Post-surgical Pain Assessment in Children: Roles of Skin Conductance and Genomics

Pain assessment in infants and toddlers is quite challenging since children in these populations are nonverbal or preverbal and cannot describe the presence and severity of pain that they perceive. Over the last decade, advances in the field have included the development of behavioral scoring systems for the assessment of acute pain . However, although they have been validated, these commonly used methods of pain assessment are largely subjective and rely on a highly trained observer. An objective continuous measure of pain would be an important addition to standard behavioral painscores which require nurses to monitor the child's behavioral responses.

After standard general anesthetic mask induction, 0.5 ml of blood will be drawn for genetic analysis when the intravenous catheter is sited. A member of the research team will manually transport an appropriately-labeled blood collection tube to the Department of Anesthesiology Perioperative Genomics Laboratory for storage and further preparation for genetic analysis. The samples will be stored until the investigators have enough to process. The results will be stored in a secure database. The surgical procedure, anesthesia technique, intraoperative analgesia treatment and initial postoperative analgesia treatment will be standardized.Upon arrival in the Post-Anesthesia Care Unit(PACU), the child will be connected to standard monitors as per standard of care. Pain scores will be recorded on a scale of 0-10 (FLACC, Face, legs,activity, cry, consolability scale) scale. A member of the research team will apply the skin conductance (SC) monitor on the child's hand or foot.This will be used to measure SC values that will be saved on a laptop computer and the SC data will be analyzed off-line.

The skin conductance monitor will be applied to all study patient. There is no second arm to the study

The Skin conductance monitor for measuring skin conductance on the palm of the hand or sole of the foot in microSiemens (µS); it then calculates the number of skin conductance responses per second and the area under the registration curve. The device records sympathetic autonomous nervous system through its effect on skin. The device (Med-Storm Innovation AS, Gimle Terrasse 4, NO-0264 Oslo, Norway, support@med-storm.com) includes cables, skin electrodes, a measurement unit and a monitor.

The skin conductance monitor will be attached to the patient in the Post-Anesthesia Care Unit (PACU) for 1 hour and the skin condutance values will be analyzed off-line. Corresponding pain scores on a scale of 0-10 using the FLACC (Face, Legs, Activity, Cry and Consolibility) scale will be noted every 5 minutes for a period of 1 hour. The skin conductance values will be measured in microsiemens, also the frequency of the skin conductance responses per second will be measured. The ability of skin conductance monitor to predict post-operative pain scores, sensitivity and specificity will be measured.

Effect of single nucleotide polymorphisms in the mu-opioid receptor A118G on post-operaive pain scores

Association of the mu-opioid receptor gene A118G polymorphisms with inter-individual differences in the pain scores with standardized treatments will be evaluated.

Inclusion Criteria: Children 0 - 3 years of age inclusive Presenting for palatal repair (palatoplasty) American Society of Anesthesiologists (ASA) physical status of 1 or 2 Exclusion Criteria: Children > 3 years of age On chronic pain treatment Pre-operative use of analgesics Allergies to any anesthetics or analgesia products Known obstructive sleep apnea Diagnosis of Cystic fibrosis American Society of Anesthesiologists (ASA) physical status ≥ 3

Eriksson M, Storm H, Fremming A, Schollin J. Skin conductance compared to a combined behavioural and physiological pain measure in newborn infants. Acta Paediatr. 2008 Jan;97(1):27-30. doi: 10.1111/j.1651-2227.2007.00586.x. Epub 2007 Dec 3.

Hullett B, Chambers N, Preuss J, Zamudio I, Lange J, Pascoe E, Ledowski T. Monitoring electrical skin conductance: a tool for the assessment of postoperative pain in children? Anesthesiology. 2009 Sep;111(3):513-7. doi: 10.1097/ALN.0b013e3181b27c18.

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 Oct;62(10):989-93. doi: 10.1111/j.1365-2044.2007.05191.x.

Storm H. Skin conductance and the stress response from heel stick in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2000 Sep;83(2):F143-7. doi: 10.1136/fn.83.2.f143.

Merkel SI, Voepel-Lewis T, Shayevitz JR, Malviya S. The FLACC: a behavioral scale for scoring postoperative pain in young children. Pediatr Nurs. 1997 May-Jun;23(3):293-7.

Storm H. Changes in skin conductance as a tool to monitor nociceptive stimulation and pain. Curr Opin Anaesthesiol. 2008 Dec;21(6):796-804. doi: 10.1097/ACO.0b013e3283183fe4.

Chou WY, Yang LC, Lu HF, Ko JY, Wang CH, Lin SH, Lee TH, Concejero A, Hsu CJ. Association of mu-opioid receptor gene polymorphism (A118G) with variations in morphine consumption for analgesia after total knee arthroplasty. Acta Anaesthesiol Scand. 2006 Aug;50(7):787-92. doi: 10.1111/j.1399-6576.2006.01058.x.

Dalal PG, Doheny KK, Klick L, Britcher S, Rebstock S, Bezinover D, Palmer C, Berlin C, Postula M, Kong L, Janicki PK. Analysis of acute pain scores and skin conductance measurements in infants. Early Hum Dev. 2013 Mar;89(3):153-8. doi: 10.1016/j.earlhumdev.2012.09.008. Epub 2012 Oct 6.

Kolesnikov Y, Gabovits B, Levin A, Voiko E, Veske A. Combined catechol-O-methyltransferase and mu-opioid receptor gene polymorphisms affect morphine postoperative analgesia and central side effects. Anesth Analg. 2011 Feb;112(2):448-53. doi: 10.1213/ANE.0b013e318202cc8d. Epub 2010 Dec 2.