The Effects of the Anesthetic Ketamine in Young Children Undergoing Procedural Sedation
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Increase in serum biomarkers of neurotoxicity (neuronal cell apoptosis)
研究概览
简要总结
In the emergency department (ED), ketamine is a popular anesthetic agent during sedation of children for painful and other short procedures. Sedation for procedures is more commonly used in children than adults, to achieve motion control and cooperation. In children, ketamine offers an ideal choice due to the fact that it is short acting, a highly effective sedative, and preserves cardio-respiratory stability. In the United States, more than one million children per year up to four years of age undergo short procedures requiring anesthestic agents, including ketamine. However, there is mounting concern from animal studies and retrospective human research regarding the safety of ketamine when administered to infants and young children with respect to its potential toxic effects on the developing . Conversely, ketamine has also been suggested as a neuroprotective agent. Prompt investigation and resolution of this issue is urgently required.
详细描述
The objectives of this study are:
Primary Objective: In otherwise healthy children between 3 and 48 months of age who present to a tertiary care emergency department and receive procedural sedation with ketamine, to determine if there is at least a 50% increase, compared to baseline in the serum concentration of any of the neurotoxicity biomarkers S100B, glial fibrillary acidic protein (GFAP) or neuronal-specific enolase (NSE), 1 to 3 hours after intravenous ketamine administration. The cut-off of 50% is a benchmark value routinely quoted in both animal and human studies, which correlated neurotoxicity biomarker levels with functional outcomes.
Secondary Objectives: In the aforementioned population:
- To determine if at least a 50% increase in the serum concentration of S100B, GFAP or NSE compared to baseline at 6 to 12 hours after intravenous ketamine administration.
- To explore if genotypes relevant to ketamine metabolism and disposition are associated with increased vulnerability to the neurotoxic effects of ketamine.
- To determine the toxic effect of ketamine administration at the cellular level (evidence of sustainable cellular damage and mitochondrial DNA changes).
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 3 Months 至 48 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All children between the ages of 3 and 48 months who receive intravenous ketamine for procedural sedation in the ED during study enrolment hours will be eligible for recruitment.
排除标准
- •Children with contraindications to procedural sedation in the ED according to SickKids (the Hospital for Sick Children) practice guidelines or to ketamine administration will not be considered.
- •Parents with an insurmountable language barrier (i.e. does not speak English and are not accompanied by another adult who cannot translate for the parent/caregiver), which prevents informed consent.
- •Child who has received procedural sedation/ or surgery under general anesthesia in the past 30 days.
- •A child who has received any central nervous system drugs (e.g. anticonvulsants, benzodiazepines) or a known neurotoxic drug (e.g., methotrexate, corticosteroids) concomitantly or in the 30 days preceding the sedation.
- •A child who has suffered traumatic head injury concomitantly or in the previous 30 days
- •A child who has CNS (Central Nervous System) illnesses or pathologies (e.g., meningitis, near drowning, hypoxic-ischemic brain injury, seizure disorder) in the 30 days prior to sedation, potentially leading to elevated baseline serum biomarkers.
- •A child whose parents are considered to be in emotional distress due to the injury or illness of the child by the attending ED physician or where the attending ED physician does not believe it is appropriate to ask the parents for consent.
结局指标
主要结局
Increase in serum biomarkers of neurotoxicity (neuronal cell apoptosis)
时间窗: 1 to 24 hours from ketamine exposure
次要结局
- Pharmacogenetics role in ketamine toxicity(1-24 hours from ketamine exposure)
- Ketamine-induced mitochondrial damage(1-24 hours from ketamine exposure)
研究者
Yaron Finkelstein
Staff Physician
The Hospital for Sick Children