Diabetic ketoacidosis (DKA) in children is associated with intracranial vascular complications, possibly due to leukocyte-endothelial interactions. Our aim was to determine whether DKA-induced inflammation promoted leukocyte adhesion to activated human cerebrovascular endothelium. Plasma was obtained from children with type 1 diabetes either in acute DKA or in an insulin-controlled state (CON). Plasma concentrations of 21 inflammatory analytes were compared between groups. DKA was associated with altered circulating levels of ↑CXCL1 (GROα), ↑CXCL8 (IL-8), ↑IL-6, ↑IFNα2, and ↓CXCL10 (IP-10) compared with CON. These plasma analyte measurements were then used to create physiologically relevant cytokine mixtures (CM). Human cerebral microvascular endothelial cells (hCMEC/D3) were stimulated with either plasma (DKA-P or CON-P) or CM (DKA-CM or CON-CM) and assessed for polymorphonuclear leukocyte (PMN) adhesion. Stimulation of hCMEC/D3 with DKA-P or DKA-CM increased PMN adhesion to hCMEC/D3 under “flow” conditions. PMN adhesion to hCMEC/D3 was suppressed with neutralizing antibodies to CXCL1/CXCL8 or their hCMEC/D3 receptors CXCR1/CXCR2. DKA-P, but not DKA-CM, initiated oxidative stress in hCMEC/D3. Expression of ICAM-1, VCAM-1, and E-selectin were unaltered on hCMEC/D3 by either DKA-P or DKA-CM. In summary, DKA elicits inflammation in children associated with changes in circulating cytokines/chemokines. Increased CXCL1/CXCL8 instigated PMN adhesion to hCMEC/D3, possibly contributing to DKA-associated intracranial vascular complications.
The incidence of central diabetes insipidus in pediatric patients with severe traumatic brain injury is 18%. Mortality was associated with early central diabetes insipidus onset and cerebral edema on head computed tomography. Central diabetes insipidus nonsurvivors were less likely to have received intracranial pressure monitoring, thiopental coma and decompressive craniectomy.
Acquired hypernatremia in hospitalized patients is often associated with poorer outcomes. Our aim was to evaluate the relationship between acquired hypernatremia and outcome in children with severe traumatic brain injury (sTBI). We performed a retrospective cohort study of all severely injured trauma patients (Injury Severity Score ≥12) with sTBI (Glasgow Coma Scale [GCS] ≤8 and Maximum Abbreviated Injury Scale [MAIS] ≥4) admitted to a Pediatric Critical Care Unit ([PCCU]; 2000-2009). In a cohort of 165 patients, 76% had normonatremia (135-150 mmol/L), 18% had hypernatremia (151-160 mmol/L), and 6% had severe hypernatremia (>160 mmol/L). The groups were similar except for lower GCS (p=0.002) and increased incidence of fixed pupil(s) on admission in both hypernatremia groups (p<0.001). Mortality rate was four-fold and six-fold greater with hypernatremia and severe hypernatremia, respectively (p<0.001), and mortality rates were unchanged when patients with fixed pupils or those with central diabetes insipidus were excluded (p<0.001). Hypernatremic patients had fewer ventilator-free days (p<0.001). Survivors with hypernatremia had greater PCCU (p=0.001) and hospital (p=0.031) lengths of stays and were less frequently discharged home (p=0.008). Logistic regression analyses of patient characteristics and sTBI interventions demonstrated that hypernatremia was independently associated with the presence of fixed pupil(s) on admission (odds ratio [OR] 5.38; p=0.003); administration of thiopental (OR 8.64; p=0.014), and development of central diabetes insipidus (OR 5.66; p=0.005). Additional logistic regression analyses demonstrated a significant association between hypernatremia and mortality (OR 6.660; p=0.034). In summary, acquired hypernatremia appears to signal higher risk of mortality in pediatric sTBI and is associated with a higher discharge level of care in sTBI survivors.
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