Skip to main content
SpringerLink
Log in

The Role of Selective Drug Therapy in Reducing Mortality in the High-risk Surgical Patients (Tranexamic Acid, Selective Bowel Tract Decontamination, Levosimendan, Beta-blockers, Insulin, Aprotinin, and Statins)

  • Chapter
  • First Online:
The High-risk Surgical Patient

  • 1404 Accesses

Abstract

Among the numerous drugs which can be used perioperatively, there are few with a documented effect on survival according to randomized trials. Tranexamic acid, selective bowel tract decontamination, and levosimendan were found to increase survival. Beta-blockers, insulin, aprotinin, and statins increase mortality in the perioperative setting.

We describe the evidence-based medicine supporting or discouraging the use of these drugs together with the physiopathology and the rationale supporting their use or their investigation. Furthermore, numerous other interventions which have at least one randomized trial to support their effect on perioperative mortality are summarized in a final table.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Head J, Ferrie JE, Alexanderson K, Westerlund H, Vahtera J, Kivimaki M. Diagnosis-specific sickness absence as a predictor of mortality: the Whitehall II prospectivecohort study. BMJ. 2008;337:a1469.

    PubMed  PubMed Central  Google Scholar 

  2. Jencks SF, Williams MV, Coleman EA. Rehospitalizations among patients in the Medicarefee-for-service program. N Engl J Med. 2009;360:1418–28.

    CAS  PubMed  Google Scholar 

  3. Khuri SF, Henderson WG, DePalma RG, Mosca C, Healey NA, Kumbhani DJ. Determinants of long-term survival after major surgery and the adverse effect of postoperative complications. Ann Surg. 2005;242:326–41.

    PubMed  PubMed Central  Google Scholar 

  4. Pearse RM, Holt PJ, Grocott MPW. Managing perioperative risk in patients undergoing elective non-cardiac surgery. BMJ. 2011;343:d5759. https://doi.org/10.1136/bmj.d5759.

    Article  PubMed  Google Scholar 

  5. Boyd O, Jackson N. How is risk defined in high-risk surgical patient management? Crit Care. 2005;9(4):390–6. https://doi.org/10.1186/cc3057. Epub 2005 Feb 9

    Article  PubMed  PubMed Central  Google Scholar 

  6. Levy JH, Ramsay JG, Guyton RA. Aprotinin in cardiac surgery. N Engl J Med. 2006;354:1953–7.

    PubMed  Google Scholar 

  7. Karkouti K, Wijeysundera DN, Yau TM, et al. The independent association of massive blood loss with mortality in cardiac surgery. Transfusion. 2004;44:1453–62.

    PubMed  Google Scholar 

  8. Karkouti K, Beattie WS, Dattilo KM, et al. A propensity score case-control comparison of aprotinin and tranexamic acid in high-transfusion-risk cardiac surgery. Transfusion. 2006;46:327–38.

    CAS  PubMed  Google Scholar 

  9. Hendrickson JE, Hillyer CD. Noninfectious serious hazards of transfusion. Anesth Analg. 2009;108:759–69.

    PubMed  Google Scholar 

  10. Jimenez JJ, Iribarren JL, Lorente L, et al. Tranexamic acid attenuates inflammatory response in cardiopulmonary bypass surgery through blockade of fibrinolysis: a case control study followed by a randomized double-blind controlled trial. Crit Care. 2007;11:R117.

    PubMed  PubMed Central  Google Scholar 

  11. CRASH-2 Trial Collaborators, Shakur H, Roberts I, Bautista R, Caballero J, Coats T, Dewan Y, et al. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010;376(9734):23–32. https://doi.org/10.1016/S0140-6736(10)60835-5.

    Article  CAS  Google Scholar 

  12. Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial.CRASH-3 trial collaborators. Lancet. 2019;394(10210):1713–23. https://doi.org/10.1016/S0140-6736(19)32233-0. Epub 2019 Oct 14.

  13. Rowell SE, Meier EN, McKnight B, Kannas D, May S, Sheehan K, et al. Effect of out-of-hospital tranexamic acid vs placebo on 6-month functional neurologic outcomes in patients with moderate or severe traumatic brain injury. JAMA. 2020;324(10):961–74. https://doi.org/10.1001/jama.2020.8958.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sprigg N, Flaherty K, Appleton JP, et al. Tranexamic acid for hyperacute primary IntraCerebralHaemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial. Lancet. 2018;391(10135):2107–15. https://doi.org/10.1016/S0140-6736(18)31033-X.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. ATACAS Investigators of the ANZCA Clinical Trials Network, Myles PS, Smith JA, Forbes A, Silbert B, Jayarajah M, Painter T, et al. Tranexamic acid in patients undergoing coronary-artery surgery. NEngl J Med. 2017;376(2):136–48. https://doi.org/10.1056/NEJMoa1606424.

    Article  Google Scholar 

  16. ATACAS Investigators and the ANZCA Clinical Trials Network, Myles PS, Smith JA, Kasza J, Silbert B, Jayarajah M, Painter T, et al. Tranexamic acid in coronary artery surgery: one-year results of the Aspirin and Tranexamic Acid for Coronary Artery Surgery (ATACAS) trial. J Thorac Cardiovasc Surg. 2019;157(2):644–652.e9. https://doi.org/10.1016/j.jtcvs.2018.09.113.

    Article  CAS  Google Scholar 

  17. Shakur H, Roberts I, Fawole B, et al. Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial. Lancet. 2017;389(10084):2105–16. https://doi.org/10.1016/S0140-6736(17)30638-4.

    Article  CAS  Google Scholar 

  18. McCormack PL. Tranexamic acid: a review of its use in the treatment of hyperfibrinolysis. Drugs. 2012;72:585–617.

    CAS  PubMed  Google Scholar 

  19. Rationale and design of the PeriOperative ISchemic Evaluation-3 (POISE-3) Trial: a protocol for an international randomized controlled trial evaluating tranexamic acid and a strategy to minimize hypotension in noncardiac surgery

    Google Scholar 

  20. Toller WG, Stranz C. Levosimendan, a new inotropic and vasodilator agent. Anesthesiology. 2006;104:556–69.

    CAS  PubMed  Google Scholar 

  21. Papp Z, Édes I, Fruhwald S, et al. Levosimendan: molecular mechanisms and clinical implications: consensus of experts on the mechanisms of action of levosimendan. Int J Cardiol. 2012;159:82–7.

    PubMed  Google Scholar 

  22. Trikas A, Antoniades C, Latsios G, et al. Long-term effects of levosimendan infusion onInflammatory processes and sFas in patients with severe heart failure. Eur J Heart Fail. 2006;8:804–9.

    CAS  PubMed  Google Scholar 

  23. Fang M, Cao H, Wang Z. Levosimendan in patients with cardiogenic shock complicating myocardial infarction: a meta-analysis. Med Intensiva. 2017;42:409–15.

    PubMed  Google Scholar 

  24. Greco T, Calabrò MG, Covello RD, et al. A Bayesian network meta-analysis on the effect of inodilatory agents on mortality. Br J Anaesth. 2015;114:746–56.

    CAS  PubMed  Google Scholar 

  25. Landoni G, Lomivorotov VV, Alvaro G, et al. Levosimendan for hemodynamic support after cardiac surgery. N Engl J Med. 2017;376(21):2021–31. https://doi.org/10.1056/NEJMoa1616325.

    Article  CAS  PubMed  Google Scholar 

  26. Cholley B, Caruba T, Grosjean S, et al. Effect of Levosimendan on low cardiac output syndrome in patients with low ejection fraction undergoing coronary artery bypass grafting with cardiopulmonary bypass: the LICORN randomized clinical trial. JAMA. 2017;318:548–56.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Landoni G, Lomivorotov VV, Alvaro G, et al. CHEETAH Study Group. Levosimendan for hemodynamic support after cardiac surgery. N Engl J Med. 2017;376(21):2021–31.

    CAS  PubMed  Google Scholar 

  28. Mehta RH, Leimberger JD, van Diepen S, et al. LEVO-CTS Investigators. Levosimendan in patients with left ventricular dysfunction undergoing cardiac surgery. N Engl J Med. 2017;376(21):2032–42.

    CAS  PubMed  Google Scholar 

  29. Fuhrmann JT, Schmeisser A, Schulze MR, Wunderlich C, Schoen SP, Rauwolf T, Weinbrenner C, Strasser RH. Levosimendan is superior to enoximone in refractory cardiogenic shock complicating acute myocardial infarction. Crit Care Med. 2008;36(8):2257–66. https://doi.org/10.1097/CCM.0b013e3181809846.

    Article  CAS  PubMed  Google Scholar 

  30. Silvestri L, de la Cal MA, van Saene HKF. Selective decontamination of the digestive tract: the mechanism of action is control of gut overgrowth. Intensive Care Med. 2021;38:1738–50.

    Google Scholar 

  31. Liberati A, D’Amico R, Pifferi S, et al. Antibiotic prophylaxis to reduce respiratory tract infections and mortality in adults receiving intensive care. Cochrane Database Syst Rev. 2009:CD000022.

    Google Scholar 

  32. Silvestri L, van Saene HKF, Milanese M, Gregori D, Gullo A. Selective decontamination of the digestive tract reduces bloodstream infections and mortality in critically ill patients: a systematic review of randomised controlled trials. J Hosp Infect. 2007;65:187–203.

    CAS  PubMed  Google Scholar 

  33. DeJonge E, Schultz MJ, Spanjaard L, et al. Effects of selective decontamination of digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled trial. Lancet. 2003;362:1011–6.

    CAS  Google Scholar 

  34. Plantinga NL, de Smet AMGA, Oostdijk EAN, et al. Selective digestive and oropharyngeal decontamination in medical and surgical ICU patients: individual patient data meta-analysis. Clin Microbiol Infect. 2018;24(5):505–13.

    CAS  PubMed  Google Scholar 

  35. Silvestri L, van Saene HKF, Weir I, Gullo A. Survival benefit of the full selective digestive decontamination regimen. J Crit Care. 2009;24:474e7–474e14.

    Google Scholar 

  36. Price R, MacLennan G, Glen J, On Behalf of the SuDDICU Collaboration. Selective digestive or oropharyngeal decontamination and topical oropharyngeal chlorhexidine for prevention of death in general intensive care: systematic review and network meta-analysis. BMJ. 2014;348:g2197.

    PubMed  PubMed Central  Google Scholar 

  37. Krueger WA, Lenhart F-P, Neeser G, et al. influence of combined intravenous and topical antibiotic prophylaxis on the incidence of infections, organ dysfunctions, and mortality in critically ill surgical patients. Am J Respir Crit Care Med. 2002;166:1029–37.

    PubMed  Google Scholar 

  38. Abis GSA, Stockman HBAC, Bonjer HJ, et al. Randomised clinical trial of selective decontamination of the digestive tract in elective colorectal cancer surgery (SELECT trial). Br J Surg. 2019;106:355–63.

    CAS  PubMed  Google Scholar 

  39. Roos D, Dijksman LM, Oudemans-van Straaten HM, et al. Randomized clinical trial of perioperative selective decontamination of the digestive tract versus placebo in elective gastrointestinal surgery. Br J Surg. 2011;98:1365–72.

    CAS  PubMed  Google Scholar 

  40. Nathens AB, Marshall JC. Selective decontamination of the digestive tract in surgical patients: a systematic review of the evidence. Arch Surg. 1999;134:170–6.

    CAS  PubMed  Google Scholar 

  41. Silvestri L, van Saene HKF, Bion J. Antipathy against SDD is justified: No. Intensive Care Med. 2018;44:1169–73.

    PubMed  Google Scholar 

  42. DeSmet AM, Kluytmans JA, Cooper BS, et al. Decontamination of the digestive tract and oropharynx in ICU patients. N Engl J Med. 2009;360:20–31.

    CAS  Google Scholar 

  43. Oostdijk EA, Kesecioglu J, Schultz MJ, et al. Effects of decontamination of the oropharynx and intestinaltracton antibiotic resistance in ICUs: a randomized clinical trial. JAMA 2014; 312(14):1429-37. Retraction JAMA. 2017;317:1583–4.

    PubMed  Google Scholar 

  44. Cruickshank JM. Beta-blockers continue to surprise us. Eur Heart J. 2000;21:354–64.

    CAS  PubMed  Google Scholar 

  45. Lindenauer PK, Pekow P, Wang K, Mamidi DK, Gutierrez B, Benjamin EM. Perioperative beta-blocker therapy and mortality after major noncardiac surgery. N Engl J Med. 2005;353(4):349–61. https://doi.org/10.1056/NEJMoa041895.

    Article  CAS  PubMed  Google Scholar 

  46. London MJ, Hur K, Schwartz GG, Henderson WG. Association of perioperative β-blockade with mortality and cardiovascular morbidity following major noncardiac surgery. JAMA. 2013;309(16):1704–13. https://doi.org/10.1001/jama.2013.4135.

    Article  CAS  PubMed  Google Scholar 

  47. POISE Study Group, Devereaux PJ, Yang H, Yusuf S, Guyatt G, Leslie K, Villar JC, Xavier D, Chrolavicius S, et al. Effects of extended-release metoprolol succinate in patients undergoing noncardiac surgery (POISE trial): a randomised controlled trial. Lancet. 2008;371(9627):1839–47. https://doi.org/10.1016/S0140-6736(08)60601-7.

    Article  CAS  Google Scholar 

  48. Wijeysundera DN, Duncan D, Nkonde-Price C, et al. Perioperative beta blockade in noncardiac surgery: a systematic review for the 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. J Am Coll Cardiol. 2014;64(22):2406–25.

    PubMed  Google Scholar 

  49. Mangano DT, Layug EL, Wallace A, Tateo I. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. Multicenter Study of Perioperative Ischemia Research Group. N Engl J Med. 1996;335(23):1713–20. https://doi.org/10.1056/NEJM199612053352301.

    Article  CAS  PubMed  Google Scholar 

  50. Flu WJ, van Kuijk JP, Chonchol M, et al. Timing of pre-operative beta-blocker treatment in vascular surgery patients: influence on post-operative outcome. J Am Coll Cardiol. 2010;56(23):1922–9. https://doi.org/10.1016/j.jacc.2010.05.056.

    Article  PubMed  Google Scholar 

  51. Fleisher LA, Fleischmann KE, Auerbach AD, et al. American College of Cardiology; American Heart Association. 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: a report of the American College of Cardiology/American English Heart Association Task Force on practice guidelines. J Am Coll Cardiol. 2014;64(22):e77–e137. https://doi.org/10.1016/j.jacc.2014.07.944.

    Article  PubMed  Google Scholar 

  52. Smilowitz NR, Berger JS. Perioperative cardiovascular risk assessment and management for noncardiac surgery: a review. JAMA. 2020;324(3):279–90. https://doi.org/10.1001/jama.2020.7840.

    Article  PubMed  Google Scholar 

  53. Mazeraud A, Polito A, Annane D, et al. Experimental and clinical evidences for glucose control in intensive care: is infused glucose the key point for study interpretation? Crit Care. 2014;18(4):232.

    PubMed  PubMed Central  Google Scholar 

  54. Marik PE, Bellomo R. Stress hyperglycemia: an essential survival response! Crit Care. 2013;17(2):305.

    PubMed  PubMed Central  Google Scholar 

  55. Schulman RC, Mechanick JI. Metabolic and nutrition support in the chronic critical illness syndrome. Respir Care. 2012;57(6):958–77.

    PubMed  Google Scholar 

  56. Pichardo-Lowden A, Gabbay RA. Management of hyperglycemia during the perioperative period. Curr Diab Rep. 2012;12:108–18.

    CAS  PubMed  Google Scholar 

  57. Wang CC, Reusch JE. Diabetes and cardiovascular disease: changing the focus from glycemic control to improving long-term survival. Am J Cardiol. 2012;110:58B–68B.

    PubMed  PubMed Central  Google Scholar 

  58. Kwon S, Thompson R, Dellinger P, et al. Importance of perioperative glycemic control in general surgery: a report from the surgical care and outcomes assessment program. Ann Surg. 2013;257:8–14.

    PubMed  Google Scholar 

  59. Sato H, Carvalho G, Sato T, et al. The association of preoperative glycemic control, intraoperative insulin sensitivity, and outcomes after cardiac surgery. J Clin Endocrinol Metab. 2010;95:4338–44.

    CAS  PubMed  Google Scholar 

  60. Capes SE, Hunt D, Malmberg K, et al. Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview. Lancet. 2000;355(9206):773–8.

    CAS  PubMed  Google Scholar 

  61. Krinsley JS. Association between hyperglycemia and increased hospital mortality in a heterogeneous population of critically ill patients. Mayo Clin Proc. 2003;78(12):1471–8.

    PubMed  Google Scholar 

  62. Van Den Berghe G. Intensive insulin therapy in critically ill patients. New Engl J Med. 2001;345(19):1359–67.

    PubMed  Google Scholar 

  63. Van Den Berghe G, Wilmer A. Intensive insulin therapy in the medical ICU. New Eng J Med. 2006;354(5):449–61.

    PubMed  Google Scholar 

  64. Brunkhorst F, Engel C, Bloos F, et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med. 2008;358:125–39.

    CAS  PubMed  Google Scholar 

  65. Preiser JC, Devos P, Ruiz-Santana S, et al. A prospective randomised multi-centre controlled trial on tight glucose control by intensive insulin therapy in adult intensive care units: the Glucontrol study. Intensive Care Med. 2009;35(10):1738–48.

    CAS  PubMed  Google Scholar 

  66. Moghissi ES, Korytkowski MT, DiNardo M, et al. American Association of Clinical Endocrinologists; American Diabetes Association. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Diabetes Care. 2009;32:1119–31.

    PubMed  PubMed Central  Google Scholar 

  67. Ahmed Z, Lockhart CH, Weiner M. Advances in diabetic management: implications for anesthesia. Anesth Analg. 2005;100:666–9.

    PubMed  Google Scholar 

  68. Sousa-Uva M, Head SJ, Milojevic M, Collet JP, Landoni G, Castella M, et al. EACTS Guidelines on perioperative medication in adult cardiac surgery. 2018;53(1):5–33. https://doi.org/10.1093/ejcts/ezx314.68.

    Article  Google Scholar 

  69. Heller SR. Abnormalities of the electrocardiogram during hypoglycaemia: the cause of the dead in bed syndrome? Int J Clin Pract Suppl. 2002;129:27–32.

    Google Scholar 

  70. Lindström T, Jorfeldt L, Tegler L, et al. Hypoglycaemia and cardiac arrhythmias in patients with type 2 diabetes mellitus. Diabet Med. 1992;9(6):536–41.

    PubMed  Google Scholar 

  71. Koivikko ML, Karsikas M, Piet S, al. Effects of controlled hypoglycaemia on cardiac repolarisation in patients with type 1 diabetes. Diabetologia. 2008;51(3):426–35.

    CAS  PubMed  Google Scholar 

  72. Egi M, et al. Pre-morbid glycemic control modifies the interaction between acute hypoglycemia and mortality. Intensive Care Med. 2016;42(4):562–71.

    CAS  PubMed  Google Scholar 

  73. Finfer S, et al. Hypoglycemia and risk of death in critically ill patients. N Engl J Med. 2012;367:1108–18.

    PubMed  Google Scholar 

  74. Wilson M, Weinreb J, Hoo GW. Intensive insulin therapy in critical care: a review of 12 protocols. Diabetes Care. 2007;30:1005–11.

    CAS  PubMed  Google Scholar 

  75. Marik PE, Bellomo R. Stress hyperglycemia: an essential survival response! Crit Care Med. 2013;41:e93–4.

    PubMed  Google Scholar 

  76. Zhou Q, Liao JK. Pleiotropic effects of statins. Basic research and clinical perspectives. Circ J. 2010;74:818–26.

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Lindenauer PK, Pekow P, Wang K, Gutierrez B, Benjamin EM. Lipid-lowering therapy and in-hospital mortality following major noncardiac surgery. JAMA. 2004;291(17):2092–9. https://doi.org/10.1001/jama.291.17.2092.

    Article  CAS  PubMed  Google Scholar 

  78. London MJ, Schwartz GG, HurK HWG. Association of perioperative statin use with mortality and morbidity after major noncardiac surgery. JAMA Intern Med. 2017;177(2):231–42. https://doi.org/10.1001/jamainternmed.2016.8005.

    Article  PubMed  Google Scholar 

  79. Berwanger O, Le Manach Y, Suzumura EA, et al. Association between pre-operative statin use and major cardiovascular complications among patients undergoing non-cardiac surgery: the VISION study. Eur Heart J. 2016;37(2):177–85. https://doi.org/10.1093/eurheartj/ehv456.

    Article  PubMed  Google Scholar 

  80. Berwanger O, de Barros E, Silva PG, Barbosa RR, et al. LOAD Investigators. Atorvastatin for high-risk statin-naive patients undergoing noncardiac surgery: the Lowering the Risk of Operative Complications Using Atorvastatin Loading Dose(LOAD) randomized trial. Am Heart J. 2017;184:88–96. https://doi.org/10.1016/j.ahj.2016.11.001.

    Article  CAS  PubMed  Google Scholar 

  81. Putzu A, Domingues P, de Carvalho E, Silva CM, Pinheiro de Almeida J, Belletti A, et al. Perioperative statin therapy in cardiac and non-cardiac surgery: a systematic review and meta-analysis of randomized controlled trials. Ann Intensive Care. 2018;8(1):95. https://doi.org/10.1186/s13613-018-0441-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Putzu A, Capelli B, Belletti A, Cassina T, Ferrari E, et al. Perioperative statin therapy in cardiac surgery: a meta-analysis of randomized controlled trials. Crit Care. 2016;20(1):395. https://doi.org/10.1186/s13054-016-1560-6.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Zhe Zheng MD, Raja Jayaram MD, Lixin Jiang MD, Jonathan Emberson PD, Yan Zhao MD, Qi Li MD, Juan Du MD, Silvia Guarguagli MD, Hill M, Chen Z, Collins R, Casadei B. Perioperative Rosuvastatin in Cardiac Surgery. N Engl J Med. 2016;374(18):1744–53. https://doi.org/10.1056/NEJMoa1507750.

    Article  CAS  PubMed  Google Scholar 

  84. Hillis LD, Smith PK, Anderson JL, et al. 2011 ACCF/AHA guideline for coronary artery bypass graft surgery. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, Society of Cardiovascular Anesthesiologists, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2011;58:e123–210.

    PubMed  Google Scholar 

  85. Fleisher LA, Fleischmann KE, Auerbach AD, et al. American College of Cardiology; American Heart Association. 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. J Am Coll Cardiol. 2014;64(22):e77–e137. https://doi.org/10.1016/j.jacc.2014.07.944.

    Article  PubMed  Google Scholar 

  86. Fergusson DA, Hebert PC, Mazer CD, et al. A comparison of aprotinin and lysine analogues in high-risk cardiac surgery. N Engl J Med. 2008;358:2319–31.

    CAS  PubMed  Google Scholar 

  87. Gagne JJ, Griesdale DE, Schneeweiss S. Aprotinin and the risk of death and renal dysfunction in patients undergoing cardiac surgery: a meta-analysis of epidemiologic studies. Pharmacoepidemiol Drug Saf. 2009;18:259–68.

    CAS  PubMed  Google Scholar 

  88. Seto S, Kher V, Scicli AG. The effect of aprotinin (a serine protease inhibitor) on renal function and renin release. Hypertension. 1983;5:893–9.

    CAS  PubMed  Google Scholar 

  89. Sartini C, Lomivrotov V, Pisano A, et al. A systematic review and international web-based survey of randomized controlled trials in the perioperative and critical care setting: interventions increasing mortality. J Cardiothorac Vasc Anesthesia. 2019;33:2685–94.

    Google Scholar 

  90. Landoni G, Baiardo Redaelli M, Sartini C, Zangrillo A, Bellomo R, editors. Reducing mortality in critically ill patients. Springer International Publishing; 2021. https://doi.org/10.1007/978-3-030-71917-3.

    Book  Google Scholar 

  91. Haase M, Haase-Fielitz A, Plass M, Kuppe H, Hetzer R, Hannon C, et al. Prophylactic perioperative sodium bicarbonate to prevent acute kidney injury following open heart surgery: a multicenter double-blinded randomized controlled trial. PLoS Med. 2013;10(4):e1001426.

    PubMed  PubMed Central  Google Scholar 

  92. Kennedy JM, van RiJ AM, Soears GE, et al. Polypharmacy in a general surgical unit and consequences of drug withdrawal. Br J Clin Pharmacol. 2000;49:353.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Giovanni Landoni, Martina Baiardo Redaelli & Alberto Zangrillo

  2. Vita-Salute San Raffaele University, Milan, Italy

    Giovanni Landoni & Alberto Zangrillo

Authors
  1. Giovanni Landoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Martina Baiardo Redaelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alberto Zangrillo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giovanni Landoni .

Editor information

Editors and Affiliations

  1. Dipartimento di Emergenza Urgenza, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy

    Paolo Aseni

  2. Divisione di Cardiochirurgia, IRCCS Fondazione Policlinico San Matteo, Pavia, Pavia, Italy

    Antonino Massimiliano Grande

  3. Div. of Emerg. Surg., Abdominal Center, Helsinki University Hospital Meilahti, Helsinki, Finland

    Ari Leppäniemi

  4. Department of Pathophysiology and Transplantation, General Surgery and Trauma Team, University of Milano, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy

    Osvaldo Chiara

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Landoni, G., Baiardo Redaelli, M., Zangrillo, A. (2023). The Role of Selective Drug Therapy in Reducing Mortality in the High-risk Surgical Patients (Tranexamic Acid, Selective Bowel Tract Decontamination, Levosimendan, Beta-blockers, Insulin, Aprotinin, and Statins). In: Aseni, P., Grande, A.M., Leppäniemi, A., Chiara, O. (eds) The High-risk Surgical Patient. Springer, Cham. https://doi.org/10.1007/978-3-031-17273-1_35

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-17273-1_35

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-17272-4

  • Online ISBN: 978-3-031-17273-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation