Correlations between activated clotting time values and heparin concentration measurements in young infants undergoing cardiopulmonary bypass.

BACKGROUND: Monitoring heparin concentration along with the activated clotting time (ACT) may provide a more accurate guide for the administration of heparin to infants during cardiopulmonary bypass (CPB). However, standard laboratory assays of heparin concentration (antifactor Xa heparin concentration) require plasma instead of whole blood, and results are not immediately available to clinicians. Alternatively, measurements of whole blood heparin concentration may be performed at the bedside using an automated protamine titration device, the Hepcon instrument (Hepcon Hemostasis Management System Plus; Medtronics, Minneapolis, MN). The purpose of this investigation was to compare ACT measurements from 3 commercially available instruments and bedside measurements of whole blood heparin concentration using the Hepcon instrument with laboratory measurements of antifactor Xa plasma heparin concentration in infants younger than 6 months of age undergoing CPB. METHODS: Forty-four pediatric patients younger than 6 months of age scheduled for elective cardiac surgery requiring CPB were enrolled in this prospective study. Blood samples were drawn 3 minutes after the initial heparin bolus and immediately before the termination of CPB to obtain measurements of heparin anticoagulation. Kaolin-activated ACTs were performed with the Hemochron (International Technidyne Corporation, Edison, NJ), Hepcon, and i-STAT (i-STAT Corporation, East Windsor, NJ) instruments. Whole blood heparin concentration was measured using the Hepcon instrument. Plasma heparin concentration was measured using an antifactor Xa chromogenic substrate assay. RESULTS: Immediately after the initial heparin bolus, none of the ACT values correlated with plasma heparin concentration. When measured immediately before the termination of CPB, only the i-STAT ACT showed a moderate correlation. Conversely, bedside measurements of whole blood heparin concentration showed satisfactory agreement with laboratory measurements of plasma heparin concentration at both time points (concordance correlation coefficients 0.30 and 0.67, respectively). There is a bias in that antifactor Xa-measured plasma heparin concentration tends to be higher than Hepcon-measured whole blood heparin concentration. CONCLUSIONS: In infants younger than 6 months old undergoing CPB, caution is warranted when using ACT values as the sole indication of adequate heparin anticoagulation. In general, ACT prolongation correlates poorly with plasma heparin concentration. Only i-STAT ACT values showed a moderate correlation when measured immediately before the termination of CPB. Alternatively, bedside measurements of whole blood heparin concentration measured by the Hepcon instrument agreed well with antifactor Xa laboratory measurements. Our data support the clinical utility of bedside measurements of heparin concentration to provide timely, convenient, and accurate measurements of heparin concentration in these infants.

The impact of aprotinin on postoperative renal dysfunction in neonates undergoing cardiopulmonary bypass: a retrospective analysis.

BACKGROUND: Recent concern about the safety of aprotinin administration to adults has led to its suspension from worldwide markets. However, few studies have examined its safety in pediatric patients. Studies in children evaluating aprotinin's safety have been hindered by the heterogeneity of pediatric patients and the inconsistency of clinical protocols. In this investigation, we retrospectively reviewed 200 neonatal cardiac surgical cases performed at our institution to examine the safety of aprotinin, focusing on postoperative renal dysfunction, using a consistent aprotinin dosing protocol. METHODS: Two-hundred consecutive neonates scheduled for palliative or corrective congenital cardiac surgery requiring cardiopulmonary bypass (CPB) from January 1, 2005 through February 28, 2007 were included in this retrospective investigation. Preoperative, intraoperative and postoperative data were collected and analyzed. Markers of safety included 72-h postoperative renal dysfunction, need for dialysis (peritoneal or hemodialysis), thrombosis and in-hospital mortality. RESULTS: Neonates were divided into those who received aprotinin (aprotinin group; n = 156) and those who did not (no aprotinin group; n = 44). Twenty-four and 72-h postoperative serum creatinine levels were significantly greater than baseline levels in both groups. The degree of change in creatinine levels was highly significant and similar between the two groups. A larger percentage of neonates in the aprotinin group developed renal dysfunction, although this difference was not statistically significant. Stepwise logistic regression, assessing the impact on renal dysfunction of all variables that indicated significance between neonates who did or did not receive aprotinin and between neonates who did or did not develop renal dysfunction, identified CPB time and age as significant predictors of postoperative renal dysfunction. All neonates who developed postoperative renal dysfunction had a CPB time of more than 100 min regardless of the use of aprotinin. Additionally, using this subset, similar percentages of renal dysfunction occurred in both groups. A second multivariable regression analysis to simultaneously account for the predictors of CPB time, age and aprotinin administration found CPB time to be the only significant predictor of renal dysfunction. Incidences of postoperative dialysis, postoperative thrombosis and in-hospital mortality were not statistically significantly different between the aprotinin and the no aprotinin groups. CONCLUSION: The occurrence of postoperative renal dysfunction in neonates was more significantly predicted by the duration of CPB than by the intraoperative administration of aprotinin. CPB times of more than 100 min appeared to be a critical marker for the development of postoperative renal dysfunction. Randomized prospective trials are needed to confirm the validity of our retrospective findings.

A comparison of heparin management strategies in infants undergoing cardiopulmonary bypass.

BACKGROUND: Recent investigations in adult patients have suggested that a heparin concentration-based anticoagulation protocol for heparin administration during cardiopulmonary bypass (CPB) significantly reduced hemostatic activation when compared with standard weight-based heparin doses. Reductions in hemostatic activation during CPB could be particularly beneficial in pediatric patients in whom CPB-related coagulation issues are complex and influenced by many variables. However, information regarding heparin levels during CPB and their correlation to hemostatic activation is lacking in children. In this investigation, we compared a patient-specific heparin concentration-based heparin management protocol with a standard weight-based protocol in infants <6-mo-of-age. The efficacy of these two protocols was assessed by comparisons of heparin concentration, levels of biochemical markers of hemostatic activation, and clinical outcome. METHODS: Twenty-five infants <6-mo-old scheduled for primary, elective repair of a congenital heart defect were enrolled in this study. Patients were randomized to receive either 400 U/kg of heparin (control group) or a patient-specific heparin dose calculated by the Hepcon Hemostasis Management System Plus (Hepcon HMS; Medtronic, Minneapolis, MN; intervention group). Heparin concentrations were compared between the two groups at predetermined intervals. Blood samples for biochemical markers of hemostatic activation were collected before and after CPB, and measurements of clinical outcome were recorded. RESULTS: Infants in the intervention group received a larger total heparin dose than infants in the control group. Heparin concentrations after the initial heparin dose and 30 min into CPB were similar between groups; however, at the start of rewarming and at the termination of CPB, infants in the intervention group had significantly higher heparin concentrations than infants in the control group. Infants in the intervention group also generated less F1.2 and consumed less factor VIII than infants in the control group. Clinically, however, infants in the intervention group received one more donor exposure from the administration of blood products post-CPB. CONCLUSION: A heparin concentration-based heparin management protocol in infants <6-mo-old resulted in higher, more constant heparin concentrations during CPB than a standard weight-based protocol. Furthermore, higher heparin concentrations were associated with greater suppression of hemostatic activation, as measured by less generation of thrombin and less consumption of factor VIII. Our findings demonstrate that use of a patient-specific heparin concentration-based protocol for heparin administration during CPB in infants may attenuate hemostatic activation. However, further research is needed to determine if this protocol has clinically beneficial hemostatic effects.