Decreased expression of serum and microvascular vascular endothelial growth factor receptor-2 in meningococcal sepsis*.

OBJECTIVES: To determine the skin microvessel expression of vascular endothelial growth factor receptor 2 and serum-soluble vascular endothelial growth factor receptor 2 levels in children with meningococcal sepsis. DESIGN: Observational study. SETTING: Two tertiary academic children hospital PICUs. PATIENTS: Children with meningococcal sepsis. INTERVENTION: Skin biopsy and blood sample collection. MEASUREMENTS AND MAIN RESULTS: Determination of skin microvessel vascular endothelial growth factor receptor 2 expression in skin biopsies by immunohistochemistry and measurement of serum-soluble vascular endothelial growth factor receptor 2 by enzyme-linked immunosorbent assay. Percentage of vascular endothelial growth factor receptor 2-positive skin microvessels and the staining intensity were significantly lower in children with meningococcal sepsis (n = 10) compared to controls (7.6% ± 8.8% vs 44.6% ± 39.2%; p = 0.009 and 0.7% ± 0.7% vs 1.7% ± 1.1%; p = 0.033, respectively). In addition, circulating serum levels of soluble vascular endothelial growth factor receptor 2 were decreased in sepsis (8,148 ± 1,140 pg/mL vs 13,414 ± 2,692 pg/mL; p < 0.001). Serum-soluble vascular endothelial growth factor receptor 2 levels (n = 28) were inversely correlated with Pediatric Risk of Mortality III score (r = -0.43; p = 0.023) and more decreased in nonsurvivors compared to survivors (5,640 ± 1,940 pg/mL vs 7,378 ± 2,336 pg/mL; p = 0.037). CONCLUSIONS: Microvascular expression of vascular endothelial growth factor receptor 2 and serum-soluble vascular endothelial growth factor receptor 2 levels are decreased in children with sepsis. Serum-soluble vascular endothelial growth factor receptor 2 levels are inversely correlated with disease severity indicated by Pediatric Risk of Mortality III score and survival. Decreased vascular endothelial growth factor receptor 2 expression may hinder natural recovery from sepsis-associated microvascular injury and the effectiveness of therapeutic strategies targeting vascular endothelial growth factor-vascular endothelial growth factor receptor 2 signaling in sepsis patients.

Improving outcome in meningococcal disease: don't forget compartment syndrome!

OBJECTIVE: To advocate a surgical intervention that can prevent the loss of limbs in patients with meningococcal disease. DESIGN: Case report. SETTING: Pediatric intensive care unit. PATIENT: A 4-month-old male infant presenting with acute circulatory failure due to meningococcal disease. INTERVENTIONS: Measurements of compartment pressures of all extremities and echo-Doppler of peripheral arteries were performed at regular intervals, starting at admittance to the pediatric intensive care unit. After compartment syndrome in the lower extremities was diagnosed, emergency surgical intervention (fasciotomy and arteriolysis) was performed in the intensive care unit. MEASUREMENTS AND MAIN RESULTS: During surgery, the compartments initially revealed pale, poorly perfused tissue. After decompression, immediate bulging of the muscles and restoration of microcirculation were seen. All digits were spared, and muscle compartments remained vital with exception of the tibialis anterior and extensor hallucis longus muscles in the left leg. Several ecchymoses and purpura of the lower extremities caused skin necrosis, necessitating skin transplants. No other surgical intervention was required. CONCLUSIONS: In meningococcal disease, compartment syndrome can occur within hours after initial presentation due to massive capillary leakage and circulatory failure. Immediate surgical intervention is the gold standard in treatment, making early recognition vital. In all patients presenting with meningococcal disease, compartment syndrome should be considered and early monitoring included in the initial evaluation.