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Hyperreninemic hypoaldosteronism syndrome, plasma concentrations of interleukin-6 and outcome in critically ill patients with liver cirrhosis

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Abstract

Objective

To investigate the relation between the adrenal production of gluco- and mineralocorticoids, the inflammatory status and the outcome in critically ill patients with liver cirrhosis.

Design

Prospective descriptive study.

Setting

Medical intensive care unit (ICU) in a university hospital.

Patients

Fifty consecutive patients with liver cirrhosis.

Interventions

A corticotropin stimulation test within 12 h following ICU admission. Plasma cortisol concentration was measured before and after the test. Renin and aldosterone concentrations, as well as interleukin-6 (IL-6) level to assess the pro-inflammatory status, were measured only before the test. Impaired adrenal function was defined as cortisol response to the test less than 9 μg/dl. Hyperreninemic hypoaldosteronism syndrome was defined as basal renin over aldosterone ratio (RRA) higher than 2.

Measurements and results

Forty-one (82%) patients had impaired adrenal function, and 26 patients (52%) presented with RRA > 2. Patients with RRA > 2 exhibited greater disease severity and organ dysfunction scores at baseline, higher levels of serum renin and IL-6, and a greater ICU mortality rate, but risk-adjusted mortality rates were not different between the two groups. Renin and IL-6 plasma concentrations were positively correlated. Finally, in a Cox regression analysis, independent predictors of 30-day mortality were hyperreninemic hypoaldosteronism syndrome, IL-6 higher than 400 pg/ml and severe renal failure.

Conclusions

Adrenal dysfunction was common in critically ill cirrhotic patients. Hyperreninemic hypoaldosteronism syndrome was related to a greater pro-inflammatory status and degree of acute organ failure, and was independently associated with a worse prognosis.

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References

  1. Shellman RG, Fulkerson WJ, DeLong E, Piantadosi CA (1988) Prognosis of patients with cirrhosis and chronic liver disease admitted to the medical intensive care unit. Crit Care Med 16:671–678

    Article  PubMed  CAS  Google Scholar 

  2. Moreau R, Hadengue A, Soupison T, Kirstetter P, Mamzer MF, Vanjak D, Vauquelin P, Assous M, Sicot C (1992) Septic shock in patients with cirrhosis: hemodynamic and metabolic characteristics and intensive care unit outcome. Crit Care Med 20:746–750

    Article  PubMed  CAS  Google Scholar 

  3. Moreau R, Lebrec D (2003) Acute renal failure in patients with cirrhosis: perspectives in the age of MELD. Hepatology 37:233–243

    Article  PubMed  Google Scholar 

  4. du Cheyron D, Bouchet B, Parienti JJ, Ramakers M, Charbonneau P (2005) The attributable mortality of acute renal failure in critically ill patients with liver cirrhosis. Intensive Care Med 31:1693–1699

    Article  PubMed  Google Scholar 

  5. Gines P, Cardenas A, Arroyo V, Rodes J (2004) Management of cirrhosis and ascites. N Engl J Med 350:1646–1654

    Article  PubMed  CAS  Google Scholar 

  6. Wong F, Bernardi M, Balk R, Christman B, Moreau R, Garcia-Tsao G, Patch D, Soriano G, Hoefs J, Navasa M (2005) Sepsis in cirrhosis: report on the 7th meeting of the International Ascites Club. Gut 54:718–725

    Article  PubMed  CAS  Google Scholar 

  7. Wasmuth HE, Kunz D, Yagmur E, Timmer-Stranghoner A, Vidacek D, Siewert E, Bach J, Geier A, Purucker EA, Gressner AM, Matern S, Lammert F (2005) Patients with acute on chronic liver failure display “sepsis-like” immune paralysis. J Hepatol 42:195–201

    Article  PubMed  CAS  Google Scholar 

  8. Annane D, Sebille V, Troche G, Raphael JC, Gajdos P, Bellissant E (2000) A 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin. JAMA 283:1038–1045

    Article  PubMed  CAS  Google Scholar 

  9. Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troche G, Chaumet-Riffaut P, Bellissant E (2002) Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 288:862–871

    Article  PubMed  CAS  Google Scholar 

  10. du Cheyron D, Lesage A, Daubin C, Ramakers M, Charbonneau P (2003) Hyperreninemic hypoaldosteronism: a possible etiological factor of septic shock-induced acute renal failure. Intensive Care Med 29:1703–1709

    Article  PubMed  CAS  Google Scholar 

  11. Zipser RD, Davenport MW, Martin KL, Tuck ML, Warner NE, Swinney RR, Davis CL, Horton R (1981) Hyperreninemic hypoaldosteronism in the critically ill: a new entity. J Clin Endocrinol Metab 53:867–873

    PubMed  CAS  Google Scholar 

  12. Davenport MW, Zipser RD (1983) Association of hypotension with hyperreninemic hypoaldosteronism in the critically ill patient. Arch Intern Med 143:735–737

    Article  PubMed  CAS  Google Scholar 

  13. Findling JW, Waters VO, Raff H (1987) The dissociation of renin and aldosterone during critical illness. J Clin Endocrinol Metab 64:592–595

    Article  PubMed  CAS  Google Scholar 

  14. Tsai MH, Peng YS, Chen YC, Liu NJ, Ho YP, Fang JT, Lien JM, Yang C, Chen PC, Wu CS (2006) Adrenal insufficiency in patients with cirrhosis, severe sepsis and septic shock. Hepatology 43:673–681

    Article  PubMed  Google Scholar 

  15. O'Connor PG, Schottenfeld RS (1998) Patients with alcohol problems. N Engl J Med 338:592–602

    Article  PubMed  Google Scholar 

  16. Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R (1973) Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 60:646–649

    Article  PubMed  CAS  Google Scholar 

  17. Kamath PS, Wiesner RH, Malinchoc M, Kremers W, Therneau TM, Kosberg CL, D'Amico G, Dickson ER, Kim WR (2001) A model to predict survival in patients with end-stage liver disease. Hepatology 33:464–470

    Article  PubMed  CAS  Google Scholar 

  18. Unger N, Lopez Schmidt I, Pitt C, Walz MK, Philipp T, Mann K, Petersenn S (2004) Comparison of active renin concentration and plasma renin activity for the diagnosis of primary hyperaldosteronism in patients with an adrenal mass. Eur J Endocrinol 150:517–523

    Article  PubMed  CAS  Google Scholar 

  19. Colle I, Moreau R, Pessione F, Rassiat E, Heller J, Chagneau C, Pateron D, Barriere E, Condat B, Sogni P, Valla D, Lebrec D (2001) Relationships between haemodynamic alterations and the development of ascites or refractory ascites in patients with cirrhosis. Eur J Gastroenterol Hepatol 13:251–256

    Article  PubMed  CAS  Google Scholar 

  20. Laragh JH, Sealey JE (1973) The renin–angiotensin–aldosterone hormonal system and regulation of sodium, potassium, and blood pressure homeostasis. In: Orloff J, Berliner RW (eds) Handbook of physiology. Am Physiol Soc, Bethesda, MD, pp 831–907

    Google Scholar 

  21. Moller S, Bendtsen F, Henriksen JH (2006) Determinants of the renin–angiotensin–aldosterone system in cirrhosis with special emphasis on the central blood volume. Scand J Gastroenterol 41:451–458

    Article  PubMed  CAS  Google Scholar 

  22. Marik PE, Gayowski T, Starzl TE (2005) The hepatoadrenal syndrome: a common yet unrecognized clinical condition. Crit Care Med 33:1254–1259

    Article  PubMed  Google Scholar 

  23. Marik PE (2006) Adrenal-exhaustion syndrome in patients with liver disease. Intensive Care Med 32:275–280

    Article  PubMed  Google Scholar 

  24. Doe RP, Fernandez R, Seal US (1964) Measurement of corticosteroid-binding globulin in man. J Clin Endocrinol Metab 24:1029–1039

    PubMed  CAS  Google Scholar 

  25. Hamrahian AH, Oseni TS, Arafah BM (2004) Measurements of serum free cortisol in critically ill patients. N Engl J Med 350:1629–1638

    Article  PubMed  CAS  Google Scholar 

  26. Beishuizen A, Thijs LG (2001) Relative adrenal failure in intensive care: an identifiable problem requiring treatment? Best Pract Res Clin Endocrinol Metab 15:513–531

    Article  PubMed  CAS  Google Scholar 

  27. Annane D, Bellissant E, Cavaillon JM (2005) Septic shock. Lancet 365:63–78

    Article  PubMed  CAS  Google Scholar 

  28. Prigent H, Maxime V, Annane D (2004) Science review: mechanisms of impaired adrenal function in sepsis and molecular actions of glucocorticoids. Crit Care 8:243–252

    Article  PubMed  Google Scholar 

  29. Deutschman CS, Cereda M, Ochroch EA, Raj NR (2006) Sepsis-induced cholestasis, steatosis, hepatocellular injury, and impaired hepatocellular regeneration are enhanced in interleukin-6 –/– mice. Crit Care Med 34:2613–2620

    Article  PubMed  CAS  Google Scholar 

  30. Kullmer T, Haak T, Winkelmann BR, Morbitzer D, Jungmann E, Meier-Sydow J (1996) Hormonal modifications in patients admitted to an internal intensive care unit for acute hypoxaemic respiratory failure. Respir Med 90:601–608

    Article  PubMed  CAS  Google Scholar 

  31. Rolih CA, Ober KP (1995) The endocrine response to critical illness. Med Clin North Am 79:211–224

    PubMed  CAS  Google Scholar 

  32. Raff H, Findling JW (1990) Aldosterone control in critically ill patients: ACTH, metoclopramide, and atrial natriuretic peptide. Crit Care Med 18:915–920

    Article  PubMed  CAS  Google Scholar 

  33. Lichtarowicz-Krynska EJ, Cole TJ, Camacho-Hubner C, Britto J, Levin M, Klein N, Aynsley-Green A (2004) Circulating aldosterone levels are unexpectedly low in children with acute meningococcal disease. J Clin Endocrinol Metab 89:1410–1414

    Article  PubMed  CAS  Google Scholar 

  34. Sellars L, Shore AC, Mott V, Wilkinson R (1985) The renin–angiotensin–aldosterone system in decompensated cirrhosis: its activity in relation to sodium balance. Q J Med 56:485–496

    PubMed  CAS  Google Scholar 

  35. Fernandez J, Escorsell A, Zabalza M, Felipe V, Navasa M, Mas A, Lacy AM, Gines P, Arroyo V (2006) Adrenal insufficiency in patients with cirrhosis and septic shock: effect of treatment with hydrocortisone on survival. Hepatology 44:1288–1295

    Article  PubMed  CAS  Google Scholar 

  36. Knaus WA, Draper EA, Wagner DP, Zimmerman JE (1985) APACHE II: a severity of disease classification system. Crit Care Med 13:818–829

    Article  PubMed  CAS  Google Scholar 

  37. Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG (1996) The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 22:707–710

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Damien du Cheyron.

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du Cheyron, D., Bouchet, B., Cauquelin, B. et al. Hyperreninemic hypoaldosteronism syndrome, plasma concentrations of interleukin-6 and outcome in critically ill patients with liver cirrhosis. Intensive Care Med 34, 116–124 (2008). https://doi.org/10.1007/s00134-007-0864-z

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  • DOI: https://doi.org/10.1007/s00134-007-0864-z

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