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

NCT02521831 | Withdrawn Phase 3

• 1 other identifier: IRB15-00125
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Inguinal Hernia

Keywords

Circumcision

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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)

Study Arms (2)

General Anesthesia

ACTIVE COMPARATOR

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)

Spinal Anesthesia

ACTIVE COMPARATOR

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)

Interventions

Spinal Anesthesia (bupivacaine) DRUG

Bupivacaine is an amide-type, long-acting local anesthetic. Brand names include Exparel, Marcaine, and Sensorcaine.

Also known as: Regional Anesthesia

Spinal Anesthesia

General Anesthesia (isoflurane) DRUG

Isoflurane is a fluorinated ether with general anesthetic and muscle relaxant effects. Brand names include Forane and Terrell.

Also known as: Standard Inhalational Anesthesia

General Anesthesia

Eligibility Criteria

• Age: Up to 1 Year
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Emmett Whitaker, M.D.: lead

MeSH Terms

Conditions

Hernia, Inguinal

Interventions

Anesthesia, Spinal; Bupivacaine; Anesthesia, Conduction; Anesthesia, General; Isoflurane

Condition Hierarchy (Ancestors)

Hernia, Abdominal; Hernia; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Anesthesia; Anesthesia and Analgesia; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Methyl Ethers; Ethers

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: July 30, 2015
• First Posted: August 13, 2015
• Study Start: October 1, 2015
• Primary Completion: December 31, 2017
• Study Completion: December 31, 2017
• Last Updated: January 25, 2018

Record last verified: 2018-01