Pilot Study: Postoperative Pain Reduction by Pre Emptive N-Acetylcysteine
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- pain score day 1 after surgery
研究概览
简要总结
Despite current available analgesic drugs, post-surgical pain management remains challenging. A potential new target for analgesic drugs are group-II metabotropic glutamate receptors subtypes (mGlu2 and mGlu3 receptors), since growing evidence from animal models show that activation of these receptors produce s analgesic effects in inflammatory and in neuropathic pain states. . N-Acetylcysteine (NAC) is a safe agent and with little to no side effects. NAC can induce analgesia by activating the glutamate:cystein antiporter, causing endogenous activation of the mGlu 2/3 receptors. However, this has only been investigated once in the peri-operative setting, were it showed preliminary promising result of reduction in opiate necessity. In healthy subjects there was a significant reduction in pain ratings to laser stimuli and amplitudes of laser evoked potentials after NAC. Based on these promising results, we hypothesize that pre emptive intravenous NAC can reduce postoperative pain and thereby cause less necessity for escape analgesics like opiates.
详细描述
Currently approximately 240 million surgical procedures are done worldwide on a yearly basis. lnguinal hernia repair is one of the most performed surgeries in ambulatory setting. Despite currently available analgesic drugs, post surgical pain management remains challenging in this group of patients, as the pain score appears inadequate (mean VAS of 5.8 +/- 1 .22 cm) one day after surgery with the use of common analgesics. Beside accounting for patient discomfort, pain is also a major contributor to prolonged length of hospital stay and is a health care quality indicator. With multimodal pain management the intention is to reduce pain with less side effects of analgesics. Multimodal pain management is the combination of different pharmacologic mechanisms of action, which work by acting at different sites within the central and peripheral nervous system, thereby having an additive or synergistic effect and reducing the necessity of opiates. With this in mind, a potential new target for analgesic drugs are group- ll metabotropic glutamate receptors subtypes (mGlu2 and mGlu3 receptors) localized in the spinal cord and other regions of the nociceptive system. Growing evidence from animal models show that activation of these receptors occur via the glutamate:cystein antiporter and can induce analgesia in models of inflammatory and neuropathic pain. They depress pain transmission at synapses between primary afferent fibers and second order sensory neurons on the dorsal horn of the spinal cord.
N-Acetylcysteine (NAC) is on the market since 1968 and is an over the counter available agent, mostly known for its role as mucolytic agent in cystic fibrosis and for the treatment of acetaminophen intoxication. lt is a safe agent with little to no side effects. Recent studies have shown NAC can inhibit nociceptive transmission in rats and in healthy humans.NAC can induce analgesia by activating the glutamate:cystein antiporter, causing endogenous activation of the mGlu2/3 receptors. Therefore, NAC can potentially become a cheap and safe additive in the multimodal pain management. However, evidence for usage of NAC in the context of multimodal pain management is still lacking. Only one available study in humans evaluated the effect of NAC in the perioperative setting. Despite being a randomised controlled trial, there are several limitations in this study; the study arms are too small and only morphine consumption is presented. Also, blinding might have not as good as suggested since oral NAC has a typical flavour and the placebo was lemonade.
Due to these limitations, still no answer on the question whether NAC can be an additive in current multimodal pain management is provided.
Objective of the study:
Primary Objective:
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects scheduled for laparoscopic unilateral inguinal hernia repair
- •Age >18 years.
排除标准
- •Pregnancy or lactating
- •Allergy to NAC
- •History of chronic pain
- •Use of opioids or neuropathic analgesics
- •Use of NAC prior to trial (< 1 month of planned surgery)
- •Alcoholism
- •Diabetes Mellitus (insulin therapy)
- •Asthma or Chronic Obstructive pulmonary Disease
- •Known renal function disorders (MDRD <ô0)
- •Known liver failure (bilirubin >1.Sx upper limit of normal)
- •No written lC by patient
研究组 & 干预措施
NAC
receive 150 mg/kg acetylcysteïne in 200 ml saline (NaCl0,9%) prior to surgery
干预措施: Acetyl cysteine (Drug)
placebo
receive only NaCl 0.9% prior to surgery (volume identical to active comparator)
干预措施: Placebos (Drug)
结局指标
主要结局
pain score day 1 after surgery
时间窗: 24 hours
To evaluate the efficacy of intravenous NAC in comparison with placebo in terms of pain relief after laparoscopic inguinal hernia repair measured by a visual analogue scale (VAS 0-100 millimeters) at day 1 after surgery. The higher the score, the more pain the patient has.
次要结局
- time to first pain medication(<4hours)
- total consumption of opiates(<4 hours)
- time to discharge(24 hours)
- postoperative dosage of analgesics(72 hours)
- Incidence of Treatment-Emergent Adverse Events (e.g. safety of acetylcystein)(<4 hours)
- adverse effects of analgesics(72 hours)
- direct postoperative pain(<1 hours)