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临床试验/NCT04391855
NCT04391855已完成4 期

Effect of Wound Infiltration With Tramadol, Dexmedetomidine, or Magnesium Sulfate as Adjuncts to the Local Anesthetic on Pain Relief After Spine Surgery

Aristotle University Of Thessaloniki1 个研究点 分布在 1 个国家目标入组 72 人开始时间: 2020年5月10日最近更新:
适应症
干预措施
相关药物

试验速览

阶段
4 期
状态
已完成
入组人数
72
试验地点
1
主要终点
Time to first analgesic request in minutes

研究概览

简要总结

The rationale for multimodal analgesia is to achieve additive or synergistic analgesic properties while decreasing the incidence of side effects by reducing the dose of each agent. Nociceptive stimuli are known to activate the release of the excitatory amino acid glutamate in the dorsal horn of the spinal cord. The resultant activation of NMDA receptors causes calcium entry into the cell and triggers central sensitization. This mechanism is involved in the perception of pain and mainly accounts for its persistence during the postoperative period.

Peri-incisional injection of local anesthetics is an effective method for pain relief after many surgical procedures, as it can reduce postoperative analgesic consumption. Ropivacaine is a propyl analog of bupivacaine with a longer duration of action with a much safer cardiotoxicity profile than bupivacaine. Thus, a combination of local anesthetic with other analgesic factors, such as opioids, dexmedetomidine, clonidine, ketamine, magnesium sulfate, dexamethasone is suggested for a better analgesic outcome.

Dexmedetomidine, a highly selective a2-adrenergic receptor agonist, has been the focus of interest for its broad spectrum (sedative, analgesic, and anesthetic sparing) properties, making it a useful and safe adjunct in many clinical applications. The intravenous, intramuscular, intrathecal, epidural, and perineural use of this agent enhances analgesic effects.

Tramadol hydrochloride is a synthetic analog of codeine that acts on both opioid (weak m receptor agonist) and nonopioid receptors (inhibits the reuptake of noradrenaline and serotonin as well as release stored serotonin from nerve endings) which play a crucial role in pain inhibition pathway. It also blocks nerve conduction which imparts its local anesthetics like action on peripheral nerves.

It was reported that NMDA antagonists could prolong the analgesic effect of bupivacaine to even a week, as well as inhibit hyperalgesia. Magnesium sulfate (MGS) is a non-competitive antagonist of N-methyl, D-aspartate (NMDA) receptors with an analgesic effect and is essential for the release of acetylcholine from the presynaptic terminals and, similar to calcium channel blockers (CCB), can prevent the entry of calcium into the cell.

Aim of the study is to evaluate and compare the postoperative analgesic efficacy of tramadol, dexmedetomidine, and magnesium when added to ropivacaine as an adjuvant for wound infiltration following spine surgery.

详细描述

Each participant will receive standard monitoring (ECG, SpO2, capnography, SBP, oesophageal temperature) and intravenous access will be established. A standard anesthesia protocol will be applied involving propofol 2mg/kg (iv) and remifentanil in TCI (target-controlled infusion). Cis-atracurium 0.2 mg/kg (iv) will be given to facilitate endotracheal intubation. Anesthesia will be maintained with desflurane in a 50% air/O2 mixture A standard anesthesia protocol will be applied involving propofol 2mg/kg (iv) and remifentanil in TCI (target-controlled infusion). Cis-atracurium 0.2 mg/kg (iv) will be given to facilitate endotracheal intubation. Anesthesia will be maintained with air to oxygen mixture of 50%, and desflurane adjusted to achieve a target BIS between 40 and 50. Remifentanil target level will be titrated according to analgesic demands defined by a > 20% change of heart rate or blood pressure compared with baseline. The duration of both anesthesia and surgical procedure will be registered. Furthermore, the level of sedation upon anesthesia emergence will be recorded using the Ramsey sedation scale.

Postoperatively pain assessment will be performed by the Visual Analogue Scale (VAS) and Numerical Rating Scale (NRS) at anesthesia emergence and at 2, 4, 6, 12, 18, and 24 h after surgery conclusion. Time to first analgesic request and total analgesics consumption postoperatively (morphine equivalents) will be recorded.

Episodes of shivering, as well as episodes of nausea and vomiting (PONV) and other postoperative adverse events, will be recorded at emergence and 24 hours thereafter.

Finally, patients' global satisfaction will be assessed the second day and one month after surgery using the Quality of Recovery Scale(QoR-40). In the meantime, blood samples will be taken at the time before the surgical stimulus, 6 hours and 24 hours after wound infiltration to measure cortisol, TNF-a, and IL-6 plasma concentration.

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
Triple (Participant, Investigator, Outcomes Assessor)

入排标准

年龄范围
18 Years 至 80 Years(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • Adult patients aged between 18 and 80 years
  • ASA Physical status 1 to 3
  • Elective or semi-elective one-level lumbar laminectomy or discectomy surgery
  • Signed informed consent

排除标准

  • Chronic use of opioids
  • Drugs or alcohol abuse
  • Neurological disorders
  • Local anesthetics toxicity
  • Cardiac conductance disturbances
  • Hepatic failure
  • Renal failure
  • Pregnancy

研究组 & 干预措施

Magnesium with ropivacaine

Experimental

Magnesium sulfate 10 mg/kg with ropivacaine (10mg/ml) 100mg for wound infiltration

干预措施: Magnesium with ropivacaine (Drug)

Tramadol with ropivacaine

Experimental

Tramadol 2mg/kg with ropivacaine (10mg/ml) 100mg for wound infiltration

干预措施: Tramadol with ropivacaine (Drug)

Dexmedetomidine with ropivacaine

Experimental

Dexmedetomidine 1μg/kg with ropivacaine (10mg/ml) 100mg for wound infiltration

干预措施: Dexmedetomidine with ropivacaine (Drug)

Placebo with ropivacaine

Placebo Comparator

Ropivacaine (10mg/ml) 100mg with 5ml isotonic saline for wound infiltration

干预措施: Ropivacaine plus normal saline (Drug)

结局指标

主要结局

Time to first analgesic request in minutes

时间窗: 24 hours after the emergence from anesthesia

The difference in the time frame (minutes) for analgesia request after emergence from anesthesia after wound infiltration with tramadol plus ropivacaine, tramadol plus ropivacaine, magnesium sulfate plus ropivacaine or ropivacaine plus isotonic saline 0.9%

次要结局

  • Plasma concentration of cortisol(Before wound infiltration, and at 6 and 24 hours thereafter)
  • Pain intensity postoperatively(At 10 minutes after emergence from anesthesia, and 2, 4, 6, 12, 18 and 24 hours after the emergence from anesthesia)
  • Plasma concentration of TNF-a and IL-6(Before wound infiltration, and at 6 and 24 hours thereafter)
  • Analgesics consumption postoperatively in morphine equivalents(24 hours after the emergence from anesthesia)

研究者

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

Georgia Tsaousi

Associate Professor

Aristotle University Of Thessaloniki

研究点 (1)

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