Neuroinflammatory and Neurocognitive Effects of Spinal vs. Inhalational Anesthesia for Elective Surgery in Infants: A Randomized, Controlled, Double-Blinded Study
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 发起方
- 主要终点
- Change in proinflammatory miRNAs
研究概览
简要总结
Significant concern regarding the safety of general anesthesia in children has arisen due to myriad animal studies suggesting neurotoxicity of commonly used anesthetic agents. Inflammation of the central nervous system after anesthesia may have a significant role in the pathogenesis of anesthetic-induced neural injury. To evaluate this hypothesis, the investigators propose to randomize healthy infants undergoing elective surgery to one of two anesthetics: 1) spinal anesthesia only; or 2) general inhalational anesthesia with isoflurane, laryngeal mask airway (LMA) or endotracheal tube (ETT), and single-shot caudal block. Primary endpoint will be serum inflammatory biomarkers and transcriptome analysis and secondary endpoint will be neurocognitive outcome at 6 months and 1 year.
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
- — 至 1 Year（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Otherwise healthy child aged 0-less than 13 months undergoing elective (non-emergent) general, urologic, orthopedic, and plastic surgery
- •Parent/guardian must provide written informed consent in accordance with human investigation committee guidelines
- •Participants must be American Society of Anesthesiologist (ASA) physical status ≤ 2
排除标准
- •Any active bacterial or viral infection within the last 14 days
- •Treatment in the last 48 hours with non-steroidal anti-inflammatory (NSAID) or corticosteroid medications, or any other drug known to suppress or induce inflammation
- •Anticoagulant administration in the last 48 hours
- •Patients that have an American Society of Anesthesiologists physical status >2
- •Infants born more than 4 weeks premature
研究组 & 干预措施
General Anesthesia
Inhalational anesthesia with Isoflurane 1-2% in 50%/50% oxygen/air mixture.
This arm will receive the General Anesthesia (isoflurane) intervention exclusively.
干预措施: General Anesthesia (isoflurane) (Drug)
Spinal Anesthesia
These infants will not receive any anesthetic gas prior to the spinal. These infants will be conscious for this procedure.
Spinal will be administered, containing 0.25% isobaric bupivacaine, 1 mg/kg (maximum 5mg), Clonidine, 1 µg/kg, and Epinephrine, 1:200,000.
This arm will receive the Spinal Anesthesia (bupivacaine) intervention exclusively.
干预措施: Spinal Anesthesia (bupivacaine) (Drug)
结局指标
主要结局
Change in proinflammatory miRNAs
时间窗: Blood will be drawn before surgical incision, at the conclusion of the surgery (typically ~1 hour after incision), and at arrival to the PACU (typically 10-30 minutes after end of surgery)
Blood samples will be analyzed for a composite measure of systemic inflammation caused by the anesthetic agent. MicroRNA (miRNA) expression will be compared between the time points for each patient and between arms. Total RNA will be extracted from whole blood using a commercially available kit. RNA will then be assayed for transcriptome analysis using microarray technology. Serum cytokines will be analyzed using Enzyme-Linked Immunosorbent Assay (ELISA) for Tumor Necrosis Factor alpha (TNF-α), Interleukin one beta (IL-1β),Monocyte Chemoattractant Protein one (MCP-1), Prostaglandin E2 (PGE2), Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-ĸB), transcription factor p65, and S100 calcium-binding protein B (S100B). miR-155, miR-146a, miR-146b, and miR-142-3p will be quantified using quantified polymerase chain reaction (qPCR).
次要结局
- Change in systemic inflammation(Blood will be drawn before surgical incision, at the conclusion of the surgery (typically ~1 hour after incision), and at arrival to the PACU (typically 10-30 minutes after end of surgery))
研究者
Emmett Whitaker, M.D.
Clinical Assistant Professor
Nationwide Children's Hospital