Skip to main content

Norepinephrine and vital organ blood flow during experimental hyperdynamic sepsis

Intensive Care Medicine volume 29, pages 1774–1781 (2003)Cite this article

Abstract

Objective

To study the effect of norepinephrine (NE) infusion on cerebral, coronary, renal and mesenteric blood flow during sepsis.

Design and setting

Randomised placebo-controlled animal trial in the animal laboratory of university physiology institute.

Animals

Seven merino cross-ewes.

Interventions

Chronic implantation of flow probes (aorta, renal, mesenteric and coronary artery and sagittal sinus). Induction of sepsis by intravenous bolus of E. coli (3×109). After the onset of hyperdynamic sepsis sheep were randomly allocated to either NE (0.4 µg kg−1 min−1) or placebo for 6 h.

Measurements and results

E. coli induced hypotension, fever, oliguria, tachycardia and tachypnoea. It increased cardiac output and renal, mesenteric and coronary blood flows. Sagittal flow remained unchanged. Compared to placebo NE infusion restored mean arterial blood pressure and further increased cardiac output. The increases in renal, mesenteric and coronary blood flow were unaffected. Sagittal flow was also unaltered. Compared to placebo NE increased myocardial performance, mean urine output and creatinine clearance at 2 h.

Conclusions

We conclude that hyperdynamic sepsis increases blood flow to heart, gut and kidney and that NE further increases cardiac output, blood pressure, myocardial performance, and urine output and creatinine clearance while maintaining regional blood flow.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1a-d.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.

References

  1. Schreuder WO, Schneider AJ, Groeneveld ABJ, Thijs LG (1989) Effect of dopamine vs. norepinephrine on hemodynamics in septic shock. Chest 95:1282–1288

    CAS  PubMed  Google Scholar 

  2. Martin C, Papazian L, Perrin G, Saux P, Gouin F (1993) Norepinephrine or dopamine for the treatment of hyperdynamic septic shock? Chest 103:1826–1831

    CAS  PubMed  Google Scholar 

  3. Desjars P, Pinaud M, Potel G, Tasseau F, Touze MD (1987) A reappraisal of norepinephrine therapy in human septic shock. Crit Care Med 15:134–137

    Google Scholar 

  4. Rudis MI, Basha MA, Zarowitz BJ (1996) Is it time to reposition vasopressors and inotropes in sepsis? Crit Care Med 24:525–537

    Google Scholar 

  5. Hesselvik JF, Brodin B (1989) Low dose norepinephrine in patients with septic shock and oliguria: effects on afterload, urine flow, and oxygen transport. Crit Care Med 17:179–180

    CAS  PubMed  Google Scholar 

  6. Meier-Hellmann A, Reinhart K (1995) Effects of catecholamines on regional perfusion and oxygenation in critically ill patients. Acta Anaesthesiol Scand 39 [Suppl 107]:239–248

  7. Task Force of the American College of Critical Care Medicine, Society of Critical Care Medicine (1999) Practice parameters for hemodynamic support of sepsis in adult patients in sepsis. Crit Care Med 27:639–660

    Google Scholar 

  8. Pawlik W, Sheperd AP, Jacobson ED (1975) Effect of vasoactive agents on intestinal oxygen consumption and blood flow in dogs. J Clin Invest 56:484–490

    CAS  PubMed  Google Scholar 

  9. Sheperd AP, Pawlik W, Mailman D, Burks TF, Jacobson ED (1976) Effects of vasoconstrictors on intestinal vascular resistance and oxygen extraction. Am J Physiol 230:298–303

    PubMed  Google Scholar 

  10. Gombos EA, Hulet WH, Bopp P (1962) Reactivity of renal and systemic circulations to vasoconstrictor agents in normotensive and hypertensive subjects. J Clin Invest 41:203–207

    CAS  Google Scholar 

  11. Mills LC, Moyer JH, Handley CA (1960) Effects of various sympathomimetic drugs on renal hemodynamics in normotensive and hypotensive dogs. Am J Physiol 198:1279–1285

    CAS  Google Scholar 

  12. Cronin RE, De Torrente A, Miller PD, Bulger RE, Burke TJ, Schrier RW (1978) Pathogenic mechanisms in early norepinephrine-induced acute renal failure: functional and histological correlates of protection. Kidney Int 14:115–125

    Google Scholar 

  13. Cronin R, Erickson AM, De Torrente A, McDonald KM, Schrier RW (1978) Norepinepherine-induced acute renal failure: a reversible ischemic model of acute renal failure. Kidney Int 14:187–190

    Google Scholar 

  14. Vincent J-L (2001) Hemodynamic support in septic shock Intensive Care Med 27:S80–S92

    Google Scholar 

  15. Abid O, Akca S, Michael PH, Vincent J-L (2000) Strong vasopressor support maybe futile in the intensive care unit patient with multiple organ failure. Crit Care Med 28:947–949

    CAS  PubMed  Google Scholar 

  16. Grant DA, Franzini C, Wild J, Walker AM (1995) Continuous measurement of blood flow in the superior sagittal sinus of the lamb. Am J Physiol 269:R274–279

    CAS  PubMed  Google Scholar 

  17. Bednarik JA, May CN (1995) Evaluation of a transit-time system for the chronic measurement of blood flow in conscious sheep. J Appl Physiol 78:524–530

    CAS  PubMed  Google Scholar 

  18. Matthews JN, Altman DG, Campbell MJ, Royston P (1990) Analysis of serial measurements in medical research. BMJ 300:230–235

    CAS  Google Scholar 

  19. Nasraway SA (2000) Norepinephrine: no more "leave 'em dead"? Crit Care Med 28:3096–3097

    Google Scholar 

  20. Bellomo R, DiGiantomasso D (2001) Noradrenaline and the kidney: friends or foes. Crit Care 5:294–298

    Article  CAS  PubMed  Google Scholar 

  21. Bersten AD, Hersch M, Cheung H, Rutledge FS, Sibbald WJ (1992) The effect of various sympathomimetics on the regional circulation in hyperdynamic sepsis. Surgery 112:549–561

    CAS  PubMed  Google Scholar 

  22. De Matteo R, May CN (1999) Inhibition of prostaglandin and nitric oxide synthesis prevents cortisol-induced renal vasodilatation in conscious sheep. Am J Physiol 276:R1125–R1131

    PubMed  Google Scholar 

  23. Booke M, Hinder F, McGuire R, Traber LD, Traber DL (2000) Noradrenaline and N-monomethyl-L-arginine (L-NMMA): effects on haemodynamics and regional blood flow in healthy and septic sheep. Clin Science 98:193–2000

    CAS  Google Scholar 

  24. Booke M, Hinder F, McGuire R, Traber LD, Traber DL (1996) Nitric oxide inhibition versus norepinephrine for the treatment of hyperdynamic sepsis in sheep. Crit Care Med 24:835–844

    CAS  PubMed  Google Scholar 

  25. Anderson WP, Korner PI, Selig SE (1981) Mechanisms involved in the renal responses to intravenous and renal artery infusions of noradrenaline in conscious dogs. J Physiol (Lond) 321:21–30

  26. Bellomo R, Kellum JA, Wisniewski SR, Pinsky MR (1999) Effects of norepinephrine on the renal vasculature in normal and endotoxemic dogs. Am J Respir Crit Care Med 159:1186–1192

    CAS  PubMed  Google Scholar 

  27. Schaer GL, Fink MP, Parrillo JE (1985) Norepinephrine alone versus norepinephrine plus low-dose dopamine: enhanced renal blood flow with combination pressor therapy. Crit Care Med 13:492–496

    Google Scholar 

  28. Zhang H, Smail N, Cabral A, Rogiers P, Vincent J-L (1997) Effects of norepinephrine on regional blood flow and oxygen extraction capabilities during endotoxic shock. Am J Respir Crit Care Med 155:1965–1971

    CAS  PubMed  Google Scholar 

  29. Bersten AD, Hersch M, Cheung H, Rutledge FS, Sibbald WJ (1992) The effect of various sympathomimetics on the regional circulations in hyperdynamic sepsis. Surgery 112:549–561

    CAS  PubMed  Google Scholar 

  30. Meier-Hellman A, Reinhart K (1995) Effects of catecholamines on regional perfusion and oxygenation in critically ill patients. Acta Anaesthesiol Scand 39 [Suppl 107]:239–248

  31. Marik PE, Mohedin M (1994) The contrasting effects of dopamine and norepinephrine on systemic and splanchnic oxygen otilization in hyperdynamic sepsis. JAMA 272:1354–1357

    CAS  PubMed  Google Scholar 

  32. Breslow MJ, Miller CF, Parker SD, Walman AT, Traystman RJ (1987) Effect of vasopressors on organ blood flow during endotoxin shock in pigs. Am J Physiol 252:H291–H300

    CAS  PubMed  Google Scholar 

  33. Cunnion RE, Schaer GL, Parker M, Natanson C, Parrillo JE (1986) The coronary circulation in human septic shock. Circulation 73:637–644

    CAS  PubMed  Google Scholar 

  34. Dhainaut J-F, Huyghebaert M-F, Monsallier JF, Lefevre G, Dall'Ava-Santucci J, Brunet F, Villemant D (1987) Coronary hemodynamics and myocardial metabolism of lactate, free fatty acids, glucose, and ketones in patients with septic shock. Circulation 75:533–541

    CAS  PubMed  Google Scholar 

  35. Parker MM, Shelhamer JH, Bacharach SL, Green MV, Natanson C, Frederick TM, Danske BA, Parrillo JE (1984) Profound but reversible myocardial depression in patients with septic shock. Ann Intern Med 100:483–490

    CAS  PubMed  Google Scholar 

  36. Leone M, Albanese J, Martin C (2002) Positive inotropic stimulation. Curr Opin Crit Care 8:395–403

    Article  PubMed  Google Scholar 

  37. Szabo L, Kovach AG, Babosa M, Greenberg JH, Revich M (1983) Effect of sustained norepinephrine infusion on local cerebral blood flow in the rat. Circ Shock 10:101–107

    CAS  PubMed  Google Scholar 

  38. Myburgh JA, Upton RN, Grant C, Martinez A (1998) A comparison of the effects of norepinephrine, epinephrine, and dopamine on cerebral blood flow and oxygen utilization. Acta Neurochir (Wien) 71:19–21

    Google Scholar 

  39. Berntman L, Dahlgren N, Siesjo BK (1978) Influence of intravenously administered catecholamines on cerebral oxygen consumption and blood flow in the rat. Acta Physiol Scand 104:101–108

    Google Scholar 

  40. Redl-Wenzel EM, Armbruster C, Edelmann G, Fischl E, Kolacny M, Wechsler-Fordos A, Sporn P (1993) The effects of norepinephrine on hemodynamics and renal function in severe septic shock states. Intensive Care Med 19:151–154

    Google Scholar 

Download references

Author information

Affiliations

  1. Howard Florey Institute, Parkville, Melbourne, Australia

    David Di Giantomasso & Clive N. May

  2. Department of Intensive Care and Department of Medicine, Melbourne University, Melbourne, Australia

    Rinaldo Bellomo

  3. Austin & Repatriation Medical Centre, 3084, Heidelberg, Melbourne, Australia

    Rinaldo Bellomo

Authors
  1. David Di Giantomasso
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Clive N. May
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rinaldo Bellomo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rinaldo Bellomo.

Additional information

This study was supported by an institute grant (no. 983001) from the National Health & Medical Research Council of Australia and by grants from the Intensive Care Foundation of the Australian and New Zealand Intensive Care Society, the Laerdal Foundation (Norway) and the ARMC Anaesthesia and Intensive Care Trust Fund.

An editorial regarding this article can be found in the same issue (http://dx.doi.org/10.1007/s00134-003-1794-z)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Di Giantomasso, D., May, C.N. & Bellomo, R. Norepinephrine and vital organ blood flow during experimental hyperdynamic sepsis. Intensive Care Med 29, 1774–1781 (2003). https://doi.org/10.1007/s00134-003-1736-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00134-003-1736-9

Keywords

  • Norepinephrine
  • Renal blood flow
  • Splanchnic circulation
  • Sepsis, coronary circulation
  • Cerebrovascular circulation