Advertisement

Intensive Care Medicine

, Volume 37, Issue 1, pp 60–67 | Cite as

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

  • Bengt Redfors
  • Gudrun Bragadottir
  • Johan Sellgren
  • Kristina Swärd
  • Sven-Erik RickstenEmail author
Original

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.

Keywords

Acute kidney failure Shock Renal circulation Glomerular filtration rate Oxygen consumption Norepinephrine 

Notes

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.

References

  1. 1.
    Landry DW, Oliver JA (2001) The pathogenesis of vasodilatory shock. N Engl J Med 345:588–595CrossRefPubMedGoogle Scholar
  2. 2.
    Kristof AS, Magder S (1999) Low systemic vascular resistance state in patients undergoing cardiopulmonary bypass. Crit Care Med 27:1121–1127CrossRefPubMedGoogle Scholar
  3. 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 CrossRefPubMedGoogle Scholar
  4. 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 34:17–60CrossRefPubMedGoogle Scholar
  5. 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 CrossRefPubMedGoogle Scholar
  6. 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 CrossRefPubMedGoogle Scholar
  7. 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–F369PubMedGoogle Scholar
  8. 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 26:260–265CrossRefPubMedGoogle Scholar
  9. 9.
    Richer M, Robert S, Lebel M (1996) Renal hemodynamics during norepinephrine and low-dose dopamine infusions in man. Crit Care Med 24:1150–1156CrossRefPubMedGoogle Scholar
  10. 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 159:1186–1192PubMedGoogle Scholar
  11. 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 CrossRefPubMedGoogle Scholar
  12. 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 CrossRefPubMedGoogle Scholar
  13. 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 19:151–154CrossRefPubMedGoogle Scholar
  14. 14.
    Desjars P, Pinaud M, Bugnon D, Tasseau F (1989) Norepinephrine therapy has no deleterious renal effects in human septic shock. Crit Care Med 17:426–429CrossRefPubMedGoogle Scholar
  15. 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 39:207–210PubMedGoogle Scholar
  16. 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 33:780–786CrossRefPubMedGoogle Scholar
  17. 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 CrossRefPubMedGoogle Scholar
  18. 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 CrossRefPubMedGoogle Scholar
  19. 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 CrossRefPubMedGoogle Scholar
  20. 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 CrossRefPubMedGoogle Scholar
  21. 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 123:1229–1239CrossRefPubMedGoogle Scholar
  22. 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 CrossRefPubMedGoogle Scholar
  23. 23.
    Tidgren B, Brodin U (1988) Plasma renin activity and oxygen content along the renal veins in hypertensive patients. Clin Physiol 8:407–416CrossRefPubMedGoogle Scholar
  24. 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 30:1776–1782CrossRefPubMedGoogle Scholar
  25. 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 14:79–85CrossRefPubMedGoogle Scholar
  26. 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–H1277PubMedGoogle Scholar
  27. 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 PubMedGoogle Scholar
  28. 28.
    Cupples WA, Braam B (2007) Assessment of renal autoregulation. Am J Physiol Renal Physiol 292:F1105–F1123. doi: 10.1152/ajprenal.00194.2006 CrossRefPubMedGoogle Scholar
  29. 29.
    Persson PB, Ehmke H, Nafz B, Kirchheim HR (1990) Resetting of renal autoregulation in conscious dogs: angiotensin II and alpha1-adrenoceptors. Pflugers Arch 417:42–47CrossRefPubMedGoogle Scholar
  30. 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 CrossRefPubMedGoogle Scholar
  31. 31.
    Schetz M (2002) Vasopressors and the kidney. Blood Purif 20:243–251CrossRefPubMedGoogle Scholar
  32. 32.
    Bakris GL, Stein JH (1993) Diabetic nephropathy. Dis Mon 39:573–611PubMedGoogle Scholar
  33. 33.
    Carmines PK (2010) The renal vascular response to diabetes. Curr Opin Nephrol Hypertens 19:85–90. doi: 10.1097/MNH.0b013e32833240fc CrossRefPubMedGoogle Scholar
  34. 34.
    Beretta-Piccoli C, Weidmann P (1981) Exaggerated pressor responsiveness to norepinephrine in nonazotemic diabetes mellitus. Am J Med 71:829–835CrossRefPubMedGoogle Scholar
  35. 35.
    Jacobs WR, Chan YL (1987) Effect of norepinephrine on renal tubular Na-K-ATPase and oxygen consumption. Life Sci 40:1571–1578CrossRefPubMedGoogle Scholar
  36. 36.
    Block CA, Manning HL (2002) Prevention of acute renal failure in the critically ill. Am J Respir Crit Care Med 165:320–324PubMedGoogle Scholar
  37. 37.
    Brezis M, Agmon Y, Epstein FH (1994) Determinants of intrarenal oxygenation. I. Effects of diuretics. Am J Physiol 267:F1059–F1062PubMedGoogle Scholar
  38. 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 CrossRefPubMedGoogle Scholar
  39. 39.
    LeDoux D, Astiz ME, Carpati CM, Rackow EC (2000) Effects of perfusion pressure on tissue perfusion in septic shock. Crit Care Med 28:2729–2732CrossRefPubMedGoogle Scholar
  40. 40.
    Nygren A, Thoren A, Ricksten SE (2007) Norepinephrine and intestinal mucosal perfusion in vasodilatory shock after cardiac surgery. Shock 28:536–543PubMedGoogle Scholar

Copyright information

© Copyright jointly held by Springer and ESICM 2010

Authors and Affiliations

  • Bengt Redfors
    • 1
  • Gudrun Bragadottir
    • 1
  • Johan Sellgren
    • 1
  • Kristina Swärd
    • 1
  • Sven-Erik Ricksten
    • 1
    Email author
  1. 1.Department of Cardiothoracic Anaesthesia and Intensive CareSahlgrenska University HospitalGothenburgSweden

Personalised recommendations