Abstract
Adequate pain control is a critical component of the perioperative approach to children undergoing repair of congenital heart disease (CHD). The impact of specific anatomic and physiologic disturbances on the management of analgesia has been largely unexplored at the present time. Studies in other pediatric populations have found an association between chronic hypoxemia and an increased sensitivity to the effects of opioid medications. The purpose of this retrospective study was to examine perioperative opioid administration and opioid-associated adverse effects in children undergoing surgical repair of CHD, with a comparison between patients with and without chronic preoperative cyanosis. Patients between the ages of 2 and 5 years whose tracheas were extubated in the operating room were included and were classified in the cyanotic group if they presented for the Fontan completion. The primary outcomes of interest were intraoperative and postoperative opioid administration. Secondary outcomes included pain scores and opioid-related side effects. The study cohort included 156 patients. Seventy-one underwent the Fontan procedure, twelve of which were fenestrated. Fontan patients received fewer opioids intraoperatively (11.33 µg/kg fentanyl equivalents versus 12.56 µg/kg, p = 0.03). However, there were no differences with regards to opioid consumption postoperatively and no correlation between preoperative oxygen saturation and total opioid administration. There were no differences between groups with regards to the respiratory rate nadir, postoperative pain scores, or the incidence of opioid-related side effects. In contrast to other populations with chronic hypoxemia exposure, children with cyanotic CHD did not appear to have increased sensitivity to the effects of opioid medications.
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References
Anand KJ, Hickey PR (1987) Pain and its effects in the human neonate and fetus. N Engl J Med 317(21):1321–1329
Weisman SJ, Bernstein B, Schechter NL (1998) Consequences of inadequate analgesia during painful procedures in children. Arch Pediatr Adolesc Med 152(2):147–149
Lucas SS, Nasr VG, Ng AJ, Joe C, Bond M, DiNardo JA (2016) Pediatric Cardiac Intensive Care Society 2014 consensus statement: pharmacotherapies in cardiac critical care: sedation, analgesia and muscle relaxant. Pediatr Crit Care Med 17(S3):S3–S15
Wolf AR, Jackman L (2011) Analgesia and sedation after pediatric cardiac surgery. Pediatr Anesth 21(5):567–576
Zeilmaker-Roest GA, Wildschut ED, van Dijk M, Anderson BJ, Breatnach C, Bogers AJ, Tibboel D (2017) An international survey of management of pain and sedation after paediatric cardiac surgery. BMJ Paediatr Open 1(1):e000046
Iodice FG, Thomas M, Walker I, Garside V, Elliott MJ (2011) Analgesia in fast-track paediatric cardiac patients. Eur J Cardiothorac Surg 40(3):610–613
Roy N, Parra MF, Brown ML, Sleeper LA, Nathan M, Sefton BA, Baird CW, Mistry KP, Del Nido PJ (2019) Initial experience introducing an enhanced recovery program in congenital cardiac surgery. J Thorac Cardiovasc Surg 160(5):1313–1321
Iguidbashian JP, Chang PH, Iguidbashian J, Lines J, Maxwell BG (2020) Enhanced recovery and early extubation after pediatric cardiac surgery using single-dose intravenous methadone. Ann Card Anaesth 23(1):70
Sadhasivam S, Chidambaran V (2012) Pharmacogenomics of opioids and perioperative pain management. Pharmacogenomics 13(15):1719–1740
Pollak U, Bronicki RA, Achuff BJ, Checchia PA (2019) Postoperative pain management in pediatric patients undergoing cardiac surgery: where are we heading? J Intensiv Care Med. https://doi.org/10.1177/0885066619871432
Zeilmaker GA, Pokorna P, Mian P, Wildschut ED, Knibbe CA, Krekels EH, Allegaert K, Tibboel D (2018) Pharmacokinetic considerations for pediatric patients receiving analgesia in the intensive care unit; targeting postoperative, ECMO and hypothermia patients. Expert Opin Drug Metab Toxicol 14(4):417–428
Dagan O, Klein J, Bohn D, Barker G, Koren G (1993) Morphine pharmacokinetics in children following cardiac surgery: effects of disease and inotropic support. J Cardiothorac Vasc Anesth 7(4):396–398
Waters KA, McBrien F, Stewart P, Hinder M, Wharton S (2002) Effects of OSA, inhalational anesthesia, and fentanyl on the airway and ventilation of children. J Appl Physiol 92(5):1987–1994
Brown KA, Laferrière A, Moss IR (2004) Recurrent hypoxemia in young children with obstructive sleep apnea is associated with reduced opioid requirement for analgesia. J Am Soc Anesthesiol 100(4):806–810
Brown KA, Laferriere A, Lakheeram I, Moss IR (2006) Recurrent hypoxemia in children is associated with increased analgesic sensitivity to opiates. J Am Soc Anesthesiol 105(4):665–669
Moss IR, Brown KA, Laferrière A (2006) Recurrent hypoxia in rats during development increases subsequent respiratory sensitivity to fentanyl. J Am Soc Anesthesiol 105(4):715–718
Rabbitts JA, Groenewald CB, Dietz NM, Morales C, Raesaenen J (2010) Perioperative opioid requirements are decreased in hypoxic children living at altitude. Pediatr Anesth 20(12):1078–1083
Turan A, You J, Egan C, Fu A, Khanna A, Eshraghi Y, Ghosh R, Bose S, Qavi S, Arora L (2015) Chronic intermittent hypoxia is independently associated with reduced postoperative opioid consumption in bariatric patients suffering from sleep-disordered breathing. PLoS ONE 10(5):e0127809
Brown KA (2009) Intermittent hypoxia and the practice of anesthesia. J Am Soc Anesthesiol 110(4):922–927
Laferrière A, Liu J-K, Moss IR (2003) Neurokinin-1 versus mu-opioid receptor binding in rat nucleus tractus solitarius after single and recurrent intermittent hypoxia. Brain Res Bull 59(4):307–313
Wu J, Li P, Wu X (2017) The effect of chronic intermittent hypoxia on respiratory sensitivity to morphine in rats. Sleep Breath 21(1):227–233
Cozowicz C, Chung F, Doufas AG, Nagappa M, Memtsoudis SG (2018) Opioids for acute pain management in patients with obstructive sleep apnea: a systematic review. Anesth Analg 127(4):988–1001
Lam KK, Kunder S, Wong J, Doufas AG, Chung F (2016) Obstructive sleep apnea, pain, and opioids: is the riddle solved? Curr Opin Anaesthesiol 29(1):134–140
Montana MC, Juriga L, Sharma A, Kharasch ED (2019) Opioid sensitivity in children with and without obstructive sleep apnea. Anesthesiology 130(6):936–945
Raghavendran S, Bagry H, Detheux G, Zhang X, Brouillette RT, Brown KA (2010) An anesthetic management protocol to decrease respiratory complications after adenotonsillectomy in children with severe sleep apnea. Anesth Analg 110(4):1093–1101
Sadhasivam S, Chidambaran V, Ngamprasertwong P, Esslinger HR, Prows C, Zhang X, Martin LJ, McAuliffe J (2012) Race and unequal burden of perioperative pain and opioid related adverse effects in children. Pediatrics 129(5):832–838
Turan A, Atim A, Dalton JE, Keeyapaj W, Chu W, Bernstein E, Fu A, Ho LJ, Saager L, Sessler DI (2013) Preoperative angiotensin-converting enzyme inhibitor use is not associated with increased postoperative pain and opioid use. Clin J Pain 29(12):1050–1056
Farag E, Atim A, Ghosh R, Bauer M, Sreenivasalu T, Kot M, Kurz A, Dalton JE, Mascha EJ, Mounir-Soliman L (2014) Comparison of three techniques for ultrasound-guided femoral nerve catheter insertion: a randomized, blinded trial. J Am Soc Anesthesiol 121(2):239–248
Merkel SI, Voepel-Lewis T, Shayevitz JR, Malviya S (1997) The FLACC: a behavioral scale for scoring postoperative pain in young children. Pediatr Nurs 23(3):293–297
Naguib AN, Dewhirst E, Winch PD, Simsic J, Galantowicz M, Tobias JD (2012) Pain management after surgery for single-ventricle palliation using the hybrid approach. Pediatr Cardiol 33(7):1104–1108
Naguib AN, Dewhirst E, Winch PD, Simsic J, Galantowicz M, Tobias JD (2013) Pain management after comprehensive stage 2 repair for hypoplastic left heart syndrome. Pediatr Cardiol 34(1):52–58
Doufas AG, Tian L, Padrez KA, Suwanprathes P, Cardell JA, Maecker HT, Panousis P (2013) Experimental pain and opioid analgesia in volunteers at high risk for obstructive sleep apnea. PLoS ONE 8(1):e54807
Doufas AG (2014) Obstructive sleep apnea, pain, and opioid analgesia in the postoperative patient. Curr Anesthesiol Rep 4(1):1–9
Baker T, Fuller D, Zabka A, Mitchell G (2001) Respiratory plasticity: differential actions of continuous and episodic hypoxia and hypercapnia. Respir Physiol 129(1–2):25–35
Devinney MJ, Huxtable AG, Nichols NL, Mitchell GS (2013) Hypoxia-induced phrenic long-term facilitation: emergent properties. Ann NY Acad Sci 1279(1):143–153
Powell F, Huey K, Dwinell M (2000) Central nervous system mechanisms of ventilatory acclimatization to hypoxia. Respir Physiol 121(2–3):223–236
Powell F, Milsom W, Mitchell G (1998) Time domains of the hypoxic ventilatory response. Respir Physiol 112(2):123–134
Guilleminault C, Lee JH, Chan A (2005) Pediatric obstructive sleep apnea syndrome. Arch Pediatr Adolesc Med 159(8):775–785
Brown OE, Manning SC, Ridenour B (1988) Cor pulmonale secondary to tonsillar and adenoidal hypertrophy: management considerations. Int J Pediatr Otorhinolaryngol 16(2):131–139
Acknowledgements
We would like to acknowledge Diane Hersey for her contribution to data extraction for this study.
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TM-T, JT, and PW contributed to conceptualization for the study. TM-T performed data extraction and analysis and were responsible for original draft preparation. TM-T, JT, and PW contributed to critical revisions and editing of the manuscript.
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This retrospective chart review study involving human participants was in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments. The Human Investigation Committee (IRB) of Nationwide Children’s Hospital approved this study.
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Murray-Torres, T.M., Tobias, J.D. & Winch, P.D. Perioperative Opioid Consumption is Not Reduced in Cyanotic Patients Presenting for the Fontan Procedure. Pediatr Cardiol 42, 1170–1179 (2021). https://doi.org/10.1007/s00246-021-02598-x
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DOI: https://doi.org/10.1007/s00246-021-02598-x