Antiplatelet Effect of Ketorolac in Children After Congenital Cardiac Surgery

Background: Ketorolac is used for pediatric analgesia after surgery despite its known platelet inhibition via the arachidonic acid (AA) pathway. The degree of platelet inhibitory effect after cardiac surgery is not well characterized. Thromboelastography with platelet mapping (TEG-PM) is emerging as a frequently used test to evaluate platelet inhibition via the AA pathway. Methods: Post hoc analysis of a data set collected in a prospective observational cohort study evaluating platelet inhibition in children after congenital heart surgery with cardiopulmonary bypass (CPB). Categorization into two groups: (1) received ketorolac and (2) did not receive ketorolac for analgesia after surgery. The TEG-PM was evaluated at two time points (prior to surgery and 12-48 hours after CPB). Results: Fifty-three children were studied; mean age was 6.6 (range: 0.07-16.7) years and 45% (n = 24) were female. Participants were distributed into two groups by ketorolac use, 41 within the ketorolac group and 12 in the no ketorolac group. All 41 participants who received ketorolac had platelet inhibition and 11 (91.7%) of 12 participants who did not receive ketorolac had normal platelet function after surgery (P < .0001). There was no difference in patient characteristics or clinical data between the two groups. Conclusions: Ketorolac use in a cohort of children after congenital cardiac surgery was associated with platelet inhibition via the AA pathway when evaluated by TEG-PM.

[1]  S. Emani,et al.  Platelet testing to guide aspirin dose adjustment in pediatric patients after cardiac surgery , 2017, The Journal of thoracic and cardiovascular surgery.

[2]  Deepak L. Bhatt,et al.  How I use laboratory monitoring of antiplatelet therapy. , 2017, Blood.

[3]  D. Borgel,et al.  Platelet‐mapping assay for monitoring antiplatelet therapy during mechanical circulatory support in children: A retrospective observational study , 2017, Research and practice in thrombosis and haemostasis.

[4]  B. McCrindle,et al.  Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association , 2017, Circulation.

[5]  X. Sheng,et al.  Platelet Inhibition in Shunted Infants on Aspirin at Short and Midterm Follow-Up , 2017, Pediatric Cardiology.

[6]  C. Witmer,et al.  Pediatric Cardiac Intensive Care Society 2014 Consensus Statement: Pharmacotherapies in Cardiac Critical Care Anticoagulation and Thrombolysis , 2016, Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

[7]  M. Desai,et al.  Thromboelastography/Platelet Mapping® and Aspirin: Is There Evidence of a Meaningful Dose-Response Relationship in Children Supported With the Berlin Heart EXCOR Ventricular Assist Device? , 2015 .

[8]  K. Schrör,et al.  Inhibition of Antiplatelet Effects of Aspirin by Nonopioid Analgesics , 2015, Clinical pharmacology and therapeutics.

[9]  Meredith K Jalkut.  Ketorolac as an analgesic agent for infants and children after cardiac surgery: safety profile and appropriate patient selection. , 2014, AACN advanced critical care.

[10]  J. L. Todd,et al.  Prevention and treatment of thrombosis in pediatric and congenital heart disease: a scientific statement from the American Heart Association. , 2013, Circulation.

[11]  R. Carroll,et al.  A Comparison of VerifyNow® with PlateletMapping® -Detected Aspirin Resistance and Correlation with Urinary Thromboxane , 2013, Anesthesia and analgesia.

[12]  R. Ichord,et al.  Bleeding and Thrombotic Emergencies in Pediatric Cardiac Intensive Care , 2012, World journal for pediatric & congenital heart surgery.

[13]  B. McCrindle,et al.  Thrombotic complications and thromboprophylaxis across all three stages of single ventricle heart palliation. , 2012, The Journal of pediatrics.

[14]  D. Cattano,et al.  Perioperative assessment of platelet function by Thromboelastograph® Platelet Mapping™ in cardiovascular patients undergoing non-cardiac surgery , 2012, Journal of Thrombosis and Thrombolysis.

[15]  S. Preisman,et al.  Modified thromboelastography evaluation of platelet dysfunction in patients undergoing coronary artery surgery. , 2010, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[16]  J. Saw,et al.  Long-term aspirin and clopidogrel response evaluated by light transmission aggregometry, VerifyNow, and thrombelastography in patients undergoing percutaneous coronary intervention. , 2010, Clinical chemistry.

[17]  M. Schuijt,et al.  The interaction of ibuprofen and diclofenac with aspirin in healthy volunteers , 2009, British journal of pharmacology.

[18]  H. Frndova,et al.  Safety and efficacy of ketorolac in children after cardiac surgery , 2009, Intensive Care Medicine.

[19]  N. Gibbs,et al.  Point-of-Care Assessment of Antiplatelet Agents in the Perioperative Period: A Review , 2009, Anaesthesia and intensive care.

[20]  J. Berridge,et al.  Assessment of platelet inhibition secondary to clopidogrel and aspirin therapy in preoperative acute surgical patients measured by Thrombelastography Platelet Mapping. , 2009, British journal of anaesthesia.

[21]  C. Krawczeski,et al.  Safety of intravenous use of ketorolac in infants following cardiothoracic surgery , 2009, Cardiology in the Young.

[22]  W. Reinhart,et al.  Influence of combinations of acetylsalicylic acid, acetaminophen, and diclofenac on platelet aggregation. , 2008, European journal of pharmacology.

[23]  G. Lip,et al.  The role of aspirin in cardiovascular prevention: implications of aspirin resistance. , 2008, Journal of the American College of Cardiology.

[24]  F. Gengo,et al.  Effects of Ibuprofen on the Magnitude and Duration of Aspirin's Inhibition of Platelet Aggregation: Clinical Consequences in Stroke Prophylaxis , 2008, Journal of clinical pharmacology.

[25]  Justin T. Newcomer,et al.  Evaluation of Dose-Related Effects of Aspirin on Platelet Function: Results From the Aspirin-Induced Platelet Effect (ASPECT) Study , 2007, Circulation.

[26]  D. Steinbrüchel,et al.  Evaluation of the TEG® platelet mapping™ assay in blood donors , 2007, Thrombosis journal.

[27]  A. Mott,et al.  Safety of ketorolac in neonates and infants after cardiac surgery , 2006, Paediatric anaesthesia.

[28]  T. MacDonald,et al.  Is there an interaction between the cardiovascular protective effects of low-dose aspirin and ibuprofen? , 2006, Basic & clinical pharmacology & toxicology.

[29]  N. Curzen,et al.  Thromboelastography: Potential bedside tool to assess the effects of antiplatelet therapy? , 2006, Platelets.

[30]  S. Israels,et al.  Antiplatelet therapy in children. , 2006, Thrombosis research.

[31]  L. Shore-lesserson,et al.  Coagulation monitoring. , 2006, Anesthesiology clinics.

[32]  P. Gurbel,et al.  Overestimation of platelet aspirin resistance detection by thrombelastograph platelet mapping and validation by conventional aggregometry using arachidonic acid stimulation. , 2005, Journal of the American College of Cardiology.

[33]  A. Michelson.  Platelet function testing in cardiovascular diseases. , 2004, Circulation.

[34]  R. Carroll,et al.  A novel modification of the Thrombelastograph assay, isolating platelet function, correlates with optical platelet aggregation. , 2004, The Journal of laboratory and clinical medicine.

[35]  E. Topol,et al.  A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. , 2003, Journal of the American College of Cardiology.

[36]  M. Reilly,et al.  Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. , 2001, The New England journal of medicine.

[37]  P. Mongan,et al.  Intravenous Ketorolac Tromethamine Worsens Platelet Function During Knee Arthroscopy Under Spinal Anesthesia , 1996, Anesthesia and analgesia.

[38]  P. Mongan,et al.  Intravenous Ketorolac Tromethamine Does Not Worsen Platelet Function During Knee Arthroscopy Under General Anesthesia , 1995, Anesthesia and analgesia.

[39]  J. Sear,et al.  Effect of ketorolac, bupivacaine and low-dose heparin on thrombelastographic variables in vitro. , 1995, British journal of anaesthesia.

[40]  C. Whitten,et al.  Influence of ketorolac tromethamine on clot elastic strength in humans as assessed by thromboelastography. , 1993, Journal of clinical anesthesia.