Skip to main content
SpringerLink
Log in

Effects of two different dosing regimens of terlipressin on organ functions in ovine endotoxemia

  • Original Research Paper
  • Published:
Inflammation Research Aims and scope Submit manuscript

Abstract

Objective and design

To test the hypothesis that a continuous infusion of the vasopressin analog terlipressin is associated with less organ dysfunction as compared to intermittent bolus infusion in an ovine sepsis model.

Subjects

Twenty-seven adult female sheep.

Treatment

All sheep were subjected to a Salmonella typhosa endotoxin infusion (10 ng/kg/min). After 16 h of endotoxemia, the surviving animals (n = 24) were randomized to (1) an untreated control group, (2) a continuous terlipressin group (2 mg/24 h), or (3) a terlipressin bolus group (1 mg/6 h).

Methods

Hemodynamic variables were measured and blood was withdrawn at specific time points for the assessment of organ functions.

Results

Continuous terlipressin infusion was associated with improved surrogate parameters of myocardial, renal, and hepatic function as compared with terlipressin bolus infusion. Reduced vascular hyperpermeability was evidenced by an attenuated decrease in plasma protein concentrations in sheep treated with continuous terlipressin infusion as compared to bolus injection or no treatment.

Conclusions

Continuous infusion of low-dose terlipressin preserved several surrogate parameters of organ function better than intermittent bolus injections in sheep with systemic inflammation.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29:1303–10.

    Article  PubMed  CAS  Google Scholar 

  2. Landry DW, Oliver JA. The pathogenesis of vasodilatory shock. N Engl J Med. 2001;345:588–95.

    Article  PubMed  CAS  Google Scholar 

  3. O’Brien A, Clapp L, Singer M. Terlipressin for norepinephrine-resistant septic shock. Lancet. 2002;359:1209–10.

    Article  PubMed  Google Scholar 

  4. Albanese J, Leone M, Delmas A, Martin C. Terlipressin or norepinephrine in hyperdynamic septic shock: a prospective, randomized study. Crit Care Med. 2005;33:1897–902.

    Article  PubMed  CAS  Google Scholar 

  5. Leone M, Albanese J, Delmas A, Chaabane W, Garnier F, Martin C. Terlipressin in catecholamine-resistant septic shock patients. Shock. 2004;22:314–9.

    Article  PubMed  CAS  Google Scholar 

  6. Ioannou G, Doust J, Rockey DC. Terlipressin for acute esophageal variceal hemorrhage. Cochrane Database Syst Rev 2001:CD002147.

  7. Medel J, Boccara G, Van de Steen E, Bertrand M, Godet G, Coriat P. Terlipressin for treating intraoperative hypotension: can it unmask myocardial ischemia? Anesth Analg. 2001;93:53–5.

    Article  PubMed  CAS  Google Scholar 

  8. Morelli A, Rocco M, Conti G, Orecchioni A, De Gaetano A, Cortese G, et al. Effects of terlipressin on systemic and regional haemodynamics in catecholamine-treated hyperkinetic septic shock. Intensive Care Med. 2004;30:597–604.

    Article  PubMed  Google Scholar 

  9. Scharte M, Meyer J, Van Aken H, Bone HG. Hemodynamic effects of terlipressin (a synthetic analog of vasopressin) in healthy and endotoxemic sheep. Crit Care Med. 2001;29:1756–60.

    Article  PubMed  CAS  Google Scholar 

  10. Asfar P, Hauser B, Ivanyi Z, Ehrmann U, Kick J, Albicini M, et al. Low-dose terlipressin during long-term hyperdynamic porcine endotoxemia: effects on hepatosplanchnic perfusion, oxygen exchange, and metabolism. Crit Care Med. 2005;33:373–80.

    Article  PubMed  CAS  Google Scholar 

  11. Morelli A, Ertmer C, Lange M, Westphal M. Continuous terlipressin infusion in patients with septic shock: less may be best, and the earlier the better? Intensive Care Med. 2007;33:1669–70.

    Article  PubMed  Google Scholar 

  12. Lange M, Morelli A, Ertmer C, Koehler G, Broking K, Hucklenbruch C, et al. Continuous versus bolus infusion of terlipressin in ovine endotoxemia. Shock. 2007;28:623–9.

    Article  PubMed  CAS  Google Scholar 

  13. Westphal M, Sielenkamper AW, Van Aken H, Stubbe HD, Daudel F, Schepers R, et al. Dopexamine reverses the vasopressin-associated impairment in tissue oxygen supply but decreases systemic blood pressure in ovine endotoxemia. Anesth Analg. 2004;99:878–85.

    Article  PubMed  CAS  Google Scholar 

  14. Westphal M, Stubbe H, Sielenkamper AW, Ball C, Van Aken H, Borgulya R, et al. Effects of titrated arginine vasopressin on hemodynamic variables and oxygen transport in healthy and endotoxemic sheep. Crit Care Med. 2003;31:1502–8.

    Article  PubMed  CAS  Google Scholar 

  15. Fincke R, Hochman JS, Lowe AM, Menon V, Slater JN, Webb JG, et al. Cardiac power is the strongest hemodynamic correlate of mortality in cardiogenic shock: a report from the SHOCK trial registry. J Am Coll Cardiol. 2004;44:340–8.

    Article  PubMed  Google Scholar 

  16. Ertmer C, Bone HG, Morelli A, Van Aken H, Erren M, Lange M, et al. Methylprednisolone reverses vasopressin hyporesponsiveness in ovine endotoxemia. Shock. 2007;27:281–8.

    Article  PubMed  CAS  Google Scholar 

  17. Rehberg S, Ertmer C, Kohler G, Spiegel HU, Morelli A, Lange M, et al. Role of arginine vasopressin and terlipressin as first-line vasopressor agents in fulminant ovine septic shock. Intensive Care Med. 2009;35:1286–96.

    Article  PubMed  CAS  Google Scholar 

  18. Petersen MB. The effect of vasopressin and related compounds at V1a and V2 receptors in animal models relevant to human disease. Basic Clin Pharmacol Toxicol. 2006;99:96–103.

    Article  PubMed  CAS  Google Scholar 

  19. Bernadich C, Bandi JC, Melin P, Bosch J. Effects of F-180, a new selective vasoconstrictor peptide, compared with terlipressin and vasopressin on systemic and splanchnic hemodynamics in a rat model of portal hypertension. Hepatology. 1998;27:351–6.

    Article  PubMed  CAS  Google Scholar 

  20. Nilsson G, Lindblom P, Ohlin M, Berling R, Vernersson E. Pharmacokinetics of terlipressin after single i.v. doses to healthy volunteers. Drugs Exp Clin Res. 1990;16:307–14.

    PubMed  CAS  Google Scholar 

  21. Morelli A, Ertmer C, Rehberg S, Lange M, Orecchioni A, Cecchini V, et al. Continuous terlipressin versus vasopressin infusion in septic shock (TERLIVAP): a randomized, controlled pilot study. Crit Care. 2009;13:R130.

    Article  PubMed  Google Scholar 

  22. Ouattara A, Landi M, Le Manach Y, Lecomte P, Leguen M, Boccara G, et al. Comparative cardiac effects of terlipressin, vasopressin, and norepinephrine on an isolated perfused rabbit heart. Anesthesiology. 2005;102:85–92.

    Article  PubMed  CAS  Google Scholar 

  23. Evora PR, Pearson PJ, Rodrigues AJ, Viaro F, Schaff HV. Effect of arginine vasopressin on the canine epicardial coronary artery: experiments on V1-receptor-mediated production of nitric oxide. Arq Bras Cardiol. 2003;80:483–94.

    PubMed  Google Scholar 

  24. Dunser MW, Mayr AJ, Stallinger A, Ulmer H, Ritsch N, Knotzer H, et al. Cardiac performance during vasopressin infusion in postcardiotomy shock. Intensive Care Med. 2002;28:746–51.

    Article  PubMed  CAS  Google Scholar 

  25. Dunser MW, Mayr AJ, Ulmer H, Knotzer H, Sumann G, Pajk W, et al. Arginine vasopressin in advanced vasodilatory shock: a prospective, randomized, controlled study. Circulation. 2003;107:2313–9.

    Article  PubMed  Google Scholar 

  26. Duenser MW, Hasibeder WR. Dear vasopressin, where is your place in septic shock? Crit Care. 2005;9:134–5.

    Article  PubMed  Google Scholar 

  27. Luckner G, Dunser MW, Jochberger S, Mayr VD, Wenzel V, Ulmer H, et al. Arginine vasopressin in 316 patients with advanced vasodilatory shock. Crit Care Med. 2005;33:2659–66.

    Article  PubMed  CAS  Google Scholar 

  28. Farand P, Hamel M, Lauzier F, Plante GE, Lesur O. Review article: organ perfusion/permeability-related effects of norepinephrine and vasopressin in sepsis. Can J Anaesth. 2006;53:934–46.

    Article  PubMed  Google Scholar 

  29. Schuller D, Mitchell JP, Calandrino FS, Schuster DP. Fluid balance during pulmonary edema. Is fluid gain a marker or a cause of poor outcome? Chest. 1991;100:1068–75.

    Article  PubMed  CAS  Google Scholar 

  30. Laporte R, Wisniewska H, Callejas L, Russell J, Landry D, Rivière P. The selective V1a receptor agonist FE202158 reverses platelet activated factor (PAF)-induced hypotension, vascular leak, impaired tissue perfusion, and mortality in rats. Shock. 2008;Suppl 1(Abstract):P21.

    Google Scholar 

  31. Traber D. Selective V1a receptor agonists in experimental septic shock. Crit Care. 2007;11(Abstract):P51.

    Google Scholar 

  32. Bichet DG, Razi M, Lonergan M, Arthus MF, Papukna V, Kortas C, et al. Hemodynamic and coagulation responses to 1-desamino[8-d-arginine] vasopressin in patients with congenital nephrogenic diabetes insipidus. N Engl J Med. 1988;318:881–7.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Katharina Goering, Markus Sporkmann, Mareike Bommert, and Marga Kaiser for expert technical assistance during the experiments. Terlipressin (Haemopressin®) was provided by Prof. Dr. Klaus D. Doehler (Medizinische Hochschule Hannover, Hannover, Germany). This study was supported by Curatis Pharma GmbH and MM GmbH, Hannover, Germany.

Author information

Authors and Affiliations

  1. Department of Anesthesiology and Intensive Care, University of Muenster, Albert-Schweitzer Str. 33, 48149, Muenster, Germany

    Matthias Lange, Christian Ertmer, Sebastian Rehberg, Tim G. Kampmeier, Hugo Van Aken & Martin Westphal

  2. Department of Anesthesiology and Intensive Care, University of Rome “La Sapienza”, Via B. Oriani 2, 00197, Rome, Italy

    Andrea Morelli

  3. Department of Pathology, University of Muenster, Domagkstr. 5, 48149, Muenster, Germany

    Gabriele Köhler

Authors
  1. Matthias Lange
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christian Ertmer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sebastian Rehberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Andrea Morelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gabriele Köhler
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tim G. Kampmeier
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hugo Van Aken
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Martin Westphal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Matthias Lange.

Additional information

Responsible Editor: Artur Bauhofer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lange, M., Ertmer, C., Rehberg, S. et al. Effects of two different dosing regimens of terlipressin on organ functions in ovine endotoxemia. Inflamm. Res. 60, 429–437 (2011). https://doi.org/10.1007/s00011-010-0299-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-010-0299-9

Keywords

Search

Navigation