Deep Brain Stimulation (DBS) Sedation

Effects of Anesthesia Drugs on Neuronal Activity in the Basal Ganglia and Thalamus During Deep Brain Stimulation Electrode Implantation Surgery

Deep brain stimulation (DBS) of different brain nuclei is a treatment for multiple brain disorders. The subthalamic nucleus (STN) and globus pallidus have been used to treat advanced Parkinson's disease for a long time. The ventral intermediate nucleus of the thalamus is an effective target for treating essential tremor patients. STN and the internal segment of the globus pallidus are useful targets for treating dystonia.

To achieve this optimal electrode localization, many centers perform electrophysiological mapping of the target nuclei using microelectrode recording (MER). This way they can achieve precise localization of the electrode. During the mapping procedure, microelectrodes are passed through the target nuclei, and the electrical neuronal activity is observed and recorded. The surgical team can identify the precise location of the target nuclei and its borders according to the typical activity of its neurons.

This study will compare the activity of neurons in several DBS targets before, during and after sedation with propofol, remifentanil and dexmedetomidine. The goal is to understand the effects of anesthetics on the neuronal activity in these targets, allowing us to choose the most appropriate sedation protocol to use during implantation of DBS electrodes in deep brain structures (bearing in mind that each structure may have a different optimal protocol).

Study Overview

• Status: Terminated
• Conditions: Sedation; Brain
• Intervention / Treatment: Drug: Propofol; Drug: Dexmedetomidine; Drug: Remifentanil

Detailed Description

Deep brain stimulation (DBS) of different brain nuclei is evolving as an essential component of the treatment for multiple brain disorders. The subthalamic nucleus (STN) and globus pallidus have been used to treat advanced Parkinson's disease for a long time. The ventral intermediate nucleus of the thalamus is an effective target for treating essential tremor patients. STN and the internal segment of the globus pallidus are useful targets for treating dystonia. Aside from movement disorders DBS has demonstrated efficacy in the treatment of other conditions such as chronic pain, obsessive compulsive disorder, depression and epilepsy. For these illnesses the specific brain region targeted depends upon the illness and the patient's characteristics. As the indications for DBS increase in number, so grows the number of patients that may be helped by this treatment. Increasing numbers of patients are undergoing these procedures for various maladies at our center and at other locations throughout the nation.

To achieve optimal clinical results and avoid side effects, the DBS electrode has to be implanted precisely within the targeted region. This was demonstrated elegantly for parkinsonian patients and the dorsolateral STN, but is likely to be the case for most DBS indications. To achieve this optimal electrode localization, many centers perform electrophysiological mapping of the target nuclei using microelectrode recording (MER). This way they can achieve precise localization of the electrode. During the mapping procedure, microelectrodes are passed through the target nuclei, and the electrical neuronal activity is observed and recorded. The surgical team can identify the precise location of the target nuclei and its borders according to the typical activity of its neurons.

Dexmedetomidine, propofol and remifentanyl are often used in awake neurosurgical procedures. Dexmedetomidine provides sedation and amnesia with minimal respiratory depression, and improves perioperative hemodynamic stability in neurosurgical patients. Propofol and remifentanil have a much shorter duration of action, and thus allow rapid titration. Both these agents allow reliable and safe sedation for awake craniotomies. However, the effects of any of these three agents on the electrical activity, and whether they will allow safe sedation during DBS electrode implantation at different targets and in different clinical conditions is unclear.

This study will compare the activity of neurons in several DBS targets before, during and after sedation with propofol, remifentanil and dexmedetomidine. The goal is to understand the effects of anesthetics on the neuronal activity in these targets, allowing the study team to choose the most appropriate sedation protocol to use during implantation of DBS electrodes in deep brain structures (bearing in mind that each structure may have a different optimal protocol).

The primary aim is to document the effects of commonly used anesthetic drugs on the neuronal activity during MER in different brain structures that are used as targets for DBS implantation.

The secondary aims is to Identifying effective sedation regimens for the different DBS targets; (2) Documenting the time course of the different drug's effect on the neuronal activity. Having this information will allow planning and performing sedation during the procedure prior to the MER without affecting the quality of the MER. This may prove useful in cases where no sedation regimen is completely devoid of effect on the MER; (3) Creating a database that includes the neuronal activity changes at multiple brain regions under the effect of different sedation drugs to enable further study of the effects of anesthetics on brain regions and the mechanisms underlying loss of consciousness.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin Hospital and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• All patients scheduled to undergo DBS electrode implantation surgery with MER that agree to participate in the experiment and sign an informed consent are candidates to participate in the study, unless one of the exclusion criteria is met

Exclusion Criteria:

1. Known or suspected obstructive sleep apnea.
2. Suspected difficult intubation.
3. Pregnancy (pregnancy test is standard care for women of childbearing age)
4. Under 18 years of age or over 85 years of age
5. Cognitive disability impairing understanding the experiment or signing the informed consent form.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Remifentanil; Remifentanil will be administered to subjects during microelectrode recordings (MER).	Drug: Remifentanil; Remifentanyl will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the bispectral index (BIS) values to normalize to awake level for the MER.
Active Comparator: Propofol; Propofol will be administered to subjects during MER.	Drug: Propofol; Propofol will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the BIS values to normalize to awake level for the MER.
Active Comparator: Dexmedetomidine; Dexmedetomidine will be administered to subjects during MER.	Drug: Dexmedetomidine; Dexmedetomidine will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the BIS values to normalize to awake level for the MER.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sedatives Drugs Effects - Percent Change in Root Mean Square (RMS) of Electrical Activity	Effects of propofol, remifentanil and dexmedetomidine on the neuronal activity during microelectrode recording (MER) in different brain structures that are used as target for DBS implantation will be measure. The RMS of the electrical activity as a measure of the spiking rate of neurons in the vicinity of the electrode tip. normalize the RMS to the baseline value recorded at the first 2-5 minutes of MER (before entering the target area) to compensate for differences between patients and recording electrodes. In order to calculate the change in the normalized RMS following sedation the investigators will compare the mean RMS during 2 minutes of the stable recording of the pre-sedation baseline to the mean RMS during stable sedation and following recovery.	45 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Time in Minutes From Sedation to Recovery	This outocme meadsures the mean time from sedation to recovery.	up to 57 minutes
Number of Individuals Examined for Neuronal Activity Changes at Multiple Brain Regions Under the Effect of Different Sedative Drugs	The number of subjects examining the neuronal activity changes at multiple brain regions under the effect of different sedation drugs to enable further study of the effects of anesthetics on brain regions and the mechanisms underlying loss of consciousness.	1hrs 30 min

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Investigators: Principal Investigator: Corey A Amlong, MD, University of Wisconsin, Madison

Publications and helpful links

General Publications

• Raz A, Eimerl D, Zaidel A, Bergman H, Israel Z. Propofol decreases neuronal population spiking activity in the subthalamic nucleus of Parkinsonian patients. Anesth Analg. 2010 Nov;111(5):1285-9. doi: 10.1213/ANE.0b013e3181f565f2. Epub 2010 Sep 14.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2017
• Primary Completion (Actual): January 20, 2022
• Study Completion (Actual): January 20, 2022

Study Registration Dates

• First Submitted: September 6, 2017
• First Submitted That Met QC Criteria: September 13, 2017
• First Posted (Actual): September 14, 2017

Study Record Updates

• Last Update Posted (Actual): July 5, 2024
• Last Update Submitted That Met QC Criteria: June 24, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Sedation; Deep Brain Stimulation(DBS); DBS Implantation; Microelectrode recording(MER)
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Analgesics, Opioid; Narcotics; Hypnotics and Sedatives; Remifentanil; Propofol; Dexmedetomidine
• Other Study ID Numbers: 2016-1420; A530900 (Other Identifier: UW Madison); SMPH\ANESTHESIOLOGY\ANESTHESIO (Other Identifier: UW Madison); Protocol Version 2/17/2020 (Other Identifier: UW Madison)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No