Study On Intranasal Dexmedetomidine For Sleep Induction In The Treatment Of Preoperative Anxiety Insomnia

Objective:The purpose of this study was to explore the safety and efficacy of intranasal dexmedetomidine in the treatment of preoperative anxiety insomnia.It provides a new treatment idea for relieving anxiety and insomnia before operation and improving sleep quality.Methods:This study is divided into two parts:animal experiment and clinical experiment.Animal experiment:32 SD rats aged two months were raised for one week under standard environment condition.One week later,SD rats were randomly divided into 4 groups,namely Dex（6 hours after administration）group（n=8）,Dex（3 days after administration）group（n=8）,normal saline（NS）group（n=8）,blank control group（n=8）.1ml disposable sterile syringe was used to administer drugs to both nasal passages of rats,and the rats were sacrificed by cervical dislocation after the specified time.The nasal mucosa of rats was quickly obtained and pathological tissue sections were made.The effect of Dex on nasal mucosa stimulation was evaluated by comparing nasal mucosa stimulation scores.Clinical experiment:This experiment was carried out after it was confirmed that Dex had no stimulating effect on nasal mucosa.Seventy-two patients with preoperative anxiety and insomnia who planned to receive elective surgical treatment in our hospital from August 2021to November 2021 were selected.One day before surgery,the general condition of the patients and the preoperative anxiety and insomnia were evaluated,and the patients who met the inclusion and exclusion criteria were selected.This study was a prospective double-blind randomized controlled study.All patients were randomly divided into two groups by random number table method,Dex group（n=36）and NS group（n=36）.Bedtime should be adjusted according to the patient’s rest habits,and the bedtime should be controlled at 21:00-23:00.After receiving good electrical monitoring,blood oxygen saturation monitoring,blood pressure monitoring,and Narcotrend,intranasal administration was performed by an anesthesiologist who did not know the group of patients.The liquid medicine is uniformly configured,and the syringe has no special label,so it cannot be distinguished as Dex or NS from its appearance.Main outcome measures:time to fall asleep,total sleep time,post-treatment insomnia severity index（ISI）and treatment effect satisfaction scale（Visual analogue scale,VAS）.Secondary outcome measures:Blood pressure saturation（SPO₂）,heart rate（HR）,mean arterial pressure（MAP）and Narcotrend Index（NII）were recorded before treatment（T₀）,10 minutes after intranasal administration（T₁）,20 minutes after intranasal administration（T₂）,30 minutes after intranasal administration（T₃）,1 hour after intranasal administration（T₄）and 2 hours after intranasal administration（T₅）.Adverse reactions were recorded 12 hours after treatment.Results:1.Pathological sections of nasal mucosa of rats after administration were observed by light microscope.According to the scoring criteria of pathological changes of nasal mucosa and inflammatory cell infiltration,it was found that cilia in normal saline group had no continuous loss,and a small amount of inflammatory cell infiltration,bleeding,necrosis and mild edema.In Dex group（6 hours,3 days after intranasal administration）,there was no continuous loss of cilia,a small amount of inflammatory cell infiltration,no bleeding,necrosis and mild edema.There was no loss of cilia,inflammatory cell infiltration,bleeding,necrosis and edema in the blank control group.Mucosal stimulation scores in Dex（6 h,3 days after intranasal administration）group were higher than those in blank control group,but the difference was not statistically significant,（P>0.05）.According to the experimental results,IT can be considered that Dex has no irritation to the nasal mucosa of rats.2.Comparison of general data between the two groups of patients:gender,age,height,weight,BMI,ASA,Hamilton Anxiety Scale（HAMA）,ISI,there was no statistical significance,（P>0.05）.3.Comparison of time to fall asleep:the average sleep time of the Dex group was22.08±3.95 min,and the average sleep time of the NS group was 89.31±54.56min,the difference was statistically significant,（P<0.001）.4.Comparison of total sleep time:the total sleep time of Dex group was 400.06±28.84min,and that of NS group was 295.19±73.51min,the difference was statistically significant,（P<0.001）.5.ISI comparison before and after treatment:ISI of Dex group was 13.53±4.14 before treatment and 4.14±1.68 after treatment,the difference was statistically significant,（P<0.001）.ISI of NS group was 13.50±4.41 before treatment and 13.78±4.80 after treatment,the difference was not statistically significant,（P=0.636）.There was no statistically significant difference in ISI between 2 groups before treatment（P=0.860）,but there was statistically significant difference in ISI after treatment（P<0.001）.6.Comparison of post-treatment satisfaction:Dex group was 8.14±0.87,NS group was3.50±1.66,the difference was statistically significant（P<0.001）.7.MAP comparison:There was no statistically significant difference in MAP at T₀ and T₁between the two groups,（P>0.05）,and the MAP at T₂-T₅ in Dex group was lower than that in NS group,with statistically significant difference,（P<0.05）.In Dex group,MAP at each time point of T₁-T₅was lower than that at T₀,and the difference was statistically significant,（P<0.05）.In the NS group,there was no statistically significant difference in the MAP at T₀,T₁and T₂（P>0.05）,and the MAP at T₃-T₅ was lower than that at T₀,with statistically significant difference,（P<0.05）.8.HR comparison:There was no significant difference in HR between the two groups at T₀ time point（P>0.05）,and HR in Dex group at T₁-T₅ time point was lower than that in NS group,the difference was statistically significant,（P<0.05）.In Dex group,HR at each time point of T₁-T₅ was lower than that at T₀,and the difference was statistically significant,（P<0.05）.In NS group,there was no statistically significant difference in HR at T₀ and T₁（P>0.05）,while HR at T₂-T₅ was lower than T₀,with statistically significant difference（P<0.05）.9.SPO₂ comparison:There was no statistically significant difference between the two groups at T₀-T₃ time points（P>0.05）,and the SPO₂ at T₄ and T₅ time points in Dex group was lower than that in NS group,with statistically significant difference（P<0.05）,but SPO₂ of all patients was not lower than 95%,so there was no practical clinical significance.In Dex group,SPO₂ at T₂ and T₄ was lower than that at T₀,and the difference was statistically significant（P<0.05）,SPO₂ was not lower than 95%,showing no clinical significance.In NS group,there was no significant difference in SPO₂at each time point（P>0.05）.10.NII comparison:There was no statistically significant difference in NII at T₀ and T₁between the two groups（P>0.05）.NII at T₂-T₅ in Dex group was lower than that in NS group,with statistically significant difference（P<0.05）.In Dex group,NII at T₂-T₅ time point was lower than T₀ time point,and the difference was statistically significant（P<0.05）,there was no statistical significance in NII at T₀ and T₁（P>0.05）.In NS group,there was no significant difference in NII at T₀,T₁,T₂and T₄（P>0.05）,and NII at T₄-T₅ was lower than that at T₀,with statistically significant difference（P<0.05）.11.Adverse reactions:There was no significant difference in adverse reactions（respiratory depression,hypotension,sinus bradycardia,nasal mucosa discomfort）between 2 groups（P<0.05）.Compared with Dex group,more patients in NS group showed drowsiness,and the difference was statistically significant（P<0.001）.Conclusion:Dex has no irritation to nasal mucosa.At the same time,intranasal Dex can be safely and effectively used to improve preoperative anxiety and insomnia,shorten the time to fall asleep,prolong the total sleep duration,and improve the sleep quality of patients on the night before surgery.