Clinical And Experimental Study Of Dexmedetomidine In The Treatment Of Acute Pancreatitis

Part 1: Dexmedetomidine inhibits inflammation by α7n ACh R mediating cholinergic anti-inflammatory pathway in severe acute pancreatitis: a mechanism studyBackground and aim:Excessive inflammatory response plays a critical role in the development of severe acute pancreatitis(SAP),and control of inflammation is vital for the management of this fatal disease.It has been demonstrated that dexmedetomidine(DEX)can suppress inflammation in several diseases by stimulating vagus nerve and activating α7n ACh R mediating cholinergic anti-inflammatory pathway(CAP).In this study,rat models of SAP will be established to investigate whether DEX can inhibit inflammation or not,and the potential anti-inflammatory mechanism of dexmedetomidine will be also elucidated.Methods: Sprague-Dawley rats were randomly assigned to control group,SAP group(SAP model was established by injection of 3.5% sodium taurocholate),DEX group(DEX was injected into the abdomen previously),DEX+VGX group(right cervical vagus nerve was transected prior to DEX injection)and DEX+α-BGT group(administration of α-BGT prior to DEX injection).MAP,HR,HRV and vagal nerve discharge activity were recorded by BL-420 F biological and functional experimental system in a set time.After 6h,arterial blood gas(ABG)was performed,blood samples were collected and the rats were killed.Serum cytokines(TNF-α and IL-6)were assessed by using an enzyme-linked immunosorbent assay(ELISA).Pancreatic histopathology was observed with hematoxylin eosin(HE)staining.Results: Compared with the control group,serum levels of TNF-α,IL-6,amylase and lactic acid of DEX group were significantly decreased.In all the set times,HRV,frequency and peak value of vagal nerve discharge activity of DEX group were markedly increased as compared with the control group.Histopathology showed that the injuries of pancreas alleviated obviously with DEX administration.Contrasted with the control group,MAP of DEX group was markedly increased and HR was decreased sharply.Serum TNF-α,IL-6,amylase and lactic acid of DEX+VGX group and DEX+α-BGT group were significantly increased as compared with those in the DEX group.Comparing with DEX group,MAP of DEX+VGX group and DEX+α-BGT were obviously decreased,whereas HR were significantly increased.Conclusions: Our study shows that DEX inhibits inflammation by α7n ACh R mediating cholinergic anti-inflammatory pathway in SAP rats.It is also demonstrated that DEX could improve hemodynamic stability of the animals.Part 2: Clinical study of dexmedetomidine administration in acute pancreatitis patients with sleep disordersBackground and aim:It is confirmed that DEX inhibits inflammation by α7n ACh R mediating cholinergic anti-inflammatory pathway in SAP rats in our previous study.However,the use of DEX in AP patients is still unknown.As a matter of fact,sleep disorders are widely existed among AP patients.Previous studies have shown that administration of DEX could improve sleep quality of patients in intensive care unit and surgical department.Nevertheless,effected on sleep function of DEX in AP patients was not clear yet.In this study,AP patients with moderate or severe sleep disorders was recruited.We aimed to explorer the effect of DEX on patient’s sleep function,and observe the potential anti-inflammation effect.This project will provide theoretical basis for the anti-inflammatory therapy of AP,and shed new light on clinical prevention and treatment of this disease.Methods: This prospective study was conducted over a time period from April 2014 to November 2017.Candidates of AP patients who complicated with moderate or severe sleep disorders were enrolled.All the patients were randomly divided into control group and DEX group.The control group was programmed to deliver conventional therapy,whereas patients in DEX group received the conventional therapy with continuous dosage of dexmedetomidine from 20:00(the first day)to 6:00(the second day)for three days.We recorded patient’s sleep function,visual analog scale pain scores,nausea and vomiting scores,the level of serum TNF-α,IL-6 and HMGB1.The APACHEⅡscores,modified CTSI(MCTSI),the length of hospital stay,and hospitalization expenses were also analysed.Results: Compared with the control group,the proportion of patients sleeping within 30 mins,total sleep time,the proportion of patients waking up once at least and the insomnia severity index of DEX group were significantly improved.The visual analog scale pain scores,nausea and vomiting scores,and dosage of dezocine of DEX group were obviously lower than those in the control group.The levels of TNF-α,IL-6 and HMGB1 in DEX group at 1week were all obviously decreased compared with control group.MCTSI of the DEX group were obviously lower than that in the control group.Although there was no significant difference in the APACHEⅡscores,the length of hospital stay,and hospitalization expenses between the two groups,the DEX group exerted an appreciably decreasing trend.Conclusions: The study confirms that DEX decreases the levels of serum TNF-α,IL-6 and HMGB1,inhibits systemic inflammatory response,and decreases MCTSI in AP patients complicated with moderate or severe sleep disorders.Furthermore,DEX is proved to be effective in the treatment of sleep disorder.Last but not least,DEX alleviates symptom of abdominal pain and nausea and vomiting in AP patients.