HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Greeley, W. J. Search for Related Content PubMed PubMed Citation Articles by Greeley, W. J.

Ann Thorac Surg 1998;65:S29-S30
© 1998 The Society of Thoracic Surgeons

Introduction

^a Department of Anesthesiology and Critical Care Medicine, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

Address reprint requests to Dr Greeley, Department of Anesthesiology and Critical Care Medicine, The Children’s Hospital of Philadelphia, 34th St and Civic Center Blvd, Philadelphia, PA 19104-4399

The many advances in the conduct of cardiopulmonary bypass together with improved surgical and anesthetic techniques have significantly improved the survival of children with congenital heart disease. However, there is still significant morbidity and mortality associated with cardiac surgical procedures in neonates and infants.

This supplement comprises the proceedings of a symposium, "Risk Assessment of Major Perioperative Issues in Pediatric Cardiac Surgery," held in Washington, DC, on May 7, 1997. An international group of expert clinicians and researchers convened to discuss strategies available for effective management of the major perioperative risk factors in pediatric surgical practice. Perioperative bleeding is a major risk factor affecting patient outcome and was the main focus of discussion at the symposium.

Hemostatic derangement due to cardiopulmonary bypass is of particular significance in pediatric cardiac surgery and may result in a more pronounced bleeding tendency than that seen in adult patients. Specific influences include a greater degree of hemodilution, the use of deep hypothermic circulatory arrest, the influence of cyanosis on hemostasis and coagulation, and the immature coagulation system of the neonate. These factors can exacerbate activation of the hemostatic and inflammatory cascades and the impaired platelet function that result from a period of extracorporeal circulation. Over the last decade, reports in the literature have highlighted two methods that have shown efficacy to improve hemostasis in pediatric cardiac surgical procedures: hemofiltration to concentrate the coagulation factors and attenuate the inflammatory reaction; and the serine protease inhibitor aprotinin to decrease hemostatic activation, improve platelet function, and reduce activation of the inflammatory cascades.

In contrast to the adult cardiac surgical population, in neonates and infants the action of aprotinin to reduce blood loss and the need for blood and blood-product transfusions has not been extensively investigated. Moreover, studies have been, in general, poorly randomized and controlled. Efficacy remains controversial, and comparisons between studies is not possible because of the use of different dose regimens, very nonhomogeneous populations and procedures, different heparin-protamine protocols, and differences in priming solutions.

Speakers at the symposium reviewed the published literature on efficacy and safety of aprotinin use in the pediatric population. A double-blind, placebo-controlled study of compassionate use of aprotinin in neonatal/pediatric surgical patients at two centers demonstrated a trend toward reduced blood and blood-product requirements, least evident in neonates and infants and particularly evident in patients undergoing repeat procedures. Aprotinin did not reduce drainage volumes in this pediatric population. However, when compared with placebo, aprotinin did appear to be safe, with no notable differences in the prevalence of adverse events or deaths. One specific patient group in whom aprotinin may be of benefit is the group of patients undergoing thoracic organ transplantation. A review of the literature and the speakers’ own investigations suggest that aprotinin is beneficial in pediatric lung transplantation and in redo heart transplantations, particularly in patients who have had previous sternotomy or previous transplantation. The repeat use of aprotinin appears to be safe and does reduce blood loss in retransplantation patients.

A pharmacoeconomic analysis of aprotinin use in children undergoing cardiac reoperations suggests that aprotinin is efficacious, safe, and cost-effective. Aprotinin-treated patients had significantly fewer exposures to banked-blood components, with no difference in overall complication rate. Aprotinin was also associated with a significant saving in patient charges for blood components, operating room time, and duration of hospitalization.

The symposium included content on the mode of action of aprotinin to block contact activation of coagulation mediated by kallikrein and to inhibit fibrinolysis. Biochemical data suggested that plasma levels of aprotinin necessary to inhibit activation of coagulation are not achieved in children, highlighting the need for better dosing schedules in the pediatric population. The action of aprotinin to reduce the whole-body inflammatory response to cardiopulmonary bypass and to improve organ outcome was discussed, and data were presented suggesting an action of aprotinin on endothelial function with a reduction in the plasma thrombomodulin level.

The question of whether the relative risk of an anaphylactic reaction to aprotinin might outweigh the benefit of the drug if given to previously sensitized patients was a further topic. This presentation, illustrated with specific case reports, reviewed the incidence of adverse reactions to aprotinin and the time course of the development of immunoglobulin G and immunoglobulin E antibodies against aprotinin. Recommendations for reducing the risk and sequelae of these adverse reactions were detailed.

Hemodilution is well recognized as a significant factor contributing to perioperative organ dysfunction in pediatric patients. The technique of modified ultrafiltration and its use, results, complications, and safety in pediatric cardiopulmonary bypass were a subject of the symposium. The presentation suggested that it probably results in improved cerebral metabolic recovery after deep hypothermic circulatory arrest, although the long-term benefit on neurobehavioral outcome is unknown. Improved pulmonary compliance in the immediate postbypass period is observed, but again, the benefit on outcome is as yet unclear.

A final major perioperative outcome issue discussed at the symposium focused on the neurologic sequelae associated with cardiac surgical procedures in young children. The studies presented strongly suggest that in infants undergoing open heart operations for complex congenital heart defects, low-flow bypass is associated with a better neurologic outcome than is deep hypothermic circulatory arrest and that the pH-stat strategy is associated with better outcome than the alpha-stat strategy when circulatory arrest is used.

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Greeley, W. J. Search for Related Content PubMed PubMed Citation Articles by Greeley, W. J.