Tolerance to Sevoflurane in Children Undergoing Repeated Drug Exposure

Evaluation of the Development of Tolerance to Sevoflurane in Children Undergoing Repeated Anesthesia Exposure

Deep sedation or general anesthesia is frequently required for infant that need radiotherapy to treat malignancies. As radiation therapy usually consist of several sessions, these patients are exposure to several consecutive anesthetic exposures (e.g. for some central nervous system tumors 30 sessions of radiotherapy are required). In our center, this 30-min anesthetic exposure are with sevoflurane. Considering that repeated daily exposure to such potent drugs, as general anesthetics, may induce tolerance, it is reasonable to explore whether this phenomenon is occurring in this population.

The aim of this observational study was to determine if a repeated exposure to sevoflurane is associated with the development of clinical and electroencephalographic tolerance.

We will enroll 16 pediatric patients, and we will measure the time needed to appropriately place the laryngeal mask (clinical effect) and we also will compare the electroencephalographic signal under anesthesia across the different sessions (electroencephalographic effect).

Study Overview

• Status: Completed
• Conditions: Anesthesia; Tolerance
• Intervention / Treatment: Drug: Sevoflurane

Detailed Description

The purpose of this study is to evaluate the development of tolerance to sevoflurane in children undergoing repeated drug exposure.

We will evaluate the development of tolerance in two ways:

Clinical: as the time needed to perform the inhalation induction, with a standardized protocol.

Electroencephalographic: we will record every 3 sessions the electroencephalographic activity of the patients. We will perform classical spectral analysis, and coherence analysis as well.

This observational study will be mainly exploratory since there are no other previous report in this topic

• Study Type: Observational
• Enrollment (Actual): 24

Contacts and Locations

Study Locations

• Chile
  • Santiago, Chile
    • Centro de Investigacion Clinica Avanzada
  • Metropolitana
    • Santiago, Metropolitana, Chile, 7563215
      • Instituto Nacional del Cancer

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 months to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All consecutive pediatric patients schedule for radiotherapy treatment under general anesthesia.

Description

Inclusion Criteria:

• Patients undergoing radiotherapy
• Requiring general anesthesia

Exclusion Criteria:

• Previous Radiotherapy
• Malignant Hyperthermia history

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Pediatric patients undergoing radiotherapy; Pediatric patients undergoing general anesthesia for radiotherapy treatment. General anesthesia will be accomplished exclusively by the administration of sevoflurane. The inhalatory induction will be performed with sevofluorane at 8% with O2 4Lt/min. The maintenance will be with sevofluorane at an end tidal of 2.5% with 1Lt/min of O2. The EEG will be obtain with SedLine monitor

Drug: Sevoflurane; Describe how a reiterative anesthesia exposure could induce tolerance to the anesthetic.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Theta power in the EEG spectrum under anesthesia	Theta power obtained from the EEG signal, with the patient under general anesthesia	Last session of radiotherapy (compare to first session) - Up to 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Laryngeal Mask insertion	The time in seconds between the induction beginning and the correct laryngeal mask placement	Last session of radiotherapy (compare to first session) - Up to 6 weeks
Alpha power in the EEG spectrum under anesthesia	Alpha power obtained from the EEG signal, with the patient under general	Last session of radiotherapy (compare to first session) - Up to 6 weeks
Coherence	Coherence between frontal electrodes in bands of the spectrum	Last session of radiotherapy (compare to first session) - Up to 6 weeks

Collaborators and Investigators

• Sponsor: University of Chile
• Investigators: Principal Investigator: Antonello Penna, MD PhD, University of Chile; Principal Investigator: Jose I Egaña, MD PhD, University of Chile; Principal Investigator: Felipe Maldonado, Md MSc, University of Chile; Principal Investigator: Rodrigo Gutierrez, MD PhD, University of Chile

Publications and helpful links

General Publications

• Keidan I, Perel A, Shabtai EL, Pfeffer RM. Children undergoing repeated exposures for radiation therapy do not develop tolerance to propofol: clinical and bispectral index data. Anesthesiology. 2004 Feb;100(2):251-4. doi: 10.1097/00000542-200402000-00011.

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2019
• Primary Completion (Actual): August 20, 2021
• Study Completion (Actual): September 22, 2021

Study Registration Dates

• First Submitted: December 3, 2019
• First Submitted That Met QC Criteria: December 5, 2019
• First Posted (Actual): December 6, 2019

Study Record Updates

• Last Update Posted (Actual): October 7, 2021
• Last Update Submitted That Met QC Criteria: October 5, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Electroencephalogram; Anesthesia; Spectral analysis
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, General; Anesthetics; Platelet Aggregation Inhibitors; Anesthetics, Inhalation; Sevoflurane
• Other Study ID Numbers: 0362019

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.: No