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Anesthesia AwarenessNCT04788732

Heart Rate Variability to Quantify General Anesthesia Depth

An observational study of Anesthesia Awareness, run by University of Sao Paulo at 1 site in Brazil.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The shortage of anesthetic agents can lead to intraoperative awareness while overdosing can trigger severe intra and postoperative problems. Therefore, monitoring anesthesia's depth (DoA: Depth of Anesthesia) is a crucial but still challenging task. Read more about this study

Who is it for?
Ages 0 months and older
Conditions the study is for
Anesthesia Awareness
What is being tested?
ECG and EEG monitoring
How many people
200 participants
Where
1 siteBrazil
Study dates
4 Jan 2021to 30 Aug 2022
How long will I take part?
1 Year
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 0 months and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Study population: Patients ASA (classification by the American Society of Anesthesiology) 1-3, of all ages, undergoing general anesthesia will be considered and divided into three groups, according to the type of anesthesia used: inhaled, total intravenous, or balanced.

Who may be able to join

  • ASA patients (classification by the American Society of Anesthesiology) 1-3, of all ages, scheduled to undergo procedures under general anesthesia.

Who cannot join

  • Patients with craniofacial deformities in which it is not possible to place the EEG sensors.
  • Patients with severe eczema, allergy, or skin atopy.
  • Patients with a history of severe autonomic dysfunction.
  • Need of autonomic cardiac blockers during the intraoperative period.
  • Absence of Consent.

Trial locations and contacts

1 site in 1 country.

Waynice N Paula-Garcia contact

+5516981154121

wgarcia@fmrp.usp.br

Brazil1 site, 1 recruiting
  • Waynice N. Paula-Garcia

    Ribeirão Preto, São Paulo, 14.048-900

    Waynice N Paula-Garcia, +5516981154121, waynicegarcia@gmail.com

    +551636021000 ext. 2211, wgarcia@fmrp.usp.br

    Recruiting

Other trials in Brazil

About this study

Official title: Heart Rate Variability as Tool for Quantification of General Anesthesia Depth in Patients

The shortage of anesthetic agents can lead to intraoperative awareness while overdosing can trigger severe intra and postoperative problems. Therefore, monitoring anesthesia's depth (DoA: Depth of Anesthesia) is a crucial but still challenging task. Although some commercial monitors are based on electroencephalogram (EEG), designed to quantify DoA, their use in clinical practice has limitations. On the other hand, heart rate variability (HRV) has valuable information about physiological states, both from the heart and the organism. Classical indices derived from HRV have been shown to be able to differentiate the different stages of anesthesia. In this study, it is proposed to create a model to monitor DoA combining several HRV indices. Patients will be divided into three groups, according to the type of anesthesia to which they will be submitted (inhalation, total or balanced intravenous) and will have the electrocardiogram recorded during the entire surgical procedure. Various HRV indices will be calculated, and machine learning techniques will be used to combine and identify the most relevant index to compose a score that reliably represents DoA. Several commercial devices have been developed to monitor the level of consciousness during anesthesia. Among the most popular tools are included: Narcotrend TM (MonitorTechnik, Bad Bramstedt, Germany); the M-Entropy TM (GE Healthcare, Helsinki, Finland); Nindex SA (Controls, Montevideo, Uruguay) and the Bi-Spectral Index (BIS, TM Medtronic-Covidien, Dublin, Ireland). In this study, BIS or Nindex will also be monitored during the entire period that the patients remain anesthetized and will later be used to compose the DoA score based on HRV. As a result, a computer program will be created to monitor DoA in real-time.

Read the detailed description

Anesthesia is a state of reversible unconsciousness induced by one or more pharmacological agents. The three main anesthesia components are analgesia (pain relief), amnesia (memory loss), and immobilization, including autonomic reflexes' inhibition for harmful stimuli.1 Drugs used to induce anesthesia, in general, have different effects on each of these three components mentioned above.

Anesthesia depth assessment ( DoA: from English, Depth of Anesthesia ) is essential for anesthetic practice. The DoA depends on two opposing factors: the amount of anesthetic agent administered to the patient and the stimuli produced during surgery, increasing the level of awareness, and the patient's nociception. The ideal level d the DoA involves the guaranteed unconsciousness and anti-nociception adequate during surgery without compromise the functions of vital organs. In other words, one of the main challenges for anesthetists is to identify the appropriate amount of anesthetic to be administered to avoid the unwanted effects of anesthetic shortages (leading, for example, to intraoperative awareness) or anesthetic overdose, which can cause severe problems during intra and postoperative periods. 2 Before using muscle relaxants, the appropriate level of DoA could be monitored by the absence of movements to painful stimuli; once, the surgical incision's lack of movements was a sure sign that the patient was not superficially anesthetized. However, with the muscle relaxants' adoption in the anesthetics protocols, other measures to ensure that anesthetic agents' concentrations were administered properly were necessary.

Becoming conscious during surgery is a major concern for patients and anesthesiologists. It is estimated that the incidence of consciousness during general anesthesia is low, around 0.04% to 0.3%. However, considering the high number of surgical interventions, accidental awareness during surgery represents thousands of cases worldwide. Therefore, despite being an old problem, awareness during anesthesia is still a very relevant issue in public health.

DoA inefficient may also lead to an imbalance nociception x anti-nociception intraoperatively, even without patient conscious pain. Nociceptive stimuli can substantially affect the physiological state, inducing, for example, tachycardia, hypertension, nausea, fainting, and, therefore, negatively influencing patients' postoperative period 1 Thus, careful and efficient monitoring of DoA is the key to minimizing both the possibility of accidental awareness in surgeries and the overdose of anesthetic agents. 3 However, despite the importance of monitoring d the DoA, it is not easy to quantify this parameter during general anesthesia, and several approaches have been proposed to accomplish this task.

Quantification of DoA:

The anesthetic depth could be identified by monitoring the sympathetic activity of the patient. However, many anesthetics substantially alter autonomic activity, both sympathetic and parasympathetic. The observation of autonomic responses such as sweating, tear formation, hypertension, tachycardia, and pupil dilation are also important indicators of adequate unconsciousness levels. However, these signals cannot guide the anesthetist, considering that the patient cannot react due to neuromuscular blockade. 3 On the other hand, some authors suggest monitoring the concentration of inspired and expired anesthetic gases as markers of DoA.4 However, to date, there is no standardized and universally accepted method for quantifying DoA, and the anesthesiologist's experience is still the most important and effective factor in determining DoA.

DoA's monitoring techniques have advanced considerably in recent years. The nature of changes in electroencephalographic patterns during the stages of anesthesia was studied in detail, opening up possibilities for monitoring DoA by identifying electroencephalogram (EEG) patterns with crucial clinical significance for anesthesia.5 The use of EEG devices made monitoring of DoA potentially easier and was recommended by NIH - Care Excellence.

Although the progress brought by EEG-based monitors to anesthetic practice is indisputable, they still have significant limitations: 1) the algorithms created to derive a single DoA index from the EEG are exclusive (owned by their creators) for each device; 2) The EEG obtained in these devices is limited, exclusively, to the activity of the frontal lobe, lacking the representation of deeper subcortical structures ; 3) EEG is recognized for being highly sensitive to a variety of sources of interference during monitoring; 4) it is high cost restricts the availability of such equipment. Several monitors have prices ranging from £ 4,687 to £ 10,285 for the initial purchase, followed by the acquisition of single-use sensors ranging from £ 0.56 to £ 14.08. (3) Also, recent studies have pointed to substantial divergences between the most common commercial displays at DoA, making the application of these electronic devices still controversial and not universally recommended. 4 Specific limitations to the use of BIS, such as the inconsistency of this index in some situations, have also been reported. 6 BIS's particular challenge involves the administration of ketamine, nitric oxide, and xenon, which do not produce the typical EEG patterns observed during general anesthesia with other anesthetic agents. Besides, as the BIS was created based on a database of volunteers under specific conditions, it must be revalidated whenever used with a new drug or even a unique patient population, whose characteristics differ from the original population database data.7

Being tested
ECG and EEG monitoring
Keywords
general anesthesia, consciousness, heart rate variability, general anaesthesia monitors, computational analysis
Medical subject headings
Intraoperative Awareness

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ECG and EEG monitoringDevice

    the ECG and EEG will also be monitored during the entire period that the patients remain anesthetized with various anesthetics drugs and will later be used to compose the DoA score based on HRV.

Study groups in NCT04788732
Study groupRoleWhat they receive
1-Inhalation Anesthesiapatients in this group will be anesthetized only with an inhaled anesthetic ( Sevoflurane ).
Receives: Device: ECG and EEG monitoring
2-Total Intravenous Anesthesiathe patients in this group will be anesthetized with only intravenous drugs such as benzodiazepícos (midazolam), opioids (alfentanil, fentanyl, sufentanil, remifentanil), hypnotics ( propofol and etomidate ), associated or not to relaxing neuromuscular (nondepolarizing/depolarizing), and adjuvant drugs such as dextrocetamina, dexmedetomidine, lidocaine, and magnesium sulfate.
Receives: Device: ECG and EEG monitoring
3-Balanced anesthesiathe patients in this group will be anesthetized with blends of anesthetic inhaled (Sevoflurane) and intravenous drugs such as benzodiazepine (midazolam), opioids (alfentanil, fentanyl, sufentanil, remifentanil), hypnotics ( propofol and etomidate ), associated or not with neuromuscular relaxants (nonpolarizing/depolarizing) and adjuvant drugs such as dextrocetamine, dexmedetomidine, lidocaine, and magnesium sulfate.
Receives: Device: ECG and EEG monitoring

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To create a new Depth of Anesthesia (DoA) Score based on Heart Rate Variability indices

    Define a score capable of reflecting DoA, combining different indices derived from ECG, such as HRV.

    Measured: 12 months

Secondary outcomes (10)
  1. Impact of the differnet anesthetic drugs on the HRV indices (derived from ECG)

    Correlate HRV indices (derived from ECG) with the concentration and final consumption of anesthetic drugs throughout the anesthetic-surgical procedure.

    Measured: 12 months

  2. Impact of the anesthesia adjuvant drugs on the HRV indices (derived from ECG)

    Correlate HRV indices (derived from ECG) with the concentration and final consumption of adjuvant drugs (for example: lidocaine, dexmedetomedine, magnesium sulfate) throughout the anesthetic-surgical procedure.

    Measured: 12 months

  3. Time to wake up

    Correlate HRV indices (derived from ECG) with the time to wake up

    Measured: 12 months

  4. Time spent in PACU

    Correlate HRV indices (derived from ECG) with the time spent in PACU

    Measured: 12 months

  5. Aldrete score

    Correlate HRV indices (derived from ECG) with the Aldrete score

    Measured: 12 months

  6. Incidence of nausea and vomiting

    Correlate HRV indices (derived from ECG) with the incidence of postoperative nausea and vomiting, .

    Measured: 12 months

  7. Incidence of delirium

    Correlate HRV indices (derived from ECG) with the incidence of postoperative delirium

    Measured: 12 months

  8. Incidence of intraoperative memory.

    Correlate HRV indices (derived from ECG) with the incidence of intraoperative memory.

    Measured: 12 months

  9. Impact of frailty on the HRV indexes (derived from ECG)

    The impact of pre-anesthetic frailty (evaluated by the Clinical Frailty Scale) on ECG and EEG variables in the intraoperative period.

    Measured: 12 months

  10. Impact of the basal cognitive status on the HRV indexes (derived from ECG)

    The impact of the basal cognitive status on ECG and EEG variables in the intraoperative period.

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Mar 2021
  2. Study start4 Jan 2021
  3. Primary completion30 May 2022 (estimated)
  4. Study completion30 Aug 2022 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
200 participants (estimated)
Target duration
1 Year
IDs, dates and publications
ClinicalTrials.gov ID
NCT04788732
Sponsor's protocol ID
CAAE: 33066620.1.0000.5440
Status last verified
Mar 2021
First submitted
1 Mar 2021
Last updated
9 Mar 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Guignard B. Monitoring analgesia. Best Pract Res Clin Anaesthesiol. 2006 Mar;20(1):161-80. doi: 10.1016/j.bpa.2005.09.002.

    PubMed 16634423
  • Fahy BG, Chau DF. The Technology of Processed Electroencephalogram Monitoring Devices for Assessment of Depth of Anesthesia. Anesth Analg. 2018 Jan;126(1):111-117. doi: 10.1213/ANE.0000000000002331.

    PubMed 28786839
  • Smith A. Literature review: Awareness of anaesthesia. J Perioper Pract. 2017 Sep;27(9):191-195. doi: 10.1177/175045891702700903.

    PubMed 29328752
  • Merry AF, Cooper JB, Soyannwo O, Wilson IH, Eichhorn JH. International Standards for a Safe Practice of Anesthesia 2010. Can J Anaesth. 2010 Nov;57(11):1027-34. doi: 10.1007/s12630-010-9381-6. Epub 2010 Sep 21. No abstract available.

    PubMed 20857254
  • Shander A, Lobel GP, Mathews DM. Brain Monitoring and the Depth of Anesthesia: Another Goldilocks Dilemma. Anesth Analg. 2018 Feb;126(2):705-709. doi: 10.1213/ANE.0000000000002383. No abstract available.

    PubMed 28787338
  • Hajat Z, Ahmad N, Andrzejowski J. The role and limitations of EEG-based depth of anaesthesia monitoring in theatres and intensive care. Anaesthesia. 2017 Jan;72 Suppl 1:38-47. doi: 10.1111/anae.13739.

    PubMed 28044337
  • Kissin I. Depth of anesthesia and bispectral index monitoring. Anesth Analg. 2000 May;90(5):1114-7. doi: 10.1097/00000539-200005000-00021. No abstract available.

    PubMed 10781463

Questions about this trial

What is this clinical trial studying?

An observational study of Anesthesia Awareness, run by University of Sao Paulo at 1 site in Brazil.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 9 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Waynice N Paula-Garcia (+5516981154121, wgarcia@fmrp.usp.br), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To create a new Depth of Anesthesia (DoA) Score based on Heart Rate Variability indices (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04788732, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2021; AzTrials last refreshed its copy on 28 Oct 2026.

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