Anticoagulation and Pediatric Extracorporeal Membrane Oxygenation: Impact of Activated Clotting Time and Heparin Dose on Survival Christopher W. Baird,

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Anticoagulation and Pediatric Extracorporeal Membrane Oxygenation: Impact of Activated Clotting Time and Heparin Dose on Survival Christopher W. Baird, MD, David Zurakowski, PhD, Barbara Robinson, MD, Sanjiv Gandhi, MD, Leighann Burdis-Koch, RCP, Joseph Tamblyn, RCP, Ricardo Munoz, MD, Karol Fortich, MD, Frank A. Pigula, MD The Annals of Thoracic Surgery Volume 83, Issue 3, Pages 912-920 (March 2007) DOI: 10.1016/j.athoracsur.2006.09.054 Copyright © 2007 The Society of Thoracic Surgeons Terms and Conditions

Fig 1 Scatter plot shows the moderate positive linear correlation between heparin dose and activated clotting time (ACT) (r = 0.48, p < 0.001). Similar moderate correlations were observed in both survivors (open triangles) (r = 0.52, p < 0.001) and nonsurvivors (filled triangles) (r = 0.43, p < 0.001). Regression line (solid line) based on all patients is drawn according to the derived linear equation for estimating ACT from heparin dose: y = 0.95x + 180. (ECMO = extracorporeal membrane oxygenation.) The Annals of Thoracic Surgery 2007 83, 912-920DOI: (10.1016/j.athoracsur.2006.09.054) Copyright © 2007 The Society of Thoracic Surgeons Terms and Conditions

Fig 2 Empirical histograms show the percentage of patients in each of 10 intervals of heparin dose for survivors (open bars) and nonsurvivors (patterned bars). For example, approximately 14% of survivors and 40% of nonsurvivors had heparin levels of less than 30 U/(kg · h) on extracorporeal membrane oxygenation (ECMO). On the other hand, 26% of survivors and 14% of nonsurvivors had heparin doses exceeding 60 U/(kg · h) on ECMO. Superimposed is a curve that shows actual percentages of patient survival for each of 10 intervals of heparin dose (circles). For instance, the percentage of patients surviving who received 21 to 30 U/(kg · h) on ECMO was 43%, whereas 70% of patients who received 51 to 60 U/(kg · h) survived, 88% who received 61 to 70 U/(kg · h) and 72% survived who received 81 to 90 U/(kg · h) on ECMO. The data indicate a survival advantage for higher levels of heparin dose up to 70 U/(kg · h) on ECMO and then a slight decline in survival for patients who received higher amounts (U-shaped pattern). The Annals of Thoracic Surgery 2007 83, 912-920DOI: (10.1016/j.athoracsur.2006.09.054) Copyright © 2007 The Society of Thoracic Surgeons Terms and Conditions

Fig 3 Relationship between heparin dose and the predicted probability of survival where the theoretic curve depicts greater protection with an increased amount of heparin usage (p < 0.001) up to 70 U/(kg · h) on extracorporeal membrane oxygenation (ECMO) and then a decline in the predicted survival for doses greater than 70 U/(kg · h) on ECMO. However no statistically significant patient survival benefit based on differences inactivated clotting times (ACTs, circles) (p = 0.36), where the probability of survival is estimated to be 58% across the range of possible values of ACT. The theoretic curve for heparin (triangles) is based on a quadratic fit to the data, suggested by the U-shaped pattern indicated in Figure 2, and confirmed by logistic regression analysis to follow a nonlinear relationship. The Annals of Thoracic Surgery 2007 83, 912-920DOI: (10.1016/j.athoracsur.2006.09.054) Copyright © 2007 The Society of Thoracic Surgeons Terms and Conditions