Intensive Care Medicine

, Volume 35, Issue 8, pp 1390–1396

Predictors of bacteraemia and mortality in patients with acute liver failure

  • Constantine J. Karvellas
  • Fred Pink
  • Mark McPhail
  • Timothy Cross
  • Georg Auzinger
  • William Bernal
  • Elizabeth Sizer
  • Demetrios J. Kutsogiannis
  • Ian Eltringham
  • Julia A. Wendon
Original

Abstract

Purpose

To determine what physiological and biochemical factors predict development of bacteraemia and mortality in patients with acute liver failure (ALF).

Methods

Retrospective analysis of 206 ALF patients admitted to a specialist liver intensive therapy unit (LITU) from January 2003 to July 2005 (data collected prospectively).

Results

A total of 206 patients were defined with ALF: 72 (35%) suffered bacteraemia (BAClf) and 134 (65%) did not (NBAClf). Gram positive organisms were observed in 44% of isolates, gram negatives in 52% and fungaemia in 4%. Median time to first bacteraemia was 10 (7–16) days. On admission, BAClf patients had higher SIRS scores and degrees of hepatic encephalopathy (HE). During their LITU course, BAClf patients had significantly increased requirements for renal replacement therapy (RRT), mechanical ventilation, and longer median LITU stay. Multivariate analysis (logistical regression) demonstrated significant predictors of bacteraemia on admission were HE grade >2 (Odds Ratio 1.6) and SIRS score >1 (OR 2.7). In all patients, independent predictors of mortality (logistical) were age (OR 1.41), maximum HE grade pre-intubation (1.76), Lactate (1.14) and Acute Physiology and Chronic Health Evaluation II score (APACHEII) (1.09), but not bacteraemia. Transplantation was protective (OR 0.20).

Conclusion

In this study, severity of hepatic encephalopathy and SIRS score >1 were predictive of bacteraemia. APACHEII was independently predictive of mortality in all ALF patients but not bacteraemia.

Keywords

Sepsis SIRS APACHE Transplantation Critical illness 

Abbreviations

ALF

Acute liver failure

BAClf

Bacteraemic acute liver failure patients

95% CI

95% confidence interval

HE

Hepatic encephalopathy

HR

Heart rate

ICU

Intensive care unit

LITU

Liver Intensive therapy (care) unit

LT

Liver transplantation

MAP

Mean arterial pressure

MV

Mechanical ventilation

NBAClf

Non-bacteraemic acute liver failure

NINSS

Nosocomial infection national surveillance scheme

OR

Odds ratio

RRT

Renal replacement therapy

SIRS

Systemic inflammatory response syndrome

TA

Tracheal aspirates

VAP

Ventilator-associated pneumonia

References

  1. 1.
    Wyke RJ, Yousif-Kadaru AG, Rajkovic IA, Eddleston AL, Williams R (1982) Serum stimulatory activity and polymorphonuclear leucocyte movement in patients with fulminant hepatic failure. Clin Exp Immunol 50:442–449PubMedGoogle Scholar
  2. 2.
    Clapperton M, Rolando N, Sandoval L, Davies E, Williams R (1997) Neutrophil superoxide and hydrogen peroxide production in patients with acute liver failure. Eur J Clin Invest 27:164–168PubMedCrossRefGoogle Scholar
  3. 3.
    Rolando N, Harvey F, Brahm J, Philpott-Howard J, Alexander G, Gimson A, Casewell M, Fagan E, Williams R (1990) Prospective study of bacterial infection in acute liver failure: an analysis of fifty patients. Hepatology 11:49–53PubMedCrossRefGoogle Scholar
  4. 4.
    Rolando N, Wade JJ, Fagan E, Philpott-Howard J, Casewell MW, Williams R (1992) An open, comparative trial of aztreonam with vancomycin and gentamicin with piperacillin in patients with fulminant hepatic failure. J Antimicrob Chemother 30:215–220PubMedCrossRefGoogle Scholar
  5. 5.
    Rolando N, Gimson A, Wade J, Philpott-Howard J, Casewell M, Williams R (1993) Prospective controlled trial of selective parenteral and enteral antimicrobial regimen in fulminant liver failure. Hepatology 17:196–201PubMedCrossRefGoogle Scholar
  6. 6.
    Rolando N, Wade JJ, Stangou A, Gimson AE, Wendon J, Philpott-Howard J, Casewell MW, Williams R (1996) Prospective study comparing the efficacy of prophylactic parenteral antimicrobials, with or without enteral decontamination, in patients with acute liver failure. Liver Transpl Surg 2:8–13PubMedCrossRefGoogle Scholar
  7. 7.
    Dirix LY, Polson RJ, Richardson A, Williams R (1989) Primary sepsis presenting as fulminant hepatic failure. Q J Med 73:1037–1043PubMedGoogle Scholar
  8. 8.
    American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20:864–874Google Scholar
  9. 9.
    Pittet D, Rangel-Frausto S, Li N, Tarara D, Costigan M, Rempe L, Jebson P, Wenzel RP (1995) Systemic inflammatory response syndrome, sepsis, severe sepsis and septic shock: incidence, morbidities and outcomes in surgical ICU patients. Intensive Care Med 21:302–309PubMedCrossRefGoogle Scholar
  10. 10.
    Billiau A, Vandekerckhove F (1991) Cytokines and their interactions with other inflammatory mediators in the pathogenesis of sepsis and septic shock. Eur J Clin Invest 21:559–573PubMedCrossRefGoogle Scholar
  11. 11.
    Glauser MP, Zanetti G, Baumgartner JD, Cohen J (1991) Septic shock: pathogenesis. Lancet 338:732–736PubMedCrossRefGoogle Scholar
  12. 12.
    Bone RC (1991) The pathogenesis of sepsis. Ann Intern Med 115:457–469PubMedGoogle Scholar
  13. 13.
    Karvellas CJ, Pink F, McPhail M, Cross T, Auzinger G, Bernal W, Sizer E, Kutsogiannis D, Eltringham I, Wendon J (2007) The incidence of bacteremia and outcomes in patients with acute liver failure. Abstract 847 in: Proceedings of the 58th Annual Meeting of the American Association for the Study of Liver Diseases. Hepatology 46(S1):612AGoogle Scholar
  14. 14.
    O’Grady JG, Schalm SW, Williams R (1993) Acute liver failure: redefining the syndromes. Lancet 342:273–275PubMedCrossRefGoogle Scholar
  15. 15.
    Document N (1997) Nosocomial Infection National Surveillance Scheme (UK): protocol for the surveillance of hospital acquired bacteremia. PHLS Central Public Health Laboratory, LondonGoogle Scholar
  16. 16.
    Vaquero J, Polson J, Chung C, Helenowski I, Schiodt FV, Reisch J, Lee WM, Blei AT (2003) Infection and the progression of hepatic encephalopathy in acute liver failure. Gastroenterology 125:755–764PubMedCrossRefGoogle Scholar
  17. 17.
    O’Grady JG, Alexander GJ, Hayllar KM, Williams R (1989) Early indicators of prognosis in fulminant hepatic failure. Gastroenterology 97:439–445PubMedGoogle Scholar
  18. 18.
    Depuydt P, Benoit D, Vogelaers D, Claeys G, Verschraegen G, Vandewoude K, Decruyenaere J, Blot S (2006) Outcome in bacteremia associated with nosocomial pneumonia and the impact of pathogen prediction by tracheal surveillance cultures. Intensive Care Med 32:1773–1781PubMedCrossRefGoogle Scholar
  19. 19.
    Depuydt P, Benoit D, Vogelaers D, Decruyenaere J, Vandijck D, Claeys G, Verschraegen G, Blot S (2008) Systematic surveillance cultures as a toolto predict involvement of multidrug antibiotic resistant bacteria in ventilator-associated pneumonia. Intensive Care Med 34:675–682PubMedCrossRefGoogle Scholar
  20. 20.
    Wade J, Rolando N, Philpott-Howard J, Wendon J (2003) Timing and aetiology of bacterial infections in a liver intensive care unit. J Hosp Infect 53:144–146PubMedCrossRefGoogle Scholar
  21. 21.
    Agodi A, Barchitta M, Cipresso R, Giaquinta L, Romeo M, Denaro C (2007) Pseudomonas aeruginosa carriage, colonization, and infection in ICU patinets. Intensive Care Med; epub (TBA)Google Scholar
  22. 22.
    Laupland KB, Kirkpatrick AW, Church DL, Ross T, Gregson DB (2004) Intensive-care-unit-acquired bloodstream infections in a regional critically ill population. J Hosp Infect 58:137–145PubMedCrossRefGoogle Scholar
  23. 23.
    Park DR (2005) The microbiology of ventilator-associated pneumonia. Respir Care 50:742–763; discussion 763–745PubMedGoogle Scholar
  24. 24.
    Garnacho-Montero J, Ortiz-Leyba C, Fernandez-Hinojosa E, Aldabo-Pallas T, Cayuela A, Marquez-Vacaro JA, Garcia-Curiel A, Jimenez-Jimenez FJ (2005) Acinetobacter baumannii ventilator-associated pneumonia: epidemiological and clinical findings. Intensive Care Med 31:649–655PubMedCrossRefGoogle Scholar
  25. 25.
    Keenan SP, Heyland DK, Jacka MJ, Cook D, Dodek P (2002) Ventilator-associated pneumonia. Prevention, diagnosis, and therapy. Crit Care Clin 18:107–125PubMedCrossRefGoogle Scholar
  26. 26.
    Heyland DK, Cook DJ, Griffith L, Keenan SP, Brun-Buisson C (1999) The attributable morbidity and mortality of ventilator-associated pneumonia in the critically ill patient. The Canadian Critical Trials Group. Am J Respir Crit Care Med 159:1249–1256PubMedGoogle Scholar
  27. 27.
    American Thoracic Society/Infectious Diseases Society of America (2005) Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 171:388–416Google Scholar
  28. 28.
    Leithead JA, Ferguson JW, Bates CM, Davidson JS, Lee A, Bathgate AJ, Hayes PC, Simpson KJ (2008) The systemic inflammatory response syndrome is predictive of renal dysfunction in patients with non-paracetamol-induced acute liver failure. Gut; epub ahead of printGoogle Scholar
  29. 29.
    Miyake Y, Iwasaki Y, Makino Y, Kobashi H, Takaguchi K, Ando M, Sakaguchi K, Shiratori Y (2007) Prognostic factors for fatal outcomes prior to receiving liver transplantation in patients with non-acetaminophen-related fulminant liver failure. J Gastroenterol Hepatol 22:855–861PubMedCrossRefGoogle Scholar
  30. 30.
    Schmidt LE, Larsen FS (2006) Prognostic implications of hyperlactatemia, multiple organ failure, and systemic inflammatory response syndrome in patients with acetaminophen-induced acute liver failure. Crit Care Med 34:337–343PubMedCrossRefGoogle Scholar
  31. 31.
    Mitchell I, Bihari D, Chang R, Wendon J, Williams R (1998) Earlier identification of patients at risk from acetaminophen-induced acute liver failure. Crit Care Med 26:279–284PubMedCrossRefGoogle Scholar
  32. 32.
    Bernal W, Wendon J, Rela M, Heaton N, Williams R (1998) Use and outcome of liver transplantation in acetaminophen-induced acute liver failure. Hepatology 27:1050–1055PubMedCrossRefGoogle Scholar
  33. 33.
    Antoniades CG, Berry PA, Wendon JA, Vergani D (2008) The importance of immune dysfunction in determining outcome in acute liver failure. J Hepatol 49:845–861PubMedCrossRefGoogle Scholar
  34. 34.
    Docke WD, Randow F, Syrbe U, Krausch D, Asadullah K, Reinke P, Volk HD, Kox W (1997) Monocyte deactivation in septic patients: restoration by IFN-gamma treatment. Nat Med 3:678–681PubMedCrossRefGoogle Scholar
  35. 35.
    Trewby PN, Williams R (1977) Pathophysiology of hypotension in patients with fulminant hepatic failure. Gut 18:1021–1026PubMedCrossRefGoogle Scholar
  36. 36.
    Peters RP, van Agtmael MA, Danner SA, Savelkoul PH, Vandenbroucke-Grauls CM (2004) New developments in the diagnosis of bloodstream infections. Lancet Infect Dis 4:751–760PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Constantine J. Karvellas
    • 1
    • 2
  • Fred Pink
    • 2
  • Mark McPhail
    • 2
  • Timothy Cross
    • 2
  • Georg Auzinger
    • 2
  • William Bernal
    • 2
  • Elizabeth Sizer
    • 2
  • Demetrios J. Kutsogiannis
    • 1
  • Ian Eltringham
    • 2
  • Julia A. Wendon
    • 2
  1. 1.Division of Critical Care MedicineUniversity of AlbertaEdmontonCanada
  2. 2.Institute of Liver StudiesKing’s College HospitalLondonUK

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