Onset Of Cardiopulmonary Bypass Research Articles

Comparison of phenoxybenzamine to sodium nitroprusside in infants undergoing surgery

The purpose of this study was to compare the effects of a direct-acting arterial dilator, sodium nitroprusside, to an alpha-adrenergic receptor blocker, phenoxybenzamine, in infants with congenital heart defects undergoing cardiac repairs on cardiopulmonary bypass. A prospective, multicenter, observational study. Tertiary care center. Sixty infants scheduled for elective congenital cardiac surgery repair requiring cardiopulmonary bypass. Patients received either sodium nitroprusside 2 to 5 microg/kg/min infusion intraoperatively and in the intensive care unit (n=30 patients) or received phenoxybenzamine 1 mg/kg slowly intravenously at the onset of cardiopulmonary bypass (n=30 patients). Despite similar mean arterial pressures during cardiopulmonary bypass in both groups, infants who received phenoxybenzamine had a significantly higher flow compared with those who received sodium nitroprusside (180+/-4.8 v 73+/-5.12 mL/kg/min, p<0.0001). Base deficit was significantly larger in the sodium nitroprusside group compared with the phenoxybenzamine group intraoperatively and postoperatively (3.4+/-0.5 v 1.3+/-0.5 mEq/L, p<0.05). The core-to-peripheral temperature gradient was significantly larger in the sodium nitroprusside group compared with the phenoxybenzamine group intra- and postoperatively at all points studied. In the intensive care unit, the left atrial pressure was significantly higher in the sodium nitroprusside group compared with the phenoxybenzamine group (9+/-0.4 v 7+/-0.4 mmHg, p<or=0.0005). The use of phenoxybenzamine can maintain organ perfusion on cardiopulmonary bypass and improve peripheral circulation as shown by less base deficit and smaller temperature gradients intraoperatively and in the intensive care unit better than nitroprusside.

Renal medullary hypoxia during experimental cardiopulmonary bypass: a pilot study

To determine the effect of cardiopulmonary bypass (CPB) on renal medullary oxygenation. Observational. Laboratory. Pigs (n=3). Following induction of general anesthesia, a Paratrend blood gas probe was placed directly into the left renal medulla. Two animals were subjected to 90 min of CPB, while a third served as a non-CPB control. A probe was also placed in the left renal pelvis of one (CPB) animal to allow direct urine PO2 measurements. Medullary hypoxia (PO2 <65 mmHg) was evident prior to CPB. With the onset of CPB, medullary PO2 further declined to nearly unmeasurable levels; PCO2 and pH were unchanged. Brief circulatory arrest during CPB in one animal resulted in rapid additional PCO2 rise and pH decline that corrected with reperfusion. Following the cessation of CPB, medullary PO2 gradually increased, but remained lower than pre-CPB levels. No changes in medullary PO2 were observed in the sham animal. Renal pelvis urine PO2, but not pH or PCO2, appeared to correlate with medullary values at all times. Our findings indicate that renal medullary hypoxia is extreme during CPB and may persist following CPB. These data suggest a basis for the vulnerability of the kidney to injury during cardiac surgery. Renal pelvis urine PO2 appears to correlate closely with medullary PO2 and may be a useful tool for studying medullary oxygenation during CPB in humans.

Effects of fresh versus old stored blood in the priming solution on whole blood lactate levels during paediatric cardiac surgery

It has been suggested that lactate levels may predict morbidity and mortality in paediatric patients during corrective open-heart surgery. Packed red blood cells (PRBC) are frequently necessary for priming the reservoir used in cardiopulmonary bypass (CPB). The storage of PRBC might cause a significant increase in lactate levels. The purpose of the present study was to quantify the increase in lactate levels in stored red blood cells over time and to compare lactate levels after transfusions of fresh (< or =12 days) versus old blood (>12 days) in 20 patients. We found an increase in lactate levels from 6.0 to 44.7mmol/L (mean 17.0+/-7.8 mmol/L) during storage. Lactate levels were also significantly higher after the onset of CPB in paediatric patients transfused with old blood than in patients transfused with fresh blood (1.43+0.36 versus 3.46+/-0.63, p=0.0006). Our results suggest that the higher lactate levels found after the initiation of CPB should be used with caution when assessing tissue hypoxia and predicting outcome.

Normothermia: Ideal temperature for cardio pulmonary bypass

Hypothermic systemic perfusion has remained as an integral part of Cardiopulmonary bypass (CPB). Myocardial and Cerebral protection has been claimed as advantage of hypothermia. Normothermic CPB has been proved to be a safe alternative with good myocardial and cerebral protection. From March 2000 to Oct 2003, 346 cases were done under CPB with normothermic Systemic and myocardial perfusion. The age range being 7 months to 80 years with a mean of 43.69±20.41 years. The M:F ratio is 236∶110. (2.14∶1). The procedures performed include congenital heart disease, valve procedures, coronary artery bypass grafting and others. The following peri- and postoperative data were analysed statistically to evaluate the efficacy of Normothermic CPB. Total CPB time was 101.24±50.45 minutes, time interval between onset of CPB and aortic cross clamp was 5.23±2.31 minutes and release of cross clamp and off CPB was 7.34±3.85 minutes. Arrhythmia occurred during weaning off CPB in 5 (1.44%) patients. Ionotropes used during weaning from CPB in 93 (26.87%) patients of which 76 (21.96%) cases required only dopamine. Vasodilators required during weaning off CPB in 15 (4.33%) patients. Development of systemic hyperthermia during rewarming was in 1 (0.28%) case & difference of central and peripheral blood pressure in 7 (2.03%) cases. Postoperative ventilation duration was 5.04±4.79 hours. Total bleeding was 237±115 mls, re-exploration was done in 6 (1.73%) cases. Postoperative neurological complication in 2 (0.57%), renal impairment requiring dialysis in 2 (0.57%) & GI bleed in 2 (0.57%) cases. Mortality was in 6 cases of which 1 (0.28%) was due to inability to wean off from CPB. We conclude normothermic systemic and myocardial perfusion during CPB is physiological, reduces morbidity and is a safe alternative to hypothermic CPB.

Cerebral ischemia caused by obstructed superior vena cava cannula is detected by near-infrared spectroscopy

Objective: Bicaval venous cannulation is being used with increasing frequency in neonates and infants to avoid circulatory arrest. However, superior vena cava (SVC) cannula obstruction may result in cerebral ischemia with no change in blood pressure or mixed venous O 2 saturation. The authors hypothesized that near-infrared spectroscopy (NIRS) would allow noninvasive detection of SVC cannula obstruction. Methods: Fifteen Yorkshire piglets (9.07 ± 0.20 kg) underwent total cardiopulmonary bypass (CPB) (100 mL/kg/min, pH-stat strategy, hematocrit of 20%) with ascending aortic and bicaval cannulations. Femoral arterial and SVC pressure were monitored as well as mixed venous O 2 saturation. NIRS monitoring of tissue oxygenation index (TOI) as well as oxyhemoglobin and deoxyhemoglobin (HHb) was undertaken. Animals were cooled to an esophageal temperature of 25°C over 20 minutes. CPB flow was reduced to 50 mL/kg/min for 20 minutes. Animals then underwent a 60-minute study period of continuous CPB at 50 mL/kg/min with manipulation of the SVC cannula: group 1, open; group 2, partial occlusion; and group 3, complete occlusion. Animals were rewarmed to 37°C at full flow with the SVC cannula open. Cerebral blood flow was assessed at onset of CPB, at end of cooling, at end of low flow, at end of SVC manipulation period, and at end of rewarming using radioactive microspheres. Results: CBF decreased to 27.9 ± 1.5 mL/min/100 g with complete occlusion ( p < 0.01 v group 1: 39.7 ± 1.9, group 2, 38.3 ± 2.0 mL/min/100 g) with no change in arterial pressure or mixed venous saturation. There were also significant differences in cerebral oxygen delivery between group 3 and other groups ( p < 0.01). SVC pressure increased to 19.5 ± 4.5 and 32.5 ± 3.1mmHg with partial and complete occlusion. NIRS indicated significant cerebral ischemia with a decrease in TOI ( p < 0.05; group 3 v group 1 and 2) and an increase in HHb ( p < 0.05; group 3 v group 1). At the end of the study, significant acidosis was found in group 3 compared with group 1 ( p < 0.05). Conclusion: SVC cannula obstruction causes cerebral ischemia with no change in blood pressure or venous oxygen saturation. In view of the difficulties and risks of CVP monitoring in babies, it is recommended to use other monitoring modalities such as NIRS to assess adequacy of cerebral perfusion if bicaval cannulation is used in neonates and infants.

Melatonin protects against lipid peroxidation and membrane rigidity in erythrocytes from patients undergoing cardiopulmonary bypass surgery.

The first aim of this study was to test whether there are changes in erythrocyte lipid peroxidation products and membrane fluidity during cardiac surgery involving cardiopulmonary bypass. Secondly, in vitro tests were performed to examine whether melatonin alters induced lipid peroxidation and reduced membrane fluidity in erythrocytes from these patients. Fifteen patients undergoing cardiac surgery involving cardiopulmonary bypass (CPB) were selected. Five blood samples were taken at different times during surgery for analysis of thiobarbituric acid reactive substances (TBARS) content and membrane fluidity of the erythrocytes. TBARS are an index of the level of lipid peroxidation. The results revealed an increase in TBARS levels and a parallel decrease in erythrocyte membrane fluidity (increased membrane rigidity) after the onset of CPB with respect to the reference sample. Likewise, in vitro induction of lipid peroxidation in the erythrocyte samples from CPB patients followed a similar pattern. The changes in TBARS levels and membrane fluidity were suppressed by pre-incubation of erythrocytes with melatonin prior to the induction (by 70 microm Fe2+ + 250 microm ascorbate) of lipid peroxidation in a concentration-dependent manner. The results constitute a persuasive argument for the use of melatonin for preventive and therapeutic purposes during CPB.

Body Weight-Related ionized hypomagnesemia in pediatric patients undergoing cardiopulmonary bypass for surgical repair of congenital cardiac defects

Study objectives To examine the serial time course of perioperative plasma ionized magnesium (iMg 2+ ) concentrations and to analyze the plasma iMg 2+ concentrations in children with different body mass who were undergoing open-heart surgery. Design Randomized, single-blinded study. Setting University-affiliated hospital of an academic medical institution. Patients 38 children undergoing open-heart surgery. Interventions Patients were divided into three groups according to their body mass: Group 1 (n = 12) <10 kg, Group 2 (n = 13) 10 kg to 20 kg, and Group 3 (n = 13) >20 kg. Measurements The relationship of iMg 2+ among the three groups of different body mass were analyzed at five different time intervals during the operation: induction of anesthesia, 5 minutes and 30 minutes after the onset of cardiopulmonary bypass (CPB), the beginning of rewarming, and the end of surgery. Main results iMg 2+ levels at 5 minutes after onset of CPB in patients weighing less than 20 kg (Groups 1 and 2) differed with those weighing more than 20 kg (Group 3) (p = 0.007 and 0.013). However, there was no difference in the iMg 2+ levels between Groups 1 and 2 (p = 0.993). In addition, iMg 2+ levels at 5 minutes after onset of bypass correlated well (r 2 = 0.66) in children with body mass less than 20 kg. Conclusions Low levels of ionized magnesium is an important finding in patients at the onset of CPB, which correlates well with the body mass of patients weighing less than 20 kg, and could be predicted by the regression curve. Based on these findings, hypomagnesemia can be prevented during CPB.

Bispectral index detects period of cerebral hypoperfusion during cardiopulmonary bypass

HE BISPECTRAL INDEX (BIS) is a processed electroencephalogram (EEG) parameter that was designed for the assessment of the depth of hypnosis or sedation and the detection of awareness. During cardiac anesthesia, BIS monitoring may be of value because the incidence of awareness is reported to be greater. 1 The authors use BIS monitoring for an anesthesia protocol, in which propofol is titrated to obtain BIS values between 50 and 40. This case report describes the use of BIS during cardiopulmonary bypass when a period of cerebral ischemia was detected with BIS monitoring. CASE REPORT A 61-year-old man (weight 93 kg, height 178 cm) was admitted for reoperation of his coronary artery bypass grafts (CABG). His first CABG was performed 16 years previously. Two years earlier he had had a myocardial infarction, congestive heart failure, and atrial fibrillation. One month before the present surgery, he complained of progressive angina pectoris (NYHA IV). Cardiac catheterization revealed occlusion of the graft to the ramus circumflex coronary artery and a 99% stenosis of the graft to the left anterior descending coronary artery. The anterior wall of the left ventricle was hypokinetic, and there was a grade II mitral valve incompetence. After placing peripheral intravenous and intra-arterial catheters, a 5-lead electrocardiogram, a pulse oximeter, and a BIS monitor (A2000, software version 1.08; Aspect Medical Systems, Newton, MA) were applied. Anesthesia was induced with an intravenous infusion of propofol at a rate of 1.86 g/h (twice body weight in mL/h). This infusion was controlled using the Rugloop (version 3.22; RUG, Gent, Belgium) computer program, which uses the pharmacokinetic model of Marsh et al. 2 The same computer program was used for data acquisition. When the patient became unresponsive to verbal command, the effect site concentration was found to be 2.0 g/mL, and, from then on, the continuous infusion mode was changed to the effect-site steering mode at that initial effect-site concentration. The effect-site concentration was thereafter adjusted to obtain a BIS value between 40 and 50. Once the patient was asleep, 10 mg of pancuronium and 1.5 g of cefuroxime were injected intravenously. A remifentanil infusion was then started at a rate of 0.33 g/kg/min, and intubation was performed 6 minutes later. From then on, the infusion rate of remifentanil was adjusted to obtain the desired systolic arterial pressure. After intubation, a pulmonary artery catheter was inserted via the right internal jugular vein, and an elevated pulmonary artery pressure (40/25 mmHg), an elevated wedge pressure (21 mmHg), and a low arterial pressure (85/55 mmHg) and cardiac index (1.8 L/min/m 2 ) were found with a spontaneous moderate recovery thereafter. The heart was not easily exposed because of adhesions and embedding in fatty tissue. Saphenous veins and the left internal mammary artery were prepared. After heparinization, the patient was put on cardiopulmonary bypass with a flow of 2.4 L/min/m 2 . The patient was cooled to a temperature of 28°C, and myocardial protection after crossclamping consisted of retrograde blood cardioplegia. Hematocrit was maintained above 22%. The mean arterial pressure was maintained between 50 and 80 mmHg, but no pharmacologic agents were used. The central venous pressure (CVP) was measured at the CVP port of the pulmonary artery catheter (distance from tip 30 cm) and was left in situ during cardiopulmonary bypass. The left marginal coronary artery was of poor quality and was ligated proximally and grafted distally with the venous graft. To obtain good access to this site of the anastomosis, the heart was twisted to the right. At this point, the CVP rose to 40 mmHg (Fig 1), and the arterial pressure decreased from 65 to 45 mmHg, leading to a severely reduced cerebral perfusion pressure. BIS values dropped from 40 to 11. The surgeon was unable to return the heart to its normal position before the anastomosis was finished. The cause of the drop in arterial pressure was not clear. No alterations in venous return or pump flow were seen at that time. The arterial pressure was restored with 20 g of intravenous norepinephrine. The BIS value returned immediately to 40. The CVP normalized after 12 minutes when the anastomosis was complete. Weaning from cardiopulmonary bypass was complicated with an elevated pulmonary artery pressure and arterial hypotension. The patient therefore received dobutamine (7 g/kg/ min), and an intra-aortic balloon pump catheter was inserted via the left femoral artery. The postoperative period was further complicated with a resternotomy for postoperative bleeding. The patient was extubated on the third postoperative day. On

How safe is the port access technique in minimally invasive coronary artery bypass grafting?

Background This study compares conventional coronary artery bypass grafting (CABG) with port access CABG via a left anterior small thoracotomy in patients requiring surgical multivessel revascularization. Clinical, neuropsychological, and angiographic outcomes were studied, as well as parameters of myocardial and cerebral protection. Pathogenicity of cardiopulmonary bypass (CPB) was further evaluated by measuring parameters of peripheral limb ischemia and inflammatory whole-body response. Methods In a prospective randomized study, 40 patients who required multivessel CABG were assigned to either conventional CABG via complete median sternotomy (group A) or port access CABG via minithoracotomy (group B). Control angiograms were performed in group B only. In addition, patients underwent neuropsychological testing after the operation. CK, CK-MB, and Troponin T levels were documented. S-100B protein and neuron-specific enolase (NSE) served to quantify cerebral injury. The terminal complement complex (C5b-9) and myeloperoxidase concentrations were determined to analyze inflammatory whole-body response after CPB. Results There was no mortality. One patient suffered a retrograde aortic dissection immediately after onset of CPB, but had an uneventful postoperative course after surgical repair. Troponin T and CK-MB showed no difference between groups. CK and myoglobin were significantly higher in the minimally invasive cohort. Changes in complement activation (C5b-9) and myeloperoxidase during CPB markers of the whole-body inflammatory response were similar in both groups. S-100B concentrations in the port access group were significantly higher, whereas NSE levels were similar in both groups. Both groups did not display any significant difference in neuropsychological testing. Conclusions Minimally invasive multivessel CABG via minithoracotomy using port access technology is feasible and safe. Though prolonged operating and CPB times with significantly higher S-100B concentrations were observed in group B, equivalent myocardial and cerebral protection and similar whole-body inflammatory response were documented.

Leukocyte depletion attenuates expression of neutrophil adhesion molecules during cardiopulmonary bypass in human beings

Background: On the basis of scanty information, the effects of a leukocyte filter during cardiac operations in human beings have been examined from the viewpoint of the expression of neutrophil adhesion molecules. This study was therefore designed to determine whether leukocyte depletion during cardiopulmonary bypass may interfere with neutrophil adhesion properties. Methods: Twenty-four patients undergoing elective heart operations were randomly allocated to a leukocyte-depletion group or a control group. Blood samples were collected at 7 points: before sternotomy, at 10, 30, and 60 minutes of cardiopulmonary bypass, at termination of cardiopulmonary bypass, 5 minutes after protamine administration, and 2 hours after cardiopulmonary bypass. The expression of the neutrophil surface adhesion molecules L-selectin and β2-integrins was determined by flow cytometric analysis in whole blood. Results: (1) CD11a expression did not change significantly in either group. There were no significant differences between control and leukocyte-depletion groups (P = .63). (2) There was a significantly higher expression of CD11b on the neutrophils during cardiopulmonary bypass in the control group than in the leukocyte-depletion group (P = .01). (3) CD11c expression was initially up-regulated from the onset of cardiopulmonary bypass, reaching a peak at 60 minutes after bypass in the control group (P = .02). The expression of CD11c did not differ significantly between groups (P = .23). (4) L-selectin expression was significantly lower in the leukocyte-depletion group than in the control group (P = .03). Conclusions: The major findings of the present study in human subjects undergoing elective cardiac operations with cardiopulmonary bypass are as follows: (1) bypass was associated with an up-regulation of the adhesion molecules L-selectin, CD11b, and CD11c but with no significant change in CD11a expression, and (2) the clinical use of a leukocyte-depleting filter could down-regulate the expression of CD11b and L-selectin.

Interleukin-8 secretion following cardiopulmonary bypass in children as a marker of early postoperative morbidity.

Interleukin (IL)-8, an 8 kDa peptide, is the first chemoattractant identified as being specific for neutrophils. Its possible association with early postoperative morbidity following cardiopulmonary bypass (CPB) in infants and children is unknown. This prospective cohort study sought possible roles of IL-8 in the inflammatory response to CPB and investigated if changes in IL-8 levels and clinical course and outcome were related. IL-8 levels were measured in 16 children undergoing CPB. Systemic blood was collected after induction of anaesthesia (baseline), at 15 min after CPB onset and cessation, and at 1, 4, 8, 12 and 24 h thereafter. Correlation coefficients between IL-8 levels and CPB time ranged from 0.45 to 0.55, heart rate 0.41--0.44, surgical time 0.41--0.63 and pH --0.56 to --0.50 (P < 0.05 for all parameters). Univariate analyses showed that patients requiring inotropic support and those with tachycardia had significantly higher postoperative IL-8 levels (P < 0.05). Furthermore, IL-8 levels were significantly higher in patients with surgical times > 200 min and in patients with an aortic clamp in place for > 65 min. There was an association between IL-8 and early postoperative heart rate, and the need for inotropic support IL-8 correlated positively with surgical time, CPB time and heart rate and negatively with pH. IL-8 release may be related to some of the haemodynamic changes in the early postoperative course following CPB. The relationship between IL-8 and late markers of patient outcome in high-risk infants awaits further studies.

Change of Tumor Necrosis Factor-alpha Concentration after Pediatric Cardiopulmonary Bypass and Its Relationship with Postoperative Course

Background: Systemic inflammatory response after open heart surgery has an adverse effect on the postoperative course of patient, and results from the release of cytokines by leukocytes activated by cardiopulmonary bypass (CPB). TNF- has an important role in inflammatory response-it has clinical effects such as fever, tachycardia, and hypotension, and also induces other cytokines. However studies about the change of blood concentration of TNF- after CPB show differing results, and so have been up to now inconclusive, we have therefore endeavored to investigate the change of TNF- level after CPB and its relationship with the postoperative course of patients. Methods: We studied 20 children undergoing open heart surgery. Serum TNF- was detected after induction (control), 5 minutes after onset of CPB (TL), 5 minutes after release of aortic cross clamp (T2), and 30 minutes after CPB (T3) by enzyme-linked immunosorbent assay. We compared the concentration of TNF- and the duration that patients stayed in intensive care unit (ICU) and were supported by mechanical ventilator in group I (CPB time 60 minutes, n = 10) and group II (CPB time > 60 minutes, n = 10). Results: TNF- levels of S2 and S3 were significantly lower than those of SI and S4 (P = 0.001), but no difference was detected between group I and II. No statistical relationship was found linking TNF- levels with the duration in ICU, or time supported by mechanical ventilator. Three children with postoperative complications showed higher level of TNF- than others (P = 0.002). Conclusions: We concluded that TNF- levels decreased during CPB, did not increased after CPB, and had no relationship to such postoperative courses as postoperative ICU time and intubation time, but there was a correlation with postoperative complications.

Perioperative serum levels of tumour-necrosis-factor alpha (TNF-alpha), IL-1 beta, IL-6, IL-10 and soluble IL-2 receptor in patients undergoing cardiac surgery with cardiopulmonary bypass without and with correction for haemodilution.

Cardiac surgery with cardiopulmonary bypass (CPB) leads to a systemic inflammatory response with secretion of cytokines. Alterations in the serum concentrations of cytokines have important prognostic significance. Reports on cytokine release during cardiac surgery with CPB have yielded conflicting results. Haemodilution occurs with the onset of CPB resulting in large fluid shifts during the perioperative course of cardiac procedures. In the present study we compare the perioperative course of serum concentrations of TNF-alpha, IL-1beta, IL-6, IL-10 and sIL-2R with and without correction for haemodilution in patients undergoing coronary artery bypass grafting (CABG) surgery. Twenty male patients undergoing elective CABG surgery with CPB and general anaesthesia using a balanced technique with sufentanil, isoflurane and midazolam were enrolled into the study. Serum levels of TNF-alpha, IL-1beta, IL-6, IL-10 and sIL-2R were measured using commercially available ELISA kits. Simultaneous haematocrit values were obtained at all sample times. Statistical analysis was performed by non-parametric analysis of variance and t-tests for data corrected for haemodilution and data that were not corrected for haemodilution. Adjusted significance level was P < 0.01. Intra-operatively, up to the second post-operative day PCV values were significantly decreased compared with preoperative values. Cytokine measurements not corrected for haemodilution were significantly lower than the corrected values. The perioperative haemodilution and decrease in PCV may lead to an underestimation of the cytokine secretion in post-operative patients. We conclude that cytokine measurements were significantly influenced by the perioperative haemodilution and the subsequent decrease in PCV and may in part account for the varying results reported in the literature regarding cytokine release in patients undergoing CABG surgery.

Hepatosplanchnic oxygenation is better preserved during mild hypothermic than during normothermic cardiopulmonary bypass.

To assess and compare the effects of normothermic and mild hypothermic cardiopulmonary bypass (CPB) on hepatosplanchnic oxygenation. We studied 14 patients scheduled for elective coronary artery bypass graft surgery who underwent normothermic (>35 degrees C; group I, n=7) or mild hypothermic (32 degrees C; group II, n=7) CPB. After induction of anesthesia, a hepatic venous catheter was inserted into the right hepatic vein to monitor hepatic venous oxygen saturation (ShvO(2)) and hepatosplanchnic blood flow by a constant infusion technique that uses indocyanine green. The ShvO(2) decreased from a baseline value in both groups during CPB and was significantly lower at ten minutes and 60 min after the onset of CPB in group I (39.5 +/- 16.2% and 40.1 +/- 9.8%, respectively) than in group II (61.1 +/- 16.2% and 61.0 +/- 17.9%, respectively; P <0.05). During CPB, the hepatosplanchnic oxygen extraction ratio was significantly higher in group I than in group II (44.0 +/- 7.2% vs 28.7 +/- 13.1%; P <0.05). Hepatosplanchnic oxygenation was better preserved during mild hypothermic CPB than during normothermic CPB.

Oscillation in the activities of MEK/ERK1/2 during cardiopulmonary bypass in pigs

Background. Because cardiopulmonary bypass (CPB) is associated with edema and vasoreactive dysfunction and ERK1/2 pathway is involved in vascular contractility and permeability, a time course study was performed to monitor MEK/ERK1/2/Elk-1 activities during CPB. Methods. Pigs were subjected to normothermic CPB for 90 minutes followed by post-CPB perfusion for 180 minutes. Atrial myocardium was sampled before CPB, 5 minutes after CPB onset, 5 minutes after weaning from CPB, and at the end of post-CPB. Skeletal muscle and mesenteric vessels samples were harvested before CPB, 5 minutes after CPB institution, and every 30 minutes thereafter to the end of post-CPB. Samples were analyzed by immunoblotting and immunofluorescence microscopy with the use of specific antibodies against active (phosphorylated) forms of ERK1/2, MEK1/2, and Elk-1. Results. Pigs that were subjected to CPB showed an increase in phospho-ERK1/2 after 30 minutes of CPB, followed by a decrease after 90 minutes. Another phosphorylation peak was observed 30 to 60 minutes of post-CPB, followed by a decrease to below baseline at the end of reperfusion. MEK1/2 and Elk-1 activation profiles paralleled ERK1/2 activity peaks. Control samples showed no significant increase above basal levels. Conclusions. Activation of MEK/ERK1/2/Elk-1 pathways closely follows major CPB surgical manipulations (institution and termination) and could be related to morbidity during and after CPB. (Surgery 2001;130:182-91.)

Time course of changes in jugular venous oxygen saturation during hypothermic or normothermic cardiopulmonary bypass in patients with diabetes mellitus

Preexisting diabetic mellitus is a risk factor determining postoperative neurological disorders. The present study assesses the effects of normothermic and hypothermic cardiopulmonary bypass (CPB) on jugular venous oxygen saturation (SjvO2)in patients with preexisting diabetic mellitus. Sixteen diabetic patients who underwent elective coronary artery bypass grafting surgery were randomly divided into two groups: Group DN (n=8, diabetic patients) underwent normothermic CPB (>35 degrees C), and group DH (n=8, diabetic patients) underwent hypothermic CPB (32 degrees C). Controls were 16 age-matched non-diabetic patients (normothemic group, CN: n=8; hypothemic group, CH: n=8). A 4.0 F fiberoptic oximetry oxygen saturation catheter was inserted into the right jugular bulb to continuously monitor SjvO2 values. Hemodynamic parameters and arterial and jugular venous blood gases were measured seven times. Cerebral desaturation, which was defined as SjvO2 values below 50%, was observed during normothermic CPB in diabetic patients (at the onset of CPB: 46+/-3%, at 20 min after onset of CPB: 49+/-3%, means+/-SD, respectively). No cerebral desaturation occurred in diabetic and control patients during hypothermic CPB. Patients with preexisting diabetes mellitus experienced cerebral desaturation during normothermic CPB.

The impact of anti-endotoxin core antibodies on endotoxin and cytokine release and ventilation time after cardiac surgery

OBJECTIVESWe hypothesized that a temporary cardiopulmonary bypass (CPB)-induced reduction of endotoxin antibody levels contributes to elevated endotoxin levels and the associated inflammatory consequences, with a significant influence on the postoperative ventilation time period.BACKGROUNDCardiac surgery using CPB induces a systemic inflammatory response syndrome with an associated risk of increased postoperative morbidity and mortality.METHODSA total of 100 consecutive patients undergoing elective coronary artery bypass graft surgery using CPB were prospectively investigated. Endotoxin core antibodies (immunoglobulin [Ig] M/IgG against lipid A and lipopolysaccharide), endotoxin, interleukin (IL)-1-beta, IL-6, IL-8 and tumor necrosis factor-alpha were measured serially from 24 h preoperatively until 72 h postoperatively.RESULTSEighty-five patients had no complications (group 1), whereas 15 patients required prolonged ventilation (group 2). In both groups, there was a decrease of all antibodies 5 min after CPB onset, compared with baseline values (p < 0.001), an increase of endotoxin and IL-8 peaking at 30 min postoperatively (p < 0.001) and an increase of IL-6 peaking 3 h postoperatively (p < 0.001). In group 2, preoperative antibody levels were lower (p < 0.01)—specifically, the decrease in IgM was significantly stronger and of longer duration (p < 0.002)—and levels of endotoxin (p < 0.001) and IL-8 (p < 0.001) were higher at 30 min postoperatively.CONCLUSIONSWe conclude that an CPB-associated temporary reduction of anti-endotoxin core antibody levels contributes to elevated endotoxin and IL-8 release. Furthermore, lower levels of IgM anti-endotoxin core antibodies were associated with a greater rise in endotoxin and IL-8, as well as prolonged respirator dependence.

Bispectral analysis during cardiopulmonary bypass: the effect of hypothermia on the hypnotic state

Study Objective: To evaluate the hypothesis that the bispectral index (BIS) is not affected by the hypothermia that is associated with cardiopulmonary bypass (CPB). Design: Prospective, observational study. Setting: Cardiac surgical operating suite of a university medical center. Patients: 100 patients undergoing cardiac surgery requiring CPB. Interventions: A constant effect site concentration of 2.2 ng/mL for fentanyl and 60 ng/mL for midazolam was maintained throughout surgery using a computer-assisted continuous infusion technique. Measurements: The BIS value, percent isoflurane administered, predicted brain concentrations of midazolam and fentanyl, and nasopharyngeal temperature were recorded before CPB, at 15 minutes after the onset of CPB, at placement of the aortic cross-clamp, at start of rewarming, on separation from CPB, and 15 minutes after the end of CPB. Data were analyzed using a repeated-measures mixed-effects method, taking into account temperature, age, and predicted level of each anesthetic. Main Results: A significant overall association between temperature and BIS was observed independent of patient age, predicted brain midazolam or fentanyl concentration, percent isoflurane administered, and surgical time point (p < 0.001). The BIS is estimated to decrease by 1.12 units for each degree Celsius decrease in body temperature. Conclusions: Hypothermia decreases the BIS by 1.12 units per degree Celsius decline in temperature.

Superior hepatic mitochondrial oxidation-reduction state in normothermic cardiopulmonary bypass

Objective: This study is the first comparative investigation of hepatic blood flow and oxygen metabolism during normothermic and hypothermic cardiopulmonary bypass. Methods: Twenty-four patients undergoing coronary bypass operations were randomly divided into 2 groups according to their perfusion temperatures, either normothermia (36°C) or hypothermia (30°C). The clearance of indocyanine green was measured at 3 points. Arterial and hepatic venous ketone body ratios (an index of mitochondrial redox potential) and hepatic venous saturation were measured. Results: Hepatic blood flow in both groups was identical before, during, and after cardiopulmonary bypass (normothermia, 499 ± 111, 479 ± 139, and 563 ± 182 mL/min, respectively; hypothermia, 476 ± 156, 491 ± 147, and 560 ± 202 mL/min, respectively). The hepatic venous saturation levels were significantly lower during cardiopulmonary bypass in the normothermic group (normothermia, 41% ± 13%; hypothermia, 61% ± 18%; P <.01), indicating a higher level of oxygen extraction use. The arterial ketone body ratio in the hypothermic group decreased severely after the onset of cardiopulmonary bypass (P <.01) and did not return to its subnormal value (>0.7) until the second postoperative day. However, the reduction in arterial ketone body ratio was less severe in the normothermic group. The difference in hepatic venous ketone body ratios was more obvious, and the hepatic venous ketone body ratios in the normothermic group were statistically superior to those of the hypothermic group throughout the course (P <.05-.01). Conclusions: Normothermic cardiopulmonary bypass provides adequate liver perfusion and results in a better hepatic mitochondrial redox potential than hypothermic cardiopulmonary bypass. Because arterial ketone body ratios reflect hepatic energy potential, normothermia was considered to be physiologically more advantageous for hepatic function. (J Thorac Cardiovasc Surg 2001;121:1179-86)

Comparative Analysis of Alpha-stat and pH-stat Strategies with a Membrane Oxygenator During Deep Hypothermic Circulatory Arrest in Young Pigs

Using young pigs, this study compared the strategies of alpha-stat and pH-stat during deep hypothermic circulatory arrest (DHCA) for the cooling time of brains during the induction of hypothermia and rewarming time with cardiopulmonary bypass (CPB); the cerebral perfusion rate and metabolism rate, and the ratio of these 2 rates; and the extent of the cerebral edema development after circulatory arrest. Fourteen young pigs were assigned to 1 of 2 strategies of gas management. Cerebral blood flow was measured with a cerebral venous outflow technique. With CPB, core cooling was initiated and continued until the nasopharyngeal temperature fell below 20 degrees C. The flow rate was set at 2,500 ml/min. Once the temperature reached below 20 degrees C, the animals were subjected to DHCA for 40 min. During the cooling period, the acid-base balance was maintained using either alpha-stat or pH-stat strategy. After DHCA, the body was rewarmed to the normal body temperature. The animals then were sacrificed, and we measured the brain water content. The cerebral perfusion and metabolism rates were measured before the onset of CPB, before cooling, before DHCA, 15 min after rewarming, and upon the completion of rewarming. The cooling time was significantly shorter with alpha-stat than with pH-stat strategy while no significant differences were observed in the rewarming time between groups. Also, no significant differences were found in cerebral blood flow volume, metabolic rate, or flow/metabolic rate ratio between groups. In each group, the cerebral blood flow volume, metabolic rate, and flow/metabolic rate ratio showed significant differences in body temperature. Brain water content showed no significant differences between the 2 groups. In summary, this study found no significant differences between alpha-stat and pH-stat strategies, except in the cooling time. The cooling time was rather shorter with the alpha-stat than with the pH-stat strategy.