title: Early clinical and laboratory risk factors of intensive care unit requirement during 2004-2008 dengue epidemics in Singapore: a matched case-control study.
abstract: BACKGROUND
  Dengue infection can result in severe clinical manifestations requiring intensive care. Effective triage is critical for early clinical management to reduce morbidity and mortality. However, there is limited knowledge on early risk factors of intensive care unit (ICU) requirement. This study aims to identify early clinical and laboratory risk factors of ICU requirement at first presentation in hospital and 24 hours prior to ICU requirement.
  
  
  METHODS
  A retrospective 1:4 matched case-control study was performed with 27 dengue patients who required ICU, and 108 dengue patients who did not require ICU from year 2004-2008, matched by year of dengue presentation. Univariate and multivariate conditional logistic regression were performed. Optimal predictive models were generated with statistically significant risk factors identified using stepwise forward and backward elimination method.
  
  
  RESULTS
  ICU dengue patients were significantly older (P=0.003) and had diabetes (P=0.031), compared with non-ICU dengue patients. There were seven deaths among ICU patients at median seven days post fever. At first presentation, the WHO 2009 classification of dengue severity was significantly associated (P<0.001) with ICU, but not the WHO 1997 classification. Early clinical risk factors at presentation associated with ICU requirement were hematocrit change ≥20% concurrent with platelet <50 K [95% confidence-interval (CI)=2.46-30.53], hypoproteinemia (95% CI=1.09-19.74), hypotension (95% CI=1.83-31.79) and severe organ involvement (95% CI=3.30-331). Early laboratory risk factors at presentation were neutrophil proportion (95% CI=1.04-1.17), serum urea (95% CI=1.02-1.56) and alanine aminotransferase level (95% CI=1.001-1.06). This predictive model has sensitivity and specificity up to 88%. Early laboratory risk factors at 24 hours prior to ICU were lymphocyte (95% CI=1.03-1.38) and monocyte proportions (95% CI=1.02-1.78), pulse rate (95% CI=1.002-1.14) and blood pressure (95% CI=0.92-0.996). This predictive model has sensitivity and specificity up to 88.9% and 78%, respectively.
  
  
  CONCLUSIONS
  This is the first matched case-control study, to our best knowledge, that identified early clinical and laboratory risk factors of ICU requirement during hospitalization. These factors suggested differential pathophysiological background of dengue patients as early as first presentation prior to ICU requirement, which may reflect the pathogenesis of dengue severity. These risk models may facilitate clinicians in triage of patients, after validating in larger independent studies.
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore. Junxiong_Pang@nuhs.edu.sg.|Infectious Diseases, Genome Institute of Singapore, Singapore, Singapore. Junxiong_Pang@nuhs.edu.sg.|Communicable Disease Center, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore, Singapore. Junxiong_Pang@nuhs.edu.sg.
authors.forename: Junxiong
authors.initials: J
authors.lastname: Pang
authors.affiliation: Communicable Disease Center, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore, Singapore. linn_thein_tun@ttsh.com.sg.
authors.forename: Tun-Linn
authors.initials: TL
authors.lastname: Thein
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore. yee_sin_leo@ttsh.com.sg.|Communicable Disease Center, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore, Singapore. yee_sin_leo@ttsh.com.sg.|Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. yee_sin_leo@ttsh.com.sg.
authors.forename: Yee-Sin
authors.initials: YS
authors.lastname: Leo
authors.affiliation: Communicable Disease Center, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore, Singapore. david_lye@ttsh.com.sg.|Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. david_lye@ttsh.com.sg.|Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore. david_lye@ttsh.com.sg.
authors.forename: David C
authors.initials: DC
authors.lastname: Lye
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003422:Critical Care / Q000706:statistics & numerical data*; D003661:Decision Support Techniques; D003715:Dengue / Q000175:diagnosis / Q000453:epidemiology / Q000628:therapy*; D058872:Epidemics; D005260:Female; D006801:Humans; D007362:Intensive Care Units / Q000706:statistics & numerical data; D016015:Logistic Models; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012846:Singapore / Q000453:epidemiology; D055815:Young Adult