Nociceptive Pupillometry: Innovation Brief

Pupillometry is being studied as an emerging tool to measure nociception in anesthetized patients.

Description
While pain control is fundamental to anesthetic care, our ability to quantify pain, especially intraoperatively, remains limited. Numerous nociceptive devices have been developed to aid in the assessment and quantification of analgesia. However, largely due to analgesia’s complex system of transduction, transmission, modulation, and perception, there continues to be a lack of standardized nociception sensors.¹ Assessment of pain can be useful to anesthesiologists to optimize anesthetic drug consumption and thus optimizing pain control while preventing overmedication which could cause dependence, nausea, vomiting, respiratory depression, and opioid-induced hyperalgesia.¹ Pupillometry is a measure of the pupil reactivity and size in response to noxious stimuli and is being studied as an emerging tool to measure nociception in anesthetized patients.

Figure 1. Illustration of the general pathway of nociception. Korean J Anesthesiol 2022;75(2):112-123 https://doi.org/10.4097/kja.22002 pISSN 2005–6419.

Assessment of analgesia using pupillometry is based on the balance of the sympathetic and parasympathetic vagal nerves controlling pupillary constriction and dilation.² The diameter of the pupil is determined by the contraction of two smooth muscles: the sphincteric muscle and the pupillary radial muscle.² The circular sphincteric muscle keeps the pupil constricted and receives parasympathetic innervation from the oculomotor nerve and short ciliary nerves through muscarinic receptors. The radial muscle dilates the pupil and receives sympathetic innervation by long ciliary nerves. The stronger of the two muscles, the circular sphincteric muscle, tends to constrict the pupil unless sympathetic activity of the radial muscle occurs, or blockade of the pupilloconstrictor neurons causes dilation.²

Figure 2. Sympathetic and parasympathetic pathways leading to pupillary changes. Pupillometry in perioperative medicine: a narrative review. Can J Anesth/J Can Anesth 68, 566–578 (2021).

After sympathetic blockade, the pupil should constrict because of the action of the circular sphincteric muscle. Active pupillary dilation occurs via sympathetic innervation and is thus activated with pain in individuals with intact sympathetic response.²

Objective quantification of pupillary dilation can be made with handheld non-invasive pupilometers to accurately quantify pupillary reflexes.² One such nociceptive pupillometer first measures pupil sizes in response to noxious stimuli, second after exposure to a one second flash of light, third and fourth a tetanus and pupillary pain index mode determining pupillary changes in response to controlled stimulations applied to the ulnar nerve. Pupillary pain indexes range from 0-10 measuring pupil reactivity, with high values (ppi>7) indicating insufficient analgesia.¹

Pupillometry has been shown to provide a quicker assessment of painful stimuli than the traditional criteria for assessing adequate anesthesia like increased heart rate and blood pressure.¹ In a single-blind prospective, randomized trial, the use of pupillometry to guide intraoperative remifentanil administration in women undergoing hysterectomy reduced postoperative morphine requirements within the first 12 hours as well as reduced persistent postoperative pain at three months.³

Despite these advantages, the use of pupillometry is still under investigation and some studies have found that some pupillometry techniques are not useful in predicting morphine consumption after surgery.⁴ A study published in 2022 BJA did not find pupillometry to predict postoperative morphine requirements in children after tonsillectomy.⁴ Unlike current nociceptive monitoring methods (heart rate, respiratory rate, and blood pressure), a limitation of pupillometry is that it does not provide continuous nociceptive monitoring. For such monitoring, corneal care would be a requisite, and there should be consideration of other mydriatic factors, such as ambient lighting or pharmacological agents.¹

References:

1. Martinez-Vazquez, Pablo, and Erik Weber Jensen. “Different Perspectives for Monitoring Nociception during General Anesthesia.” Korean Journal of Anesthesiology, U.S. National Library of Medicine, Apr. 2022, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8980281/.

2. Packiasabapathy, S., Rangasamy, V. & Sadhasivam, S. Pupillometry in perioperative medicine: a narrative review. Can J Anesth/J Can Anesth 68, 566–578 (2021). https://doi.org/10.1007/s12630-020-01905-z.

3. Nada Sabourdin, Jérôme Barrois, Nicolas Louvet, Agnès Rigouzzo, Marie-Laurence Guye, Christophe Dadure, Isabelle Constant; Pupillometry-guided Intraoperative Remifentanil Administration versus Standard Practice Influences Opioid Use: A Randomized Study. Anesthesiology 2017; 127:284–292 doi: https://doi.org/10.1097/ALN.0000000000001705.

4. Bruno Evrard, Cyrielle Lefebvre, and Paul Spiry, et al. “Evaluation of the Analgesia Nociception Index and videopupillometry to predict post-tonsillectomy morphine requirements in children: a single-centre, prospective interventional study.” BJA Open, Volume 3, 2022, 100024, ISSN 2772-6096, https://doi.org/10.1016/j.bjao.2022.100024.