Intensive Care Medicine

, Volume 41, Issue 8, pp 1445–1453 | Cite as

Early fluid accumulation in children with shock and ICU mortality: a matched case–control study

  • Priya Bhaskar
  • Archana V. Dhar
  • Marita Thompson
  • Raymond Quigley
  • Vinai ModemEmail author



The purpose of this study was to evaluate the association between early fluid accumulation and mortality in children with shock states.


We retrospectively reviewed children admitted in shock states to the pediatric intensive care unit (ICU) at a tertiary level children’s hospital over a 7-month period. The study was designed as a matched case–control study. Children with early fluid overload, defined as fluid accumulation of ≥10 % of admission body weight during the initial 3 days, were designated as the cases. They were compared with matched controls without early fluid accumulation. Cases and controls were matched for age, severity of illness at ICU admission and need for organ support. They were compared with respect to all-cause ICU mortality and other secondary outcomes.


A total of 114 children (age range 0–17.4 years; N = 42 cases and 72 matched controls) met the study criteria. Mortality rate was 13 % (15/114) in this cohort. Multivariable logistic regression analysis identified the presence of early fluid overload [adjusted odds ratio (OR) 9.17, 95 % confidence interval (CI) 2.22–55.57], its severity (adjusted OR 1.11, 95 % CI 1.05–1.19) and its duration (adjusted OR 1.61, 95 % CI 1.21–2.28) as independent predictors of mortality. Cases had higher mortality than the controls (26 vs. 6 %; p 0.003), and this difference remained significant in the matched analysis (37 vs. 3 %; p 0.002).


The presence, severity and duration of early fluid are associated with increased ICU mortality in children admitted to the pediatric ICU in shock states.


Fluid overload Early fluid accumulation Mortality Children Shock 


Conflicts of interest

None of the authors have any conflicts of interest or financial disclosures to report. The study was funded by Internal Departmental Funds, Department of Pediatrics at the University of Texas Southwestern Medical School.

Supplementary material

134_2015_3851_MOESM1_ESM.docx (31 kb)
Supplementary material 1 (DOCX 31.2 kb)


  1. 1.
    Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M, Early Goal-Directed Therapy Collaborative G (2001) Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 345(19):1368–1377. doi: 10.1056/NEJMoa010307 PubMedCrossRefGoogle Scholar
  2. 2.
    Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb S, Beale RJ, Vincent JL, Moreno R, Surviving Sepsis Campaign Guidelines Committee including the Pediatric S (2013) Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock. Intensive Care Med 39(2):165–228. doi: 10.1007/s00134-012-2769-8 PubMedCrossRefGoogle Scholar
  3. 3.
    Prowle JR, Echeverri JE, Ligabo EV, Ronco C, Bellomo R (2010) Fluid balance and acute kidney injury. Nat Rev Nephrol 6(2):107–115. doi: 10.1038/nrneph.2009.213 PubMedCrossRefGoogle Scholar
  4. 4.
    D’Orio V, Mendes P, Carlier P, Fatemi M, Marcelle R (1991) Lung fluid dynamics and supply dependency of oxygen uptake during experimental endotoxic shock and volume resuscitation. Crit Care Med 19(7):955–962PubMedCrossRefGoogle Scholar
  5. 5.
    Hill SL, Elings VB, Lewis FR (1980) Changes in lung water and capillary permeability following sepsis and fluid overload. J Surg Res 28(2):140–150PubMedCrossRefGoogle Scholar
  6. 6.
    Bagshaw SM, Brophy PD, Cruz D, Ronco C (2008) Fluid balance as a biomarker: impact of fluid overload on outcome in critically ill patients with acute kidney injury. Crit Care 12(4):169. doi: 10.1186/cc6948 PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Mehta RL, Bouchard J (2011) Controversies in acute kidney injury: effects of fluid overload on outcome. Contrib Nephrol 174:200–211. doi: 10.1159/000329410 PubMedCrossRefGoogle Scholar
  8. 8.
    Sutherland SM, Zappitelli M, Alexander SR, Chua AN, Brophy PD, Bunchman TE, Hackbarth R, Somers MJ, Baum M, Symons JM, Flores FX, Benfield M, Askenazi D, Chand D, Fortenberry JD, Mahan JD, McBryde K, Blowey D, Goldstein SL (2010) Fluid overload and mortality in children receiving continuous renal replacement therapy: the prospective pediatric continuous renal replacement therapy registry. Am J Kidney Dis Off J Natl Kidney Found 55(2):316–325. doi: 10.1053/j.ajkd.2009.10.048 CrossRefGoogle Scholar
  9. 9.
    Foland JA, Fortenberry JD, Warshaw BL, Pettignano R, Merritt RK, Heard ML, Rogers K, Reid C, Tanner AJ, Easley KA (2004) Fluid overload before continuous hemofiltration and survival in critically ill children: a retrospective analysis. Crit Care Med 32(8):1771–1776PubMedCrossRefGoogle Scholar
  10. 10.
    Gillespie RS, Seidel K, Symons JM (2004) Effect of fluid overload and dose of replacement fluid on survival in hemofiltration. Pediatr Nephrol 19(12):1394–1399. doi: 10.1007/s00467-004-1655-1 PubMedCrossRefGoogle Scholar
  11. 11.
    Arikan AA, Zappitelli M, Goldstein SL, Naipaul A, Jefferson LS, Loftis LL (2012) Fluid overload is associated with impaired oxygenation and morbidity in critically ill children. Pediatr Crit Care Med 13(3):253–258. doi: 10.1097/PCC.0b013e31822882a3 PubMedCrossRefGoogle Scholar
  12. 12.
    National Heart L, Blood Institute Acute Respiratory Distress Syndrome Clinical Trials N, Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, deBoisblanc B, Connors AF Jr, Hite RD, Harabin AL (2006) Comparison of two fluid-management strategies in acute lung injury. N Engl J Med 354(24):2564–2575. doi: 10.1056/NEJMoa062200 CrossRefGoogle Scholar
  13. 13.
    Torgersen C, Dunser MW, Schmittinger CA, Pettila V, Ruokonen E, Wenzel V, Jakob SM, Takala J (2011) Current approach to the haemodynamic management of septic shock patients in European intensive care units: a cross-sectional, self-reported questionnaire-based survey. Eur J Anaesthesiol 28(4):284–290. doi: 10.1097/EJA.0b013e3283405062 PubMedGoogle Scholar
  14. 14.
    Stewart RM, Park PK, Hunt JP, McIntyre RC Jr, McCarthy J, Zarzabal LA, Michalek JE, National Institutes of Health/National Heart L, Blood Institute Acute Respiratory Distress Syndrome Clinical Trials N (2009) Less is more: improved outcomes in surgical patients with conservative fluid administration and central venous catheter monitoring. J Am Coll Surg 208(5):725–735. doi: 10.1016/j.jamcollsurg.2009.01.026 discussion 735–727PubMedCrossRefGoogle Scholar
  15. 15.
    Rosenberg AL, Dechert RE, Park PK, Bartlett RH, Network NNA (2009) Review of a large clinical series: association of cumulative fluid balance on outcome in acute lung injury: a retrospective review of the ARDSnet tidal volume study cohort. J Intensive Care Med 24(1):35–46. doi: 10.1177/0885066608329850 PubMedCrossRefGoogle Scholar
  16. 16.
    Valentine SL, Sapru A, Higgerson RA, Spinella PC, Flori HR, Graham DA, Brett M, Convery M, Christie LM, Karamessinis L, Randolph AG, Pediatric Acute Lung I, Sepsis Investigator’s N, Acute Respiratory Distress Syndrome Clinical Research Network (ARDSNet) (2012) Fluid balance in critically ill children with acute lung injury. Crit Care Med 40(10):2883–2889. doi: 10.1097/CCM.0b013e31825bc54d PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Maitland K, Kiguli S, Opoka RO, Engoru C, Olupot-Olupot P, Akech SO, Nyeko R, Mtove G, Reyburn H, Lang T, Brent B, Evans JA, Tibenderana JK, Crawley J, Russell EC, Levin M, Babiker AG, Gibb DM, Group FT (2011) Mortality after fluid bolus in African children with severe infection. N Engl J Med 364(26):2483–2495. doi: 10.1056/NEJMoa1101549 PubMedCrossRefGoogle Scholar
  18. 18.
    Slater A, Shann F, Pearson G, Paediatric Index of Mortality Study G (2003) PIM2: a revised version of the Paediatric Index of mortality. Intensive Care Med 29(2):278–285. doi: 10.1007/s00134-002-1601-2 PubMedGoogle Scholar
  19. 19.
    Visser IH, Hazelzet JA, Albers MJ, Verlaat CW, Hogenbirk K, van Woensel JB, van Heerde M, van Waardenburg DA, Jansen NJ, Steyerberg EW (2013) Mortality prediction models for pediatric intensive care: comparison of overall and subgroup specific performance. Intensive Care Med 39(5):942–950. doi: 10.1007/s00134-013-2857-4 PubMedCrossRefGoogle Scholar
  20. 20.
    Akcan-Arikan A, Zappitelli M, Loftis LL, Washburn KK, Jefferson LS, Goldstein SL (2007) Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney Int 71(10):1028–1035. doi: 10.1038/ PubMedCrossRefGoogle Scholar
  21. 21.
    Schwartz GJ, Brion LP, Spitzer A (1987) The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin North Am 34(3):571–590PubMedGoogle Scholar
  22. 22.
    Goldstein SL, Currier H, Graf C, Cosio CC, Brewer ED, Sachdeva R (2001) Outcome in children receiving continuous venovenous hemofiltration. Pediatrics 107(6):1309–1312PubMedCrossRefGoogle Scholar
  23. 23.
    Sekhon JS (2011) Multivariate and propensity score Matching Software with automated balance optimization: the Matching Package for R. J Stat Softw 42(7):1–52Google Scholar
  24. 24.
    R Core Team (2014) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna. Available at: http://www.R-projectorg/. Accessed 1 July 2014
  25. 25.
    Mwitondi KS (2013) Statistical computing in C plus plus and R. J Appl Stat 40(4):916. Available at: doi: 10.1080/02664763.2012.749033 CrossRefGoogle Scholar
  26. 26.
    Dean AG SK, Soe MM (2014) OpenEpi: open source epidemiologic statistics for public health, version updated 09/22/2014. Available at: Accessed 15 Apr 2015)
  27. 27.
    Grams ME, Estrella MM, Coresh J, Brower RG, Liu KD, National Heart L, Blood Institute Acute Respiratory Distress Syndrome N (2011) Fluid balance, diuretic use, and mortality in acute kidney injury. Clin J Am Soc Nephrol 6(5):966–973. doi: 10.2215/CJN.08781010 PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Citerio G, Bakker J, Bassetti M, Benoit D, Cecconi M, Curtis JR, Hernandez G, Herridge M, Jaber S, Joannidis M, Papazian L, Peters M, Singer P, Smith M, Soares M, Torres A, Vieillard-Baron A, Timsit JF, Azoulay E (2014) Year in review in Intensive Care Medicine 2013: I. acute kidney injury, ultrasound, hemodynamics, cardiac arrest, transfusion, neurocritical care, and nutrition. Intensive Care Med 40(2):147–159. doi: 10.1007/s00134-013-3184-5 PubMedCrossRefGoogle Scholar
  29. 29.
    Boulain T, Boisrame-Helms J, Ehrmann S, Lascarrou JB, Bougle A, Chiche A, Lakhal K, Gaudry S, Perbet S, Desachy A, Cabasson S, Geneau I, Courouble P, Clavieras N, Massanet PL, Bellec F, Falquet Y, Reminiac F, Vignon P, Dequin PF, Meziani F (2015) Volume expansion in the first 4 days of shock: a prospective multicentre study in 19 French intensive care units. Intensive Care Med 41(2):248–256. doi: 10.1007/s00134-014-3576-1 PubMedCrossRefGoogle Scholar
  30. 30.
    Timsit JF, Citerio G, Bakker J, Bassetti M, Benoit D, Cecconi M, Curtis JR, Hernandez G, Herridge M, Jaber S, Joannidis M, Papazian L, Peters M, Singer P, Smith M, Soares M, Torres A, Vieillard-Baron A, Azoulay E (2014) Year in review in Intensive Care Medicine 2013: III. sepsis, infections, respiratory diseases, pediatrics. Intensive Care Med 40(4):471–483. doi: 10.1007/s00134-014-3235-6 PubMedCrossRefGoogle Scholar
  31. 31.
    Abulebda K, Cvijanovich NZ, Thomas NJ, Allen GL, Anas N, Bigham MT, Hall M, Freishtat RJ, Sen A, Meyer K, Checchia PA, Shanley TP, Nowak J, Quasney M, Weiss SL, Chopra A, Banschbach S, Beckman E, Lindsell CJ, Wong HR (2014) Post-ICU admission fluid balance and pediatric septic shock outcomes: a risk-stratified analysis. Crit Care Med 42(2):397–403. doi: 10.1097/CCM.0b013e3182a64607 PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Bouchard J, Soroko SB, Chertow GM, Himmelfarb J, Ikizler TA, Paganini EP, Mehta RL, Program to Improve Care in Acute Renal Disease Study G (2009) Fluid accumulation, survival and recovery of kidney function in critically ill patients with acute kidney injury. Kidney Int 76(4):422–427. doi: 10.1038/ki.2009.159 PubMedCrossRefGoogle Scholar
  33. 33.
    Boyd JH, Forbes J, Nakada TA, Walley KR, Russell JA (2011) Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality. Crit Care Med 39(2):259–265. doi: 10.1097/CCM.0b013e3181feeb15 PubMedCrossRefGoogle Scholar
  34. 34.
    Willson DF, Thomas NJ, Tamburro R, Truemper E, Truwit J, Conaway M, Traul C, Egan EE, Pediatric Acute L, Sepsis Investigators N (2013) The relationship of fluid administration to outcome in the pediatric calfactant in acute respiratory distress syndrome trial. Pediatr Crit Care Med 14(7):666–672. doi: 10.1097/PCC.0b013e3182917cb5 PubMedCrossRefGoogle Scholar
  35. 35.
    Carlsen S, Perner A, East Danish Septic Shock Cohort I (2011) Initial fluid resuscitation of patients with septic shock in the intensive care unit. Acta Anaesthesiol Scand 55(4):394–400. doi: 10.1111/j.1399-6576.2011.02399.x PubMedCrossRefGoogle Scholar
  36. 36.
    Murphy CV, Schramm GE, Doherty JA, Reichley RM, Gajic O, Afessa B, Micek ST, Kollef MH (2009) The importance of fluid management in acute lung injury secondary to septic shock. Chest 136(1):102–109. doi: 10.1378/chest.08-2706 PubMedCrossRefGoogle Scholar
  37. 37.
    Shum HP, Lee FM, Chan KC, Yan WW (2011) Interaction between fluid balance and disease severity on patient outcome in the critically ill. J Crit Care 26(6):613–619. doi: 10.1016/j.jcrc.2011.02.008 PubMedCrossRefGoogle Scholar
  38. 38.
    Waechter J, Kumar A, Lapinsky SE, Marshall J, Dodek P, Arabi Y, Parrillo JE, Dellinger RP, Garland A, Cooperative Antimicrobial Therapy of Septic Shock Database Research Group (2014) Interaction between fluids and vasoactive agents on mortality in septic shock: a multicenter, observational study. Crit Care Med 42(10):2158–2168. doi: 10.1097/CCM.0000000000000520 PubMedCrossRefGoogle Scholar
  39. 39.
    Maitland K, George EC, Evans JA, Kiguli S, Olupot-Olupot P, Akech SO, Opoka RO, Engoru C, Nyeko R, Mtove G, Reyburn H, Brent B, Nteziyaremye J, Mpoya A, Prevatt N, Dambisya CM, Semakula D, Ddungu A, Okuuny V, Wokulira R, Timbwa M, Otii B, Levin M, Crawley J, Babiker AG, Gibb DM, Group Ft (2013) Exploring mechanisms of excess mortality with early fluid resuscitation: insights from the FEAST trial. BMC Med 11:68. doi: 10.1186/1741-7015-11-68 PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Myburgh J, Finfer S (2013) Causes of death after fluid bolus resuscitation: new insights from FEAST. BMC Med 11:67. doi: 10.1186/1741-7015-11-67 PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2015

Authors and Affiliations

  • Priya Bhaskar
    • 1
  • Archana V. Dhar
    • 2
  • Marita Thompson
    • 3
  • Raymond Quigley
    • 2
  • Vinai Modem
    • 2
    Email author
  1. 1.Cardiac Intensive Care Unit, Department of Pediatrics, Feinberg School of Medicine, Ann and Robert H. Lurie Children’s Hospital of ChicagoNorthwestern UniversityChicagoUSA
  2. 2.Division of Critical Care Medicine, Department of PediatricsUniversity of Texas Southwestern Medical CenterDallasUSA
  3. 3.Pediatric Critical Care Medicine, Department of Pediatrics, Children’s Mercy HospitalUniversity of Missouri–Kansas City School of MedicineKansas CityUSA

Personalised recommendations