Intensive Care Medicine

, Volume 36, Issue 4, pp 702–706 | Cite as

Plasma citrulline kinetics and prognostic value in critically ill patients

  • Gaël Piton
  • Cyril Manzon
  • Elisabeth Monnet
  • Benoit Cypriani
  • Olivier Barbot
  • Jean-Christophe Navellou
  • Franck Carbonnel
  • Gilles Capellier
Brief Report



Multiple organ failure is a leading cause of death in critically ill patients and could be secondary to early gut ischemia. Plasma citrulline is a biomarker of enterocyte mass, and critically ill patients may have enterocyte mass reduction. The objectives of this study were to assess plasma citrulline kinetics and its prognostic value in critically ill patients.


This prospective observational study included adults without small bowel disease and without chronic renal failure consecutively admitted to a single intensive care unit. Prognostic variables as well as plasma citrulline concentrations were studied at admission, 12, 24, 48 h, and the 7th day after admission. Univariate and multivariate analyses including plasma citrulline (0–10, 11–20, and >20 μmol l−1) and other variables were performed.


Sixty-seven patients were included, and the 28-day mortality was 34%. During the 1st day mean plasma citrulline decreased from 18.8 to 13.5 μmol l−1. Low plasma citrulline at 24 h was associated with low plasma glutamine and arginine (p = 0.01 and 0.04), and high plasma CRP concentration, nosocomial infection rate, and 28-day mortality (p = 0.008, 0.03, and 0.02, respectively). In multivariate analysis plasma citrulline ≤10 μmol l−1 at 24 h and SOFA score ≥8 at 24 h were associated with 28-day mortality (odds ratios 8.70 and 15.08).


In critically ill patients, low plasma citrulline at 24 h is an independent factor of mortality and could be a marker of acute intestinal failure.


Plasma citrulline Multiple organ failure Shock Prognosis 



Intensive Care Unit


  1. 1.
    Deitch EA (1992) Multiple organ failure. Pathophysiology and potential future therapy. Ann Surg 216:117–134CrossRefPubMedGoogle Scholar
  2. 2.
    Fiddian-Green RG (1988) Splanchnic ischaemia and multiple organ failure in the critically ill. Ann R Coll Surg Engl 70:128–134PubMedGoogle Scholar
  3. 3.
    Khadaroo RG, Marshall JC (2008) Gastrointestinal dysfunction in the critically ill: can we measure it? Crit Care 12:180CrossRefPubMedGoogle Scholar
  4. 4.
    Reintam A, Parm P, Kitus R, Starkopf J, Kern H (2008) Gastrointestinal failure score in critically ill patients: a prospective observational study. Crit Care 12:R90CrossRefPubMedGoogle Scholar
  5. 5.
    Crenn P, Coudray-Lucas C, Thuillier F, Cynober L, Messing B (2000) Postabsorptive plasma citrulline concentration is a marker of absorptive enterocyte mass and intestinal failure in humans. Gastroenterology 119:1496–1505CrossRefPubMedGoogle Scholar
  6. 6.
    Crenn P, Vahedi K, Lavergne-Slove A, Cynober L, Matuchansky C, Messing B (2003) Plasma citrulline: a marker of enterocyte mass in villous atrophy-associated small bowel disease. Gastroenterology 124:1210–1219CrossRefPubMedGoogle Scholar
  7. 7.
    Kao CC, Bandi V, Guntupalli KK, Wu M, Castillo L, Jahoor F (2009) Arginine, citrulline, and nitric oxide metabolism in sepsis. Clin Sci (Lond) 117(1):23–30Google Scholar
  8. 8.
    Luiking YC, Poeze M, Ramsay G, Deutz NE (2009) Reduced citrulline production in sepsis is related to diminished de novo arginine and nitric oxide production. Am J Clin Nutr 89:142–152CrossRefPubMedGoogle Scholar
  9. 9.
    Le Boucher J, Charret C, Coudray-Lucas C, Giboudeau J, Cynober L (1997) Amino acid determination in biological fluids by automated ion-exchange chromatography: performance of Hitachi L-8500A. Clin Chem 43:1421–1428PubMedGoogle Scholar
  10. 10.
    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 22:707–710CrossRefPubMedGoogle Scholar
  11. 11.
    Fagon JY, Chastre J, Novara A, Medioni P, Gibert C (1993) Characterization of intensive care unit patients using a model based on the presence or absence of organ dysfunctions and/or infection: the ODIN model. Intensive Care Med 19:137–144CrossRefPubMedGoogle Scholar
  12. 12.
    Le Gall JR, Lemeshow S, Saulnier F (1993) A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA 270:2957–2963CrossRefPubMedGoogle Scholar
  13. 13.
    Curis E, Nicolis I, Moinard C, Osowska S, Zerrouk N, Benazeth S, Cynober L (2005) Almost all about citrulline in mammals. Amino Acids 29:177–205CrossRefPubMedGoogle Scholar
  14. 14.
    Peters J, Wierdsma N, Teerlink T, van Leeuwen P, Mulder C, van Bodegraven A (2007) Poor diagnostic accuracy of a single fasting plasma citrulline concentration to assess intestinal energy absorption capacity. Am J Gastroenterol 102:2814–2819CrossRefPubMedGoogle Scholar
  15. 15.
    Tizianello A, De Ferrari G, Garibotto G, Gurreri G, Robaudo C (1980) Renal metabolism of amino acids and ammonia in subjects with normal renal function and in patients with chronic renal insufficiency. J Clin Invest 65:1162–1173CrossRefPubMedGoogle Scholar
  16. 16.
    Chang JX, Chen S, Ma LP, Jiang LY, Chen JW, Chang RM, Wen LQ, Wu W, Jiang ZP, Huang ZT (2005) Functional and morphological changes of the gut barrier during the restitution process after hemorrhagic shock. World J Gastroenterol 11:5485–5491PubMedGoogle Scholar
  17. 17.
    van Waardenburg DA, de Betue CT, Luiking YC, Engel M, Deutz NE (2007) Plasma arginine and citrulline concentrations in critically ill children: strong relation with inflammation. Am J Clin Nutr 86:1438–1444PubMedGoogle Scholar
  18. 18.
    Swank GM, Deitch EA (1996) Role of the gut in multiple organ failure: bacterial translocation and permeability changes. World J Surg 20:411–417CrossRefPubMedGoogle Scholar
  19. 19.
    Freund H, Atamian S, Holroyde J, Fischer JE (1979) Plasma amino acids as predictors of the severity and outcome of sepsis. Ann Surg 190:571–576PubMedCrossRefGoogle Scholar
  20. 20.
    Luiking YC, Deutz NE (2007) Exogenous arginine in sepsis. Crit Care Med 35:S557–S563CrossRefPubMedGoogle Scholar

Copyright information

© Copyright jointly hold by Springer and ESICM 2010

Authors and Affiliations

  • Gaël Piton
    • 1
    • 5
  • Cyril Manzon
    • 1
  • Elisabeth Monnet
    • 2
  • Benoit Cypriani
    • 3
  • Olivier Barbot
    • 1
  • Jean-Christophe Navellou
    • 1
  • Franck Carbonnel
    • 4
  • Gilles Capellier
    • 1
  1. 1.Intensive Care UnitBesançon University HospitalBesançonFrance
  2. 2.Department of Public HealthBesançon University HospitalBesançonFrance
  3. 3.Clinical Chemistry UnitBesançon University HospitalBesançonFrance
  4. 4.Gastroenterology and Nutrition UnitBesançon University HospitalBesançonFrance
  5. 5.Service de Réanimation MédicaleHôpital Jean MinjozBesançonFrance

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