The Effect of Neuromuscular Blockade on the Composite Variability Index (CVI) During Laryngoscopy

The Effect of Rocuronium on the Response of Composite Variability Index (CVI) to Laryngoscopy

The Bispectral Index (BIS) monitor is used in many operating rooms to provide information to the anesthesiologist about a patient's level of consciousness. The Composite Variability Index (CVI) is a new index that may provide the anesthesiologist with more information about the condition of the patient. The CVI is a measure of the combined variability in BIS (bispectral index) and frontal electromyography (EMG) activity that may be useful in assessing the nociception/anti-nociception balance for patients under general anesthesia.The purpose of this study is to determine if a commonly used anesthetic drug (rocuronium) affects the CVI measurement differently with different doses. Rocuronium is a neuromuscular blocking agent (NMBA) routinely used during surgery. It is expected that the group given the highest dose of rocuronium will have diminished CVI values.

This study will randomize patients to one of four doses of rocuronium: no rocuronium, 0.2, 0.4, and 0.6 milligrams per kilo of body weight; the last dose is the standard amount for adults. It is expected that the group given the highest dose of rocuronium will have diminished CVI values. By including intermediate doses, information about the function of CVI in states of less than full muscle relaxation, or paralysis, will be obtained. This information is critically important for the development of the composite variability index, because during general anesthesia patients are usually maintained in a state of less than full paralysis. If the CVI response to stimulation in the intermediate groups is similar to the group receiving no rocuronium, the monitor may find wide clinical applicability. If the response is similar to the maximal rocuronium group, the index may only be reliable in states with no muscle relaxant, which will greatly limit clinical utility.

Study Overview

• Status: Completed
• Conditions: Anesthesia; Neuromuscular Blockade
• Intervention / Treatment: Drug: Saline 0.06 ml/kg; Drug: Rocuronium 0.2 mg/kg; Drug: Rocuronium 0.4 mg/kg; Drug: Rocuronium 0.6 mg/kg

Detailed Description

Consented subjects randomized to one of four doses of rocuronium will be transported to the operating room and be connected to routine monitors that included a BIS (Covidien), M-Entropy sensor (GE Healthcare) and TOF (train of four) monitor. Following preoxygenation, general anesthesia will be induced with propofol and remifentanil using traditional syringe pumps. The induction doses given and subsequent infusion rates will be determined by utilizing pharmacokinetic (Pk) models (Marsh model for propofol, Minto model for remifentanil). Unconsciousness will be confirmed by performing the usual clinical assessments and by obtaining a BIS value between 40 and 50. Once the subject is unconsciousness, they will be given the assigned dose of rocuronium, after which the study anesthesiologist will perform a laryngoscopy. The anesthesiologist performing the laryngoscopy will not know what dose of rocuronium the subject received. Neuromuscular blockade (NMB) will be monitored by a train-of-four twitch monitor (TOF Watch-SX) at the adductor pollicis muscle (2 HZ, 50mAmp) every 15 seconds.

At three minutes after the rocuronium administration, a standardized 20-second laryngoscopy will be applied. The CVI, entropy, and hemodynamic responses (heart rate, blood pressure measurement each minute) and train-of-four measurements will be monitored for three minutes before and after the laryngoscopy.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Vermont
    • Burlington, Vermont, United States, 05405
      • Fletcher Allen Health Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• American Society of Anesthesia (ASA) physical status class I or II.
• Body mass index between 18 and 35 kg m-2.
• No use of psychotropic or neuropsychiatric medications.
• A airway assessment with no indication of a difficult intubation including a class I or II Mallampati airway and a mandible-to-hyoid distance of greater than three fingerbreadths.
• Age between 18-75 years.

Exclusion Criteria:

• Does not meet inclusion criteria.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Group 1; Saline 0.06 ml/kg	Drug: Saline 0.06 ml/kg; IV Infusion x1 prior to laryngoscopy; Other Names: Normal Saline
Active Comparator: Group 2; Rocuronium 0.2 mg/kg	Drug: Rocuronium 0.2 mg/kg; IV Infusion x1 prior to laryngoscopy; Other Names: Rocuronium bromide: Zemuron
Active Comparator: Group 3; Rocuronium 0.4 mg/kg	Drug: Rocuronium 0.4 mg/kg; IV Infusion x1 prior to laryngoscopy; Other Names: Rocuronium bromide: Zemuron
Active Comparator: Group 4; Rocuronium 0.6 mg/kg	Drug: Rocuronium 0.6 mg/kg; IV Infusion x1 prior to laryngoscopy; Other Names: Rocuronium bromide: Zemuron

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Mean Difference in CVI Between Pre-laryngoscopy and Post-laryngoscopy for Each of the Four Rocuronium Groups	The difference between the mean CVI in three minutes prior to laryngoscopy and three minutes following laryngoscopy reported as the mean change in CVI and the +/- 95% confidence interval for each group. The Composite Variability Index (CVI) scale is a logistic regression of three measures of processed electroencephalography (EEG) signals. These signals are Bispectral Index (BIS), the variability of electromyelogram (sEMG), and the variability of BIS (sBIS). The scale ranges from 0 to 100 where a lower CVI value represents a lower likelihood of intraoperative somatic responses, and a higher CVI value represents a higher likelihood of intraoperative somatic responses.	Six minutes after the dose of rocuronium with laryngoscopy at 3 minutes after the study intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Average CVI During the Maintenance Phase of Anesthesia for the Two Remifentanil Groups	Mean CVI from incision to propofol off reported as the mean CVI +/- 95% confidence interval for the two groups	Maintenance Anesthesia

Collaborators and Investigators

• Sponsor: Medtronic - MITG
• Investigators: Principal Investigator: Donald M Mathews, MD, University of Vermont

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: September 22, 2011
• First Submitted That Met QC Criteria: October 11, 2011
• First Posted (Estimate): October 12, 2011

Study Record Updates

• Last Update Posted (Actual): May 12, 2017
• Last Update Submitted That Met QC Criteria: April 4, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Anticonvulsants; Neuromuscular Agents; Neuromuscular Nondepolarizing Agents; Neuromuscular Blocking Agents; Bromides; Rocuronium
• Other Study ID Numbers: COVMOPR0176

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data collected was for device algorithm development