According to the CDC, opioid prescriptions in the United States have more than tripled from 1999-2014, which has correlated with the staggering increase in opioid-involved drug overdose deaths. This pattern of prescription is thought to be a major contributory factor to the increase in drug overdose in America, as four out of five new heroin users started by misusing prescription painkillers. Providers need the means to objectively monitor analgesic efficacy of treatment in patients with pain to mitigate unnecessary analgesic prescribing.
It is well established that mu opioid agonists like morphine cause miosis, an effect to which tolerance does not occur. This suggests a utility in using pupil size and responsiveness as a pharmacokinetic analogue of bioavailability. An infrared pupillometer is a device that produces a short light stimulus and subsequently measures parameters of the pupillary light reflex (PLR) including maximum and minimum pupil size (MAX, MIN), maximum constriction velocity (MCV), latency period before constriction onset (LAT), change in pupil size (DELTA), and average constriction velocity (ACV). Current data supports the efficacy of using infrared pupillometry to detect high dose opioid presence, but no research exists judging its efficacy in monitoring low dose therapeutic levels.
We enrolled 15 patients between the ages of 7 and 18 on the pain medicine service receiving low dose opioids on patient controlled analgesia (PCA). The pupillometer was used to take a baseline PLR, and repeated measures were taken 10 and 15-minutes post PCA dose infusion.
We found that the pupil size at 10 and 15-minute time points were significantly smaller than the baseline for the parameters MAX (p=.0016, p=.0010) and MIN (p=.0250, p=.0070). Additionally, it was found that LAT was significantly longer from baseline at the 15-minute measure (p=.0350), and there was a significant difference between the 10 and 15-minute time points for the MIN (p=0.0251).
This evidence supports the sensitivity of the pupillometer in evaluating opioid activity. Furthermore, in concordance with previous research, the MIN is significantly correlated with opioid concentration dose-dependently across the 15-minute measurement window.
Before applying the pupillometer to clinical pain medicine, more research comparing pupillometric parameters with blood levels of opioid metabolites will serve to determine detection limits. Providers could use this tool to monitor treatment efficacy by using these parameters to assess steady state equilibrium and to determine dosing intervals. Furthermore, the pupillometric parameters could elucidate individuals’ metabolic capacity for different opioids in order to prescribe therapeutic levels