Low-dose adjuvant dexmedetomidine did not decrease propofol sedation requirements in children undergoing gastrointestinal endoscopy.

BACKGROUND: Propofol is the cornerstone of deep sedation during pediatric esophagogastroduodenoscopy (EGD), though adjuvant dexmedetomidine may provide propofol-sparing benefits. OBJECTIVE: The objective of the study was to evaluate whether adjuvant dexmedetomidine decreases the total propofol dose in pediatric patients undergoing EGD. METHODS: This single-center, retrospective, cohort study evaluated the total propofol dose in pediatric patients undergoing EGD with and without the use of adjuvant dexmedetomidine. Secondary outcomes included the change in hemodynamics across the perioperative continuum and post-procedure recovery time. A multivariable general linear regression was performed to identify associated variables for recovery time post-procedure. RESULTS: A total of 159 patients were included in the study; 88 patients received dexmedetomidine and propofol (DEX-PRO), and 71 patients received propofol only (PRO). The median [interquartile range (IQR)] propofol dose in the DEX-PRO group was 0.26 [IQR, 0.17-0.36] mg kg-1  min-1 which was not significantly different than the PRO group at 0.27 [IQR, 0.21-0.34] mg kg-1  min-1 , p = 0.730. Evaluation of secondary end points showed the DEX-PRO group had more cases of post-anesthesia care unit (PACU) hypotension (61% vs. 34%, p = 0.001) and a longer recovery time (32.9 ± 14.1 vs. 25.6 ± 10.8 min, p < 0.001) versus the PRO group, respectively. Multivariable linear regression demonstrated that age and the use of dexmedetomidine were associated with prolonged recovery. CONCLUSION: Adjuvant dexmedetomidine did not reduce propofol requirements compared with propofol alone in pediatric patients undergoing EGD. More hypotension and a longer postoperative recovery time were also seen in patients receiving adjuvant dexmedetomidine for their endoscopic procedure.

Reduced synthesis of the Ybt siderophore or production of aberrant Ybt-like molecules activates transcription of yersiniabactin genes in Yersinia pestis.

Synthesis of the siderophore yersiniabactin (Ybt) proceeds by a mixed nonribosomal peptide synthetase/polyketide synthase mechanism. Transcription of ybt genes encoding biosynthetic and transport functions is repressed under excess iron conditions by Fur, but is also activated by Ybt via the transcriptional regulator YbtA. While mutations in most biosynthetic genes and ybtA negate transcription activation from the regulated promoters, three biosynthetic mutations do not reduce this transcriptional activation. Here we show that two of these mutants, one lacking the putative type II thioesterase (TE) YbtT and the other with a mutation in the TE domain of HMWP1, produce reduced levels of authentic Ybt that are capable of signalling activity. Alanine substitutions in two residues of YbtT that are essential for catalytic activity in other type II TEs reduced the ability of Yersinia pestis to grow under iron-chelated conditions. The third mutant, which lacks the salicylate synthase YbtS, did not make authentic Ybt but did produce a signalling molecule. Finally, a Delta pgm strain of Y. pestis, which lacks essential Ybt biosynthetic genes, also produced a signalling molecule that can activate transcription of ybt genes. The non-Ybt signal molecules from these two mutants are likely separate compounds. While these compounds are not biologically relevant to normal Ybt regulation, a comparison of the structures of Ybt and other signalling molecules will help in determining the chemical structures recognized as a Ybt signal.