Developing an objective method for analyzing vital signs changes in neonates during general anesthesia.

BACKGROUND: Commonly used general anesthetics are considered to be neurotoxic to the developing rodent brain, leading to poor long-term outcome. However, it is unclear whether these rodent studies can be extrapolated to the human neonate. Given that anesthesia for urgent neonatal surgery cannot be avoided, it is vitally important to assess other factors that may impact neurological outcome following anesthesia and surgery. OBJECTIVE: The purpose of this study is to identify thresholds for detecting vital sign deviations, which may have the potential for affecting neurological outcome following anesthesia and surgery in neonates. These data may be suitable to identify targets for prospective quality improvement projects and guide future research for strategies to reduce detrimental neurocognitive outcomes. METHODS: A retrospective analysis of vital sign data was performed for neonates (age ≤28 days), undergoing noncardiac surgery over a 4-year period (2010-2013). Thresholds for detecting bradycardia, tachycardia, hypothermia, hyperthermia, hypertension, hypotension, hypocarbia, hypoxemia, significant changes in mean arterial blood pressure, and periods of high inspired oxygen concentration, were proposed. Selected chart review, to identify additional risk factors, and identify sources of data artifact, was performed for 224 cases. RESULTS: Data from 435 procedures in neonates, with median (IQR [range]) ages of 6 (2-16 [0-28]) days were available for analysis. Five (3-6 [0-12]) rule deviations per case were observed; only 11 cases had no rule deviations. Hypothermia was observed in 285/435 (70%), moderate hypocapnia in 298/430 (69%), and severe hypotension in 270/435 (62%) cases. CONCLUSION: An objective method of comparing cases has been created with a method to automatically identify neonatal vital sign deviations. With further validation the method has the potential to be a powerful tool to drive future quality improvement projects in neonatal anesthesia.

Staphylococcus aureus enterotoxins A- and B: binding to the enterocyte brush border and uptake by perturbation of the apical endocytic membrane traffic.

Enterotoxins of Staphylococcus aureus are among the most common causes of food poisoning. Acting as superantigens they intoxicate the organism by causing a massive uncontrolled T cell activation that ultimately may lead to toxic shock and death. In contrast to our detailed knowledge regarding their interaction with the immune system, little is known about how they penetrate the epithelial barrier to gain access to their targets. We therefore studied the uptake of two staphylococcal enterotoxins (SEs), SEA and SEB, using organ cultured porcine jejunal explants as model system. Attachment of both toxins to the villus surface was scarce and patchy compared with that of cholera toxin B (CTB). SEA and SEB also bound to microvillus membrane vesicles in vitro, but less efficiently than CTB, and the binding was sensitive to treatment with endoglycoceramidase II, indicating that a glycolipid, possibly digalactosylceramide, acts as cell surface receptor at the brush border. Both SEs partitioned poorly with detergent resistant membranes (DRMs) of the microvillus, suggesting a weak association with lipid raft microdomains. Where attachment occurred, cellular uptake of SEA and SEB was also observed. In enterocytes, constitutive apical endocytosis normally proceeds only to subapical early endosomes present in the actomyosin-rich "terminal web" region. But, like CTB, both SEA and SEB penetrated deep into the cytoplasm. In conclusion, the data show that after binding to the enterocyte brush border SEA and SEB perturb the apical membrane trafficking, enabling them to engage in transcytosis to reach their target cells in the subepithelial lamina propria.