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临床试验/NCT00971178
NCT00971178已完成3 期

Effectiveness of Peripheral Dexmedetomidine for Bilateral Third Molar Surgery Under General Anaesthesia

The University of Hong Kong0 个研究点目标入组 105 人开始时间: 2006年2月最近更新:
适应症
干预措施
相关药物

试验速览

阶段
3 期
状态
已完成
入组人数
105
主要终点
Pain Score at Rest

研究概览

简要总结

Dexmedetomidine is an alpha 2-adrenoreceptor agonist, which provides sedation, analgesia and anxiolysis in clinical practice (Cortinez et al., 2004,Hall et al., 2000). Three types of alpha 2-adrenergic receptor subtypes are found in the human body and they have been designated alpha 2A, alpha 2B and alpha 2C. The alpha 2A subtype is most likely responsible for the analgesic properties of dexmedetomidine in both peripheral and central sites (Kingery et al., 2000, Smith et al., 2001). Activation of central alpha 2-adrenoreceptors in the locus ceruleus (Correa-Sales et al., 1992) and the dorsal horn of the spinal cord (Gaumann et al., 1992b) are responsible for both analgesic and sedative effects. Dexmedetomidine has a very high alpha 2 to alpha 1 selectivity, 1620 to 1, or approximately 8 times that of clonidine. It is also 4 to 6 times more potent than clonidine by weight (Bhana et al., 2000).

Although dexmedetomidine produces dose dependent sedation upon intravenous administration, its the analgesic effect is of dexmedetomidine is more variable and controversial. In an ischaemic pain model in healthy volunteers, a single bolus of dexmedetomidine produced a 50% reduction in pain scores when compared to placebo (Jaakola et al., 1991). In another volunteer study using the cold pressor test, dexmedetomidine 1 µg/kg over 10 minutes followed by an infusion of 0.2 to 0.6 µg/kg/hour reduced pain by approximately 30% (Hall et al., 2000). However, when administered as a target controlled infusion at concentrations ranging from 0.09 to 1.23 ng/mL, dexmedetomidine had no analgesic effect in human volunteers subjected to heat and electrical pain, although sedation was produced (Memis et al., 2004).

Clonidine and dexmedetomidine are two common alpha 2 agonists used clinically. Although clonidine former has been used successfully in regional analgesia and anesthesia (Gabriel et al., 2001)., There are only very few studies evaluating the peripheral analgesic effects of dexmedetomidine. Since acute postoperative dental pain is a common analgesia model (Cooper, 1991; US Food and Drug Administration 1992), the investigators conducted this study, aiming to assess the postoperative analgesic efficacy of peripheral dexmedetomidine after bilateral third molar surgery under general anaesthesia. The analgesic effects were compared up to the 72nd hour postoperatively in order to evaluate any potential preventive analgesic effect.

详细描述

The study protocol was approved by our local Institutional Review Board and written consent was obtained from all the participants. Eligibility for recruitment included American Society of Anesthesiologists (ASA) physical status I and II, age between 18 and 50 years of age with 4 bilateral impacted third molar teeth scheduled for extraction under general anaesthesia. Exclusion criteria included clinical history or electrocardiographic evidence of heart block, ischaemic heart disease, asthma, sleep apnoea syndrome, impaired liver or renal function, alcohol consumption in excess of 28 units per week, pregnancy, patient refusal, known psychiatric illness, chronic sedative or analgesic use, and regular use of or known allergy to dexmedetomidine, paracetamol or dextropropoxypheneopioids. Patients with preoperative inflammation at the site of surgery were also excluded.

After obtaining written, informed consent, patients were randomly allocated to receive 1)Preoperative IV dexmedetomidine 1mcg/kg and normal saline infiltrated to wound at the end of surgery; 2) Preoperative normal saline IV infusion and dexmedetomidine 1mcg/kg infiltrated to wound or 3) Preoperative IV normal saline infusion and normal saline infiltrated to wound at the end of surgery. A computer generated random sequence was used for drug allocation and this was prepared by a statistician who was unaware of the clinical nature of the study. The patients were assessed by the list anaesthetist the day before surgery. They were fasted for at least 6 hours and did not receive any premedication before arrival at the operation theatre. Patients were educated on the use of the Numerical Rating Scale (NRS) for pain assessment, where zero corresponds to no pain and 10 represents the worst pain imaginable.

A P-deletion test was performed in the ward preoperatively. The P-deletionThis test consists of 58 lines of closely typed text containing between 74 to 97 occurrences of the letter "p". The patients are instructed to cross out every letter "p" they can find as quickly as possible, reading from left to right down the page. The number deleted in 180 seconds and the number of errors counts. This test assesses speed, accuracy, concentration, mental activity, hand-eye coordination and vigilance. It was firstly described by Dixon and colleagues who found it to be an accurate test for psychomotor recovery from anesthesia and sedation (Dixon et al., 1973).

On arrival at the operating theatre, a 20-gauge intravenous cannula was inserted in the dorsum of each patient's left hand. Either dexmedetomidine 1 µg/kg (Group D) diluted to 4ml with normal saline or the same volume of 0.9% saline alone (Group P) was prepared by another anaesthetist who did not participate in patient management or data collection. Both preparations were clear solutions, therefore patients, medical, nursing staff, and data collectors were all blinded to the allocated drug. Heart rate, blood pressure, respiratory rate and oxygen saturation were recorded (S/5 Anesthesia Monitor, Datex-Ohmeda, WI, USA) before general anaesthesia and thereafter at five-minute intervals from the time of commencing surgery until discharge from the recovery room.

Induction and maintenance of anaesthesia were done according to a standard protocol. Anaesthesia was induced with propofol titration of 2 to 3 mg/kg, fentanyl 1 µg/kg and muscle relaxation was achieved with rocuronium 1 mg/kg. The trachea was intubated via the nasal route. General anaesthesia was maintained with a mixture of air, oxygen and sevoflurane at 1 to 1.5 MAC. Before the start of the surgical procedures, regional anaesthesia were performed by infiltrating 2.7 mL of 2% lignocaine with 1 in 80,000 adrenaline around the base of the gum of each third molar by the same team of dental surgeons. Sevoflurane was stopped when the last suture had been inserted. andVolume of 1 ml of either dexmedetomidine (Group D, totally dexmedetomidine 1 µg/kg for 4 surgical sites) or saline (Group P) was infiltrated to the submucosa of each surgical site. Neuromuscular block was antagonized with neostigmine 50 µg/kg and atropine 20 µg/kg, and followed by extubation after recovery of consciousness. The patients were then monitored in the recovery room for at least 30 minutes. Resting pain scores, blood pressure, heart rate, oxygen saturation and the Ramsay sedation score (RSS) (appendix 1) were assessed and recorded every 5 minutes. Intravenous ketorolac or morphine would be administered upon patients' request. Patients were transferred back to the general ward when fully consciousness with normal physiological parameters.

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Parallel
主要目的
Treatment
盲法
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

入排标准

年龄范围
18 Years 至 50 Years(Adult)
性别
All
接受健康志愿者

入选标准

  • American Society of Anesthesiologists (ASA) physical status I and II
  • Age between 18 and 50 years of age with 4 bilateral impacted third molar teeth scheduled for extraction under general anaesthesia
  • Exclusion criteria:
  • Clinical history or electrocardiographic evidence of heart block
  • Ischaemic heart disease
  • Sleep apnoea syndrome
  • Impaired liver or renal function
  • Alcohol consumption in excess of 28 units per week
  • Pregnancy
  • Patient refusal
  • Known psychiatric illness
  • Chronic sedative or analgesic use, and regular use of or known allergy to dexmedetomidine, paracetamol or dextropropoxypheneopioids
  • Patients with preoperative inflammation at the site of surgery were also excluded

排除标准

  • 未提供

研究组 & 干预措施

Local Dexmedetomidine

Active Comparator

干预措施: local dexmedetomidine (Drug)

Normal Saline

Placebo Comparator

干预措施: Peripheral normal saline (Drug)

IV dexmedetomidine

Active Comparator

干预措施: IV dexmedetomidine (Drug)

结局指标

主要结局

Pain Score at Rest

时间窗: 72 hours after surgery

The Numerical Rating Scale (NRS) is used for pain score assessment at rest. It is a scale consists of 11 numbers in which 0 corresponds to no pain and 10 represents the worst pain imaginable. The NRS pain scores over postoperative 72 hours is expressed as Area Under Curve using the trapezoid rule and compared among the 3 groups using the Kruskal-Wallis test.

次要结局

未报告次要终点

研究者

申办方类型
Other
责任方
Principal Investigator
主要研究者

Dr. Chi-Wai Cheung

Professor

The University of Hong Kong

相似试验

Analgesic Effect of Peripheral Dexmedetomidine | 临床试验