The Influence of Age on Dexmedetomidine Pharmacodynamic

Study Overview
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Brief Summary
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Dexmedetomidine(DEX) is a novel , highly selective α2 adrenergic receptor agonists , and its selectivity for α2 receptor is 1600 times higher than α1.It also could provide dose-dependent sedation , analgesia , anti-anxiety and inhibition of sympathetic nerves and other effects .At earlier time It was approved by the FDA only for short-time sedation during mechanical ventilation of adult patients (<24h) in ICU. Because of its minimal impact on the respiratory , currently it was more and more widely used to sedate patients undergoing regional anesthesia.Many anesthetic pharmacokinetics and pharmacodynamics are often affected by age and gender,such as the drug sensitivity of propofol and remifentanil is increased with age,while the current study also demonstrated that gender may influence the sedate efficacy of propofol and the sensitivity of muscle loose of rocuronium. Current studies with regard to the effects of age and gender on dexmedetomidine pharmacodynamic are rare. The study is aim to explore the right DEX dose of different Age of patients to produce suitable sedation.Dexmedetomidine be used in patients with combined spinal and epidural anesthesia for sedation,which is monitored by the BIS,during the operation.The relation between BIS values and the depth of sedation for patients is also investigated.

Detailed Description
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120 patients scheduled to undergo lower extremity surgery were included in one of three groups. Determination of median effective (ED50) doses was performed by the Dixon and Mood up-and-down method. Initial doses was 1μg/kg, with dose adjustment intervals of 0.05μg/kg, in the youth,and middle-aged group. The initial doses of DEX was 0.7 μg/kg,also with dose adjustment intervals of 0.05μg/kg.Sedative efficacy was defined as an OAA/S of ≤2, or an OAA/S of 3 but with an BIS value of ≤46, 26 min after the beginning of drug administration.

Official Title
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The Influence of Age on Dexmedetomidine Pharmacodynamic in Lower Extremity Surgery

Conditions
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Spinal Anesthesia

Intervention / Treatment
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* Drug: Dexmedetomidine 01
* Drug: Dexmedetomidine 02


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ASA Ⅰ   Ⅱ patient undergoing lower extremity surgery Written informed consent from the patient or the relatives of the participating patient. BMI:18.5～25 Exclusion Criteria: Mental illness can not match epidural anesthesia contraindicated People who have Slow-type arrhythmias People who were language or hearing impaired Sensory block reached to T8 or higher. People who had lung infection or sleep apnea syndrome. Pregnancy Chronic renal failure Alcohol or drug abuse Already taking gabapentin, pregabalin, benzodiazepin or antidepression drug

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Youth Group<br>People in this group, aged 18 39,were accepted an initial dose of 1μg/kg, with dose adjustment intervals of 0.05μg/kg. | Drug: Dexmedetomidine 01<br>* Initial doses was 1μg/kg, with dose adjustment intervals of 0.05μg/kg.<br>|
| Experimental: Middle-aged Group<br>People in this group, aged 40 64,were accepted an initial dose of 1μg/kg, with dose adjustment intervals of 0.05μg/kg. | Drug: Dexmedetomidine 01<br>* Initial doses was 1μg/kg, with dose adjustment intervals of 0.05μg/kg.<br>|
| Experimental: Older Group<br>People in this group, aged 65 80,were accepted an initial dose of 0.7μg/kg, with dose adjustment intervals of 0.05μg/kg. | Drug: Dexmedetomidine 02<br>* Initial doses was 0.7μg/kg, with dose adjustment intervals of 0.05μg/kg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The ED50 of DEX | The aim of our study is to define the median effective sedative doses (ED50s) of DEX to determine the effect of age on the pharmacodynamic of DEX in lower extremity surgery using the Dixon and Mood up-and-down method。 | 26min after the start of the infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The ED95 of DEX | To determine the optimum bolus dose (ED95) of dexmedetomidine for producing adequate sedation during spinal anesthesia in lower limb orthopedic surgery. | 26min after the start of the infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Age, Pharmacodynamics, dexmedetomidine