Today, November 4, 2021 is Diwali. One of the most popular festivals of Hinduism, “Diwali is a festival of lights and symbolizes the spiritual "victory of light over darkness, good over evil, and knowledge over ignorance". During Diwali, people wear their finest clothes, illuminate the interior and exterior of their homes with diyas and rangoli, perform worship ceremonies of Lakshmi, the goddess of prosperity and wealth, light fireworks, and partake in family feasts, where mithai (sweets) and gifts are shared” (from Wikipedia). So, to my Hindu, Sikh and Buddhist friends “Happy Diwali”!
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 absolute monitor you would take with you. After much discussion, the consensus choices included pulse oximetry and capnography. This past week Rob Friesen remembered and discussed the introduction of non-invasive automated blood pressure monitoring. Today and next week we’ll be reviewing pupillometry, a monitor that isn’t ready for prime time but may be game changing and worthy of consideration in the near future. Myron Yaster MD
Original article
Senthil Packiasabapathy, Xue Zhang, Lili Ding, Blessed W Aruldhas, Dhanashri Pawale, Senthilkumar Sadhasivam. Quantitative Pupillometry as a Predictor of Pediatric Postoperative Opioid-Induced Respiratory Depression. Anesth Analg. 2021 Oct 1;133(4):991-999. PMID: 34029273
We all know that assessment of pupil size and the pupillary light reflex is a critical component of the neurological exam because it involves the assessment of the functional status of two cranial nerves (CN) – the optic nerve (CN II) and the oculomotor nerve (CN III). Cranial nerve dysfunction may signal increased ICP and/or an increased risk of brain herniation. Thus, in patients with traumatic brain injury, cerebral edema/brain herniation, stroke, cardiac arrest, etc. pupillary findings can be both diagnostic and prognostic. Unfortunately, manual pupil assessments (using a penlight, flashlight, or your cell phone) are subjective and fraught with a high degree of inter-examiner variability. Thus, obtaining accurate, reliable, reproducible, and objective pupil assessment data with a hand-held device, that can also be downloaded into the EMR, has been the holy grail of pupillary light reflex measurement. A relatively new FDA approved device made and sold by NeurOptics, Irvine CA (www.NeurOptics.com ) may be the solution and may become a new critical care and pain management desert island monitor.
The authors of today’s original article, thinking outside of the box, reasoned that quantitative pupillometry could also be used as a predictor of opioid-induced respiratory depression. Several previous studies have suggested that this could be the case.1-4 “Opioid-related respiratory depression is mainly due to its central depressive effects on respiratory centers in the brainstem. Pupillary constriction reaction to light involves the oculomotor nerve and its Edinger-Westphal nucleus in the brainstem. Since the same brainstem effect-site concentration of opioid is likely to have similar effects on the respiratory centers and oculomotor nucleus, this study aimed to investigate the correlation of pupillary response following perioperative morphine administration with postoperative respiratory depression”. Thus, the authors “invented a technology to use quantitative pupillometry as a bedside predictor of postoperative respiratory depression” and licensed it through Cincinnati Children’s Hospital to NeurOptics (from the authors disclosure).
Let’s cut to the chase...it worked! In this study of T&A patients with and without sleep disordered breathing the authors found: “there were significant differences in pupillometry parameters between children who experienced postoperative respiratory depression and those who did not. A multi-parameter model that includes pre- and intraoperative pupillometry parameters along with morphine dose per body weight and BMI had good predictive performance for postoperative respiratory depression. Pupillometry is a technique with the potential to be used as a bedside predictor of opioid-induced respiratory depression. Proactive and early risk identification for postoperative opioid-induced respiratory depression and tailored use of the right doses of the right analgesics could reduce life-threatening respiratory depression and prolonged hospital stays. Large future studies in different cohorts exposed to opioids are needed to validate the utility of pupillometry in predicting and preventing central opioid adverse effects in real time at bedside”.
OK, some important caveats. As the authors point out much more work needs to be done to assess whether this technology truly predicts respiratory depression. Further, we normally titrate opioids to pain relief not respiratory depression. Were the patients in the study in pain? We don’t know. What is the interaction between opioids, pain, and the pupillary light reflex? (We will be discussing this in an upcoming PAAD, so stay turned). Can it be used to titrate opioids to analgesic needs? The authors also found substantial depression of the pupillary reflex by the general anesthetic sevoflurane. Indeed, sevoflurane produced a greater effect than morphine! Would a propofol anesthetic produce different results? What does all of this mean, particularly if the device is used in the PACU to determine opioid dosing? Lots of clinical research opportunities for those of you building a career!
The authors found a strong correlation “between postoperative respiratory depression and weight-based opioid dose administered intraoperatively and in the PACU”. To be honest this was a bit confusing to us. Morphine was the intraoperative opioid and could be given in the PACU as needed for breakthrough pain. How supplemental opioids were administered in the PACU was not described in the paper. We do know that supplemental morphine was given as well as fentanyl, and according to the paper, the addition of fentanyl produced more respiratory depression than morphine alone. Indeed, we think it would be interesting to know the timing of the occurrence of respiratory depression with postoperative opioid administration. Further, the opioid doses were weight based. Was this also true for the obese? Indeed, how should opioids be given to patients with sleep disordered breathing with and without obesity? Could this device help in making these decisions?
Finally, the NeurOptics device used in the study was the NeurOptics PLR-100 QP. On the website this is no longer available and has been replaced with the 200 and 300 models which appear to download their info wirelessly to the EMR. Nevertheless, we think this device is a powerful new tool in our armamentarium with intriguing clinical and research possibilities.
Myron Yaster MD and Lynne Maxwell MD
References
1. Larson MD, Sessler DI: Pupillometry to guide postoperative analgesia. Anesthesiology 2012; 116: 980-2
2. McKay RE, Larson MD: Detection of opioid effect with pupillometry. Auton Neurosci 2021; 235: 102869
3. Connelly MA, Brown JT, Kearns GL, Anderson RA, St Peter SD, Neville KA: Pupillometry: a non-invasive technique for pain assessment in paediatric patients. Arch Dis Child 2014; 99: 1125-31
4. Sabourdin N, Barrois J, Louvet N, Rigouzzo A, Guye ML, Dadure C, Constant I: Pupillometry-guided Intraoperative Remifentanil Administration versus Standard Practice Influences Opioid Use: A Randomized Study. Anesthesiology 2017; 127: 284-292