Relationship between serum citrulline levels and progression to parenteral nutrition independence in children with short bowel syndrome

Abstract

Objective: Although bowel length is an important prognostic variable used in the management of children with short bowel syndrome (SBS), reliable measurements can be difficult to obtain. Plasma citrulline (CIT) levels have been proposed as surrogate markers for bowel length and function. We sought to evaluate the relationship between CIT and parenteral nutrition (PN) independence in children with SBS.

Study design: A retrospective chart review performed for all patients seen in a multidisciplinary pediatric intestinal rehabilitation clinic with a recorded CIT between January 2005 and December 2007 (n = 27).

Results: Median age at time of CIT determination was 2.4 years. Diagnoses included necrotizing enterocolitis (26%), intestinal atresias (19%), and gastroschisis (22%). Citrulline levels correlated well with bowel length (R = 0.73; P < .0001) and was a strong predictor of PN independence (P Wilcoxon = 0.002; area under the receiver operating characteristic curve = 0.88; 95% confidence interval, 0.75-1.00). The optimal CIT cutoff point distinguishing patients who reached PN independence was 15 micromol/L (sensitivity = 89%; specificity = 78%).

Conclusion: Plasma CIT levels are strong predictors of PN independence in children with SBS and correlate well with a patient's recorded bowel length. A cutoff CIT level of 15 micromol/L may serve as a prognostic measure in counseling patients regarding the likelihood of future PN independence.

Fig. 1

Association between bowel length and plasma citrulline level. Scatterplot with the fitted regression line (solid line), equation with estimated coefficients, and P value of F test for the coefficient of bowel length (n = 27 patients with 30 citrulline levels).

Fig. 2

Association between plasma citrulline levels and recorded percentage of enteral intake (% enteral intake). Scatterplot with the fitted regression line (solid line), equation with estimated coefficients, and P value of F test for the coefficient of citrulline level (n = 23 patients with 33 citrulline levels).

Fig. 3

Distribution of plasma citrulline levels comparing patients who attained PN independence to those who did not. The solid bar within the box represents the median value; upper boundary, 75th percentile; lower boundary, 25th percentile; whiskers extend to the most extreme observation within 1.5 interquartile range units of the 25th and 75th percentiles.

Fig. 4

Sensitivity and specificity curves of citrulline testing to predict attainment of parenteral nutrition independence as a function of test levels. The vertical line was drawn at the point in which sensitivity and specificity are optimal (ie, 15 μmol/L that corresponds to the citrulline level that minimizes the square root of [{1 − sensitivity}² + {1 − specificity}²]).