Effect of Dexmedetomidine on Levels of Plasma Inflammatory Factor in Asthma Patients Undergoing General Anesthesia

Effect of Dexmedetomidine on Levels of Plasma Inflammatory Factor in Asthma Patients Undergoing General Anesthesia-single Center,Randomized,Double-blind，Controlled Trial

The study try to illustrate the possible mechanisms of tending to induce airway spasms and the impact of dexmedetomidine on inflammatory reaction in general anesthesia patients with asthma，by detecting the differences of plasma inflammatory factor interleukin(IL)-4, IL-5, IL-13, IL-17, IL-33, MBP and immunoglobulin E(IgE) levels between asthma patients and non-asthma patients.

Study Overview

• Status: Unknown
• Conditions: Asthma; Anesthesia
• Intervention / Treatment: Drug: Anesthesia induction; Drug: Anesthesia maintenance; Drug: Assisted anesthesia

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Obtain informed consent
• Elective general anesthesia surgery, surgery time 1 ~ 3 hours.
• 20 patients with a history of asthma.
• 60 patients with no history of asthma.
• American Society of Anesthesiologists (ASA)classification:class I~II.
• Aged between 18 and 65 years old.

Exclusion Criteria:

• SBP≥180 mmHg or <90 mmHg, DBP≥110 mmHg or <60 mmHg.
• Serious heart, brain, liver, kidney, lung, endocrine diseases or serious infections.
• Hematopoietic dysfunction or bleeding tendency and hemorrhagic disease.
• A neuromuscular system disease.
• Airway and lung surgery.
• Predict possible or happened difficult airway.
• Immune function defect.
• Sure/suspected abuse of narcotic analgesics or drugs or alcohol dependence.
• The test drug allergy or have other contraindications in patients.
• Childbearing age women not to take appropriate contraception, pregnancy or lactation.
• Participated in other clinical drug research in the last 30 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: non-asthma group; Non-asthma history; Infusion of normal saline(1μg/kg) at 10 minutes before anesthesia induction.; Infusion of normal saline at 0.4μg•kg-1•h-1during anesthesia maintenance.; Stop infusion of normal saline at 10 minutes before the end of surgery.	Drug: Anesthesia induction; -Intravenous injection midazolam 0.05 mg/Kg,fentanyl 4μg/Kg,etomidate 0.2 mg/Kg,cisatracurium 0.15 mg/Kg in proper order.; Drug: Anesthesia maintenance; Continuous intravenous remifentanil O.2μg/(kg•h) and propofol 3~8mg/(kg•h).; Intermittent intravenous atracurium 0.05mg/kg. Maintain partial pressure of carbon dioxide(PETCO2) to 30~40 mmHg and bispectral index (BIS) to 45~60.
Experimental: Dexmedetomidine A; With a history of asthma; Infusion of dexmedetomidine(1μg/kg) at 10 minutes before anesthesia induction.; Infusion of dexmedetomidine at 0.4μg•kg-1•h-1during anesthesia maintenance.; Stop infusion of dexmedetomidine at 10 minutes before the end of surgery.	Drug: Anesthesia induction; -Intravenous injection midazolam 0.05 mg/Kg,fentanyl 4μg/Kg,etomidate 0.2 mg/Kg,cisatracurium 0.15 mg/Kg in proper order.; Drug: Anesthesia maintenance; Continuous intravenous remifentanil O.2μg/(kg•h) and propofol 3~8mg/(kg•h).; Intermittent intravenous atracurium 0.05mg/kg. Maintain partial pressure of carbon dioxide(PETCO2) to 30~40 mmHg and bispectral index (BIS) to 45~60.; Drug: Assisted anesthesia; Intervention 'Assisted anesthesia' has been included in Arm Descriptions.
Experimental: Dexmedetomidine B; With a history of asthma; Infusion of dexmedetomidine(1μg/kg) at 10 minutes before anesthesia induction.; Infusion of dexmedetomidine at 0.7μg•kg-1•h-1during anesthesia maintenance.; Stop infusion of dexmedetomidine at 10 minutes before the end of surgery.	Drug: Anesthesia induction; -Intravenous injection midazolam 0.05 mg/Kg,fentanyl 4μg/Kg,etomidate 0.2 mg/Kg,cisatracurium 0.15 mg/Kg in proper order.; Drug: Anesthesia maintenance; Continuous intravenous remifentanil O.2μg/(kg•h) and propofol 3~8mg/(kg•h).; Intermittent intravenous atracurium 0.05mg/kg. Maintain partial pressure of carbon dioxide(PETCO2) to 30~40 mmHg and bispectral index (BIS) to 45~60.; Drug: Assisted anesthesia; Intervention 'Assisted anesthesia' has been included in Arm Descriptions.
Placebo Comparator: Control group; With a history of asthma; Infusion of normal saline(1μg/kg) at 10 minutes before anesthesia induction.; Infusion of normal saline at 0.4μg•kg-1•h-1during anesthesia maintenance.; Stop infusion of normal saline at 10 minutes before the end of surgery.	Drug: Anesthesia induction; -Intravenous injection midazolam 0.05 mg/Kg,fentanyl 4μg/Kg,etomidate 0.2 mg/Kg,cisatracurium 0.15 mg/Kg in proper order.; Drug: Anesthesia maintenance; Continuous intravenous remifentanil O.2μg/(kg•h) and propofol 3~8mg/(kg•h).; Intermittent intravenous atracurium 0.05mg/kg. Maintain partial pressure of carbon dioxide(PETCO2) to 30~40 mmHg and bispectral index (BIS) to 45~60.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
IL-4，IL-5，IL-13, IL-17, IL-33 concentration in the Plasma	enter the operation room(T0)、10min after intubation(T1)、 skin incision(T2)、the end of surgery(T3)、24H after surgery(T4)
Histamine concentration	enter the operation room(T0)、10min after intubation(T1)、 skin incision(T2)、the end of surgery(T3)、24H after surgery(T4)
Myelin Basic Protein concentration （MBP)	enter the operation room(T0)、10min after intubation(T1)、 skin incision(T2)、the end of surgery(T3)、24H after surgery(T4)
IgE concentration	enter the operation room(T0)、10min after intubation(T1)、 skin incision(T2)、the end of surgery(T3)、24H after surgery(T4)

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean arterial pressure（MAP）	enter the operation room(T0)、10min after intubation(T1)、 skin incision(T2)、the end of surgery(T3)、24H after surgery(T4)
Heart rate（HR）	enter the operation room(T0)、10min after intubation(T1)、 skin incision(T2)、the end of surgery(T3)、24H after surgery(T4)
Respiratory rate（RR）	enter the operation room(T0)、10min after intubation(T1)、 skin incision(T2)、the end of surgery(T3)、24H after surgery(T4)

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Xi'an Jiaotong University

Publications and helpful links

General Publications

• Taniguchi T, Kidani Y, Kanakura H, Takemoto Y, Yamamoto K. Effects of dexmedetomidine on mortality rate and inflammatory responses to endotoxin-induced shock in rats. Crit Care Med. 2004 Jun;32(6):1322-6. doi: 10.1097/01.ccm.0000128579.84228.2a.
• Barnes PJ. The cytokine network in asthma and chronic obstructive pulmonary disease. J Clin Invest. 2008 Nov;118(11):3546-56. doi: 10.1172/JCI36130.
• Saito A, Okazaki H, Sugawara I, Yamamoto K, Takizawa H. Potential action of IL-4 and IL-13 as fibrogenic factors on lung fibroblasts in vitro. Int Arch Allergy Immunol. 2003 Oct;132(2):168-76. doi: 10.1159/000073718.
• Wen FQ, Kohyama T, Liu X, Zhu YK, Wang H, Kim HJ, Kobayashi T, Abe S, Spurzem JR, Rennard SI. Interleukin-4- and interleukin-13-enhanced transforming growth factor-beta2 production in cultured human bronchial epithelial cells is attenuated by interferon-gamma. Am J Respir Cell Mol Biol. 2002 Apr;26(4):484-90. doi: 10.1165/ajrcmb.26.4.4784.
• Laporte JC, Moore PE, Baraldo S, Jouvin MH, Church TL, Schwartzman IN, Panettieri RA Jr, Kinet JP, Shore SA. Direct effects of interleukin-13 on signaling pathways for physiological responses in cultured human airway smooth muscle cells. Am J Respir Crit Care Med. 2001 Jul 1;164(1):141-8. doi: 10.1164/ajrccm.164.1.2008060.
• Kumar RK, Herbert C, Yang M, Koskinen AM, McKenzie AN, Foster PS. Role of interleukin-13 in eosinophil accumulation and airway remodelling in a mouse model of chronic asthma. Clin Exp Allergy. 2002 Jul;32(7):1104-11. doi: 10.1046/j.1365-2222.2002.01420.x.

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Anticipated): December 1, 2015
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: November 10, 2014
• First Submitted That Met QC Criteria: November 10, 2014
• First Posted (Estimate): November 13, 2014

Study Record Updates

• Last Update Posted (Estimate): November 13, 2014
• Last Update Submitted That Met QC Criteria: November 10, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: Asthma; Cytokines; Dexmedetomidine; Inflammatory factor; Inflammatory mediator
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics
• Other Study ID Numbers: Dexmedetomidine-14115