Log in | Register

Clinical course and outcome for critically ill children with Down syndrome: a retrospective cohort study

Shane M. Tibby| Andrew Durward| Chong Tien Goh| Kentigern Thorburn| Kevin Morris| Mike Broadhead| Mark J. Peters
Pediatric Original
Volume 38, Issue 8 / August , 2012

Pages 1365 - 1371

Abstract

Purpose

Children with Down syndrome (DS) have several genetic anomalies within chromosome 21 which may influence their response to critical illness. We compared the intensive care course and outcome of children with DS versus those without.

Methods

Retrospective cohort study in four English paediatric intensive care units (ICUs) (2003–2009, n = 33,485). We examined, via a competing risks model, whether risk (subhazard) for ICU mortality differed for children with DS, after adjusting for important confounders.

Results

DS patients exhibited lower disease severity at ICU admission but subsequently required a higher proportion of cardiovascular support, and similar renal support to non-DS patients. Children with DS (n = 1,278) had lower crude mortality than those without (4.2 versus 6.2 %, p = 0.003). This was not significant when expressed as standardized mortality ratio: 0.83 [95 % confidence interval (CI) 0.63–1.09] versus 0.90 (95 % CI 0.86–0.94). However, the competing risks model showed that mortality risk was influenced by length of ICU stay. At admission, DS patients exhibited a subhazard for mortality of 0.63 (95 % CI 0.46–0.85), which increased to 1.00 by day 10 of admission, and continued rising above that of non-DS children thereafter.

Conclusions

Children with DS require a higher proportion of organ support than expected by disease severity at ICU admission. In addition, the mortality risk for children with DS is dependent upon length of ICU stay. These findings could reflect differences in case mix, but are also compatible with different response to critical illness in this group.

Keywords

References

  1. Bittles AH, Bower C, Hussain R, Glasson EJ (2007) The four ages of Down syndrome. Eur J Public Health 17:221–225
    • View reference on PubMed
    • View reference on publisher's website
  2. Ross JA, Spector LG, Robison LL, Olshan AF (2005) Epidemiology of leukemia in children with Down syndrome. Pediatr Blood Cancer 44:8–12
    • View reference on PubMed
    • View reference on publisher's website
  3. Lott IT, Dierssen M (2010) Cognitive deficits and associated neurological complications in individuals with Down’s syndrome. Lancet Neurol 9:623–633
    • View reference on PubMed
    • View reference on publisher's website
  4. Yang Q, Rasmussen SA, Friedman JM (2002) Mortality associated with Down’s syndrome in the USA from 1983 to 1997: a population-based study. Lancet 359:1019–1025
    • View reference on PubMed
    • View reference on publisher's website
  5. Michielon G, Marino B, Oricchio G, Digilio MC, Iorio F, Filippelli S, Placidi S, Di Donato RM (2009) Impact of DEL22q11, trisomy 21, and other genetic syndromes on surgical outcome of conotruncal heart defects. J Thorac Cardiovasc Surg 138:565–570 e2
    • View reference on PubMed
    • View reference on publisher's website
  6. Fudge JC Jr, Li S, Jaggers J, O’Brien SM, Peterson ED, Jacobs JP, Welke KF, Jacobs ML, Li JS, Pasquali SK (2010) Congenital heart surgery outcomes in Down syndrome: analysis of a national clinical database. Pediatrics 126:315–322
    • View reference on PubMed
    • View reference on publisher's website
  7. Bruijn M, van der Aa LB, van Rijn RR, Bos AP, van Woensel JB (2007) High incidence of acute lung injury in children with Down syndrome. Intensive Care Med 33:2179–2182
  8. Garrison MM, Jeffries H, Christakis DA (2005) Risk of death for children with Down syndrome and sepsis. J Pediatr 147:748–752
    • View reference on PubMed
    • View reference on publisher's website
  9. Proulx F, Gauthier M, Nadeau D, Lacroix J, Farrell CA (1994) Timing and predictors of death in pediatric patients with multiple organ system failure. Crit Care Med 22:1025–1031
    • View reference on PubMed
    • View reference on publisher's website
  10. Wilkinson JD, Pollack MM, Ruttimann UE, Glass NL, Yeh TS (1986) Outcome of pediatric patients with multiple organ system failure. Crit Care Med 14:271–274
    • View reference on PubMed
    • View reference on publisher's website
  11. Wilkinson JD, Pollack MM, Glass NL, Kanter RK, Katz RW, Steinhart CM (1987) Mortality associated with multiple organ system failure and sepsis in pediatric intensive care unit. J Pediatr 111:324–328
    • View reference on PubMed
    • View reference on publisher's website
  12. Abraham E, Singer M (2007) Mechanisms of sepsis-induced organ dysfunction. Crit Care Med 35:2408–2416
    • View reference on PubMed
    • View reference on publisher's website
  13. Mongardon N, Dyson A, Singer M (2009) Is MOF an outcome parameter or a transient, adaptive state in critical illness? Curr Opin Crit Care 15:431–436
    • View reference on PubMed
    • View reference on publisher's website
  14. Singer M, De Santis V, Vitale D, Jeffcoate W (2004) Multiorgan failure is an adaptive, endocrine-mediated, metabolic response to overwhelming systemic inflammation. Lancet 364:545–548
    • View reference on PubMed
    • View reference on publisher's website
  15. Pallardó FV, Degan P, d’Ischia M, Kelly FJ, Zatterale A, Calzone R, Castello G, Fernandez-Delgado R, Dunster C, Lloret A, Manini P, Pisanti MA, Vuttariello E, Pagano G (2006) Multiple evidence for an early age pro-oxidant state in Down Syndrome patients. Biogerontology 7:211–220
    • View reference on PubMed
    • View reference on publisher's website
  16. Hawli Y, Nasrallah M, El-Hajj Fuleihan G (2009) Endocrine and musculoskeletal abnormalities in patients with Down syndrome. Nat Rev Endocrinol 5:327–334
    • View reference on PubMed
    • View reference on publisher's website
  17. http://www.picanet.org.uk/. Accessed 30 April 2011
  18. PICANET REPORT (2003–2004). http://www.picanet.org.uk/documentation.html. Accessed 8 May 2012
  19. Pintile M (2006) Competing risks: a practical perspective. Wiley-Blackwell. ISBN-10: 0470870680
  20. Royston P, Altman DG (1994) Regression using fractional polynomials of continuous covariates: parsimonious parametric modeling. Appl Stat 43:429–467
    • View reference on publisher's website
  21. Slater A, Shann F, Pearson G (2003) PIM2: a revised version of the Paediatric Index of Mortality. Intensive Care Med 29:278–285
    • View reference on PubMed
  22. Balfour-Lynn IM, Tasker RC (1996) At the coalface–medical ethics in practice. Futility and death in paediatric medical intensive care. J Med Ethics 22:279–281
    • View reference on PubMed
    • View reference on publisher's website
  23. Azevedo LC (2010) Mitochondrial dysfunction during sepsis. Endocr Metab Immune Disord Drug Targets 10:214–223
    • View reference on PubMed
  24. Singer M (2007) Mitochondrial function in sepsis: acute phase versus multiple organ failure. Crit Care Med 35(9 Suppl):S441–S448
    • View reference on PubMed
    • View reference on publisher's website
  25. Carré JE, Orban JC, Re L, Felsmann K, Iffert W, Bauer M, Suliman HB, Piantadosi CA, Mayhew TM, Breen P, Stotz M, Singer M (2010) Survival in critical illness is associated with early activation of mitochondrial biogenesis. Am J Respir Crit Care Med 182:745–751
    • View reference on PubMed
    • View reference on publisher's website
  26. Zitnanová I, Korytár P, Aruoma OI, Sustrová M, Garaiová I, Muchová J, Kalnovicová T, Pueschel S, Duracková Z (2004) Uric acid and allantoin levels in Down syndrome: antioxidant and oxidative stress mechanisms? Clin Chim Acta 341:139–146
    • View reference on PubMed
    • View reference on publisher's website
  27. Clementi E, Brown GC, Feelisch M, Moncada S (1998) Persistent inhibition of cell respiration by nitric oxide: crucial role of S-nitrosylation of mitochondrial complex I and protective action of glutathione. Proc Natl Acad Sci USA 95:7631–7636
    • View reference on PubMed
    • View reference on publisher's website
  28. Arron JR, Winslow MM, Polleri A, Chang CP, Wu H, Gao X, Neilson JR, Chen L, Heit JJ, Kim SK, Yamasaki N, Miyakawa T, Francke U, Graef IA, Crabtree GR (2006) NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21. Nature 441(7093):595–600
    • View reference on PubMed
    • View reference on publisher's website
  29. Hermann-Kleiter N, Baier G (2010) NFAT pulls the strings during CD4+ T helper cell effector functions. Blood 115:2989–2997
    • View reference on PubMed
    • View reference on publisher's website
  30. Minami T, Yano K, Miura M, Kobayashi M, Suehiro J, Reid PC, Hamakubo T, Ryeom S, Aird WC, Kodama T (2009) The Down syndrome critical region gene 1 short variant promoters direct vascular bed-specific gene expression during inflammation in mice. J Clin Invest 119:2257–2270
    • View reference on PubMed

Sign In

Connect with ICM

Top 5 Articles Editors Picks Supplement