Pupillary reflex dilation in response to incremental nociceptive stimuli in patients receiving intravenous ketamine

J Clin Monit Comput. 2018 Oct;32(5):921-928. doi: 10.1007/s10877-017-0072-5. Epub 2017 Oct 17.


Pupillometry is a non-invasive monitoring technique, which allows dynamic pupillary diameter measurement by an infrared camera. Pupillary diameter increases in response to nociceptive stimuli. In patients anesthetized with propofol or volatile agents, the magnitude of this pupillary dilation is related to the intensity of the stimulus. Pupillary response to nociceptive stimuli has never been studied under ketamine anesthesia. Our objective was to describe pupillary reflex dilation after calibrated tetanic stimulations in patients receiving intravenous ketamine. After written consent, 24 patients of our pediatric burn care unit were included. They received an oral morphine premedication (0.3 mg kg-1) 1 h before their scheduled daily dressing change. Just before the procedure, they received 1 mg kg-1 of intravenous ketamine. Two minutes after this bolus, tetanic stimulations of incremental intensities were performed on the arm of each patient (5-10-20-30-40-60 mA, 60 s interval between stimulations). Pupillary diameter, heart rate and movements were recorded before and after each stimulation. Tetanic stimulations were associated with changes in pupillary diameter and heart rate. The magnitude of these changes was significantly influenced by the intensity of stimulation (ANOVA for repeated measures, p < 0.001). Movement was associated with a 32% increase in diameter (ROC curves, AUC 0.758) with 65% sensitivity and 77% specificity. In children, pupillary reflex dilation to nociceptive stimuli persists under deep sedation obtained with 1 mg kg-1 of intravenous ketamine combined with a 0.3 mg kg-1 oral morphine premedication, and its magnitude depends on the intensity of the stimulation. Our results confirm that pupillometry could be a relevant way to monitor nociception in anaesthetised subjects, including those receiving ketamine. Trial registration clinicaltrials.gov, NCT 02648412.

Keywords: Anesthesia; Ketamine; Monitoring; Nociception; Pain; Pupillometry.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Anesthesia, Intravenous
  • Anesthetics, Intravenous / administration & dosage*
  • Burn Units
  • Child
  • Child, Preschool
  • Electric Stimulation
  • Female
  • Humans
  • Infant
  • Ketamine / administration & dosage*
  • Male
  • Monitoring, Physiologic / methods*
  • Nociception / drug effects
  • Nociception / physiology
  • Pain Management / methods
  • Prospective Studies
  • Reflex, Pupillary / drug effects*
  • Reflex, Pupillary / physiology


  • Anesthetics, Intravenous
  • Ketamine