Prevalence and Predictors of Adverse Events during Procedural Sedation Anesthesia-Outside the Operating Room for Esophagogastroduodenoscopy and Colonoscopy in Children: Age Is an Independent Predictor of Outcomes.

OBJECTIVES: Procedural sedation/anesthesia outside the operating room for a variety of procedures is well described with an overall low adverse event rate in certain settings. Adverse event associated with procedural sedation/anesthesia outside the operating room for gastrointestinal procedures have been described, albeit in small, single-center studies with wide variance in outcomes. Predictors of such outcomes are unclear. We aimed to estimate the prevalence of adverse event in children undergoing procedural sedation/anesthesia outside the operating room for esophagogastroduodenoscopy, colonoscopy, or both to identify predictors of adverse event. DESIGN/SETTING/PATIENTS: Retrospective analysis of Pediatric Sedation Research Consortium database, a large data repository of pediatric patients aged 21 years old or younger undergoing procedural sedation/anesthesia outside the operating room during September 2007 to November 2011. Twenty-two of the 40 centers provided data pertaining to the procedure of interest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome variable is any adverse event. Independent variables include: age (five groups), sex, American Societyof Anaesthesiologists status, procedure (esophagogastroduodenoscopy, colonoscopy, or both), provider responsible, medication used, location, and presence of coexisting medical conditions. Descriptive statistics used to summarize the data. Using multivariablelogistic regression model, odds ratio, 95% CI) were computed. A total of 12,030 procedures were performed (esophagogastroduodenoscopy, 7,970; colonoscopy, 1,378; and both, 2,682). A total of 96.9% of patients received propofol. Eighty-three percent were performed in a sedation unit. Prevalence of adverse event was 4.8%. The most common adverse event were persistent desaturations (1.5%), airway obstruction (1%), cough (0.9%), and laryngospasm (0.6%). No deaths or CPR occurred. Infants and children aged 5 years old or younger had a higher adverse event rate than older children (15.8%, 7.8% vs 4%). Regression analysis revealed age 5 years old or younger, American Society of Anaesthesiologists greater than or equal to 2, esophagogastroduodenoscopy ± colonoscopy, and coexisting medical conditions of obesity and lower airway disease were independent predictors of higher adverse event. CONCLUSIONS: Overall prevalence of any adverse event was 4.8%. Independent predictors of adverse events in procedural sedation/anesthesia outside the operating room in pediatric esophagogastroduodenoscopy/colonoscopy onoscopy were identified. Recognition of such risk factors may enable optimization of procedural sedation.

VEGF secretion is inhibited by interferon-alpha in several melanoma cell lines.

Interferon-alpha (IFN-alpha) is employed in the treatment of malignant melanoma; however, it mediates regression of disease in only 10-15% of patients. Currently, its mechanism of action is uncharacterized. Low-dose IFN-alpha exerts anti-angiogenic effects when used in the treatment of life-threatening hemangiomas of infancy, suggesting anti-angiogenesis as a mechanism of action. IFN-alpha may exert its anti-tumor effect in the setting of advanced malignancy by inhibiting the secretion of vascular endothelial growth factor (VEGF), a pro-angiogenic substance. We hypothesized that IFN-alpha would decrease the release of VEGF by melanoma tumors. We studied the effect of IFN-alpha on VEGF production in nine human melanoma cell lines. We also examined VEGF levels in 49 patients with advanced malignancies who received low-dose IFN-alpha and interleukin-12 (IL-12) on an NCI-sponsored phase I trial. Human melanoma cell lines produced varying amounts of VEGF in vitro (60-1500 pg/mL at 48 h). Certain melanoma cell lines such as 18105 MEL secreted low levels of VEGF (152 pg/mL) after 48 h of culture, whereas other lines secreted very high levels (FO-1 3,802 pg/mL). Treatment of melanoma cells with IFN-alpha (2000 U/mL) decreased VEGF secretion by 40-60% in VEGF-high cell lines; however, this effect was not demonstrated in VEGF-low cell lines. In cancer patients, pretreatment VEGF plasma levels varied from 471 to 4200 pg/mL. A decrease in VEGF plasma levels after treatment directly correlated with the number of treatment cycles administered (Pearson correlation, p = 0.04). In summary, IFN-alpha inhibits VEGF secretion by melanoma cell lines in vitro and may have similar actions in malignancies that respond to IFN-alpha treatment.

Administration of two macrophage-derived interferon-gamma-inducing factors (IL-12 and IL-15) induces a lethal systemic inflammatory response in mice that is dependent on natural killer cells but does not require interferon-gamma.

Activation of macrophages by microbes results in the rapid production of monokines (e.g., interleukin-12 (IL-12), IL-15, and IL-18), which induce production of interferon-gamma (IFN-gamma) by natural killer (NK) cells. We examined the effects of administering IL-15 in combination with IL-12 in a murine toxicity model to determine how these two cytokines might contribute to the inflammatory state that accompanies infectious processes. The daily, simultaneous administration of IL-15 (3 x 10(5)U) and IL-12 (1 microg) to normal mice resulted in shock and 100% mortality within 3-7 days, whereas minimal toxicity was observed following the administration of IL-15 or IL-12 alone. Mice treated with IL-15 plus IL-12 exhibited lesions of the gastrointestinal tract, elevated serum levels of acute phase reactants and pro-inflammatory cytokines, and NK cell apoptosis. Neutralization of IFN-gamma, TNF-alpha, and IL-1beta was not protective in cytokine-treated mice, however, toxicity and death could be completely abrogated by depletion of NK cells. Mice deficient in the STAT4 transcription factor also exhibited complete protection while mice deficient in IFN-gamma or its downstream mediator, STAT1, did not. These findings suggest that cytokine- stimulated NK cells are able to promote systemic inflammation via the induction of STAT4-responsive genes other than IFN-gamma or TNF-alpha.