BACKGROUND:Physiological responses to nociception are complex and involve intricate associations between the central, peripheral, and autonomic nervous systems. To optimize intraoperative analgesic titration, several monitoring devices have been developed, each targeting specific physiologic variables. However, existing devices primarily focus on isolated components of the nociceptive response, such as autonomic or cortical activity, without integrating these perspectives comprehensively. Our aim was to compare the performance of different nociception monitors in response to standardized tetanic stimulation and to investigate the correlation between these monitors' responses and varying concentrations of remifentanil. METHODS:In this study, we evaluated and compared the responses of the Nociception Level index (NOL), Analgesia Nociception Index (ANI), Pupillary Reflex Dilation (PRD) and both raw and processed electroencephalogram (EEG) under varying concentrations of propofol and remifentanil. Standardized tetanic stimuli were administered to patients under general anesthesia with target-controlled infusion of propofol and remifentanil. EEG, PRD, NOL, ANI, heart rate (HR), Bispectral index (BIS), and CONOX monitor indices (qCON and qNOX) were concomitantly recorded. RESULTS:ANI, BIS, HR, NOL, PRD, and qNOX significantly changed after noxious stimulation. In our dataset, PRD had the strongest correlation with varying remifentanil concentrations, while ANI, NOL, and qNOX did not show significant correlations with remifentanil concentrations. Following a noxious stimulus, the raw EEG in patients with low PRD exhibited a significant increase in power in the high EEG frequencies around 25 Hz and decreased power in frequencies corresponding to the alpha range (8-12 Hz) in the power spectral density. CONCLUSIONS:PRD, HR, and BIS correlated with varying levels of remifentanil, with PRD exhibiting the strongest correlation. When CE remifentanil are low, noxious stimuli are more likely to dilate the pupil and be detected in the EEG. Considering the complexity of the nociceptive response, integrating multimodal neurophysiologic monitoring with pharmacological data may improve the anesthesiologist's ability to assess on the nociception-antinociception balance. However, further studies are needed to validate these findings and address the study's limitations.

Opioid-induced respiratory depression (OIRD) remains a critical safety concern, particularly in older adults, yet timely, reliable detection methods are limited. Decline of pupillary unrest in ambient light (PUAL) has demonstrated potential as a marker of opioid effect in young adult subjects. We evaluated whether previously observed PUAL thresholds for high-risk opioid exposure in younger adults remain valid in 40-60-year-old subjects. Ten healthy volunteers 40–60 years of age underwent PUAL measurement at baseline and every 2.5 min during a 10-minute remifentanil infusion (0.2–0.3 µg/kg/min) and 25-minute recovery period. High-risk opioid exposure was defined primarily by modeled remifentanil effect-site concentration (CEREMI) threshold during infusion. Findings were then combined with previously collected data from 20 younger subjects (aged 20–39 years) undergoing an identical infusion protocol. PUAL declined consistently during infusion and increased toward baseline during recovery (p < 0.001). During infusion no significant difference in slope over time or CEREMI was observed between age groups, but during recovery a flatter slope was observed in older subjects (p = 0.016). PUAL reliably distinguished between high-versus low-risk opioid exposure during infusion (AUROC = 0.9833 [95

INTRODUCTION:Pupillary unrest in ambient light (PUAL) describes the fluctuation of pupil diameter observed in normal, awake subjects under typical levels of indoor light. PUAL becomes low to absent in young healthy subjects during opioid intoxication. We sought to determine the age-related distribution of PUAL values in a random sample of ambulatory participants. METHODS:Subjects ≥18 years of age were recruited. All were identified by age range (18-29, 30-49, 50-69, and ≥70), and surveyed for diabetes, beta-blocker use, and prior 24-hour opioid use. Relationship between mean PUAL, age group, comorbidity and opioid use were examined by Kruskal Wallis test, and PUAL and was modeled using stepwise multilevel linear regression, including diabetes, beta blocker use, prior 24-hour opioid use, autonomic dysfunction, and pupil diameter as fixed effects and subject as random effect. RESULTS:Among 150 subjects, 17 reported diabetes, 12 reported beta-blocker use, 14 reported prior 24-hour opioid use, and 120 reported no comorbid conditions. PUAL declined in higher age categories (by 0.0307, P < 0.001), with diabetes (by 0.0481, P = 0.025), and with beta-blocker use (by 0.0616, P = 0.005). Opioid related PUAL decline was observed, but statistical significance varied by model. Among healthy subjects, no PUAL value fell within range indicating high likelihood of opioid toxicity based on previous data from healthy subjects undergoing opioid infusion. CONCLUSION:PUAL declined in higher age groups, diabetes and beta-blocker use, conditions associated with impaired autonomic function, and with opioid use but significance varied depending on the chosen model.

In intensive care patients with disorders of consciousness, the pupillary light reflex is a measure of pupillary parasympathetic function. By contrast, the pupillary light-off reflex leads to pupil dilation in response to an abrupt change from light to darkness (“light-off”) and reflects combined parasympathetic and sympathetic pupillary function. To our knowledge, this reflex has not been systematically investigated in patients with disorders of consciousness. We hypothesized that the pupillary light-off reflex correlates with consciousness levels after acute brain injury. From November 2022 to March 2023, we enrolled 100 study participants: 25 clinically unresponsive (coma or unresponsive wakefulness syndrome) and 25 clinically low-responsive (minimally conscious state or better) patients from the intensive care units of a tertiary referral center, and 50 age-matched and sex-matched healthy controls. Exclusion criteria were active or chronic eye disease. We used automated pupillometry to assess the pupillary light-off reflex and the pupillary light reflex of both eyes under scotopic conditions in all study participants. The pupillary light-off reflex was strongly correlated with consciousness levels (r = 0.62, p < 0.001), the increase in pupillary diameters being smallest in unresponsive patients (mean ± standard deviation 20

Abstract Statement: The quality of the pupillary light reflex as measured by portable pupillometers made by different companies is not the same.

The pupil displays chaotic oscillations, also referred to as pupillary unrest in ambient light (PUAL). As pain has previously been shown to increase pupillary unrest, the quantitative assessment of PUAL has been considered a possible tool to identify and quantify pain. Nevertheless, PUAL is affected by various states, such as vigilance, cognitive load, or emotional arousal, independent of pain. Furthermore, systematically applied opioids are known to reduce PUAL, thus potentially limiting its usefulness to detect pain or changes in pain intensity. To test the hypothesis that PUAL can reliably identify changes in pain intensity in a clinical setting, we measured PUAL in patients experiencing substantial pain relief when regional anesthesia interventions were applied after surgery. We conducted an observational study at an academic surgery centre following institutional review board approval. Eighteen patients with unsatisfactory pain control following surgery underwent regional anesthesia procedures to improve pain control. We used infrared pupillometry to assess pupillary unrest before and after the regional block. We then compared the changes in pupillary unrest with the changes in pain scores (numeric rating scale [NRS], range 0–10). Eighteen patients received epidural anesthesia (n = 14) or peripheral nerve blocks (n = 4), resulting in improvement of mean (standard deviation [SD]) NRS pain scores from 7.2 (1.7) to 1.9 (1.8) (difference in means, −2.2; 95

Background. In intensive care patients with disorders of consciousness (DoC), the pupillary light reflex is a measure of pupillary parasympathetic function. By contrast, the pupillary dark reflex leads to pupil dilation in response to darkness and primarily reflects the sympathetic function of the pupil. To our knowledge, this reflex has not been systematically investigated in DoC patients. We hypothesized that the pupillary dark reflex correlates with consciousness levels after acute brain injury, and that this correlation is not necessarily the same as that of the pupillary light reflex. Methods. From November 2022 to March 2023, we enrolled 100 study participants: 25 clinically unresponsive (coma or unresponsive wakefulness syndrome) and 25 clinically low-responsive (minimally conscious state or better) patients from the intensive care units of a tertiary referral center, and 50 age- and sex-matched healthy controls. Exclusion criteria were active or chronic eye disease. We used automated pupillometry to assess the pupillary dark reflex and the pupillary light reflex of both eyes under scotopic conditions in all study participants. Results. The pupillary dark reflex was strongly correlated with consciousness levels (r = 0.62, p < 0.001), the increase in pupillary diameters being smallest in unresponsive patients (mean ± SD: 20% ± 21%), followed by low-responsive patients (47% ± 26%) and healthy controls (67 % ± 17%; p < 0.001). Similar, yet less pronounced patterns were observed for the pupillary light reflex. Twenty-one of 25 unresponsive patients had preserved pupillary light reflexes, but only seven had preserved pupillary dark reflexes (p < 0.0001). Of these seven patients, five regained awareness. Conclusion. The pupillary dark reflex is more sensitive to consciousness levels after brain injury than the pupillary light reflex. The clinical implications of this finding seem worthy of further investigation, particularly regarding possible benefits for neuromonitoring and prognostication after brain injury.

This journal recently published an article by Gregoire et al that examined the relationship between pain and two measurements taken by a portable pupillometer. (Gregoire et al., 2023) Their conclusion is that pain cannot be measured objectively by the pupillary light reflex or by pupillary unrest in ambient light (PUAL). Previous studies did show that pain was correlated to the light reflex and to spontaneous fluctuations of pupil size as measured by the variation coefficient of diameter (VCPD). The difference in their results presumably relates to different algorithms, and to several other issues that are discussed in their manuscript. An obvious question arises as to why anyone would try to objectively measure pain. By definition, pain is a subjective experience that can only be assessed by the patient. A measure of pain is usually accomplished by using numerical scales. If a patient states that they have 8 out of 10 pain, could the caregiver doubt that because the pupillometer reading indicated that they do not have pain? On the contrary, would the caregiver tell the patient they have severe pain when the patient denies it? Of course, there are patients who cannot communicate pain scores and then an objective measure could be useful. It would be an advance in pain management if a noninvasive and rapid objective measure of pain was available to use in these cases. Pupillometry is noninvasive, inexpensive and provides rapid assessments that can be performed by the nursing staff. But it does not measure pain in the emergency room (ER). These authors reported that the patients with moderate pain did not have pupils that were larger than those with less pain. The pupil is a ‘novel stimulus detector’ that results in a brief dilation, but the dilation is not sustained if the stimulus persists. Accordingly, pupillary measurements can detect pain in labouring women who have intermittent acute pain. Patients in the ER have sustained constant pain that does not dilate the pupil, as these authors have demonstrated. PUAL decreases when opioids are given to patients with severe acute pain. Pain is also diminished, but the decrease in PUAL does not occur because there is less pain after medication. Rather the decrease is brought about by the effect of opioids on the pupil. The decrease in PUAL occurs even in patients who have no pain. Do these results mean that pupillary measures are useless when treating a patient with severe pain in the ER? Although the authors of this report did not treat pain with opioids, these drugs are effective for severe pain and if used responsibly can relieve suffering. But overdose with these agents can still occur in the ER and after discharge. PUAL is thought to be generated by the opposing actions of light and inhibition at the EW (Edinger-Westphal) nucleus. Opioids depress inhibition at the EW nucleus and reduce PUAL. Total block of inhibition by opioids at the EW nucleus depresses PUAL to near zero and that measure is associated with severe respiratory depression unless the patient is engaged in an interactive environment (McKay et al., 2022). Nerve blocks can be dangerous in patients with low PUAL values resulting from opioid therapy (McKay et al., 2018). And discharging a patient with a PUAL of zero would be inadvisable. This author proposes that pupillometry has the potential to provide a guide for adjusting opioid therapy when treating severe pain in the ER.

There is an urgent need for easy-to-perform bedside measures to detect residual consciousness in clinically unresponsive patients with acute brain injury. Interestingly, the sympathetic control of pupil size is thought to be lost in states of unconsciousness. We therefore hypothesized that administration of brimonidine (an alpha-2-adrenergic agonist) eye drops into one eye should produce a pharmacologic Horner’s syndrome if the clinically unresponsive patient is conscious, but not if the patient is unconscious. Here, in a first step to explore this hypothesis, we investigated the potential of brimonidine eye drops to distinguish preserved sympathetic pupillary function in awake volunteers from impairment of sympathetic tone in patients in a coma. We enrolled comatose patients admitted for acute brain injury to one of the intensive care units (ICU) of a tertiary referral center, in whom EEG and/or neuroimaging for all practical purposes had ruled out residual consciousness. Exclusion criteria were deep sedation, medications with known drug interactions with brimonidine, and a history of eye disease. Age- and sex-matched healthy and awake volunteers served as controls. We measured pupils of both eyes, under scotopic conditions, at baseline and five times 5–120 min after administering brimonidine into the right eye, using automated pupillometry. Primary outcomes were miosis and anisocoria at the individual and group levels. We included 15 comatose ICU patients (seven women, mean age 59 ± 13.8 years) and 15 controls (seven women, mean age 55 ± 16.3 years). At 30 min, miosis and anisocoria were seen in all 15 controls (mean difference between the brimonidine-treated pupil and the control pupil: − 1.31 mm, 95

Fidel Pagés, a Spanish surgeon, tragically died in 1923 at the age of 37, just 2 years after his publication "Anestesia Metamérica," the first description of human thoracolumbar epidural anesthesia. In the intervening 100 years, epidural anesthesia has faced countless obstacles, starting with the dissemination of his initial report, which was not widely read nor appreciated at the time. However, the merits of the technique have fueled innovations to meet these challenges over the years. Even today, while epidural anesthesia is widely embraced, particularly in obstetric and chronic pain medicine, the pressures of the operating room for efficiency and a low tolerance for failure, pose modern-day challenges. Here, we revisit Pagés' original report and highlight the key innovations that have allowed for the evolution of this essential anesthesia technique.

Anesthesiology has evolved to be a leader in addressing patient safety. Our specialty has overcome serious morbidities including explosions, fires, organ toxicity, fatal arrhythmias, and hypoxic brain damage. Anesthesia safety has been significantly improved due to modern drug development, technical advances, and a strong leadership willing to apply human factors and systems’ research strategies, but patient safety concerns remain at the forefront as we strive to improve patient care even further. This year marks the centennial year since the publication of the first issue of Anesthesia & Analgesia. Today, the International Anesthesia Research Society (IARS) and Anesthesia & Analgesia continue to advance the boundaries of patient safety by disseminating practice standards, serving as a forum for novel ideas, and supporting research advancements. This review will discuss several topics published in Anesthesia & Analgesia that exemplify steady changes leading to the safe practices that we rely on currently as well as other IARS activities that have advocated and elevated patient safety within the specialty.

Background: Palliative sedation is sometimes interrupted by undesired arousals. Pupillometry has been used in anesthesiology to monitor pain and sedation but has never been used during palliative sedation. Actual case: A 48 years-old patient, with multi-metastatic cancer, underwent palliative sedation to manage global suffering. On the second day, the patient experienced arousal which required medication adjustments to ensure pain relief and increased sedation. Possible course of action: Depth of sedation is monitored with clinical scales, such as the Richmond Agitation-Sedation Scale. But these scales do not measure brain stem activity and are poor at predicting arousal. Formulation of a plan: During palliative sedation, an infrared pupillometer was used to monitor pupil size and pupillary reactivity (Neurolight®, IDMed®, Marseille, France). Outcome: The pupillary light reflex was depressed during deep sedation. In our case, we observed a low-normal reflex along with dilated pupil before arousal. Lessons from the case: Our case suggests that reflex intensity and pupil size might predict arousals during palliative sedation. View on research problems, objectives, or questions generated by the case: Prospective studies are needed to confirm our findings. Pupillometry’s acceptability should also be questioned from patient’s, families’, and caregivers’ perspectives.

Background: Opioids produce pupillary constriction but their impact on pupillary unrest and the dynamic parameters of the pupillary light reflex have not been characterized. Given the increasing use of portable pupillometers for care of critically ill patients, it is important to distinguish between opioid effects on the pupil versus those that have been reported to arise from traumatic and ischemic brain insults. We undertook this study to determine which pupillary responses are most profoundly and consistently affected by a progressive infusion of remifentanil. Methods: We studied the effect of remifentanil on the pupil using two portable infrared pupillometers in 18 volunteers. One pupillometer measured pupillary unrest in ambient light (PUAL) and the other pupillometer measured neurological pupillary index (NPi), constriction velocity (CV), pupil diameter (PD), latency, and % reflex (% reflex) following a transient light flash. Remifentanil was administered at predetermined weight-adjusted rates to raise opioid effect site concentration up to a range known to produce respiratory depression and oxyhemoglobin desaturation, based on a previously published pharmacokinetic model. Results: PUAL was ablated by remifentanil, declining 94 +/- 6% from baseline at the time of maximum drug effect. Other pupillary measurements decreased 50-65% from baseline. NPi was unchanged. At the time of oxyhemoglobin desaturation, deviations in PD, CV, and % reflex were widely scattered, whereas PUAL consistently approached zero. Conclusion: PUAL is a highly specific indicator of central opioid effect. As a non-invasive measure, it may provide useful data to clinicians who prescribe opioids.

Intraoperative targeting of the analgesic effect still lacks an optimal solution. Opioids are currently the main drug used to achieve antinociception, and although underdosing can lead to an increased stress response, overdose can also lead to undesirable adverse effects. To better understand how to achieve the optimal analgesic effect of opioids, we studied the influence of remifentanil on the pupillary reflex dilation (PRD) and its relationship with the reflex movement response to a standardized noxious stimulus. The main objective was to generate population pharmacodynamic models relating remifentanil predicted concentrations to movement and to pupillary dilation during general anesthesia. A total of 78 patients undergoing gynecological surgery under general anesthesia were recruited for the study. PRD and movement response to a tetanic stimulus were measured multiple times before and after surgery. We used nonlinear mixed effects modeling to generate a population pharmacodynamic model to describe both the time profiles of PRD and movement responses to noxious stimulation. Our model demonstrated that movement and PRD are equally depressed by remifentanil. Using the developed model, we changed the intensity of stimulation and simulated remifentanil predicted concentrations maximizing the probability of absence of movement response. An estimated effect site concentration of 2 ng/ml of remifentanil was found to inhibit movement to a tetanic stimulation with a probability of 81%.

Opioid-induced respiratory depression (OIRD) confers significant morbidity, but its onset can be challenging to recognize. Pain or stimulation effects of conversation may mask or attenuate common clinical manifestations of OIRD. We asked whether pupillary unrest could provide an objective signal of opioid exposure, and whether this signal would be independent from the confounding influence of extrinsic stimulation. We conducted a cross-over trial of healthy volunteers using identical remifentanil infusions separated by a washout period; in both, pupillary unrest in ambient light (PUAL) was measured at 2.5-min intervals. During one infusion, investigators continuously engaged the subject in conversation, while in the other, a quiet environment was maintained; measures of respiratory depression were compared under each condition. We tested PUAL’s relationship to estimated opioid concentration under quiet conditions, measured PUAL’s discrimination of lower versus higher opioid exposure using receiver operating characteristic (ROC) analysis, and assessed the effect of stimulation on PUAL versus opioid using mixed effects regression. Respiratory depression occurred more frequently under quiet conditions (p < 0.0001). Under both conditions, PUAL declined significantly over the course of the remifentanil infusion and rose during recovery (p < 0.0001). PUAL showed excellent discrimination in distinguishing higher versus absent-moderate opioid exposure (AUROC = 0.957 [0.929 to 0.985]), but was unaffected by interactive versus quiet conditions (mean difference, interactive – quiet = − 0.007, 95% CI − 0.016 to 0.002). PUAL is a consistent indicator of opioid effect, and distinguishes higher opioid concentrations independently of the stimulating effects of conversational interaction. Under equivalent opioid exposure, conversational interaction delayed the onset and minimized the severity of OIRD. Clinical trial registration: NCT 04301895

Background: Pupillometers have been proposed as clinical assessment tools. We compared two pupillometers to assess measurement agreement. Materials & methods: We enrolled 30 subjects and simultaneously measured the pupil diameter and light reflex amplitude with an iPhone pupillometer and a portable infrared pupillometer. We then enrolled 40 additional subjects and made serial measurements with each device. Results: Failure occurred in 30% of attempts made with the iPhone pupillometer compared with 4% of attempts made with the infrared pupillometer (Fisher’s exact p = 0.0001). Method comparison of the two devices used simultaneously showed significant disagreement in dynamic measurements. Conclusion: The iPhone pupillometer had poor repeatability and suggests that it is not a practical tool to support clinical decisions.

Background: Levels of consciousness in patients with acute and chronic brain injury are notoriously underestimated.Paradigms based on electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) may detect covert consciousness in clinically unresponsive patients but are subject to logistical challenges and the need for advanced statistical analysis.Methods: To assess the feasibility of automated pupillometry for the detection of command following, we enrolled 20 healthy volunteers and 48 patients with a wide range of neurological disorders, including 7 patients in the intensive care unit (ICU), who were asked to engage in mental arithmetic.Results: Fourteen of 20 (70%) healthy volunteers and 17 of 43 (39.5%)neurological patients, including 1 in the ICU, fulfilled prespecified criteria for command following by showing pupillary dilations during ≥4 of 5 arithmetic tasks.None of the 5 sedated and unconscious ICU patients passed this threshold.Conclusions: Automated pupillometry combined with mental arithmetic appears to be a promising paradigm for the detection of covert consciousness in people with brain injury.We plan to build on this study by focusing on non-communicating ICU patients in whom the level of consciousness is unknown.If some of these patients show reproducible pupillary dilation during mental arithmetic, this would suggest that the present paradigm can reveal covert consciousness in unresponsive patients in whom standard investigations have failed to detect signs of consciousness.

Editor—The recent review in the British Journal of Anaesthesia of monitors of nociception was an excellent discussion of a complex subject.1Ledowski T. Objective monitoring of nociception: a review of current commercial solutions.Br J Anaesth. 2019; 123: e312-e321Abstract Full Text Full Text PDF PubMed Scopus (92) Google Scholar Nociception monitors, broadly defined, are now diverging into two distinct types, with different clinical uses. The first group is designed to detect nociception during anaesthesia or deep sedation, whereas the second type is designed to help assess and treat pain in awake subjects. Monitors of both types were described in the review, but the emerging distinction was not commented upon. These two groups of monitoring devices are generally concerned with distinct physiologic pathways and lend themselves to different types of treatments. Specifically, during anaesthesia the nociceptive reflexes are primarily limited to the brainstem and spinal cord, whereas in the awake patient pain involves cortical structures such as the prefrontal cortex, sensory and motor cortices, insula, and the anterior cingulate cortex.2Ossipov M. Dussor G. Porreca F. Central modulation of pain.J Clin Invest. 2010; 120: 3779-3787Crossref PubMed Scopus (700) Google Scholar As such, 'pain' can involve complex emotional content such as catastrophising, hopelessness, and despair. This consideration raises the question of whether data from pain monitors could be useful at all in the treatment of pain because clinicians are always compelled to rely on the patient's own pain assessment. We would argue that the answer is yes, with a caveat: physiological data from a monitor should not be used as a surrogate for reported pain, but rather as a way to measure end-organ effects of therapies for pain. To be more precise, this approach simply attempts to answer the question of whether and to what extent a given pain therapy (e.g. opioid, nerve blocks, N-methyl-d-aspartate [NMDA] receptor antagonist) has saturated its end-organ target. If there is evidence of saturation, then there is minimal clinical value in further use of that therapeutic approach, regardless of the patient's pain scores. In some contexts, this approach is so obvious that it has become the standard of care. For example, if a patient has a central or peripheral nerve block but still reports pain, most acute pain physicians assess whether there is a sensory loss in the intended distribution. If there is not, the block is either repeated or adjusted to provide an appropriate sensory block. If the block does cover the intended distribution, then other therapeutic agents or techniques are used to treat the pain. We advocate the development of tools that allow expansion of this approach to new agents—for example use of opioids as the therapy and pupillary unrest as the physiologic endpoint. If a patient has a pattern of pupillary unrest consistent with a high degree of central opioid effect, then escalating doses of opioids are not advisable and other therapies should be used such as nerve blocks or ketamine.3Neice A.E. Behrends M. Bokoch M.P. Seligman K.M. Conrad N.M. Larson M.D. Prediction of opioid analgesic efficacy by measurement of pupillary unrest.Anesth Analg. 2017; 124: 915-921Crossref PubMed Scopus (26) Google Scholar, 4McKay R. Neice A. Larson M. Pupillary unrest in ambient light and prediction of opioid responsiveness: case report on its utility in the management of 2 patients with challenging acute pain conditions.Anesth Analg. 2018; 10: 279-282Google Scholar Within this framework there are a number of drug–physiological effect pairs that could potentially prove useful. In the anaesthetised patient, the value of nociception monitoring is different. As Ledowski1Ledowski T. Objective monitoring of nociception: a review of current commercial solutions.Br J Anaesth. 2019; 123: e312-e321Abstract Full Text Full Text PDF PubMed Scopus (92) Google Scholar points out, nociception monitoring during anaesthesia could be used to tailor opioid requirements for each patient and reduce the stress response to surgery. However, many of these monitors rely on the detection of sympathetic responses that might be obtunded by commonly used antihypertensive medications. For example a recent evaluation of some of these monitors' associated indices (namely the nociception index, the surgical plethysmograph index, the pulse plethysmograph amplitude, and heart rate) eliminated 12% of enrolled patients because they were taking beta-adrenergic receptor blockers.5Edry R. Recea V. Dikust Y. Sessler D.I. Preliminary intraoperative validation of the nociception level index: a noninvasive nociception monitor.Anesthesiology. 2018; 125: 193-203Google Scholar Interestingly, many pupillary indices appear to be less affected by sympathetic tone (or sympatholytic antihypertensives) compared to cardiovascular indices. For example painful stimulus reflex dilation of the pupil during anaesthesia is not a sympathetic reflex.6Loewenfeld I.E. The pupil: anatomy, physiology and clinical applications. Wayne State University Press, Detroit, MI1999Google Scholar Rather, it is brought about through inhibition of the Edinger–Westphal nucleus, and is therefore entirely a parasympathetic reflex. Like pupillary unrest, it is inhibited by opioids, and thus it is potentially useful for assessment of central opioid effect rather than global sympathetic tone (or blockade). Based on this and other examples, we believe pupillary indices have the potential to provide distinct and complimentary diagnostic information compared to cardiovascular indices. It is clear that there is potential for future research into the important issue of nociception monitoring. The authors declare that they have no conflicts of interest. Objective monitoring of nociception: a review of current commercial solutionsBritish Journal of AnaesthesiaVol. 123Issue 2PreviewNociception, in contrast to pain, is not a subjective feeling, but the physiological encoding and processing of nociceptive stimuli. However, monitoring nociception remains a challenge in attempts to lower the incidence of acute postoperative pain and the move towards a more automated approach to analgesia and anaesthesia. To date, several commercialised devices promise a more accurate reflection of nociception than the traditionally used vital signs, blood pressure and heart rate. This narrative review presents an overview of existing technologies and commercially available devices, and offers a perspective for future research. Full-Text PDF Open Archive