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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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The effect of intravenous magnesium sulfate on serum levels of N-terminal pro-brain natriuretic peptide (NT pro-BNP) in elective CABG with cardiopulmonary bypass.
Dabbagh, A, Bastanifar, E, Foroughi, M, Rajaei, S, Keramatinia, AA
Journal of anesthesia. 2013;(5):693-8
Abstract
INTRODUCTION Nowadays, many patients undergo coronary artery bypass grafting (CABG) with a cardiopulmonary bypass (CPB); while a number of therapeutic agents have been used to suppress its related inflammatory process. Magnesium sulfate (MgSO4) solution has been used as an anti-inflammatory agent. Among the cardiac biomarkers, N-terminal pro brain natriuretic peptide (NT Pro-BNP) is one of the most widely recognized. We performed this study to assess the effect of MgSO4 solution on NT Pro-BNP levels in patients undergoing CABG with CPB. MATERIALS AND METHODS In a double-blind clinical trial, after IRB approval for ethical considerations, during a 12-month period, 88 adult patients aged 40-70 years qualified for the study after inclusion and exclusion criteria were considered. After random allocation of the patients between the two groups, anesthesia, surgical procedure, cardiopulmonary bypass (CPB) methods, and postoperative care were made as similar as possible; however, one group received a MgSO4 infusion (15 mg/kg/h) and the other group saline (placebo). Pre- and post-operative levels of NT Pro-BNP were assessed using an electrochemical luminescence immunoassay in an Elecsys 2010 (Roche, Indianapolis, IN, USA). The results were compared using a Student's t-test. A P value less than 5% was considered significant. RESULTS The MgSO4 group had shorter postoperative mechanical ventilation, lower postoperative morphine requirements and lower postoperative pain scores. Also, 24 h postoperative NT Pro-BNP levels were significantly lower in the MgSO4 group. CONCLUSION Administration of MgSO4 in elective CABG with CPB can decrease the postoperative NT Pro-BNP levels; also, it decreases their time of postoperative mechanical ventilation.
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Predictors of short-term neurocognitive outcome following coronary revascularisation (CABG) depending on the use of cardiopulmonary bypass.
Lazibat, I, Sutlić, Z, Brkić, K, Nevajda, B, Sikić, J, Mestrović, AH
Collegium antropologicum. 2012;(3):827-33
Abstract
The purpose of our study was to investigate the association between perioperative cerebral microembolization, expressed as high-intensity transient signals (HITS) and postoperative dynamics of the neuromarker S100P in patients operated using cardiopulmonary bypass, and to assess their impact upon the neurocognitive function in the early postoperative stage. The study involved 62 consecutive male patients aged 60 or above, alls scheduled for elective aortocoronary bypass. The patients were recruited from two groups with respect to the use of CPB: on-pump group (CPB+, N = 30) and off-pump group (CPB-, N = 32). In all patients we performed intraoperative monitoring of cerebral haemodynamics using transcranial Doppler, with the goal of quantifying perioperative cerebral microembolization. The serum levels of the neuromarker S100l were measured immediately after surgery, and then 12, 24 and 48 hours after the surgery. Neurocognitive status was assessed before and after the surgery and in three cognitive domains. Results of the study have shown that with respect to the short-term postoperative neurocognitive outcome there is no significant difference between the on-pump and off-pump surgical technique of coronary revascularization'. Perioperative cerebral microembolization was significantly more pronounced in the on-pump group yet it did not affect early postoperative neurocognitive function, while the increase in the neuromarker S100beta serum level 48 hours after surgery may have prognostic value as a predictor of postoperative neurocognitive dysfunction.
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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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Preoperative statin treatment reduces systemic inflammatory response and myocardial damage in cardiac surgery.
Martínez-Comendador, JM, Alvarez, JR, Mosquera, I, Sierra, J, Adrio, B, Carro, JG, Fernández, A, Bengochea, J
European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. 2009;(6):998-1005
Abstract
OBJECTIVE To determine if preoperative statin treatment is associated with a reduction in systemic inflammatory response (SIR) and myocardial damage markers following cardiac surgery with cardiopulmonary bypass (CPB). METHODS We study a prospective cohort of 138 patients who underwent coronary and valvular surgery with CPB. We differentiate two study groups: patients with (group A, n=72) or without (group B, n=66) statins. Plasma levels of pro-inflammatory interleukins (tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-8 and IL-2R), creatine phosphokinase (CPK), CPK-MB and troponin I were measured before and 1, 6, 24 and >72 h after surgery. RESULTS The baseline, operative and postoperative morbidity and mortality characteristics were similar for both the groups. Group A had significantly lower postoperative levels of IL-6 than group B at 6h (68.8+/-5 pg ml(-1) vs 108.9+/-108 pg ml(-1), p=0.01), 24h (71.7+/-7 pg ml(-1) vs 110.4+/-106 pg ml(-1), p=0.01) and before hospital discharge (21.6+/-12 pg ml(-1) vs 32.8+/-27 pg ml(-1), p=0.005), as well as significantly lower average IL-6 levels in the first 24h following surgery (71.8+/-5 pgml(-1) vs 112.8+/-82 pg ml(-1), p=0.002). The postoperative CPK-MB at 24h (19.7+/-23 ng ml(-1) vs 33.1+/-32 ng ml(-1), p=0.02) and troponin I levels at the end of the intervention (2.2+/-2.2 ng ml(-1) vs 3.3+/-3.1 ng ml(-1), p=0.03) and at 24h (4.1+/-3.5 ng ml(-1) vs 6.6+/-8 ng ml(-1), p=0.04) were also significantly lower in the group treated with statins prior to surgery. CONCLUSIONS Preoperative treatment with statins is associated with a lower biochemical parameters of SIR and myocardial damage following cardiac surgery with CPB, regardless of it being coronary bypass grafting (CABG) or valvular surgery.
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Bicarbonate-buffered ultrafiltration during pediatric cardiac surgery prevents electrolyte and acid-base balance disturbances.
Osthaus, WA, Görler, H, Sievers, J, Rahe-Meyer, N, Optenhöfel, J, Breymann, T, Theilmeier, G, Suempelmann, R
Perfusion. 2009;(1):19-25
Abstract
Pediatric cardiopulmonary bypass is still a challenge because of electrolyte disturbances and inflammation. Many investigations deal with different types of hemofiltration to reduce these potentially harmful side effects. We tested the hypothesis of whether bicarbonate-buffered hemofiltration of the priming solution minimizes electrolyte and acid-base disturbances during the initiation of cardiopulmonary bypass and whether bicarbonate-buffered hemofiltration performed during cardiopulmonary bypass could reduce cytokine levels. Twenty children younger than 2 years of age (mean age 166 +/- 191 days; mean weight 6.42 +/- 3.22 kg) scheduled for pediatric cardiac surgery with cardiopulmonary bypass were enrolled in this prospective clinical study. Cardiopulmonary bypass circuits were primed with a bicarbonate-buffered hemofiltration solution, gelatin and 1 unit of packed red blood cells. The priming was hemofiltered using an ultrahemofilter until approximately 1000 mL of ultrafiltrate was restored with the buffered solution. Further hemofiltration was performed throughout the whole bypass time, especially during rewarming. Blood gas analyses and inflammatory mediators were monitored during the operation. Blood gas analysis results after initiation of cardiopulmonary bypass and throughout the entire study remained within the physiologic ranges. Even potassium decreased from 4.0 +/- 0.3 to 3.4 +/- 0.4 mmol l(-1) after initiation of cardiopulmonary bypass. Plasma levels of tumor necrosis factor alpha decreased significantly (47 +/- 44 vs. 24 +/- 21 pg mL(-1)) whereas complement factor C3a (5.0 +/- 2.9 vs. 16.8 +/- 6.6 ng mL(-1)) and interleukin-6 (7.3 +/- 15.2 vs. 110 +/- 173 pg mL(-1)) increased despite hemofiltration. In conclusion, this study shows that bicarbonate-buffered ultrafiltration is an efficient, simple and safe method for performing hemofiltration, both of the priming solution and during the entire bypass time. The use of a physiological restitution solution prevents electrolyte and acid-base balance disturbances. The elimination of inflammatory mediators seems to be as effective as other ultrafiltration methods.
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Plasma biomarkers in pediatric patients undergoing cardiopulmonary bypass.
Lull, ME, Carkaci-Salli, N, Freeman, WM, Myers, JL, Midgley, FM, Thomas, NJ, Kimatian, SJ, Vrana, KE, Undar, A
Pediatric research. 2008;(6):638-44
Abstract
It is critical to identify at-risk patients and minimize the deleterious effects of cardiopulmonary bypass (CPB) procedures in pediatric populations. The present study screened the plasma proteome of pediatric patients undergoing CPB procedures to identify potential clinical biomarkers related to tissue damage, inflammation, or other pathologies. Blood samples were collected at five different time points from 10 children undergoing a CPB procedure. Plasma was isolated and analyzed using two-dimensional differential in-gel electrophoresis and matrix-assisted laser desorption ionization time of flight mass spectrometry. Levels of differentially regulated proteins identified by two-dimensional differential in-gel electrophoresis, and related proteins were then measured in all time points and patients. As well, associated small molecules and ions were measured. The present study identified 13 proteins and protein isoforms altered in expression, including hemopexin, ceruloplasmin, inter-alpha inhibitor H4, and alpha-2-macroglobulin. Immunoblot analysis revealed significant decreases in each of these proteins during the CPB procedure. Significant changes in the levels of copper, iron, Hb, epinephrine, norepinephrine, and serotonin were observed. The potential markers of pathology (inflammation, oxidative stress) identified during this preliminary study may illuminate opportunities for preventative measures and/or treatments during and following CPB procedures in pediatric patients.
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Moderate hypothermia with low flow rate cardiopulmonary bypass used in surgeries for congenital heart defects.
Huang, H, Wang, W, Zhu, D
ASAIO journal (American Society for Artificial Internal Organs : 1992). 2007;(6):684-6
Abstract
Low flow rate perfusion has been recommended in profound hypothermic cardiopulmonary bypass (CPB) in recent years. However, most patients with congenital heart defects are still operated on under moderate hypothermic CPB, where high flow rate perfusion has been adopted by most perfusionists. Fifty patients with congenital heart defects, ranging from 1 to 11 yr of age and 6.5 to 25 kg of weight, were included in the trial. Once on CPB, a high flow rate of 2.37 +/- 0.39 L/min/m was used to cool the patient to 27.3 degrees C +/- 0.84 degrees C rectal temperature, followed by a low flow rate of 1.31 +/- 0.09 L/min/m until the main intracardiac repair was completed and rewarming started. High flow rate was still used in rewarming the patients to a rectal temperature of 35 degrees C-36 degrees C. The total CPB, cross-clamp, and low flow rate perfusion time were 86.4 +/- 26.6, 46.4 +/- 22.3, and 40.7 +/- 22.4 min, respectively. After 24-99 min low flow rate perfusion, venous oxygen saturation remained above 80% for all the patients, and lactate concentration did not increase. Only three patients showed slight metabolic acidosis during CPB and required an extra 6-12 mEq sodium bicarbonate. Average urine output was 199 +/- 155 (50-600) ml during CPB. All patients recovered well after operation. No surgical death or neurologic complications occurred. Low flow rate perfusion might be safely used in moderate hypothermic CPB as long as the oxygen saturation of returned venous blood was kept above 80%.
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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.