Howard J. Nathan

Skeletonized Internal Thoracic Artery Harvest Reduces Pain and Dysesthesia and Improves Sternal Perfusion After Coronary Artery Bypass Surgery: A Randomized, Double-Blind, Within-Patient Comparison

Background— Observational studies suggest that skeletonization of the internal thoracic artery (ITA) can improve conduit flow and length and reduce deep sternal infections and postoperative pain. We performed a randomized, double-blind, within-patient comparison of skeletonized and nonskeletonized ITAs in patients undergoing coronary surgery. Methods and Results— Patients (n=48) undergoing bilateral ITA harvest were randomized to receive 1 skeletonized and 1 nonskeletonized ITA. Intraoperatively, ITA flow was assessed directly and with a Doppler flow probe before and after topical application of papaverine. ITA harvest time and conduit length were recorded. A blinded assessment of pain (visual analog scale) and dysesthesia (physical examination) was performed at discharge, at 2 weeks, and at a 3-month follow-up. Sternal perfusion was assessed with nuclear imaging (n=7). Skeletonization required longer ITA harvest times (27±1 versus 24±1 minutes; P=0.04). There was a trend toward increased ITA length in the skeletonized group (18.2±0.3 versus 17.7±0.3 cm; P=0.09). In situ ITA flow was lower in skeletonized arteries (7.4±0.9 versus 10.1±1.0 mL/min; P=0.01) and increased significantly after ITA division and papaverine application. Postanastomotic flows were similar between groups. Skeletonization was associated with decreased pain at the 3-month follow-up and a reduction in major sensory deficits at the 4-week and 3-month (17% versus 50%; P=0.002) follow-ups. Baseline adjusted sternal perfusion was significantly greater by 17±6% (P=0.03) on the skeletonized side. Conclusions— Skeletonization results in reduced postoperative pain and dysesthesia and increased sternal perfusion at follow-up but does not produce increased conduit flow. ITA skeletonization may be a strategy for reducing morbidity after CABG.

The Cardiotomy Trial: A Randomized, Double-Blind Study to Assess the Effect of Processing of Shed Blood During Cardiopulmonary Bypass on Transfusion and Neurocognitive Function

Background— Reinfusion of unprocessed cardiotomy blood during cardiac surgery can introduce particulate material into the cardiopulmonary bypass circuit, which may contribute to postoperative cognitive dysfunction. On the other hand, processing of this blood by centrifugation and filtration removes coagulation factors and may potentially contribute to coagulopathy. We sought to evaluate the effects of cardiotomy blood processing on blood product use and neurocognitive functioning after cardiac surgery. Methods and Results— Patients undergoing coronary and/or aortic valve surgery using cardiopulmonary bypass were randomized to receive unprocessed blood (control, n=134) or cardiotomy blood that had been processed by centrifugal washing and lipid filtration (treatment, n=132). Patients and treating physicians were blinded to treatment assignment. A strict transfusion protocol was followed. Blood transfusion data were analyzed using Poisson regression models. The treatment group received more intraoperative red blood cell transfusions (0.23±0.69 U versus 0.08±0.34 U, P=0.004). Both red blood cell and nonred blood cell blood product use was greater in the treatment group and postoperative bleeding was greater in the treatment group. Patients were monitored intraoperatively by transcranial Doppler and they underwent neuropsychometric testing before surgery and at 5 days and 3 months after surgery. There was no difference in the incidence of postoperative cognitive dysfunction in the 2 groups (relative risk: 1.16, 95% CI: 0.86 to 1.57 at 5 days postoperatively; relative risk: 1.05, 95% CI: 0.58 to 1.90 at 3 months). There was no difference in the quality of life nor was there a difference in the number of emboli detected in the 2 groups. Conclusions— Contrary to expectations, processing of cardiotomy blood before reinfusion results in greater blood product use with greater postoperative bleeding in patients undergoing cardiac surgery. There is no clinical evidence of any neurologic benefit with this approach in terms of postoperative cognitive function.

The cardiac anesthesia risk evaluation score: a clinically useful predictor of mortality and morbidity after cardiac surgery.

BackgroundThe Cardiac Anesthesia Risk Evaluation (CARE) score is a simple risk classification for cardiac surgical patients. It is based on clinical judgment and three clinical variables: comorbid conditions categorized as controlled or uncontrolled, surgical complexity, and urgency of the procedure. This study compared the CARE score with the Parsonnet, Tuman, and Tu multifactorial risk indexes for prediction of mortality and morbidity after cardiac surgery. MethodsIn this prospective study, 3,548 cardiac surgical patients from one institution were risk stratified by two investigators using the CARE score and the three tested multifactorial risk indexes. All patients were also given a CARE score by their attending cardiac anesthesiologist. The first 2,000 patients served as a reference group to determine discrimination of each classification with receiver operating characteristic curves. The following 1,548 patients were used to evaluate calibration using the Pearson chi-square goodness-of-fit test. ResultsThe areas under the receiver operating characteristic curves for mortality and morbidity were 0.801 and 0.721, respectively, with the CARE score rating by the investigators; 0.786 and 0.710, respectively, with the CARE score rating by the attending anesthesiologists (n = 8); 0.808 and 0.726, respectively, with the Parsonnet index; 0.782 and 0.697, respectively, with the Tuman index; 0.770 and 0.724 with the Tu index, respectively. All risk models had acceptable calibration in predicting mortality and morbidity, except for the Parsonnet classification, which failed calibration for morbidity (P = 0.026). ConclusionsThe CARE score performs as well as multifactorial risk indexes for outcome prediction in cardiac surgery. Cardiac anesthesiologists can integrate this score in their practice and predict patient outcome with acceptable accuracy.

Effects of Mild Hypothermia and Rewarming on Renal Function After Coronary Artery Bypass Grafting

BACKGROUND Hypothermia is a potential strategy for visceral organ protection during cardiopulmonary bypass (CPB). We report data from two randomized studies evaluating mild hypothermia and rewarming on postoperative renal function in cardiac surgical patients. METHODS Patients undergoing nonemergency, isolated coronary artery bypass grafting were enrolled into two studies. In the first, 223 patients were cooled to 32 degrees C during CPB and randomly assigned to rewarming to 37 degrees C (RW-37 degrees) or 34 degrees C (RW-34 degrees). The second study randomized 267 patients to sustained mild hypothermia at 34 degrees C (S-34 degrees) or normothermia (S-37 degrees) without rewarming. Serum creatinine levels were measured. Creatinine clearance was calculated. Significant renal dysfunction was defined as a 25% increase in serum creatinine or a 25% decrease in creatinine clearance postoperatively. RESULTS Postoperative serum creatinine levels were persistently higher in the RW-37 degrees patients than in the RW-34 degrees group (p < 0.01). RW-37 degrees patients had a higher incidence of renal dysfunction (17%) than RW-34 degrees patients (9%, p = 0.07). Sustained mild hypothermia had no beneficial effect on postoperative serum creatinine levels (p = 0.44) or significant renal dysfunction: S-34 degrees, 20% vs S-37 degrees, 15% (p = 0.28). Diabetes (odds ratio [OR], 1.6; 95% confidence interval [CI] 1.3 to 2.1), prolonged CPB time (OR, 1.1; 95% CI, 1.0 to 1.2), and rewarming (OR, 1.4; 95% CI, 1.0 to 1.9) were independent risk factors for significant renal dysfunction. Renal dysfunction was associated with longer hospital stay (8.4 +/- 0.8 vs 6.8 +/- 04 days, p < 0.001). CONCLUSIONS Sustained mild hypothermia does not improve renal outcome. However, rewarming on CPB is associated with increased renal injury and should be avoided.

Amrinone and dobutamine as primary treatment of low cardiac output syndrome following coronary artery surgery: A comparison of their effects on hemodynamics and outcome

This study was undertaken in order to compare the effectiveness of amrinone and dobutamine as primary treatment of a low cardiac output (CO) after coronary artery bypass graft (CABG) surgery. Thirty patients with preoperative left ventricular dysfunction participated in this open-label randomized study. Patients were included if they failed to separate from cardiopulmonary bypass (CPB) without inotropic support or if they had a cardiac index (CI) less than 2.4 L/min/m2 after CPB regardless of the blood pressure, in the presence of adequate filling pressures. The treatment objectives were to separate from CPB and achieve a CI > or = 2.4 L/min/m2 and a mean arterial pressure > or = 70 mmHg. Patients treated with amrinone received 0.75 mg/kg followed by 10 micrograms/kg/min; when the objectives were not achieved within five minutes, another 0.75 mg/kg was given. Patients treated with dobutamine received an initial infusion of 5 micrograms/kg/min increased stepwise to 15 micrograms/kg/min if necessary. Eleven of 15 amrinone versus 6 of 15 dobutamine patients achieved the predefined treatment objectives with the test drug alone (P = NS). Comparisons of hemodynamics in patients treated solely with amrinone (n = 7) or dobutamine (n = 6) after CPB showed no significant differences between the treatment groups. The incidence of myocardial ischemia as detected by Holter monitor was 36% with amrinone and 33% with dobutamine. Two patients suffered ventricular fibrillation and two had significant supraventricular tachyarrhythmias (heart rate > 130/min) during treatment with dobutamine alone, whereas no significant arrhythmias occurred in the amrinone group (P = NS). Six dobutamine patients (40%) had postoperative myocardial infarction (MI) as opposed to none among the amrinone patients (P = 0.017). These results indicate that amrinone compares favorably with dobutamine as a primary treatment of low CO after CABG. Further study in a larger number of patients will be required in order to determine if the lower incidence of MI in the amrinone group was due to the treatment drug.

Predictors of Early Neurocognitive Deficits in Low-Risk Patients Undergoing On-Pump Coronary Artery Bypass Surgery

Background— Postoperative cognitive deficits (POCDs) are a source of morbidity and occur frequently even in low-risk patients undergoing cardiac surgery. Predictors of neurocognitive deficits can identify potentially modifiable risk factors as well as high-risk patients in whom alternate revascularization strategies may be considered. Methods and Results— 448 patients undergoing coronary surgery (coronary artery bypass graft [CABG]) underwent standardized preoperative and postoperative neurocognitive testing as part of 2 randomized trials evaluating the effects of mild hypothermia during coronary surgery. Prospectively collected data were used to identify univariate predictors of POCDs and multivariable logistic regression models were constructed. Models were bootstrapped 1000 times. POCDs occurred in 59% of patients. Significant univariate predictors included intraoperative normothermia, impaired left ventricular (LV) function, higher educational level, elevated serum creatinine and reduced creatinine clearance, prolonged intubation time, intensive care unit (ICU) stay, and hospital stay. Advanced age, presence of carotid disease, and cardiopulmonary bypass time were not associated with increased POCDs in this cohort. Multivariable modeling identified intraoperative normothermia (odds ratio [95% confidence interval] −1.15 [1.01, 1.31]), poor LV function (1.53 [1.02, 2.30]), and elevated preoperative creatinine (1.01 [1.00 to 1.03] for every 1 mmol/L increase), prolonged (>24 hours) ICU stay (1.88 [1.27 to 2.79]), and higher educational level (1.52 [1.01 to 2.28]) as independent predictors of POCD occurrence. Conclusions— Mild hypothermia, in the intraoperative and perioperative period, may be a protective strategy for the prevention of POCDs. Patients with elevated pre-operative creatinine and poor LV function carry a higher risk of POCDs and may benefit from revascularization strategies other than conventional on-pump CABG.

Fentanyl Infusion Anesthesia for Aortocoronary Bypass Surgery: Plasma Levels and Hemodynamic Response

Plasma fentanyl concentrations were measured by radioimmunoassay in patients during aortocoronary bypass surgery and correlated with hemodynamic responses to surgical stimulation. Thirty patients scheduled for aortocoronary bypass surgery were divided into three groups of 10. Patients in group 1 received fentanyl, 30 μg/kg, as a loading dose followed by an infusion of 0.3 μg/kg/min; those in group 2 received 40 μg/kg as a loading dose followed by an infusion of 0.4 μg/kg/min; and those in group 3 received 50 mg/kg as the loading dose followed by an infusion of 0.5 μg/kg/min. The total dose of fentanyl administered to each group up to the time of rewarming on cardiopulmonary bypass was 60 jug/kg, 90 μg/kg, and 100 μg/kg, respectively. Each of the dose regimens produced stable plasma concentrations starting approximately 20 minutes after induction and continuing until the infusion was discontinued. Patients in group 1 had a mean plasma concentration of 10 to 12 ng/ml in the stable period compared with 12 to 14 ng/ml in group 2 and 15 to 18 ng/ml in group 3. Fewer patients in group 3 responded to intubation and surgical stimulation than in the other groups, although the differences between groups were not statistically significant. Response to stimulation was treated by the administration of droperidol or volatile anesthetic agents. At a plasma concentration of 15 ng/ml, 50% of patients had an increase in systolic blood pressure which required treatment. This minimal intra-arterial concentration, analogous to MAC, can be achieved by the administration of fentanyl as a loading dose of 50 μg/kg followed by an infusion of 0.5 μg/kg/min.

Effect of perfusionist technique on cerebral embolization during cardiopulmonary bypass

Objective: To determine the association between high-intensity transient signals (HITS) and perfusionist interventions, purging techniques, pump flows and venous reservoir blood volume levels during cardiopulmonary bypass. Methods: Transcranial Doppler was used to detect HITS in the middle cerebral artery during the period of aortic crossclamping in patients undergoing coronary artery bypass grafting. Perfusionist-related interventions were recorded and included blood sampling (including the number of times that the oxygenator sampling manifold was purged), drug bolus injections and infusions (vasopressors, crystalloid and mannitol). Pump flows and venous reservoir volume levels were also documented. Results: There were 534 interventions in 90 patients [median number of interventions per patient: 6 (quartiles: 4, 8)]. The median total HITS count from all interventions was 17 (5, 37). This represented 38% of the total HITS counts during aortic crossclamping. Factors contributing to differences in the HITS count included type of intervention (p<0.0001) and perfusionist (p=0.0012). Blood sampling (p<0.001) and drug bolus injections (p=0.06) had higher HITS counts per patient than infusions. Repetitive purging significantly increased HITS counts (r=0.74; p<0.001). Purging perfusionists (purging: 1 - 10 times) had higher HITS counts per patient [5 HITS (1, 15) than nonpurgers [0 HITS (0, 1) p<0.0001]. HITS counts were significantly correlated with reservoir volumes (r=-0.20, p=0.017) and pump flow rates (r=0.21, p=0.008). Reservoir volume levels ≤ 800 mL were associated with higher HITS counts per intervention [11 HITS (2, 27)] during blood sampling compared with higher volume levels [3 HITS (1, 10), p=0.001]. Conclusions: Cerebral emboli associated with perfusionist interventions can be minimized by not purging the sampling manifold, using continuous infusions rather than bolus injections, and maintaining high blood-volume levels (>800 mL) in the venous reservoir.

Cerebral Emboli Detected by Transcranial Doppler During Cardiopulmonary Bypass Are Not Correlated With Postoperative Cognitive Deficits

Background and Purpose— High-intensity transient signals (HITS) are the transcranial Doppler representation of both air and solid cerebral emboli. We studied the frequency of HITS associated with different surgical maneuvers during cardiopulmonary bypass for coronary artery bypass graft surgery and their association with postoperative cognitive dysfunction (POCD). Methods— We combined 356 patients undergoing coronary artery bypass graft from 2 clinical trials who had both neuropsychological testing (before, 1 week and 3 months after surgery) and transcranial Doppler during cardiopulmonary bypass. HITS were grouped into periods that included: cannulation, cardiopulmonary bypass onset, aortic crossclamp-on, aortic crossclamp-off, side clamp-on, side clamp-off, and decannulation. POCD was defined by a decreased combined Z-score of at least 2.0 or reduction in Z-scores of at least 2.0 in 20% of the individual tests. Results— Incidence of POCD was 47.3% and 6.3% at 1 week and 3 months after surgery. There was no association between cardiopulmonary bypass counts of HITS and POCD at 1 week (P=0.617) and 3 months (P=0.110). No differences in HITS counts were identified at any of the surgical periods between patients with and without POCD. Factors affecting HITS counts were surgical period (P<0.0001), blood flow velocity (P=0.012), cardiopulmonary bypass duration (P=0.040), and clinical study (P=0.048). Conclusions— Although cerebral microemboli have been implicated in the pathogenesis of POCD, in this study that included low-risk patients undergoing coronary artery bypass surgery, there was no demonstrable correlation between the counts of HITS and POCD.

The management of temperature during hypothermic cardiopulmonary bypass: I — Canadian survey

During hypothermic cardiopulmonary. bypass (CPB) patients are cooled, usually to between 30–32° C, and, after myocardial blood flow is restored, they are rewarmed with blood heated in the pump-oxygenator. We audited our local practice by recording tympanic and nasopharyngeal temperatures in 11 patients undergoing hypothermie CPB. We found that, during rewarming, nasopharyngeal and tympanic temperatures commonly exceeded 35° C although temperature measured in the bladder was <37° C. A survey of cardiac surgery centres in Canada suggested that most centres induce hyperthermia in highly perfused tissues during rewarming, sometimes inadvertently. This may be of some importance because it has become widely appreciated by neuroscientists that mild degrees of brain cooling (2–5° C) are capable, of conferring dramatic protection from ischaemic brain injury and, conversely, mild temperature elevation may be markedly deleterious. If control of brain temperature is considered desirable then we would suggest that nasopharyngeal temperature be monitored during rewarming on CPB.RésuméPendant la circulation extracorporelle (CEC) hypothermique, les patients sont ordinairement refroidis à 30°–32°C et, une fois le débit coronarien rétabli, réchauffés avec le sang du circuit de CEC. Nous avons contrôlé notre pratique usuelle en enregistrant les températures tympanique et oropharyngée chez 11 patients opérés pour revascularisation myocardique. Nous avons trouvé que, pendant le réchauffement, les températures nasopharyngée et tympanique dépassaient généralement 38° quoique la température mesurée dans la vessie ait été inférieure à 37° C. Une enquête réalisée sur la chirurgie cardiaque au Canada montre que dans la plupart des centres, l’hyperthermie est induite dans les tissus à perfusion élevée pendant le réchauffement et, cela, parfois par mégarde. Ce facteur a son importance parce qu’il est maintenant reconnu que le refroidissement cérébral, même sïl est minime (2–5° C), peut protéger efficacement du dommage cérébral ischémique et qu’au contraire, une augmentation de la température, même légère, peut être très nuisible. Comme il est désirable que la température cérébrale soit contrôlée, nous suggérons le monitorage de la température nasopharyngée pendant le réchauffement sous CEC.