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  • Baird 2007 Gandhi Annthoracic Surg

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    32 Ansichten7 Seiten

    Baird 2007 Gandhi Annthoracic Surg

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    Pabintmc CaRDInG URGENT QD teeiaierscre nn torent ee te emcee ts member subscription to the journal 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, and Frank A. Pigula, MD Cikden’s Hospi Putsburgh, Pusbaegh, Pennsylvania Background. Anticoagulation during pediatric extracor- poreal membrane oxygenation (ECMO) is accomplished. by titrating heparia administration to maintain an acti- vated clotting time (ACT) of between 180 and 220 acc nds. We hypothesized that an ACT of 180to 220 seconds results in inadequate anticoagulation during, pediatric ECMO and that increased heparin levels will lead to increased survival. Methods. A retrospective review was conducted of 604 consecutive pediatric ECMO patients ata single tion between 1960 and 2001, Multiple logistic regressions were used to assess the impact on survival of ACT, heparin, age, weight, diagnosis, and previous surgery. Results, There were 319 survivors (578%), and 255 (42.2%) nonsurvivors. Mean hours on ECMO were 162 134 (range, 3 to 957 hours), mean ACT was 227 + 50 seconds (range, 158 to 620 seconds), and the mean hourly heparin dose was 45 = 21 Unkg ange, 6 to 134 Uke), Regression analysis indicated ‘that increased heparin jediatric extracorporeal membrane oxygenation (ECMO) has been used to treat thousands of neu- nates and children with severe respiratory distress and congenital heart disease. Despite many technical ad vances and the refinement in management techniques, ‘we continue to be faced with the challenge of balancing anticoagulation. An ideal anticoagulant would avoid thrombotic and hemorrhagic complications, be readily titratable, and easy to control. Uniractionated heparin (UFH) has been available com: mercially for more than half a century and is the most ‘Reseed Tor puttin Sop 16 206 Prantid at h orystcondAadal Mesing of The Soi of Those Surgeons Chap Jan 50-Fb 1, 2006, Adres corepondence to Dr Figs, Department of Crise Sngey oder 275 Boson Children's Hosp Heston MA IZI, cma © 2407 by The Society of Thrace Surgeons Pablched by Bests tne 7: Dovenlado from otsnetjoumals. org by on November 12, Boston, Boston, Massachuscts; St Louls Children's Hospital, St, Lous, Missouri and Children’s Hospital .dministration was predictive of survival (p < 0.0001), independent of all other variables. The ACT was not 2 predictor of survival (j) = 0.096). Although previous ‘surgery was independently associated with an increased likelihood of ECMO death (p < 0.000, increased heparin administration again exerted a survival advantage ow. Conclusions. Adherence to the recommended ACT of 180 to 220 seconds in pediatric ECMO patients may result in inadequate anticoagulation. Survival is improved by increased heparin administration independent of the ACT. The ACT may be too inseasitive to maintain adequate long-term systematic anticoagulation, and other methods, such a5 heparin levels or functional parameters such as antieFactor Xa activity or thrombin ‘generation, should be investigated. (Ann Thorac Surg 2007;85:912-20) © 2007 by The Society of Thoracic Surgeons widely used anticoagulont. It quickly binds to and acti- vates antithrombin, which then inhibits activated factors in the intrinsic clotting cascade. Its short half-lite and the fact that its action can be reversed readily with protamine ‘make itan almost ideal antithrombotic agent. The ability to aceuratcly monitor heparin anticoagulation has been dificult, however In 1966, owing to the ack of epecific and sensitive tests for determining coagulation, activated coagulation time (ACT) of whole blood was created. Two milliliters of ‘venous blood were placed into a warmed tube containing diatomaceous earth, which was tilted and observed for clot formation [1]. It has subsequently been applied to ‘monitor heparin therapy in a multitude of settings. Soon after its introduction, Bull and colleagues [1] began investigating ACT protocols for heparin therapy used during, extracorporeal circulation for open heart surgery and made several important fundamental obser- 0003.1875/071832.00 ot 40.016), athorscsur 2609.98 2010 vations. They first observed that similar ACTS indifferent patients resulted in inadequate heparinization or neu tralization of heparin by protamine. Next, they recog sized that the amount of heparin required to produce an arbitrary prolongation of ACT varied threefold between pationts. Finally, the rapidity with whieh heparin disap- [pears from the blood may vary fourfold, To correct for the Inherent inadequacies of the ACT test, dose-response: curves relating heparin dosage and effective ACT were achieved, making, it possible to maintain safer ranges fof anticoagulation during extracorporeal circulatory support [2 31 iva recent study by Graves and colleagues [4] survey- ing ll active neonatal ECMO programs in the United States, ACT was the predominant anticoagulation test, but there was no consensus on the type of heparin, frequency of ACT testing, or methods for dealing with abnormal ACT results. Some programs had 2 minimum heparin dose despite ACT levels, some strictly followed ACT results, and others discontinued heparin for various reasons [6], Furthermore, previous studies suggest that an ACT rate of between 180 to 220 seconds results in adequate anticoagulation during extracorporeal circula- tion [5]. The purpose ofthis study was to determine the relationships between heparin dose, ACT, and survival Patients and Methods Owing to the large retrospective nature of the study, individual consent was waived and Institutional Review Board approval was granted. General Extracorporeal Membrane Oxygenation Protocols Retrospectively reviewed were 604 consecutive pediatric ECMO patients at Children’s Hospital of Pittsburgh from 1980 t0 2001. ECMO was initiated for respiratory failure, “cardiac faire, and sepsis when all ofhcr options filed ‘The causes Tor respiratory failure in these patients were meconium aspiration, congenital diaphragmatic hernia, primary pulmonary hypertension, and pneumonia, The ‘ariac patients had undergone primary cardiac repair, omthotopic heart transplant. snd rage 1 WaMspTaT ‘Venoarteral ECMO was used in all patients with size-appropriate cannulas, For all primary respiratory failure patients, che right internal jugular vein was can- ‘ulated, and posteardiotomy patients were routinely can ulated through the right atrium and aorta. Farly in the ‘experience, al children were supported with roller pump ECMO, whereas during the last half of the experience, children weighing more than 15 kg were supported with centrifugal pumps. ECMO flows were initiated at 100 (0 150 mld min), Anticoagulation Methods Patients received an unfractionated heparin (UFH) load- Ing dose of 100 Urkg immediately betore cannulation, with an additional 100 Urkg in the blood prime. Initial ACTs were checked immediately after cannulation and allowed to drift down to the target ACT of 180 to 220 mamDer aL 913 PEDIATRIC ECMO: ACT, HEPARIN PREDICTABILITY Table 1. Comparison of ECMO Duration. ACTS, and Hparin Requirements Between Strotoors and Nonsurvivors Survivors? Nonsurvivons_p Value ‘Al patients (=) 3 ECMO time (hours) T97= 166 OO ACT (second) = 962 036 Heparin (Uilkg -b) 4922039222 <000T No previous surgery (0) 322 201 ECMO time (hours) 175228 2k aT ane ACT (se) 26940-28585 Heparin (Uitke “4921938228 0am" Previous gery (9) a 5 ECMO time (hous) 08-267 TBH 18003 [ACT (second) mae eras OAS Heparin (Uiikg hy) 502753619 OT ata eprsin the man 2 SD, StaiicallySigucat sam pe Sadat ot ACT = activate tng tines ECMO ~ eatescaeporcal membrane seconds. The heparin dose was then adjusted based on ACT levels as well as the perceived bleeding risk. Whole blood ACTS were determined hourly for the first 48 hours, every 4 hours after 7 hours, and as necessary thereafic, Prom 198) Through 1990, the ACT was deter= ‘mined with Celite diatomaceous earth (Celite Corpora- tion, Goleta, CA) as the primary reagent, and the Hemo- chron JR (international Technidyne, Edison, NJ), which tuses kaolin‘silca reagents, was used betwcen 1990 and 2001. Although the “target” ACT veas 180 to 220 seconds, modifications were made at the discretion of attending, physicians, and ACTS were sometimes modilied to reflect the clinical situation such as bleeding, or hypercoagula~ bility and thrombus formation in the cteut, which often requited replacement of the circuit. Statistical Analysis ACT and heparin doses reflect an average over the ‘course of 24 hours and 7 days. Continuous dal, inchad- ing ECMO duration, heparin dose, and ACTS, were tested for normality using the Kolmojguroy-Smirnoys83- Ustic, and no significant departures were detected Therefore, theve variables were compared between sur vivors and nonsurvivors using the two-sample Student Feat and stratified according to previous surgery slats ‘The Pearson prucemumen ulation belie) was ised fo sutmarize the aasociation between heparin dose and ACTS. ee = “Muliple sicpwise logistic regressions were applied to determine the independent predicturs of patient survival, considering ACT level, heparin dose, ECMO duration, ‘nd previous surgery status as variables in the mulivar- inte analysis. Based on the plotted empirical data, model fing for determining the most aceurte Functional rela- tionship between heparin dose and survival inchided testing whether a quadratie ht captured the relationship better than a linear 8 [. Dovinloadod from atsctsnetoumals.org by en November 12,2010 M = = Se 914 pamper aL Sori ‘Table 2. Univariate and Multivariate Predictors of Patient Survival Univariate ‘Revs of Multivariate Logistic Regression A Variable se oR 35% Cl pValue EMO duration thous) 001 09 0997-0999 os ACT (Ge) ois 0996 ag-.0n, 19% Heparin (10 Uffkg » oon" 0050 uz 3-142 on" No previous surgery om 0289 an 212-667

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