Skip to main content
Log in

Effects of norepinephrine on renal perfusion, filtration and oxygenation in vasodilatory shock and acute kidney injury

  • Original
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

Abstract

Purpose

The use of norepinephrine (NE) in patients with volume-resuscitated vasodilatory shock and acute kidney injury (AKI) remains the subject of much debate and controversy. The effects of NE-induced variations in mean arterial blood pressure (MAP) on renal blood flow (RBF), oxygen delivery (RDO2), glomerular filtration rate (GFR) and the renal oxygen supply/demand relationship (renal oxygenation) in vasodilatory shock with AKI have not been previously studied.

Methods

Twelve post-cardiac surgery patients with NE-dependent vasodilatory shock and AKI were studied 2–6 days after surgery. NE infusion rate was randomly and sequentially titrated to target MAPs of 60, 75 and 90 mmHg. At each target MAP, data on systemic haemodynamics, RBF, GFR and renal oxygen extraction were obtained by pulmonary artery catheter, by the renal vein thermodilution technique and by renal extraction of 51Cr-ethylenediamine tetraacetic acid (51Cr-EDTA), respectively.

Results

At target MAP of 75 mmHg, RDO2 (13%), GFR (27%) and urine flow were higher and renal oxygen extraction was lower (−7.4%) compared with at target MAP of 60 mmHg. However, the renal variables did not differ when compared at target MAPs of 75 and 90 mmHg. Cardiac index increased dose-dependently with NE.

Conclusions

Restoration of MAP from 60 to 75 mmHg improves renal oxygen delivery, GFR and the renal oxygen supply/demand relationship in post-cardiac surgery patients with vasodilatory shock and AKI. This pressure-dependent renal perfusion, filtration and oxygenation at levels of MAP below 75 mmHg reflect a more or less exhausted renal autoregulatory reserve.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Landry DW, Oliver JA (2001) The pathogenesis of vasodilatory shock. N Engl J Med 345:588–595

    Article  CAS  PubMed  Google Scholar 

  2. Kristof AS, Magder S (1999) Low systemic vascular resistance state in patients undergoing cardiopulmonary bypass. Crit Care Med 27:1121–1127

    Article  CAS  PubMed  Google Scholar 

  3. Holmes CL, Walley KR (2009) Vasoactive drugs for vasodilatory shock in ICU. Curr Opin Crit Care 15:398–402. doi:10.1097/MCC.0b013e32832e96ef

    Article  PubMed  Google Scholar 

  4. Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL (2008) Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med 34:17–60

    Article  PubMed  Google Scholar 

  5. Rosner MH, Portilla D, Okusa MD (2008) Cardiac surgery as a cause of acute kidney injury: pathogenesis and potential therapies. J Intensive Care Med 23:3–18. doi:10.1177/0885066607309998

    Article  PubMed  Google Scholar 

  6. Rosner MH, Okusa MD (2006) Acute kidney injury associated with cardiac surgery. Clin J Am Soc Nephrol 1:19–32. doi:10.2215/CJN.00240605

    Article  PubMed  Google Scholar 

  7. Schrier RW, Arnold PE, Gordon JA, Burke TJ (1984) Protection of mitochondrial function by mannitol in ischemic acute renal failure. Am J Physiol 247:F365–F369

    CAS  PubMed  Google Scholar 

  8. Hoogenberg K, Smit AJ, Girbes AR (1998) Effects of low-dose dopamine on renal and systemic hemodynamics during incremental norepinephrine infusion in healthy volunteers. Crit Care Med 26:260–265

    Article  CAS  PubMed  Google Scholar 

  9. Richer M, Robert S, Lebel M (1996) Renal hemodynamics during norepinephrine and low-dose dopamine infusions in man. Crit Care Med 24:1150–1156

    Article  CAS  PubMed  Google Scholar 

  10. 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 

  11. Peng ZY, Critchley LA, Fok BS (2005) The effects of increasing doses of noradrenaline on systemic and renal circulations in acute bacteraemic dogs. Intensive Care Med 31:1558–1563. doi:10.1007/s00134-005-2741-y

    Article  PubMed  Google Scholar 

  12. Joannidis M, Druml W, Forni LG, Groeneveld AB, Honore P, Oudemans-van Straaten HM, Ronco C, Schetz MR, Woittiez AJ, Critical Care Nephrology Working Group of the European Society of Intensive Care Medicine (2010) Prevention of acute kidney injury and protection of renal function in the intensive care unit. Expert opinion of the Working Group for Nephrology, ESICM. Intensive Care Med 36:392–411. doi:10.1007/s00134-009-1678-y

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  14. Desjars P, Pinaud M, Bugnon D, Tasseau F (1989) Norepinephrine therapy has no deleterious renal effects in human septic shock. Crit Care Med 17:426–429

    Article  CAS  PubMed  Google Scholar 

  15. Cesare JF, Ligas JR, Hirvela ER (1993) Enhancement of urine output and glomerular filtration in acutely oliguric patients using low-dose norepinephrine. Circ Shock 39:207–210

    CAS  PubMed  Google Scholar 

  16. Bourgoin A, Leone M, Delmas A, Garnier F, Albanèse J, Martin C (2005) Increasing mean arterial pressure in patients with septic shock: effects on oxygen variables and renal function. Crit Care Med 33:780–786

    Article  CAS  PubMed  Google Scholar 

  17. Bragadottir G, Redfors B, Nygren A, Sellgren J, Ricksten SE (2009) Low-dose vasopressin increases glomerular filtration rate, but impairs renal oxygenation in post-cardiac surgery patients. Acta Anaesthesiol Scand 53:1052–1059. doi:10.1111/j.1399-6576.2009.02037.x

    Article  CAS  PubMed  Google Scholar 

  18. Redfors B, Sward K, Sellgren J, Ricksten SE (2009) Effects of mannitol alone and mannitol plus furosemide on renal oxygen consumption, blood flow and glomerular filtration after cardiac surgery. Intensive Care Med 35:115–122. doi:10.1007/s00134-008-1206-5

    Article  CAS  PubMed  Google Scholar 

  19. Redfors B, Bragadottir G, Sellgren J, Swärd K, Ricksten SE (2010) Dopamine increases renal oxygenation: a clinical study in post-cardiac surgery patients. Acta Anaesthesiol Scand 54:183–190. doi:10.1111/j.1399-6576.2009.02121.x

    Article  CAS  PubMed  Google Scholar 

  20. Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A, Network Acute Kidney Injury (2007) Acute kidney injury network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 11:R31. doi:10.1186/cc5713

    Article  PubMed  Google Scholar 

  21. Ceriani R, Mazzoni M, Bortone F, Gandini S, Solinas C, Susini G, Parodi O (2003) Application of the sequential organ failure assessment score to cardiac surgical patients. Chest 123:1229–1239

    Article  PubMed  Google Scholar 

  22. Kristiansson M, Holmquist F, Nyman U (2009) Ultralow contrast medium doses at CT to diagnose pulmonary embolism in patients with moderate to severe renal impairment: a feasibility study. Eur Radiol 20:1321–1330. doi:10.1007/s00330-009-1691-0

    Article  PubMed  Google Scholar 

  23. Tidgren B, Brodin U (1988) Plasma renin activity and oxygen content along the renal veins in hypertensive patients. Clin Physiol 8:407–416

    Article  CAS  PubMed  Google Scholar 

  24. Sward K, Valsson F, Sellgren J, Ricksten SE (2004) Bedside estimation of absolute renal blood flow and glomerular filtration rate in the intensive care unit. A validation of two independent methods. Intensive Care Med 30:1776–1782

    Article  PubMed  Google Scholar 

  25. Andersson LG, Bratteby LE, Ekroth R, Wesslén O, Hallhagen S (1994) Calculation of renal extraction during high diuresis and low renal plasma flow conditions. Clin Physiol 14:79–85

    Article  CAS  PubMed  Google Scholar 

  26. Hellebrekers LJ, Liard JF, Laborde AL, Greene AS, Cowley AW Jr (1990) Regional autoregulatory responses during infusion of vasoconstrictor agents in conscious dogs. Am J Physiol 259:H1270–H1277

    CAS  PubMed  Google Scholar 

  27. Loutzenhiser R, Griffin K, Williamson G, Bidani A (2006) Renal autoregulation: new perspectives regarding the protective and regulatory roles of the underlying mechanisms. Am J Physiol Regul Integr Comp Physiol 290:R1153–R1167. doi:10.1152/ajpregu.00402.2005

    CAS  PubMed  Google Scholar 

  28. Cupples WA, Braam B (2007) Assessment of renal autoregulation. Am J Physiol Renal Physiol 292:F1105–F1123. doi:10.1152/ajprenal.00194.2006

    Article  CAS  PubMed  Google Scholar 

  29. Persson PB, Ehmke H, Nafz B, Kirchheim HR (1990) Resetting of renal autoregulation in conscious dogs: angiotensin II and alpha1-adrenoceptors. Pflugers Arch 417:42–47

    Article  CAS  PubMed  Google Scholar 

  30. Dünser MW, Takala J, Ulmer H, Mayr VD, Luckner G, Jochberger S, Daudel F, Lepper P, Hasibeder WR, Jakob SM (2009) Arterial blood pressure during early sepsis and outcome. Intensive Care Med 35:1225–1233. doi:10.1007/s00134-009-1427-2

    Article  PubMed  Google Scholar 

  31. Schetz M (2002) Vasopressors and the kidney. Blood Purif 20:243–251

    Article  CAS  PubMed  Google Scholar 

  32. Bakris GL, Stein JH (1993) Diabetic nephropathy. Dis Mon 39:573–611

    CAS  PubMed  Google Scholar 

  33. Carmines PK (2010) The renal vascular response to diabetes. Curr Opin Nephrol Hypertens 19:85–90. doi:10.1097/MNH.0b013e32833240fc

    Article  CAS  PubMed  Google Scholar 

  34. Beretta-Piccoli C, Weidmann P (1981) Exaggerated pressor responsiveness to norepinephrine in nonazotemic diabetes mellitus. Am J Med 71:829–835

    Article  CAS  PubMed  Google Scholar 

  35. Jacobs WR, Chan YL (1987) Effect of norepinephrine on renal tubular Na-K-ATPase and oxygen consumption. Life Sci 40:1571–1578

    Article  CAS  PubMed  Google Scholar 

  36. Block CA, Manning HL (2002) Prevention of acute renal failure in the critically ill. Am J Respir Crit Care Med 165:320–324

    PubMed  Google Scholar 

  37. Brezis M, Agmon Y, Epstein FH (1994) Determinants of intrarenal oxygenation. I. Effects of diuretics. Am J Physiol 267:F1059–F1062

    CAS  PubMed  Google Scholar 

  38. Schachinger H, Klarhöfer M, Linder L, Drewe J, Scheffler K (2006) Angiotensin II decreases the renal MRI blood oxygenation level-dependent signal. Hypertension 47:1062–1066. doi:10.1161/01.HYP.0000220109.98142.a3

    Article  CAS  PubMed  Google Scholar 

  39. LeDoux D, Astiz ME, Carpati CM, Rackow EC (2000) Effects of perfusion pressure on tissue perfusion in septic shock. Crit Care Med 28:2729–2732

    Article  CAS  PubMed  Google Scholar 

  40. Nygren A, Thoren A, Ricksten SE (2007) Norepinephrine and intestinal mucosal perfusion in vasodilatory shock after cardiac surgery. Shock 28:536–543

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We appreciate the skillful technical assistance of Mrs. Marita Ahlqvist, and we are grateful for the support from the nursing staff of the Cardiothoracic Intensive Care Unit of the Sahlgrenska University Hospital. This study was supported by grants from the Swedish Medical Research Council (no. 13156), Medical Faculty of Gothenburg (LUA) and Gothenburg Medical Society.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sven-Erik Ricksten.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Redfors, B., Bragadottir, G., Sellgren, J. et al. Effects of norepinephrine on renal perfusion, filtration and oxygenation in vasodilatory shock and acute kidney injury. Intensive Care Med 37, 60–67 (2011). https://doi.org/10.1007/s00134-010-2057-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00134-010-2057-4

Keywords

Navigation