Frontal Electroencephalography of Neonatal Patients Under Sedation With Opioids and General Anesthesia With Propofol.
Condition: Anesthesia; Surgery; Neonate; Depth of Anesthesia
Study type: Interventional

Summary: 
      Frequently, neonates hospitalized in neonatology units require anesthesia for surgery. The
      drugs used for this purpose are opioids and other anesthetics, such as propofol.

      Currently, the administration of anesthesia is difficult in neonates due to the neurological
      immaturity of these patients, the scarcity of adequate pharmacological studies, the prolonged
      use of one or more sedatives prior to surgery and the limited usefulness of current
      anesthetic monitoring devices in this population.

      Electroencephalography (EEG), which has allowed estimation of anesthetic depth in other
      populations, has been less explored in neonates. To date, there are no EEG markers,
      correlated with a given dose of anesthesia, that allow an adequate administration in this
      kind of patients. In this context, a better understanding of the anesthetic effect in the
      neonatal brain would allow defining characteristic EEG patterns, improving the estimation of
      anesthetic depth and anesthetic dosage in neonates.
    

Detailed description: 
      As a consequence of the cerebral immaturity of newborns (1,2), together with the fact that in
      the NICU it is common to find patients requiring surgery who are sedated with multiple drugs,
      it is necessary to define characteristic EEG patterns that allow estimation of the anesthetic
      depth and adequate dosage of anesthetics, avoiding the the risk of under- or overdosing of
      anesthetics (3).

      The investigators will conduct an exploratory study. The aim of the study is to determine, by
      frontal electroencephalography, markers of brain electrical activity associated with the
      administration of propofol in term newborns requiring surgery in the NICU. A sample of 20
      term neonatal patients admitted to the NICU UC with a diagnosis of surgical pathology will be
      included.

      General objective:

      To describe the characteristics of the frontal electroencephalographic pattern associated
      with increasing doses of propofol, in term neonates, requiring surgery in the NICU and its
      correlation with a clinical response, to the surgical stimulus.

      Specific objectives:

        -  Identify the association between electroencephalographic parameters and different levels
           of sedation prior to surgery.

        -  To identify the association between electroencephalographic parameters and increasing
           doses (plasma concentration) of propofol administered in a previously sedated patient.

        -  To relate the clinical response observed to the surgical stimulus and increasing doses
           (plasma concentration) of propofol in a previously sedated patient (dose (concentration)
           - response curve).

        -  To describe the temporal profile of propofol anesthesia, based on the changes in
           electroencephalographic parameters observed over time, during the period of
           administration and suspension of the anesthetic.

      On the scheduled day of surgery in the NICU and prior to anesthetic induction, in sedated and
      standardly monitored patients (ECG, SpO2, PAI, temperature, diuresis). A four-channel
      SedLine® monitor (Masimo Corporation, Irvine, CA, USA) will be used to monitor frontal brain
      electrical activity 10 minutes before the induction of anesthesia. At the end of this period,
      the level of sedation will be evaluated with the N-PASS clinical scale (4) and the types,
      doses and duration of sedative drugs administered up to that time will be recorded. Then,
      patients will be randomized into 4 groups, of 5 patients each, to receive manual total
      intravenous anesthesia, with different propofol infusion rates: Group 1, Propofol 2.0
      mg/kg/hr; Group 2, Propofol 4.0 mg/kg/hr; Group 3, Propofol 6.0 mg/kg/hr; Group 4, Propofol
      8.0 mg/kg/hrs. At 10 and 20 minutes after the start of the propofol infusion, arterial blood
      samples will be taken to determine the plasma concentration of propofol reached during the
      anesthetic induction. In case of hemodynamic alteration (heart rate and/or blood pressure
      drop by 20%) during the propofol infusion, a 25% decrease of the original dose will be
      performed. At the end of this period, surgery will be initiated. The hemodynamic and motor
      response to the surgical stimulus will be observed and recorded. If there is hemodynamic
      response (increase in heart rate and/or blood pressure by 20%) and/or motor response, after
      the surgical stimulus, fentanyl rescue 5 mcg/kg/iv will be administered. Subsequent
      anesthesia will be in the hands of the treating anesthesiologist in the doses and forms
      he/she deems convenient. Electroencephalographic tracing will be maintained continuously
      throughout the procedure (from 10 minutes before and up to 10 minutes after surgery). Changes
      and adjustments to the anesthesia and analgesia given, hemodynamic changes occurring during
      the procedure and anesthetic and surgical times will be recorded.
    

Intervention name(s): Propofol Group 1; Propofol Group 2; Propofol Group 3; Propofol Group 4
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Propofol 2.0 mg/kg/hr per 10 min; Propofol 4.0 mg/kg/hr per 10 min; Propofol 6.0 mg/kg/hr per 10 min; Propofol 8.0 mg/kg/hr per 10 min
Other intervention name(s): Group 1; Group 2; Group 3; Group 4
Intervention MeSH terms: Propofol
Allocation: Randomized
Intervention model: Factorial Assignment
Intervention model description: Patients will be randomized into 4 groups, of 5 patients each, to receive total intravenous anesthesia, with different propofol induction infusion rates: Group 1 (Propofol 2.0 mg/kg/hr); Group 2 (Propofol 4.0 mg/kg/hr); Group 3 (Propofol 6.0 mg/kg/hr); Group 4 (Propofol 8.0 mg/kg/hr).
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Diagnostic
Keywords: propofol; neonate; deph of anesthesia; Electroencephalography; surgery