Tolerance to Miotic Effects of Opioids

Kollars, Joshua P.; Larson, Merlín D.

doi:10.1097/00000542-200503000-00047

Cited by 8 publications

(3 citation statements)

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“…Complicating this matter further, however, tolerance to the effects of opioids on the pupil does occur. 30 The effects of opioids on the pupillary dark re ex after brain injury may thus change over time (and perhaps with the etiology of the brain injury). Although we accounted for sedation in the statistical analysis, all these considerations must be addressed by replication studies with serial pupillary measurements of DoC cohorts with large enough numbers to account for the heterogeneity of sedation and brain injury etiologies.…”

Section: Discussionmentioning

confidence: 99%

The pupillary dark reflex in acute disorders of consciousness

Zarifkar,

Othman,

Hansen

et al. 2024

Preprint

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Background. In intensive care patients with disorders of consciousness (DoC), the pupillary light reflex is a measure of pupillary parasympathetic function. By contrast, the pupillary dark reflex leads to pupil dilation in response to darkness and primarily reflects the sympathetic function of the pupil. To our knowledge, this reflex has not been systematically investigated in DoC patients. We hypothesized that the pupillary dark reflex correlates with consciousness levels after acute brain injury, and that this correlation is not necessarily the same as that of the pupillary light reflex. Methods. From November 2022 to March 2023, we enrolled 100 study participants: 25 clinically unresponsive (coma or unresponsive wakefulness syndrome) and 25 clinically low-responsive (minimally conscious state or better) patients from the intensive care units of a tertiary referral center, and 50 age- and sex-matched healthy controls. Exclusion criteria were active or chronic eye disease. We used automated pupillometry to assess the pupillary dark reflex and the pupillary light reflex of both eyes under scotopic conditions in all study participants. Results. The pupillary dark reflex was strongly correlated with consciousness levels (r = 0.62, p < 0.001), the increase in pupillary diameters being smallest in unresponsive patients (mean ± SD: 20% ± 21%), followed by low-responsive patients (47% ± 26%) and healthy controls (67 % ± 17%; p < 0.001). Similar, yet less pronounced patterns were observed for the pupillary light reflex. Twenty-one of 25 unresponsive patients had preserved pupillary light reflexes, but only seven had preserved pupillary dark reflexes (p < 0.0001). Of these seven patients, five regained awareness. Conclusion. The pupillary dark reflex is more sensitive to consciousness levels after brain injury than the pupillary light reflex. The clinical implications of this finding seem worthy of further investigation, particularly regarding possible benefits for neuromonitoring and prognostication after brain injury.

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Section: Discussionmentioning

confidence: 99%

The pupillary dark reflex in acute disorders of consciousness

Zarifkar,

Othman,

Hansen

et al. 2024

Preprint

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“…As a consideration in patients receiving long-term opioids, tolerance to miotic effects can develop. 13…”

Section: Introductionmentioning

confidence: 99%

Effects of buprenorphine buccal film and oral oxycodone on pupil diameter in a respiratory study

Webster¹,

Cater²,

Smith³

2022

J of Opioid Management

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Objective: Evaluate the pupillary-constricting effects following administration of buprenorphine buccal film (BBF) and immediate-release (IR) oxycodone.Design: A double-blind, double-dummy, six-treatment, six-period, placebo-controlled, randomized crossover study.Setting: Single-center, phase 1 exploratory pharmacodynamics.Participants: Healthy individuals who self-identify as recreational opioid users, confirmed via a naloxone challenge test on day 1.Interventions: Placebo: BBF 300, 600, and 900 mcg and IR oxycodone 30 and 60 mg.Main outcome measure: Minute ventilation (measured by the ventilator response to hypercapnia) and pupil diameter (determined via standard pupillometry) were assessed predose and at 0.5, 1, 1.5, 2, 2.5, 3, and 4 hours post-dose. Results: Change from baseline in minute ventilation was moderately correlated with change from baseline in pupil diameter during treatment with BBF (Pearson's r = 0.38-0.40; p ≤ 0.0011) or oxycodone (Pearson's r = 0.34-0.37; p ≤ 0.005). The initial onset of significant (p 0.05) pupil constriction relative to placebo occurred at 2, 1.5, and 1 hour after dosing with BBF 300, 600, and 900 mcg, respectively, and at 0.5 hours after dosing with oxycodone 30 or 60 mg.Conclusions: Although BBF and IR oxycodone achieved similar levels of pupil constriction, there was a delayed miosis seen with BBF relative to that found with oxycodone.

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“…However, some claim that tolerance to the miotic effects of opioid agonists exists [10][11][12][13]. Clinicians treating cancer patients on high-dose opioids have also noticed that a few patients on high-dose opioids do not always present with small pupil size [14].…”

Section: Introductionmentioning

confidence: 99%

Dynamic assessment of the pupillary reflex in patients on high-dose opioids

Kongsgaard

Høiseth

2019

Scandinavian Journal of Pain

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Abstract 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.

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Tolerance to Miotic Effects of Opioids

Cited by 8 publications

References 0 publications

The pupillary dark reflex in acute disorders of consciousness

The pupillary dark reflex in acute disorders of consciousness

Effects of buprenorphine buccal film and oral oxycodone on pupil diameter in a respiratory study

Dynamic assessment of the pupillary reflex in patients on high-dose opioids

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