Topical Anesthesia and Intra-arterial Chemotherapy for Retinoblastoma (TOPIAC)

Topical Anesthesia to Decrease the Trigeminal-Cardiac Reflex During Intra-arterial Injection of Chemotherapy for Retinoblastoma in Children.

The objective of this study is to use local topical anesthesia to numb the sensory input, captured by branches of the Trigeminal nerve found on the skin in and around the eye, to decrease a hemodynamic reflex seen during placement of a catheter for intra-arterial chemotherapy (IAC) for eye tumors in children. This Trigeminal-cardiac reflex brings about hemodynamic instability during general anesthesia.

Normally, one could block this sensorial input with ophthalmic peribulbar placement of local anesthetics, but these eyes have malignant growth and invasive procedures may cause more harm. The investigators are aiming to numb the sensory branches of the trigeminal nerve non-invasively and observe for any decrease in these events.

Study Overview

• Status: Withdrawn
• Conditions: Hemodynamic Instability
• Intervention / Treatment: Drug: Tetracaine 0.5%; Drug: Lidocaine hydrochloride ophthalmic gel 3.5%

Detailed Description

Retinoblastoma is a rare tumor of the eye and accounts for 6% of malignancies in children less than 5 years of age. Pediatric anesthesiologists have observed a series of hemodynamic instability following the insertion of a catheter into the cavernous segment of the internal carotid artery or during manipulation of a micro-catheter into the ophthalmic artery for intra-arterial chemotherapy (IAC) of retinoblastoma cases by neuroradiologists. This reaction has been recently published in case reports and observational studies as the treatment of these tumors have moved into the interventional imaging suites. This reaction closely resembles the "diving reflex" seen when a person is submerged in cold water; known as the trigeminal-cardiac reflex. It manifests as a sudden hemodynamic disturbance in arterial blood pressure, heart rate, arrhythmia and changes in pulmonary compliance.Rescue from a trigeminal-cardiac reflex entails increasing intravascular volume, administrating mild to resuscitative doses of epinephrine and ventilatory support.

Catheter manipulation around the ophthalmic artery can stimulate the afferent pathway of the trigeminal nerve, branches V1 and V2, originating around the eye to be treated.The ethmoidal nerve, from the nasal passage on the same side, is also stimulated. This in turn triggers a response by the vagus nerve with hemodynamic instability.

Method: Participants are placed under general endotracheal anesthesia for this scheduled procedure. One drop of ocular antiseptic (betadine 5%) will be placed in the eye to be treated followed by a drop of topical FDA approved local anesthetic, Tetracaine 0.5%, to the nasolacrimal duct ( inner corner of the eye) on the eye to be treated. This will numb the ethmoidal nerve in the nasal passage. This is followed by 1 ml of 3.5% Lidocaine gel to the surface of the eye. This gel is placed on the surface of the eye and skin around the eye to numb V1 and V2 fibers of the trigeminal nerve. The study will observe if there is any decrease in the intensity of the reflex or incidence of the reflex during placement of the micro-catheter.

• Study Type: Interventional
• Phase: Early Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Children with Retinoblastoma diagnosis scheduled for Intra-arterial chemotherapy under general anesthesia

Exclusion Criteria:

• any candidate with history of allergy to anesthetics or preservatives used in local anesthetics any candidate that has a history of allergic dermatitis any candidate that has an open wound in and around the eye to be treated

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment session 1a; Topical ophthalmic anesthesia to participants (#) on each session (letter) of intra-arterial chemotherapy. where #1 is the participant identifier and letter-a is the start session with study protocol (most candidates will receive more than 4 sessions in a 6 month period)	Drug: Tetracaine 0.5%; One drop of 0.5% Proparacaine to nasolacrimal Duct to numb the ethmoidal nerve in the nasal passage on the side of the eye to be treated.; Drug: Lidocaine hydrochloride ophthalmic gel 3.5%; 1ml of lidocaine gel is placed over the conjunctivae of the eye to be treated after the patient is under general anesthesia and before the procedure; Other Names: Akten

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decrease in systolic Blood Pressure	Interventionalist will communicate to the investigator of the catheter placement and our outcome measure will be recorded soon after.	5 seconds
Drop in end-tidal C02	Interventionalist will communicate to the investigator of the catheter placement and our outcome measure will be recorded soon after.	5 seconds
Decrease in lung compliance	Interventionalist will communicate to the investigator of the catheter placement and our outcome measure will be recorded soon after.	5 seconds
Decrease in oxygen saturation	Interventionalist will communicate to the investigator of the catheter placement and our outcome measure will be recorded soon after.	5 seconds
Cardiac arrythmia	Interventionalist will communicate to the investigator of the catheter placement and our outcome measure will be recorded soon after.	5 seconds

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recovery from Trigeminal-cardiac event	Investigator will communicate when the event is over or rescue drugs given.	2 minutes

Collaborators and Investigators

• Sponsor: University of Miami
• Investigators: Principal Investigator: Jacqueline Tutiven, MD, Director Pediatric Anesthesia Fellowship/Assistant Professor; Study Chair: Norman Halliday, MD, Chief, Pediatric Anesthesiology

Publications and helpful links

General Publications

• Scharoun JH, Han JH, Gobin YP. Anesthesia for Ophthalmic Artery Chemosurgery. Anesthesiology. 2017 Jan;126(1):165-172. doi: 10.1097/ALN.0000000000001381. No abstract available.
• Jabbour P, Chalouhi N, Tjoumakaris S, Gonzalez LF, Dumont AS, Chitale R, Rosenwasser R, Bianciotto CG, Shields C. Pearls and pitfalls of intraarterial chemotherapy for retinoblastoma. J Neurosurg Pediatr. 2012 Sep;10(3):175-81. doi: 10.3171/2012.5.PEDS1277. Epub 2012 Jul 13.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): March 1, 2018
• Primary Completion (ANTICIPATED): June 1, 2020
• Study Completion (ANTICIPATED): December 1, 2020

Study Registration Dates

• First Submitted: November 2, 2016
• First Submitted That Met QC Criteria: November 3, 2016
• First Posted (ESTIMATE): November 4, 2016

Study Record Updates

• Last Update Posted (ACTUAL): April 20, 2018
• Last Update Submitted That Met QC Criteria: April 18, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Eye Diseases; Retinal Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Eye Diseases, Hereditary; Eye Neoplasms; Retinal Neoplasms; Retinoblastoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Lidocaine; Tetracaine
• Other Study ID Numbers: 20161001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes