A study involving a specially modified pupillometer has shown a correlation between pupillary unrest under ambient light (PUAL) and pain response to opioid medications, suggesting that this instrument could one day help physicians determine the risk/benefit of giving patients additional opioids.
“In this study, decreased levels of pupillary unrest were associated with decreased responsiveness to opioids as measured by changes in pain scores,” said Andrew Neice, MD, assistant professor of anesthesiology at Oregon Health & Science University in Portland. “Because pupillary unrest is a quick and noninvasive measure that is well tolerated by patients, this test might potentially be used to guide treatment of pain when the provider is choosing between opioid and nonopioid treatments.”
As Dr. Neice reported at the 2015 annual meeting of the American Society of Anesthesiologists (ASA; abstract A4010), opioids have been shown to markedly decrease PUAL. However, patients with PUAL levels that are similar to preoperative values have little evidence of systemic opioid effect and therefore may be more responsive to opioid pain medicine than those with diminished PUAL.
For this study, Dr. Neice and his colleagues enrolled 21 patients (15 males, six females) with ASA physical status I or II, undergoing arthroscopic knee surgery, followed by an additional 16 patients (eight males, eight females) at a different site. PUAL scores were taken upon arrival in the PACU. After surgery, changes in numeric rating system (NRS) pain scores after opioid administration were measured, along with preadministration PUAL. The researchers then attempted to correlate PUAL with change in NRS score from first dose of opioid, change in NRS score from each individual dose of opioid and overall change in NRS score after opioid treatment.
“We essentially had three data sets: how well pupillary unrest correlates with how well opioids work overall, regardless of how much a patient receives; how well the first dose works upon arrival in the PACU; and then, how well each individual dose works as a patient is recovering in the PACU,” Dr. Neice explained.
Higher Unrest Suggests Better Response
As Dr. Neice reported, all three changes correlated reasonably well with pain score change and were statistically significant (P=0.02, 0.005, 0.01, respectively).
“In this relatively homogeneous patient population,” said Dr. Neice, “we were able to correlate pupillary unrest with the efficacy of opioid treatment; patients with higher pupillary unrest tended to respond better to pain medicines.”
According to Dr. Neice, these results could not be explained by obvious confounders. Researchers observed little to no correlations between PUAL and initial pain scores as well as little to no correlation between initial PUAL and total opioid dose administered. For example, when only data points corresponding to 100 mcg of fentanyl were used, preadministration PUAL was still strongly correlated with effectiveness as measured by change in NRS score (R2=0.54;P=0.016).
“We would like to repeat these studies using a different class of pain medicines to get a sense of whether this is an opioid-specific effect or simply related to analgesics in general. At this point we don’t know,” Dr. Neice concluded. “Although they were not part of the study, we have seen patients with very little pupillary unrest that had significant pain relief from regional techniques, so our sense is that this appears to be an opioid-only effect.”
Pupil size also was measured at the same time as pupillary unrest. Although there was a slight correlation between pupil size and patient response to opioid medications, with these sample sizes, said Dr. Neice, the effect was not statistically significant.
Expert Commentary
The moderator of the session, John F. Butterworth IV, MD, professor and chairman of the Department of Anesthesiology at Virginia Commonwealth University Medical Center in Richmond, said an objective, physiologic measure of analgesia would be useful because there are times—with young children or very sick patients, for example—when effectiveness is difficult to quantify.
“It would be nice to know that by this physiological measurement, we’ve given [patients] enough analgesia to be comfortable,” said Dr. Butterworth.
Despite the theoretical utility of this instrument, however, Dr. Butterworth found certain features of the study lacking.
“If you wanted to provide convincing scientific evidence that a change in the pupils was due to analgesia as opposed to just an opioid, it would be very important to study that response with other drugs—for example, ketorolac, which is a nonsteroidal anti-inflammatory). … Because then, if you saw the same effect, you wouldn’t think it was just an opioid dosing effect,” Dr. Butterworth concluded.
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