“Achieving Hemostasis in the Surgical Field: Some Views of a Cardiothoracic Anesthesiologist and a Health-System Pharmacist”

"Achieving Hemostasis in the Surgical Field: Some Views of a Cardiothoracic Anesthesiologist and a Health-System Pharmacist"

Bradley A. Boucher, PharmD, FCCP, FCCM, BCPS, and Jerrold H. Levy, MD,
FAHA, FCCM

June 22, 2013

INTRODUCTION

Maintaining hemostasis is a balancing act involving multiple intravascular systems—vessel wall, platelets, coagulation and fibrinolytic systems—to ensure the arrest of bleeding following injury.1-4 Disruption of the balance between procoagulant and anticoagulant forces may result in severe bleeding or thrombotic complications,2 with the challenge for clinicians becoming one of maintaining patient physiology between these 2 forces so that patients do not bleed or clot to death.1,3

Surgical Bleeding and Hemostasis

Bleeding is a complication of many types of surgery and the most common cause of major blood loss in a medical setting.2,5 Patients often present for surgery with an acquired hemostatic imbalance due to preoperative antithrombotic therapy.6-8 Moreover, patients are increasingly receiving anticoagulants, including heparin and thrombin inhibitors, for perioperative thromboprophylaxis and as therapy for ischemic cardiovascular disease, which may exacerbate bleeding.6,9,10 As a result, it is not uncommon for clinicians to manage patients who are receiving one or more anticoagulant therapies.6 The novel anticoagulants dabigatran and rivaroxaban pose an additional challenge to clinicians because there is no antidote to reverse their effects in the event of uncontrolled bleeding.11,12

Knowing what to do when is key to surgical success. For optimal patient outcomes, intraoperative control of bleeding is essential.13 Various methods are employed to maintain perioperative hemostasis—a multimodal approach that includes the use of systemic and topical agents.13 By way of a cardiac case example (up to 5% of cardiac surgery patients require reexploration for bleeding13), a cardiothoracic anesthesiologist and a health-system pharmacist provide differing perspectives on a shared goal: achieving hemostasis in the surgical field.

CASE CHALLENGE: LOUIS B.

Clinical Profile
Louis B. is a 68-year-old white man with unstable angina who presents for urgent repeat on-pump coronary artery bypass grafting (CABG). He has a history of myocardial infarctions, which resulted in a CABG with saphenous vein grafts 15 years earlier. Comorbidities include heart failure, non-insulin-dependent diabetes, and hypertension. His medications include lisinopril for the heart failure and clopidogrel 75 mg qd.

Cardiac catheterization revealed proximal 3-vessel disease, with occlusion of both grafts. The ejection fraction (EF) was 25%. Low-molecular-weight heparin was administered. The patient's vital signs at this time included the following: BP, 120/70 mm Hg; HR, 76 BPM; HCT, 42%; and platelet count, 220,000.

INTRAOPERATIVE STATUS

The patient had global hypokinesis and anterior wall dyskinesis. Transesophageal echocardiography (TEE) probe revealed a low EF and a 2+ mitral regurgitation. At this point, his BP was 110/75 mm Hg; HR, 72 BPM; pulmonary artery pressure, 45/26 mm Hg; and pulmonary artery occlusion pressure, 15 mm Hg. Blood conservation technique consisted of administration of tranexamic acid 1 g given postintubation, followed by infusion of 200 mg/min. Heparin 400 U/kg was administered after the left internal mammary artery (LIMA) was taken down.

The patient underwent a LIMA to LAD (left anterior descending artery) graft, as well as several vein grafts. He came off bypass relatively easily, and TEE revealed resolution of anterior dyskinesis; there were no new wall motion abnormalities but persistent global hypokinesis.

Due to subsequent biventricular dysfunction, placement of an intra-aortic balloon pump (IABP) to his femoral artery was needed. He was separated from cardiopulmonary bypass with infusions of norepinephrine 6 mcg/min and milrinone 0.5 mcg/kg/min. Protamine 200 mg was also administered to reverse the activated clotting time (ACT) back to a baseline of approximately 125 seconds. Following protamine administration, the patient appeared oozy.

CASE CHALLENGE: LOUIS B.
Expert Q&A with Jerrold H. Levy, MD, FAHA, FCCM
POSTOPERATIVE STATUS

The patient continues to bleed in the ICU. Protamine is administered ≈200 mL/h for the first hour.

Postoperative Days 1 and 2

The patient was extubated and weaned from IV norepinephrine. He continued to receive milrinone infused at a rate of 0.25 mcg/kg/min. A transthoracic echocardiogram on postop day 2 demonstrated persistent evidence of systolic and diastolic dysfunction, with an EF of approximately 30% on IV milrinone with IABP in place.

Postoperative Day 3

The IABP was weaned and removed, and oral clopidogrel was restarted at 75 mg once daily. The right foot/extremity was noted to be cold and pulseless in the area where the IABP had been placed. A consult with a vascular surgeon determined that a femoral embolectomy was necessary, so the patient was returned to the OR. The pulse was temporarily restored to the right foot, and the extremity regained blood flow.

CASE CHALLENGE: LOUIS B.
Expert Q&A with Jerrold H. Levy, MD, FAHA, FCCM and
Bradley A. Boucher, PharmD, FCCP, FCCM, BCPS
RESTORATION OF HEMOSTASIS: SYSTEMIC HEMOSTATIC AGENTS
Pharmacologic agents are an important component of the multimodal approach to achieving perioperative hemostasis. Systemic agents represent a mainstay therapeutic option for the management of bleeding
(Table 1).9,10,14-22
BONUS AUDIO
Dr. Levy discuss several systemic hemostatic agents
RESTORATION OF HEMOSTASIS: TOPICAL HEMOSTATIC AGENTS

Humankind's attempts to arrest bleeding date back many thousands of years, beginning with the ancient Egyptians and Greeks, who used such topical "agents" as wax, grease, and barley mixtures, as well as hemostatic herbs, to manage bleeds.23 It has only been within the past decade that advances in biotechnology have resulted in an abundance of topical hemostatic agents available to modern-day surgeons (Table 2).23-30



CASE CHALLENGE: LOUIS B.
Expert Q&A with Bradley A. Boucher,
PharmD, FCCP, FCCM, BCPS
CONCLUSION

A multimodal approach involving the use of systemic and topical hemostatic agents is integral to maintaining perioperative hemostasis and achieving positive patient outcomes.

REFERENCES
  • 1. Sniecinski RM, Hursting MJ, Paidas MJ, Levy JH. Etiology and assessment of hypercoagulability with lessons from heparin-induced thrombocytopenia. Anesth Analg. 2011;112:46-58.
  • 2. Porte RJ, Leebeek FWG. Pharmacologic strategies to decrease transfusion requirements in patients undergoing surgery. Drugs. 2002;62:2193-2211.
  • 3. Lawson JH, Murphy MP. Challenges for providing effective hemostasis in surgery and trauma. Semin Hematol. 2004;41(suppl 1):55-64.
  • 4. Gabay M. Absorbable hemostatic agents. Am J Health-Syst Pharm. 2006;63:1244-1253.
  • 5. Mannucci PM, Levi M. Prevention and treatment of major blood loss. N Engl J Med. 2007;356:2301-2311.
  • 6. Levy JH, Key NS, Azran MS. Novel oral anticoagulants: implications in the perioperative setting. Anesthesiology. 2010;113:726-745.
  • 7. Ferraris VA, Ferraris SP, Saha SP, et al; Society of Thoracic Surgeons Blood Conservation Guideline Task Force and Society of Cardiovascular Anesthesiologists Special Task Force on Blood Transfusion. Perioperative blood transfusion and blood conservation in cardiac surgery: the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists clinical practice guideline. Ann Thorac Surg. 2007;83(5 suppl):S27-S86.
  • 8. Ferraris VA, Brown JR, Despotis GJ, et al; Society of Thoracic Surgeons Blood Conservation Guideline Task Force, Society of Cardiovascular Anesthesiologists Special Task Force on Blood Transfusion, International Consortium for Evidence Based Perfusion. 2011 update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists blood conservation clinical practice guidelines. Ann Thorac Surg. 2011;91:944-982.
  • 9. Sniecinski RM, Levy JH. Bleeding and management of coagulopathy. J Thorac Cardiovasc Surg. 2011;142:662-667.
  • 10. Sniecinski RM, Karkouti K, Levy JH. Managing clotting: a North American perspective. Curr Opin Anaesthesiol. 2012;25:74-79.
  • 11. Pradaxa [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2012.
  • 12. Xarelto [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc; 2011.
  • 13. Sileshi B, Achneck HE, Lawson JH. Management of surgical hemostasis: topical agents. Vascular. 2008;16(suppl 1):S22-S28.
  • 14. Shander A, Javidroozi M, Perelman S, Puzio T, Lobel G. From bloodless surgery to patient blood management. Mt Sinai J Med. 2012;79:56-65.
  • 15. Voils S. Pharmacologic interventions for the management of critical bleeding. Pharmacotherapy. 2007;27(9 pt 2):69S-84S.
  • 16. Carless PA, Stokes BJ, Moxey AJ, Henry DA. Desmopressin use for minimising perioperative allogeneic blood transfusion. Cochrane Library. 2008:4.
  • 17. NovoSeven RT [prescribing information]. Princeton, NJ: Novo Nordisk Inc; 2012.
  • 18. Yank V, Tuohy CV, Logan AC, et al. Systematic review: benefits and harms of in-hospital use of recombinant factor VIIa for off-label indications. Ann Intern Med. 2011;154:529-540.
  • 19. Logan AC, Yank V, Stafford RS. Off-label use of recombinant factor VIIa in US hospitals: analysis of hospital records. Ann Intern Med. 2011;154:516-522.
  • 20. Gödje O, Gallmeier U, Schelian M, Grünewald M, Mair H. Coagulation factor XIII reduces postoperative bleeding after coronary surgery with extracorporeal circulation. Thorac Cardiovasc Surg. 2006;54:26-33.
  • 21. Gödje O, Haushofer M, Lamm P, Reichert B. The effect of factor XIII on bleeding in coronary surgery. Thorac Cardiovasc Surg. 1998;46:263-267.
  • 22. Inbal A, Oldenburg J, Carcao M, Rosholm A, Tehranchi R, Nugent D. Recombinant factor XIII: a safe and novel treatment for congenital factor XIII deficiency. Blood. 2012;119:5111-5117.
  • 23. Achneck HE, Sileshi B, Jamiolkowski RM, Albala DM, Shapiro ML, Lawson JH. A comprehensive review of topical hemostatic agents: efficacy and recommendations for use. Ann Surg. 2010;251:217-228.
  • 24. Streiff MB, Ness PM. Acquired FV inhibitors: a needless iatrogenic complication of bovine thrombin exposure. Transfusion. 2002;42:18-26.
  • 25. Ortel TL, Mercer MC, Thames EH, Moore KD, Lawson JH. Immunologic impact and clinical outcomes after surgical exposure to bovine thrombin. Ann Surg. 2001;233:88-96.
  • 26. Randleman CD, Singla NK, Renkens KL, Pribble JP, Alexander WA. Persistence of antibodies to the topical hemostat bovine thrombin. Poster presented at: American College of Clinical Pharmacy Annual Meeting; October 18-21, 2009; Anaheim, CA.
  • 27. Cheng CM, Meyer-Massetti C, Kayser SR. A review of three stand-alone topical thrombins for surgical hemostasis. Clin Ther. 2009;31:32-41.
  • 28. Chapman WC, Singla N, Genyk Y, et al. A phase 3, randomized, double-blind comparative study of the efficacy and safety of topical recombinant human thrombin and bovine thrombin in surgical hemostasis. J Am Coll Surg. 2007;205:256-265.
  • 29. Recothrom [prescribing information]. Seattle, WA: ZymoGenetics; 2009.
  • 30. Spotnitz WD, Burks S. Hemostats, sealants, and adhesives II: update as well as how and when to use the components of the surgical toolbox. Clin Appl Thromb Hemost. 2010;16:497-514.