Intranasal Dexmedetomidine Premedication In Suspension Laryngoscopy Under General Anesthesia: A Randomized Controlled Study

Background Most of the patients have preoperative varying degrees of stress andanxiety, which enhance the stress response of the patients and affect the normal conduct ofanesthesia and surgery. In addition, hyperexcitability of the sympathetic system wouldcause adverse cardiovascular events, which affect the postoperative recovery. Therefore, itis necessary to use some anti-anxiety and sedative drugs pre-operation. Premedication,having the advantages of sedative、anxiolytic and less adverse reactions, is an importantcomponent of anesthesia and the beginning of anesthesia. As the traditional premedication,Phenobarbital has some shortcomings, such as less sedative and weak anxiolytic. Havingsuperior sedative, hypnotic and anterograde amnesia than phenobarbital, Midazolam is thefirst choice for premedication in most developed countries. However, Midazolam isaccompanied by inhibition of respiration, excessive sedation, easily induced delirium,wake prolonged recovery and other shortcomings, which exist certain security risks andmay result in delayed recovery in the absence of monitoring conditions.That is why theapplication of Midazolam is limited.Dexmedetomidine (Dexmedetomidine,Dex), a highly selective agonist of alpha2, wouldbe sedative, anxiolytic, inhibiting the sympathetic, analgesic, hemodynamic stability andsave narcotic drugs with minimal respiratory depressant effect. As premedication,Dexmedetomidine has a variety of modes of administration, such as, intramuscularinjection, intranasal administration. intravenous injection of dexmedetomidine wouldimpact on circulatory system.In addition, continuous infusion may result in delayedrecovery. Intravenous injection and intramuscular injection are invasive, which contrary tononinvasive premedication. Dexmedetomidine is colorless, odorless, non-mucosal stimulation, convenient intranasal administration, good patient acceptance and comfort.Intranasal Dexmedetomidine would slowly and gradually increase the concentration of thedrug of the plasma, which may weaken its effect on blood pressure and heart rate and canensure the safety of premedication. Therefore, intranasal dexmedetomidine premedicationhas certain advantages.Suspension laryngoscopic operation is a minimally invasive surgery and shortens theoperative time. However, using the laryngoscope to exposure the glottis in the operationwould largely directly stimulate the epiglottis, tongue and neck muscles deep receptors,which would increase the amount of catecholamine in vivo, cause hemodynamic volatility,and easily lead to serious cardiovascular adverse events, especially in patients withcardiovascular and cerebrovascular disease. The ideal anesthesia in suspensionlaryngoscopic operation should effectively inhibit the stress response, increase the stabilityof perioperative hemodynamics, promote rapid awakening and early recover the upperrespiratory protective reflexes. Therefore, bisides deepening anesthesia，some adjuvantdrugs including selective β1-blocker, calcium channel blocker and glucocorticoids or localanesthetics would be used in suspension laryngoscopy under general anesthesia. However,the drups mentioned above inhibit the blood pressure (BP) and heart rate (HR) changes,which increase the risk of inadequate depth of anesthesia and the incidence ofintraoperative awareness. Intraoperative awareness, cause psychological harm and mentaldisorders in surgery patients, is a very serious complication of anesthesia. If experiencingpsychological trauma, the patients may suffer post-traumatic stress syndrome and nervefunction disorder, which would cause serious mental or sleep disorders.As an adjunct to anesthesia, loading dose intraoperative injection combined withcontinuous infusion is the usual mode of administration of the Dex. It can improvehemodynamic stability, provide appropriate sedation, but continuous infusion of Dexwould induce revive delay. Studies have shown that a single intravenous dose beforeinduction of anesthesia can reduce the amount of Dex, improve perioperativehemodynamic stability and facilitate fast recovery. For those very short time operationswith strong stress reaction, such as suspension laryngoscopic operation, could a single-dose intranasal dexmedetomidine improve hemodynamic stability and quality ofawakening? Studies have shown that intravenous dexmedetomidine can reduce EC50ofpropofol on loss of consciousness in patients. How intranasal dexmedetomidine influenceEC50of propofol on loss of consciousness?Objective The purpose of the study is to obsere the level of sedation and safety ofintranasal dexmedetomidine premedication, to obsere the narcotic effects of intranasaldexmedetomidine premedication in suspension laryngoscopy under general anesthesia,and to explore how intranasal dexmedetomidine influence EC50of propofol on loss ofconsciousness.Part I: The feasibility study of intranasal dexmedetomidinepremedication in suspension laryngoscopyObjective1.Obsere the level of sedation and safety of intranasal dexmedetomidinepremedication.2.Obsere the narcotic effects of intranasal dexmedetomidine premedicationin suspension laryngoscopy under general anesthesia.Methods Eighty patients in suspension laryngoscopic elective surgery with benign vocalfold lesions were randomized in a double-blinded manner to receive intranasaldexmedetomidine1μg/kg (Group D) or intranasal0.9%saline (Group N),45~60minbefore induction of anesthesia (n=40per group). Narcotrend Index was maintainedbetween “D0” and “E1” by adjusting the target-controlled infusion (TCI) plasmaconcentration of propofol during anesthesia. The initial TCI effect-site concentration ofremifentanil was3.0ng/mL at induction, and was adjusted to maintain systolic bloodpressure(SBP) within a range of25%from preanesthesia level and HR <90bpm.Followed by intravenous injection of rocuronium0.9mg/kg and went endotrachealintubation after60s. Recorded changes in HR, BP, SpO2, OAA/S and anxiety level beforeand after intranasal administration; recorded awakening and extubation time; recordedNarcotrend Index achieving “D0” level, before operation and operation end of the target concentration of propofol, recorded before operation, operation start and operation end ofthe target concentration of remifentanil, recorded recovery of spontaneous respiration,awakening and extubation of the target concentration of propofol and remifentanil;recorded intraoperative adverse cardiovascular events; recorded patient satisfaction withanesthesia.Results Before induction of anesthesia, the OAA/S score of group D was4.58±0.12,which is lower than that of group N,4point anxiety score was3.30±0.08, which washigher than that of group N. In group D, the OAA/S score before induction of anesthesiawas lower than that before administration,4point anxiety score before induction ofanesthesia was higher than that before administration.The concentration oftarget-controlled infusion of propofol and remifentanil of group D were lower than that ofgroup N. There was no significant difference between group N and group D in theanesthesia time, the operation time, recovery time of spontaneous respiration, awakeningtime and extubation time.（P>0.05）10patients suffered postoperative tachycardia (8ingroup N and2in group D, P=0.04).19patients suffered postoperative hypertension (14ingroup N and5in group D, P=0.017). To the over-all anesthesia and the operation, thepercent of satisfaction of group D is higher than that of group N.(36in guoup D versus23in group N).Conclusion1.For suspension laryngoscopy, intranasal dexmedetomidine1μg/kg could produce effectivesedation and anxiolytic effect with minimal hemodynamic and respiratory depressanteffect. It could reduce anesthetic requirements, improve postoperative hemodynamicstability, not affect awakening time and extubation time, and increase satisfaction ofpatients without increasing the risk of inadequate anesthesia. Part Ⅱ:Effect of intranasal dexmedetomidine on EC50ofpropofol on loss of consciousnessObjective Explore how intranasal dexmedetomidine influence EC50of propofol on lossof consciousness.Methods Twenty-four patients were received intranasal dexmedetomidine1μg/kg45~60min before induction of anesthesia. The initial target-controlled infusion (TCI) plasmaconcentration of propofol (Cp) was2.0ug/ml. When Cp and the TCI effect-siteconcentration of propofol (Ce) balanced, the consciousness was recorded. The standard ofloss of consciousness was that the patient could not open their eyes when being called andthat eyelash reflex disappears. Cp was adjusted according to consciousness of patients. Theconsciousness of patients was recorded. The balance time between Cp and Ce wasrecorded.Results After intranasal dexmedetomidine1μg/kg, the EC50of propofol on loss ofconsciousness was1.38ug/ml.95%CI of EC50was1.373~1.395ug/ml. The balance timebetween Cp and Ce was13.21±0.72min.Conclusion After intranasal dexmedetomidine1μg/kg, the EC50of propofol on loss ofconsciousness was1.38ug/ml.95%CI of EC50was1.373~1.395ug/ml.