Evaluation of the Nociception Guided by NoL Index and PK of Fentanyl in Pediatric Patients Under General Anesthesia
Condition: Pain; Anesthesia; Pediatric ALL
Study type: Observational

Summary: 
      Fentanyl is one of the most common used opioids for analgesia during general anesthesia,
      however there are few studies that describe the relationship between its pharmacokinetics and
      pharmacodynamics, especially in the pediatric population. The monitoring of the analgesia
      component during general anesthesia has been traditionally by changes in patient's vital
      signs, with new devices that measure nociceptive indexes like the Nociception level (NoL)
      index currently being validated for adults. There is still lacking evidence with nociceptive
      indexes in the pediatric population.

      Insufficient dose of opioids may cause sympathetic response, respiratory complications,
      development of persistent post-surgical pain and even prolonged hospitalization. In the other
      hand, and overdose of opioids may cause over sedation, postoperatory nausea and vomiting,
      respiratory depression, hyperalgesia and tolerance.

      Given the lack of evidence on the Pharmacokinetic and pharmacodynamic (PK/PD) of fentanyl in
      this group of patients, has led to raise the development of this observational prospective
      study; which is to describe a PK/PD model of fentanyl in pediatric population, through
      evaluation of the NoL index, in patients submitted to elective general non-cardiac surgery.
    

Detailed description: 
      Patients will be invited to participate before surgery, the inclusion criteria will be
      revised and the informed consent will be signed by one of the parents or legal tutor.

      In the operating room will be recorded demographic data and relevant background such as: Age,
      Weight, Size, BMI.

      Afterwards, in the operating room, the patient will be monitored regularly: EKG, pulse
      oximetry, non invasive blood pressure.

      Induction of anesthesia with sevoflurane 6% in 100% oxygen, once loss of consciousness, 2
      peripheral IV lines will be installed, one for medication and the other in the contralateral
      arm for blood samples. After that, a laryngeal mask device (LMA) appropriate for the weight
      for the management of the airway. In addition, the EEG will be monitored through a frontal
      electroencephalographic monitoring (BIS) system and a NoL index sensor, both of which will be
      recorded throughout the surgery.

      Once all monitors are installed, a caudal block with 0,5-1 ml of bupivacaine 0,25% will be
      performed, in the left decubitus lateral position. Ventilator and vaporizer adjustments for
      an EtCO2 of 35-40 mmHg and a BIS index of 50-60 with Sevoflurane. After 12 minutes, because
      of the latency of caudal block; surgeons may start. If an effective caudal block is proven,
      the study will continue; if there is movement of the child, laryngospasm or an increase of
      more than 10% in the base values of heart rate or blood pressure, the patient will be
      excluded from the study.

      Standardized nociceptive stimulus will be administered through a tetanic stimulus (70 Hz, 80
      mA) for 5 seconds in the forearm. An initial tetanic stimulus will be performed, 2 minutes
      afterwards a unique dose of fentanyl of 2 micrograms per kg will be administered. New tetanic
      stimulus will be applied at 5, 15, 30 and 45 minutes after the fentanyl dose and blood
      samples for fentanyl plasmatic levels will be taken at the same time in the operating room
      and at 75 or 120 minutes in the post anesthesia care unit (PACU). NoL index values will be
      recorded after each tetanic stimulus.

      After surgery, sevoflurane will be discontinued, LMA removed and the patients transferred to
      the PACU. Pain scores will be evaluated in the PACU using Visual analogue scale. Analgesic
      management with NSAIDs and Acetaminophen.

      PK/PD profile of fentanyl will be evaluated with NONMEM (non-linear mixed effects modelling)
      software for the analysis.
    

Intervention name(s): Fentanyl; Tetanic stimulation
Intervention type(s): Drug; Other
Intervention description(s): Standard dose of 2 ug/kg after tetanic stimulation.; Standard tetanic stimulation will be used as the stimulus to evaluate response of the intraoperative pain index (NoL) at a standard fentanyl dose.
Intervention MeSH terms: Fentanyl
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        ASA I or II children from 3 up to 10 years requiring elective non-cardiac surgery, under
        general anesthesia and caudal block.
      
Keywords: NoL; Nociception level; Fentanyl; Pediatric anesthesia; Pharmacokinetics