Survivors versus nonsurvivors postburn: differences in inflammatory and hypermetabolic trajectories

Abstract

Objective: To evaluate whether a panel of common biomedical markers can be utilized as trajectories to determine survival in pediatric burn patients.

Background: Despite major advances in clinical care, of the more than 1 million people burned in the United States each year, more than 4500 die as a result of their burn injuries. The ability to predict patient outcome or anticipate clinical trajectories using plasma protein expression would allow personalization of clinical care to optimize the potential for patient survival.

Methods: A total of 230 severely burned children with burns exceeding 30% of the total body surface, requiring at least 1 surgical procedure were enrolled in this prospective cohort study. Demographics, clinical outcomes, and inflammatory and acute-phase responses (serum cytokines, hormones, and proteins) were determined at admission and at 11 time points for up to 180 days postburn. Statistical analysis was performed using a 1-way analysis of variance, the Student t test, χ test, and Mann-Whitney test where appropriate.

Results: Survivors and nonsurvivors exhibited profound differences in critical markers of inflammation and metabolism at each time point. Nonsurvivors had significantly higher serum levels of interleukin (IL)-6, IL-8, granulocyte colony-stimulating factor, monocyte chemoattractant protein-1, C-reactive protein, glucose, insulin, blood urea nitrogen, creatinine, and bilirubin (P < 0.05). Furthermore, nonsurvivors exhibited a vastly increased hypermetabolic response that was associated with increases in organ dysfunction and sepsis when compared with survivors (P < 0.05).

Conclusions: Nonsurvivors have different trajectories in inflammatory, metabolic, and acute phase responses allowing differentiation of nonsurvivors from survivors and now possibly allowing novel predictive models to improve and personalize burn outcomes.

Fig. 1

Time-dependent changes in survival after burn.

Fig. 2

Inflammatory profiles of survivors and non-survivors. Serum levels of IL-2 (A), IL-4 (B), IL-6 (C), IL-8 (D), IL-10 (E), GM-CSF (F), IFN-γ (G), TNF-α (H), IL-1β (I), IL-5 (J), IL-7 (K), IL-12 (p70) (L), IL-13 (M), IL-17 (N), G-CSF (O), MCP-1 (P), and MIP-1β (Q). Data are expressed as the mean ± SEM. *p<0.05 for survivors vs. non-survivors.

Fig. 3

Hepatic protein levels in survivors and non-survivors. Serum levels of complement C3 (A), α2-macroglobulin (B), haptoglobin (HAP) (C), α1-acidglycoprotein (D), C-reactive protein (E), transferrin (F), pre-albumin (G), retinol-binding protein (H), apolipoprotein A1 (I), apolipoprotein B (J), and triglycerides (K). Data are expressed as the mean ± SEM. *p<0.05 for survivors vs. non-survivors.

Fig. 4

Glucose and insulin levels in survivors and non-survivors. Serum levels of glucose (A) and insulin (B). Data are expressed as the mean ± SEM. *p<0.05 for survivors vs. non-survivors.

Fig. 5

Common markers of organ function in survivors and non-survivors. Serum levels of alanine aminotransferase (A), aspartate aminotransferase (B), albumin (C), alkaline phosphatase (D), blood urea nitrogen (E), creatinine (F), and total bilirubin (G). Data are expressed as the mean ± SEM. *p<0·05 for survivors vs. non-survivors.

Fig. 6

Hypermetabolism in survivors and non-survivors. Predicted REE (A) and change in REE from admission to discharge (B). Data are expressed as the mean ± SEM. *p<0.05 for survivors vs. non-survivors.

Fig.7

Cardiac function in survivors and non-survivors. Cardiac output (A), cardiac index (B), stroke volume (C), and heart rate (D). Data are expressed as the mean ± SEM. *p<0·05 for survivors vs. non-survivors.

Fig.8

Comparison of serum profiles for cytokines, hormones, and other factors in survivors and non-survivors.