Intermittent antegrade tepid versus cold blood cardioplegia in elective myocardial revascularization. Influence of normothermic systemic perfusion during coronary artery bypass operations: a randomized prospective study. Which techniques of cardioplegia prevent ischemia? Cardiopulmonary bypass, temperature, and central nervous system dysfunction. Randomized trial comparing intermittent antegrade warm blood cardioplegia with multidose cold blood cardioplegia for coronary artery bypass. Prospective, randomized trial of retrograde warm blood cardioplegia: myocardial benefit and neurologic threat. Continuous warm versus intermittent cold blood cardioplegia for coronary bypass surgery in patients with left ventricular dysfunction. Cerebral dysfunction after coronary artery bypass grafting done with mild or moderate hypothermia. A prospective randomised study of continuous warm versus intermittent cold blood cardioplegia for coronary artery surgery: preliminary report. Cardiopulmonary bypass temperature, hematocrit, and cerebral oxygen delivery in humans. Normothermia versus hypothermia during cardiopulmonary bypass: a randomized, controlled trial. The effects of cardiopulmonary bypass temperature on neuropsychologic outcome after coronary artery operations: a prospective randomized trial. What is the best perfusion temperature for coronary revascularization? Intermittent antegrade warm versus cold blood cardioplegia: a prospective, randomized study. Temperature during cardiopulmonary bypass for coronary artery operations does not influence postoperative cognitive function: a prospective, randomized trial. Effects of hypothermic and normothermic cardiopulmonary bypass on brain oxygenation.
The ideal temperature for blood cardioplegia administration remains controversial.
                Fifty-two patients who required elective myocardial revascularization were prospectively randomized to receive intermittent antegrade tepid (29 degrees C; group T, 25 patients) or cold (4 degrees C; group C, 27 patients) blood cardioplegia.
                The two cohorts were similar with respect to all preoperative and intraoperative variables. The mean septal temperature was higher in group T (T, 29.6 degrees +/- 1.1 degrees C versus 17.5 degrees +/- 3.0 degrees C; p < 0.0001). After reperfusion, group T exhibited significantly greater lactate and acid release despite similar levels of oxygen extraction (p < 0.05). The creatine kinase-MB isoenzyme release was significantly lower in group T (764 +/- 89 versus 1,120 +/- 141 U x h/L; p < 0.04). Hearts protected with tepid cardioplegia demonstrated significantly increased ejection fraction with volume loading, improvement in left ventricular function at 12 hours, and decreased need for postoperative inotropic support (p < 0.05). The frequency of ventricular defibrillation after cross-clamp removal was lower in this cohort (p < 0.05). There were no hospital deaths, and both groups had similar postoperative courses.
                Intermittent antegrade tepid blood cardioplegia is a safe and efficacious method of myocardial protection and demonstrates advantages when compared with cold blood cardioplegia in elective myocardial revascularization. Normothermic cardiopulmonary bypass has been proposed as a more physiologic technique than hypothermic bypass for the maintenance of the body during cardiac surgery. The aims of this study were to investigate the effects of systemic perfusion temperature on clinical outcome after coronary revascularization.
                Three hundred patients (mean age 60 +/- 9 years, 88% male) were prospectively randomized into three groups: hypothermia (28 degrees C, n = 100), moderate hypothermia (32 degrees C, n = 100), and normothermia (37 degrees C, n = 100). All patients received cold antegrade St. Thomas' Hospital crystalloid cardioplegic solution, and patients in the normothermic group were actively rewarmed during cardiopulmonary bypass (nasopharyngeal temperature 37 degrees C).
                No differences were found between groups with respect to mortality (1%), intraaortic balloon pump use, perioperative infarction rates, focal neurologic deficits (1%), intubation time, intensive care unit stay, and postoperative hospital stay. Further stepwise regression analysis identified age and intensive care unit stay as important predictors of the variability in postoperative stay (both R2 = 0.114; p < 0.001), whereas perfusion temperature remained a nonsignificant explanator. Normothermic perfusion necessitated larger doses of phenylephrine to maintain arterial pressure above 50 mm Hg during cardiopulmonary bypass (p < 0.0001 vs 28 degrees C, p < 0.01 vs 32 degrees C) but less requirement for electrical defibrillation during reperfusion (p < 0.05 vs 32 degrees C, p < 0.01 vs 28 degrees C). Total chest drainage was not different between groups, but patients undergoing normothermic cardiopulmonary bypass required less transfusion of blood (p < 0.05 vs 28 degrees C and 32 degrees C) and platelets (p < 0.04 vs 32 degrees C, p < 0.001 vs 28 degrees C) in the postoperative period.
                Cardiopulmonary bypass temperature did not influence early clinical outcome after routine coronary artery bypass operations. Normothermic systemic perfusion was associated with an increased requirement for vasoconstrictors and reduced requirements for electrical defibrillation and transfusion of blood products. One hundred seven patients undergoing coronary artery bypass grafting were randomized to receive warm antegrade (n = 21), warm retrograde (n = 22), cold antegrade (n = 20), cold retrograde (n = 22), or intermittent cold antegrade (n = 22) blood cardioplegia. Myocardial oxygen consumption and lactate production, adenine nucleotides, and adenine nucleotide degradation products were measured during the operation, and creatine kinase-MB release was assessed postoperatively. Warm cardioplegia resulted in greater myocardial lactate production than cold cardioplegia (p = 0.048). Retrograde cardioplegia was associated with greater lactate production than antegrade cardioplegia (p = 0.015). Adenosine triphosphate depletion was similar among groups. However, poorly diffusible metabolites of adenosine triphosphate accumulated to the greatest extent in the intermittent cold group. Levels of hypoxanthine were highest after warm retrograde cardioplegia. Operative mortality and morbidity were low and were not different among groups. In summary, none of the five techniques of cardioplegia evaluated in this study was able to completely prevent myocardial ischemia. Anaerobic lactate production was minimized with cold cardioplegia and with antegrade cardioplegic delivery. Hypothermia may have impaired regeneration of adenosine triphosphate, however, particularly in association with inadequate or intermittent cardioplegic flow. Neurological injury is an important cause of morbidity and mortality after cardiac surgery. With the advent of warm heart surgery, the neuroprotective role of hypothermic cardiopulmonary bypass (CPB) has come under increasing scrutiny. Preliminary work by us in the area found no increased risk of neurological morbidity with normothermic CPB in a small group of patients and suggested a possible benefit. The purpose of the present study is to compare the incidence of neurological and neuropsychological dysfunction in a larger number of patients randomized to warm or cold aortocoronary bypass surgery.
                With the approval of the institutional research ethics committee, 201 aortocoronary bypass patients were randomized to normothermic or moderate hypothermic CPB and subjected to neurological and neuropsychological evaluation. These subjects were a subset of patients enrolled in a large multicenter trial comparing warm versus cold heart surgery. The examinations took place preoperatively, 5 days after operation, and a 3-month follow-up. The examination consisted of a clinical neurological examination and a brief neuropsychological test battery. The neuropsychological tests included the Buschke selective reminding procedure, the Wechsler memory scale-revised visual reproduction subtest, the trial making test (parts A and B), the Wechsler adult intelligence scale-revised digit symbol subtest, and the grooved pegboard test. The examiner and subjects were unaware of the CPB temperature allocation (warm, > 34 degrees C; cold, < or = 28 degrees C). Statistical analysis was performed using the SAS statistical software package. Two hundred one patients were enrolled in the study. Of these, 155 patients completed the entire protocol and were included in the final analysis (warm group, n = 78; cold group, n = 77). One patient in the warm group died perioperatively from a massive hemispheric stroke. Another warm group patient was unable to complete neuropsychological evaluation because of a perioperative stroke. Thus, 153 patients completed the entire series of neuropsychological tests. A total of 6 patients (warm group, n = 2; cold group, n = 4; P = NS) suffered from perioperative focal neurological deficits. There was a consistent deterioration in scores from tests of psychomotor speed/coordination (trial making, digit symbol, pegboard) in the early postoperative period, which resolved by the 3-month follow-up. Tests of memory (Buschke, Wechsler memory scale) showed no evidence of patient deterioration in the postoperative period. No difference was seen between the warm and cold groups.
                In this randomized trial of normothermic versus hypothermic CPB, we found deterioration in scores of tests of psychomotor speed but not of memory in the early postoperative period. We were unable to demonstrate any neuroprotective effect from moderate hypothermia in this patient population. Forty patients were randomized to receive antegrade multidose warm (WBC) or cold blood cardioplegia (CBC) during coronary artery bypass. Cardioplegia was infused at a predetermined dose every 10 min during cardioplegia arrest and core temperature was maintained at 37 degrees C in both groups during extracorporeal circulation. Patient profiles were similar in the two groups. Cardiac index, left ventricular stroke work index, and myocardial oxygen consumption were measured before bypass and during the first 7 h of reperfusion. There was no significant difference in myocardial metabolic and function recovery, the incidence of myocardial infarction, low cardiac output or death. Our data suggests that similar protection is provided with the two techniques of myocardial protection. From March 1991 through July 1992, 1,001 patients having elective coronary artery bypass grafting were randomized to receive either continuous warm (> or = 35 degrees C) blood cardioplegia with systemic normothermia (> or = 35 degrees C) or intermittent cold (< or = 8 degrees C) oxygenated crystalloid cardioplegia and moderate systemic hypothermia (< or = 28 degrees C). Preoperative variables including age, sex, prior coronary bypass grafting, hypertension, prior myocardial infarction, diabetes, angina class, and preoperative heart failure class were similar in both groups, as were the intraoperative variables of number of coronary grafts, mammary artery use, and cardiopulmonary bypass time. Aortic cross-clamp time was significantly longer in the warm group (46 +/- 23 minutes versus 40 +/- 21 minutes). Most postoperative variables including mortality (warm, 1.0%, and cold, 1.6%), Q wave infarction (warm, 1.4%, and cold, 0.8%), and need of an intraaortic balloon pump (warm, 1.4%, and cold, 2.0%) were similar between groups. Total neurologic events (warm, 4.5%, and cold, 1.4%; p < 0.005) and perioperative strokes (warm, 3.1%, and cold, 1.0%; p < or = 0.02) were significantly higher in the warm group. Neurologic events included perioperative stroke (warm, 15 patients, and cold, 5 patients; p < 0.02), perioperative encephalopathy (warm, 2 patients, and cold, 1 patient), and delayed (> or = 3 in-hospital days) stroke (warm, 5 patients, and cold, 1 patient). All patients experiencing a stroke had a persistent neurologic deficit at the time of discharge. Encephalopathy resolved completely in all instances.(ABSTRACT TRUNCATED AT 250 WORDS) Between October 1991 and March 1994, 108 consecutive patients with moderate to severe left ventricular dysfunction underwent non-emergency isolated coronary artery surgery under the care of one surgeon (A.R.). They were prospectively randomised to receiving either intermittent cold (Group 1-50 patients) or continuous warm (Group 2-58 patients) blood cardioplegia for myocardial protection. There were no significant differences in clinical outcome between the two groups, as judged by operative mortality, rates of perioperative myocardial infarction, the serum CKMB isoenzyme level at 2 and 18 h after operation, need for circulatory support, postoperative neurological deficit, or duration of hospital stay. Group 2 patients required significantly more potassium (68 vs 29 mmol, P < 0.001) to maintain diastolic arrest and also had higher serum potassium levels after removal of the cross-clamp (P < 0.001). However, sinus rhythm returned spontaneously with greater frequency (91.2% vs 45.8%, P < 0.001) in Group 2 patients. In conclusion this report suggests that retrograde continuous warm blood cardioplegia provides comparable myocardial protection to that achieved with retrograde intermittent cold blood cardioplegia in patients with moderate to severe left ventricular dysfunction undergoing isolated coronary artery surgery. Ninety-nine patients undergoing elective coronary artery bypass grafting were enrolled in a prospective, randomized study to evaluate the incidence of cerebral dysfunction after "mild" or "moderate" hypothermia during cardiopulmonary bypass.
                Patients were evaluated before and after operation before hospital discharge and in some cases at follow-up at least 6 weeks later with a complete neurologic examination (85 patients) and a battery of standard neuropsychometric tests (86 patients).
                Postoperative changes detected by neurologic examination consisted of the appearance of new primitive reflexes in both groups. No statistically significant differences in incidence were found. The neuropsychometric performances of the two groups were statistically similar by either event-rate or group-rate analysis.
                There is no detectable difference in postoperative cerebral dysfunction in patients undergoing coronary artery bypass grafting who are supported by cardiopulmonary bypass with either mild or moderate hypothermia. Between October 1991 and March 1993, 281 consecutive patients underwent non-emergency isolated coronary artery surgery under the care of one surgeon (A.R.). They were prospectively randomised to receive either intermittent cold (Group I-144 patients) or continuous warm (Group II-137 patients) blood cardioplegia for myocardial protection. There were no significant differences in clinical outcome between the two groups, as judged by operative mortality, rates of peri-operative myocardial infarction, blood loss, need for circulatory support, post-operative neurological deficit, or duration of intensive care or hospital stay. However, sinus rhythm returned spontaneously with greater frequency (91.2% vs 45.8%, P < 0.001) in Group II patients. There was greater transmyocardial oxidative stress in Group I patients, as evidenced by a significant rise in oxidised glutathione in coronary sinus blood on myocardial reperfusion. Also, the serum CKMb isoenzyme level 2 h post-operatively was significantly raised in Group I patients, although this difference had disappeared by the day after surgery. In conclusion this preliminary report suggests that continuous warm blood cardioplegia provides comparable myocardial protection to that achieved with standard hypothermic techniques in patients undergoing coronary artery surgery. The neurologic effects of warm heart operations is a subject of popular interest. The purpose of this study was to examine the adequacy of cerebral oxygenation during normothermic cardiopulmonary bypass and better define the relationship between hematocrit, temperature, and brain oxygen delivery.
                Cerebral blood flow, metabolic rate, and oxygen delivery were measured in 60 patients randomized to normothermic (37 degrees C) or hypothermic (27 degrees C) cardiopulmonary bypass. The nitrous oxide saturation technique of Kety and Schmidt was used for cerebral blood flow determinations. Both temperature groups underwent moderate (31%) hemodilution.
                During normothermic cardiopulmonary bypass, cerebral blood flow increased secondary to hemodilution and decreased cerebral vascular resistance; a normal matching of oxygen demand and delivery was maintained. During hypothermic bypass, hemodilution and hypothermia had essentially equal, opposing effects on cerebral vascular resistance and blood flow. With hypothermia, brain oxygen demand and delivery were both reduced but not closely coupled.
                From the standpoint of global cerebral perfusion and oxygenation, our data support the practice of "warm" heart operations. It clarifies the marked influence of hematocrit on cerebral blood flow and delineates the interaction of temperature and hematocrit on cerebral oxygen delivery. It also suggests that additional investigation to better define "temperature-appropriate" hemodilution during cardiopulmonary bypass is indicated. To evaluate the influence of perfusion temperature on systemic effects of cardiopulmonary bypass (CPB), 30 patients undergoing elective coronary artery bypass grafting were randomly assigned to either normothermic (warm, n = 14, 36 degrees C) or hypothermic (cold, n = 16, 28 degrees C) CPB. Serial hemodynamic measurements and blood samples were obtained before, during and after the CPB procedure. During CPB, there were no differences between both groups in the need for vasopressors (norepinephrine, phenylephrine), urinary output, or fluid balance. In the early postoperative period, normothermic CPB patients had significantly lower systemic vascular resistance and higher cardiac index measurements (mean +/- standard error: systemic vascular resistance, 880 +/- 27 versus 1,060 +/- 57 dyne.s.cm-5, p = 0.025; cardiac index, 3.6 +/- 0.1 versus 2.9 +/- 0.1 L.min-1.m-2, p = 0.01) without differences in the administration of vasoactive drugs. Blood loss was significantly higher in patients after hypothermic CPB (median [range] body surface area: 370 [180-560] versus 490 [280-2,120] mL/m2, p = 0.0006), with a greater need for transfusion of erythrocytes and fresh frozen plasma. Plasma levels of tumor necrosis factor and soluble tumor necrosis factor receptors increased during and after CPB, independent of perfusion temperature. This study suggests a significant influence of CPB temperature and respective perfusion management on postoperative hemodynamics and blood loss. Normothermic CPB is not associated with additional systemic adverse effects. The effect of systemic perfusion temperature on postoperative cognitive function was investigated in 96 adult patients undergoing elective coronary revascularization with cardiopulmonary bypass at 28 degrees C, 32 degrees C, or 37 degrees C. Neuropsychologic performance was assessed 1 day before the operation and 6 weeks after the operation. Five tests were adapted from the Wechsler Adult Intelligence Scale and two from the Wechsler Memory Scale.
                No patients had major neurologic complications. Ninety-three patients completed the five Wechsler Adult Intelligence Scale tests, but only 70 went on to complete the Wechsler Memory Scale tests as well. In these, there was an effect of cardiopulmonary bypass temperature on the number of neuropsychologic tests in which there was a preoperative to postoperative deterioration (p = 0.021), the number with bypass at 37 degrees C being significantly greater than the number with bypass at 32 degrees C (p = 0.015). Subsidiary analyses using a multivariate linear model examined the effect of cardiopulmonary bypass temperature on the magnitude of change, with or without allowing for other possible confounding influences. There was an adverse effect of normothermic (37 degrees C) versus moderately hypothermic (32 degrees C) perfusion---more convincingly displayed in the analyses of all seven scores rather than just the Wechsler Adult Intelligence Scale scores. Further cooling to 28 degrees C conferred no additional benefit in terms of cognitive function. The importance of the deterioration is open to question. [corrected] A National Institutes of Health-funded clinical trial of patients undergoing coronary artery bypass randomized perfusate and myocardial preservation to cold, tepid, or warm temperatures. The goal of the trial was to evaluate neurologic function before and after operation (4 days and 1 month after operation) and to measure hematologic data for fibrinolytic potential.
                The three groups comprised 116 patients who completed neurologic evaluation by means of the Mathew scale out of 130 entered into the trial (37 cold group, 50 tepid, and 43 warm). Twenty-five patients had complete hematologic studies done. All three groups were comparable before operation. The myocardial preservation protocol used blood cardioplegic solution at cold (8 degrees to 10 degrees C), tepid (32 degrees C), or warm (37 degrees C) temperature and the systemic perfusate temperature during cardiopulmonary bypass was 20 degrees (cold), 32 degrees C (tepid), or 37 degrees (warm).
                Patients in the cold group had a longer duration of intubation and postoperative hospitalization and a slightly but significantly higher peak postoperative creatine kinase MB level than patients in the warm group. There were no deaths. There was deterioration in Mathew scale findings in all three groups, and no distinction could be made between groups. However, a significantly higher number in the cold group had an abnormal postoperative neurologic examination result that prompted computed tomographic scanning (18.9% cold, 2% tepid, 9.3% warm). A cerebrovascular accident was documented by computed tomographic scanning in 8.1%, 0%, and 4.7% of patients in the cold, tepid, and warm groups, respectively (not significant). Hematologic data documented significantly increased fibrinolytic potential in the warm group.
                Perfusion temperature is a factor in recovery from cardiopulmonary bypass. Cold has more adverse neurologic sequelae that prompt computed tomographic scanning whereas warm has more activation of fibrinolytic potential. Tepid is the best temperature for optimizing recovery from cardiopulmonary bypass. A prospective, randomized study was performed in 200 patients undergoing coronary artery bypass grafting to compare the myocardial protection obtained with intermittent antegrade warm versus cold blood cardioplegia. Preoperative and surgical characteristics of the two cohorts were similar. Intermittent antegrade infusion of warm blood cardioplegia failed to achieve sustained electromechanical arrest of the heart in 13%. The only difference in clinical outcomes was the more frequent spontaneous return to sinus rhythm after the unclamping of the aorta in the warm group (88% versus 70%, p = 0.002). Mortality (1% each) and myocardial infarction (2% and 4%) rates were similar. Rates of increase in serum activity of the isoenzyme of creatine kinase (CK-MB), CK-MB mass concentration, and cardiac troponin-T level as well as total release of troponin T were significantly lower in the warm group, and fewer patients in this group had a clinically significant increase in serum CK-MB mass (20% versus 39%, p = 0.005) and troponin T (20% versus 56%, p = 0.00001). Thus, intermittent antegrade warm blood cardioplegia is appropriate and clinically safe; the lower release of biochemical markers of myocardial damage suggests improved protection during first-time coronary artery bypass grafting. The objective was to examine the effect of temperature (28 degrees vs 36 degrees C) during cardiopulmonary bypass on postoperative cognitive functions in a prospective, double-blind, and randomized manner.
                Sixty-two patients scheduled for coronary operations were randomized to warm or cold cardiopulmonary bypass. Preoperative and postoperative (7 days) neuropsychologic evaluations were performed by an observer unaware of cardiopulmonary bypass temperature.
                Fifty-four patients completed the study (cold bypass, n = 24; warm bypass, n = 30). Significant (p < 0.01) postoperative deterioration for tests of psychomotor coordination and verbal memory was noted in both warm and cold groups, but no differences were observed between groups.
                Temperature during cardiopulmonary bypass for coronary operations does not influence postoperative cognitive function. In this study, we assessed the effects of normothermia and hypothermia during cardiopulmonary bypass (CPB) both on internal jugular venous oxygen saturation (SjvO2) and the regional cerebral oxygenation state (rSO2) estimated by near infrared spectroscopy (NIRS).
                Thirty patients scheduled for elective coronary artery bypass graft surgery (CABG) were randomly divided into two groups. Group 1 (n = 15) underwent surgery for normothermic (> 35 degrees C) CPB, and group 2 (n = 15) underwent surgery for hypothermic (30 degrees C) CPB, and alpha-stat regulation was applied. A 4.0-French fiberoptic oximetry oxygen saturation catheter was inserted into the right jugular bulb to continuously monitor the SjvO2 value. To estimate the rSO2 state, a spectrophotometer probe was attached to the mid-forehead. SjvO2 and rSO2 values were then collected simultaneously using a computer.
                Neither the cerebral desaturation time (duration during SjvO2 value below 50%), nor the ratio of the cerebral desaturation time to the total CPB time significantly differed (normothermic group: 18+/-6 min, 15+/-6%; hypothermic group: 17+/-6 min, 13+/-6%, respectively). The rSO2 value in the normothermic group decreased during the CPB period compared with the pre-CPB period. The rSO2 value in the hypothermic group did not change throughout the perioperative period.
                These findings suggest that near infrared spectroscopy might be sensitive enough to detect subtle changes in regional cerebral oxygenation.
This review could find no definite advantage of hypothermia over normothermia in the incidence of clinical events. Hypothermia was associated with a reduced stroke rate, but this is off set by a trend towards an increase in non stroke related perioperative mortality and myocardial damage. There is insufficient data to date to draw any conclusions about the use of mild hypothermia. Similarly, there is insufficient data to date to comment on the effect of temperature during CPB on subtle neurological deficits, and further trials are needed in these areas.