Inadequate Sedation During Therapeutic Paralysis: Use of Bispectral Index in Critically Ill Patients

Background: Patients receiving therapeutic paralysis may experience inadequate sedation due to intrinsic limitations of behavioral sedation assessment. Bispectral index (BISTM) provides an objective measure of sedation; however, the role of BISTM is not well defined in intensive care unit (ICU) patients on neuromuscular blocking agents (NMBA). Objective: The aim of this study was to delineate the relationship between BISTM and level of sedation for critically ill patients during therapeutic paralysis. Methods: This was a retrospective observational study conducted in ICU patients receiving continuous infusion NMBA and BISTM monitoring. The primary endpoint was the correlation of BISTM\60 during therapeutic paralysis with a Richmond Agitation Sedation Score (RASS) of -4 to -5 (i.e., deep or unarousable sedation) at the time of emergence from therapeutic paralysis. Results: Thirty-one patients were included in the analysis. Three of these patients (9.6 %) were inadequately sedated upon emergence from paralysis; that is, restless or agitated (RASS ?1 to ?2). We did not observe a correlation between BISTM and RASS upon emergence from paralysis (r = 0.27, p = 0.14). The sensitivity of BISTM\60 in predicting deep sedation (RASS -5 to -4) was 100 % (95 % confidence interval [CI] 0–100) with a positive predictive value of 35.7 %. The sensitivity and positive predictive value of BISTM\60 in predicting light sedation or deeper (RASS -5 to -2) was 92.9 % (95 %CI 83.3–100) and 92.9 %, respectively. Conclusion: These results suggest that 1 in 10 critically ill patients receiving therapeutic paralysis may be inadequately sedated. BISTM monitoring may serve as a useful adjunctive measure of sedation in critically ill patients receiving therapeutic paralysis

Inadequate Sedation During Therapeutic Paralysis: Use of Bispectral Index in Critically Ill Patients

Background Patients receiving therapeutic paralysis may experience inadequate sedation due to intrinsic limitations of behavioral sedation assessment. Bispectral index (BIS™) provides an objective measure of sedation; however, the role of BIS™ is not well defined in intensive care unit (ICU) patients on neuromuscular blocking agents (NMBA). Objective The aim of this study was to delineate the relationship between BIS™ and level of sedation for critically ill patients during therapeutic paralysis. Methods This was a retrospective observational study conducted in ICU patients receiving continuous infusion NMBA and BIS™ monitoring. The primary endpoint was the correlation of BIS™ \u3c 60 during therapeutic paralysis with a Richmond Agitation Sedation Score (RASS) of −4 to −5 (i.e., deep or unarousable sedation) at the time of emergence from therapeutic paralysis. Results Thirty-one patients were included in the analysis. Three of these patients (9.6 %) were inadequately sedated upon emergence from paralysis; that is, restless or agitated (RASS +1 to +2). We did not observe a correlation between BIS™ and RASS upon emergence from paralysis (r = 0.27, p = 0.14). The sensitivity of BIS™ \u3c 60 in predicting deep sedation (RASS −5 to −4) was 100 % (95 % confidence interval [CI] 0–100) with a positive predictive value of 35.7 %. The sensitivity and positive predictive value of BIS™ \u3c 60 in predicting light sedation or deeper (RASS −5 to −2) was 92.9 % (95 %CI 83.3–100) and 92.9 %, respectively. Conclusion These results suggest that 1 in 10 critically ill patients receiving therapeutic paralysis may be inadequately sedated. BIS™ monitoring may serve as a useful adjunctive measure of sedation in critically ill patients receiving therapeutic paralysis

Diethyl 4-[5-(biphenyl-4-yl)-1H-pyrazol-4-yl]-2,6-dimethyl-1,4-dihydro­pyridine-3,5-dicarboxyl­ate ethanol monosolvate

In the title compound, C28H29N3O4·C2H6O, the benzene ring makes dihedral angles of 33.72 (13) and 32.86 (13)°, respectively, with the adjacent pyrazole and phenyl rings. In the crystal, the components are connected via inter­molecular N—H⋯O, N—H⋯N, O—H⋯O and C—H⋯O hydrogen bonds, forming a layer parallel to the bc plane

Platelet endothelial cell adhesion molecule-1 in neutrophil emigration during acute bacterial pneumonia in mice and rats

Platelet endothelial cell adhesion molecule-1 (PECAM-1) (CD31) is an adhesion molecule believed to mediate transendothelial migration of neutrophils and other leukocytes after CD11/CD18-mediated adhesion. Our study evaluated the role of PECAM-1 in neutrophil emigration across the pulmonary capillaries and the bronchial microvasculature using blocking anti-PECAM-1 antibodies in mice and rats. Neutrophil emigration was induced by Escherichia coli, a stimulus eliciting CD11/CD18-dependent emigration, or Streptococcus pneumoniae, a stimulus inducing CD11/CD18-independent emigration. Although anti-PECAM-1 antibodies partially inhibited glycogen-induced neutrophil emigration into the peritoneum, neutrophil emigration across either the pulmonary capillaries or the bronchial microvasculature in response to either E. coli or S. pneumoniae was not prevented when the function of PECAM-1 was inhibited in either mice or rats. There was also no increase in the number of intravascular neutrophils within the bronchial vessels after treatment with anti-PECAM-1 antibody. These studies indicate that either CD11/CD18-dependent or -independent adhesion pathways may lead to PECAM-1-independent transendothelial migration through the pulmonary or the bronchial endothelium

Borrelia burgdorferi membranes are the primary targets of reactive oxygen species

Spirochetes living in an oxygen-rich environment or when challenged by host immune cells are exposed to reactive oxygen species (ROS). These species can harm/destroy cysteinyl residues, iron-sulphur clusters, DNA and polyunsaturated lipids, leading to inhibition of growth or cell death. Because Borrelia burgdorferi contains no intracellular iron, DNA is most likely not a major target for ROS via Fenton reaction. In support of this, growth of B. burgdorferi in the presence of 5 mM H2O2 had no effect on the DNA mutation rate (spontaneous coumermycin A1 resistance), and cells treated with 10 mM t-butyl hydroperoxide or 10 mM H2O2 show no increase in DNA damage. Unlike most bacteria, B. burgdorferi incorporates ROS-susceptible polyunsaturated fatty acids from the environment into their membranes. Analysis of lipoxidase-treated B. burgdorferi cells by Electron Microscopy showed significant irregularities indicative of membrane damage. Fatty acid analysis of cells treated with lipoxidase indicated that host-derived linoleic acid had been dramatically reduced (50-fold) in these cells, with a corresponding increase in the levels of malondialdehyde by-product (fourfold). These data suggest that B. burgdorferi membrane lipids are targets for attack by ROS encountered in the various stages of the infective cycle