Skip to main content
Top
Published in: Intensive Care Medicine 10/2003

01-10-2003 | Original

Norepinephrine and vital organ blood flow during experimental hyperdynamic sepsis

Authors: David Di Giantomasso, Clive N. May, Rinaldo Bellomo

Published in: Intensive Care Medicine | Issue 10/2003

Login to get access

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.
Literature
1.
go back to reference Schreuder WO, Schneider AJ, Groeneveld ABJ, Thijs LG (1989) Effect of dopamine vs. norepinephrine on hemodynamics in septic shock. Chest 95:1282–1288PubMed Schreuder WO, Schneider AJ, Groeneveld ABJ, Thijs LG (1989) Effect of dopamine vs. norepinephrine on hemodynamics in septic shock. Chest 95:1282–1288PubMed
2.
go back to reference Martin C, Papazian L, Perrin G, Saux P, Gouin F (1993) Norepinephrine or dopamine for the treatment of hyperdynamic septic shock? Chest 103:1826–1831PubMed Martin C, Papazian L, Perrin G, Saux P, Gouin F (1993) Norepinephrine or dopamine for the treatment of hyperdynamic septic shock? Chest 103:1826–1831PubMed
3.
go back to reference 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 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
4.
go back to reference Rudis MI, Basha MA, Zarowitz BJ (1996) Is it time to reposition vasopressors and inotropes in sepsis? Crit Care Med 24:525–537 Rudis MI, Basha MA, Zarowitz BJ (1996) Is it time to reposition vasopressors and inotropes in sepsis? Crit Care Med 24:525–537
5.
go back to reference 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 17:179–180PubMed 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 17:179–180PubMed
6.
go back to reference 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 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.
go back to reference 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 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
8.
go back to reference Pawlik W, Sheperd AP, Jacobson ED (1975) Effect of vasoactive agents on intestinal oxygen consumption and blood flow in dogs. J Clin Invest 56:484–490PubMed Pawlik W, Sheperd AP, Jacobson ED (1975) Effect of vasoactive agents on intestinal oxygen consumption and blood flow in dogs. J Clin Invest 56:484–490PubMed
9.
go back to reference Sheperd AP, Pawlik W, Mailman D, Burks TF, Jacobson ED (1976) Effects of vasoconstrictors on intestinal vascular resistance and oxygen extraction. Am J Physiol 230:298–303PubMed Sheperd AP, Pawlik W, Mailman D, Burks TF, Jacobson ED (1976) Effects of vasoconstrictors on intestinal vascular resistance and oxygen extraction. Am J Physiol 230:298–303PubMed
10.
go back to reference 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 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
11.
go back to reference 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 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
12.
go back to reference 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 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
13.
go back to reference 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 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
14.
go back to reference Vincent J-L (2001) Hemodynamic support in septic shock Intensive Care Med 27:S80–S92 Vincent J-L (2001) Hemodynamic support in septic shock Intensive Care Med 27:S80–S92
15.
go back to reference 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 28:947–949PubMed 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 28:947–949PubMed
16.
go back to reference 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:R274–279PubMed 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:R274–279PubMed
17.
go back to reference Bednarik JA, May CN (1995) Evaluation of a transit-time system for the chronic measurement of blood flow in conscious sheep. J Appl Physiol 78:524–530PubMed Bednarik JA, May CN (1995) Evaluation of a transit-time system for the chronic measurement of blood flow in conscious sheep. J Appl Physiol 78:524–530PubMed
18.
go back to reference Matthews JN, Altman DG, Campbell MJ, Royston P (1990) Analysis of serial measurements in medical research. BMJ 300:230–235 Matthews JN, Altman DG, Campbell MJ, Royston P (1990) Analysis of serial measurements in medical research. BMJ 300:230–235
19.
go back to reference Nasraway SA (2000) Norepinephrine: no more "leave 'em dead"? Crit Care Med 28:3096–3097 Nasraway SA (2000) Norepinephrine: no more "leave 'em dead"? Crit Care Med 28:3096–3097
20.
go back to reference Bellomo R, DiGiantomasso D (2001) Noradrenaline and the kidney: friends or foes. Crit Care 5:294–298CrossRefPubMed Bellomo R, DiGiantomasso D (2001) Noradrenaline and the kidney: friends or foes. Crit Care 5:294–298CrossRefPubMed
21.
go back to reference Bersten AD, Hersch M, Cheung H, Rutledge FS, Sibbald WJ (1992) The effect of various sympathomimetics on the regional circulation in hyperdynamic sepsis. Surgery 112:549–561PubMed Bersten AD, Hersch M, Cheung H, Rutledge FS, Sibbald WJ (1992) The effect of various sympathomimetics on the regional circulation in hyperdynamic sepsis. Surgery 112:549–561PubMed
22.
go back to reference 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–R1131PubMed 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–R1131PubMed
23.
go back to reference 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 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
24.
go back to reference 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 24:835–844PubMed 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 24:835–844PubMed
25.
go back to reference 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 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.
go back to reference 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 159:1186–1192PubMed 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 159:1186–1192PubMed
27.
go back to reference 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 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
28.
go back to reference 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 155:1965–1971PubMed 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 155:1965–1971PubMed
29.
go back to reference Bersten AD, Hersch M, Cheung H, Rutledge FS, Sibbald WJ (1992) The effect of various sympathomimetics on the regional circulations in hyperdynamic sepsis. Surgery 112:549–561PubMed Bersten AD, Hersch M, Cheung H, Rutledge FS, Sibbald WJ (1992) The effect of various sympathomimetics on the regional circulations in hyperdynamic sepsis. Surgery 112:549–561PubMed
30.
go back to reference 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 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.
go back to reference Marik PE, Mohedin M (1994) The contrasting effects of dopamine and norepinephrine on systemic and splanchnic oxygen otilization in hyperdynamic sepsis. JAMA 272:1354–1357PubMed Marik PE, Mohedin M (1994) The contrasting effects of dopamine and norepinephrine on systemic and splanchnic oxygen otilization in hyperdynamic sepsis. JAMA 272:1354–1357PubMed
32.
go back to reference 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–H300PubMed 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–H300PubMed
33.
go back to reference Cunnion RE, Schaer GL, Parker M, Natanson C, Parrillo JE (1986) The coronary circulation in human septic shock. Circulation 73:637–644PubMed Cunnion RE, Schaer GL, Parker M, Natanson C, Parrillo JE (1986) The coronary circulation in human septic shock. Circulation 73:637–644PubMed
34.
go back to reference 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 75:533–541PubMed 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 75:533–541PubMed
35.
go back to reference 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 100:483–490PubMed 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 100:483–490PubMed
36.
go back to reference Leone M, Albanese J, Martin C (2002) Positive inotropic stimulation. Curr Opin Crit Care 8:395–403CrossRefPubMed Leone M, Albanese J, Martin C (2002) Positive inotropic stimulation. Curr Opin Crit Care 8:395–403CrossRefPubMed
37.
go back to reference 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 10:101–107PubMed 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 10:101–107PubMed
38.
go back to reference 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 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
39.
go back to reference 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 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
40.
go back to reference 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 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
Metadata
Title
Norepinephrine and vital organ blood flow during experimental hyperdynamic sepsis
Authors
David Di Giantomasso
Clive N. May
Rinaldo Bellomo
Publication date
01-10-2003
Publisher
Springer-Verlag
Published in
Intensive Care Medicine / Issue 10/2003
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-003-1736-9

Other articles of this Issue 10/2003

Intensive Care Medicine 10/2003 Go to the issue