Is Anesthetic Loss of Consciousness a Top Down or Bottom up Phenomenon. What Does the Neurologic Examination Say?. (Top&Bottom)

Is Anesthetic Loss of Consciousness a Cortical or Brainstem Phenomenon? What Does the Neurological Examination Say?

Using very slow or fast propofol intravenous injection, monitored using standard American Society of Anesthesiology (ASA) standard and SEDLine EEG (Med Tech), the patient was evaluate by a neurologist every 30 sec using the FOUR coma scale.

Study Overview

• Status: Completed
• Conditions: Anesthesia; Functional
• Intervention / Treatment: Diagnostic test: FOUR coma scale and frontal espectrograpy evaluation

Detailed Description

Clinical experimental randomized study, approved by the Ethic Committee, with informed consent, included ASA I- II adults, without neurological illness and normal physical exam.

The patient randomized in two groups, rapid induction (GR) with propofol in target controlled infusion (TCI) effect site mode using the phamacokinetic (PK) model from Marsh ke0 1,21 min-1 using a calculated target of 5.4 ug/ml (loss of counsciousness EC95) and slow induction (GL) 10 mg/kg/h with calculated effect site concentrations (CeCALC) same PK model.

The same neurologist, blind to the correspondent group, evaluated all the patients every 30 sec using the coma FOUR scale until loss of counsciousness (LOC), defined as a FOUR (E0 no eyes opening response and /or M0 no motor response). At LOC the existance of brainstem reflex was evaluated (B no pupil and corneal reflex), respiratory pattern (R apnoea), CeCALC and patient state index (PSI) SEDline™ was recorded during all the examination.

After LOC in both groups we maintain in GR the initial target (5.3 ug/ml) and the LOC CeCALC during 10 min without intervention, except respiratory support if it was required.

Frontal EEG 4 channel and spectrogram from SEDline monitor was extracted for each case and posterior analysis.

Fisher exact test was used to describe primary outcome and difference between B and R for each group. The difference in time to reach LOC LOC, Ce and PSI was analysed with T- Student.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Chile
  • Region Metropolitana
    • Santiago, Region Metropolitana, Chile, 7600000
      • Clínica Alemana de Santiago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: ASA 1-2 patients programmed for elective surgery, normal neurologic examination -

Exclusion Criteria: neurologic illness, receiving drugs that affect Central Nervous System during the last 48 hours

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: GR fast induction; propofol TCI effect site mode infusion using the PK Marsh model ke0 1,21 min-1 target 5.4 ug/ml (LOC EC95) util loss of consciousness (LOC) After LOC we maintain initial target during 10 min without intervention, except respiratory support if required.	Diagnostic test: FOUR coma scale and frontal espectrograpy evaluation; systematic evaluation using the validated FOUR coma scale during propofol administration; Other Names: 4 channel EEG record with SEDline monitor; Non Invasive Blood presure, Saturation 02, Electrocardiogram; propofol infusion in Target controlled infusion using Primea Orchestra infusion pump Fressenius Kabi
Active Comparator: GL slow induction; propofol infused at 10 mg/kg/h with CeCALC PK Marsh model ke0 1,21 min-1 same PK model After LOC we maintain the CeCALC observed al LOC during 10 min without intervention, except respiratory support if it was required.	Diagnostic test: FOUR coma scale and frontal espectrograpy evaluation; systematic evaluation using the validated FOUR coma scale during propofol administration; Other Names: 4 channel EEG record with SEDline monitor; Non Invasive Blood presure, Saturation 02, Electrocardiogram; propofol infusion in Target controlled infusion using Primea Orchestra infusion pump Fressenius Kabi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
loss of consciousness a cortical or brainsteam phenomenon	with fast and slow induction we use the FOUR coma scale ( Ann Neurol. 2005;58(4): 585-93) to identify lost of brain stem activities.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
evaluation of the alfa band behavior after fast and slow inductions	the investigators analyze the time delay in stabilizing the frontal alfa band after fast and slow anesthesia inductions	1 year

Collaborators and Investigators

• Sponsor: Universidad del Desarrollo
• Investigators: Study Chair: Pablo Lavados, MD, Clinica Alemana Comité Cientifico

Publications and helpful links

General Publications

• Brown EN, Lydic R, Schiff ND. General anesthesia, sleep, and coma. N Engl J Med. 2010 Dec 30;363(27):2638-50. doi: 10.1056/NEJMra0808281. No abstract available.
• Mashour GA. Top-down mechanisms of anesthetic-induced unconsciousness. Front Syst Neurosci. 2014 Jun 23;8:115. doi: 10.3389/fnsys.2014.00115. eCollection 2014.
• Wijdicks EF, Bamlet WR, Maramattom BV, Manno EM, McClelland RL. Validation of a new coma scale: The FOUR score. Ann Neurol. 2005 Oct;58(4):585-93. doi: 10.1002/ana.20611.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2016
• Primary Completion (Actual): December 15, 2016
• Study Completion (Actual): December 15, 2016

Study Registration Dates

• First Submitted: April 10, 2017
• First Submitted That Met QC Criteria: May 3, 2017
• First Posted (Actual): May 4, 2017

Study Record Updates

• Last Update Posted (Actual): May 31, 2017
• Last Update Submitted That Met QC Criteria: May 26, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: propofol; pharmacology; anesthesic induction; drug titration
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Consciousness Disorders; Unconsciousness; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Hypnotics and Sedatives; Propofol
• Other Study ID Numbers: Centro Bioetica 2016-05

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