Con: deep hypothermic circulatory arrest must be used selectively and discreetly.
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Biomedical subjects
Publications and source records attributed to W J Greeley.
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We evaluated the efficacy of a computer-assisted continuous infusion device (CACI) using a two-drug infusion of midazolam and sufentanil as an anesthetic technique during pediatric cardiac surgery. Seventeen pediatric patients were anesthetized with CACI using age-appropriate pharmacokinetic models for administering sufentanil and midazolam. Predicted CACI plasma concentrations were correlated with assayed plasma drug concentrations at eight predefined intervals. The accuracy was assessed using median absolute prediction error. We found that plasma levels predicted by CACI provided a reasonable approximation of measured plasma concentrations for both drugs. The median absolute prediction error for sufentanil during cardiopulmonary bypass was compared with measurements made off of cardiopulmonary bypass (both pre and post cardiopulmonary bypass) and were 49% and 32%, respectively, and for midazolam 44% and 32%, respectively. We conclude that (a) current kinetic models provide a reasonable estimate of plasma drug concentrations, and (b) the ease of administration and targeted plasma level provided by the CACI system is an alternative to inhalation anesthesia using calibrated vaporizers.
To study the effect of deep hypothermic cardiopulmonary bypass and total circulatory arrest on cerebral metabolism and oxygenation, we measured the cerebral metabolic rate for oxygen (CMRO2) and assessed brain oxygenation by near infrared spectroscopy before, during, and after hypothermic bypass in 15 pediatric patients. One group underwent repair during deep hypothermic bypass (18 degrees C) with continuous flow (n = 9); the second group underwent deep hypothermic bypass with total circulatory arrest (n = 6). In the continuous-flow group, CMRO2 returned to control during rewarming and after cardiopulmonary bypass, as did oxyhemoglobin and deoxyhemoglobin in brain tissue. In the total circulatory arrest group, the oxyhemoglobin and the oxidation state of cytochrome aa3 oxidase decreased significantly during circulatory arrest. After cardiopulmonary bypass, the cytochrome oxidation state and the CMRO2 were significantly lower than control measurements, and brain tissue deoxyhemoglobin was elevated. Results of this study indicate that intracellular brain oxygenation decreases significantly during circulatory arrest and remains impaired after rewarming and cardiopulmonary bypass despite normalization of oxygen availability.
We examined the relationship of changes in partial pressure of carbon dioxide on cerebral blood flow responsiveness in 20 pediatric patients undergoing hypothermic cardiopulmonary bypass. Cerebral blood flow was measured during steady-state hypothermic cardiopulmonary bypass with the use of xenon 133 clearance methodology at two different arterial carbon dioxide tensions. During these measurements there was no significant change in mean arterial pressure, nasopharyngeal temperature, pump flow rate, or hematocrit value. Cerebral blood flow was found to be significantly greater at higher arterial carbon dioxide tensions (p less than 0.01), so that for every millimeter of mercury rise in arterial carbon dioxide tension there was a 1.2 ml.100 gm-1.min-1 increase in cerebral blood flow. Two factors, deep hypothermia (18 degrees to 22 degrees C) and reduced age (less than 1 year), diminished the effect carbon dioxide had on cerebral blood flow responsiveness but did not eliminate it. We conclude that cerebral blood flow remains responsive to changes in arterial carbon dioxide tension during hypothermic cardiopulmonary bypass in infants and children; that is, increasing arterial carbon dioxide tension will independently increase cerebral blood flow.
Cardiopulmonary bypass management in neonates, infants, and children often requires the use of deep hypothermia at 18 degrees C with occasional periods of circulatory arrest and represents marked physiologic extremes of temperature and perfusion. The safety of these techniques is largely dependent on the reduction of metabolism, particularly cerebral metabolism. We studied the effect of hypothermia on cerebral metabolism during cardiac surgery and quantified the changes. Cerebral metabolism was measured before, during, and after hypothermic cardiopulmonary bypass in 46 pediatric patients, aged 1 day to 14 years. Patients were grouped on the basis of the different bypass techniques commonly used in children: group A--moderate hypothermic bypass at 28 degrees C; group B--deep hypothermic bypass at 18 degrees to 20 degrees C with maintenance of continuous flow; and group C--deep hypothermic circulatory arrest at 18 degrees C. Cerebral metabolism significantly decreased under hypothermic conditions in all groups compared with control levels at normothermia, the data demonstrating an exponential relationship between temperature and cerebral metabolism and an average temperature coefficient of 3.65. There was no significant difference in the rate of metabolism reduction (temperature coefficient) in patients cooled to 28 degrees and 18 degrees C. From these data we were able to derive an equation that numerically expresses a hypothermic metabolic index, which quantitates duration of brain protection provided by reduction of cerebral metabolism owing to hypothermic bypass over any temperature range. Based on this index, patients cooled to 28 degrees C have a predicted ischemic tolerance of 11 to 19 minutes. The predicted duration that the brain can tolerate ischemia ("safe" period of deep hypothermic circulatory arrest) in patients cooled to 18 degrees C, based on our metabolic index, is 39 to 65 minutes, similar to the safe period of deep hypothermic circulatory arrest known to be tolerated clinically. In groups A and B (no circulatory arrest), cerebral metabolism returned to control in the rewarming phase of bypass and after bypass. In group C (circulatory arrest), cerebral metabolism and oxygen extraction remained significantly reduced during rewarming and after bypass, suggesting disordered cerebral metabolism and oxygen utilization after deep hypothermic circulatory arrest. The results of this study suggest that cerebral metabolism is exponentially related to temperature during hypothermic bypass with a temperature coefficient of 3.65 in neonates infants and children. Deep hypothermic circulatory arrest changes cerebral metabolism and blood flow after the arrest period despite adequate hypothermic suppression of metabolism.
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We tested the hypothesis that insulin-dependent diabetic patients with coronary artery bypass graft surgery experience altered coupling of cerebral blood flow and oxygen consumption. In a study of 23 patients (11 diabetics and 12 age-matched controls), cerebral blood flow was measured using 133Xe clearance during nonpulsatile, alpha-stat blood gas managed cardiopulmonary bypass at the conditions of hypothermia and normothermia. In diabetic patients, the cerebral blood flow at 26.6 +/- 2.42 degrees C was 25.3 +/- 14.34 ml/100 g/min and at 36.9 +/- 0.58 degrees C it was 27.3 +/- 7.40 ml/100 g/min (p = NS). The control patients increased cerebral blood flow from 20.7 +/- 6.78 ml/100 g/min at 28.4 +/- 2.81 degrees C to 37.6 +/- 8.81 ml/100 g/min at 36.5 +/- 0.45 degrees C (p less than or equal to 0.005). The oxygen consumption was calculated from jugular bulb effluent and increased from hypothermic values of 0.52 +/- 0.20 ml/100 g/min in diabetics to 1.26 +/- 0.28 ml/100 g/min (p = 0.001) at normothermia and rose from 0.60 +/- 0.27 to 1.49 +/- 0.35 ml/100 g/min (p = 0.0005) in the controls. Thus, despite temperature-mediated changes in oxygen consumption, diabetic patients did not increase cerebral blood flow as metabolism increased. Arteriovenous oxygen saturation gradients and oxygen extraction across the brain were calculated from arterial and jugular bulb blood samples. The increase in arteriovenous oxygen difference between temperature conditions in diabetic patients and controls was significantly different (p = 0.01). These data reveal that diabetic patients lose cerebral autoregulation during cardiopulmonary bypass and compensate for an imbalance in adequate oxygen delivery by increasing oxygen extraction.
Routine epicardial two-dimensional echocardiography, Doppler, and Doppler color flow imaging studies were performed before and after cardiopulmonary bypass in 328 patients undergoing operations for congenital heart disease. Ages ranged from 1 day to 59 years (mean 5.9 years); the smallest patient was 1.8 kg. Complete examinations were conducted in 3.6 +/- 1.7 minutes. Prebypass examinations demonstrated previously unappreciated details of anatomy in 60 patients (18%), which did not relate to whether catheterization had been performed, and they were believed to play a role in surgical planning in 143 patients (44%). Discovery of previously unrecognized features of anatomy increased the impact of echo-Doppler color flow imaging on operative planning by 2.5 times. After bypass, echo-Doppler color flow imaging disclosed unsuspected residual defects in 22 patients (7%) who were doing well clinically and enabled an attempt at immediate revision of the procedure. When ultimate clinical outcome was compared to postbypass findings of echo-Doppler color flow imaging, the presence of a residual defect, right or left ventricular dysfunction, or any concern with the heart by echo-Doppler color flow imaging appeared to serve as a predictor of unfavorable outcome (p less than 0.001 for each when compared with absence of these difficulties). Thus routine intraoperative echo-Doppler color flow imaging is useful in aiding the planning, conduct, and assessment of results in operations for congenital heart disease.
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Surgical repair of congenital cardiac defects (CCD) has undergone a remarkable evolution in the past decade. Major defects are now often completely corrected in early infancy with continually improving rates of survival. It has become clear that the next major focus will be improvements in the long-term quality of life and this has promoted many innovations in surgical technique and approach. One advance is the use of intraoperative echo with Doppler color flow imaging (echo-DCFI) to evaluate the exactness of operative repair. Aside from anecdotal reports, very little information is available regarding the interpretation of images produced by this technology in the operating room. Furthermore there have been no studies addressing the predictive value of intraoperative echo-DCFI findings with respect to outcome for patients undergoing repair of CCD. The prospective data obtained by following the course of 273 patients receiving intraoperative echo-DCFI has been reviewed after repair of a variety of CCD (age range, 1 to 53 years; mean 5.3 years; smallest patient, 1.8 kg). Forty-seven patients (17%) had initially unacceptable results, by echo, at the completion of their repair. Eighteen of these patients (7% of entire series) had no clinical problems and the defects were discernible only by echo. Twenty-six patients with initially unacceptable results had their repairs revised in the operating room and left with an acceptable result by echo. Twenty-one patients were allowed to leave the operating room with echo-discernible defects. Follow-up of these patients demonstrated a significantly higher (p less than 0.006) rate of reoperation (42% vs. 3%) and of early death (29% vs. 10%) for those patients whose defects were left unrepaired compared to those whose problems were corrected before leaving the operating room. Sixty-eight patients (25%) had some alteration of ventricular function (compared to their prebypass evaluation) at the completion of their repair. Regardless of whether the dysfunction was limited to the right ventricle, left ventricle, or was biventricular, patients in this group had a significantly higher incidence (p less than 0.004) of early, but not late, death compared to patients without alteration of ventricular function (35% vs. 4%). Patients who left the operating room with no problems of concern by echo-DCFI had a greater than 90% likelihood of a long-term acceptable outcome compared to patients who had any problem of concern (residual defect, anatomic or technical imperfection, ventricular dysfunction, and so on) whose long-term likelihood of an acceptable outcome approached 50% (p less than 0.0125).(ABSTRACT TRUNCATED AT 400 WORDS)
Cardiopulmonary bypass management in infants and children involves extensive alterations in temperature, hemodilution, and perfusion pressure, with occasional periods of circulatory arrest. Despite the use of these biologic extremes of temperature and perfusion, their effects on cerebral blood flow are unknown. This study was designed to examine the relationship of mean arterial pressure and nasopharyngeal temperature to cerebral blood flow during deep hypothermic cardiopulmonary bypass (18 degrees to 22 degrees C) with and without periods of total circulatory arrest. Cerebral blood flow was measured before, during, and after deep hypothermic cardiopulmonary bypass using xenon clearance techniques in 25 children, aged 2 days to 60 months. Fourteen patients underwent repair with circulatory arrest. There was a highly significant correlation of cerebral blood flow with temperature during cardiopulmonary bypass (p = 0.007). During deep hypothermic bypass there was a significant association between cerebral blood flow and mean arterial pressure (p = 0.027). In infants undergoing repair with deep hypothermia alone, cerebral blood flow returned to prebypass levels in the rewarming phase of bypass. However, in patients undergoing repair with circulatory arrest, no significant increase in cerebral blood flow during rewarming or even after bypass was observed (p = 0.01). These data show that deep hypothermic cardiopulmonary bypass significantly decreases cerebral blood flow because of temperature reduction. Under conditions of deep hypothermia, cerebral pressure-flow autoregulation is lost. This study also demonstrates that cerebral reperfusion after deep hypothermia is impaired if the patient is exposed to a period of total circulatory arrest.
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The use of intraoperative epicardial Doppler echocardiography with color flow imaging both before and after cardiopulmonary bypass to assist repair of congenital heart defects in infants and small children has not been reported. To demonstrate its simplicity and utility, we obtained immediately prebypass and postbypass examinations from 18 consecutive patients undergoing repair of atrioventricular septal defects between March 1987 and March 1988 (aged newborn to 3 years, smallest 2.4 kg, 11 patients less than 1 year old). Direct application of a sterile transducer to the epicardial surface eliminates any restriction imposed by the transesophageal approach, and the routine use of color flow imaging enables the operating surgeon to directly evaluate intracardiac anatomy and flows in a variety of orientations. Average examination time was 3.95 +/- 1.96 minutes. Prebypass studies disclosed that a short-axis inspection through the common atrioventricular valve orifice produced a unique visualization of the dynamic commitments of atrioventricular valve tissue throughout systole and diastole that was helpful in planning valve allocation during repair. In addition, echocardiography demonstrated features not previously appreciated in seven of 18 patients (39%). In all, image quality and resolution were vastly superior to preoperative chest wall studies. Postbypass studies revealed significant residual interventricular shunts in two of 18 patients (11%). Views obtained from various orientations directed specific and efficient repair immediately so that all patients left the operating room with documented, surgically acceptable results. Comparison of ventricular function between prebypass and postbypass studies enabled appropriate application of pharmacologic agents in the operating room if necessary. All patients survived their operation. There have been two late deaths, and 16 patients are alive and doing well (follow-up: 9 to 21 months). These experiences indicate that intraoperative epicardial Doppler color flow imaging (1) can be easily learned and applied by the surgeon, (2) enhances the repair of atrioventricular septal defect by providing unique spatial, anatomic, and flow information in the beating heart at the time of repair, (3) increases confidence of a surgically acceptable repair before the patients leave the operating room, (4) guides specific surgical or anesthetic adjustments to optimize results, and (5) works as a valuable aid that may help reduce poor results in the repair of complex congenital cardiac lesions.
Cardiopulmonary bypass (CPB) management in neonates, infants, and children requires extensive alterations in temperature, pump flow rate, and perfusion pressure, with occasional periods of circulatory arrest. The effect of these alterations on cerebral blood flow (CBF) are unknown. This study was designed to determine the relation of temperature and mean arterial pressure to CBF during hypothermic CPB (18 degrees-32 degrees C), with and without periods of total circulatory arrest. CBF was measured before, during, and after hypothermic CPB with xenon-clearance techniques in 67 pediatric patients, aged 1 day-16 years. Patients were grouped based on different CPB techniques: group A, repair during moderate-hypothermic bypass at 25 degrees-32 degrees C; group B, repair during deep-hypothermic bypass at 18 degrees-22 degrees C; and group C, repair with total circulatory arrest at 18 degrees C. There was a significant correlation of CBF with temperature during CPB. CBF significantly decreased under hypothermic conditions in all groups compared with prebypass levels under normothermia. In groups A and B, CBF returned to baseline levels in the rewarming phase of CPB and exceeded baseline levels after bypass. In group C, no significant increase in CBF was observed during rewarming after total circulatory arrest (32 +/- 12 minutes) or after weaning from CPB. During moderate-hypothermic CPB (25 degrees-32 degrees C), there was no association between CBF and mean arterial pressure. However, during deep-hypothermic CPB (18 degrees-22 degrees C), there was an association between CBF and mean arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
CLINICAL PERSPECTIVE: The first prospective trial in which both echocardiography and Doppler color flow imaging (echo-DCFI) are used routinely during surgery for congenital heart lesions has been undertaken at Duke Medical Center. Precardiopulmonary bypass (CPB) echo-DCFI examinations have revealed previously unsuspected cardiac findings in several of the patients. These examinations have influenced the surgical course in some way in many of the cases. Post-CPB ultrasound evaluation of the quality of the surgical repairs alone has resulted in immediate additional corrective surgery in several patients, most of whom then left the operating room with an optimum repair.
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Cardiopulmonary bypass in children with congenital heart disease is associated with significant morbidity manifested by increased complement degradation products, heightened pulmonary vascular activity, and coagulopathy. In adults with cardiac disease, the prostaglandins (eicosanoids) have been shown to contribute to the pathophysiologic response to extracorporeal circulation. This study assessed the effect of cardiopulmonary bypass in infants and children on two potent eicosanoids: thromboxane, a vasoconstrictor and platelet aggregating agent, and prostacyclin, a vasodilator and platelet disaggregating agent. The biochemical profiles of thromboxane and prostacyclin were evaluated in temporal relationship to selected parameters of platelet loss and pulmonary vascular hemodynamics during and after cardiopulmonary bypass. Twenty-one children, aged 3 days to 9 years, with congenital heart defects who were undergoing repair with cardiopulmonary bypass were studied. Nine pediatric patients undergoing palliative heart operations with no cardiopulmonary bypass served as the control group. In the group having cardiopulmonary bypass, the thromboxane concentration significantly increased during bypass (195 +/- 10 to 910 +/- 240 pg/ml, +/- standard error of the mean, p less than 0.005), whereas the control group demonstrated no significant change in thromboxane concentration. The highest thromboxane values were seen in the youngest patients (p less than 0.002). There was no significant correlation between thromboxane changes with alterations in pulmonary vascular resistance, platelet loss, duration of cardiopulmonary bypass or aortic cross-clamping. Prostacyclin levels rose significantly in both the bypass group (100 +/- 20 to 570 +/- 80 pg/ml, p less than 0.01) and in the control group (109 +/- 44 to 589 +/- 222 pg/ml, p less than 0.01), which apparently is due to surgical manipulation of vascular endothelium. These data show that eicosanoid production is significantly altered in children during cardiopulmonary bypass. Although thromboxane, a potent vasoconstrictor, is produced in significant amounts during and after cardiopulmonary bypass, our data show that thromboxane does not directly mediate changes in pulmonary artery hypertension and is not quantitatively related to platelet loss during pediatric cardiovascular operations.