Perspectives of Autonomic nervous system perioperative monitoring –focus on selected tools.




perioperative monitoring, autonomic nerve system


Autonomic nervous system’s role as a “life-sustaining†system is well known. However, the anatomically and functionally complexity of ANS, makes difficult its monitoring in perioperative setting. Various methods have been proposed for measuring its activity. The current review focuses on selected tools-  electrodermal activity, pupilometry, heart rate variability, surgical skin index and  salivatory-a amylase- and their application in the field of anesthesia, intensive care and emergency medicine.

Author Biography

Theodoros Aslanidis, Mobile Intensive Care Units, National Center of Emergency Care Thessaloniki Dep. Greece

Mobile ICU

Attending physician


Hopley L,Van Schalkwyk J. FANZCA Part I Notes on the Autonomic Nervous System.[Internet] 24 Oct. 2006. Accessed: Web. 17 Sept. 2014. Availabale from:

Bucsein W. Principles of Electrodermal Phenomena. In: Bucsein W, editor Electrodermal Activity, 2nd ed. New York: Springer Science & Business Media.2012 pp.2-31.

Aslanidis T. Electrodermal activity: Applications in Perioperative setting. Int J Med Res Health Sci.2014; 3(3):687-95.

Nisbet W, Norris W, Brown J. Objective measurement of sedation. IV: The measurement and interpretation of electrical changes in the skin. Br J Anaesth 1967; 39:798-804.

Storm H, Myre K, Rostrup M, Stokland O, Lien MD, Raeder JC. Skin conductance correlates with perioperative stress. Acta Anaesthesiol Scand. 2002; 46:887-9

Storm H, Shafiei M, Myre K, Raeder J. Palmar skin conductance compared to a developed stress score and to noxious and awakening stimuli on patients in anaesthesia. Acta Anaesthesiol Scand. 2005;49:798-803

Ledowski T, Bromilow J, Paech MJ, Storm H, Hacking R, Schug SA Monitoring of skin conductance to assess postoperative pain intensity. British Journal of Anaesthesia 2006; 97: 862–5.

Ledowski T, Bromilow J, Paech MJ, Storm H,Hacking R, Schug SA Skin conductance monitoring compared with Bispectral Index to assess emergence from total i.v. anaesthesia using propofol and remifentanil. Br J Anaesth. 2006; 97(6):817-21.

Ledowski T, Bromilow J, Wu J, Paech MJ,Storm H, Schug SA. The assessment of postoperative pain by monitoring skin conductance: results of a prospective study. Anaesthesia 2007; 62: 989–93.

Gjerstad AC, Storm H, Hagen R, Huiku M, Ovigstad E, Raeder J. Skin conductance or entropy for detection of non-noxious stimulation during different clinical levels of sedation. Acta Anaesthesiol Scand 2007; 51:1-7.

Gjerstad AC, Storm H, Hagen R, Huiku M, Ovigstad E, Raeder J. Comparison of skin conductance with entropy during intubation, tetanic stimulation and emergence from general anaesthesia. Acta Anaesthesiol Scand 2007; 51:8-15.

Sabourdin N, Arnaout M, Louvet N, Guye ML, Piana F. Constant I. Pain monitoring in anesthetized children: first assessment of skin conductance and analgesia nociception index at different infusion rates of remifentanil. Paediatr Anaesth. 2013; 23:149-55

Storm H. "Pain monitoring in anesthetized children: first assessment of skin conductance and analgesia-nociception index at different infusion rates of remifentanil", recommended preset values for the skin conductance equipment was not used. Paediatr Anaesth. 2013; 23:761-3.

Czaplik M, Hübner C, Köny M, Kaliciak J, Kezze F, Leonhardt S, et al. Acute pain therapy in postanesthesia care unit directed by skin conductance: a randomized controlled trial. PLoS One. 2012;7: e41758

Scaramuzzo RT, Faraoni M, Polica E, Pagani V, Vagli E, Boldrini A. Skin conductance variations compared to ABC scale for pain evaluation in newborns. J Matern Fetal Neonatal Med. 2013; 26:1399-403

Macko J, Moravcikova D, Kantor L, Kotikova M, Humpolicek P. Skin conductance as a marker of pain in infants of different gestational age. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2013 doi: 10.5507/bp.2013.066. [Epub ahead of print]

Jesus JA. Skin conductance as pain indicator in newborns: a comparison study with heart rate, oxygen saturation and pain behavioral scales.Arq Neuropsiquiatr. 2013; 71:645.

Günther AC, Bottai M, Schandl AR, Storm H, Rossi P, Sackey PV. Palmar skin conductance variability and the relation to stimulation, pain and the motor activity assessment scale in intensive care unit patients. Crit Care. 2013; 17:R51.

Karpe J, Misiołek A, Daszkiewicz A, Misiołek H. Objective assessment of pain-related stress in mechanically ventilated newborns based on skin conductance fluctuations. Anaesthesiol Intensive Ther. 2013; 45:134-7.

Gjerstad AC, Wagner K, Henrichsen T, Storm H. Skin conductance versus the modified COMFORT sedation score as a measure of discomfort in artificially ventilated children. Pediatrics. 2008; 122:e848-53

Strehle EM, Gray WK. Comparison of skin conductance measurements and subjective pain scores in children with minor injuries. Acta Paediatr. 2013;102:e502-6

Aslanidis T., Kontogounis G. Perioperative digital pupilometry – the future? Greek e journal of Perioperative Medicine. Forthcoming 2015

Constant I, Nghe MC, Boudet L, Berniere J, Schrayer S, Seeman R, et al. 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.

Bourgeois E, Sabourdin N, Louvet N, Donette FX, Guye ML, Constant I. Minimal alveolar concentration of sevoflurane inhibiting the reflex pupillary dilatation after noxious stimulation in children and young adults.Br J Anaesth. 2012 ;108:648-54

Larson MD, Berry PD, May J, Bjorksten A, Sessler DI. Latenchy of papillary reflex during general anesthesia. J Appl Physiol 2004; 97:725-30.

Kantor E, Montravers P, Longrois D, Guglielminotti J. Pain assessment in the postanaesthesia care unit using pupillometry: A cross-sectional study after standard anaesthetic care. Eur J Anaesthesiol. 2014; 31:91-7.

Charier D, l Zantour D, Pichot V, Barthelemy JC, Molliex S. Evaluation of Analgesia During General Anesthesia: Pupillometry Versus Heart Rate Variability. ASA meeting abstracts 2012; A187.

Guglielminotti J, Mentré F, Gaillard J, Ghalayini M, Montravers P, Longrois D. Assessment of pain during labor with pupillometry: a prospective observational study. Anesth Analg. 2013; 116:1057-62.

Clinical [internet] National Institutes of Health (US). Does the Measurement of Pupillary Reactivity by an Automated Pupillometer Determine the Effectiveness of Local Anesthesia Under General Anesthesia? (ALGISCAN). Available from : Identifier: NCT01685645

Clinical [internet] National Institutes of Health (US) Prediction of Postoperative Pain by Measuring Nociception at the End of Surgery (PREPOP) Identifier: NCT01828424

Behrends M, Niemann CU, Larson MD. Infrared pupillometry to detect the light reflex during cardiopulmonary resuscitation: A case series. Resuscitation. 2012 ;83 :1223-8

Breckwoldt J, Arntz H-R. Infrared pupillometry during cardiopulmonary resuscitation for prognostication—A new tool on the horizon? Resuscitation. 2012 ;83 :1181-2.

Okada K, Ohde S, Otani N, Sera T, Mochizuki T, Aoki M, et al. Prediction protocol for neurological outcome for survivors of out-of-hospital cardiac arrest treated with targeted temperature management. Resuscitation. 2012 ;83 :734-9.

Suys T, Sala N, Rosetti AO, Oddo M. Infrared pupillometry for outcome prediction after cardiac arrest and therapeutic hypothermia. Crit. Care 2013; 17 (Supp2):P310.

Suys T, Bouzat P, Marques-Vidal P, Sala N, Payen JF, Rosetti A, et al. Automated Quantitative Pupillometry for the Prognostication of Coma After Cardiac Arrest. NeuroCrit. Care 2014; 21:300-8.

Paulus J, Roquilly A, Beloeil H, Theraud J, Ashnoune K, Lejus C. Pupillary reflex measurement predicts insufficient analgesia before endotracheal suction in critically ill patients. Crit. Care 2013; 17:R161.

Payen JF, Isnardon S, Lavolaine J, Bouzat P, Vinclair M, Francony G. Pupillometry in anesthesia and critical care. Ann Fr Anesth Reanim. 2012; 31:155-9.

Chaudhuri K, Malhma GM, Rosenfield JV. Survival of patients with coma and bilateral fixed pupils. Injury 2009; 40:28-32.

Schnell D, Arnaud L, Lemial V, Legriel S. Pupillary hippus in nonconvulsive status epilepticus. Epileptic Disord. 2012; 14:310-2.

Legriel S, Azoulay E, Resche-Rigon M, Lemiale V, Mourvillier A, Kouatchet A., et al. Functional outcome after convulsive status epilepticus. Crit Care Med 2010; 38: 2295-303.

Chen JW, Gombart ZJ, Rogers S, Gardiner SK, Cecil S, Bullock R. Pupillary reactivity as an early indicator of increased intracranial pressure: The introduction of the neurological pupil index. Surg Neurol Int 2011; 2:82.

Ledowski T. Perioperative monitoring of autonomic nervous activity- methods and clinical application. Australasian Anesthesia 2007:33-9.

Deschamps Al, Denault A. Analysis of heart rate and blood pressure variability to assess autonomic reserves: its role in anesthesiology. Anesthesiology rounds 2007; 6(2):1-6.

Mazzeo AT, Monaca EL, Di Leo R, Vita G, Santamaria LB. Heart rate variability: a diagnostic tool in anesthesia and intensive care, Acta Anaesthsiol Scand 2011;55:797-811.

Clinical [internet] National Institutes of Health (US) Heart rate in anesthesia. Available from:

Fujiwara Y, Sato Y, Shibata Y, Asakura Y, Nishiwaki K, Komatsu T. A greater decrease in blood pressure after spinal anaesthesia in patients with low entropy of the RR interval. , Acta Anaesthsiol Scand 2007; 51(9):1161-5.

McGrane S, Atria NP, Barwise JA. Perioperative implications of the patient with autonomic dysfunction. Curr Opin Anaesthesiol. 2014; 27(3):365-70.

Raimondi F, Colombo R, Spazzolini A, Corona A, Castelli A, Rech R, et al. Preoperative autonomic nervous system analysis may stratify the risk of hypotension after spinal anaesthesia. Minerva Anestesiologica 2014 Nov 11 [E Pub ahead of print]

Hanss R, Renner J, Ilies C, Moikow L, Buell O, Steinfath M, et al. Does heart rate variability predict hypotension and bradycardia after induction of general anaesthesia in high risk cardiovascular patients? Anaesthesia. 2008; 63(2):129-35.

Barnaby D, Ferrick K, Kaplan DT, Shah S, Bijur P, Gallagher EJ.Heart Rate Variability in Emergency Department Patients with Sepsis. Acad Emerg Med. 2002; 9(7):661-70.

Harris PR, Stein PK, Fung GL, Drew BJ. Heart rate variability measured early in patients with evolving acute coronary syndrome and 1-year outcomes of rehospitalization and mortality. Vasc Health Risk Manag.2014; 5(10):451-64.

Cooke WH, Salinas J, Convertino VA, Ludwig DA, Hinds D, Duke JH, et al. Heart rate variability and its association with mortality in prehospital trauma patients. J Trauma. 2006; 60(2):363-70.

Claret PG, Bobbia X, Ariabod A, De La Coussaye JE, Heart rate variability measures as predictors of mortality in emergency department patients, Advances in Life Sciences and Health 2014;1(1):64-9.

Biswas AK, Scott WA, Sommerauer JF, Luckett PM, Heart rate variability after acute traumatic brain injury in children. Crit Care Med 2000; 28:3907-12.

Mowery NT, Norris PR, Riordan W, Jenkins JM, Wiliams AE, Morris JA Jr. Cardiac uncoupling and heart rate variability are associated with intracranial hypertension and mortality: a study of 145 trauma patients with continuous monitoring. J Trauma 2008; 65:621-7.

Jurák P, ZvoníÄek V, Leinveber P, Halámek J, Vondra V. Respiratory induced heart rate and blood pressure variability during mechanical ventilation in critically ill and brain death patients. Conf Proc IEEE Eng Med Biol Soc. 2012; 2012:3821-4.

Malmqvist L, Biering-Sørensen T, Bartholdy K, Krassioukov A, Welling KL, Svendsen JH, et al. Assessment of autonomic function after acute spinal cord injury using heart rate variability analyses. Spinal Cord. 2014 Nov 18 [Epub ahead of print].

Günther A, Salzmann I, Nowack S, Schwab M, Surber R, Hoyer H, et al. Heart rate variability - a potential early marker of sub-acute post-stroke infections. Acta Neurol Scand. 2012; 126(3):189-96.

Chen CF, Lai CL, Lin HF, Liou LM, Lin RT. Reappraisal of heart rate variability in acute ischemic stroke. Kaohsiung J Med Sci. 2011; 27(6):215-21.

Papaioannou V, Pneumatikos I, Maglaveras N. Association of heart rate variability and inflammatory response in patients with cardiovascular diseases: current strength and limitations. Front. Physiol. 2013;4:174

Buccelletti E, Gilardi E, Scaini E, Giaouto L, Persiani R, Biondi A, et al. Heart rate variability and myocardial infarction: systemic literature review and meta-analysis. Eur Rev Med Pharmacol Sci 2009; 13:299-307.

Ilies C, Gruenewald M, Ludwigs J, Thee C, Höcker J, Hanss R, et al. Evaluation of the surgical stress index during spinal and general anaesthesia Br. J. Anaesth. 2010; 105(4): 533-7.

Chen X, Thee C, Gruenewald M, Wnent J, Illies C, Hoecker J, et al. Comparison of surgical stress index-guided analgesia with standard clinical practice during routine general anesthesia: a pilot study.Anesthesiology. 2010; 112(5):1175-83.

Mater UN, Rohleder N, Salivary a-amylase as an non-invasive biomarker for the sympathetic nervous system: current state of research. Psychoneuroendocrinology 2009; 34:486-96.

Chiffer McKay KA, Buen JE, Bohan KJ, Maye JP. Determining the Relationship of Acute Stress, Anxiety, and Salivary a-Amylase Level With Performance of Student Nurse Anesthetists During Human-Based Anesthesia Simulator Training. AANA journal 2010;78(4):301-9.

Morrison, WE, Haas, EC, Shaffner, DH, Garrett, ES, Fackler, JC. Noise, stress, and annoyance in a pediatric intensive care unit. Crit Care Med 2003; 31: 113-9.

Minowa C, Koitabashi K, Salivary alpha-amylase activity—An indicator of relaxation response in perioperative patients. Open journal Nursing 2012; 2:208-14.

Shen YS, Chan CM, Chen WL, Chen JH, Chang HY, Chu H. Initial salivary α-amylase activity predicts malignant ventricular arrhythmias and short-term prognosis after ST-segment elevation myocardial infarction. Emerg Med J. 2011; 28(12):1041-5.

Shen YS, Chan CM, Chen WL, Chen JH, Chang HY, Chu H. Diagnostic performance of initial salivary alpha-amylase activity for acute myocardial infarction in patients with acute chest pain. J Emerg Med. 2012;43(4):553-60.

Kienbaum P, Heuter T, Michel MC, Peters J. Racemic ketamine decreases muscle sympathetic activity but maintains the neural response to hypotensive challenges in humans. Anesthesiology. 2000 ;92(1):94-101.

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(5):725-33.

Ebert TJ, Trotier TS, Arain SR, Uhrich TD, Barney JA. High concentrations of isoflurane do not block the sympathetic nervous system activation from desflurane. Can J Anaesth. 2001; 48(2):133-8.

Neukirchen M, Hipp J, Schaefer MS, Brandenburger T, Bauer I, Winterhalter M, et al. Cardiovascular stability and unchanged muscle sympathetic activity during xenon anaesthesia: role of norepinephrine uptake inhibition. Br J Anaesth. 2012 ;109(6):887-96.

Zhu L, Tian C, Li M, Peng MQ, Ma KL, Wang ZL, et al. The stress response and anesthetic potency of unilateral spinal anesthesia for total Hip Replacement in geriatric patients. Pak J Pharm Sci. 2014; 27(6 Suppl):2029-34.

Watanabe K, Kashiwagi K, Kamiyama T, Yamamoto M, Fukunaga M, Inada E, et al. High-dose remifentanil suppresses stress response associated with pneumoperitoneum during laparoscopic colectomy. J Anesth. 2014; 28(3):334-40.






Anesthesiology & Emergency Medicine