Lymphopenia, hypoprolactinemia and lymphocyte depletion in pediatric multiple organ failure

Introduction

Lymphopenia is associated with secondary infection, multiple organ failure (MOF) and death in adults. Lymphocyte apoptosis has been described in autopsies of adults dying of MOF. In experimental models, prolactin protects against lymphocyte apoptosis.

Hypothesis

Lymphocyte apoptosis occurs in pediatric patients with MOF and is associated with prolonged hypoprolactinemia and lymphopenia.

Methods

Blood was collected on days 1, 3, 7, and 14 from 55 critically ill children without MOF and 58 with MOF (organ failure index ≥ 2 for ≥ 3 days.) Lymphopenia was defined as lymphocyte count < 1000 × 10⁶/l. Hypoprolactinemia was defined as < 2.5 ng/ml in patients > 6 months and < 20 ng/ml in patients > 6 months (chemiluminescent assay; DPC, Los Angeles, CA, USA). Both were considered prolonged when lasting ≥ 1 week. Severe lymphocyte depletion (SLD) was determined by a pathologist's histologic evaluation of lymph nodes and spleen at autopsy. Linear and logistic regression models were used to control for immune suppression, steroid use, and severity of illness (PRISM score).

Results

Lymphocyte counts were lower in children with MOF than in those without (median [range]: 864 [0–5525], n = 58 vs 1787 [0–16,250], n = 55; P = 0.001, rank sum) even when controlling for immune suppression and steroid use (P = 0.001). Prolonged lymphopenia was only seen in children with MOF (17/58 vs 0/55) and was independently associated with secondary infection (OR = 5.5, 95% CI = 1.7–17, P = 0.004) and death (OR = 6.8, 95% CI = 1.3–34, P = 0.02). Sixteen patients died; 11 underwent autopsy. SLD was seen in 89% of those dying of MOF. Two patients died without MOF; neither had autopsy evidence of SLD. In patients with MOF, prolonged hypoprolactinemia (OR = 12.2, 95% CI = 2.2–65, P = 0.01) and prolonged (OR = 42.2, 95% CI = 3.7–473, P = 0.001) were independently associated with SLD.

Conclusions

Prolonged lymphopenia and SLD occur in pediatric MOF. Prolonged lymphopenia predicts death independent of severity of illness. Unrecognized hypoprolactinemia may contribute to SLD.