Use Of Terlipressin In Septic Shock

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  • Septic shock is a distributive type of shock where there is widespread vasodilatation following sepsis (Leone and Martin, 2006). Due to the distributive nature of the shock, vigorous resuscitation measures may fail. In those cases, cardio-stimulants and vasopressors are widely used namely noradrenalin (NE), dopamine, dobutamine etc. (Claessens et al. 2007). Nonetheless, the responsiveness of the blood vessels to these drugs gradually fades away resulting in fatalities (Goncalves et al. 1998, Landry and Oliver, 2001, Bennett et al. 2004). Terlipressin (TP) is an analogue of AVP that has been used primarily in the management of variceal bleeding, diabetes insipidus and hepatorenal syndrome (Soederlund, 1993). However, its use in the management of patients with refractory septic shock has been documented revealing its certain advantages over other drugs like longer duration of action and less side effects (O’Brien et al, 2002, ).
  • As a physician working in the Emergency Medicine and Critical Care the author comes across patients with septic shock who do not respond to conventional treatment with intravenous fluids, antibiotics, steroids and catecholamines.
  • RCT= Randomised controlled trials
  • Use Of Terlipressin In Septic Shock

    1. 1. To examine the role of Terlipressin in the management of patients with refractory septic shock.
    2. 2. Introduction <ul><li>The mainstay of management of septic shock is fluid resuscitation, antibiotics and steroids (Sprigings and Chambers 2008). </li></ul><ul><li>In the recent years, vasopressin and its analogues were introduced in the management of patients with noradrenaline resistant septic shock (O’Brien et al, 2002). </li></ul>
    3. 3. <ul><li>Terlipressin is an analogue of Vasopressin that has been used primarily in the management of variceal bleeding, diabetes insipidus and hepatorenal syndrome (Soederlund, 1993). </li></ul><ul><li>Its use in the management of patients with refractory septic shock has been documented in recent year revealing its certain advantages (O’Brien et al. 2002). </li></ul>Introduction
    4. 4. Aims <ul><li>To examine the role of Terlipressin in the management of patients with refractory vasodilatory septic shock </li></ul><ul><li>To evaluate the appropriateness of its use in author’s practice. </li></ul>
    5. 5. Search strategy <ul><li>Initial search with Medline, Ovid and Google scholar. </li></ul><ul><li>Key words: Terlipressin, septic shock, refractory. </li></ul><ul><li>Medline database :53 initial search results with the first two key words but that was cut down to 14 with all the three key words. </li></ul><ul><li>Inclusion criteria: </li></ul><ul><ul><li>Articles in English language </li></ul></ul><ul><ul><li>Published within the last 5 years </li></ul></ul><ul><li>Exclusion criteria: </li></ul><ul><ul><li>Articles in any language other than English were excluded due to the language barrier of the author. </li></ul></ul><ul><ul><li>All animal studies were excluded as they were not relevant to author’s current practice. </li></ul></ul><ul><li>Further evidence was gathered by backward chaining of the literature. </li></ul>
    6. 6. Critical appraisal tools: <ul><li>Critical Appraisal Skills Programme (CASP) tools were used for critical appraisal of evidence. </li></ul><ul><li>Types of papers analysed: case reports, cohort studies and randomised controlled studies. </li></ul><ul><li>The Oxford Centre for Evidence Based Medicine (CEBM) Level of Evidence (March 2009) has been used as a guideline for the hierarchy of evidence. </li></ul>
    7. 7. Summary of evidence
    8. 8. Hierarchy of evidence
    9. 9. Conclusion <ul><li>Even after taking vigorous measures in septic shock, the mortality rate is about 50% (Ruokonen et al.1991). </li></ul><ul><li>Therefore, there has been a need to evaluate new approaches of therapy. </li></ul><ul><li>Terlipressin is one of the new drugs that has been showing some promises in the management of septic shock as has been first reported by O’Brien et al. (2002). </li></ul><ul><li>Occasionally, it has been used as a last resort with significant effects as has been documented by Rodrıguez-Nunez et al. (2006), Leone and Martin (2006) and Filippi et al. (2008). </li></ul>
    10. 10. <ul><li>Although the works of Albanèse at al. (2005), Morelli et al. (2009) and Morelli et al. (2008) revealed the effectiveness of Terlipressin in septic shock, the studies have their own fallacies. </li></ul><ul><li>Lack of further studies made the author cautious about its regular application in his practice. </li></ul><ul><li>It can be concluded from the above discussion that multicentre RCTs with higher number of patients are needed before informing the practice about the applicability of Terlipressin in the management of septic shock patients. </li></ul>Conclusion
    11. 11. References <ul><li>Albanèse, J. Leone, M. Delmas, A. and Martin, C. 2005. Terlipressin or norepinephrine in hyperdynamic septic shock: A prospective, randomized study. Critical Care Medicine 33(9), pp. 1897 – 1902. </li></ul><ul><li>Auzinger, G.M. O’Callaghan, P.G. Harry, R.A. and Wendon, J.A.2002. Terlipressin in the treatment of catecholamine resistant septic shock. 22nd International Symposium on Intensive Care and Emergency Medicine . Brussels, Belgium, 19–22 March 2002 . P131. [Online]. Available at: http://ccforum.com/supplements/6/S1.[Accessed: 19 February 2010]. </li></ul><ul><li>Barrett, L.K. Orie, N.N. Taylor, V. Stidwill. R.P. Clapp, L.H. Singer, M. 2007. Differential effects of vasopressin and norepinephrine on vascular reactivity in a long term rodent model of sepsis. Critical Care Medicine 35, pp. 2337-2343. </li></ul><ul><li>Bennet, T. Mahajan, R.P. March, J.E. Kemp, P.A. Gardiner, S.M. 2004. Regional and temporal changes in cardiovascular responses to norepinephrine and vasopressin during continuous infusion of lipopolysaccharide in conscious rats. British Journal of Anaesthesia 93, pp. 400–407. </li></ul><ul><li>Claessens, Y. and Dhainaut, J.F. 2007. Diagnosis and treatment of severe sepsis. Critical Care 11(Suppl 5), pp.1-8. </li></ul><ul><li>Filippi, L. Poggi, C. Serafini, L. and Fiorini, P. 2008. Terlipressin as rescue treatment of refractory shock in a neonate. Acta Paediatrica 97, pp. 500–512. </li></ul><ul><li>Goncalves JA Jr, Hydo LJ, and Baries PS. 1998. Factors influencing outcome of prolonged norepinephrine therapy for shock in critical surgical illness. Shock , 10, pp. 231-236. </li></ul><ul><li>Hajjar, L. Ticom, T. Magro, M. Galas, F. Sampaio, L. and Auler Jr, J. 2008. Terlipressin in catecholamine-resistant hyperdynamic shock patients after cardiac surgery. Critical Care 12(2),P406 [Online]. Available at: http://ccforum.com/supplements/12/S2 . [Accessed: 19 February 2010]. </li></ul><ul><li>Klein, M. Weksler, N. Borer, A. Koyfman, L. Kesslin, J. and Gurman, G.M. 2006. Terlipressin Facilitates Transport of Septic Patients Treated with Norepinephrine. Israeli Medical Association Journal 8, pp. 691-693. </li></ul><ul><li>Landry, D.W. and Oliver, J.A. 2001. The pathogenesis of vasodilatory shock. New </li></ul><ul><li>England Journal of Medicine 23, pp. 588–95. </li></ul><ul><li>Leone, M. Albanese, J. Delmas, A. Chaabane, W. Garnier, F. and Martin, C. 2004. Terlipressin in catecholamine-resistant septic shock patients. Shock 22(4), pp.314-319. </li></ul><ul><li>Leone, M. and Martin, C. 2006. Rescue therapy in septic shock – is TP the last frontier? Critical care 10, pp. 131-132. </li></ul><ul><li>Levy, M.M. et al. 2003. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Critical Care Medicine 31, pp. 1250-6. </li></ul><ul><li>Matok, I. Vard, A. Efrati, O. Rubinshtein, M. Vishne, T. Leibovitch, L. et al.2005. Terlipressin as rescue therapy for intractable hypotension due to septic shock in children. Shock 23, pp.305–10. </li></ul><ul><li>Morelli, A. Rocco, M. Conti, G. et al. 2004. Effects of terlipressin on systemic and regional haemodynamics in catecholamine-treated hyperkinetic septic shock. Intensive Care Medicine 30, pp.597–604 </li></ul><ul><li>Morelli, A. Ertmer, C. Lange, M. Du¨nser, M. Rehberg, S. Van Aken, H. Pietropaoli, P. and Westphal, M. 2008. Effects of short-term simultaneous infusion of dobutamine and terlipressin in patients with septic shock: the DOBUPRESS study. British Journal of Anaesthesia 100 (4), pp. 494–503. </li></ul>
    12. 12. References <ul><li>Morelli, A. Ertmer, C. Rehberg, S. Lange, M. Orecchioni, A. Cecchini, V. Bachetoni, A. D'Alessandro, M. Van Aken, H. Pietropaoli, P. and Westphal, M. 2009. Continuous TP versus vasopressin infusion in septic shock (TERLIVAP): a randomized, controlled pilot study. Critical Care 13, R130 [Online]. Available at: http://ccforum.com/content/13/4/R130 . [Accessed: 28 December 2009]. </li></ul><ul><li>O’Brien, A. Clapp, L. and Singer, M. 2002. Terlipressin for norepinephrine resistant septic shock. Lancet 359, pp.1209-1210. </li></ul><ul><li>Phillips, B. Ball, C. Sackett, D. Badenoch, D. Straus, S. Haynes, B. Dawes, M. and Howick, J. 2009. Oxford Centre for Evidence-based Medicine Levels of Evidence [Online]. Available at: http:// www.cebm.net/index.aspx?o =1025 . [Accessed: 17 November 2009]. </li></ul><ul><li>Public Health Resource Unit. 2006. Critical Appraisal Skills Programme (CASP) [Online]. Available at: http:// www.phru.nhs.uk/Pages/PHD/resouces.htm . [Accessed: 17 November 2009]. </li></ul><ul><li>Rodr´ıguez-Nu´n˜ ez, A. Lo´pez-Herce, J. Gil-Anto´n, J. Herna´ndez, A. Rey, C. 2006. Rescue treatment with terlipressin in children with refractory septic shock: a clinical study. Critical Care 10, R20.[Online]. Available at: http://ccforum.com/content/10/1/R20 . [Accessed: 28 December 2009] </li></ul><ul><li>Ruokonen, E. Takala, J. Kari, A. and Alhava, E. 1991. Septic shock and multiple </li></ul><ul><li>organ failure . Critical Care Medicine 19,pp.1146-1151. </li></ul><ul><li>Russell, J.A. Walley, K.R. Singer, J. Gordon, A.C. Hébert, P.C. Cooper, D.J. Holmes, C.L. Mehta, S. Granton, J.T. Storms, M.M. Cook, D.J. Presneill, J.J. Ayers, D. 2008. VASST Investigators: Vasopressin versus norepinephrine infusion in patients with septic shock. New England Journal of Medicine 358, pp. 877-887. </li></ul><ul><li>Salluh, J.I.F. Martins, G. A. R. Santino, M. S. Arau´ Jo, L. V. Freitas, G. G. and Verdeal, J. C. R. 2007. Early use of terlipressin in catecholamine resistant shock improves cerebral perfusion pressure in severe traumatic brain injury. Acta Anaesthesiologica Scandinavica 51, pp.505–508. </li></ul><ul><li>Soederlund, C. 1993. Terlipressin (glypressin) in the treatment of bleeding esophageal varices. State of the art. Regulatory Peptides 45 (1-2), pp. 299-302. </li></ul><ul><li>Sprigings, D. and Chambers, J. 2008. Acute medicine- a practical guide to the management of medical emergencies. 4th edition. Oxford: Blackwell Publishing. </li></ul><ul><li>Tsuneyoshi, I. Yamada, H. Kakihana, Y. Nakamura, M. Nakano, Y. </li></ul><ul><li>Boyle, W.A. 2001. Hemodynamic and metabolic effects of low-dose vasopressin </li></ul><ul><li>infusions in vasodilatory septic shock. Critical Care Medicine 29, pp. 487–493. </li></ul><ul><li>Westphal, M. Stubbe, H. Sielenkämper, A.W. Borgulya, R. Van Aken, H. Ball, C. and </li></ul><ul><li>Bone, H.G. 2003. TP dose response in healthy and endotoxemic sheep: impact on cardiopulmonary performance and global oxygen transport. Intensive Care Medicine 29, pp. 301–308. </li></ul><ul><li>Wikipedia 2010. Analysis of variance [Online]. Available at: http:// en.wikipedia.org/wiki/Anova [Accessed: 21 February 2010]. </li></ul><ul><li>Yeh, C.C. Wu, C.T. Lu, C.H. Yang, C.P. Wong, C.S. 2003. Early use of small-dose vasopressin for unstable hemodynamics in an acute brain injury patient refractory to catecholamine treatment: a case report. Anesth Analg 97,pp. 577–579. </li></ul><ul><li>Zeballos, G. Lopez-Herce, J. Fernandez, C. Brandstrup, K.B. and Rodriguez-Nunez, A. 2006. Rescue therapy with terlipressin by continuous infusion in a child with catecholamine-resistant septic shock. Resuscitation 68,pp. 151–153. </li></ul>
    13. 13. <ul><li>Thank you </li></ul>

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