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Background and aims Pupil size and reaction are influenced by opioids, an effect that is not considered to be affected by opioid tolerance. As clinicians have observed patients on high-dose opioids who exhibited seemingly normal pupil sizes, we wanted to dynamically assess the pupillary reflex in cancer patients on high-dose opioids. Methods We performed a dynamic assessment of the pupillary reflex in cancer patients on high-dose opioids and a control group of healthy volunteers using a portable, monocular, infrared pupillometer. We also performed a clinical examination and measured blood concentrations of opioids and their active metabolites. Results Sixty three patients who were on opioids for 2 months (median time) and on an oral morphine equivalent dose of 250 mg (median dose) were investigated. Most patients used more than one opioid. When correcting for age, pupil size in the group that had received no increase of opioid dose over the last 14 days was not significantly different from pupil size in the healthy volunteer group (p = 0.76), while the group that had increased the dose of opioids differed significantly from healthy volunteers (p = 0.006). We found no statistically significant correlation between total oral morphine equivalents and pupillary reactions or between blood opioid or opioid metabolite concentrations and baseline pupillary changes. Conclusion Pupillary changes do take place in patients on opioids. However, tolerance to these changes occurs when medication is not increased over time. Dynamic pupillometry can give additional information about the degree of tolerance to opioids. Implications These findings elucidate previous misconceptions regarding pupillary effects and tolerance to opioids.

Titel:	Dynamic assessment of the pupillary reflex in patients on high-dose opioids.
Autor/in / Beteiligte Person:	Kongsgaard, UE ; Høiseth, G
Zeitschrift:	Scandinavian journal of pain, Jg. 19 (2019-07-26), Heft 3, S. 465-471
Veröffentlichung:	2018- : [Berlin] : De Gruyter ; <i>Original Publication</i>: [Maryland Heights, MO] : Elsevier Science, c2010-, 2019
Medientyp:	academicJournal
ISSN:	1877-8879 (electronic)
DOI:	10.1515/sjpain-2019-0032
Schlagwort:	Drug Tolerance Female Humans Male Middle Aged Neoplasms blood Norway Analgesics, Opioid administration & dosage Morphine administration & dosage Neoplasms drug therapy Reflex, Pupillary drug effects
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Scand J Pain] 2019 Jul 26; Vol. 19 (3), pp. 465-471. MeSH Terms: Analgesics, Opioid / administration & dosage ; Morphine / administration & dosage ; Neoplasms / drug therapy ; Reflex, Pupillary / drug effects ; Drug Tolerance ; Female ; Humans ; Male ; Middle Aged ; Neoplasms / blood ; Norway References: Mitra S, Sinatra RS. Perioperative management of acute pain in the opioid-dependent patient. Anesthesiology 2004;101:212–27. ; Freye E, Latasch L. [Development of opioid tolerance – molecular mechanisms and clinical consequences]. Anasthesiol Intensivmed Notfallmed Schmerzther 2003;38:14–26. ; Gustin H, Akil H. Opioids analgesics. Hardman J, Limbird L, editors. New York: McGraw-Hill, 2001. ; Jaffe J, Martin W. Opioid analgesics and antagonists. In: Goodm L, Gilman A, editors. 6th ed. 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Dynamic assessment of the pupillary reflex in patients on high-dose opioids.