg(-1).h(-1), n = 20) or placebo (n = 20). Patients and clinical staff were blinded to group assignment. Transmural left ventricular biopsy specimens collected before and at the end of cardiopulmonary bypass were subjected to immunocytochemical staining against 8-iso-prostaglandin-F(2)alpha (primary measure) as an indicator for reactive oxygen species-mediated lipid peroxidation and nitrotyrosine (coprimary measure) as a marker for peroxynitrite-mediated tissue injury. Cardiomyocyte staining was quantitatively determined by using densitometry (in gray units). Global left ventricular function was measured on the basis of fractional area of contraction by using transesophageal echocardiography. RESULTS Patient characteristics in both groups were comparable. The change in left ventricular cardiomyocyte staining (end of cardiopulmonary bypass--before cardiopulmonary bypass) differed significantly between groups for both primary measures: 8-iso-prostaglandin-F(2)alpha, -1.8 +/- 7.5 gray units (mean +/- SD, N-acetylcysteine group) versus 5.0 +/- 4.1 gray units (placebo group; 95% confidence interval, 2.6-11.0, P =.003); nitrotyrosine, -6.4 +/- 10.0 gray units (N-acetylcysteine group) versus 9.2 +/- 8.4 gray units (placebo group; 95% confidence interval, 9.4-21.7, P <.001). Hemodynamics and clinical outcomes were comparable in both groups. CONCLUSIONS Reactive oxygen species scavenging with N-acetylcysteine attenuates myocardial oxidative stress in the hearts of patients subjected to cardiopulmonary bypass and cardioplegic arrest.
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Magnesium-flush infusion into the aortic root just before reperfusion reduces the requirement for internal defibrillation and early post-perfusion arrhythmias.
Beşoğul, Y, Tünerir, B, Ozdemir, C, Aslan, R
The Journal of international medical research. 2003;(3):202-9
Abstract
Pre- and post-operative administration of magnesium has beneficial effects on post-operative ischaemia and reperfusion arrhythmias, but few studies have examined whether intra-operatively administered magnesium can prevent the effects of intra-operative arrhythmias. The aim of this randomized, double-blind study was to compare the effects of intra-operative magnesium or placebo on intra-operative arrhythmias in patients undergoing coronary bypass grafting. Patients received a flush infusion of magnesium or placebo into the aortic root before cross-clamp removal. The results showed that rate of spontaneous resumption of a cardiac rhythm was significantly higher, and number of shocks for defibrillation, energy requirement for defibrillation and rate of intra-operative ventricular tachyarrhythmias were significantly lower in the magnesium group, compared with the placebo group. The differences in need for temporary pacing, and in serum magnesium levels, were not significant. Intra-operative administration of magnesium has beneficial effects on the outcome of surgery. Larger, multicentre clinical investigations should now be undertaken.