1. Hemostatic Agents in the OR: Are You Providing Safe Care? Peggy Camp, RN, BSN, MSN September 13, 2012

2. Hemostatic Agents in the OR: Are You Providing Safe Care?  Today’s presentation will provide a review and update on: The types and properties of topical haemostatic sealants commonly used in the Peri-operative setting. Common surgical applications FDA approved Products/applications Clinical Facts for the Peri-operative Nurse Potential Complications “Take-aways” for Clinicians

3. Hemostatic Agents in the OR: Are You Providing Safe Care? Historical Overview Major Factors affecting today’s surgical environment  Cost Containment  Growing Aging Population Impact on today’s care delivery systems  Growth in less invasive procedures  Emergence of new products to control bleeding, enhance clinical outcomes

4. Hemostatic Agents in the OR: Are You Providing Safe Care? What has changed in the past 5 years in health care delivery?  Emphasis on controlling costs  Increase in minimally invasive procedures in the OR and other clinical areas (IR, Cath Lab)  Expectation of improved clinical outcomes  High level of oversight on clinical interventions and outcomes Surgical Complications including SSI, readmissions Blood Transfusions Implants Advanced Haemostatic Agents

5. Hemostatic Agents in the OR: Are You Providing Safe Care? Haemostatic Agent Characteristics CATEGOR Y SAFETYEFFICACYEASE OF USECOST MechanicalRelatively Safe Swelling Minimal BleedingEasy to prepare/use Inexpensive ActivePotential for: Antibody Formation, Disease Transmission: Viral, Prion Recombinant Effective for localized & diffuse bleeding Relatively easy to prepare/use Moderately priced FlowableDisease Transmission: Viral, Prion Localized BleedingRelatively easy to prepare/use More expensive than active Fibrin SealantDisease Transmission: Viral, Prion Antibody formation/swelling Coagulation profile important to know Localized and Diffuse Bleeding More difficult to prepare/use Most expensive

6. Hemostatic Agents in the OR: Are You Providing Safe Care? Current products -MECHANICAL CATEGORYACTIONCOMPOSITION/ORIGINCLINICAL CONSIDERATIONSCOMMERCIAL NAME MechanicalMinimal Bleeding Porcine GelatinSwelling (do not use in confined areas); do not use in infected cases; may cause foreign body reaction if not removed Gelfoam Powder /Sponge Surgifoam Powder /Sponge Bovine CollagenSwelling (do not use in confined areas); do not use in infected cases; may cause foreign body reaction if not removed; adhesion formation Avitene sponge & flour; Helistat and Helitene; Instat Oxidized Regenerated Cellulose Swelling (do not use in confined areas); do not use in infected cases; may cause foreign body reaction if not removed; adhesion formation Surgicel, Surgicel Fibrillar, and Nu-Knit Polysaccharide Spheres Swelling (do not use in confined areas); no demonstrated safety studies in neurologic, urologic and ophthalmic surgery; should not be injected Arista

7. Hemostatic Agents in the OR: Are You Providing Safe Care? Current products -ACTIVES CATEGORYACTIONCOMPOSITION/ORIGINCLINICAL CONSIDERATIONSCOMMERCIAL NAME ActivesLocalized and Diffuse Bleeding Bovine Thrombin Pooled Human Thrombin Recombinant Thrombin Should not be used for patients with bovine allergies; can stimulate Antigen formation and interrupt clotting cascade ; potential for infection transmission; has Black Box Warning Swelling risk; Do not use in patients with allergies to Human blood products; unknown potential for infection transmission and interruption of clotting cascade Commercially manufactured; to date clinical studies have not demonstrated this product has produced antigens or impacted clotting cascade Thrombin Evithrom Recothrom

8. Hemostatic Agents in the OR: Are You Providing Safe Care? Current Products -FLOWABLES CATEGORYACTIONCOMPOSITION/ORIGINCLINICAL CONSIDERATIONSCOMMERCIAL NAME FlowablesLocalized bleeding Bovine Gelatin and Human Thrombin Porcine Gelatin with/without Thrombin Should not be used for patients with bovine allergies; swelling risk – approved for use in all specialties EXCEPT Ophthalmology; absorption 6- 8 weeks; not to be used with blood Salvage devices or Cardio-pulmonary Bypass circuits; potential for infection transmission Swelling risk; absorption in 4-6 weeks. Do not use in patients with Porcine allergies; not to be used with blood Salvage devices or Cardio-pulmonary Bypass circuits; potential for infection transmission * Can be used in combination with Recothrom Floseal Surgiflo

9. Hemostatic Agents in the OR: Are You Providing Safe Care? Current Products –Fibrin Sealants CATEGORYACTIONCOMPOSITION/ ORIGIN CLINICAL CONSIDERATIONSCOMMERCIAL NAME Fibrin Sealants Localized and Diffuse Bleeding Human Plasma- Derived Fibrin Sealant Patient ‘s Own Plasma with Bovine Collagen/Throm bin Patient ‘s Own Plasma to create Fibrinogen and thrombin 2 component hemostat & sealant –contains pooled human plasma fibrinogen and & thrombin – doesn’t need active bleeding or blood –derived fibrinogen for activation - do not to use with Blood Salvage devices or CP- Bypass circuits; potential concerns infection transmission, air embolus, tissue rupture and gas entrapment. Systems differ in terms of storage and application. Potential concerns –do not use in patients with Bovine allergies, infection/ foreign body reaction/swelling/tissue compression ; immunologic and coagulation complications. Requires trained technician for processing; not be used in patients with acquired or hereditary hematologic or coagulation disorders; not be used with patients on active heparin or Coumadin therapy or non-steroidal anti- flammatory agent use (48 hrs); adjunct for liver resection surgery; studies indicate clot stability and Fibrinogen less effective than commercially prepared products Tisseal Evicel Crosseal Vitagel Cryoseal

10. Hemostatic Agents in the OR: Are You Providing Safe Care? CATEGORYACTIONCOMPOSITION /ORIGIN CLINICAL CONSIDERATIONSCOMMERCIAL NAME Peg Polymers Cyanoacrylates Glutaraldehydes Two synthetic polymers that mix and cross link at the wound site Monomers form polymers in presence of water and serves to glue surfaces together Achieves 65% binding power in 20 sec; full strength in 2 min regardless of temperature /air /water Polyethylene glycol hydrogels Liquid monomers Glutaraldehyde cross linked with bovine albumin Can prevent pericardial adhesions; good agent for vascular reconstructions; does not cause inflammation; infection risks minimal; should not be used in closed spaces because of swelling risk Used as a replacement for sutures primarily on facial, extremity and torso wounds; attains strength of healed tissue after 7 days Commonly used in vascular procedures for sealing holes around staple lines; good agent for arterial bleeds; hyper-sensitivity a concern; inert substance that is NEVER absorbed Coseal Dermabond Indermil Bioglue Current Products –Peg Polymers,Cyanoacrylates, Glutaraldehydes

11. Hemostatic Agents in the OR: Are You Providing Safe Care? Common Surgical Applications* General Surgery - Hernia Mesh Fixation, Fundoplication, Bariatric Surgery, Colostomy Closure, Burns Cardiac Surgery - Effective agent for active bleeding sites ; some agents help to prevent adhesions Head & Neck Surgery – thyroidectomies, septoplasties - good agent for controlling active bleeding Neurosurgery - Control active bleeding in intra-cerebral hemorrhage, effective in sealing CSF Leakage Orthopedic Surgery - Limited applications include Achilles Tendon Repairs; should not be used with methylmethacrylates OB-GYN Surgery - Laparoscopic Ovarian Cystectomies, Abdominal Myomectomy, Laparoscopic Ovarian Cystectomies

12. Hemostatic Agents in the OR: Are You Providing Safe Care? Common Surgical Applications Ophthalmologic Surgery – Eyelid procedures to seal suture lines/tissues; limited applications for treatment of corneal perforations or glaucoma bleb leaks Thoracic Surgery – seal air leaks in Lung Resections Urologic Surgery - Laparoscopic Nephrectomy Vascular Surgery – Broad applications for active bleeding – Aortic Aneurysms, Peripheral Vascular Procedures, i.e. Carotid Endarterectomy, Av Access Procedures *Note – there are a number of outcome studies in all specialties that indicate less intra/post bleeding and new applications are emerging on a daily basis.

13. FDA FDA Approved Hemostats CATEGORY CLASS PRODUCT MECHANICALPorcine Gelatin Bovine Collagen Oxidized Regenerated Cellulose Polysaccharide Spheres Gelfoam/Surgifoam Powder and Sponge Avitene, Helistat, Instat, Ultrafoam Surgical, Surgicel Fibrillar, Nu-Knit Arista, Hemostase, Vitasure ACTIVEBovine Thrombin Pooled Human Thrombin Recombinant Thrombin Thrombin – JMI Evithrom Recothrom FLOWABLEBovine Gelatin & Pooled Human Thrombin Porcine Gelatin (+/- Thrombin) Floseal. Surgiflo FIBRIN SEALANTPooled human Plasma Individual Human Plasma W Bovine Collagen & Bovine Thrombin Individual Human Plasma Tisseal, Evicel Vitagel Cryoseal Haemostatic Agents in the OR: Are You Providing Safe Care? FDA Approved Products

14. Hemostatic Agents in the OR: Are You Providing Safe Care? FACTS TO CONSIDER What is the origin of the product being used & what are the patient implications? What clinical studies are there to support the application being considered How easy is the product to use? What benefits are there for this product? What limitations are there for this product? What does the product cost & does clinical outcomes justify this expense? What safety mechanisms are in place to insure optimal patient outcomes ---what needs to be considered?

15. Hemostatic Agents in the OR: Are You Providing Safe Care? IMMUNE-MEDIATED COAGULOPATHY (IMC) Iatrogenic medical condition resulting from exposure to non-human coagulation proteins (porcine and bovine) thrombin Has been noted in all surgical specialties (Trauma) True incidence unknown due largely to under reporting (2000) Delayed onset – most often following surgical procedures where Bovine Thrombin used Increased Morbidity and Mortality Difficult to Diagnose and Manage Is an AVOIDABLE complication

16. Hemostatic Agents in the OR: Are You Providing Safe Care? IMMUNE-MEDIATED COAGULOPATHY (IMC) Strategies to improve patient outcomes Patient Assessment Identification of high risk/at risk patients Education of Surgical Team (including Physicians) Using the right product for the right reason Timely intervention

17. Hemostatic Agents in the OR: Are You Providing Safe Care? “Take-aways” for the Peri-operative Nurse  Understand the Risks and Benefits and Cost of Haemostatic Agents  Read the labels on the packaging including Black Box Warnings  Assessment is key for ALL patients – never assume that there have been no previous exposures  Educate yourself, your peers and your surgeons – stay current on published studies  When in doubt, STOP and ask questions

18. Hemostatic Agents in the OR: Are You Providing Safe Care?

19. References Achneck, H., Bantayehu,S., Jamiolkowski, R., Alba, D., Shapiro, M., Lawson, J. A comprehensive Review of Topical Hemostatic Agents. Annals of Surgery. 2010; 251: 217-228. Ness,P., Creer,M., Rodgers,G., Naoum, J., Renkens,K., Voils, S., Alexander, W., (RETACC Panel). Building an immune-mediated coagulopathy consensus: early recognition and evaluation to enhance post-surgical patient safety. Patient Safety in Surgery. 2009: 10.1186-/1754-9493-3-8. Rodgers, G. Immune-mediated Coagulopathy Associated With Bovine Thrombin: Review of the Pediatric Literature. Journal of Pediatric Hematology/Oncology. 33: 2 86-88 Spahn, R & Rossaint, R. Coagulopathy and blood component transfusion in trauma. British Journal of Anesthesia.2005: 95(2). 130-139. Spotnitz, W and Burks, S. State-of-the-Art Review: Hemostats, Sealants,and Adhesives II: Update as Well as How and When to Use the Components of the Surgical Toolbox. Clinical and Applied Thrombosis/Hemostasis. 2010:16:497 – 513.