Neurological injury markers in children with septic shock.

OBJECTIVE: To determine whether known serum markers of neurologic injury are increased in children with septic shock. DESIGN: Prospective, observational study. SETTING: Tertiary-care, pediatric intensive care unit. PATIENTS: Two cohorts of children (n = 24) with septic shock were prospectively enrolled within 24 hrs of their diagnosis. In cohort 1, serum markers (S100beta, neuron-specific enolase [NSE], and glial fibrillary acidic protein [GFAP]) were determined (n = 18). In cohort 2, in addition to serum markers, urine S100beta and GFAP were determined, and continuous electroencephalography (cEEG) was performed. Children who presented to the emergency room with a fever served as controls (n = 32). Children with known neurologic conditions were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serum and urine were collected daily for up to 7 days or until pediatric intensive care unit discharge. Biomarker concentrations were determined by commercially available enzyme-linked immunosorbent assays. cEEG was performed on days 1, 2, 4, and 7 in a 16-channel montage for at least 6 hrs. Physical examinations did not reveal focal neurologic deficits. Children with septic shock demonstrated increased serum S100beta and NSE compared with controls (mean +/- SEM: 10.5 microg/L +/- 2.4 vs. .9 microg/L +/- .1, p < .001; 96.6 microg/L +/- 8.9 vs. 4.0 microg/L +/- 1.3, p < .001, respectively). Serum GFAP was detectable in five septic children and none of the controls. In cohort 2, urine of four patients demonstrated measurable S100beta levels, and GFAP was detected in one child (nonsurvivor). cEEG demonstrated moderate to severe encephalopathy in all children studied. CONCLUSIONS: Markers of neurologic injuries are increased in children with septic shock. This may indicate subclinical injuries that are either transient or permanent. Studies that correlate the long-term neurologic outcome of children with these markers are needed to identify children at risk for neurologic injuries from septic shock.

Characterization of the cortisol stress response to sedation and anesthesia in children.

CONTEXT: The cortisol stress response to sedation and anesthesia in children is not well characterized. It is not clear whether it is necessary to give stress doses of corticosteroids to children with adrenal insufficiency undergoing sedated procedures. OBJECTIVE: Our objective was to describe the cortisol stress response to sedation and anesthesia in normal children. DESIGN, SETTING, AND PATIENTS: This was a prospective cohort study of 149 children ages 1 month to 17 yr who presented for routine sedated procedures. Salivary cortisol was measured at baseline, every 30 min during procedures, at completion, and at recovery. MAIN OUTCOME MEASURES: We evaluated relative change in salivary cortisol from baseline for level of sedation achieved and type of procedure performed. RESULTS: In total, 117 patients had adequate samples collected, and 110 were included in the main analysis. Twenty-five percent of patients showed an increase in salivary cortisol greater than four times baseline, consistent with a stress response. Mean salivary cortisol increased more than 3-fold from baseline (3.7±0.4, P<0.001) for all patients in the study. There was no difference for change in cortisol when comparing by level of sedation achieved or by type of procedure performed. The majority of patients with a stress response had their highest levels in the recovery phase, after their procedure was completed. CONCLUSION: Sedation and anesthesia can induce a significant rise in cortisol in children. Additional studies should be performed to validate our results and to determine whether stress dosing of corticosteroids may be needed for children with adrenal insufficiency undergoing sedated procedures.

Correlation of cerebral Near-infrared spectroscopy (cNIRS) and neurological markers in critically ill children.

OBJECTIVE: To correlate regional brain saturations (RSO(2)) measured by cerebral Near-infrared spectroscopy (cNIRS) with serological markers indicative of neurological injury (neuron-specific enolase (NSE) and S100beta). METHODS: Children with at least one organ failure who were undergoing cNIRS monitoring were eligible for enrollment, while children with hyperbilirubinemia and cyanotic heart disease were excluded. Children were further analyzed based on the presence of an acute neurological injury (defined as hypoxic/ischemic injury after cardiac arrest, status epilepticus, meningitis, encephalopathy) as well as survival. RSO(2) was measured continuously (every 30 s) and averages were obtained at 6 h and 24 h epochs prior to serum collection (E6 and E24, respectively). Serum was collected for NSE and S100beta, which were both determined by ELISA. Serum from children undergoing evaluation for fever in the Emergency department served as serological controls. Correlations were determined using the Pearson Product Moment Correlations. RESULTS: A total of 26 children underwent cNIRS monitoring for a total of 47 days. Overall NSE was greater in critically ill children compared to controls, as well as in all subsets of children analyzed (acute CNS injuries, no acute CNS injuries, survivors and non-survivors). S100beta tended to be greater in critically ill children, but this did not reach statistical significance. Average RSO(2) in E6 and E24 was 68.0% +/- 1.5 and 68.6% +/- 1.6, respectively, in a total of 131,036 measurements and E6 RSO(2) was strongly, negatively correlated with S100beta in children with acute neurological injuries. CONCLUSIONS: This is the first study to correlate averaged RSO(2) measured by cNIRS with neurological injury markers in critically ill children. We believe that this data can be used to establish thresholds for RSO(2) that can be tested in future trials to determine if this technology is predictive of long-term neurological outcome.