Intensive Care Medicine

, Volume 43, Issue 8, pp 1085–1096 | Cite as

Prediction of pediatric sepsis mortality within 1 h of intensive care admission

  • Luregn J. Schlapbach
  • Graeme MacLaren
  • Marino Festa
  • Janet Alexander
  • Simon Erickson
  • John Beca
  • Anthony Slater
  • Andreas Schibler
  • David Pilcher
  • Johnny Millar
  • Lahn Straney
  • On behalf of the Australian & New Zealand Intensive Care Society (ANZICS) Centre for Outcomes & Resource Evaluation (CORE) and Australian & New Zealand Intensive Care Society (ANZICS) Paediatric Study Group
Pediatric Original

Abstract

Purpose

The definitions of sepsis and septic shock have recently been revised in adults, but contemporary data are needed to inform similar approaches in children.

Methods

Multicenter cohort study including children <16 years admitted with sepsis or septic shock to ICUs in Australia and New Zealand in the period 2012–2015. We assessed septic shock criteria at ICU admission to define sepsis severity, using 30-day mortality as outcome. Through multivariable logistic regression, a pediatric sepsis score was derived using variables available within 60 min of ICU admission.

Results

Of 42,523 pediatric admissions, 4403 children were admitted with invasive infection, including 1697 diagnosed as having sepsis/septic shock on admission. Mortality was 8.5% (144/1697) and 50.7% of deaths occurred within 48 h of admission. The presence of septic shock as defined by the 2005 consensus was sensitive but not specific in predicting mortality (AUC = 0.69; 95% CI 0.65–0.72). Combinations of hypotension, vasopressor therapy, and lactate >2 mmol/l discriminated poorly (AUC <0.60). Multivariate models showed that oxygenation markers, ventilatory support, hypotension, cardiac arrest, serum lactate, pupil responsiveness, and immunosuppression were the best-performing predictors (0.843; 0.811–0.875). We derived a pediatric sepsis score (0.817; 0.779–0.855), and every one-point increase was associated with a 28.5% (23.8–33.2%) increase in the odds of death. Children with a score ≥6 had 19.8% mortality and accounted for 74.3% of deaths. The sepsis score performed comparably when applied to all children admitted with invasive infection (0.810; 0.781–0.840).

Conclusions

We observed mortality patterns specific to pediatric sepsis that support the need for specialized definitions of sepsis severity in children. We demonstrated the importance of lactate, cardiovascular, and respiratory derangements at ICU admission for the identification of children with substantially higher risk of sepsis mortality.

Keywords

Childhood Mortality Infection Sepsis Septic shock 

Abbreviations

BMT

Bone marrow transplant

ECMO

Extracorporeal membrane oxygenation

OR

Odds ratio

PICU

Pediatric intensive care unit

PIM

Pediatric index of mortality

SSC

Surviving Sepsis Campaign

SOFA

Sequential (Sepsis-related) Organ Failure Assessment

Supplementary material

134_2017_4701_MOESM1_ESM.docx (101 kb)
Supplementary material 1 (DOCX 101 kb)
134_2017_4701_MOESM2_ESM.docx (15 kb)
Supplementary material 2 (DOCX 15 kb)

References

  1. 1.
    Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC (2016) The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 315:801–810CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Shankar-Hari M, Phillips GS, Levy ML, Seymour CW, Liu VX, Deutschman CS, Angus DC, Rubenfeld GD, Singer M, Sepsis Definitions Task Force (2016) Developing a new definition and assessing new clinical criteria for septic shock: for the third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 315:775–787CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A, Rubenfeld G, Kahn JM, Shankar-Hari M, Singer M, Deutschman CS, Escobar GJ, Angus DC (2016) Assessment of clinical criteria for sepsis: for the third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 315:762–774CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Singer M (2016) The new sepsis consensus definitions (Sepsis-3): the good, the not-so-bad, and the actually-quite-pretty. Intensive Care Med 42:2027–2029CrossRefPubMedGoogle Scholar
  5. 5.
    Goldstein B, Giroir B, Randolph A (2005) International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 6:2–8CrossRefPubMedGoogle Scholar
  6. 6.
    Weiss SL, Fitzgerald JC, Pappachan J, Wheeler D, Jaramillo-Bustamante JC, Salloo A, Singhi SC, Erickson S, Roy JA, Bush JL, Nadkarni VM, Thomas NJ, Sepsis Prevalence, Outcomes, and Therapies (SPROUT) Study Investigators, Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network (2015) Global epidemiology of pediatric severe sepsis: the sepsis prevalence, outcomes, and therapies study. Am J Respir Crit Care Med 191:1147–1157CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Schlapbach LJ, Straney L, Alexander J, MacLaren G, Festa M, Schibler A, Slater A, ANZICS Paediatric Study Group (2015) Mortality related to invasive infections, sepsis, and septic shock in critically ill children in Australia and New Zealand 2002–13: a multicentre retrospective cohort study. Lancet Infect Dis 15:46–54CrossRefPubMedGoogle Scholar
  8. 8.
    Hartman ME, Linde-Zwirble WT, Angus DC, Watson RS (2013) Trends in the epidemiology of pediatric severe sepsis. Pediatr Crit Care Med 14:686–693CrossRefPubMedGoogle Scholar
  9. 9.
    (2012) For sepsis, the drugs don’t work. Lancet Infect Dis 12:89Google Scholar
  10. 10.
    Nadel S, Goldstein B, Williams MD, Dalton H, Peters M, Macias WL, Abd-Allah SA, Levy H, Angle R, Wang D, Sundin DP, Giroir B, REsearching severe Sepsis and Organ dysfunction in children: a gLobal perspectiVE (RESOLVE) study group (2007) Drotrecogin alfa (activated) in children with severe sepsis: a multicentre phase III randomised controlled trial. Lancet 369:836–843CrossRefPubMedGoogle Scholar
  11. 11.
    Levin M, Quint PA, Goldstein B, Barton P, Bradley JS, Shemie SD, Yeh T, Kim SS, Cafaro DP, Scannon PJ, Giroir BP (2000) Recombinant bactericidal/permeability-increasing protein (rBPI21) as adjunctive treatment for children with severe meningococcal sepsis: a randomised trial. rBPI21 Meningococcal Sepsis Study Group. Lancet 356:961–967CrossRefPubMedGoogle Scholar
  12. 12.
    Wiens MO, Larson CP, Kumbakumba E, Kissoon N, Ansermino JM, Singer J, Wong H, Ndamira A, Kabakyenga J, Moschovis P, Kiwanuka J (2016) Application of sepsis definitions to pediatric patients admitted with suspected infections in Uganda. Pediatr Crit Care Med 17:400–405CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Kaukonen KM, Bailey M, Pilcher D, Cooper DJ, Bellomo R (2015) Systemic inflammatory response syndrome criteria in defining severe sepsis. N Engl J Med 372:1629–1638CrossRefPubMedGoogle Scholar
  14. 14.
    Straney L, Clements A, Parslow RC, Pearson G, Shann F, Alexander J, Slater A (2013) Paediatric index of mortality 3: an updated model for predicting mortality in pediatric intensive care. Pediatr Crit Care Med 14:673–681CrossRefPubMedGoogle Scholar
  15. 15.
    Weiss SL, Fitzgerald JC, Maffei FA, Kane JM, Rodriguez-Nunez A, Hsing DD, Franzon D, Kee SY, Bush JL, Roy JA, Thomas NJ, Nadkarni VM, SPROUT Study Investigators, Pediatric Acute Lung Injury and Sepsis Investigators Network (2015) Discordant identification of pediatric severe sepsis by research and clinical definitions in the SPROUT international point prevalence study. Crit Care 19:325CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Khemani RG, Patel NR, Bart RD 3rd, Newth CJ (2009) Comparison of the pulse oximetric saturation/fraction of inspired oxygen ratio and the PaO2/fraction of inspired oxygen ratio in children. Chest 135:662–668CrossRefPubMedGoogle Scholar
  17. 17.
    Haque IU, Zaritsky AL (2007) Analysis of the evidence for the lower limit of systolic and mean arterial pressure in children. Pediatr Crit Care Med 8:138–144CrossRefPubMedGoogle Scholar
  18. 18.
    Leteurtre S, Duhamel A, Salleron J, Grandbastien B, Lacroix J, Leclerc F, Groupe Francophone de Reanimation et d’Urgences Pédiatriques (GFRUP) (2013) PELOD-2: an update of the PEdiatric logistic organ dysfunction score. Crit Care Med 41:1761–1773CrossRefPubMedGoogle Scholar
  19. 19.
    Pediatric Acute Lung Injury Consensus Conference Group (2015) Pediatric acute respiratory distress syndrome: consensus recommendations from the pediatric acute lung injury consensus conference. Pediatr Crit Care Med 16:428–439CrossRefGoogle Scholar
  20. 20.
    Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche J-D, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent J-L, Wiersinga WJ, Zimmerman JL, Dellinger RP (2017) Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. doi:10.1007/s00134-017-4683-6
  21. 21.
    Launay E, Gras-Le Guen C, Martinot A, Assathiany R, Martin E, Blanchais T, Deneux-Tharaux C, Roze JC, Chalumeau M (2014) Why children with severe bacterial infection die: a population-based study of determinants and consequences of suboptimal care with a special emphasis on methodological issues. PLoS One 9:e107286CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Brierley J, Carcillo JA, Choong K, Cornell T, Decaen A, Deymann A, Doctor A, Davis A, Duff J, Dugas MA, Duncan A, Evans B, Feldman J, Felmet K, Fisher G, Frankel L, Jeffries H, Greenwald B, Gutierrez J, Hall M, Han YY, Hanson J, Hazelzet J, Hernan L, Kiff J, Kissoon N, Kon A, Irazuzta J, Lin J, Lorts A, Mariscalco M, Mehta R, Nadel S, Nguyen T, Nicholson C, Peters M, Okhuysen-Cawley R, Poulton T, Relves M, Rodriguez A, Rozenfeld R, Schnitzler E, Shanley T, Kache S, Skippen P, Torres A, von Dessauer B, Weingarten J, Yeh T, Zaritsky A, Stojadinovic B, Zimmerman J, Zuckerberg A (2009) Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine. Crit Care Med 37:666–688CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Carcillo JA, Fields AI, American College of Critical Care Medicine Task Force Committee Members (2002) Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock. Crit Care Med 30:1365–1378CrossRefPubMedGoogle Scholar
  24. 24.
    Morin L, Ray S, Wilson C, Remy S, Benissa MR, Jansen NJ, Javouhey E, Peters MJ, Kneyber M, De Luca D, Nadel S, Schlapbach LJ, Maclaren G, Tissieres P, ESPNIC Refractory Septic Shock Definition Taskforce, the Infection Systemic Inflammation Sepsis section of ESPNIC (2016) Refractory septic shock in children: a European Society of Paediatric and Neonatal Intensive Care definition. Intensive Care Med 42:1948–1957CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Park TK, Yang JH, Jeon K, Choi SH, Choi JH, Gwon HC, Chung CR, Park CM, Cho YH, Sung K, Suh GY (2015) Extracorporeal membrane oxygenation for refractory septic shock in adults. Eur J Cardiothorac Surg 47:e68–e74CrossRefPubMedGoogle Scholar
  26. 26.
    Morris KP, McShane P, Stickley J, Parslow RC (2012) The relationship between blood lactate concentration, the Paediatric Index of Mortality 2 (PIM2) and mortality in paediatric intensive care. Intensive Care Med 38:2042–2046CrossRefPubMedGoogle Scholar
  27. 27.
    MacLaren G, Butt W, Best D, Donath S (2011) Central extracorporeal membrane oxygenation for refractory pediatric septic shock. Pediatr Crit Care Med 12:133–136CrossRefPubMedGoogle Scholar
  28. 28.
    Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M (2001) Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 345:1368–1377CrossRefPubMedGoogle Scholar
  29. 29.
    Smith S, Butt W, Best D, MacLaren G (2016) Long-term survival after extracorporeal life support in children with neutropenic sepsis. Intensive Care Med 42:942–943CrossRefPubMedGoogle Scholar
  30. 30.
    Sprung CL, Schein RM, Balk RA (2016) The new sepsis consensus definitions: the good, the bad and the ugly. Intensive Care Med 42:2024–2026CrossRefPubMedGoogle Scholar
  31. 31.
    Musa N, Murthy S, Kissoon N (2016) Pediatric sepsis and septic shock management in resource-limited settings. Intensive Care Med 42:2037–2039CrossRefPubMedGoogle Scholar
  32. 32.
    Cvetkovic M, Lutman D, Ramnarayan P, Pathan N, Inwald DP, Peters MJ (2015) Timing of death in children referred for intensive care with severe sepsis: implications for interventional studies. Pediatr Crit Care Med 16:410–417CrossRefPubMedGoogle Scholar
  33. 33.
    Maclaren G, Butt W, Best D, Donath S, Taylor A (2007) Extracorporeal membrane oxygenation for refractory septic shock in children: one institution’s experience. Pediatr Crit Care Med 8:447–451CrossRefPubMedGoogle Scholar
  34. 34.
    Asgari S, McLaren PJ, Peake J, Wong M, Wong R, Bartha I, Francis JR, Abarca K, Gelderman KA, Agyeman P, Aebi C, Berger C, Fellay J, Schlapbach LJ, for the Swiss Pediatric Sepsis Study (2016) Exome sequencing reveals primary immunodeficiencies in children with community-acquired pseudomonas aeruginosa sepsis. Front Immunol 7:357PubMedPubMedCentralGoogle Scholar
  35. 35.
    Leteurtre S, Leclerc F, Martinot A, Cremer R, Fourier C, Sadik A, Grandbastien B (2001) Can generic scores (Pediatric Risk of Mortality and Pediatric Index of Mortality) replace specific scores in predicting the outcome of presumed meningococcal septic shock in children? Crit Care Med 29:1239–1246CrossRefPubMedGoogle Scholar
  36. 36.
    Weiss SL, Parker B, Bullock ME, Swartz S, Price C, Wainwright MS, Goodman DM (2012) Defining pediatric sepsis by different criteria: discrepancies in populations and implications for clinical practice. Pediatr Crit Care Med 13:e219–e226CrossRefPubMedGoogle Scholar
  37. 37.
    Wong HR, Atkinson SJ, Cvijanovich NZ, Anas N, Allen GL, Thomas NJ, Bigham MT, Weiss SL, Fitzgerald JC, Checchia PA, Meyer K, Quasney M, Hall M, Gedeit R, Freishtat RJ, Nowak J, Raj SS, Gertz S, Lindsell CJ (2016) Combining prognostic and predictive enrichment strategies to identify children with septic shock responsive to corticosteroids. Crit Care Med 44:e1000–e1003CrossRefPubMedGoogle Scholar
  38. 38.
    Wong HR, Cvijanovich NZ, Anas N, Allen GL, Thomas NJ, Bigham MT, Weiss SL, Fitzgerald J, Checchia PA, Meyer K, Shanley TP, Quasney M, Hall M, Gedeit R, Freishtat RJ, Nowak J, Shekhar RS, Gertz S, Dawson E, Howard K, Harmon K, Beckman E, Frank E, Lindsell CJ (2015) Developing a clinically feasible personalized medicine approach to pediatric septic shock. Am J Respir Crit Care Med 191:309–315CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Scott HF, Brou L, Deakyne SJ, Kempe A, Fairclough DL, Bajaj L (2017) Association between early lactate levels and 30-day mortality in clinically suspected sepsis in children. JAMA Pediatr. doi:10.1001/jamapediatrics.2016.3681

Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2017

Authors and Affiliations

  • Luregn J. Schlapbach
    • 1
    • 2
    • 3
  • Graeme MacLaren
    • 4
    • 5
  • Marino Festa
    • 6
  • Janet Alexander
    • 7
    • 8
  • Simon Erickson
    • 9
  • John Beca
    • 10
  • Anthony Slater
    • 2
  • Andreas Schibler
    • 1
    • 2
  • David Pilcher
    • 7
    • 11
    • 12
  • Johnny Millar
    • 5
  • Lahn Straney
    • 13
  • On behalf of the Australian & New Zealand Intensive Care Society (ANZICS) Centre for Outcomes & Resource Evaluation (CORE) and Australian & New Zealand Intensive Care Society (ANZICS) Paediatric Study Group
  1. 1.Paediatric Critical Care Research Group, Mater Research InstituteUniversity of QueenslandBrisbaneAustralia
  2. 2.Paediatric Intensive Care UnitLady Cilento Children’s HospitalBrisbaneAustralia
  3. 3.Department of Pediatrics, Inselspital, Bern University HospitalUniversity of BernBernSwitzerland
  4. 4.Cardiothoracic Intensive Care UnitNational University Health SystemSingaporeSingapore
  5. 5.Paediatric Intensive Care UnitThe Royal Children’s HospitalMelbourneAustralia
  6. 6.Paediatric Intensive Care UnitChildren’s Hospital WestmeadSydneyAustralia
  7. 7.The Australian and New Zealand Intensive Care Society (ANZICS) Centre for Outcome and Resource Evaluation (CORE)MelbourneAustralia
  8. 8.School of MedicineUniversity of QueenslandBrisbaneAustralia
  9. 9.Paediatric Intensive Care UnitPrincess Margaret Hospital for ChildrenPerthAustralia
  10. 10.Paediatric Intensive Care UnitStarship Children’s HospitalAucklandNew Zealand
  11. 11.Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive MedicineMonash UniversityMelbourneAustralia
  12. 12.Department of Intensive CareThe Alfred HospitalPrahranAustralia
  13. 13.Department of Epidemiology and Preventive MedicineMonash UniversityMelbourneAustralia

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