Search

Fifty years ago, on August 1, 1971, William A. Lell became the first cardiac anesthesia fellow at Harvard's Massachusetts General Hospital (MGH) Department of Anesthesiology, training with the world's first group of anesthesiologists whose clinical practice, teaching, and research efforts were exclusively devoted to cardiac anesthesia. Lell's early interest in cardiovascular medicine and how mentors, particularly at the MGH, influenced his early career development are recounted. The challenges a young pioneer faced in establishing and maintaining an academic cardiac anesthesia program during the initial and rapid growth of an exciting new subspecialty are described. Dr Lell's experience emphasizes the importance of seizing new opportunities and establishing meaningful working relationships with colleagues based on mutual trust as fundamental to successful career development and research in a new medical subspecialty.

Factors and Their Influence on Regional Cerebral Blood Flow during Nonpulsatile Cardiopulmonary Bypass. By Govier AV, Reves JG, McKay RD, Karp RB, Zorn GL, Morawetz RB, Smith LR, Adams M, and Freeman AM. Ann Thorac Surg. 1984; 38:609–13. Reprinted with permission. In this study, we examined the relationship of regional cerebral blood flow (CBF) to mean arterial pressure, systemic blood flow, partial pressure of arterial carbon dioxide (PaCO2), nasopharyngeal temperature, and hemoglobin during hypothermic nonpulsatile cardiopulmonary bypass (CPB). Regional CBF was determined by clearance of xenon 133 in 67 patients undergoing coronary bypass grafting procedures. There was a significant decrease in regional CBF (55% decrease) during CPB, with nasopharyngeal temperature and PaCO2 being the only two significant factors (p < 0.05). In a subgroup of 10 patients, variation of pump flow between 1.0 and 2.0 L/min/m2 did not significantly affect regional CBF. We conclude that cerebral autoregulation is retained during hypothermic CPB. Under the usual conditions of CPB, variations in flow and pressure are not associated with important physiologic or detrimental clinical effects.

Summary Non-operating room anaesthesia (NORA) describes anaesthesia delivered outside a traditional operating room (OR) setting. Non-operating room anaesthesia cases have increased significantly in the last 20 yr and are projected to account for half of all anaesthetics delivered in the next decade. In contrast to most other medication administration contexts, NORA is performed in high-volume fast-paced environments not optimised for anaesthesia care. These predisposing factors combined with increasing case volume, less provider experience, and higher-acuity patients increase the potential for preventable adverse events. Our narrative review examines morbidity and mortality in NORA settings compared with the OR and the systems factors impacting safety in NORA. A review of the literature from January 1, 1994 to March 5, 2021 was conducted using PubMed, CINAHL, Scopus, and ProQuest. After completing abstract screening and full-text review, 30 articles were selected for inclusion. These articles suggested higher rates of morbidity and mortality in NORA cases compared with OR cases. This included a higher proportion of death claims and complications attributable to inadequate oxygenation, and a higher likelihood that adverse events are preventable. Despite relatively few attempts to quantify safety concerns, it was possible to find a range of systems safety concerns repeated across multiple studies, including insufficient lighting, noise, cramped workspace, and restricted access to patients. Old and unfamiliar equipment, lack of team familiarity, and limited preoperative evaluation are also commonly noted challenges. Applying a systems view of safety, it is possible to suggest a range of methods to improve NORA safety and performance.

This article describes a pilot trial of an internet-distributable online software package that provides course materials and built-in evaluation tools to train healthcare workers in high-risk infectious disease response. It includes (1) an online self-study component, (2) a "hands-on" simulation workshop, and (3) a data-driven performance assessment toolset to support debriefing and course reporting. This study describes a pilot trial of the software package using a course designed to provide education in Ebola response to prepare healthcare workers to safely function as a measurable, high-reliability team in an Ebola simulated environment. Eighteen adult volunteer healthcare workers, including 9 novices and 9 experienced participants, completed an online curriculum with pre- and posttest, 13 programmed simulation training scenarios with a companion assessment tool, and a confidence survey. Both groups increased their knowledge test scores after completing the online curriculum. Simulation scenario outcomes were similar between groups. The confidence survey revealed participants had a high degree of confidence after the course, with a median confidence level of 4.5 out of 5.0 (IQR = 0.5). This study demonstrated the feasibility of using the online software package for the creation and application of an Ebola response course. Future studies could advance knowledge gained from this pilot trial by assessing timely distribution and multi-site effectiveness with standard education.

Background: Highly infectious but rare diseases require rapid dissemination of safety critical skills to health-care workers (HCWs). Simulation is an effective method of education; however, it requires competent instructors. We evaluated the efficacy of an internet-delivered train-the-trainer course to prepare HCWs to care for patients with Ebola virus disease (EVD). Methods: Twenty-four individuals without prior EVD training were recruited and divided into two groups. Group A included nine trainees taught by three experienced trainers with previous EVD training. Group B included 15 trainees taught by five novice trainers without previous EVD training who completed the train-the-trainer course. We compared the efficacy of the train-the-trainer course by examining subject performance, measured by time to complete 13 tasks and the proportion of steps per task flagged for critical errors and risky and positive actions. Trainees’ confidence in their ability to safely care for EVD patients was compared with a self-reported survey after training. Results: Overall trainees’ confidence in ability to safely care for EVD patients did not differ by group. Participants trained by the novice trainers were statistically significantly faster at waste bagging (P = 0.002), lab specimen bagging (P = 0.004), spill clean-up (P = 0.01), and the body bagging (P = 0.008) scenarios compared to those trained by experienced trainers. There were no significant differences in the completion time in the remaining nine training tasks. Participants trained by novice and experienced trainers did not differ significantly with regard to the proportion of steps in a task flagged for critical errors, risky actions, or positive actions with the exception of the task “Man Down in Gown” (12.5% of steps graded by experienced trainers compared to 0 graded by novice trainers, P = 0.007). Discussion: The online train-the-trainer EVD course is effective at teaching novices to train HCWs in protective measures and can be accomplished swiftly.

Merel Harmel, MD, was the first anesthesiologist to give anesthesia for a palliative congenital heart operation performed by Alfred Blalock, MD. He was the first resident in anesthesiology at Johns Hopkins and was the first academic department chairman at 3 different universities during his long career. He was successful because of his steadfast belief that academic anesthesia could and must flourish and his incessant optimism no matter how daunting the many obstacles in his professional life.

Background Strategies for neuroprotection including hypothermia and hemodilution have been routinely practiced since the inception of cardiopulmonary bypass. Yet postoperative neurocognitive deficits that diminish the quality of life of cardiac surgery patients are frequent. Because there is uncertainty regarding the impact of hemodilution on perioperative organ function, the authors hypothesized that extreme hemodilution during cardiac surgery would increase the frequency and severity of postoperative neurocognitive deficits. Methods Patients undergoing coronary artery bypass grafting surgery were randomly assigned to either moderate hemodilution (hematocrit on cardiopulmonary bypass >or=27%) or profound hemodilution (hematocrit on cardiopulmonary bypass of 15-18%). Cognitive function was measured preoperatively and 6 weeks postoperatively. The effect of hemodilution on postoperative cognition was tested using multivariable modeling accounting for age, years of education, and baseline levels of cognition. Results After randomization of 108 patients, the trial was terminated by the Data Safety and Monitoring Board due to the significant occurrence of adverse events, which primarily involved pulmonary complications in the moderate hemodilution group. Multivariable analysis revealed an interaction between hemodilution and age wherein older patients in the profound hemodilution group experienced greater neurocognitive decline (P = 0.03). Conclusions In this prospective, randomized study of hemodilution during cardiac surgery with cardiopulmonary bypass in adults, the authors report an early termination of the study because of an increase in adverse events. They also observed greater neurocognitive impairment among older patients receiving extreme hemodilution.

Study objective To determine anesthetic drug utilization in different age groups. Design Retrospective, automated, intraoperative database study. Setting Tertiary care medical center. Measurements 30,842 noncardiac general anesthesia case records between January 1991 and July 1997 were studied. We investigated the effect of age on anesthetic requirements for fentanyl (F), midazolam (M), thiopental sodium (T), propofol (P), isoflurane (I), and nitrous oxide (N). Because drugs are not given in isolation we looked at the most common drug combinations, IFNTM, IFNPM, INFT, and PFNM. Regression analyses on log-transformed drug dosages were used to test the significance of age on individual requirements. Results In each of the above anesthetic drug combinations, reduced doses of fentanyl, propofol, midazolam, thiopental, and isoflurane were used with increasing age. Fentanyl, propofol, thiopental, and isoflurane showed a 10%, 8%, 6%, and 4% reduction in dose per decade of age, respectively, from age of maximum dose to age 80 years. Conclusions In clinical practice, increasing age results in decreased anesthetic drug administration. The mechanism of this observation needs to be determined.

Neurocognitive decline is a continuing source of morbidity after cardiac surgery. Atrial fibrillation occurs often after cardiac surgery and has been linked to adverse neurologic events. We sought to determine whether postoperative atrial fibrillation was associated with postoperative cognitive dysfunction. Four-hundred-eleven patients were enrolled to receive a battery of neurocognitive tests both preoperatively and 6 wk after elective coronary artery bypass graft surgery. Neurocognitive test scores were separated into four cognitive domains, with a composite cognitive index (the mean of the four domain scores) determined for each patient at every testing period. Multivariable analysis controlling for age, years of education, diabetes mellitus, left ventricular ejection fraction, and preoperative atrial fibrillation compared the presence of postoperative atrial fibrillation with change in cognitive function. Three-hundred-eight patients completed both pre- and postoperative cognitive testing; 69 patients (22%) had postoperative atrial fibrillation. Those who developed atrial fibrillation showed more cognitive decline than those who did not develop postoperative atrial fibrillation (P = 0.036). Atrial fibrillation was associated with poorer cognitive function 6 wk after surgery. Although the mechanism of this association is yet to be determined, prevention of atrial fibrillation may result in improved neurocognitive function.Neurocognitive dysfunction is common after coronary artery bypass graft surgery. The relationship between atrial fibrillation and neurocognitive dysfunction has not been examined. Our study shows that postoperative atrial fibrillation is associated with neurocognitive decline.

Background and Purpose — Temperature is a well-known modulator of experimental cerebral injury. We hypothesized that hyperthermia would be associated with a worsened cognitive outcome after coronary artery bypass graft surgery (CABG). Methods — Three hundred consenting patients undergoing cardiopulmonary bypass for CABG had hourly postoperative temperatures recorded. The degree of postoperative hyperthermia was determined by using the maximum temperature within the first 24 hours as well as by calculating the area under the curve for temperatures >37°C. Patients underwent a battery of cognitive testing both before surgery and 6 weeks after surgery. By use of factor analysis, 4 cognitive domains (scores) were identified, and the mean of the 4 scores was used to calculate the cognitive index (CI). Cognitive change was calculated as the 6-week CI minus the baseline CI. Multivariable linear regression (controlling for age, baseline cognitive function, and temperature during cardiopulmonary bypass) was used to compare postoperative hyperthermia with the postoperative cognitive change. Results — The maximum temperature within the first 24 hours after CABG ranged from 37.2°C to 39.3°C. There was no relationship between area under the curve for temperatures >37°C and cognitive dysfunction ( P =0.45). However, the maximum postoperative temperature was associated with a greater amount of cognitive dysfunction at 6 weeks ( P =0.05). Conclusions — This is the first report relating postoperative hyperthermia to cognitive dysfunction after cardiac surgery. Whether the hyperthermia caused the worsened outcome or whether processes that resulted in the worsened cognitive outcome also produced hyperthermia requires further investigation. In addition, interventions to avoid postoperative hyperthermia may be warranted to improve cerebral outcome after cardiac surgery.

This is an historical account of the accomplishments of the Society of Cardiovascular Anesthesiologists from its founding in 1989 to the present. It is written on the occasion of the 35th anniversary of the founding of this organization. The society accomplishments include providing a means to educate anesthesiologists and others about the perioperative care of patients undergoing cardiac, thoracic, and vascular surgery. The society has led accreditation of transesophageal echocardiography and education in cardiothoracic anesthesia. The society publishes a section within Anesthesia & Analgesia and supports investigation by providing a forum for the discussion of research and funding peer-reviewed projects. The first 35 years of the Society of Cardiovascular Anesthesiologists has been remarkable in all that has been accomplished.

Background and Purpose — The importance of perioperative cognitive decline has long been debated. We recently demonstrated a significant correlation between perioperative cognitive decline and long-term cognitive dysfunction. Despite this association, some still question the importance of these changes in cognitive function to the quality of life of patients and their families. The purpose of our investigation was to determine the association between cognitive dysfunction and long-term quality of life after cardiac surgery. Methods — After institutional review board approval and patient informed consent, 261 patients undergoing cardiac surgery with cardiopulmonary bypass were enrolled and followed for 5 years. Cognitive function was measured with a battery of tests at baseline, discharge, and 6 weeks and 5 years postoperatively. Quality of life was assessed with well-validated, standardized assessments at the 5-year end point. Results — Our results demonstrate significant correlations between cognitive function and quality of life in patients after cardiac surgery. Lower 5-year overall cognitive function scores were associated with lower general health and a less productive working status. Multivariable logistic and linear regression controlling for age, sex, education, and diabetes confirmed this strong association in the majority of areas of quality of life. Conclusions — Five years after cardiac surgery, there is a strong relationship between neurocognitive functioning and quality of life. This has important social and financial implications for preoperative evaluation and postoperative care of patients undergoing cardiac surgery.

Background . Renal dysfunction remains a major complication of cardiac operations. There is concern regarding the possibility of increased renal injury during warm cardiopulmonary bypass (CPB). Therefore, we tested the hypothesis that warm CPB is associated with a greater reduction in creatinine clearance after cardiac surgery than hypothermic CPB. Methods . We randomly assigned 300 patients who had elective coronary artery bypass grafting to warm (35.5 to 36.5°C) or cold (28°C to 30°C) CPB. Preoperative and peak postoperative serum creatinine values were recorded. Creatinine clearance was estimated using the Cockroft Gault equation. Univariate and multivariable analyses were performed to test the association of CPB temperature and perioperative change in creatinine clearance. Results . Demographic variables were similar between groups. Multivariable analysis did not confirm an association between temperature and change in creatinine clearance ( p = 0.87). Conclusions . We did not confirm an association between warm CPB and increased renal dysfunction after cardiac operations compared with hypothermic CPB.

Executive summary Most randomized, controlled trials evaluating the effectiveness of pharmaceutical, surgical, and device interventions for the prevention and treatment of cardiovascular disease have excluded patients over 75 years of age. Consequently, the use of these therapies in the older population is based on extrapolation of safety and effectiveness data obtained from younger patients. However, there are many registries and observational databases that contain large amounts of data on patients 75 years of age and older, as well as on younger patients. Although conclusions from such data are limited, it is possible to define the characteristics of patients who did well and those who did poorly. The goal of this conference was to convene the principal investigators of these databases, and others in the field of geriatric cardiology, to address questions relating to the safety and effectiveness of treatment interventions for several cardiovascular conditions in the elderly. Seven committees discussed the following topics: I. Risk Factor Modification in the Elderly II. Chronic Heart Failure III. Chronic Coronary Artery Disease: Role of Revacularization IV. Acute Myocardial Infarction V. Valve Surgery in the Elderly VI. Electrophysiology, Pacemaker, and Automatic Internal Cardioverter Defibrillators Databases VII. VII. Carotid Endarterectomy in the Elderly The chairs of these committees were asked to invite principal investigators of key databases in each of these areas to discuss and prepare a written statement concerning the available safety and efficacy data regarding interventions for these conditions and to identify and prioritize areas for future study. The ultimate goal is to stimulate further collaborative outcomes research in the elderly so as to place the treatment of cardiovascular disease on a more scientific basis.

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.

Background . The objective of this study was to examine the effects of temperature on a variety of indices of psychologic adjustment and quality of life. Methods . A total of 209 patients randomly received normothermic (warm) or hypothermic (cold) conditions during coronary artery bypass surgery (CABS), and a number of physical, social, and psychologic measures were assessed before as well as 6 weeks and 6 months after CABS. Results . Repeated measures analyses of covariance revealed significant temperature group main effects for anxiety ( p = 0.008) and depression ( p = 0.039), with the normothermic group obtaining lower anxiety and depression levels than the hypothermic group at both 6 weeks and 6 months after surgery. Additionally, among patients who entered the study with higher depression levels, those in the hypothermic group tended to have higher depression scores at follow-up compared with patients in the normothermic condition ( p = 0.012). No temperature group differences were observed on other quality of life indices. Conclusions . The results of the present study indicate that hypothermic conditions during CABS are associated with higher levels of emotional distress after CABS than normothermic conditions, particularly for patients with greater stress to begin with.

Abstract —Cardiac G protein–coupled receptors that couple to Gα s and stimulate cAMP formation (eg, β-adrenergic, histamine, serotonin, and glucagon receptors) play a key role in cardiac inotropy. Recent studies in rodent cardiac myocytes and transfected cells have revealed that one of these receptors, the β 2 -adrenergic receptor (AR), also couples to the inhibitory G protein Gα i (activation of which inhibits cAMP formation). If β 2 ARs could be shown to couple to Gα i in the human heart, it would have important ramifications, because levels of Gα i increase with age and in failing human heart. Therefore, we investigated whether β 2 ARs in the human heart activate Gα i . By photoaffinity labeling human atrial membranes with [ 32 P]azidoanilido-GTP, followed by immunoprecipitation with antibodies specific for Gα i , we found that Gα i is activated by stimulation of β 2 ARs but not of β 1 ARs. In addition, we found that other Gα s -coupled receptors also couple to Gα i , including histamine, serotonin, and glucagon. When coupling of these receptors to Gα i is disrupted by pertussis toxin, their ability to stimulate adenylyl cyclase is enhanced. These data provide the first evidence that β 2 AR and many other Gα s -coupled receptors in human atrium also couple to Gα i and that abolishing the coupling of these receptors to Gα i increases the receptor-mediated adenylyl cyclase activity.

Risk stratification schemes have been developed to predict outcome of coronary artery bypass grafting (CABG) procedures, which are predominately based upon unalterable preoperative patient characteristics. The purpose of this study was to determine if minimum intraoperative hematocrit, maximum glucose concentration, mean arterial pressure on cardiopulmonary bypass, or duration of bypass influence risk-adjusted in-hospital mortality after CABG.Outcome data from 2,862 CABG patients were merged with intraoperative physiologic data. A preoperative mortality risk index was calculated for each patient. Variables found significant (p0.05) by univariate logistic regression were tested in a multiple variable model to determine risk-adjusted association with mortality.Overall mortality rate was 1.85%. The preoperative risk index was significantly associated with mortality (p = 0.0001). No significant association was present between mortality and intraoperative variables. Preexisting hypertension was an independent predictor of mortality after controlling for risk index and bypass duration.Preexisting hypertension proved to be an independent predictor of mortality in our patient population. This study found no evidence to support the hypothesis that mean arterial pressure less than 50 mm Hg, lower hematocrit, or elevated glucose while on bypass increases in-hospital mortality.

We performed a financial analysis at a large university tertiary care hospital to determine the incremental cost of replacing its anesthesiology residents with alternative dependent providers (i.e., certified registered nurse anesthetists in the operating room, advanced practice nurses and physician assistants outside the operating room). The annual average net cost of an anesthesiology resident during a 3-yr residency is approximately $38,000, and residents performed an average of $89,000 of essential clinical work annually based on replacement costs. The incremental cost (replacement labor cost minus net resident cost) to replace all essential clinical duties performed by an anesthesiology resident at Duke University Medical Center and affiliated hospitals is approximately $153,000 throughout 3 yr of clinical anesthesiology training. If this approach were applied nationwide, incremental costs of substitution would range from $36,000,000 to $93,000,000 per year. We conclude that maintaining clinical service in the face of anesthesiology residency reductions can have a marked impact on the overall cost of providing anesthesiology services in teaching hospitals. Simply replacing residents with alternate nonphysician providers is a very expensive option. Implications: We sought to calculate the financial burden resulting from a decreased number of anesthesiology residents. Replacing each resident’s essential clinical work with similarly skilled healthcare providers would cost hospitals approximately $153,000 over the course of a 3-yr residency. Varying projections yield future nationwide costs of $36,000,000 to $93,000,000 per year. Simply replacing residents with alternate nonphysician providers is a very expensive option. (Anesth Analg 1998;87:245-54)

UNLABELLED In this study, we examined the cerebral oxygenation effects of two methods of pharmacologic burst suppression during cardiopulmonary bypass (CPB) in valvular heart surgery patients. Patients were randomly entered into one of three groups: control (n = 13, fentanyl and midazolam), control plus burst suppression doses of thiopental (n = 15), or control plus burst suppression doses of isoflurane (n = 16). Burst suppression (80% suppression) was accomplished in the thiopental and isoflurane groups 15 min before aortic cannulation and was maintained through aortic decannulation. Cerebral physiologic measurements were made during hypothermia (27-28 degrees C) and on rewarming to 36 degrees C. During hypothermia, burst suppression produced significant (P < 0.005) differences with regard to cerebral vascular resistance (P = 0.003), cerebral arterial venous oxygen difference [C(a-v)O2] (P = 0.032), cerebral blood flow (CBF) (P = 0.009), and cerebral oxygen delivery (P = 0.027). There was a similar pattern on rewarming, with groups differing significantly (P < 0.05) with respect to CBF (P = 0.016), cerebral vascular resistance (P = 0.008), oxygen delivery (P = 0.004), C(a-v)O2 (P = 0.043), and cerebral oxygen extraction (P = 0.046). Rewarming rates were similar among groups. There was no difference in neurologic outcome or requirement for inotropic support among groups. The time to awakening was increased (P = 0.0005) in the thiopental group. The thiopental group had lower cerebral oxygen delivery, but not lower cerebral metabolic rate of oxygen consumption, compared with the control group, resulting in widening C(a-v)O2 during CPB. This lack of coupling of oxygen delivery and consumption suggests that pharmacologic neuroprotective mechanisms are complex and involve more than an improvement in the ratio of global cerebral oxygen supply to demand. IMPLICATIONS This study demonstrates that the balance of cerebral oxygen delivery to consumption during cardiopulmonary bypass is altered differently by thiopental and isoflurane. As others have noted, it seems that cerebral protection is more complex than a simple improvement in the balance of oxygen delivery and consumption.

Introduction. We evaluated whether automated anesthesia information systems can be used to calculate reference limits (population-based “normal values”) for vital signs. We considered four populations of women undergoing cesarean section: healthy under spinal anesthesia, healthy under general anesthesia, pre-eclamptic/eclamptic under spinal anesthesia, and pre-eclamptic/eclamptic under general anesthesia. Methods. Reference limits were calculated for each of the study populations by determination of percentiles for: minimum heart rate, maximum heart rate, minimum arterial oxyhemoglobin saturation (SaO2), minimum mean arterial pressure (MAP), maximum MAP, decrease in MAP, and increase in MAP. Results.There was one adverse anesthetic outcome among the 1,300 women in the study; the woman sustained a post-dural puncture headache. The 5th percentiles of SaO2 were at least 95% saturation under spinal versus90% under general. Under spinal anesthesia, 95th percentiles for decreases in MAP from baseline were 63 mmHg for healthy and 75 mmHg for pre-eclamptic/eclamptic women. Under general anesthesia, the 95th percentiles for maximum MAP were 161 and 177 mmHg, respectively. Two women of the 1,300 patients experienced simultaneously a minimum SaO2

Background Recent subgroup analyses of randomized trials have suggested that percutaneous intervention in diabetic patients with multivessel disease results in higher mortality than coronary artery bypass graft surgery (CABG). We studied the relationship between diabetes and survival after revascularization in a large prospective cohort of patients with multivessel coronary artery disease. Methods and Results By analyzing data for 3220 patients (24% diabetic) with symptomatic two- or three-vessel coronary disease who were undergoing percutaneous transluminal coronary angioplasty (PTCA) or CABG at Duke University Medical Center between 1984 and 1990, we found that at 5 years, unadjusted survival in the group of patients undergoing CABG was 74% in diabetics and 86% in nondiabetics. Similarly, 5-year survival among PTCA patients was 76% in diabetics and 88% in patients without diabetes. After adjustment for baseline characteristics, diabetic patients receiving either PTCA or CABG had significantly poorer survival than nondiabetics (χ 2 =43.56, P 2 =0.01, P =.91). Conclusions Although diabetes was associated with a worse long-term outcome after both PTCA and CABG in patients with multivessel coronary artery disease, the effect of diabetes on prognosis was similar in both treatment groups. Thus, our findings support the concept that the choice of initial revascularization strategy should not be based exclusively on a history of diabetes but rather should rely on other factors, such as angiographic suitability and clinical status.

Background . Changes in memory and cognition frequently follow cardiac operations. We hypothesized that patients with the apolipoprotein E-ϵ4 allele are genetically predisposed to cognitive dysfunction after cardiac operations. Methods . The apolipoprotein E-ϵ4 allele was evaluated as a predictor variable for postoperative cognitive dysfunction in 65 patients undergoing cardiac bypass grafting at Duke University Medical Center. The primary outcome measure was performance on a cognitive battery administered preoperatively and at 6 weeks postoperatively. Results . In a multivariable logistic regression analysis including apolipoprotein E-ϵ4, preoperative score, age, and years of education, a significant association was found between apolipoprotein E-ϵ4 and change in cognitive test score in measures of short-term memory at 6 weeks postoperatively. Patients with lower educational levels were more likely to show a decline in cognitive function associated with the apolipoprotein E-ϵ4 allele. Conclusions . This study suggests that apolipoprotein E genotype is related to cognitive dysfunction after cardiopulmonary bypass. Cardiac surgical patients may be susceptible to deterioration after physiologic stress as a result of impaired genetically determined neuronal mechanisms of maintenance and repair.

epsilon-Aminocaproic acid (EACA) concentrations achieved during cardiopulmonary bypass (CPB) have not been previously reported. It is unknown whether plasma concentrations reported to inhibit fibrinolysis in vitro (130 microg/mL) are achieved or whether differences in these levels relate to variability in postoperative bleeding. EACA (total intraoperative dose 270 mg/kg) was administered to 27 patients undergoing cardiac reoperation. The plasma EACA concentration was measured by using high-pressure liquid chromatography: 1) 30 min after initiation of drug administration (baseline); 2) 30 min (CPB + 30) after initiation of CPB; 3) 90 min after initiation of CPB. (CPB + 90); and 4) at cardiopulmonary bypass termination (end CPB). Plasma EACA concentrations (microg/mL, min - max, mean +/- SD) were 276-998, 593 +/- 154 at baseline; 147-527, 302 +/- 95 at CPB + 30; 112-500, 314 +/- 100 at CPB + 90; and 84-537, 317 +/- 100 at end CPB. Twenty-four-hour postoperative thoracic drainage and allogeneic red blood cell transfusions were not associated with plasma levels at any time. Although plasma EACA concentrations greater than 130 microg/mL were consistently achieved, we observed a marked variability (more than sixfold) in plasma concentrations and bleeding outcomes despite the use of a weight-based dosing regimen. This variability in drug levels appears to have little relevance to bleeding outcomes, possibly since mean plasma levels exceeded 130 microg/mL during CPB, and nearly all patients (26 of 27) achieved that target level.

To compare jugular venous to nasopharyngeal temperature during hypothermic cardiopulmonary bypass (CPB).Prospective observational study.Tertiary care teaching hospital.5 ASA physical status IV patients (40 to 65 years of age) having cardiac surgery with hypothermic CPB. INTERVENTIONS, MEASUREMENTS AND MAIN RESULTS: Jugular venous and nasopharyngeal temperatures were recorded throughout the procedure with comparisons made during four time periods: pre-CPB, during CPB, during rewarming, and post-CPB. The patients underwent 85.8 +/- 45.8 minutes (mean +/- SD) of hypothermic CPB, cooling to 26.3 +/- 7.6 degrees C (nasopharyngeal) followed by rewarming at 0.35 +/- 0.1 degree C (nasopharyngeal)/min. There was a high degree of precision between the two temperature sites, but marked differences in bias. In particular, temperature bias was more pronounced during rewarming from CPB compared with other time periods (p0.05) where jugular venous temperature was greater than nasopharyngeal temperature by 3.4 degrees C.Nasopharyngeal temperature underestimates jugular venous temperature during rewarming from hypothermic CPB. As a result, the brain may be exposed to periods of hyperthermia, possibly increasing the risk of neurologic injury associated with CPB.

Background Although approximately 2,000 medical practice guidelines have been proposed, few have been successfully implemented and sustained. We hypothesized that we could develop and institute practice guidelines to promote more appropriate use of costly anesthetics, to generate and sustain widespread compliance from a large physician group, and to decrease costs without adversely affecting clinical outcomes. Methods A prospective before and after comparison study was performed at a tertiary care medical center. Clinical outcomes data and times indicative of perioperative patient flow were collected on the first of two sets of patients 1 month before discussion of practice guidelines. Practice guidelines were developed by the physicians and their associated care team for the intraoperative use of anesthetic drugs. A drug distribution process was developed to aid compliance. Clinical outcomes data and times indicative of perioperative patient flow were collected on the second set of patients 1 month after institution of practice guidelines. Hospital drug costs and adherence to guidelines were noted throughout the study period and for each of the following 9 months by querying the database of an automated anesthesia record keeper. Results A total of 1,744 patients were studied. Drug costs decreased from 56 dollars per case to 32 dollars per case as a result of adherence to practice guidelines. Perioperative patient flow was minimally affected. Time (mean +/- SD) from end of surgery to arrival in the post-anesthesia care unit (PACU) increased from 11 +/- 7 min before the authors instituted practice guidelines to 14 +/- 8 min after practice guidelines (P < 0.0001). Admission of inpatients to the PACU receiving monitored anesthesia care increased from 6.5 to 12.9% (P < 0.02). Perioperative patient flow and clinical outcomes were not otherwise adversely affected. Compliance and cost savings have been sustained. Conclusions This study is an example of a successful physician-directed program to promote more appropriate utilization of health care resources. Cost savings were obtained without any substantial changes in clinical outcomes. Institution of similar practice guidelines should result in pharmaceutical savings in the range of 50% at tertiary care centers around the country, with a slightly smaller degree of savings expected at institutions with more ambulatory surgery.

Background Medical informatics provide a new way to evaluate the practice of medicine. Anesthesia automated record keepers have introduced anesthesiologists to computerized medical records. To derive useful information from the stored data requires programming that is not currently commercially available. The authors describe how they custom-programmed an automated record keeper's database to perform cost calculations, how they validated the programming, and how they used the data in a successful pharmaceutical cost-containment program. Methods The Arkive (San Diego, CA) automated record keeper database was programmed at Duke University Medical Center as an independent noncommercial project to calculate costs according to standard formulae and to follow adherence to Duke University Department of Anesthesiology's prescribing guidelines for anesthetic drugs. Validation of that programming (including analysis of discarded drugs) was accomplished by comparing database calculated costs with actual pharmacy distribution of drugs during a 1-month period. Results Validation data demonstrated a 99% accuracy rate for total costs of the drugs studied (atracurium, vecuronium, rocuronium, propofol, midazolam, fentanyl, and isoflurane). The study drugs represented approximately 67% of all drug costs for the period studied. Conclusions Programming of an anesthesia automated record keeper's database yields essential information for management of an anesthetic practice. Accurate economic evaluation of anesthetic drug use is now possible. In the future, as definitive identification of best anesthetic practices that yield optimal patient outcomes and higher measures of patient satisfaction is pursued, large numbers of patients should be studied. This is only possible through database analysis and complete computerization of the perioperative medical record.

Aprotinin concentrations in the range of 127-191 kallikrein inactivator units (KIU)/mL at the end of cardiopulmonary bypass (CPB) (< 2 h duration) reduce transfusion requirements. It has been suggested that prolonged CPB may require higher infusion rates which significantly increase cost. We tested the hypothesis that large-dose aprotinin maintains therapeutic plasma levels during prolonged periods of CPB (< 2 h). Aprotinin was administered as follows: 2 x 10(6) KIU upon skin incision; 0.5 x 10(6) KIU/h x 4-h infusion on initiation of CPB; and 2 x 10(6) KIU added to the CPB prime solution. Aprotinin activity was measured 1) 30 min after initiation of drug administration (Pre-CPB); 2) 30 min after initiation of CPB (CPB + 30); 3) 90 min after initiation of CPB (CPB + 90); and 4) at CPB termination (End CPB). CPB duration (mean +/- SD) was 158 +/- 51 min. Plasma aprotinin concentrations (KIU/mL, mean +/- SD) were: 234 +/- 30 at Pre-CPB; 229 +/- 35 at CPB + 30; 184 +/- 27 at CPB + 90; and 179 +/- 22 at End CPB. In all patients, aprotinin levels at the completion of CPB were in the range previously reported to be effective. The authors conclude that large-dose regimen limited to 6 x 10(6) KIU maintained therapeutic plasma aprotinin concentrations during prolonged CPB.

The purpose of this study was to evaluate long-term survival benefits of bypass surgery and angioplasty versus medical therapy in 9263 patients at Duke University Medical Center between 1984 and 1990 with coronary artery disease confirmed by cardiac catheterization to involve one, two, or three vessels. Clinical data were prospectively entered into an established cardiovascular database, and annual follow-up was 97% complete for a mean interval of 5.3 years and a maximal interval of 10 years. Outcomes were analyzed with the Coronary Artery Surgery Study "method A" to define patient groups treated by medicine ( n = 2449), angioplasty ( n = 2924), or bypass surgery ( n = 3890). Differences among treatment groups in baseline characteristics were adjusted by Cox proportional hazard models. The anatomic severity of coronary artery stenosis best defined survival benefit from bypass surgery and angioplasty versus medical treatment. One or both interventional treatments provided better long-term survival than did medical treatment for all levels of disease severity. All patients with single-vessel disease, except those with at least 95% proximal left anterior descending stenosis, benefited from angioplasty versus bypass. All patients with three-vessel disease and those two-vessel patients with ≥95% proximal left anterior descending stenosis benefited from bypass surgery versus angioplasty. All other patients with two-vessel disease and those with ≥95% proximal left anterior descending stenosis only had similar survival with either interventional treatment. The absolute survival benefit was greatest for patients with severe three-vessel disease treated with bypass surgery. (J THORAC CARDIOVASC SURG 1996;111:1013-25)

INTRODUCTION: Each year millions of patients undergo procedures that require moderate sedation. These patients are at risk of complications from oversedation that can progress to respiratory depression or even death. This article describes the creation of a simulation-based medical education course for nonanesthesiologists who use sedation in their specialty practice and preliminary data from our precourse and postcourse assessments. METHODS: Our course combined online and lecture-based didactics with simulation education to teach moderate sedation and basic emergency airway management to nonanesthesiologists. After online precourse materials were reviewed, participants attended an 8-hour simulation-based training course focused on the recognition of different levels of sedation, medication titration, sedation reversal, and airway support and rescue. To evaluate the course, precourse, and postcourse educational impacts, cognitive and simulation tests were administered. Participants completed a postcourse survey. RESULTS: To date, 45 physicians have participated in the course. We have cognitive performance data on 19 participants and survey data for 45 participants. Postcourse simulation tests results were improved compared with precourse tests. Our course was rated “better” or “much better” in comparison to courses using lecture-only format by 100% of the participants. CONCLUSIONS: A course using a combination of didactic and simulation education to teach moderate sedation is described. Our initial data demonstrated a significant increase in knowledge, skills, and clinical judgment. Future research efforts should focus on examining the validity and reliability of scenario scoring and the impact of training on clinical practice.

Central nervous system (CNS) complications are common after cardiac surgery. Death due to cardiac causes has decreased, but the number of deaths due to CNS injury has increased. As a first stage in the evaluation of its cerebral protection potential, we evaluated the cerebral physiologic effects of burst suppression doses of propofol during nonpulsatile cardiopulmonary bypass. Thirty patients without history of cerebral vascular disease were randomized to two study groups: control group (n = 15) who received sufentanil and vecuronium, or propofol group (n = 15) who received the control anesthetic and propofol infused to maintain electroencephalogram (EEG) burst suppression. Catheters were placed in the radial artery and right jugular bulb for sampling of systemic arterial and jugular bulb venous blood. 133Xe clearance was used to determine cerebral blood flow (CBF) at the start of normothermic bypass, during stable hypothermia, and when rewarmed to 35-37 degrees C nasopharyngeal temperature. Pharmacologic burst suppression with propofol produced a statistically significant reduction in CBF, cerebral oxygen delivery (DO2), and cerebral metabolic rate (CMRO2) at each measurement interval (P < 0..05 vs control). Cerebral arterial venous oxygen difference (C(a-v)O2), and jugular bulb venous oxygen saturation (SJvO2) were not statistically different between groups, indicating maintenance of cerebral metabolic autoregulation (coupling). The reduction in CBF and CMRO2, prominent during the normothermic phases of cardiopulmonary bypass (CPB), indicates a potential for propofol to reduce cerebral exposure to the embolic load during CPB.

Central nervous system dysfunction is a common consequence of otherwise uncomplicated cardiac surgery. Many mechanisms have been postulated for the cognitive dysfunction that is part of these neurologic sequelae. The purpose of our investigation was to evaluate the effects of mean arterial pressure (MAP) during cardiopulmonary bypass (CPB) and the rate of rewarming on cognitive decline after cardiac surgery. Two hundred thirty-seven patients completed preoperative and predischarge neuropsychologic testing. MAP and temperature were recorded at 1-min intervals using an automated anesthesia record keeper. MAP area less than 50 mm Hg (time and degree of hypotension), as well as the maximal rewarming rate, were determined for each patient. Multivariable linear regression revealed that the rate of rewarming and MAP were unrelated to cognitive decline. However, interactions significantly associated with cognitive decline were found between age and MAP area less than 50 mm Hg on one measure, and between age and rewarming rate in another, identifying susceptibility of the elderly to these factors. Although MAP and rewarming were not the primary determinates of cognitive decline in this surgical population, hypotension and rapid rewarming contributed significantly to cognitive dysfunction in the elderly.

Despite major advances in cardiopulmonary bypass technology, surgical techniques, and anesthesia management, central nervous system complications remain a common problem after cardiopulmonary bypass. The etiology of neuropsychologic dysfunction after cardiopulmonary bypass remains unresolved and is probably multifactorial. Demographic predictors of cognitive decline include age and years of education; perioperative factors including number of cerebral emboli, temperature, mean arterial pressure, and jugular bulb oxygen saturation have varying predictive power. Recent data suggest a genetic predisposition for cognitive decline after cardiac surgery in patients possessing the apolipoprotein E epsilon-4 allele, known to be associated with late-onset and sporadic forms of Alzheimer's disease. Predicting patients at risk for cognitive decline allows the possibility of many important interventions. Predictive power and weapons to reduce cellular injury associated with neurologic insults lend hope of a future ability to markedly decrease the impact of cardiopulmonary bypass on short-term and long-term neurologic, cognitive, and quality-of-life outcomes.

The present longitudinal study was designed to determine the prevalence of depression in male and female patients undergoing cardiac surgery, and to examine what factors are associated with depression before and after surgery. One day prior to surgery (T1), and one day prior to discharge from the hospital (T2), 141 patients completed a psychometric test battery including the Center for Epidemiological Studies Depression Scale (CES-D), the State-Trait Anxiety Inventory (STAI), and the Perceived Social Support Scale (PSSS). Data were also collected on 13 physiological measures. Forty-seven per cent of patients were depressed (defined as a score of 16 or above on the CES-D) at T1. Scores on the CES-D significantly increased from T1 (M = 15) to T2 (M = 20), with 61 per cent of patients classified as depressed at T2. Factors associated with depression at T1 were female gender, higher state anxiety, and less social support. Depressed patients at T2 were characterized by higher scores on the STAI at T2 and higher scores on the CES-D at T1. The prevalence of depression in cardiac surgery patients, particularly women, may be underrecognized and warrants increased attention.

The effect of aging on the pharmacodynamics of midazolam was investigated in a double-blinded study involving 39 consenting patients ranging in age from 39 to 77 yr. Midazolam was infused intravenously (i.v.) using a pharmacokinetic model-driven drug infusion device to achieve a plasma midazolam concentration that was held constant for the 10-min duration of the study. Blood samples were obtained from the radial artery at 5 and 10 min for subsequent measurement of the plasma midazolam concentrations. With the 10-min sample, the patients were also assessed for the presence or absence of responsiveness to verbal command. To ensure that the pharmacodynamic end-point was assessed under the condition of a relative steady-state effect-site midazolam concentration, only those patients (n = 33) in whom the plasma midazolam concentration at 10 min was within 30% of the measured concentration at 5 min were included in the subsequent data analyses. Logistic regression was used to fit the verbal command response/no response data to a mathematical model that included patient age and the plasma midazolam concentration measured at 10 min. Cp50, the steady-state plasma midazolam concentration at which 50% of patients would be expected not to respond to a specific stimulus (e.g., verbal command), was calculated as a function of age from the parameterized logistic model. The midazolam Cp50 for response to verbal command decreased significantly (P = 0.034) with increasing patient age, demonstrating that aging increases pharmacodynamic sensitivity to the hypnotic effects of midazolam independent of pharmacokinetic factors.

The effects of reduced pump flow rate (PFR) on cerebral blood flow, cerebral oxygen consumption (CMRO2), oxygen extraction, cerebral vascular resistance, and total body vascular resistance were examined in 27 pediatric patients during hypothermic cardiopulmonary bypass (hCPB). During steady state hCPB the extracorporeal flows were randomly adjusted to a conventional PFR and a reduced PFR for each patient. The reduced pump flow rates were dictated by surgical needs. Cerebral blood flow measured using Xenon 133 clearance, and CMRO2 and oxygen extraction were calculated. Our results demonstrated that cerebral blood flow and CMRO2 are unchanged if pump flow rates are reduced by 35% to 45% of conventional PFRs at moderate and deep hypothermic temperatures. Reductions in PFR of 45%-70% from conventional PFRs affect the brain differently during either moderate or deep hCPB. At moderate hCPB (26 degrees to 29 degrees C), reductions in PFRs of 45% to 70% resulted in a significant decrease in cerebral blood flow and CMRO2, whereas oxygen extraction increased in a compensatory manner. During deep hCPB (18 degrees to 22 degrees C), PFR reductions of 45% to 70% of conventional PFR significantly reduced cerebral blood flow and CMRO2 but did not increase oxygen extraction, suggesting that at deep hypothermic temperatures, cerebral blood flow and CMRO2 exceed cerebral metabolic needs. Cerebral vascular resistance increased significantly with decreasing temperature but was not affected by pump flow reductions. We have derived indices for minimal acceptable low-flow cardiopulmonary bypass based on the known effects of temperature on cerebral metabolism and have speculated on its utility based on our limited data and a literature review.

Having examined the options for adjuvant drug use during cardiac anesthesia, it becomes increasingly apparent that midazolam is "the drug" of choice and that supplementation with an opioid is an ideal adjuvant. In the hands of experienced cardiac anesthesiologists, the majority of the drugs discussed could provide adequate anesthesia with outcomes that would be difficult to distinguish, with the exception of awakening and time to extubation. Regardless of the inability to differentiate overall outcome, when comparing ease of providing complete "balanced" anesthesia, minimal cost increase, ease of use, hemodynamic stability, reliability of amnesia and ability to decrease narcotic requirement and allow early extubation, midazolam is a clear winner. Given as a continuous infusion or a bolus, potent opioids such as alfentanil, fentanyl or sufentanil enhance the amnestic and hypnotic effect of midazolam, decreasing the required dose. In addition, the combination of midazolam and narcotics decreases the catecholamine response that either one alone would produce. This removes the necessity of marked narcotic overdose required when narcotics alone are used. The result of this anesthetic combination is a technique that can be used in the majority of cardiac patients regardless of their ventricular performance, allowing options for earlier awakening, earlier extubation and decreased ICU stay. The goal of complete "balanced" anesthesia is best achieved with continuous infusions of midazolam and opioids. Accepting recall of intraoperative events as a necessary evil is unacceptable in the stable cardiac surgery patient.(ABSTRACT TRUNCATED AT 250 WORDS)

The objective of this study was to characterize cerebral venous effluent during normothermic nonpulsatile cardiopulmonary bypass. Thirty-one (23%) of 133 patients met desaturation criteria (defined as jugular bulb venous oxygen saturation less than or equal to 50% or jugular bulb venous oxygen tension less than or equal to 25 mm Hg) during normothermic cardiopulmonary bypass (after hypothermic cardiopulmonary bypass at 27 degrees to 28 degrees C). Cerebral blood flow, calculated using xenon 133 clearance methodology, was significantly (p less than 0.005) higher in the saturated group (33.7 +/- 10.3 mL.100 g-1.min-1) than in the desaturated group (26.2 +/- 6.9 mL.100 g-1.min-1), whereas the cerebral metabolic rate for oxygen was significantly lower (p less than 0.005) in the saturated group (1.28 +/- 0.39 mL.100 g-.min-1) than in the desaturated group (1.52 +/- 0.36 mL.100 g-1.min-1) at normothermia. The arteriovenous oxygen difference at normothermia was lower in the saturated group (3.92 +/- 1.12 mL/dL) than in the desaturated group (5.97 +/- 1.05 mL/dL). Neuropsychological testing was performed in 74 of the 133 patients preoperatively and on day 7 postoperatively. There was a general decline in mean scores of all tests postoperatively in both groups with no significant difference between the groups. We conclude that cerebral venous desaturation represents a global imbalance in cerebral oxygen supply-demand that occurs during normothermic cardiopulmonary bypass and may represent transient cerebral ischemia. These episodes, however, are not associated with impared neuropsychological test performance as compared with the performance of patients with no evidence of desaturation.

The effect of temperature on cerebral blood flow and metabolism was studied in 41 adult patients scheduled for operations requiring cardiopulmonary bypass. Plasma levels of midazolam and fentanyl were kept constant by a pharmacokinetic model-driven infusion system. Cerebral blood flow was measured by xenon 133 clearance (initial slope index) methods. Cerebral blood flow determinations were made at 27 degrees C (hypothermia) and 37 degrees C (normothermia) at constant cardiopulmonary bypass pump flows of 2 L/min/m2. Blood gas management was conducted to maintain arterial carbon dioxide tension (not corrected for temperature) 35 to 40 mm Hg and arterial oxygen tension of 150 to 250 mm Hg. Blood gas samples were taken from the radial artery and the jugular bulb. With decreased temperature there was a significant (p less than 0.0001) decrease in the arterial venous-oxygen content difference, suggesting brain flow in excess of metabolic need. For each patient, the cerebral metabolic rate of oxygen consumption at 37 degrees C and 27 degrees C was calculated from the two measured points at normothermia and hypothermia with the use of a linear relationship between the logarithm of cerebral metabolic rate of oxygen consumption and temperature. The temperature coefficient was then computed as the ratio of cerebral metabolic rate of oxygen consumption at 37 degrees C to that at 27 degrees C. The median temperature coefficient for man on nonpulsatile cardiopulmonary bypass is 2.8. Thus reducing the temperature from 37 degrees to 27 degrees C reduces cerebral metabolic rate of oxygen consumption by 64%.

Cardiopulmonary bypass management in neonates, infants, and children often requires the use of deep hypothermia at 18° 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° C; group B—deep hypothermic bypass at 18° to 20° C with maintenance of continuous flow; and group C—deep hypothermic circulatory arrest at 18° 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° and 18° 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° 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° 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.

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.