Editorial Views  |   May 2012
Pupillometry to Guide Postoperative Analgesia
Author Affiliations & Notes
  • Merlin D. Larson, M.D.
  • Daniel I. Sessler, M.D.
  • *Department of Anesthesia, University of California, San Francisco, San Francisco, California. Department of Outcomes Research, Cleveland Clinic, Cleveland, Ohio.
Article Information
Editorial Views / Central and Peripheral Nervous Systems / Ophthalmologic Anesthesia / Pain Medicine
Editorial Views   |   May 2012
Pupillometry to Guide Postoperative Analgesia
Anesthesiology 5 2012, Vol.116, 980-982. doi:10.1097/ALN.0b013e318251d21b
Anesthesiology 5 2012, Vol.116, 980-982. doi:10.1097/ALN.0b013e318251d21b
POSTOPERATIVE pain, by its very nature, is unpleasant for patients and can prolong their recovery. Although it provokes a variety of autonomic responses that are likely to be harmful, pain by definition is subjective. In conscious subjects, pain is thus best evaluated simply by asking. And of course this is the routine clinical approach in which visual analog or verbal response scores are used to guide therapy. However, Aissou et al.  make the valid point that many patients in the immediate postoperative period have difficulty evaluating and/or communicating pain intensity.1 
“The [pupillary dilation response] can … be used as a measure of pain, but only in controlled situations when confounding factors are well controlled.”
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Infants, the demented, nonverbal patients, and those with delirium cannot accurately convey pain intensity. Patients who are obtunded from residual effects of anesthetics may also be unable to distinguish pain from other sensations, or to express the amount of pain they experience. In addition, some patients will relate pain scores that are inconsistent with their behavior, as mentioned by Aissou et al. 
Adverse effects of untreated acute postoperative pain include limited mobility, impaired ventilation, and increased stress hormones. Untreated perioperative pain may lead to a greater risk for chronic postsurgical pain.2,3 Conversely, overtreatment of drug-seeking or especially expressive patients promotes respiratory toxicity and aggravates opioid-induced side effects such as nausea and vomiting, ileus, sedation, and hyperalgesia.4,5 An objective measure of perioperative pain that is independent of patient consciousness and communication would thus help guide postoperative opioid administration.
Aissou et al.  evaluated a simple and well-known bedside test: pupillary dilation in response to a standardized noxious stimulus (PDR).6 Although their proposed use is to guide opioid administration in patients who cannot accurately convey their need, these investigators compared verbal response pain scores with the PDR in conscious and communicative patients. They found a direct relationship between the magnitude of the PDR brought about by a controlled amount of pressure on the surgical wound and the patient's requirements for morphine in the postanesthesia care unit. Magnitude of the PDR was also directly related to the patient's own verbal assessment of their pain.
These are important findings, and readers who are interested in this technique might find reviews of the subject useful.7 The PDR has been studied extensively since it was described more than 300 yr ago by Philippe de La Hire.8 The imminent 19thcentury physiologist Moritz Schiff (1823–1896) thought the PDR was an accurate measure of pain and promoted the reflex as an “anesthesiometer.”9 His work on the pupil and nociception are a logical starting point for those interested in this fascinating subject. There is copious literature on the PDR, and several contemporary investigators have studied the PDR as a measure of nociception and analgesia.10  14 There are several overriding themes.
First, the PDR is not specific for pain. Rather it is an alerting response that can be elicited by any stimulus that is strong enough to increase the level of arousal. The PDR can thus be used as a measure of pain, but only in controlled situations when confounding factors are well controlled. Only under these circumstances is the PDR magnitude closely related to noxious stimulus intensity and reliably demonstrates dose-dependent depression by opioids and nitrous oxide.12,14 
Second, it would be a mistake to conclude that “pain dilates the pupil and opioids ablate pain, and thus decrease pupillary dilation.” Anyone who makes acute pain rounds will observe patients with constricted pupils consequent to opioid administration who nonetheless have severe pain. And as Aissou et al.  have shown, patients with severe pain in the postanesthesia care unit had constricted pupils just like other patients. It was thus not their pupil size that differed; instead, it was their pupillary response to an evoked stimulus, wound pressure, which confirmed the need for additional morphine.
Third, although pupillary response is brisker and more robust than either hemodynamic or electroencephalograhic responses to painful stimuli,15 dilation nevertheless is too sluggish to be quantified without an infrared pupillometer.6,16 For example, Aissou et al.  found that the average pupillary dilation was less than 1 mm over a 10-s time period, which is far too small to be observed by the unaided eye.
Fourth, the PDR is a supraspinal parasympathetic reflex during general anesthesia. Nerve blocks prevent transmission of noxious stimuli to the brain. But the dilation reflex to perceived noxious stimulation remains intact in the presence of general anesthesia, and coadministration of sympatholytic drugs. Blocking the preganglionic sympathetic fibers during thoracic epidural does not block the PDR.17 Consequently, pupillary dilation in response to noxious stimulation can be used to determine the dermatomal extent of epidural anesthesia, even during general anesthesia, and with block of the upper thoracic dermatomes.18 An unexplored use of PDR is to test for the efficacy of extremity blocks during general anesthesia. In unanesthetized subjects, PDR is primarily a sympathetic reflex, so interventions that interfere with sympathetic reflexes might conceivably block PDR and leave sensory pain mediated fibers intact.
And finally, there are important species differences in the pharmacological and physiologic properties of the PDR. It is thus best to rely on human studies when extrapolating to clinical situations. In cats, for example, the PDR has a strong humoral component that is not observed in humans, and the pharmacological properties of the reflex differ substantially.6,19,20 Furthermore, the strong suppressant effect of opioids on the PDR that is observed in humans has not been observed in any experimental animal.13 
The PDR has substantial potential value to the extent that can be used as a measure of analgesia, especially in uncommunicative patients. Certainly, pupillary dilation as a measure of analgesia has distinct advantages over other autonomic responses to pain, such as blood pressure and heart rate, neither of which is sensitive or specific.21 Special brain imaging techniques and cerebral evoked potentials might be used in certain situations to measure pain, but they are impractical at the bedside.22,23 
Clinicians need to consider, though, that pupil size and the pupillary response to pain are influenced by various factors besides pain. For example, ambient light falling on the unmeasured pupil reduces dilation of the measured pupil in response to painful stimuli. Similarly, miosis that accompanies accommodation can result if patients focus on near objects. There are also various rare syndromes that impair pupillary responses to noxious stimulation, including Adie's pupil, senile miosis, Horner's syndrome, and tonic pupils.24 An intraocular lens can alter the dynamic characteristics of pupillary reflexes. Dopamine 2 receptor antagonists such as metoclopramide can depress the PDR,25 and the effects of residual neostigmine on the PDR remains to be evaluated. Fortunately, most of these problems are rare or can be minimized by good technique.
More seriously, Aissou et al.  only evaluated alert and cooperative patients. Measuring PDR in the nonverbal subjects may prove more difficult. For example, obtunded patients tend to blink and squint, and are unlikely to remain still when pain is elicited by wound pressure. It remains to be confirmed that their technique can be extended to the very population that would benefit most: those who cannot themselves evaluate or communicate pain intensity. Validating the proposed method in its designated target population is thus an obvious next step. That said, the method Aissou et al.  propose is novel and has substantial potential for improving our ability to titrate our analgesic agents in the perioperative period.
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