Neuroinflammatory and Neurocognitive Effects of Spinal vs. Inhalational Anesthesia for Elective Surgery in Infants

Neuroinflammatory and Neurocognitive Effects of Spinal vs. Inhalational Anesthesia for Elective Surgery in Infants: A Randomized, Controlled, Double-Blinded Study

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.

Study Overview

• Status: Withdrawn
• Conditions: Inguinal Hernia
• Intervention / Treatment: Drug: General Anesthesia (isoflurane); Drug: Spinal Anesthesia (bupivacaine)

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 year (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Otherwise healthy child aged 0-less than 13 months undergoing elective (non-emergent) general, urologic, orthopedic, and plastic surgery
2. Parent/guardian must provide written informed consent in accordance with human investigation committee guidelines
3. Participants must be American Society of Anesthesiologist (ASA) physical status ≤ 2

Exclusion Criteria:

1. Any active bacterial or viral infection within the last 14 days
2. 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
3. Anticoagulant administration in the last 48 hours
4. Patients that have an American Society of Anesthesiologists physical status >2
5. Infants born more than 4 weeks premature

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: General Anesthesia; Inhalational anesthesia with Isoflurane 1-2% in 50%/50% oxygen/air mixture. This arm will receive the General Anesthesia (isoflurane) intervention exclusively.	Drug: General Anesthesia (isoflurane); Isoflurane is a fluorinated ether with general anesthetic and muscle relaxant effects. Brand names include Forane and Terrell.; Other Names: Standard Inhalational Anesthesia
ACTIVE_COMPARATOR: 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.	Drug: Spinal Anesthesia (bupivacaine); Bupivacaine is an amide-type, long-acting local anesthetic. Brand names include Exparel, Marcaine, and Sensorcaine.; Other Names: Regional Anesthesia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in proinflammatory miRNAs	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).	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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in systemic inflammation	Inflammatory biomarkers in the serum will be compared between time points and between arms.	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)

Collaborators and Investigators

• Sponsor: Emmett Whitaker, M.D.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2015
• Primary Completion (ACTUAL): December 31, 2017
• Study Completion (ACTUAL): December 31, 2017

Study Registration Dates

• First Submitted: July 30, 2015
• First Submitted That Met QC Criteria: August 10, 2015
• First Posted (ESTIMATE): August 13, 2015

Study Record Updates

• Last Update Posted (ACTUAL): January 25, 2018
• Last Update Submitted That Met QC Criteria: January 23, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Circumcision
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Hernia, Abdominal; Hernia; Hernia, Inguinal; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics, General; Anesthetics, Local; Anesthetics, Inhalation; Anesthetics; Bupivacaine; Isoflurane
• Other Study ID Numbers: IRB15-00125