The heart rate variability-derived Newborn Infant Parasympathetic Evaluation (NIPE™) Index in pediatric surgical patients from 0 to 2 years under sevoflurane anesthesia-A prospective observational pilot study

Paediatr Anaesth. 2019 Apr;29(4):377-384. doi: 10.1111/pan.13613. Epub 2019 Mar 21.


Background: The heart rate variability-derived Newborn Infant Parasympathetic Evaluation (NIPE™) Index is a continuous noninvasive tool to assess pain and discomfort in infants <2 years. Initial studies focused on pain monitoring in the neonatal intensive care unit environment.

Aims: The aim of this study was to investigate the performance of the NIPE in infants under sevoflurane anesthesia. The primary objective of this study was to compare the NIPE and heart rate as tools to help recognize the need for additional opioid drugs. Secondary objectives were the course of the NIPE and heart rate around specific standardized noxious procedural mile-stones.

Methods: NIPE and heart rate values recorded during a 120 seconds interval before the anesthetist's decision to administer additional opioid due to the perceived insufficient antinociception and during a 120 seconds interval after drug administration were analyzed by means of a repeated measures ANOVA. The same analyses were performed for datasets around per protocol administration of morphine for postoperative analgesia, performance of a caudal block and surgical incision.

Results: In patients with a NIPE value <50, an additional opioid drug administration resulted in a rise of NIPE values, reaching a maximum increase of 5.1 (95% CI: 0.22-9.99) units 120 seconds after drug administration (P = 0.041). There was no evidence of a change in heart rate during these two 120 seconds periods. Per protocol administration of morphine, caudal block, and surgical incision did not result in changes of the NIPE, which was around 65 units on these occasions, and heart rate.

Conclusion: In infants anesthetized with sevoflurane, NIPE values <50 might be indicative of insufficient antinociception. The results of this observational pilot study might suggest that the NIPE could be a better measure of the nociception/antinociception balance than heart rate.

Keywords: general anesthesia; infant; monitors; pain.

Publication types

  • Observational Study

MeSH terms

  • Analgesics, Opioid / administration & dosage
  • Anesthesia, Inhalation / methods
  • Anesthetics, Inhalation / administration & dosage*
  • Female
  • Heart Rate / drug effects*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Morphine / administration & dosage
  • Nerve Block / methods
  • Pain Measurement
  • Parasympathetic Nervous System / drug effects*
  • Pilot Projects
  • Prospective Studies
  • Sevoflurane / administration & dosage*


  • Analgesics, Opioid
  • Anesthetics, Inhalation
  • Sevoflurane
  • Morphine