Research Presentations. Thomas W. White, MD, FACS, CNSC. Annika Bickford, PA-C

Transcription

1 Research Presentations Thomas W. White, MD, FACS, CNSC Trauma Surgery/Critical Care, Medical Director Nutrition Support Service, Shock Trauma ICU Attending, Intermountain Medical Center; Clinical Professor of Surgery, University of Utah Surgery Residency Program; Salt Lake City, Utah Annika Bickford, PA-C Physician Assistant, Trauma and Critical Care, Intermountain Medical Center, Intermountain Healthcare Salt Lake City, Utah Objectives: Discuss the current recommendations for venous thromboprophylaxis Identify patients as high risk for venous thromboprophylaxis Discuss why one size fits all may ot be the best approach for venous thromboprophylaxis Review the reasosn/rationale for weight-based dosing of enoxaparin in obese patients

2 Research? It doesn t have to make you feel like this guy Thomas W. White, MD, FACS, CNSC Annika Bickford, PA-C, MPAS Trauma & Critical Care Intermountain Medical Center

3 Where Do I Start? Patient Population Who to target? Who to include? Who to exclude? Intervention What intervention do you want to study? Comparison What will you compare? What are your groups? Outcome What is the primary outcome? Secondary outcomes?

4 What we asked ourselves: Why is incidence of VTE, especially DVTs, still so rampant? Is what we are doing adequate? Should all patients really be getting the same dose of enoxaparin for DVT prophylaxis? So we reviewed the literature and came up with a clinical question Is weight-based dosing of enoxaparin for DVT prophylaxis in obese trauma patients efficacious, as assesed by anti-xa levels and incidence of VTE?

5 Elements & Concepts The Research Question What is the research question you are trying to answer? Be as SPECIFIC as possible!

6 Elements & Concepts Null Hypothesis Restate the research question as a null hypothesis What is the NULL HYPOTHESIS?? A general statement or default position that states there is no relationship between two measured phenomena. Generally, you are trying to prove an alternative hypothesis is true *P-value!

7 Elements & Concepts Significance Why does this research matter? What is know or unknown about this topic? A comprehensive literature review is key! How does it relate to your work, and patient care/outcomes? What is the potential impact of this work?

8 Elements & Concepts Design Prospective vs. retrospective Randomized vs. cohort Observational vs. experimental

9 Elements & Concepts Subjects Selection criteria Who are the subjects and how will they be selected? Inclusion and exclusion criteria Sampling Design Consecutive: all patients seen in concession Convenience: all patients seen during business hours Chart review: review of medical records

10 Elements & Concepts Variables Predictor variables What measurements will be made before and after the study? i.e. MOI, age, gender, ISS Outcome variables List your main outcome variables i.e. mortality, LOS, cost

11 Elements & Concepts Statistics Statistical and analytical issues How large is the study? How will it be analyzed? Power? GET HELP!

12 Elements & Concepts Next steps Anticipated problems or barriers? Create a list of bite-size goals IRB (internal review board) Look for a journal for submission Write and submit your abstract Keep track and collect all your references Write a manuscript the time sucker

13 How we did it 1. Created new trauma team protocol, approved by attending surgeons 2. IRB approval 3. Collected and analyzed data 4. Chose a meeting/journal for submission 5. Wrote and submitted an abstract 6. Abstract accepted 7. Wrote a manuscript 8. Podium presentation 9. Manuscript publication process 10.Manuscript in print!

14 PUBLISHED! American Journal of Surgery QuickTime and a decompressor are needed to see this picture.

15 Weight-Based Enoxaparin Dosing For Venousthromboembolism Prophylaxis in the Obese Trauma Patient Annika Bickford, PA-C, MPAS Trauma Services Intermountain Medical Center Murray, UT

16 Venous Thromboembolism (VTE) Deep venous thrombosis Blood clot formation within a deep vein, commonly in the leg or pelvis Virchow s Triad 1. Blood hypercoagulability 2. Venous stasis/immobility 3. Vessel wall injury Pulmonary embolism Blood clot travels to lung and lodges in one or more pulmonary arteries

17 VTE Incidence and Risks o o Nearly 6 million cases of serious VTE are reported in the U.S. each year Significant short- and long-term complications and a tremendous financial burden Risk Factors o o o o o Surgery Trauma Obesity Cancer Inherited thrombophilia

18 VTE In Trauma Incidence (without chemoprophylaxis) DVT: 28-65% PE: up to 9% VTE: up to 70% in critical trauma pts PE is most common cause of preventable hospital death NEJM study identified independent risk factors Age LE (femur or tibia) injury Spinal cord injury Blood transfusion in first 24 hrs of trauma

19 VTE and Obesity o o o o Obesity is a critical risk factor for developing VTE Relative risk of 2.50! Mayo clinic autopsy series of surgical patients revealed obesity alone as an independent risk factor for fatal postop PEs In gastric bypass surgery, the number one cause of unexpected early and late postoperative death is PE Obesity is associated with increased prothrombotic factors

20 DVT Prophylaxis in Trauma o o Sequential compression devices alone have not shown benefit in preventing DVT Low-molecular-weight heparin (LMWH) is more efficacious than unfractionated heparin (UFH) in preventing VTE after major trauma o Despite chemoprophylaxis, DVT rates still up to 31% 6% to 15% proximal

21 Can One Size Fit All? Enoxaparin has a high volume of distribution Affected by fat tissue and fluid accumulation Fixed-dose LMWH may not provide adequate VTE prophylaxis in obese patients or in trauma patients QuickTime and a decompressor are needed to see this picture.

22 VTE Prophylaxis Current ACCP Guidelines, 9 th ed. (2012) LMWH is recommended for VTE prophylaxis in major trauma No definitive recommendations for or against weight-based dosing in obese patients 8th ed.(2008) guidelines do recommend weight-based dosing for prophylaxis in obese patients Routine coagulation monitoring not recommended Exceptions include pregnancy, obesity, and renal dysfunction Plasma anti-xa activity

23 OUR STUDY WEIGHT-BASED ENOXAPARIN DOSING FOR VENOUSTHROMBOEMBOLISM PROPHYLAXIS IN THE OBESE TRAUMA PATIENT Purpose Is a weight-based dosing regimen of enoxaparin for VTE prophylaxis in obese trauma patients efficacious? Primary outcome = plasma anti-xa level Secondary outcome = incidence of VTE Is it safe? Bleeding complications

24 Our Study Inclusion criteria Obese (BMI >30kg/m 2 ) Adult (>18 years) Admitted to level I trauma center, January 2011-July 2012 Exclusion criteria Acute traumatic intracranial hemorrhage Active internal bleeding Renal insufficiency (CrCl<30mL/min) Pregnancy Epidural anesthesia Coagulopathy (factor deficiencies) Thrombocytopenia (plts<50k or drop>50% baseline) Heparin allergy or h/o HIT

25 Dosing & Monitoring Prospective Dosing Enoxaparin 0.5 mg/kg subcutaneously twice daily Total body weight on admission Monitoring Peak anti-xa levels, drawn 4 hours after 3 rd /4 th dose Target range: IU/mL Bilateral lower extremity duplex ultrasound Computed tomography of chest if PE suspected

26 Enoxaparin dose adjustments Anti-Xa level (IU/mL) Dose adjustment <0.2 Increase total daily dose by 20 mg No change Decrease total daily dose by 20 mg >1.0 Decrease total daily dose by 50% *Repeat peak anti-xa level after the adjusted dose

27 Results Demographics 86 patients met study criteria 60 (70%) males, 26 (30%) females Mean age years Median BMI 35.3 kg/m 2, IQR of 9.8 Median weight kg, IQR of 30 Median ISS 14, IQR of 12 *BMI = body mass index *IQR = interquartile range *ISS = injury severity score

28 Results Primary Outcome Measure 74 patients (86%) reached target anti-xa level Mean = IU/mL 12 patients were out of range: 8 above and 4 below Dose adjustments achieved target anti-xa levels No significant differences in age, weight, or BMI between those above and those below target anti-xa range No dramatic weight gain/loss during hospitalization.

29 Weight versus anti-xa level in obese trauma patients Weight (kg) No correlation was found between weight and anti-xa level r 2 = -0.01

30 Results Secondary Outcome Measures Incidence of VTE? 18 patients (21%) diagnosed with DVT In 16 patients, DVT was present prior to or on the day of starting weight-based LMWH DVT group non-dvt group p-value Age, yr 52.4 (3.8) 51.3 (2.03) 0.40 Weight, kg (8.02) (3.63) Body mass index, kg/m (1.02) 39.7 (1.3) Injury severity score 23.9 (3.1) 12.7 (0.77) <0.001 No cases of PE identified

31 Conclusions One size does NOT fit all Weight-based enoxaparin for VTE prophylaxis in obese trauma patients works Majority reached target anti-xa levels Nomogram for dose adjustments led to appropriate levels 100% of the time

32 Conclusions Controlling for obesity with weight-based dosing leads to equal and adequate prophylaxis No correlation between weight and anti-xa DVT incidence should not be attributed to inadequate prophylaxis Majority diagnosed prior to start of LMWH

33 Conclusions Lack of data regarding the relationship between weight-based dosing and/or anti-xa levels with VTE incidence Larger randomized trials are needed

34 THANK YOU!

35 ? QUESTIONS?

36 References 1. Geerts WH, Jay RM, Code KI, et al. A comparison of low-does heparin with low-molecular-weight heparin as prophylaxis against venous thromboembolism after major trauma. N Engl J Med. 1996;335: Geerts WH, Code KI, Jay RM, Chen E, Szalai JP. A prospective study of venous thromboembolism after major trauma. N Engl J Med. 1994; 331: Knudson MM, Morabito D, Paiement GD, Shackleford S. Use of low molecular weight heparin in preventing thromboembolism in trauma patients. J Trauma. 1996;41: Stein PD, Beemath A, Olson RE. Obesity as a risk factor in venous thromboembolism. Am J Med Sep;118(9): Knudson MM, Ikossi DG, Khaw L, et al. Thromboembolism after trauma. Ann Surg. 2004;240: Hama GG, Choban PS. Enoxaparin for thromboprophylaxis in morbidly obese patients undergoing bariatric surgery: findings of the prophylaxis against VTE outcomes in bariatric surgery patients receiving enoxaparin (PROBE) study. Obes Surg. 2005;15: Rondina MT, et al, Weight-based dosing of enoxaparin for VTE prophylaxis in morbidly obese, medically-ill patients. Thromb Res. 2009; 8. Eichinger S, Hron G, Bialonczyk C, et al. Overweight, obesity, and the risk of recurrent venous thromboembolism. Arch Intern Med. 2008;168: Garcia DA, Baglin TP, Weitz JI, Samama MM. Parenteral anticoagulants: antithrombotic therapy and prevention of thrombosis, 9 th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141;e24S-e43S. 10. Nutescu EA, Spinler SA, Wittkowsky A, Dager WE. Low-molecular-weight heparins in renal impairment and obesity: available evidence and clinical practice recommendations across medical and surgical settings. Ann Pharmacother. 2009;43: Hirsh J, Bauer KA, Donati MB, et al. Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest. 2008;133:141s 159s. 12. Frederiksen SG, Hedenbro JL, Norgren L. Enoxaparin effect depends on body-weight and current doses may be inadequate in obese patients. Br J Surg 2003;90: Rutherford EJ, Schooler WG, Sredzienski E, et al. Optimal dose of enoxaparin in critically ill trauma and surgical patients. J Trauma. 2005;58:

37 References 14. Malinoski D, Jafari F, Ewing T, et al. Standard prophylactic enoxaparin dosing leads to inadequate anti-xa levels and increased deep venous thrombosis rates in critically ill trauma and surgical patients. J Trauma. 2010;68: Simone EP, Madan AK, Tichansky DS, et al. Comparison of two low-molecular-weight heparin dosing regimens for patients undergoing laparoscopic bariatric surgery. Surg Endosc. 2008;22: Borkgren-Okonek MJ, Hart RW, Pantano JA, et al. Enoxaparin thromboprophylaxis in gastric bypass patients: extended duration, dose stratification, and antifactor Xa activity. Surg Obes Relat Dis Sep-Oct;4(5): Rowan BO, Kuhl DA, Lee MD, et al. Anti-Xa levels in bariatric surgery patients receiving prophylactic enoxaparin. Obes Surg. 2008;18: Ludwig KP, Simons HJ, Mone M, et al. Implementation of an enoxaparin protocol for venous thromboembolism prophylaxis in obese surgical intensive care unit patients. Ann Pharmacother. 2011;45: ARUP National Reference Laboratory. Heparin anti-xa, low molecular weight heparin. Available at: Accessed on February 24, Pierce CA, Haut ER, Kardooni S, et al. Surveillance bias and deep vein thrombosis in the national trauma data bank: the more we look, the more we find. J Trauma. 2008;64: Haut ER, Schneider EB, Patel A, et al. Duplex ultrasound screening for deep vein thrombosis in asymptomatic trauma patients: a survey of individual trauma surgeon opinions and current trauma center practices. J Trauma. 2011;70: Haas CE, Nelsen JL, Raghavendran K, et al. Pharmacokinetics and pharmacodynamics of enoxaparin in multiple trauma patients. J Trauma. 2005;59: Constantini TW, Min E, Box K, et al. Dose adjusting enoxaparin is necessary to achieve adequate venous thromboembolism prophylaxis in trauma patients. J Trauma. 2013;74: Fareed J, Hoppensteadt D, Walenga J, et al. Pharmacodynamic and pharmacokinetic properties of enoxaparin. Clin Pharmacokinet. 2003;42(12): Sanderink GJ, Le Liboux A, Jariwala N, et al. The pharmacokinetics and pharmacodynamics of enoxaparin in obese volunteers. Clin Pharmacol Ther. 2002;72(3): Van PY, Cho SD, Underwood SJ, et al. Thrombelastography versus antifactor Xa levels in the assessment of prophylactic-dose enoxaparin in critically ill patients. J Trauma. 2009;66: