Anesthetic Management for Awake Tubeless Suspension Microlaryngoscopy.

OBJECTIVES/HYPOTHESIS: Patients' eligibility for bilateral selective laryngeal reinnervation surgery is evaluated by suspension microlaryngoscopy (SML) examination with laryngeal electromyography (LEMG). Maintaining spontaneous ventilation, with remifentanil sedation/analgesia without endotracheal tube, to allow the patient to phonate with the surgeon during awake, LEMG is a major challenge for the anesthesiologist and the otorhinololaryngologist. The objective of this study was to evaluate the safety and efficacy of a novel anesthesia protocol to manage airway access during awake tubeless SML. STUDY DESIGN: Retrospective study. METHODS: Anesthesia records of patients undergoing awake SML with LEMG were retrospectively analyzed. Procedures were performed with remifentanil sedation/analgesia with targeted controlled infusion (TCI) in combination with local anesthesia. The main outcome was the failure rate of the anesthesia protocol during the procedure. Secondary outcomes were as follows: rate of apnea requiring ventilation, airway bleeding, regurgitation, hemodynamic data as well as vasopressor use, complications, and surgeon satisfaction with the procedure. RESULTS: Data were obtained for 39 patients between November 2017 and September 2019, the mean age was 52 years and 29 (74%) were female. All procedures were completed without complications (0% [0-9]). Three patients (8% [1.6-20.8]) had an intraoperative episode of hypoxemia requiring mask reventilation. There was no airway bleeding, no regurgitation, and no hypotensive episode. Three patients (8% [1.6-20.8]) had noninvasive ventilation for respiratory distress after the end of the procedure. CONCLUSIONS: Our results show that awake tubeless SML allowing phonation during LEMG can be realized under sedation and local anesthesia. However, further data are needed concerning the intraoperative and postoperative safety of the procedure. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E2669-E2675, 2021.

Increased Hypothalamic Levels of Endozepines, Endogenous Ligands of Benzodiazepine Receptors, in a Rat Model of Sepsis.

BACKGROUND: The mechanisms involved in septic anorexia are mainly related to the secretion of inflammatory cytokines. The term endozepines designates a family of neuropeptides, including the octadecaneuropeptide (ODN), originally isolated as endogenous ligands of benzodiazepine receptors. Previous data showed that ODN, produced and released by astrocytes, is a potent anorexigenic peptide. We have studied the effect of sepsis by means of a model of cecal ligation and puncture (CLP) on the hypothalamic expression of endozepines (DBI mRNA and protein levels), as well as on the level of neuropeptides controlling energy homeostasis mRNAs: pro-opiomelanocortin, neuropeptide Y, and corticotropin-releasing hormone. In addition, we have investigated the effects of two inflammatory cytokines, TNF-α and IL-1ß, on DBI mRNA levels in cultured rat astrocytes. METHODS: Studies were performed on Sprague-Dawley male rats and on cultures of rat cortical astrocytes. Sepsis was induced using the CLP method. Sham-operated control animals underwent the same procedure, but the cecum was neither ligated nor incised. RESULTS: Sepsis caused by CLP evoked an increase of DBI mRNA levels in ependymal cells bordering the third ventricle and in tanycytes of the median eminence. CLP-induced sepsis was also associated with stimulated ODN-like immunoreactivity (ODN-LI) in the hypothalamus. In addition, TNF-α, but not IL-1ß, induced a dose-dependent increase in DBI mRNA in cultured rat astrocytes. An increase in the mRNA encoding the precursor of the anorexigenic peptide α-melanocyte stimulating hormone, the pro-opiomelanocortin, and the corticotropin-releasing hormone was observed in the hypothalamus. CONCLUSION: These results suggest that during sepsis, hypothalamic mRNA encoding endozepines, anorexigenic peptide as well as stress hormone could play a role in the anorexia/cachexia associated with inflammation due to sepsis and we suggest that this hypothalamic mRNA expression could involve TNF-α.

Gliotransmission and brain glucose sensing: critical role of endozepines.

Hypothalamic glucose sensing is involved in the control of feeding behavior and peripheral glucose homeostasis, and glial cells are suggested to play an important role in this process. Diazepam-binding inhibitor (DBI) and its processing product the octadecaneuropeptide (ODN), collectively named endozepines, are secreted by astroglia, and ODN is a potent anorexigenic factor. Therefore, we investigated the involvement of endozepines in brain glucose sensing. First, we showed that intracerebroventricular administration of glucose in rats increases DBI expression in hypothalamic glial-like tanycytes. We then demonstrated that glucose stimulates endozepine secretion from hypothalamic explants. Feeding experiments indicate that the anorexigenic effect of central administration of glucose was blunted by coinjection of an ODN antagonist. Conversely, the hyperphagic response elicited by central glucoprivation was suppressed by an ODN agonist. The anorexigenic effects of centrally injected glucose or ODN agonist were suppressed by blockade of the melanocortin-3/4 receptors, suggesting that glucose sensing involves endozepinergic control of the melanocortin pathway. Finally, we found that brain endozepines modulate blood glucose levels, suggesting their involvement in a feedback loop controlling whole-body glucose homeostasis. Collectively, these data indicate that endozepines are a critical relay in brain glucose sensing and potentially new targets in treatment of metabolic disorders.