BIS Monitoring of the Depth of Anaesthesia in Children
Condition: General Surgery; Anaesthesia
Study type: Interventional

Summary: 
      General anaesthesia (GA) is, according to many definitions, the greatest gift presented to
      the medical art (S. B. Nuland). One of the aims of GA is to achieve the optimal depth of
      anaesthesia and rapid emergence from general anaesthesia. In order to achieve this goal, it
      is necessary to observe the clinical condition of the patient, and at the same time monitor
      the patient's overall condition. With the currently available options of GA management (e.g.
      use of intravenous anaesthetics, strong analgesics and modern volatile anaesthetics, in
      combination with various methods of topical anaesthesia) the importance of methods measuring
      the depth of GA increases. The depth of GA may be defined as a continuous progressive
      decreasing of the central nervous system, together with a decreased reactivity to stimuli. In
      the course of GA, perioperative awareness is detected in 0.1-0.2% of cases. Awakening during
      a surgical procedure may result in significant psychological complications (e.g.
      post-traumatic stress disorder), and the patient may suffer from a serious long-time
      disorder.
    

Detailed description: 
      In order to prevent, or minimize the perioperative awareness, it is possible to utilize two
      different methods of depth of anaesthesia monitoring. The options may be divided into two
      basic groups: A/ The use of clinical monitoring and other methods (apart from CNS), and B/
      Methods based on monitoring of the electrical activity of the brain. In the first group, it
      is possible to list the following options: 1. clinical assessment (Evans's score), 2. skin
      conductance, 3. isolated method of measurement at the forearm, 4. spontaneous superficial
      electromyogram (SEMG), 5. lower oesophageal contractility, and 6. various hearth rate. The
      possibilities of depth of GA monitoring using the scanning of electrical brain activity may
      be further subdivided into two groups: a/ methods based on EEG, and b/ methods assessing
      evoked potentials. In the group of methods based on EEG, the following devices may be used to
      monitor the depth of GA in practice:

      a/ BIS monitor, b/ E-Entropy, c/ Narcotrend, and d/ SedLine Sedation Monitor. In the second
      group using evoked potentials it is possible to utilize monitors measuring electrical
      activity in certain areas of the brain, in relation to stimulation of specific sensory nerve
      pathways: a/ somatosensory, b/ visual, and c/ auditive evoked potentials.

      Aims of the Study:

      Null hypothesis: The use of depth of general anaesthesia monitoring in children in the course
      of a surgical procedure does not affect the number of post-operative complications related to
      the depth of GA, does not shorten the period of emergence from GA, does not decrease the
      amount of inhalation anaesthetics used, and does not decrease the amount of opioids used.

      Primary aim: To test, whether the administration of anaesthesia in children in the course of
      a surgical procedure with the depth of general anaesthesia monitoring with the BIS monitor
      results in a decrease in the number of complications related to inappropriate depth of GA.

      Secondary aim: To verify, whether the administration of anaesthesia in children in the course
      of a surgical procedure with the depth of general anaesthesia monitoring with the BIS
      monitor:

        1. results in a shortening of the emergence from general anaesthesia

        2. results in a decrease in the amount of inhalation anaesthetic used

        3. results in a decrease in the amount of analgesics used

      Tertiary aim: To verify, whether the administration of general anaesthesia in children in the
      course of a surgical procedure with the depth of general anaesthesia monitoring with the BIS
      monitor:

      a/results in a decrease of early post-operative complications at the recovery room.

      Study design:

      Procedure to achieve the study aims The study is a prospective, interventional study,
      performed at the Anaesthesiology-Resuscitation Department of the University Hospital Ostrava.
      The study has been approved by the Head of the Department, prof. Pavel Ševčík, MD, CSc.
      Furthermore, the study has been approved by the Ethics Committee of the University Hospital
      Ostrava and is in compliance with the principles of the Declaration of Helsinki. Informed
      consent will be obtained for every paediatric patient, the Informed consent form has also
      been approved by the Ethics Committee, and will be signed by both parents.

      The study group will include paediatric patients at the age from 28 days to 15 years of age
      (including), ASA I classification.

      Interventional arm of the study will be characterized by the BIS monitoring and management of
      the hypnotic component of general anaesthesia towards the values of BIS 40-60.

      Conventional arm of the study will be performed without the depth of anaesthesia monitoring
      (however, the BIS value will be recorded by an independent participant), and management of
      the hypnotic component of general anaesthesia according to MAC value appropriate for the age
      of the child.

      Each study arm will include the total of 100 paediatric study subjects. Randomization will be
      performed by the envelope method.

      Definition of terms

        -  BIS group: group of patients, in whom the hypnotic component of GA will be managed
           towards the value of BIS 40-60.

        -  Non-BIS group: group of patients, in whom the hypnotic component of GA will be managed
           towards the MAC value appropriate for the age of the child. Depth of GA will be also
           monitored with the BIS monitor, however, the BIS value will be unknown to the
           investigator.

        -  Period of emergence from anaesthesia: time interval from the moment of setting the zero
           concentration of inhalation anaesthetics on the vaporizer to the moment when the child
           manifests the signs of complete awareness: spontaneous ventilation, spontaneous
           motility, rising of the head, clasping of the hand, or crying.

        -  Consumption of inhalation anaesthetic: consumption of inhalation anaesthetic will be
           measured in two follow-up time phases of GA:

             1. Phase 1: from the moment when administration of the inhalation anaesthetic is
                initiated to the moment when breathing passageways are secured (LM, OTI). This
                phase of GA is characterized with a higher concentration of the inhalation
                anaesthetic and standard flows: O2, AIR in proportion of 2:2 l/min,

             2. Phase 2: continues after Phase 1, from the moment when breathing passageways are
                secured to the moment, when the zero value is set on the vaporizer. This phase of
                GA is characterized with gas flows: O2, AIR in proportion of 0.5:0.5 l/min.

        -  Consumption of analgesics: the amount of analgesics used during GA

        -  Early post-operative complications (assessed in the recovery room): the need of
           re-intubation, need to apply antidotes, laryngospasm, bronchospasm, hyperalgesia (pain
           assessment according to standard scales), vomiting

        -  Emergence from GA (Phase 3): continues after Phase 2, from the moment when the zero
           value is set on the vaporizer to the moment of LM or intubation cannula removal.

      5.2.2. Protocol of GA management in the "BIS group": BIS monitor will be used during the GA
      monitoring, the BIS value will be known to the anaesthetist (investigator)

        -  GA induction (Phase 1):

             1. inhalation introduction (Sevorane, 02,AIR (flow 2:2 l/min)) or

             2. intra-venous introduction: (Suphentanil: (0.1-0.3 ug/kg iv.), Propofol (2-2,5 mg/kg
                iv.), or Mivacron (0.15-2mg/kg ),Tracrium (0.3-0.6mg/kg)

        -  anaesthesia (Phase 2, Phase 3):

             1. hypnotic component: titration of Sevorane concentration, with the aim of achieving
                the BIS values of 40-60%, bearing gas mixture: O2/AIR (in proportion of 1:1, with
                0.5:0.5 flows)

             2. analgesic component: Suphentanil (continuous dose of 0.1-0.3ug/kg iv. every 20-30
                min)

             3. relaxation: Mivacron (continuous dose of 0.1mg/kg iv.), Tracrium(0.3-0.6 mg/kg)
                5.2.3. Protocol of GA management in the "Non-BIS group" BIS monitor will be used
                during the GA monitoring, however the BIS value will not be known to the
                anaesthetist (investigator)

        -  GA induction (Phase 1):

             1. inhalation introduction (Sevorane, 02,AIR (flow 2:2 l/min)) or

             2. intra-venous introduction: (Suphentanil: (0.1-0.3 ug/kg iv.), Propofol (2-2,5 mg/kg
                iv.), or Mivacron (0.15-2mg/kg ),Tracrium (0.3-0.6mg/kg)

        -  anaesthesia (Phase 2, Phase 3):

             1. hypnotic component: titration of Sevorane concentration, with the aim of achieving
                the MAC value appropriate for the age of the child, bearing gas mixture: O2/AIR (in
                proportion of 1:1, with 0.5:0.5 flows)

             2. analgesic component: Suphentanil (continuous dose of 0.1-0.3ug/kg iv. every 20-30
                min)

             3. relaxation: Mivacron (continuous dose of 0.1mg/kg iv.), Tracrium(0.3-0.6 mg/kg)

      Assessment:

      The following parameters will be observed in the "BIS group" and the "Non-BIS group":

        -  occurrence of perioperative complications

        -  period of emergence from GA

        -  consumption of opioids

        -  consumption of inhalation anaesthetic

        -  occurrence of early post-operative complications at the recovery room

        -  BIS value

      Statistical processing:

      The obtained statistical data will be processed using statistical methods and presented in
      the form of tables and charts.
    

Intervention name(s): BIS Group; Non-BIS Group; Anaesthetics
Intervention type(s): Procedure; Procedure; Drug
Intervention description(s): BIS monitoring will be used in the BIS Group patients. The BIS value will be known to the anaesthetist, who will be able to act accordingly.; BIS monitoring will be used in the Non-BIS Group patients. The BIS value will NOT be known to the anaesthetist and will be observed by a trained co-investigator, with subsequent evaluation.; Anaesthetics will be administered in both experimental groups, in order to maintain the required general anaesthesia.
Intervention MeSH terms: Anesthetics
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: General Surgery; Child; Anaesthesia; Depth of anaesthesia; BIS monitoring