Pain assessment by pupil dilation reflex in response to noxious stimulation in anaesthetized adults

D Wildemeersch, N Peeters, V Saldien, M Vercauteren, G Hans, D Wildemeersch, N Peeters, V Saldien, M Vercauteren, G Hans

Abstract

Background: In response to noxious stimulation, pupillary dilation reflex (PDR) occurs even in anaesthetized patients. The aim of the study was to evaluate the ability of pupillometry with an automated increasing stimulus intensity to monitor intraoperative opioid administration.

Methods: Thirty-four patients undergoing elective surgery were enrolled. Induction by propofol anaesthesia was increased progressively until the sedation depth criteria (SeD) were attained. Subsequently, a first dynamic pupil measurement was performed by applying standardized nociceptive stimulation (SNS). A second PDR evaluation was performed when remifentanil reached a target effect-site concentration. Automated infrared pupillometry was used to determine PDR during nociceptive stimulations generating a unique pupillary pain index (PPI). Vital signs were measured.

Results: After opioid administration, anaesthetized patients required a higher stimulation intensity (57.43 mA vs 32.29 mA, P < .0005). Pupil variation in response to the nociceptive stimulations was significantly reduced after opioid administration (8 mm vs 28 mm, P < .0005). The PPI score decreased after analgesic treatment (8 vs 2, P < .0005), corresponding to a 30% decrease. The elicitation of PDR by nociceptive stimulation was performed without changes in vital signs before (HR 76 vs 74/min, P = .09; SBP 123 vs 113 mm Hg, P = .001) and after opioid administration (HR 63 vs 62/min, P = .4; SBP 98.66 vs 93.77 mm Hg, P = .032).

Conclusions: During propofol anaesthesia, pupillometry with the possibility of low-intensity standardized noxious stimulation via PPI protocol can be used for PDR assessment in response to remifentanil administration.

Keywords: analgesia; assessment; monitoring; reflex.

© The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.

Figures

Figure 1
Figure 1
Summary of study timeline. TCA, target controlled analgesia; SeD, sedation depth; PPI, pupillary pain index; Ce, effect‐site concentration
Figure 2
Figure 2
(A), Boxplots of necessary stimulation intensity to elicit PDR via a PPI stimulation protocol. The thick horizontal line indicates the median, the limits of the box indicate the 25th (Q1) and 75th (Q3) percentiles, and the whiskers denote the extreme values (Q1 − 1.5*[IQR]; Q3 + 1.5*[IQR]). (B), Boxplots of baseline pupil diameter in millimetres (mm) before stimulation. (C), Boxplots of pupil dilation in millimetres (mm) evoked by the standardized noxious stimulation. (D), Boxplots of the pupillary pain index (PPI) score based on stimulation intensity and pupil variation

References

    1. De Jonckheere J, Bonhomme V, Jeanne M, et al. Physiological signal processing for individualized anti‐nociception management during general anesthesia: a review. Yearb Med Inform. 2015;10:95‐101.
    1. Cowen R, Stasiowska MK, Laycock H, Bantel C. Assessing pain objectively: the use of physiological markers. Anaesthesia. 2015;70:828‐847.
    1. Constant I, Sabourdin N. Monitoring depth of anesthesia: from consciousness to nociception. A window on subcortical brain activity. Paediatr Anaesth. 2015;25:73‐82.
    1. Guignard B. Monitoring analgesia. Best Pract Res Clin Anaesthesiol. 2006;20:161‐180.
    1. Ly‐Liu D, Reinoso‐Barbero F. Immediate postoperative pain can also be predicted by pupillary pain index in children. Br J Anaesth. 2015;114:345‐346.
    1. Wildemeersch D, Baeten M, Peeters N, Saldien V, Vercauteren M, Hans G. Pupillary dilation reflex and pupillary pain index evaluation during general anaesthesia: a pilot study. Rom J Anaesth Intensive Care. 2018;25:1‐5.
    1. Larson MD, Kurz A, Sessler DI, Dechert M, Bjorksten AR, Tayefeh F. Alfentanil blocks reflex pupillary dilation in response to noxious stimulation but does not diminish the light reflex. Anesthesiology. 1997;87:849‐855.
    1. Paulus J, Roquilly A, Beloeil H, Theraud J, Asehnoune K, Lejus C. Pupillary reflex measurement predicts insufficient analgesia before endotracheal suctioning in critically ill patients. Crit Care. 2013;17:R161.
    1. Guglielminotti J, Grillot N, Paule M, et al. Prediction of movement to surgical stimulation by the pupillary dilatation reflex amplitude evoked by a standardized noxious test. Anesthesiology. 2015;122:985‐993.
    1. Couret D, Boumaza D, Grisotto C, et al. Reliability of standard pupillometry practice in neurocritical care: an observational, double‐blinded study. Crit Care. 2016;20:99.
    1. Larson MD, Sessler DI, Washington DE, Merrifield BR, Hynson JA, McGuire J. Pupillary response to noxious stimulation during isoflurane and propofol anesthesia. Anesth Analg. 1993;76:1072‐1078.
    1. Larson MD, Sessler DI. Pupillometry to guide postoperative analgesia. Anesthesiology. 2012;116:980‐982.
    1. Larson MD, Behrends M. Portable infrared pupillometry: a review. Anesth Analg. 2015;120:1242‐1253.
    1. Larson MD. The effect of antiemetics on pupillary reflex dilation during epidural/general anesthesia. Anesth Analg. 2003;97:1652‐1656.
    1. Rollins MD, Feiner JR, Lee JM, Shah S, Larson M. Pupillary effects of high‐dose opioid quantified with infrared pupillometry. Anesthesiology. 2014;121:1037‐1044.
    1. Marsh B, White M, Morton N, Kenny GN. Pharmacokinetic model driven infusion of propofol in children. Br J Anaesth. 1991;67:41‐48.
    1. Shafer SL, Gregg KM. Algorithms to rapidly achieve and maintain stable drug concentrations at the site of drug effect with a computer‐controlled infusion pump. J Pharmacokinet Biopharm. 1992;20:147‐169.
    1. Minto CF, Schnider TW, Egan TD, et al. Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil. I. Model development. Anesthesiology. 1997;86:10‐23.
    1. Larson MD, Tayefeh F, Sessler DI, Daniel M, Noorani M. Sympathetic nervous system does not mediate reflex pupillary dilation during desflurane anesthesia. Anesthesiology. 1996;85:748‐754.
    1. Larson MD, Major MA. The effect of hexobarbital on the duration of the recurrent IPSP in cat motoneurons. Brain Res. 1970;21:309‐311.
    1. Gray AT, Krejci ST, Larson MD. Neuromuscular blocking drugs do not alter the pupillary light reflex of anesthetized humans. Arch Neurol. 1997;54:579‐584.
    1. Ebert TJ, Muzi M, Berens R, Goff D, Kampine JP. Sympathetic responses to induction of anesthesia in humans with propofol or etomidate. Anesthesiology. 1992;76:725‐733.
    1. 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;91:347‐352.
    1. Guignard B, Menigaux C, Dupont X, Fletcher D, Chauvin M. The effect of remifentanil on the bispectral index change and hemodynamic responses after orotracheal intubation. Anesth Analg. 2000;90:161‐167.
    1. Jakuscheit A, Weth J, Lichtner G, Jurth C, Rehberg B, von Dincklage F. Intraoperative monitoring of analgesia using nociceptive reflexes correlates with delayed extubation and immediate postoperative pain: a prospective observational study. Eur J Anaesthesiol. 2017;34:297‐305.
    1. Larson MD. Mechanism of opioid‐induced pupillary effects. Clin Neurophysiol. 2008;119:1358‐1364.
    1. Sabourdin N, Peretout JB, Khalil E, Guye ML, Louvet N, Constant I. Influence of Depth of Hypnosis on Pupillary Reactivity to a Standardized Tetanic Stimulus in Patients Under Propofol‐Remifentanil Target‐Controlled Infusion: a Crossover Randomized Pilot Study. Anesth Analg. 2018;126:70‐77.
    1. Neice AE, Behrends M, Bokoch MP, Seligman KM, Conrad NM, Larson MD. Prediction of Opioid Analgesic Efficacy by Measurement of Pupillary Unrest. Anesth Analg. 2017;124:915‐921.
    1. Larson MD, Berry PD, May J, Bjorksten A, Sessler DI. Latency of pupillary reflex dilation during general anesthesia. J Appl Physiol. 1985;2004:725‐730.
    1. Fan X, Hearne L, Lei B, Miles JH, Takahashi N, Yao G. Weak gender effects on transient pupillary light reflex. Auton Neurosci. 2009;147:9‐13.
    1. Fan X, Yao G. Modeling transient pupillary light reflex induced by a short light flash. IEEE Trans Biomed Eng. 2011;58:36‐42.

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