Comprehensive multimodality blood conservation: 100 consecutive CABG operations without transfusion.

BACKGROUND: Despite the recent introduction of a number of technical and pharmacologic blood conservation measures, bleeding and allogeneic transfusion remain persistent problems in open heart surgical procedures. We hypothesized that a comprehensive multimodality blood conservation program applied algorithmically on the basis of bleeding and transfusion risk would provide a maximum, cost-effective, and safe reduction in postoperative bleeding and allogeneic blood transfusion. METHODS: One hundred consecutive patients undergoing coronary artery bypass grafting were prospectively enrolled in a risk factor-based multimodality blood conservation program (MMD group). To evaluate the relative efficacy and safety of this comprehensive approach, comparison was made with a similar group of 90 patients undergoing coronary artery bypass grafting to whom the multimodality blood conservation program was not applied but in whom an identical set of transfusion guidelines was enforced (control group). To evaluate the cost effectiveness of the multimodality program, comparison was also made between patients in the MMD group and a consecutive series of contemporaneous, diagnostic-related group-matched patients. RESULTS: One hundred consecutive patients in the MMD group underwent coronary artery bypass grafting without allogeneic transfusion. This compared favorably with the control population in whom a mean of 2.2 +/- 6.7 units of allogeneic blood was transfused per patient (34 patients [38%] received transfusion). In addition, the volume of postoperative blood loss at 12 hours in the control group was almost double that of the MMD group (660 +/- 270 mL versus 370 +/- 180 mL [p < 0.001]). Total costs for the MMD group in each of the three major diagnostic-related groups were equivalent to or significantly less than those in the consecutive series of diagnostic-related group-matched patients. CONCLUSIONS: Comprehensive risk factor-based application of multiple blood conservation measures in an optimized, integrated, and algorithmic manner can significantly decrease bleeding and need of allogeneic transfusion in coronary artery bypass grafting in a safe and cost-effective manner.

Impact of minimum hematocrit during cardiopulmonary bypass on mortality in patients undergoing coronary artery surgery.

BACKGROUND: The hematocrit on cardiopulmonary bypass (CPB) frequently falls to a low level during many cardiac surgical procedures. This study was designed to explore the impact on mortality of minimum hematocrit level achieved during the CPB after coronary artery surgery. METHODS AND RESULTS: Two thousand seven hundred thirty-eight sequential isolated coronary artery surgery patients during a 42-month period at a tertiary academic center were included in this study. Thirty-one standardized preoperative risk factors used in a multiple logistic regression revealed eight statistically significant independent predictors for postoperative mortality. Minimum hematocrit level during CPB was then added to the regression model and was found to be an independent risk factor for mortality. The entire patient population was divided into dichotomous groups using different minimum hematocrit levels on CPB for the determination of cutoff points by multiple logistic regression. After adjusting for other risk factors, the minimum hematocrit level of 14% was found to be a statistically significant cutoff point. Patients with minimum hematocrit levels < or =14% were found to have an increased probability of risk-adjusted mortality (odds ratio, 2.70; P=.002). A subgroup analysis revealed that high-risk patients with minimum hematocrit levels < or =17% were found to have a significantly increased probability of postoperative mortality (odds ratio, 2.20; P=.017). CONCLUSIONS: Minimum hematocrit level during CPB is an independent risk factor for mortality after coronary artery surgery. There is a significantly increased risk of mortality for hematocrit levels < or =14%. For high-risk patients, there is a significantly increased risk of mortality for hematocrit levels < or =17%.

Open heart operations without transfusion using a multimodality blood conservation strategy in 50 Jehovah's Witness patients: implications for a "bloodless" surgical technique.

BACKGROUND: Blood transfusion persists as an important risk of open heart operations despite the recent introduction of a variety of new pharmacologic agents and blood conservation techniques as independent therapies. A comprehensive multimodality blood conservation program was developed to minimize this risk. STUDY DESIGN: To provide a strategy for operating without transfusion, this program was prospectively applied to 50 adult patients who are Jehovah's Witnesses and have undergone open heart operation at our institution since 1992. The blood conservation program used for these patients included the use of high-dose erythropoietin (800 U/kg load, 500 U/kg every other day), aprotinin (6 million U total dose full Hammersmith regimen), "maximal" volume intraoperative autologous blood donation, intraoperative cell salvage, continuous shed blood reinfusion, and drawing as few blood specimens as possible. RESULTS: Procedures performed included first-time coronary bypass operations (n = 30) and more complex operations, including reoperations, valve replacements, and multiple valve replacements with or without coronary bypass (n = 20). Despite the absence of transfusion, the mean discharge hematocrit in these patients was greater than 30 percent, and there was no anemia-related mortality rate in this group. The overall in-hospital mortality for the group was 4 percent. A subset analysis was performed between the 30 first-time coronary bypass patients (group 1) and a control group of 30 consecutive patients who were not Jehovah's Witnesses but had undergone first-time coronary bypass during the same period (group 2). The blood conservation program described in the previous paragraph was not used in group 2 patients and specific transfusion criteria were prospectively applied. The chest tube output in group 1 patients was less than 40 percent of that for group 2 patients at all points measured after operation (p < 0.01). Postoperative hematocrit levels in group 1 were greater than those for group 2, despite the absence of red blood cell transfusion and despite a significantly lower admission hematocrit and red blood cell mass in group 1. The average length of stay and ancillary costs for the two groups were equivalent. Although group 1 and 2 patients were well matched for preoperative transfusion risk factors, none of the group 1 patients required transfusion, but 17 (57 percent) group 2 patients met transfusion criteria and received 3.0 +/- 4.8 U (mean plus or minus standard deviation) of homologous blood or blood products. CONCLUSIONS: These results suggest that even complex open heart operations can be performed without homologous transfusion by optimally applying available blood conservation techniques. More generalized application of these measures may increasingly allow "bloodless" operations in all patients.

Intraoperative autologous blood donation preserves red cell mass but does not decrease postoperative bleeding.

BACKGROUND: Postoperative bleeding and transfusion remain a source of morbidity and cost after open heart operations. The benefit of the acute removal and reinfusion of fresh autologous blood around the time of cardiopulmonary bypass-a technique known as intraoperative autologous donation (IAD)-has not been universally accepted. We sought to more clearly evaluate the effects of IAD on allogeneic transfusion and postoperative bleeding by removing, preserving, and reinfusing a calculated maximum volume of fresh autologous whole blood. METHODS: Ninety patients undergoing coronary artery bypass grafting or valvular operations were prospectively randomized to either have (IAD group) or not have (control group) calculated maximum volume IAD performed. Treatment was otherwise identical. Transfusion guidelines were uniformly applied to all patients. RESULTS: An average volume of 1,540 +/- 302 mL of fresh autologous blood was removed and reinfused in the IAD group. Postoperative hematocrits were significantly greater at 12 and 24 hours postoperatively in the IAD group versus the control group despite a significant decrease in both the percentage of patients in whom allogeneic red blood cells were transfused (17% versus 52%; p < 0.01) and the number of red blood cell units transfused per patient per group (0.28 +/- 0.66 and 1.14 +/- 1.19 units; p < 0.01). Conversely, chest tube output, incidence of excessive postoperative bleeding, postoperative prothrombin time, and platelet and coagulation factor transfusion requirement did not differ between groups. CONCLUSIONS: These results indicate that intraoperative autologous donation serves to preserve red blood cell mass. Its routine use in eligible patients is therefore justified. However, the removal and reinfusion of an individually calculated maximum volume of fresh autologous blood had no effect on postoperative bleeding or platelet and coagulation factor transfusion requirement. This lack of hemostatic effect belies the beliefs of many about the primary action of IAD, helps to delineate the optimal way in which to perform IAD, and carries implications regarding the use of allogeneic platelet and coagulation factors for the treatment of early postoperative bleeding.

Triiodothyronine therapy lowers the incidence of atrial fibrillation after cardiac operations.

BACKGROUND: Cardiopulmonary bypass results in a euthyroid sick state, and recent evidence suggests that perioperative triiodothyronine (T3) supplementation may have hemodynamic benefits. In light of the known effects of thyroid hormone on atrial electrophysiology, we investigated the effects of perioperative T3 supplementation on the incidence of postoperative arrhythmias. METHODS: One hundred forty-two patients with depressed left ventricular function (ejection fraction < 0.40) undergoing coronary artery bypass grafting were randomized to either T3 or placebo treatment groups in a prospective, double-blind fashion. Triiodothyronine was administered as a 0.8 micrograms/kg intravenous bolus at the time of aortic cross-clamp removal followed by an infusion of 0.113 micrograms.kg-1.h-1 for 6 hours. Patients were monitored for the development of arrhythmias during the first 5 postoperative days. RESULTS: The incidence of sinus tachycardia and ventricular arrhythmias were similar between groups. Triiodothyronine-treated patients had a lower incidence of atrial fibrillation (24% versus 46%; p = 0.009), and fewer required cardioversion (0 versus 6; p = 0.012) or anticoagulation (2 versus 10; p = 0.013) during hospitalization. Six patients in the T3 group versus 16 in the placebo group required antiarrhythmic therapy at discharge (p = 0.019). CONCLUSIONS: Perioperative T3 administration decreased the incidence and need for treatment of postoperative atrial fibrillation.

Thyroid hormone treatment after coronary-artery bypass surgery.

BACKGROUND: Thyroid hormone has many effects on the cardiovascular system. During and after cardiopulmonary bypass, serum triiodothyronine concentrations decline transiently, which may contribute to postoperative hemodynamic dysfunction. We investigated whether the perioperative administration of triiodothyronine (liothyronine sodium) enhances cardiovascular performance in high-risk patients undergoing coronary-artery bypass surgery. METHODS: We administered triiodothyronine or placebo to 142 patients with coronary artery disease and depressed left ventricular function. The hormone was administered as an intravenous bolus of 0.8 microgram per kilogram of body weight when the aortic cross-clamp was removed after the completion of bypass surgery and then as an infusion of 0.113 microgram per kilogram per hour for six hours. Clinical and hemodynamic responses were serially recorded, as was any need for inotropic or vasodilator drugs. RESULTS: The patients' preoperative serum triiodothyronine concentrations were normal (mean [+/- SD] value, 81 +/- 22 ng per deciliter [1.2 +/- 0.3 nmol per liter]), and they decreased by 40 percent (P < 0.001) 30 minutes after the onset of cardiopulmonary bypass. The concentrations in patients given intravenous triiodothyronine became supranormal and were significantly higher than those in patients given placebo (P < 0.001). However, the concentrations were once again similar in the two groups 24 hours after surgery. The mean postoperative cardiac index was higher in the triiodothyronine group (2.97 +/- 0.72 vs. 2.67 +/- 0.61 liters per minute per square meter of body-surface area, P = 0.007), and systemic vascular resistance was lower (1073 +/- 314 vs. 1235 +/- 387 dyn.sec.cm-5, P = 0.003). The two groups did not differ significantly in the incidence of arrhythmia or the need for therapy with inotropic and vasodilator drugs during the 24 hours after surgery, or in perioperative mortality and morbidity. CONCLUSIONS: Raising serum triiodothyronine concentrations in patients undergoing coronary-artery bypass surgery increases cardiac output and lowers systemic vascular resistance, but does not change outcome or alter the need for standard postoperative therapy.

Triiodothyronine improves left ventricular function without oxygen wasting effects after global hypothermic ischemia.

Cardiopulmonary bypass results in a "euthyroid sick" state. Recently, interest has focused on the relationship between low serum triiodothyronine levels and postoperative cardiovascular hemodynamics. The present study was undertaken to more clearly define the acute effects of triiodothyronine on myocardial mechanics and energetics after hypothermic global ischemia using an ex-vivo canine heart preparation to model the clinical condition. Experiments were performed on isolated hearts subjected to hyperkalemic arrest with 90 minutes of hypothermic (10 degrees C) ischemia. Isolated hearts were cross-perfused by euthyroid support dogs in which triiodothyronine levels spontaneously decreased by 65% to 75% (p < 0.01) after the initiation of cross-perfusion. In nine heart preparations, triiodothyronine (Triostat) was given as a bolus dose (0.2 micrograms/kg) after 1 hour of baseline data collection with a subsequent measurable rise in serum triiodothyronine levels (p < 0.01). In six postischemic hearts, reverse triiodothyronine was given as a 0.2 micrograms/kg bolus. Triiodothyronine was also administered to a group of eight nonischemic, continuously perfused isolated hearts. Intrinsic myocardial contractility was assessed by analysis of the preload recruitable stroke work area, energetic efficiency from the myocardial oxygen consumption-pressure-volume area relationship, and coronary vascular resistance from analysis of coronary flow and perfusion pressure. Acute administration of triiodothyronine to postischemic hearts improved the preload recruitable stroke work area from 9.5 +/- 1.42 to 14.9 +/- 2.03 x 10(7) erg/ml, a 56% increase from baseline (p < 0.001), but had no effect on the preload recruitable stroke work area of the nonischemic hearts. The inotropic response resulting from triiodothyronine treatment did not alter the myocardial oxygen consumption-pressure-volume area relationship. Triiodothyronine treatment was associated with significantly decreased coronary resistance and increased coronary flow through a range of diastolic loading conditions in the postischemic hearts. The biologically inactive thyroid hormone metabolite reverse triiodothyronine was without effect on any of the measured parameters. On the basis of these results, we conclude that the low triiodothyronine state of cardiopulmonary bypass can be reproduced in this isolated heart model and that acute triiodothyronine treatment results in a unique inotropic action manifest only in the postischemic reperfused myocardium and is accomplished without oxygen wasting effects.

Combined aprotinin and erythropoietin use for blood conservation: results with Jehovah's Witnesses.

Despite recent advances in blood conservation techniques, major risks persist for excessive bleeding and blood transfusion after open heart operations. We reviewed the records of 100 consecutive patients undergoing first-time coronary artery bypass grafting at our institution to define these risks and develop a multimodality blood conservation program based on the results. This program was subsequently applied on a prospective basis to a select group of patients who refuse blood transfusion on religious grounds (Jehovah's Witnesses [JW]) (n = 15). Encouraging initial results with coronary artery bypass grafting in this group (n = 8) led to the application of the program to more complex operations (n = 7), including repeat bypass grafting with use of the internal mammary artery, repeat mitral valve replacement, aortic and mitral valve replacement with coronary artery bypass grafting, mitral valve replacement with bypass grafting, chronic type 1 dissection repair, aortic valve replacement, and atrial septal defect repair in 1 patient each. The blood conservation program employed in these patients included the use of (1) aprotinin (full Hammersmith regimen), (2) high-dose erythropoietin, (3) "maximal"-volume intraoperative autologous blood donation, (4) low-prime cardiopulmonary bypass, (5) exclusive use of intraoperative cell salvage, and (6) continuous reinfusion of shed mediastinal blood. There were no deaths in the JW group. Thromboembolic complications consisted of a transient posterior circulation stroke in only 1 patient (dissection repair). No blood or blood products were transfused compared with the transfusion of 5.1 +/- 7.8 units (mean +/- standard deviation) in the 100 primary coronary bypass patients in whom the blood conservation program was not employed.(ABSTRACT TRUNCATED AT 250 WORDS)

Erythropoietin in cardiac surgery.

Erythropoietin is the primary growth factor for red blood cells. A glycoprotein hormone synthesized by the kidneys, erythropoietin serves to increase red blood cell production in response to tissue hypoxia. It exerts its effect by increasing the numbers of erythroid progenitor cells in the bone marrow, and by increasing the rate at which their development is accomplished. With the introduction of recombinant erythropoietin in 1987, an important pharmacological agent became available for the manipulation of erythropoiesis. While used primarily for the treatment of the anemia of renal failure, recombinant erythropoietin has also shown usefulness in treating other types of anemias in which the endogenous erythropoietin response is insufficient. Perioperative use of the drug grew as a natural extension of this, and erythropoietin has been applied to correct preoperative anemia, augment autologous blood donation, and improve postoperative red cell recovery. Analysis of these perioperative clinical studies reveals success in these areas, but it also reveals that closer attention to the physiology of the natural response, and to the pharmacology of the recombinant product, might significantly improve results. Such an improvement in efficacy is both desirable and necessary when use of the drug is viewed in the setting of today's changing health care environment. By optimizing dosing schedules and targeting the drug to those most at risk for red cell transfusion, recombinant erythropoietin will likely become an important tool in efforts to achieve the elusive goal of bloodless cardiac surgery.

Sodium-N-butyrate induces cytoskeletal rearrangements and formation of cornified envelopes in cultured adult human keratinocytes.

The technique developed in our laboratory allows us to culture multilayered, stratified sheets of human keratinocytes, which can be used to cover the burn wounds of patients. Organization of cells in these cultures resembles stratum germinativum and stratum spinosum but there are only a few fully keratinized cells and the stratum corneum is not developed. Since the fully differentiated sheets may offer additional advantages as epidermal transplants, attempts were made to enhance the degree of differentiation in vitro. In the present study sodium-N-butyrate (NaB) was used as a differentiating agent and its effect on the cell cycle and cytoarchitecture of epidermal cells was investigated. Incubation of keratinocytes in the presence of 2.5 mM NaB induced the appearance of enucleated cornified envelopes, covering approximately 70-80% of the surface of the cultures. Their appearance correlated with a decrease in expression of keratin K13, previously shown to be inhibited during terminal differentiation of human keratinocytes. An increase in transglutaminase transferase activity was also observed. The induction of cornified layers also correlated with an increase in the amount of microfilament (MF)-associated actin. NaB also induced changes in the cell cycle distribution of the keratinocyte cultures. A decrease in the proportion of S and G1B phase cells was paralleled by an increase in G1A cells, maximally expressed 30-48 h following addition of the inducer. Interestingly, NaB also induced a cell arrest in G2 phase. These cell cycle perturbations preceded the onset of keratinocyte differentiation. The results indicate that the enhanced differentiation of human keratinocytes in the presence of NaB may serve as a means to produce epidermal sheets with improved properties for transplantation in a clinical setting. It also serves as an in vitro model system to study the interrelationships between biochemical events and cell cycle changes accompanying differentiation.