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Updated: Mar 10, 2026
Objective Nociceptive Assessment in Ventilated ICU Patients: A Feasibility Study Using Pupillometry and the Nociceptive Flexion Reflex
Published on: July 4, 2018
Prediction of Opioid Analgesic Efficacy by Measurement of Pupillary Unrest
Andrew E Neice1, Matthias Behrends, Michael P Bokoch
1From the *Department of Anesthesia, Oregon Health and Science University, Portland, Oregon; †Department of Anesthesia and Perioperative Care, University of California, San Francisco, California; ‡Department of Anesthesiology and Critical Care Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico; and §Department of Anesthesiology, University of North Carolina, Chapel Hill, North Carolina.
Background:
Pupillary unrest under ambient light (PUAL) is the fluctuation in pupil diameter in time around a mean value. PUAL is augmented by light and diminished by administration of opioids. We hypothesized that, because pupillary unrest is a marker of opioid effect, low levels of PUAL may be associated with reduced opioid efficacy, as measured by changes in the numerical rating scale (NRS) pain scores of patients in the postanesthesia care unit (PACU).
Methods:
We used an infrared pupillometer to measure PUAL in patients recovering from ambulatory surgery at 2 different institutions. At both sites, PUAL was quantified using spectral analysis of the Fourier transform of pupil diameter versus time. We measured PUAL and pain scores before and after opioid administration. Protocols for total capture time and lighting conditions varied between the 2 sites. Correlations between PUAL and change in NRS scores were examined using significance testing of Pearson correlation coefficients. Correlations between change in PUAL and change in NRS scores were also examined. Patients were divided into high and low PUAL groups, and high and low response to opioid. A Fisher exact test was used to determine whether there was a significant association between PUAL and opioid response.
Results:
For patients with pain in the PACU, low levels of pupillary unrest before opioid therapy were associated with minimal or no reduction in pain scores after opioid administration. We noted a significant correlation at both sites between PUAL and pain score reduction with opioids (r = 0.59, P = .0053, and r = 0.57, P = .022.) The Fisher exact test confirmed that patients with PUAL levels above the mean had a more beneficial analgesic effect from opioids than those with low PUAL levels (P = .018). We also noted that change in PUAL was significantly correlated with change in pain score at both sites (r = 0.56, P = .03 and r = 0.55, P = .01).
Conclusions:
We observe that the pretreatment magnitude of PUAL is correlated with the analgesic response to opioid therapy, and that patients who exhibit higher levels of PUAL change after opioid administration have a more beneficial analgesic effect from opioids. Larger studies with uniform measurement protocols are required to confirm these preliminary results.
