Objective To determine prevalence of delirium in critically-ill children and explore associated risk factors. Design Multi-institutional point-prevalence study. Setting Twenty-five pediatric critical care units in the United States, the Netherlands, New Zealand, Australia, and Saudi Arabia. Patients All children admitted to the pediatric critical care units on designated study days (n=994). Intervention Children were screened for delirium using the Cornell Assessment of Pediatric Delirium (CAPD) by the bedside nurse. Demographic and treatment-related variables were collected. Measurements and Main Results Primary study outcome measure was prevalence of delirium. In 159 children, a final determination of mental status could not be ascertained. Of the 835 remaining subjects, 25% screened positive for delirium, 13% were classified as comatose, and 62% were delirium-free and coma-free. Delirium prevalence rates varied significantly with reason for ICU admission, with highest delirium rates found in children admitted with an infectious or inflammatory disorder. For children who were in the PICU for 6 or more days, delirium prevalence rate was 38%. In a multivariate model, risk factors independently associated with development of delirium included age < 2 years, mechanical ventilation, benzodiazepines, narcotics, use of physical restraints, and exposure to vasopressors and anti-epileptics. Conclusions Delirium is a prevalent complication of critical illness in children, with identifiable risk factors. Further multi-institutional, longitudinal studies are required to investigate effect of delirium on long-term outcomes, and possible preventive and treatment measures. Universal delirium screening is practical and can be implemented in pediatric critical care units.

Adverse tracheal intubation associated events and desaturations are common and associated with longer mechanical ventilation in critically ill children. Severe tracheal intubation associated events are associated with higher ICU mortality. Potential interventions to decrease tracheal intubation associated events and oxygen desaturation, such as tracheal intubation checklist, use of apneic oxygenation, and video laryngoscopy, may need to be considered to improve ICU outcomes.

As a hemoprotein, Hb, 2 in the presence of oxidizing equivalents such as H 2 O 2 , can act as a peroxidase with very high oxidizing potential (1). In red blood cells, this potentially dangerous activity is strictly regulated by the reducing environment and the lack of oxidizing equivalents. The inadvertently appearing ferric forms of Hb are short-lived, and the hemoprotein is effectively converted into ferro-Hb (deoxyHb) by metHb reductase (2). Normally, less than 2% of total Hb exists in the form of MetHb because the rate of Hb reduction is far greater than its oxidation (2). For stroma-free Hb, however, this intracellular regulation is lost, and the likelihood for Hb to act as a peroxidase is high. This possibility is markedly increased in the course of severe inflammation (e.g. in sepsis) by the generation of superoxide radicals by immune cells. The latter can be spontaneously or catalytically (by extracellular superoxide dismutase) converted into H 2 O 2 , a fuel for Hb peroxidase activity. In line with this, several clinical and experimental investigations have established that lethality in sepsis is increased in the setting of hemolysis (3-5).Circulating haptoglobin (Hp) provides an important endogenous defense against the toxic effects of Hb (6, 7). The major biological function of this abundant plasma protein is binding and recycling of stroma-free Hb via the macrophage CD163 receptor-mediated pathway (8, 9). It has been proposed that Hp possesses antioxidant activity and diminishes oxidative stress induced by stroma-free Hb (10 -12). The antioxidant action of Hp toward Hb has been associated, at least in part, with weakening of its peroxidase activity (10) or preventing oxidation and cross-linking of Hb (7).Previous work has demonstrated that peroxidase activity of different hemoproteins, including Hb, can induce protein self-oxidation leading to covalent cross-linking and aggregation (13-16). Whether these hetero-oligomeric covalent aggregates retain the peroxidase activity is unknown. If the aggregates retain peroxidase activity, they may continue to be a source of oxidative stress both in circulation as well as in phagocytizing cells involved in their clearance such as macrophages.In the current work, we determined the extent to which: (i) Hb peroxidase activity is decreased by binding with Hp; (ii) peroxidase activity of Hb⅐Hp complexes initiates cross-linking into covalent hetero-oligomers; (iii) peroxidase activity of Hb⅐Hp complexes and aggregates utilizes nitric oxide (NO ⅐ ); (iv) Hb⅐Hp aggregates are taken up by macrophages as compared with noncovalent Hb⅐Hp complexes; and (v) the engulfed Hb⅐Hp aggregates induce oxidative stress and cytotoxicity. Here, we report that Hb⅐Hp complexes and aggregates are potent peroxidases capable of inducing oxidative stress in both plasma and macrophages. We further demonstrate the presence of Hb⅐Hp aggregates in septic plasma.

In this large tracheal intubation quality improvement database, we found moderate and severe desaturation are reported among 19% and 13% of all tracheal intubation encounters. Moderate and severe desaturations were independently associated with the occurrence of adverse hemodynamic events. Future quality improvement interventions may focus to reduce desaturation events.

Using National Emergency Airway Registry for Children data, we described patient-centered adverse outcomes associated with video laryngoscopy compared with direct laryngoscopy for tracheal intubation in the largest reported international cohort of children to date. Data from this study may be used to design sufficiently powered prospective studies comparing patient-centered outcomes for video laryngoscopy versus direct laryngoscopy during endotracheal intubation.