Anticoagulation Monitoring in Pediatric Patients
Transcription
Anticoagulation Monitoring in Pediatric Patients
5/5/2015 Introduction Anticoagulation Monitoring in Pediatric Patients Undergoing Extracorporeal Membrane Oxygenation (ECMO) Julie Dang, Pharm.D. PGY-1 Pharmacy Practice Resident Detroit Medical Center, Children’s Hospital of Michigan The speaker has no actual or potential conflicts of interest in relation to this presentation. • ECMO is a form of prolonged cardiopulmonary bypass to support patients with respiratory and/or cardiac failure refractory to conventional treatment • Improvement in ECMO technology, research, and outcomes continues to grow through collaborative efforts of the Extracorporeal Life Support Organization (ELSO) Maslach-Hubbard A, Bratton SL. World J Crit Care Med. 2013;2(4):29-39. ECMO Indications Goals of ECMO • • • • • • • • • Decrease respiratory and/or cardiac work load • Increase healing time • Minimize complications Meconium aspiration syndrome Persistent pulmonary hypertension Congenital diaphragmatic hernia Severe sepsis Severe respiratory distress Bridge to transplant Post-surgical repair of congenital cardiac defects Cardiopulmonary support for organ donation Maslach-Hubbard A, Bratton SL. World J Crit Care Med. 2013;2(4):29-39. Photo adapted from: http://s593.photobucket.com/user/stevs102/media/Rhys/Rhys_152.jpg.html ECMO Statistics Extracorporeal Life Support Organization. ECLS Registry Report International Summary. Published January 2015. Buck ML. Clin Pharmacokinet. 2003;42(5):403-17. 1 5/5/2015 Complications of ECMO Hemostatic Balance During ECMO • • • • • • Continuous contact between blood and ECMO circuit leads to chronic hemostatic activation Hemorrhage/hemolysis Thrombosis Neurologic deficits Acute kidney injury Infection – Hypercoagulable state • Anticoagulation is necessary to prevent thrombotic complications – Anticoagulant of choice: unfractionated heparin (UFH) • Bleeding complications may occur due to coagulation instability in critically ill patients Maslach-Hubbard A, Bratton SL. World J Crit Care Med. 2013;2(4):29-39. Anticoagulation and ECMO • Anticoagulation management varies across each ECMO centers • No definitive guidelines or consensus for the most appropriate management of anticoagulation during ECMO available Extracorporeal Life Support Organization. ELSO Anticoagulation Guideline. Published 2014. Annich G, Adachi I. Pediatr Crit Care Med 2013; 14:S37-S42. Anticoagulation and ECMO Activated Clotting Time (ACT) • Measures clotting time of whole blood • Goal: 180-220 seconds Activated Partial Thromboplastin Time (aPTT) • Measures time to clot formation within intrinsic pathway • Goal: 48-78 seconds Anti-Factor Xa (anti-Xa) levels • Measures heparin effect and factor Xa inhibition • Goal: 0.3-0.7 units/mL Antithrombin III (ATIII) Levels • Binds to heparin to inhibit factor Xa and thrombin formation • Goal: 50-120% Extracorporeal Life Support Organization. ELSO Anticoagulation Guideline. Published 2014. Annich G, Adachi I. Pediatr Crit Care Med 2013; 14:S37-S42. Extracorporeal Life Support Organization. ELSO Anticoagulation Guideline. Published 2014. Annich G, Adachi I. Pediatr Crit Care Med 2013; 14:S37-S42. Learning Question #1 Learning Question #2 • Which of the following is the anticoagulant of choice for patients on ECMO? • Which of the following is not an appropriate laboratory test to utilize to ensure efficacy of anticoagulation in ECMO patients? A. B. C. D. Low molecular weight heparin Vitamin K antagonists Unfractionated heparin Direct thrombin inhibitors A. B. C. D. Anti-Factor Xa Level (Anti-Xa) Activated Clotting Time (ACT) Activated Partial Thromboplastin Time (aPTT) Mean Corpuscular Volume (MCV) 2 5/5/2015 Anticoagulation Monitoring in Pediatric Patients Undergoing ECMO Goal Anticoagulation Monitoring in Pediatric Patients Undergoing Extracorporeal Membrane Oxygenation (ECMO) • To evaluate heparin infusion rate changes based on various laboratory coagulation parameters • To assess efficacy in preventing thrombotic and bleeding complications Julie Dang, Pharm.D.1 Preceptor: Joanna Ditouras, Pharm.D.1 Co-Investigators: Michelle Veenstra, M.D.2, Paul Stockmann, M.D.2, and Kelly Holzhausen, Pharm.D.1 1Department of Pharmacy Services, Children’s Hospital of Michigan, Detroit, Michigan Pediatric Surgery, Children’s Hospital of Michigan, Detroit, Michigan 2Department of Study Design Retrospective Chart Review • January 1, 2013 to February 28, 2015 • 220-bed tertiary pediatric hospital in Detroit, MI Inclusion Criteria • Level I pediatric trauma center • Patients <18 years of age on ECMO at Children’s Hospital of Michigan (CHM) – 38-bed pediatric intensive care unit (PICU) • Level IV neonatal center Exclusion Criteria • Patients >18 years of age – 43-bed neonatal intensive care unit (NICU) • ECMO Center of Excellence Statistical Analysis • Descriptive statistics http://www.childrensdmc.org/ Data Collection Therapeutic Monitoring Parameters • Patient demographics • Hospital service • • • • • – PICU – Cardiovascular (CV) Surgery – NICU • Type of ECMO • Number of hours on ECMO ACT Anti-Xa levels APTT ATIII levels Number of fresh frozen plasma (FFP) administrations • Number of platelet administrations 3 5/5/2015 Complications Survival Outcomes Hemorrhagic • Incidences of bleeding defined as: • Symptomatic bleeding in a critical area or organ • Bleeding requiring surgical intervention • Bleeding resulting in death • Number of packed red blood cell (PRBC) administrations Thrombotic • Systemic thrombosis • Number of oxygenator changes • Number of ECMO circuit changes CHM ECMO Anticoagulation Protocol Before Protocol After Protocol • Bolus: 100 units/kg • Bolus: 100 units/kg • Continuous infusion • All patients: • 20 units/kg/hr • Continuous infusion • Patients ≤5 kg: • 20 units/kg/hr • Patients >5 kg: • 10 units/kg/hr CHM ECMO Anticoagulation Protocol • • • • Survival to decannulation 30 day survival post decannulation Surgical procedures while on ECMO Culture positive infections CHM ECMO Anticoagulation Protocol Heparin Titration Before Protocol • Managed by ECMO Respiratory Therapists • Doses adjusted based on ACTs alone • Target Coagulation • Managed by primary service • Doses adjusted by antiXa levels and other clinical factors • Target Coagulation • ACT: 180-220 sec • Anti-Xa: 0.3-0.7 units/mL • ATIII Activity: ≥70% • ACT: 200-300 sec Results 46 Total Patients • No standard • Transfusions given as needed Transfusions • ATIII levels were not tested or corrected Before Protocol • Platelets <100,000/mm3: 10 mL/kg • PRBC (Hgb <10 gm/dL): 10 mL/kg • ATIII Activity Transfusions • >70%: No correction • 50-70%: administer FFP 10 mL/kg After • <50%: Correct to 100-120% Protocol Heparin Titration After Protocol 7 patients excluded due to no ECMO information from EMR 39 Patients Included 24 Patients Before Protocol NICU: 10 Patients PICU: 5 Patients 15 Patients After Protocol CV Surgery: 9 Patients NICU: 6 Patients PICU: 3 Patients CV Surgery: 6 Patients 4 5/5/2015 Patient Demographics Before Protocol (n=24) Median [Range] After Protocol (n=15) Median [Range] 7.1 mos [17 hrs-5 yrs] 1.8 yrs [1 day-15 yrs] Average ACT: 204.7 sec (Range: 135-712 sec) 70 60 Weight 5.29 kg [2.2-16.3 kg] 8.54 kg [2.8-36 kg] Height 58.56 cm [45-117 cm] 69.2 cm [49-152 cm] ECMO Hours 120 hrs [11 hrs-12.4 days] 211 hrs [32 hrs– 44.6 days] Gender Male: 13 (54%) Female: 11 (46%) Male: 10 (67%) Female: 5 (33%) VV: 4 (17%) VA: 19 (79%) VV VA: 1 (4%) VV: 0 (0%) VA: 14 (93%) VV VA: 1 (7%) Type of ECMO 80 Percentage Age Therapeutic Monitoring Before Protocol 50 ACT aPTT 40 30 20 10 0 Within Range ACT Trends Before Protocol Above Range Therapeutic Monitoring After Protocol 400 90 Average Heparin Dose: 31.4 units/kg/hr (Range: 0-79.5 units/kg/hr) 350 Average Anti-Xa Level: 0.45 units/mL (Range: 0-1.68 units/mL) Average ACT: 231.7 sec (Range: 100-575 sec) 80 70 300 Percentage ACT Level (seconds) Below Range 250 200 60 50 40 Anti-Xa 30 ACT 20 150 10 100 15 20 25 30 35 40 45 0 50 Heparin Dose (units/kg/hr) Within Range Anti-Xa Level Trends After Protocol 400 350 0.8 ACT Level (seconds) Anti-Xa Level (units/mL) Below Range ACT Trends After Protocol Average Heparin Dose: 33 units/kg/hr (Range: 0-58.1 units/kg/hr) 1 0.9 Above Range 0.7 0.6 0.5 0.4 0.3 300 250 200 150 100 0.2 50 0.1 0 0 0 10 20 30 Heparin Dose (units/kg/hr) 40 50 0 10 20 30 40 50 Heparin Dose (units/kg/hr) 5 5/5/2015 Platelet and FFP Transfusions Hemorrhagic Complications Before Protocol 8/24 Patients (33%) Before Protocol After Protocol Platelets •No. of transfusions •Average [range] 135 112/mm3 [23-490/mm3] 138 115.3/mm3 [27.4-200/mm3] FFP •No. of transfusions 36 79 ATIII •No. of transfusions •Average [range] 0 N/A 22 59.9% [18-101%] PRBC Transfusions After Protocol 6/15 Patients (40%) CV Surgery 2 (25%) CV Surgery 2 (33%) NICU 4 (50%) NICU 3 (50%) PICU 2 (25%) PICU 1 (17%) Systemic Thrombotic Complications Before Protocol 4/24 Patients (17%) Before Protocol After Protocol No. of transfusions 94 73 Average Hgb [range] 12.39 gm/dL [6.3-21.8 gm/dL] 11.06 gm/dL [7.2-18.6 gm/dL] Average Hct [range] 36.2% [18.5-61.4%] 33% [22.4-48%] ECMO Circuit Thrombotic Complications After Protocol 5/15 Patients (33%) NICU 1 (25%) CV Surgery 2 (40%) PICU 3 (75%) NICU 1 (20%) PICU 2 (40%) Survival Outcomes 90 80 • Before Protocol: 4 • After Protocol: 9 70 n=19 n=12 n=17 60 Percentage Oxygenator Changes 50 n=7 40 Before Protocol After Protocol 30 ECMO Circuit Changes • Before Protocol: 11 • After Protocol: 4 20 10 0 Survival To Decannulation 30 Day Survival After Decannulation 6 5/5/2015 Survival Outcomes – Surgical Procedures Before Protocol After Protocol 11 Total Surgical Procedures 12 Total Surgical Procedures Survival Outcomes – Infection Risk Before Protocol 9/24 Patients (37.5%) NICU 1 (8%) PICU 4 (36%) CV Surgery 7 (64%) CV Surgery 7 (58%) PICU 4 (33%) • 11 Infections • Average ECMO Hours: 118 After Protocol 5/15 Patients (33%) • 10 Infections • Average ECMO Hours: 383 Study Limitations Future Directions • Statistical testing for significance was not performed • Older pediatric patients underrepresented • Continual reassessment of protocol • Utilizing fibrinogen levels and cryoprecipitate transfusions to optimize anticoagulation efficacy • Expanding multidisciplinary care to utilize hematology/oncology services • Creating separate anticoagulation protocols for different populations or age groups Acknowledgements References • • • • • Dr. Joanna Ditouras, Pharm.D. Dr. Michelle Veenstra, M.D. Dr. Kelly Holzhausen, Pharm.D. Dr. Paul T. Stockmann, M.D. • • • • Maslach-Hubbard A, Bratton SL. Extracorporeal membrane oxygenation for pediatric respiratory failure: History, development and current status. World J Crit Care Med. 2013;2(4):29-39. Extracorporeal Life Support Organization. ECLS Registry Report International Summary. http://www.elso.org/Registry/Statistics/InternationalSummary.aspx. Published January 2015. Accessed March 22, 2015. Buck ML. Pharmacokinetic changes during extracorporeal membrane oxygenation: implications for drug therapy of neonates. Clin Pharmacokinet. 2003;42(5):403-17. Extracorporeal Life Support Organization. ELSO Anticoagulation Guideline. http://www.elso.org. Published 2014. Accessed March 22, 2015. Annich G, Adachi I. Anticoagulation for pediatric mechanical circulatory support. Pediatr Crit Care Med 2013; 14:S37-S42. 7 5/5/2015 Anticoagulation Monitoring in Pediatric Patients Undergoing Extracorporeal Membrane Oxygenation (ECMO) Julie Dang, Pharm.D. PGY-1 Pharmacy Practice Resident Detroit Medical Center, Children’s Hospital of Michigan The speaker has no actual or potential conflicts of interest in relation to this presentation. 8