Pupillometry for Pain Assessment in Paediatric Patients
Pupillometry for Pain Assessment in Paediatric Patients
We found statistically significant associations between self-reported pain intensity and several measures of pupillary response in children who were evaluated after a uniform, painful surgical procedure. Of the associations tested, the relationship between maximum pupillary constriction velocity and VAS pain intensity (figure 1) provided the best surrogate for quantitating pain intensity in children.
Expressing pupillary function as a percentage (increase) in pupil constriction functionally provides a measure of maximum effect (Emax) for a given observation (figure 2). This 'ceiling' could potentially be impacted by differences in the concentration versus effect profile for agents used to manage pain (eg, opioids, clonidine, ropivacaine, lidocaine) in our cohort. This is especially pertinent to the use of clonidine, a centrally acting α2 adrenergic agonist which has been shown to have pupillary effects. Maximum constriction velocity on the other hand is a dynamic parameter, which reflects how efficiently the pupil responds to a given stimulus. Given that an increase of 2 or more on the 0–10 VAS scale is associated with a clinically significant change in pain intensity, an observed change in maximal pupil constriction velocity of ≥0.22 mm/sec could be used to guide intervention to optimise pain management. It could also provide an objective surrogate to aid in the differentiation of pain perception versus actual pain intensity. Finally, it is important to recognise that either maximal constriction velocity or the per cent of pupil constriction is dependent upon the baseline status of the pupil, as illustrated by our finding of a significant correlation between maximum constriction velocity and resting pupil diameter. This caveat does not limit the utility of pupillometry, especially when maximum constriction velocity is used as the surrogate end point.
The association between daily drug dose (expressed as morphine equivalents) and pupil size (figure 3) was expected. Nonetheless, controlling for opioid effect in HLM analyses, we were able to demonstrate the independent effect of pain on pupillary response. However, further research is needed to support the use of pupil size as a predictor of analgesic dose requirement given potential confounders in our uncontrolled study (eg, different drug combinations including non-opioid compounds).
Our findings are consistent with previous studies that have examined pupillometry with traditional physiological surrogates of pain assessment in adults and children. Barvais et al compared pupil response with arterial pressure, heart rate and bispectral index (BIS) variations following a painful stimulus in healthy adult patients receiving propofol and remifentanil. They found that in response to a noxious stimulus, pupil dilatation was more sensitive and better correlated with opioid concentrations than heart rate, blood pressure and BIS monitoring. In a similar study performed in anaesthetised children, Constant et al compared changes in pupil diameter with heart rate, blood pressure and BIS monitor variation in response to a skin incision on the lower limb. Similar to the adult data, these investigators were able to show that the change in pupil diameter had a greater effect size than BIS variation or haemodynamic markers.
While precise pupil measurements and subjective pain assessment have not been previously compared in children, Aissou et al performed a study in 100 adults comparing changes in the pupil dilatation reflex and self-reported pain scores via a 5-point verbal rating scale. Shortly after extubation, patients receiving intravenous morphine in a postoperative setting had their pupil size monitored and recorded for 10 s during a standardised stimulus of constant pressure (200 kPa) within 2–3 cm from their skin incision. A statistically significant relationship was observed between the VAS and maximum pupil diameter, as well as a threshold of per cent change in pupil diameter in patients who required additional doses of morphine.
As with all physiological surrogates, pupillometry does have limitations. These include the lack of specificity of the pupil dilatation reflex in response to pain and clinical situations in which a patient is in pain but has constricted pupils. Also, as our study enrolled verbal, cognitively appropriate participants capable of self-reporting pain, additional research is needed to generalise findings to non-verbal patients or those with significant cognitive impairment.
Discussion
We found statistically significant associations between self-reported pain intensity and several measures of pupillary response in children who were evaluated after a uniform, painful surgical procedure. Of the associations tested, the relationship between maximum pupillary constriction velocity and VAS pain intensity (figure 1) provided the best surrogate for quantitating pain intensity in children.
Expressing pupillary function as a percentage (increase) in pupil constriction functionally provides a measure of maximum effect (Emax) for a given observation (figure 2). This 'ceiling' could potentially be impacted by differences in the concentration versus effect profile for agents used to manage pain (eg, opioids, clonidine, ropivacaine, lidocaine) in our cohort. This is especially pertinent to the use of clonidine, a centrally acting α2 adrenergic agonist which has been shown to have pupillary effects. Maximum constriction velocity on the other hand is a dynamic parameter, which reflects how efficiently the pupil responds to a given stimulus. Given that an increase of 2 or more on the 0–10 VAS scale is associated with a clinically significant change in pain intensity, an observed change in maximal pupil constriction velocity of ≥0.22 mm/sec could be used to guide intervention to optimise pain management. It could also provide an objective surrogate to aid in the differentiation of pain perception versus actual pain intensity. Finally, it is important to recognise that either maximal constriction velocity or the per cent of pupil constriction is dependent upon the baseline status of the pupil, as illustrated by our finding of a significant correlation between maximum constriction velocity and resting pupil diameter. This caveat does not limit the utility of pupillometry, especially when maximum constriction velocity is used as the surrogate end point.
The association between daily drug dose (expressed as morphine equivalents) and pupil size (figure 3) was expected. Nonetheless, controlling for opioid effect in HLM analyses, we were able to demonstrate the independent effect of pain on pupillary response. However, further research is needed to support the use of pupil size as a predictor of analgesic dose requirement given potential confounders in our uncontrolled study (eg, different drug combinations including non-opioid compounds).
Our findings are consistent with previous studies that have examined pupillometry with traditional physiological surrogates of pain assessment in adults and children. Barvais et al compared pupil response with arterial pressure, heart rate and bispectral index (BIS) variations following a painful stimulus in healthy adult patients receiving propofol and remifentanil. They found that in response to a noxious stimulus, pupil dilatation was more sensitive and better correlated with opioid concentrations than heart rate, blood pressure and BIS monitoring. In a similar study performed in anaesthetised children, Constant et al compared changes in pupil diameter with heart rate, blood pressure and BIS monitor variation in response to a skin incision on the lower limb. Similar to the adult data, these investigators were able to show that the change in pupil diameter had a greater effect size than BIS variation or haemodynamic markers.
While precise pupil measurements and subjective pain assessment have not been previously compared in children, Aissou et al performed a study in 100 adults comparing changes in the pupil dilatation reflex and self-reported pain scores via a 5-point verbal rating scale. Shortly after extubation, patients receiving intravenous morphine in a postoperative setting had their pupil size monitored and recorded for 10 s during a standardised stimulus of constant pressure (200 kPa) within 2–3 cm from their skin incision. A statistically significant relationship was observed between the VAS and maximum pupil diameter, as well as a threshold of per cent change in pupil diameter in patients who required additional doses of morphine.
As with all physiological surrogates, pupillometry does have limitations. These include the lack of specificity of the pupil dilatation reflex in response to pain and clinical situations in which a patient is in pain but has constricted pupils. Also, as our study enrolled verbal, cognitively appropriate participants capable of self-reporting pain, additional research is needed to generalise findings to non-verbal patients or those with significant cognitive impairment.
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