Hemodynamic-Directed Cardiopulmonary Resuscitation Improves Neurologic Outcomes and Mitochondrial Function in the Heart and Brain.

OBJECTIVES: Less than half of the thousands of children who suffer in-hospital cardiac arrests annually survive, and neurologic injury is common among survivors. Hemodynamic-directed cardiopulmonary resuscitation improves short-term survival, but its impact on longer term survival and mitochondrial respiration-a potential neurotherapeutic target-remains unknown. The primary objectives of this study were to compare rates of 24-hour survival with favorable neurologic outcome after cardiac arrest treated with hemodynamic-directed cardiopulmonary resuscitation versus standard depth-guided cardiopulmonary resuscitation and to compare brain and heart mitochondrial respiration between groups 24 hours after resuscitation. DESIGN: Randomized preclinical large animal trial. SETTING: A large animal resuscitation laboratory at a large academic children's hospital. SUBJECTS: Twenty-eight 4-week-old female piglets (8-11 kg). INTERVENTIONS: Twenty-two swine underwent 7 minutes of asphyxia followed by ventricular fibrillation and randomized treatment with either hemodynamic-directed cardiopulmonary resuscitation (n = 10; compression depth titrated to aortic systolic pressure of 90 mm Hg, vasopressors titrated to coronary perfusion pressure ≥ 20 mm Hg) or depth-guided cardiopulmonary resuscitation (n = 12; depth 1/3 chest diameter, epinephrine every 4 min). Six animals (sham group) underwent anesthesia and instrumentation without cardiac arrest. The primary outcomes were favorable neurologic outcome (swine Cerebral Performance Category ≤ 2) and mitochondrial maximal oxidative phosphorylation utilizing substrate for complex I and complex II (OXPHOSCI+CII) in the cerebral cortex and hippocampus. MEASUREMENTS AND MAIN RESULTS: Favorable neurologic outcome was more likely with hemodynamic-directed cardiopulmonary resuscitation (7/10) than depth-guided cardiopulmonary resuscitation (1/12; p = 0.006). Hemodynamic-directed cardiopulmonary resuscitation resulted in higher intra-arrest coronary perfusion pressure, aortic pressures, and brain tissue oxygenation. Hemodynamic-directed cardiopulmonary resuscitation resulted in higher OXPHOSCI+CII (pmol oxygen/s × mg/citrate synthase) in the cortex (6.00 ± 0.28 vs 3.88 ± 0.43; p < 0.05) and hippocampus (6.26 ± 0.67 vs 3.55 ± 0.65; p < 0.05) and higher complex I respiration (pmol oxygen/s × mg) in the right (20.62 ± 1.06 vs 15.88 ± 0.81; p < 0.05) and left ventricles (20.14 ± 1.40 vs 14.17 ± 1.53; p < 0.05). CONCLUSIONS: In a model of asphyxia-associated pediatric cardiac arrest, hemodynamic-directed cardiopulmonary resuscitation increases rates of 24-hour survival with favorable neurologic outcome, intra-arrest hemodynamics, and cerebral and myocardial mitochondrial respiration.

Value of Procalcitonin Measurement for Early Evidence of Severe Bacterial Infections in the Pediatric Intensive Care Unit.

OBJECTIVES: To determine whether peak blood procalcitonin (PCT) measured within 48 hours of pediatric intensive care unit (PICU) admission can differentiate severe bacterial infections from sterile inflammation and viral infection and identify potential subgroups of PICU patients for whom PCT may not have clinical utility. STUDY DESIGN: This was a retrospective, observational study of 646 critically ill children who had PCT measured within 48 hours of admission to an urban, academic PICU. Patients were stratified into 6 categories by infection status. We compared test characteristics for peak PCT, C-reactive protein (CRP), white blood cell count (WBC), absolute neutrophil count (ANC), and % immature neutrophils. The area under the receiver operating characteristic curve was determined for each biomarker to discriminate bacterial infection. RESULTS: The area under the receiver operating characteristic curve was similar for PCT (0.73, 95% CI 0.69, 0.77) and CRP (0.75, 95% CI 0.71, 0.79; P = .36), but both outperformed WBC, ANC, and % immature neutrophils (P < .01 for all pairwise comparisons). The combination of PCT and CRP was no better than either PCT or CRP alone. Diagnostic patterns prone to false-positive and false-negative PCT values were identified. CONCLUSIONS: Peak blood PCT measured close to PICU admission was not superior to CRP in differentiating severe bacterial infection from viral illness and sterile inflammation; both PCT and CRP outperformed WBC, ANC, and % immature neutrophils. PCT appeared especially prone to inaccuracies in detecting localized bacterial central nervous system infections or bacterial coinfection in acute viral illness causing respiratory failure.