Intensive Care Medicine

, Volume 30, Issue 4, pp 597–604

Effects of terlipressin on systemic and regional haemodynamics in catecholamine-treated hyperkinetic septic shock

  • Andrea Morelli
  • Monica Rocco
  • Giorgio Conti
  • Alessandra Orecchioni
  • Andrea De Gaetano
  • Giuliana Cortese
  • Flaminia Coluzzi
  • Enrico Vernaglione
  • Paolo Pelaia
  • Paolo Pietropaoli
Original

Abstract

Objectives

To determine the effects of an intravenous bolus dose of a vasopressin analogue, terlipressin (1 mg), on systemic haemodynamic parameters and gastric mucosal perfusion (GMP) in patients with catecholamine-treated septic shock using a gastric tonometry and laser-Doppler flowmetry technique.

Design

Prospective open label study.

Settings

Two multidisciplinary intensive care units.

Patients

Fifteen patients with norepinephrine-treated septic shock.

Interventions

Every patient with mean arterial pressure between 50 and 55 mmHg treated with high dose norepinephrine received an intravenous bolus dose of terlipressin as last resort therapy. A laser-Doppler probe and tonometer were introduced into the gastric lumen.

Measurements and main results

Terlipressin produced a decrease in cardiac output (p<0.05), a progressive increase in mean arterial pressure (p<0.05) and in GMP, detected by laser-Doppler flowmetry (p<0.05) over 30 min and sustained for at least 24 h. The ratio of GMP to systemic oxygen delivery increased after terlipressin bolus dose (p<0.05). The gradient between gastric mucosal and arterial PCO2 tended to be lower after terlipressin, and the difference was statistically significant (p<0.05) after 8 h. Terlipressin administration significantly increased (p<0.05) urine output compared to baseline and higher values were found at each set of measurement. The terlipressin-induced increase in urine output was associated with a significantly increased creatinine clearance (p<0.05). Reduction of the high-dose norepinephrine was observed in all patients (p<0.05).

Conclusions

Our findings showed that, in patients with norepinephrine-treated septic shock, terlipressin increased GMP, urine output and creatinine clearance by an increase in mean arterial pressure.

Keywords

Gastric mucosal perfusion Septic shock Terlipressin Norepinephrine Laser-Doppler, tonometry 

References

  1. 1.
    Landry DW, Levin HR, Gallant EM, Seo S, D’Alessandro D, Oz MC, Oliver JA (1997) Vasopressin pressor hypersensivity in vasodilatatory septic shock. Crit Care Med 25:1279–1282PubMedGoogle Scholar
  2. 2.
    Landry DW, Levin HR, Gallant EM, Asthon RC Jr, Seo S, D’Alessandro D, Oz MC, Oliver JA (1997) Vasopressin deficiency contributes to the vasodilatation of septic shock. Circulation 95:1122–1125PubMedGoogle Scholar
  3. 3.
    Chernow B, Roth B (1986) Pharmacologic manipulation of the peripheral vasculature in septic shock: clinical and experimental approaches. Circ Shock 18:141–155PubMedGoogle Scholar
  4. 4.
    Schaller MD, Waeber B, Nusseberger Brunner HR (1985) Angiotensin I, vasopressin and sympathetic activity in conscious rats with endotoxemia. Am J Physiol 18:H1086-H1092Google Scholar
  5. 5.
    Hollenberg SM, Tangora JJ, Piotrowsky MJ, Easington C, Parrillo JE (1997) Impaired micro-vascular vasoconstrictive responses to vasopressin in septic rats. Crit Care Med 25:869–873PubMedGoogle Scholar
  6. 6.
    Wilson MF, Brackett DJ, Hinshaw LB, Tompkins P, Archer LT, Benjamin BA (1981) Vasopressin releasing during sepsis and septic shock in baboons and dogs. Surg Gynecol Obstet 153:869–872PubMedGoogle Scholar
  7. 7.
    Brackett DJ, Schaefer CF, Tompkins P, Fragaeus L, Peters LG, Wilson MF (1985) Evaluation of cardiac output, total peripheral resistances and plasma concentrations of vasopressin in the conscious, unrestrained rat during endotoxemia. Circ Shock 17:273–284PubMedGoogle Scholar
  8. 8.
    Egan JW, Jugus M, Kinter LB, Lee K, Smith EF (1989) Effect of a selective vasopressin receptor antagonist on the sequelae of endotoxemia in the conscious rat. Circ Res 29:155–166Google Scholar
  9. 9.
    Malay MB, Asthon RCJ, Landry DW, Townsend RN (1999) Low-dose vasopressin in the treatment of vasodilatatory septic shock. J Trauma 47:699–705PubMedGoogle Scholar
  10. 10.
    Heyndrickx GR, Boettcher DH, Vatner SF (1976) Effects of angiotensin, vasopressin and methoxamine on cardiac function and blood flow distribution in conscious dogs. Am J Physiol 231:1579–1587PubMedGoogle Scholar
  11. 11.
    Tsuneyoshi I, Yamada H, Kakihana Y, Nakamura L, Nakano Y, Boyle WA (2001) Haemodynamic and metabolic effects of low dose vasopressin infusions in vasodilatatory septic shock. Crit Care Med 29:487–493PubMedGoogle Scholar
  12. 12.
    Bernadich C, Bandi JC, Bosch J (1988) Effects of F-180, a new selective vasoconstrictor peptide compared with terlipressin and vasopressin on systemic and splanchnic haemodynamics in rat model of portal hypertension. Hepatology 27:351–356Google Scholar
  13. 13.
    Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 101:1644–1655PubMedGoogle Scholar
  14. 14.
    Duranteau J, Sitbon P, Teboul JL, Vicaut E, Anguel N, Richard C, Samii K (1999) Effects of epinephrine, norepinephrine or combination of norepinephrine and dobutamine on gastric mucosa in septic shock. Crit Care Med 27:893–900PubMedGoogle Scholar
  15. 15.
    Parvianen I, Vaisanen O, Ruokonen E, Takala J (1996) Effect of nasogastric suction and ranitidine on the calculated gastric intramucosal pH. Intensive Care Med 22:319–323PubMedGoogle Scholar
  16. 16.
    Kvietys PR, Shepherd AP, Neil Granger D (1985) Laser-Döppler, H2 clearance and microsphere estimates of mucosal blood flow. Am J Physiol 249:G221-G227PubMedGoogle Scholar
  17. 17.
    Nicholson CD, Schmitt RA, Wilke R (1985) The effect of acute and chronic femoral artery ligation on the blood flow through the gastrocnemius muscle of the rat examined using laser-Doppler flowmetry and Xenon133 clearance. Int J Microcirc Clin Exp 4:151–171Google Scholar
  18. 18.
    Oberg A (1990) Laser-Doppler flowmetry. Biomedical Engineering 18:125–163Google Scholar
  19. 19.
    Krohg-Sorensen K, Line PD, Kvernebo K (1993) The significance of probe design in evaluation of colonic perfusion with laser-Doppler flowmetry. Scand J Gastroenterol 28:381–386PubMedGoogle Scholar
  20. 20.
    Abboud FM, Floras JS, Aylward PE, Guo GP, Gupta BN, Schmid PG (1990) Role of vasopressin in cardiovascular and blood pressure regulation. Blood Vessels 27:106–115PubMedGoogle Scholar
  21. 21.
    Schwartz J, Reid IA (1981) Effect of vasopressin blockade on blood pressure regulation during hemorrhage in conscious dogs. Endocrinology 109:1778–1780PubMedGoogle Scholar
  22. 22.
    Laslo FA, Laslo F Jr, De Wied D (1991) Pharmacology and clinical perspective of vasopressin antagonists. Pharmacol Rev 43:73–108PubMedGoogle Scholar
  23. 23.
    Minaker KL, Meneilly GS, Youn GJ, Landberg L, Stoff JS, Robertson GL, Rowe JW (1991) Blood pressure, pulse and neurohumoral responses to nitroprusside-induced hypotension in normotensive aging men. J Gerontol 46:M151–154PubMedGoogle Scholar
  24. 24.
    Schrier RW, Berl T, Anderson RJ (1979) Osmotic and non osmotic control of vasopressin release. Am J Physiol 236:F321-F332PubMedGoogle Scholar
  25. 25.
    Holmes CL, Patel BM, Russell JA, Walley KR (2001) Physiology of vasopressin relevant to management of septic shock. Chest 120:989–1002PubMedGoogle Scholar
  26. 26.
    Iwao T, Toyonaga A, Oho K, Shigemori H, Sakai T, Tayama C, Masumoto H, Sato M, Tanikawa K (1996) Vasopressin plus oxygen vs vasopressin alone in cirrhotic patients with portal-hypertensive gastropathy: effects on gastric mucosal haemodynamics and oxygenation. J Gastroenterol Hepatol 11:216–222PubMedGoogle Scholar
  27. 27.
    Laszlo F, Karacsony G, Pavo I, Varga C, Rojik I, Laszlo FA (1994) Aggressive role of vasopressin in development of different gastric lesions in rats. Eur J Pharmacol 258:15–22PubMedGoogle Scholar
  28. 28.
    Montani JP, Liard JF, Schoun J, Mohring J (1980) Haemodynamic effects of exogenous and endogenous vasopressin at low plasma concentrations in conscious dogs. Circ Res 47:346–355PubMedGoogle Scholar
  29. 29.
    Undesser KP, Hasser EM, Haywood JR, Johonson AK, Bishop VS (1985) Interactions of vasopressin with the area postrema in arterial baroreflex function in conscious rabbits. Circ Res 56:410–417PubMedGoogle Scholar
  30. 30.
    Asfar P, Pierrot M, Veal N, Moal F, Oberti F, Croquet V, Douay O, Gallois Y, Saumet JL, Alquier P, Cales P (2003) Low-dose terlipressin improves systemic and splanchnic haemodynamics in fluid-challenged endotoxic rats. Crit Care Med 31:215–220PubMedGoogle Scholar
  31. 31.
    Auzinger GM, O’Callaghan PG, Harry RA (2002) Terlipressin in the treatment of the catecholamine resistant septic shock (abstract). Crit Care 6:61CrossRefGoogle Scholar
  32. 32.
    Klinzing S, Schiergens V, Reinhart K (2002) Could vasopressin be an alternative for vasopressor therapy in sepsis? (abstract) Eur J Anaesthesiol 19:169–170Google Scholar
  33. 33.
    Russel JA (1997) Gastric tonometry: does it work? Intensive Care Med 23:3-6CrossRefPubMedGoogle Scholar
  34. 34.
    Edwards RM, Trizna W, Kinter LB (1989) Renal effects of vasopressin and vasopressin antagonists. Am J Physiol 256:F274–278PubMedGoogle Scholar
  35. 35.
    Schreuder WO, Schneider AJ, Groeneveld AB, Thijs LG (1989) Effect of dopamine vs norepinephrine on haemodynamics in septic shock: emphasis on right ventricular performance. Chest 95:1282–1288PubMedGoogle Scholar
  36. 36.
    Bomzon L, Rosendorff C, Scriven DR, Farr J (1975) The effect of noradrenaline, adrenergic blocking agents and tyramine on the intrarenal distribution of blood flow in the baboon. Cardiovasc Res 9:314–322PubMedGoogle Scholar
  37. 37.
    Patel BM, Chittok DR, Russel JA, Walley KR (2002) Beneficial effects of short-term vasopressin infusion during severe septic shock. Anaesthesiology 96:576–582Google Scholar
  38. 38.
    O’Brien A, Clapp L, Singer M (2002) Terlipressin for norepinephrine-resistant septic shock. Lancet 359:1209–1210CrossRefPubMedGoogle Scholar
  39. 39.
    Sharshar T, Blanchard A, Paillard M, Raphael JC, Gajdos P, Annane D (2003) Circulating vasopressin levels in septic shock. Crit Care Med 31(6):1752–1758CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Andrea Morelli
    • 1
    • 5
  • Monica Rocco
    • 1
  • Giorgio Conti
    • 2
  • Alessandra Orecchioni
    • 1
  • Andrea De Gaetano
    • 3
  • Giuliana Cortese
    • 3
  • Flaminia Coluzzi
    • 1
  • Enrico Vernaglione
    • 1
  • Paolo Pelaia
    • 4
  • Paolo Pietropaoli
    • 1
  1. 1.Department of Anaesthesiology and Intensive CareUniversity of Rome “La Sapienza”RomeItaly
  2. 2.Department of Anaesthesiology and Intensive CareCatholic University of RomeRomeItaly
  3. 3.CNR IASI Biomath LaboratoryRomeItaly
  4. 4.Department of Anaesthesiology and Intensive Care, Ospedale TorretteUniversity of AnconaAnconaItaly
  5. 5.Via B. Oriani 2RomeItaly

Personalised recommendations