The Impact of Concomitant Ultra Low Dose Infusion Naloxone and Therapeutic Infusion Opioid on Opioid Requirements in Pediatric ICU Patients
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 128
- 试验地点
- 2
- 主要终点
- Maximum Cummulative Daily Fentanyl Dose
研究概览
简要总结
Recently there has been an increased awareness in the need for adequate sedation and pain control for Pediatric Intensive Care Unit (ICU) patients. Fentanyl is an opioid commonly used in Pediatric ICU patients to decrease pain and increase sedation. Although opioids (e.g. morphine and fentanyl) provide excellent pain relief, they have many side effects including dependence, tolerance and withdrawal. These side effects lead to increased doses in order to maintain pain control and/or sedation. There have been a few adult studies pointing to some possible treatments. For example, giving low dose naloxone along with opioids. Adult studies show that this combination not only decreases the frequency of opioid side effects, but also improves pain control and prevents the development of tolerance. We propose that children who receive low dose naloxone infusions along with fentanyl infusions will demonstrate: 1) decreased total daily doses of Fentanyl, 2) decreased frequency of withdrawal and 3) increased pain and sedation control. In this randomized, blinded prospective trial we will enroll 168 Pediatric ICU patients. Patients will receive either low dose naloxone or placebo simultaneously with their fentanyl infusion. Pain and sedation will be assessed using the Modified Motor Activity Assessment Scale (MMAAS). The fentanyl infusion will be increased to provide adequate pain control and/or sedation. Naloxone infusion will not be adjusted. Approximately 48 hours prior to removal from the ventilator, patients will have their fentanyl infusions decreased while being monitored for withdrawal. Patients showing signs of withdrawal will receive methadone, an opioid taken by mouth. Once off fentanyl, naloxone will be stopped. Patients will continue to be monitored for withdrawal for 4 days or until ICU discharge. If this study works, patients who receive low dose naloxone along with opioid infusions will have less tolerance and dependence and demonstrate less withdrawal. This may cause shorter Intensive Care Unit stays.
详细描述
Objective:
To determine if Naloxone administration to pediatric ICU patients on Fentanyl infusions require less Fentanyl compared to control patients.
Background:
During recent years there has been an increased awareness of the need for adequate sedation and analgesia of critically ill pediatric patients. The choices of the treatment of pain are numerous, but in the Pediatric ICU parenteral opioids are most commonly used. At equipotent doses, all mu agonist opioids (Morphine, Fentanyl, Meperidine and Codeine) produce similar physiologic effects and side effects. Opioids can cause hypoventilation, hypotension, constipation and cause urinary retention. Patients receiving continuous opioid infusions experience not only these physiologic side effects, but also the side effects of dependence, tolerance and withdrawal. These last side effects complicate medical issues and contribute to longer ICU admissions.
Anand wrote a review article addressing the problems of drug dependence and withdrawal in the PICU. In his article he discussed the mechanisms, pharmacology and presentation of opioid withdrawal. He also discussed prevention of opioid withdrawal including such therapies as the concomitant infusion of opioid agonists and low dose Naloxone. Tobias also wrote a review article describing the consequences of the prolonged use of sedative and analgesic agents in the Pediatric ICU. Among the problems of note are tolerance, dependence and withdrawal in the Pediatric ICU. He discussed several possible therapies for the treatment and prevention of opioid withdrawal. Among these was the concomitant infusion of opioid agonist and low dose Naloxone, an opioid agonist. Naloxone selectively blocks those opioid receptors that are coupled with stimulatory G proteins, thus blocking mechanisms for super-activation of the cAMP pathway. This improves the efficacy of analgesia and prevents the development of acute tolerance.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Double
入排标准
- 年龄范围
- 1 Day 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children age one (1) day to eighteen (18) years, requiring admission to the Pediatric ICU, requiring continuous infusion of Fentanyl analgesic anticipated to last greater than 4 days will be eligible for enrollment. Patients from both genders, all races and ethnic backgrounds will be eligible. Patients meeting the above criteria will be eligible regardless of nutritional status, performance status or recovery from prior medical treatment. They will not be excluded if they require simultaneous infusions of sedation with Midazolam. Enrollment will require parental consent.
排除标准
- •Patients will not be eligible if they meet any of the following criteria:
- •Patients who are currently on oral analgesia or sedation
- •Patients who have a prior history of drug or alcohol dependence/abuse.
- •History of significant or preexisting cardiovascular disease, they are receiving pro-arrhythmia medications, such as class I, II, III or IV antiarrhythmic agents.
- •Patients who are allergic to opioids or opioid antagonists.
- •Patients with documented chromosomal abnormality impairing perception of pain/discomfort.
- •Unable to obtain parental or legal guardian's informed consent
- •Concurrent admission to another study.
结局指标
主要结局
Maximum Cummulative Daily Fentanyl Dose
次要结局
- Number of Rescue Fentanyl Boluses
- Number of Rescue Midazolam Boluses
- Total Midazolam Dose
- Narcotic Withdrawal Scale Score
- Modified Motor Activity Assessment Score