Celia D'Errico

The efficacy and cost of aprotinin in children undergoing reoperative open heart surgery.

We performed a prospective, randomized, placebo-controlled, double-blind trial to assess the efficacy of aprotinin in 61 children (median age 3.7 yr) undergoing reoperative open heart surgery (OHS). Three demographically similar groups were studied: large-dose aprotinin (ALD), small-dose aprotinin (ASD), and placebo (P). Over the first 24 postoperative hours fewer patients in the aprotinin groups received packed red cells (ALD, 53%; ASD, 89%; and P, 95%; P = 0.001), platelets (ALD, 32%; ASD, 50%; and P, 65%; P = 0.04), and fresh frozen plasma (ALD, 16%; ASD, 17%; and P, 60%; P = 0.003) than placebo patients. Most importantly, aprotinin patients had fewer exposures to banked blood components (ALD, median 1 U; and ASD, median 2 U) than P (median 6 U; P = 0.001), with no difference in overall complication rate. Use of aprotinin was associated with a savings in the patient charges for blood components, operating room time, and duration of hospitalization. In conclusion, aprotinin decreased the number of units of banked blood components used during the first 24 postoperative hours in reoperative pediatric OHS. Aprotinin thus decreases the risks associated with exposure to banked blood components and reduces hospital charges. (Anesth Analg 1996;83:1193-9)

The activated coagulation time: Suitability for monitoring heparin effect and neutralization during pediatric cardiac surgery

OBJECTIVES To determine how the stage of surgery affects the relationship between activated clotting time (ACT) and heparin effect in children undergoing cardiac surgery using cardiopulmonary bypass (CPB) and to compare the results of ACT determinations made with two different coagulation timers using different clot detection technologies and activator compositions. DESIGN Prospective, paired observation. SETTING Tertiary care childrens hospital affiliated with an academic medical center. PARTICIPANTS Fifty-eight children scheduled for nonprimary cardiac surgery. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS ACTs were measured by two different commercially available automated coagulation timers (Hepcon Hemostasis Management System [HP] and the Hemochron model 801 [HM]) at four different time points over the course of cardiac surgery requiring CPB in patients ranging in age from 0.16 to 19 years. Simultaneous determinations of whole blood heparin concentration using heparin-protamine titrations were made as well. When the two methods of ACT determination were compared, baseline ACTs were not significantly different. HP ACT prolongation after heparin administration but before bypass was significantly less than HM ACT prolongation (median ACT range HM > or = 999 seconds; HP, 560 to 679; p = 0.006). Twenty-one percent of the HP ACTs and none of the HM ACTs fell below the 480 seconds required at this institution for the initiation of CPB (p = 0.008). Both instruments showed a significant further prolongation of ACT after initiation of bypass (median ACT range HP > or = 999 seconds; HM > or = 999; p < 0.001 for both), whereas the heparin concentration decreased significantly (before, 3.5 +/- 0.2 U/mL; after, 2.7 +/- 0.1; p < 0.001). After termination of CPB and heparin neutralization, no significant difference between the ACTs was found. However, four HP ACTs were > or = 999 seconds despite simultaneous HM baseline values and whole blood heparin concentrations of zero. Heparin concentration correlated with ACT prolongation using both the HM (Spearman p = 0.36; p = 0.02) and the HP (Spearman p = 0.57; p = 0.0025) instruments before, but not 10 minutes after, initiation of bypass. CONCLUSIONS In pediatric cardiac surgery, the relationship between ACT and heparin concentration changes depending on when during the surgery the ACT is measured. ACT prolongation in children anticoagulated for CPB correlates poorly with heparin concentrations during CPB. HP and HM ACT tests are not interchangeable. The HM ACT is a better indicator of heparin neutralization than the HP ACT. On the other hand, continued prolongation of the HP ACT after heparin neutralization may be related to risk of postoperative hemorrhagic complications. If devices from different manufactures are freely substituted for each other, clinical practice may be altered in an uncontrolled manner.

Age-related differences in heparin sensitivity and heparin-protamine interactions in cardiac surgery patients.

OBJECTIVE The present study was conducted to determine how children and adults differ (it at all) with respect to sensitivity to heparin activity and heparin-protamine interactions during cardiac surgery requiring cardiopulmonary bypass (CPB). DESIGN A prospective study of both children and adults undergoing CPB. SETTING A tertiary care academic medical center between July 1992 and October 1994. PARTICIPANTS Ninety patients who had cardiac or aortic arch surgery using CPB. The median age of the entire study sample was 15.8 years (range 2 months to 72 years). INTERVENTION Data were obtained using the Medtronic Hemotec Hepcon Hemostasis Management System (Englewood, CO). An ex vivo heparin dose-response (HDR) curve was generated for each patient before skin incision to determine the target heparin concentration (THC) needed to achieve an activated coagulation time (ACT) of at least 480 seconds. Protamine dose was determined on the basis of whole blood heparin concentration estimated by means of a heparin-protamine titration. MEASUREMENTS AND MAIN RESULTS The study population was divided into four groups based on age: infants (< 1 year), preschool (1 to 5 years), school-age (5 to 14 years) and adults (> 14 years). The mean +/- SD THC for the preschool group was 4.0 +/- 1.1; for infants, 3.3 +/- 0.7; for school-age, 3.1 +/- 0.7; and for adults, 3.4 +/- 0.7. The initial dose of heparin needed to achieve this THC (mean +/- SD) was significantly higher in infants (578 +/- 220 U/kg) and preschool children (477 +/- 159 U/kg) than in school-age children (327 +/- 57 U/kg) and adults (332 +/- 64 U/kg). The ratio of protamine to heparin was significantly higher in adults (1.4 +/- 0.5) and school-age children (1.3 +/- 0.6) than in infants (1.1 +/- 0.7) and preschool children (1.1 +/- 0.4). CONCLUSIONS Pre-school children are less sensitive to heparin but also display a wider range of sensitivity. The data in this study support the use of 300 U/kg of heparin before CPB in patients > or = 5 years but suggest that heparin requirements may be greater in the younger patient who may require as much as 500 U/kg to achieve what is believed to be an appropriate target heparin concentration for initiating CPB.

Should pregnancy testing be routine in adolescent patients prior to surgery

The reliability of the preoperative history obtained from adolescent patients in ruling out pregnancy was prospectively evaluated.Four hundred forty-four patients who underwent 525 procedures were questioned preoperatively regarding the possibility of pregnancy. Regardless of the history, a urine pregnancy test was ordered in accordance with institutional practice. In 508 cases, patients denied the possibility of pregnancy. Eight patients stated that they might be pregnant, and in six cases the parents responded for the patients and denied the possibility of pregnancy. Seventeen patients were not tested due to patient/parent refusal (n = 9) or inability to void (n = 8). All pregnancy tests were negative except one that was questionably negative. This patient had denied the possibility of pregnancy and had been anesthetized prior to test results. Follow-up revealed that the patient was not pregnant. Our data demonstrate that the preoperative history obtained from adolescent patients at our institution regarding their pregnancy status was in agreement with pregnancy test results. We suggest that a detailed history regarding last menstrual period, contraception, sexual activity, and the possibility of pregnancy be obtained in all postmenarchal patients presenting for surgery. Although in other populations history and pregnancy testing did not agree 100% of the time, for our adolescent population, human chorionic gonadotrophin (HCG) testing appears to be necessary only if indicated by patient history. (Anesth Analg 1996;83:854-8)

Oral granisetron for strabismus surgery in children.

PurposeTo determine the efficacy of oral granisetron in preventing postoperative vomiting (POV) following strabismus repair in children.MethodsIn a randomized, double-blind, placebo-controlled trial, 73 pediatric patients received either placebo, 20 μg·kg−1 or 40 μg·kg−1 granisetronpo 20 min before induction of anesthesia. No premedication was given, induction was with halothane and all children breathed spontaneously via a laryngeal mask airway. Maintenance was with isoflurane without the use of opioids. Ketorolac and acetaminophen were used for analgesia. The number of episodes and the severity of vomiting and retching were recorded for the first 24 hr postoperatively, as was the use of rescue antiemetics.ResultsGranisetron 20 μ·kg−1 and 40 μg·kg−1 were more effective than placebo in reducing the incidence of POV during the first 24 hr (29% in both the granisetron groupsvs 84% in the placebo group,P < 0.05). In addition, the number of children experiencing severe vomiting (≥ 3 episodes) was reduced in the granisetron 20 μg·kg−1 and 40 μg·kg−1 groups compared with placebo (4%, 8% and 48% respectively,P < 0.05). Patients in the granisetron group were discharged home earlier ( 105 min vs 124 min,P = 0.04). There was no difference in the incidence of POV between the two granisetron groups.ConclusionPreoperative oral granisetron in a dose of 20 μg·kg−1 provided effective prophylaxis against POV in children undergoing stabismus repair.RésuméObjectifDéterminer l’efficacité du granisétron, administré par voie orale, à prévenir les vomissements postopératoires (VPO) suivant la correction du strabisme chez des enfants.MéthodeLors d’un essai contre placebo, en double aveugle, 73 patients pédiatriques ont reçu soit un placebo, soit 20 μg·kg−1 ou 40 μg·kg−1 de granisétronpo 20 min avant l’induction de l’anesthésie. Aucune prémédication n’a été administrée, l’induction s’est faite avec de l’halothane et l’anesthésie a été maintenue chez tous les enfants en utilisant la ventilation spontanée au moyen d’un masque laryngé. On a maintenu l’anesthésie avec de l’isoflurane sans employer d’opioïdes. Les analgésiques étaient du kétorolac et de l’acétaminophène. Le nombre et la sévérité des épisodes de vomissements et de haut-le-coeur ont été notés, pendant les vingt-quatre premières heures postopératoires, de même que le recours à des antiémétiques.RésultatsLe granisétron à 20 μg·kg−1 et à 40 μg·kg−1 a été plus efficace que le placebo en réduisant l’incidence des VPO pendant les vingt-quatre premières heures (29 % dans les deux groupes qui ont reçu du granisétron vs 84 % dans le groupe qui a reçu le placebo, P < 0,05). De plus, le nombre d’enfants qui ont eu des vomissements sévères (≥ 3 épisodes) était réduit dans les groupes recevant du granisétron en doses de 20 μg·kg−1 et de 40 μg·kg−1 à comparer au groupe recevant le placebo (4 %, 8% et 48 % respectivement,P < 0,05). Les patients du groupe granisétron ont reçu leur congé plus tôt ( 105 min vs 124 min,P = 0,04). Il n’y a pas eu de différence entre les deux groupes qui ont reçu du granisétron concernant l’incidence des VPO.ConclusionLadministration orale préopératoire de granisétron en doses de 20 μg·kg−1 prévenait de façon efficace les VPO chez les enfants ayant subi une correction de strabisme.

Pro: The routine use of aprotinin during pediatric cardiac surgery is a benefit

ORE THAN HALF of the children undergoing cardiopulmonary bypass (CPB) in North America are younger than 1 year old, and neonates comprise approximately 36% of this group. 1 Many of these children undergo multiple-stage reconstructive procedures as well as repeat operations to replace conduits and valves, which are often performed at low temperatures with long bypass times. Bleeding complications are common and are secondary to increased tissue friability, extensive suture lines, and increasingly complicated surgical repairs. In addition, clotting mechanisms are incompletely developed in infants, and they tolerate hemorrhage and tamponade poorly. These issues underscore the need to develop therapeutic modalities directed at the attenuation of the inflammatory reaction and coagulation cascade initiated by CPB. Several studies in children suggest that aprotinin is beneficial for pediatric patients during cardiac surgery. Aprotinin, isolated in 1930, is a serine protease inhibitor that has been used in numerous clinical settings, including acute pancreatitis, adult respiratory distress syndrome, trauma, and septic shock. In the 1960s, aprotinin was used in adult cardiac surgery in an attempt to reduce excessive blood loss thought to be due to increased fibrinolysis. By 1984, the benefits of aprotinin in pediatric CPB were being studied, and decreases in postoperative blood loss and fibrin split products were demonstrated. 2 Attention has turned to aprotinins potential as a kallikrein inhibitor to attenuate the inflammatory response associated with CPB. Numerous studies have demonstrated a reduction in blood loss associated with aprotinin use in pediatric CPB. Herynkopf et aP noted that homologous donor exposure was decreased by about half in the patients who received aprotinin. A study of children undergoing repair of tetralogy of Fallot showed significant decreases in the total volume of blood loss and blood transfused. 4 Penkoske et al 5 showed similar decreases in blood loss, volume of transfusion, and number of units transfused. In pediatric lung transplants, Jaquiss et al6 demonstrated that high-risk patients receiving aprotinin bled less than, or similar to, low-risk transplant patients who had not received aprotinin. In a study at this institution, aprotinin decreased the number of