A semi-centennial report on the participants depicted in Joel Babb's portrait, 'the first successful kidney transplantation'.

Joseph Murray performed the first successful human kidney transplant on December 23, 1954. Forty-three years later, he along with participants Francis Moore and Leroy Vandam, commissioned a painting of the event from artist Joel Babb (1). To document this unique record of medical history, we identify all those present at the operation and depicted in the portrait, describe how the artist created the work, explain irregularities and inaccuracies in the painting, provide a 50-year follow-up on everyone involved, and comment on any influence this landmark event may have had on their subsequent careers.

Protein kinase C-alpha and -epsilon modulate connexin-43 phosphorylation in human heart.

We have previously demonstrated that protein kinase C (PKC)- alpha expression is significantly elevated in failing human left ventricle, with immunostaining showing increased PKC- alpha localization at the intercalated disks of cardiomyocytes. In the present study we sought to determine, in the failing heart, if PKC- alpha interacted with connexin-43 (Cx-43) both spatially and functionally, and to compare the association of PKC- alpha/Cx-43 with that of PKC- epsilon, a PKC isozyme that does not significantly increase in failing hearts. The possibility of a PKC- alpha or PKC- epsilon/Cx-43 association in non-failing hearts was also investigated. Co-immunoprecipitation of PKC- alpha or PKC- epsilon and Cx-43 in non-failing and failing left ventricle was achieved using antibodies to PKC- alpha or Cx-43. Confocal microscopy confirmed that PKC- alpha distribution within the cardiomyocyte included co-localization with connexin-43 in both failing and non-failing myocardium. In a similar manner, confocal imaging of PKC- epsilon showed cardiomyocyte distribution in both cytosol and membrane, and colocalization of PKC- epsilon with Cx-43. Recombinant PKC- alpha or - epsilon increased PKC activity significantly above endogenous levels in the co-immunoprecipitated Cx-43 complexes (P<0.05). However, phosphorylation of purified human Cx-43 (isolated from failing human left ventricle) by recombinant PKC- alpha or PKC- epsilon resulted in only PKC- epsilon mediated Cx-43 phosphorylation. Thus, in the human heart PKC- alpha, PKC- epsilon, and Cx-43 appear to form a closely associated complex. Whereas only PKC- epsilon directly phosphorylates Cx-43, both PKC isoforms result in increased phosphorylation within the Cx-43 co-immunoprecipitated complex.

Institutional variability in red blood cell conservation practices for coronary artery bypass graft surgery. Institutions of the MultiCenter Study of Perioperative Ischemia Research Group.

OBJECTIVE: To assess whether substantial institutional variability exists in red blood cell conservation practices associated with coronary artery bypass graft (CABG) surgery. DESIGN: Prospective, randomized patient enrollment and data collection. SETTING: Twenty-four U.S. academic institutions participating in the Multicenter Study of Perioperative Ischemia. PARTICIPANTS: A well-defined subset of primary CABG surgery patients (n = 713) expected to be at low risk for bleeding and exposure to allogeneic transfusion. INTERVENTIONS: None (observational study). MEASUREMENTS AND MAIN RESULTS: Frequency of use of red blood cell conservation techniques was determined among institutions. Correlation was determined between use of each technique and transfusion of allogeneic red blood cells and between use of each technique and median institutional blood loss. Significant variability (p < 0.01) was detected in institutional transfusion practice with respect to the use of predonated autologous whole blood, normovolemic hemodilution, red cell salvage, and reinfusion of shed mediastinal blood. The frequency of institutional use of these techniques was not associated with allogeneic transfusion (r2 < 0.15) or blood loss (r2 < 0.10) in the low-risk population of patients examined. CONCLUSIONS: Institutions vary significantly in perioperative blood conservation practices for CABG surgery. Further study to determine the appropriate use of these techniques is warranted.

Effect of propofol with and without EDTA on haemodynamics and calcium and magnesium homeostasis during and after cardiac surgery.

OBJECTIVE: To determine the effect of the addition of disodium edetate (EDTA) to propofol on haemodynamics, ionised calcium and magnesium serum concentrations, and adverse events during cardiac surgery. DESIGN: Double-blind, randomised, multicenter trial. SETTING: Operating room and intensive care unit of 5 academic health centres. PATIENTS: A total of 102 evaluable patients, aged 34 to 85 years, undergoing first-time, elective coronary artery bypass graft surgery. INTERVENTIONS: Comparison of propofol with EDTA and propofol without EDTA, each in conjunction with the opioid sufentanil, for intraoperative anaesthesia and postoperative sedation. MEASUREMENTS AND RESULTS: There were no significant differences at any time between the two formulations in any clinical chemistry measurements, including ionised calcium, ionised magnesium, total calcium, parathyroid hormone, blood urea nitrogen, creatinine, sodium, potassium, and phosphate. During bypass, the mean concentration of ionised calcium decreased to below the normal range, but the decrease was similar in both groups (propofol with EDTA, 0.98 +/- 0.07 mmol/L [N = 51]; propofol, 0.99 +/- 0.10 mmol/ L [N = 51]; p = NS). Calcium concentration returned to normal after rewarming. Mean ionised magnesium concentrations remained within normal limits in both groups. Similarly, there were no clinically meaningful differences between treatments with respect to haemodynamic variables, efficacy variables, or incidence of adverse events. CONCLUSIONS: The inclusion of EDTA in the current formulation of propofol appears to have no significant effects on calcium and magnesium profiles, renal function, haemodynamic variables, or other indicators of safety and efficacy during intraoperative anaesthesia and postoperative sedation in patients undergoing cardiac surgery.

Safety and efficacy of shed mediastinal blood transfusion after cardiac surgery: a multicenter observational study. Multicenter Study of Perioperative Ischemia Research Group.

OBJECTIVE: To examine the efficacy and safety of shed mediastinal blood (SMB) transfusion in preventing allogenic red blood cell (RBC) transfusion. DESIGN: An observational clinical study. SETTING: Twelve US academic medical centers. PARTICIPANTS: Six hundred seventeen patients undergoing elective primary coronary artery bypass grafting. INTERVENTIONS: Patients were administered SMB transfusion or not, according to institutional and individual practice, without random assignment. MEASUREMENTS AND RESULTS: The independent effect of SMB transfusion on postoperative RBC transfusion was examined by multivariable modeling. Potential complications of SMB transfusion, such as bleeding and infection, were examined. Three hundred twelve of the study patients (51%) received postoperative SMB transfusion (mean volume, 554 +/- 359 mL). Patients transfused with SMB had significantly lower volumes of RBC transfusion than those not receiving SMB (0.86 +/- 1.50 v 1.08 +/- 1.65 units; p < 0.05). However, multivariable analysis showed that SMB transfusion was not predictive of postoperative RBC transfusion. Demographic factors (older age, female sex), institution, and postoperative events (greater chest tube drainage, lower hemoglobin level on arrival to the intensive care unit, and use of inotropes) were significant predictors of RBC transfusion. The volume of chest tube drainage on the operative day (707 +/- 392 v 673 +/- 460 mL; p = 0.30), reoperation for hemorrhage (3.1% v2.5%; p = 0.68), and overall frequency of infection (5.8% v 6.6%; p = 0.81) were similar between patients receiving and not receiving SMB, respectively. However, in patients who did not receive allogenic RBC transfusion, there was a significantly greater frequency of wound infection in the SMB group (3.6% v0%; p = 0.02). CONCLUSION: These data suggest that SMB is ineffective as a blood conservation method and may be associated with a greater frequency of wound infection.

QEEG changes during cardiopulmonary bypass: relationship to postoperative neuropsychological function.

The relationship of changes in intraoperative QEEG and postoperative cognitive function was studied in 32 patients undergoing cardiac surgical procedures requiring cardiopulmonary bypass (CPB). All patients were anesthetized with a high dose narcotic technique in which CPB was carried out using moderate hypothermia. EEG recorded continuously throughout each procedure was analyzed using the neurometric technique. Neuropsychological (NP) evaluations were administered to all patients before, 1 week and 2-3 months postoperatively. A decrement in postoperative performance of 2 standard deviations in two or more tests from preoperative testing was defined as a new cognitive deficit. Of the patients studied, 40.6% demonstrated a new postoperative cognitive deficit at 1 week. At 2-3 months postoperatively, 28.1% continued to show a cognitive deficit. Discriminant analysis of the QEEG as a function of NP performance was calculated at select times during the surgical procedure. QEEG prediction of NP performance was just above chance at the 1 week comparison but excellent for the 2-3 month comparisons. This study suggests that with appropriate monitoring protocols, intraoperative QEEG may predict cognitive dysfunction experienced by patients 2-3 months postoperatively.

Hematocrit value on intensive care unit entry influences the frequency of Q-wave myocardial infarction after coronary artery bypass grafting. The Institutions of the Multicenter Study of Perioperative Ischemia (McSPI) Research Group.

OBJECTIVES: No data exist regarding "the best" hematocrit value after coronary artery bypass graft surgery. Transfusion practice varies, because neither an optimal hematocrit value nor a uniform transfusion trigger criterion has been determined. METHODS: To investigate the optimal hematocrit value, we studied 2202 patients undergoing coronary bypass. The hematocrit value on entry into the intensive care unit (IHCT) was categorized into three groups: high (> or = 34%), medium (25% to 33%), and low (< or = 24%). Characteristics and adverse events (outcomes) were compared, and the effect of IHCT on the risk of myocardial infarction was determined by logistic regression. RESULTS: High IHCT (> or = 34%) was associated with an increased rate of myocardial infarction (8.3% vs 5.5% vs 3.6%; p < or = 0.03, high, medium vs low) and with more severe left ventricular dysfunction (11.7% vs 7.4% and 5.7%; p=0.006, high, medium vs low). Mortality rate increased with higher IHCT when all the high-risk subgroups were combined (8.6% vs 4.5% vs 3.2%; p < 0.001, high, medium vs low). By multivariate analysis, IHCT remained the most significant predictor of adverse outcomes (relative risk high vs low 2.22, 95% confidence interval: 1.04 to 4.76). No characteristic, event, medication, or transfusion therapy confounded the relationship between IHCT and outcome. CONCLUSION: High IHCT is associated with a higher rate of myocardial infarction and is an independent predictor of infarction. On the basis of the risk of myocardial infarction, there is no rationale for transfusion to an arbitrary level after coronary artery bypass grafting.

Variability in transfusion practice for coronary artery bypass surgery persists despite national consensus guidelines: a 24-institution study. Institutions of the Multicenter Study of Perioperative Ischemia Research Group.

BACKGROUND: An estimated 20% of allogeneic blood transfusions in the United States are associated with cardiac surgery. National consensus guidelines for allogeneic transfusion associated with coronary artery bypass graft (CABG) surgery have existed since the mid- to late 1980s. The appropriateness and uniformity of institutional transfusion practice was questioned in 1991. An assessment of current transfusion practice patterns was warranted. METHODS: The Multicenter Study of Perioperative Ischemia database consists of comprehensive information on the course of surgery in 2,417 randomly selected patients undergoing CABG surgery at 24 institutions. A subset of 713 patients expected to be at low risk for transfusion was examined. Allogeneic transfusion was evaluated across institutions. Institution as an independent risk factor for allogeneic transfusion was determined in a multivariable model. RESULTS: Significant variability in institutional transfusion practice was observed for allogeneic packed red blood cells (PRBCs) (27-92% of patients transfused) and hemostatic blood components (platelets, 0-36%; fresh frozen plasma, 0-36%; cryoprecipitate, 0-17% of patients transfused). For patients at institutions with liberal rather than conservative transfusion practice, the odds ratio for transfusion of PRBCs was 6.5 (95% confidence interval [CI], 3.8-10.8) and for hemostatic blood components it was 2 (95% CI, 1.2-3.4). Institution was an independent determinant of transfusion risk associated with CABG surgery. CONCLUSIONS: Institutions continue to vary significantly in their transfusion practices for CABG surgery. A more rational and conservative approach to transfusion practice at the institutional level is warranted.

QEEG and neuropsychological profiles of patients after undergoing cardiopulmonary bypass surgical procedures.

One week after surgery neuropsychological (NP) deficits were quite common, occurring in 40.6% of the patients, with QEEG abnormality developing or increasing in the majority of patients. This change in the QEEG was an accurate predictor of NP performance 1 week after surgery. Two to three months after surgery evidence of continued NP performance deficits were still present in 28.1% of the patients. Preoperative versus one week postoperative QEEG change showed higher levels of sensitivity and specificity for predicting neuropsychological performance 3 months after CPB surgery than did preoperative versus one week postoperative NP performance. The mean values of specificity plus sensitivity were 74.5% for NP performance and 89.1% for the QEEG. These high levels of sensitivity and specificity for QEEG change for predicting postoperative cognitive function may justify the utility of performing these evaluations in the general CPB surgical population. In addition, this evidence supports the need to study the role of intraoperative QEEG monitoring to determine when QEEG change occurs so that possible remediational measures can be taken as soon as possible.

QEEG and neuropsychological profiles of patients prior to undergoing cardiopulmonary bypass surgical procedures.

Within our patient population undergoing cardiopulmonary bypass (CPB) surgery, evidence of pre-existing cortical dysfunction was highly prevalent, with 39.5% displaying QEEG and/or neuropsychological (NP) abnormality. These patients with pre-existing QEEG or NP abnormality were at increased risk for developing both short and long-term postoperative deficits in NP performance. Preoperative QEEG showed increased sensitivity and specificity over preoperative NP performance for predicting NP performance one week after surgery. One week after surgery NP deficits were quite common occurring in 40.6% of the patients. Two to three months after surgery evidence of continued NP performance deficits were still present in 28.1% of the patients. Preoperative NP performance predicted 3 month postoperative NP performance quite well, although preoperative QEEG proved equally effective.

Aprotinin for primary coronary artery bypass grafting: a multicenter trial of three dose regimens.

BACKGROUND: High-dose aprotinin reduces transfusion requirements in patients undergoing coronary artery bypass grafting, but the safety and effectiveness of smaller doses is unclear. Furthermore, patient selection criteria for optimal use of the drug are not well defined. METHODS: Seven hundred and four first-time coronary artery bypass grafting patients were randomized to receive one of three doses of aprotinin (high, low, and pump-prime-only) or placebo. The patients were stratified as to risk of excessive bleeding. RESULTS: All three aprotinin doses were highly effective in reducing bleeding and transfusion requirements. Consistent efficacy was not, however, demonstrated in the subgroup of patients at low risk for bleeding. There were no differences in mortality or the incidences of renal failure, strokes, or definite myocardial infarctions between the groups, although the pump-prime-only dose was associated with a small increase in definite, probable, or possible myocardial infarctions (p = 0.045). CONCLUSIONS: Low-dose and pump-prime-only aprotinin regimens provide reductions in bleeding and transfusion requirements that are similar to those of high-dose regimens. Although safe, aprotinin is not routinely indicated for the first-time coronary artery bypass grafting patient who is at low risk for postoperative bleeding. The pump-prime-only dose is not currently recommended because of a possible association with more frequent myocardial infarctions.

Aprotinin in primary valve replacement and reconstruction: a multicenter, double-blind, placebo-controlled trial.

BACKGROUND: Patients having cardiac operations often require blood transfusions. Aprotinin reduces the need for blood transfusions during coronary artery bypass graft operations. To determine the safety and effectiveness of aprotinin in reducing the use of allogeneic blood and postoperative mediastinal chest tube drainage, we studied 212 patients undergoing primary sternotomy for valve replacement or repair. METHODS: This study was multicenter, randomized, prospective, double-blind, and placebo-controlled. Patients received high-dose aprotinin (n = 71), low-dose aprotinin (n = 70), or placebo (n = 71). The study medication was given as a loading dose followed by a continuous infusion and pump prime dose. Heparin administration was standardized. Transfusions, postoperative mediastinal shed blood, and adverse events were tracked. RESULTS: Demographic profiles were similar among the treatment groups. Aprotinin did not decrease the percentage of patients receiving transfusions when compared with placebo (high-dose aprotinin, 63%, p = 0.092; low-dose aprotinin, 52%, p = 0.592; placebo, 48%). Aprotinin was associated with a reduction in the volume of mediastinal shed blood (high-dose aprotinin vs placebo, p = 0.002; low-dose aprotinin vs placebo, p = 0.017). Adverse events were equally distributed among the treatment groups except for postoperative renal dysfunction (high-dose aprotinin, 11%; low-dose aprotinin, 7%; placebo, 0%; p = 0.01). A disproportionate number of patients in the high-dose aprotinin group with postoperative renal dysfunction also had diabetes mellitus. CONCLUSIONS: Aprotinin treatment in this population did not reduce allogeneic blood use, although there were significant reductions in the volume of mediastinal shed blood.

Anticoagulation and hemostasis in cardiac surgical patients.

Optimizing anticoagulation and hemostasis during cardiopulmonary bypass and perioperatively helps to ensure the best possible clinical outcome. This article reviews the pharmacology of unfractionated and low-molecular weight heparin, aprotinin, desmopressin, dextran, antiplatelet agents, warfarin, and direct thrombin inhibitors. Their use is discussed in the context of coronary artery surgery, valvular surgery, and mechanical cardiac support devices, as well as in the management of acute ischemic syndromes, atrial fibrillation, and prevention and treatment of venous thromboembolism. Progress in the development and utilization of these anticoagulants and antiplatelet agents has supported the major advances that have been achieved in cardiac surgery.

Intraoperative somatosensory evoked potential monitoring predicts peripheral nerve injury during cardiac surgery.

BACKGROUND: Brachial plexus injury may occur without obvious cause in patients undergoing cardiac surgery. To determine whether such peripheral nerve injury can be predicted intraoperatively, we monitored somatosensory evoked potentials (SEPs) from bilateral median and ulnar nerves in 30 patients undergoing coronary artery bypass surgery. METHODS: SEPs were analyzed for changes during central venous cannulation and during use of the Favoloro and Canadian self-retaining sternal retractors, events hereto implicated in brachial plexus injury. Brachial plexus injury was evaluated during physical examination in the postoperative period by an individual blinded to results of SEP monitoring. RESULTS: Central venous cannulation was associated with transient changes in SEPs in four patients (13%). These changes occurred intermittently during insertion of the cannula but completely resolved within 5 min. Postoperative neurologic deficits did not occur in these cases. Use of the Canadian and Favoloro retractors was associated with significant changes in 21 patients (70%). In 16 of these, waveforms reverted toward baseline levels intraoperatively and were not associated with postoperative neurologic deficits. Five patients demonstrated a neurologic deficit postoperatively. In each of these, SEP change associated with use of surgical retractors persisted to the end of surgery compared to the immediate pre-bypass period. CONCLUSION: Intraoperative upper extremity SEPs may be used to predict peripheral nerve injury occurring during cardiac surgery.

Hypomagnesemia is common following cardiac surgery.

Hypomagnesemia is a common disorder in noncardiac surgical patients in the postoperative period, but the effect of cardiac surgery on serum magnesium concentrations remains unclear. The authors hypothesized that cardiac surgery is associated with hypomagnesemia, and prospectively studied 101 subjects (60 +/- 13.1 years of age) undergoing coronary artery revascularization (n = 70), valve replacement (n = 24), or both simultaneously (n = 7). Blood samples and clinical biochemical data were collected before induction of anesthesia, prior to cardiopulmonary bypass (CPB), immediately after CPB, and on postoperative day 1. Blood samples were analyzed for ultrafilterable magnesium, total magnesium, ionized calcium, parathyroid hormone, and free fatty acid concentrations. Outcome variables were also determined. Eighteen of 99 (18.2%) subjects had hypomagnesemia preinduction and this number increased to 71 of 100 (71.0%) following cessation of CPB (P less than 0.05). Patients with postoperative hypomagnesemia had a higher frequency of atrial dysrhythmias (22 of 71 [31.0%] v 3 of 29 [10.3%], P less than 0.05) and required prolonged mechanical ventilatory support (22 of 63 [34.9%] v 4 of 33 [12.1%], P less than 0.05). Hypomagnesemia is common following cardiac surgical procedures with CPB and is associated with clinically important postoperative morbidity.

Evaluation of a new cutaneous topical anesthesia preparation.

Topical anesthetic agents are usually not effective on intact skin because of poor penetration. EMLA is a new topical anesthetic formulation consisting of a eutectic mixture of the local anesthetics lidocaine 5% and prilocaine 5%. We evaluated the ability of this preparation to prevent or ameliorate the pain associated with the percutaneous placement of large IV catheters. Under double-blind randomized conditions, either EMLA or placebo was applied to the dorsum of both hands and an occlusive bandage then placed over each application site. The creams were placed 30, 45 or 60 minutes prior to IV cannulation. A 16-gauge catheter was inserted through each application area. Patients were asked to evaluate the relative degree of pain at each venous puncture site. The EMLA site was preferred when the formulation was applied for 45 to 60 minutes prior to cannula placement (p less than 0.01, confidence limits for the binomial distribution). Cusum analysis confirmed this minimal effective application time. The results indicate that EMLA is an effective cutaneous anesthetic formulation when applied with an occlusive bandage for a minimal time period of 45 minutes.

Continuous noninvasive monitoring of cardiac output with esophageal Doppler ultrasound during cardiac surgery.

Esophageal Doppler ultrasonography offers a continuous and noninvasive alternative to standard thermodilution cardiac output monitoring. A total of 372 simultaneous measurements of Doppler and thermodilution cardiac output were compared in 16 patients undergoing cardiac surgery. In addition, echocardiographic aortic diameter measurement, necessary for Doppler calibration, was compared with direct surgical measurement in 23 patients. Echocardiographic aortic measurement was often time consuming and correlated poorly (r = 0.31) with surgical measurement. On the other hand, Doppler cardiac output was determined easily and accurately tracked thermodilution cardiac output (R2 = 0.95, common slope coefficient 1.050, by multiple linear regression). Furthermore, Doppler cardiac output was more reproducible, showing less short-term variability than thermodilution cardiac output. The esophageal Doppler technique allows cardiac output monitoring in patients for whom invasive monitoring is not warranted.

Disadvantages of prostacyclin infusion during cardiopulmonary bypass: a double-blind study of 50 patients having coronary revascularization.

Prostacyclin (PGI2) has been suggested for use in cardiopulmonary bypass (CPB) because of its positive effects on platelet number and function. Fifty patients who underwent coronary artery bypass grafting using a bubble oxygenator received heparin, 3 mg per kilogram of body weight, and then were randomly assigned to receive PGI2, 25 ng/kg/min, beginning 5 minutes before and until the end of CPB (26 patients) or a placebo (24 patients). Both groups were similar in sex, age, heparin dose, protamine dose, and CPB time. During CPB, mean arterial pressure fell significantly with PGI2 (76 +/- 2 mm Hg to 53 +/- 2 mm Hg; p less than 0.05) and necessitated pressor substances. Platelet counts fell significantly in both groups with the start of CPB, but after 60 minutes were similar in both groups (118 +/- 9 X 10(3) versus 130 +/- 8 X 10(3); not significant [NS]) and were unchanged 3 hours after CPB. Total chest tube output was 647 +/- 51 ml (placebo group) versus 576 +/- 34 ml (PGI2 group) (NS); 18 of the patients given PGI2 required 26 transfusions compared with 16 transfusions in 8 of the patients given a placebo (p less than 0.05). In PGI2 patients, arterial oxygen tension on 100% oxygen fell from 281 +/- 18 mm Hg before CPB to 223 +/- 17 mm Hg immediately after CPB (p less than 0.05). The placebo patients did not show a change in this variable.(ABSTRACT TRUNCATED AT 250 WORDS)