Pupillometry and Pain
Myron Yaster MD, Lynne Maxwell MD, and Rita Agarwal MD
Over the past few weeks, we’ve discussed desert island monitors, that is, if you were stranded on a desert island what is the one monitor you would absolutely take with you. After much discussion, the consensus choices came down to pulse oximetry and capnography. This past week, Rob Friesen remembered the introduction of non-invasive automated blood pressure monitoring into pediatric anesthetic practice. I think we can all agree this would also be a worthy contender as a desert island monitor. On the horizon comes pupillometry, a potential predictor of post-operative respiratory depression (Nov 4th PAAD, Quantitative Pupillometry: A future desert island monitor?). Today another group reports on a different pupillometer which may be an INTRAOPERATIVE monitor to assist in determining the depth of intraoperative analgesia and could help guide opioid administration in anesthetized patients. Finally we can recommend a good primer/review on this topic: Packiasabapathy S, Rangasamy V, Sadhasivam S. Pupillometry in perioperative medicine: a narrative review. Can J Anaesth. 2021 Apr;68(4):566-578. PMID: 33432497
Myron Yaster MD
Original Article
Nada Sabourdin, Loïc Del Bove, Nicolas Louvet, Sarah Luzon-Chetrit, Benoît Tavernier, Isabelle Constant. Relationship between pre-incision Pupillary Pain Index and post-incision heart rate and pupillary diameter variation in children. Paediatr Anaesth. 2021 Oct;31(10):1121-1128. PMID: 34233066
Last week’s PAAD reviewed the use of the NeurOptics pupillometer as a predictor of pediatric postoperative opioid-induced respiratory depression (Anesth Analg. 2021 Oct 1;133(4):991-999. PMID: 34029273). Today’s PAAD uses a different pupillometer, Algiscan (version 1.15.12, IDMED), to help gauge the level of analgesia in anesthetized pediatric patients. In this preliminary feasibility study, pupillometry and the Pupillary Pain Index (PPI) were used to predict a patient’s level of reactivity to surgical incisional pain.
“The PPI score ranges from 1 to 10. Its aim is to predict a patient's level of reactivity to nociception, before an intended nociceptive stimulation actually occurs. To achieve this goal, the PPI evaluates pupillary reactivity to mild tetanic stimuli. The level of reactivity provides information about the depth of analgesia: a high level of reactivity (high PPI score) corresponds to light analgesia, whereas a low level of reactivity (low PPI score) corresponds to robust analgesia”. The “pupillometer can deliver calibrated tetanic stimulations (5–60 milliamps, 100 Hz, continuous current with 200-microseconds impulses) via two cutaneous electrodes placed in the ulnar nerve territory. One electrode is placed just above the wrist, the second approximately 4 cm above”.
BP, HR, and BIS measurements were made after the induction of general anesthesia, before incision, and 2 minutes after incision. PPI was measured only before incision with the pupillometer measuring change in pupillary dilation from baseline after incision. Changes in HR of > 15% were regarded as the indicator of nociception in response to surgery, i.e., inadequate analgesia to which the PPI was compared. The authors found that “PPI was moderately correlated to heart rate increase and pupillary dilation following incision. Patients with higher pre-incision PPI had a higher heart rate increase and a wider pupillary dilation after incision than patients with lower PPI. In addition, our results suggest that a pre-incision PPI <3 might predict the absence of heart rate reaction to incision”.
This French pediatric study confirmed the utility of PPI as a predictor of the intraoperative response to pain that was previously found in adult studies.1,2 Interestingly, and previously unknown to any of the three of us, there are a number of commercially available intraoperative nociception monitors, including: “the Analgesia Nociception Index (ANI, Mdoloris), Nociception Level (NoL, Medasense Biometrics), and the Surgical Pleth Index (SPI, GE-Healthcare). All of these monitors have “demonstrated a higher sensitivity3,4 and a better specificity5,6 with respect to nociception than heart rate, blood pressure, or BIS variations”. However, are any of these monitors routinely used in- or out-side of the United States? We don’t know. Indeed, if any of you have experience with the clinical use of pupillometry in adults or pediatrics, please let us know and we’ll post your experiences in our bi-weekly reader’s response PAAD. Finally, we recall that awhile back, Dr, Julie Finkel of the Children’s National Medical Center in Washington DC, presented some of her preliminary data at a SPA meeting using pupillometry as a tool in chronic pain management. In preparation for today’s PAAD, we did a Pubmed search and couldn’t find any peer-reviewed published material with Julie’s early experiences and prototypes. If Julie or any of her colleagues reading this have some follow up data please let us know.
Why should we care? Predictability of the depth of pain response may help us titrate opioids and general anesthetic agents used intraoperatively better than changes in HR, BP, and BIS. Further studies would be needed correlating PPI with amount/type of analgesics and anesthetics administered. As discussed in the Nov 4th PAAD, “Quantitative Pupillometry: A future desert island monitor?”, Packiasabapathy et al., {PMID 34029273} found that pupillometry may be useful in predicting opioid-induced respiratory depression and could theoretically be used to titrate opioid administration and provide guidance in postoperative respiratory monitoring.
Although the PPI may be useful in the setting of anesthetized patients, we don’t think it can be used after emergence from anesthesia because of the tetanic stimuli employed to derive the measurement (“hello laryngospasm”). Other unknowns included the time course (PK/PD) of the change in PPI after administration of an opioid (e.g. one would expect a greater delay after morphine compared to remifentanil administration). This variable time lag could lead to misinterpretation of the level of analgesia as measurement of the PPI too early may result in a higher value (lower analgesia) if the peak pupillary effect is delayed. Much more work needs to be done but this is a tantalizing new approach to how we titrate analgesics, particularly opioids, and general anesthetics in the OR.
Thus, this may be another step along the long and winding road seeking the “holy grail” of an accurate, objective, and easily measured surrogate indicator of patients’ pain/analgesic level (see galvanic skin resistance, EEG measures, etc.), but it may be yet another detour.
Myron Yaster MD, Lynne Maxwell MD, and Rita Agarwal MD
References
1. Guglielminotti J, Grillot N, Paule M, Mentré F, Servin F, Montravers P, Longrois D: Prediction of movement to surgical stimulation by the pupillary dilatation reflex amplitude evoked by a standardized noxious test. Anesthesiology 2015; 122: 985-93
2. Barvais L, Engelman E, Eba JM, Coussaert E, Cantraine F, Kenny GN: Effect site concentrations of remifentanil and pupil response to noxious stimulation. Br J Anaesth 2003; 91: 347-52
3. Funcke S, Sauerlaender S, Pinnschmidt HO, Saugel B, Bremer K, Reuter DA, Nitzschke R: Validation of Innovative Techniques for Monitoring Nociception during General Anesthesia: A Clinical Study Using Tetanic and Intracutaneous Electrical Stimulation. Anesthesiology 2017; 127: 272-283
4. Constant I, Nghe MC, Boudet L, Berniere J, Schrayer S, Seeman R, Murat I: Reflex pupillary dilatation in response to skin incision and alfentanil in children anaesthetized with sevoflurane: a more sensitive measure of noxious stimulation than the commonly used variables. Br J Anaesth 2006; 96: 614-9
5. Weber F, Geerts NJE, Roeleveld HG, Warmenhoven AT, Liebrand CA: The predictive value of the heart rate variability-derived Analgesia Nociception Index in children anaesthetized with sevoflurane: An observational pilot study. Eur J Pain 2018; 22: 1597-1605
6. Logier R, De Jonckheere J, Delecroix M, Keribedj A, Jeanne M, Jounwaz R, Tavernier B: Heart rate variability analysis for arterial hypertension etiological diagnosis during surgical procedures under tourniquet. Annu Int Conf IEEE Eng Med Biol Soc 2011; 2011: 3776-9