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Chapter 19 - Anesthetic-Induced Neurotoxicity

Published online by Cambridge University Press:  02 November 2018

By
Mary Ellen McCann
Edited by
Sulpicio G. Soriano  and
Craig D. McClain
Sulpicio G. Soriano
Affiliation:
Boston Children’s Hospital
Craig D. McClain
Affiliation:
Boston Children’s Hospital
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Essentials of Pediatric Neuroanesthesia , pp. 159 - 172
Publisher: Cambridge University Press
Print publication year: 2018

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References

McCann, ME, Schouten, AN, Dobija, N, Munoz, C, Stephenson, L, Poussaint, TY, et al. Infantile postoperative encephalopathy: perioperative factors as a cause for concern. Pediatrics. 2014;133:e751–7.CrossRefGoogle ScholarPubMed
Centers for Disease Control and Prevention. Update on overall prevalence of major birth defects—Atlanta, Georgia, 1978–2005. MMWR Morb Mortal Wkly Rep. 2008;57:1–5.Google Scholar
Flick, RP, Sprung, J, Harrison, TE, Gleich, SJ, Schroeder, DR, Hanson, AC, et al. Perioperative cardiac arrests in children between 1988 and 2005 at a tertiary referral center: a study of 92,881 patients. Anesthesiology. 2007;106:226–37; quiz 413–14.Google Scholar
Wilder, RT, Flick, RP, Sprung, J, Katusic, SK, Barbaresi, WJ, Mickelson, C, et al. Early exposure to anesthesia and learning disabilities in a population-based birth cohort. Anesthesiology. 2009;110:796–804.CrossRefGoogle Scholar
Ing, C, Dimaggio, C, Whitehouse, A, Hegarty, MK, Brady, J, von Ungern, BS, et al. Long-term differences in language and cognitive function after childhood exposure to anesthesia. Pediatrics. 2012;130(3):e476–85.Google Scholar
Jevtovic-Todorovic, V, Hartman, RE, Izumi, Y, Benshoff, ND, Dikranian, K, Zorumski, CF, et al. Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J Neurosci. 2003;23:876–82.Google Scholar
Ikonomidou, C, Bosch, F, Miksa, M, Bittigau, P, Vockler, J, Dikranian, K, et al. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science. 1999;283:70–4.CrossRefGoogle ScholarPubMed
Lu, Y, Wu, X, Dong, Y, Xu, Z, Zhang, Y, Xie, Z. Anesthetic sevoflurane causes neurotoxicity differently in neonatal naive and Alzheimer disease transgenic mice. Anesthesiology. 2010;112:1404–16.CrossRefGoogle ScholarPubMed
Rizzi, S, Carter, LB, Ori, C, Jevtovic-Todorovic, V. Clinical anesthesia causes permanent damage to the fetal guinea pig brain. Brain Pathol. 2008;18:198–210.Google Scholar
Brambrink, AM, Back, SA, Riddle, A, Gong, X, Moravec, MD, Dissen, GA, et al. Isoflurane-induced apoptosis of oligodendrocytes in the neonatal primate brain. Ann Neurol. 2012;72:525–35.Google Scholar
Brambrink, AM, Evers, AS, Avidan, MS, Farber, NB, Smith, DJ, Zhang, X, et al. Isoflurane-induced neuroapoptosis in the neonatal rhesus macaque brain. Anesthesiology. 2010;112:834–41.CrossRefGoogle ScholarPubMed
Olney, JW. Fetal alcohol syndrome at the cellular level. Addict Biol. 2004;9:137–49; discussion 51.Google Scholar
Dobbing, J, Sands, J. Comparative aspects of the brain growth spurt. Early Hum Dev. 1979;3:79–83.CrossRefGoogle ScholarPubMed
Cande, C, Cohen, I, Daugas, E, Ravagnan, L, Larochette, N, Zamzami, N, et al. Apoptosis-inducing factor (AIF): a novel caspase-independent death effector released from mitochondria. Biochimie. 2002;84:215–22.Google Scholar
Stratmann, G, Sall, JW, May, LD, Bell, JS, Magnusson, KR, Rau, V, et al. Isoflurane differentially affects neurogenesis and long-term neurocognitive function in 60-day-old and 7-day-old rats. Anesthesiology. 2009;110:834–48.Google Scholar
Culley, DJ, Cotran, EK, Karlsson, E, Palanisamy, A, Boyd, JD, Xie, Z, et al. Isoflurane affects the cytoskeleton but not survival, proliferation, or synaptogenic properties of rat astrocytes in vitro. Br J Anaesth. 2013;110(suppl 1):i19–28.Google Scholar
Hofacer, RD, Deng, M, Ward, CG, Joseph, B, Hughes, EA, Jiang, C, et al. Cell-age specific vulnerability of neurons to anesthetic toxicity. Ann Neurol. 2013;73(6):695–704.Google Scholar
Culley, DJ, Boyd, JD, Palanisamy, A, Xie, Z, Kojima, K, Vacanti, CA, et al. Isoflurane decreases self-renewal capacity of rat cultured neural stem cells. Anesthesiology. 2011;115:754–63.Google Scholar
De Roo, M, Klauser, P, Briner, A, Nikonenko, I, Mendez, P, Dayer, A, et al. Anesthetics rapidly promote synaptogenesis during a critical period of brain development. PLOS ONE. 2009;4:e7043.Google Scholar
Briner, A, De Roo, M, Dayer, A, Muller, D, Habre, W, Vutskits, L. Volatile anesthetics rapidly increase dendritic spine density in the rat medial prefrontal cortex during synaptogenesis. Anesthesiology. 2010;112:546–56.Google Scholar
Lu, LX, Yon, JH, Carter, LB, Jevtovic-Todorovic, V. General anesthesia activates BDNF-dependent neuroapoptosis in the developing rat brain. Apoptosis. 2006;11:1603–15.Google Scholar
Creeley, CE, Dikranian, KT, Dissen, GA, Back, SA, Olney, JW, Brambrink, AM. Isoflurane-induced apoptosis of neurons and oligodendrocytes in the fetal rhesus macaque brain. Anesthesiology. 2014;120:626–38.Google Scholar
Sanders, RD, Xu, J, Shu, Y, Fidalgo, A, Ma, D, Maze, M. General anesthetics induce apoptotic neurodegeneration in the neonatal rat spinal cord. Anesth Analg. 2008;106:1708–11.Google Scholar
Walker, SM, Westin, BD, Deumens, R, Grafe, M, Yaksh, TL. Effects of intrathecal ketamine in the neonatal rat: evaluation of apoptosis and long-term functional outcome. Anesthesiology. 2010;113:147–59.Google Scholar
Yahalom, B, Athiraman, U, Soriano, SG, Zurakowski, D, Carpino, EA, Corfas, G, et al. Spinal anesthesia in infant rats: development of a model and assessment of neurologic outcomes. Anesthesiology. 2011;114:1325–35.Google Scholar
Strunk, T, Inder, T, Wang, X, Burgner, D, Mallard, C, Levy, O. Infection-induced inflammation and cerebral injury in preterm infants. Lancet Infect Dis. 2014;14:751–62.CrossRefGoogle ScholarPubMed
Tao, G, Zhang, J, Zhang, L, Dong, Y, Yu, B, Crobsy, G, et al. Sevoflurane induces tau phosphorylation and glycogen synthase kinase 3 beta activation in young mice. Anesthesiology. 2014;121:510–27.CrossRefGoogle ScholarPubMed
Anand, KJ, Garg, S, Rovnaghi, CR, Narsinghani, U, Bhutta, AT, Hall, RW. Ketamine reduces the cell death following inflammatory pain in newborn rat brain. Pediatr Res. 2007;62:283–90.Google Scholar
Paule, MG, Li, M, Allen, RR, Liu, F, Zou, X, Hotchkiss, C, et al. Ketamine anesthesia during the first week of life can cause long-lasting cognitive deficits in rhesus monkeys. Neurotoxicol Teratol. 2011;33:220–30.Google Scholar
Paule, MG, Li, M, Allen, RR, Liu, F, Zou, X, Hotchkiss, C, et al. Ketamine anesthesia during the first week of life can cause long-lasting cognitive deficits in rhesus monkeys. Neurotoxicol Teratol. 2011;33(2): 220–30.CrossRefGoogle ScholarPubMed
Soriano, SG, Anand, KJ. Anesthetics and brain toxicity. Curr Opin Anaesthesiol. 2005;18:293–7.Google Scholar
Istaphanous, GK, Howard, J, Nan, X, Hughes, EA, McCann, JC, McAuliffe, JJ, et al. Comparison of the neuroapoptotic properties of equipotent anesthetic concentrations of desflurane, isoflurane, or sevoflurane in neonatal mice. Anesthesiology. 2011;114:578–87.Google Scholar
Massa, H, Lacoh, CM, Vutskits, L. Effects of morphine on the differentiation and survival of developing pyramidal neurons during the brain growth spurt. Toxicol Sci. 2012;130:168–79.Google Scholar
Sanders, RD, Xu, J, Shu, Y, Januszewski, A, Halder, S, Fidalgo, A, et al. Dexmedetomidine attenuates isoflurane-induced neurocognitive impairment in neonatal rats. Anesthesiology. 2009;110:1077–85.Google Scholar
Shih, J, May, LD, Gonzalez, HE, Lee, EW, Alvi, RS, Sall, JW, et al. Delayed environmental enrichment reverses sevoflurane-induced memory impairment in rats. Anesthesiology. 2012;116:586–602.CrossRefGoogle ScholarPubMed
Hayashi, H, Dikkes, P, Soriano, SG. Repeated administration of ketamine may lead to neuronal degeneration in the developing rat brain. Paediatr Anaesth. 2002;12:770–4.CrossRefGoogle ScholarPubMed
Scallet, AC, Schmued, LC, Slikker, W Jr., Grunberg, N, Faustino, PJ, Davis, H, et al. Developmental neurotoxicity of ketamine: morphometric confirmation, exposure parameters, and multiple fluorescent labeling of apoptotic neurons. Toxicol Sci. 2004;81:364–70.CrossRefGoogle ScholarPubMed
Rudin, M, Ben-Abraham, R, Gazit, V, Tendler, Y, Tashlykov, V, Katz, Y. Single-dose ketamine administration induces apoptosis in neonatal mouse brain. J Basic Clin Physiol Pharmacol. 2005;16:231–43.CrossRefGoogle ScholarPubMed
Fredriksson, A, Ponten, E, Gordh, T, Eriksson, P. Neonatal exposure to a combination of N-methyl-D-aspartate and gamma-aminobutyric acid type A receptor anesthetic agents potentiates apoptotic neurodegeneration and persistent behavioral deficits. Anesthesiology. 2007;107:427–36.CrossRefGoogle ScholarPubMed
Yon, JH, Daniel-Johnson, J, Carter, LB, Jevtovic-Todorovic, V. Anesthesia induces neuronal cell death in the developing rat brain via the intrinsic and extrinsic apoptotic pathways. Neuroscience. 2005;135:815–27.CrossRefGoogle Scholar
Haelewyn, B, David, HN, Rouillon, C, Chazalviel, L, Lecocq, M, Risso, JJ, et al. Neuroprotection by nitrous oxide: facts and evidence. Crit Care Med. 2008;36:2651–9.Google Scholar
Chan, MT, Wan, AC, Gin, T, Leslie, K, Myles, PS. Chronic postsurgical pain after nitrous oxide anesthesia. Pain. 2011;152:2514–20.CrossRefGoogle ScholarPubMed
Edwards, DA, Shah, HP, Cao, W, Gravenstein, N, Seubert, CN, Martynyuk, AE. Bumetanide alleviates epileptogenic and neurotoxic effects of sevoflurane in neonatal rat brain. Anesthesiology. 2010;112:567–75.Google Scholar
Bittigau, P, Sifringer, M, Genz, K, Reith, E, Pospischil, D, Govindarajalu, S, et al. Antiepileptic drugs and apoptotic neurodegeneration in the developing brain. Proc Natl Acad Sci USA. 2002;99:15089–94.Google Scholar
Asimiadou, S, Bittigau, P, Felderhoff-Mueser, U, Manthey, D, Sifringer, M, Pesditschek, S, et al. Protection with estradiol in developmental models of apoptotic neurodegeneration. Ann Neurol. 2005;58:266–76.CrossRefGoogle ScholarPubMed
Cattano, D, Young, C, Straiko, MM, Olney, JW. Subanesthetic doses of propofol induce neuroapoptosis in the infant mouse brain. Anesth Analg. 2008;106:1712–14.Google Scholar
Zhang, X, Xue, Z, Sun, A. Subclinical concentration of sevoflurane potentiates neuronal apoptosis in the developing C57BL/6 mouse brain. Neurosci Lett. 2008;447:109–14.Google Scholar
Yon, JH, Carter, LB, Reiter, RJ, Jevtovic-Todorovic, V. Melatonin reduces the severity of anesthesia-induced apoptotic neurodegeneration in the developing rat brain. Neurobiol Dis. 2006;21:522–30.Google Scholar
Xu, S, Pi, H, Zhang, L, Zhang, N, Li, Y, Zhang, H, et al. Melatonin prevents abnormal mitochondrial dynamics resulting from the neurotoxicity of cadmium by blocking calcium-dependent translocation of Drp1 to the mitochondria. J Pineal Res. 2016;60:291–302.Google Scholar
Cattano, D, Williamson, P, Fukui, K, Avidan, M, Evers, AS, Olney, JW, et al. Potential of xenon to induce or to protect against neuroapoptosis in the developing mouse brain. Can J Anaesth. 2008;55:429–36.Google Scholar
Ma, D, Williamson, P, Januszewski, A, Nogaro, MC, Hossain, M, Ong, LP, et al. Xenon mitigates isoflurane-induced neuronal apoptosis in the developing rodent brain. Anesthesiology. 2007;106:746–53.Google Scholar
Shu, Y, Patel, SM, Pac-Soo, C, Fidalgo, AR, Wan, Y, Maze, M, et al. Xenon pretreatment attenuates anesthetic-induced apoptosis in the developing brain in comparison with nitrous oxide and hypoxia. Anesthesiology. 2010;113:360–8.Google Scholar
Liu, F, Rainosek, SW, Sadovova, N, Fogle, CM, Patterson, TA, Hanig, JP, et al. Protective effect of acetyl-L-carnitine on propofol-induced toxicity in embryonic neural stem cells. Neurotoxicology. 2014;42:49–57.Google Scholar
Zou, X, Sadovova, N, Patterson, TA, Divine, RL, Hotchkiss, CE, Ali, SF, et al. The effects of L-carnitine on the combination of, inhalation anesthetic-induced developmental, neuronal apoptosis in the rat frontal cortex. Neuroscience. 2008;151:1053–65.Google Scholar
Straiko, MM, Young, C, Cattano, D, Creeley, CE, Wang, H, Smith, DJ, et al. Lithium protects against anesthesia-induced developmental neuroapoptosis. Anesthesiology. 2009;110:862–8.Google Scholar
Eberspacher, E, Werner, C, Engelhard, K, Pape, M, Gelb, A, Hutzler, P, et al. The effect of hypothermia on the expression of the apoptosis-regulating protein Bax after incomplete cerebral ischemia and reperfusion in rats. J Neurosurg Anesthesiol. 2003;15:200–8.CrossRefGoogle ScholarPubMed
Mason, KP, Zgleszewski, S, Forman, RE, Stark, C, DiNardo, JA. An exaggerated hypertensive response to glycopyrrolate therapy for bradycardia associated with high-dose dexmedetomidine. Anesth Analg. 2009;108:906–8.CrossRefGoogle ScholarPubMed
Johnson, ME, Uhl, CB, Spittler, KH, Wang, H, Gores, GJ. Mitochondrial injury and caspase activation by the local anesthetic lidocaine. Anesthesiology. 2004;101:1184–94.Google Scholar
Werdehausen, R, Fazeli, S, Braun, S, Hermanns, H, Essmann, F, Hollmann, MW, et al. Apoptosis induction by different local anaesthetics in a neuroblastoma cell line. Br J Anaesth. 2009;103:711–18.Google Scholar
Loepke, AW, McCann, JC, Kurth, CD, McAuliffe, JJ. The physiologic effects of isoflurane anesthesia in neonatal mice. Anesth Analg. 2006;102:75–80.Google Scholar
Brooker, RW, Keenan, WJ. Inguinal hernia: relationship to respiratory disease in prematurity. J Pediatr Surg. 2006;41:1818–21.Google Scholar
Stolwijk, LJ, Lemmers, PM, Harmsen, M, Groenendaal, F, de Vries, LS, van der Zee, DC, et al. Neurodevelopmental outcomes after neonatal surgery for major noncardiac anomalies. Pediatrics. 2016;137:e20151728.Google Scholar
Davidson, AJ, Disma, N, de Graaff, JC, Withington, DE, Dorris, L, Bell, G, et al. Neurodevelopmental outcome at 2 years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): an international multicentre, randomised controlled trial. Lancet. 2016;387:239–50.CrossRefGoogle ScholarPubMed
Eishima, K. The effects of obstetric conditions on neonatal behaviour in Japanese infants. Early Hum Dev. 1992;28:253–63.Google Scholar
Sprung, J, Flick, RP, Wilder, RT, Katusic, SK, Pike, TL, Dingli, M, et al. Anesthesia for cesarean delivery and learning disabilities in a population-based birth cohort. Anesthesiology. 2009;111:302–10.Google Scholar
Flick, RP, Lee, K, Hofer, RE, Hambel, EM, Klein, MK, Gunn, PW, et al. Neuraxial labor analgesia for vaginal delivery and its effects on childhood learning disabilities. Anesth Analg. 2011;112:1424–31.Google Scholar
Victorian Infant Collaborative Study Group. Surgery and the tiny baby: sensorineural outcome at 5 years of age. J Paediatr Child Health. 1996;32:167–72.Google Scholar
Blakely, ML, Tyson, JE, Lally, KP, McDonald, S, Stoll, BJ, Stevenson, DK, et al. Laparotomy versus peritoneal drainage for necrotizing enterocolitis or isolated intestinal perforation in extremely low birth weight infants: outcomes through 18 months adjusted age. Pediatrics. 2006;117:e680–7.CrossRefGoogle ScholarPubMed
Hintz, SR, Kendrick, DE, Stoll, BJ, Vohr, BR, Fanaroff, AA, Donovan, EF, et al. Neurodevelopmental and growth outcomes of extremely low birth weight infants after necrotizing enterocolitis. Pediatrics. 2005;115:696–703.Google Scholar
Walsh, MC, Kliegman, RM, Hack, M. Severity of necrotizing enterocolitis: influence on outcome at 2 years of age. Pediatrics. 1989;84:808–14.Google Scholar
Tobiansky, R, Lui, K, Roberts, S, Veddovi, M. Neurodevelopmental outcome in very low birthweight infants with necrotizing enterocolitis requiring surgery. J Paediatr Child Health. 1995;31:233–6.CrossRefGoogle ScholarPubMed
Lindahl, H. Long-term prognosis of successfully operated oesophageal atresia—with aspects on physical and psychological development. Z Kinderchir. 1984;39:6–10.Google Scholar
Bouman, NH, Koot, HM, Hazebroek, FW. Long-term physical, psychological, and social functioning of children with esophageal atresia. J Pediatr Surg. 1999;34:399–404.Google Scholar
Bellinger, DC, Rappaport, LA, Wypij, D, Wernovsky, G, Newburger, JW. Patterns of developmental dysfunction after surgery during infancy to correct transposition of the great arteries. J Dev Behav Pediatr. 1997;18:75–83.Google Scholar
Bellinger, DC, Wypij, D, duPlessis, AJ, Rappaport, LA, Jonas, RA, Wernovsky, G, et al. Neurodevelopmental status at eight years in children with dextro-transposition of the great arteries: the Boston Circulatory Arrest Trial. J Thorac Cardiovasc Surg. 2003;126:1385–96.Google Scholar
Bellinger, DC, Wypij, D, Kuban, KC, Rappaport, LA, Hickey, PR, Wernovsky, G, et al. Developmental and neurological status of children at 4 years of age after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass. Circulation. 1999;100:526–32.CrossRefGoogle ScholarPubMed
Hovels-Gurich, HH, Seghaye, MC, Dabritz, S, Messmer, BJ, von Bernuth, G. Cognitive and motor development in preschool and school-aged children after neonatal arterial switch operation. J Thorac Cardiovasc Surg. 1997;114:578–85.Google Scholar
Miller, SP, McQuillen, PS, Hamrick, S, Glidden, DV, Charlton, N, Karl, T, et al. Abnormal brain development in newborns with congenital heart disease. N Engl J Med. 2007;357:1928–38.Google Scholar
CJSL, DiMaggio, Kakavouli, A, Li, G. A retrospective cohort study of the association of anesthesia and hernia repair surgery with behavioral and developmental disorders in young children. J Neurosurg Anesthesiol. 2009;21(4):286–91.Google Scholar
Kalkman, CJ, Peelen, L, Moons, KG, Veenhuizen, M, Bruens, M, Sinnema, G, et al. Behavior and development in children and age at the time of first anesthetic exposure. Anesthesiology. 2009;110:805–12.CrossRefGoogle ScholarPubMed
Dimaggio, C, Sun, L, Li, G. Early childhood exposure to anesthesia and risk of developmental and behavioral disorders in a sibling birth cohort. Anesth Analg. 2011;113(5):1143–51.Google Scholar
Ing, C, Sun, M, Olfson, M, DiMaggio, CJ, Sun, LS, Wall, MM, et al. Age at exposure to surgery and anesthesia in children and association with mental disorder diagnosis. Anesth Analg. 2017;125:1988–98.Google Scholar
Backeljauw, B, Holland, SK, Altaye, M, Loepke, AW. Cognition and brain structure following early childhood surgery with anesthesia. Pediatrics. 2015;136:e1–12.CrossRefGoogle ScholarPubMed
O’Leary, JD, Janus, M, Duku, E, Wijeysundera, DN, To, T, Li, P, et al. A population-based study evaluating the association between surgery in early life and child development at primary school entry. Anesthesiology. 2016;125:272–9.Google Scholar
Graham, MR, Brownell, M, Chateau, DG, Dragan, RD, Burchill, C, Fransoo, RR. Neurodevelopmental assessment in kindergarten in children exposed to general anesthesia before the age of 4 years: a retrospective matched cohort study. Anesthesiology. 2016;125:667–77.Google Scholar
Glatz, P, Sandin, RH, Pedersen, NL, Bonamy, AK, Eriksson, LI, Granath, F. Association of anesthesia and surgery during childhood with long-term academic performance. JAMA Pediatr. 2017;171:e163470.Google Scholar
Whitton, JP, Polley, DB. Evaluating the perceptual and pathophysiological consequences of auditory deprivation in early postnatal life: a comparison of basic and clinical studies. J Assoc Res Otolaryngol. 2011;12:535–47.Google Scholar
Hansen, TG, Pedersen, JK, Henneberg, SW, Pedersen, DA, Murray, JC, Morton, NS, et al. Academic performance in adolescence after inguinal hernia repair in infancy: a nationwide cohort study. Anesthesiology. 2011;114(5):1076–85.Google Scholar
Bartels, M, Althoff, RR, Boomsma, DI. Anesthesia and cognitive performance in children: no evidence for a causal relationship. Twin Res Hum Genet. 2009;12:246–53.Google Scholar
Davidson, AJ, Disma, N, de Graaff, JC, Withington, DE, Dorris, L, Bell, G, et al. Neurodevelopmental outcome at 2 years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): an international multicentre, randomised controlled trial. Lancet. 2016;387:239–50.Google Scholar
Sun, LS, Li, G, Miller, TL, Salorio, C, Byrne, MW, Bellinger, DC, et al. Association between a single general anesthesia exposure before age 36 months and neurocognitive outcomes in later childhood. JAMA. 2016;315:2312–20.Google Scholar
Rappaport, B, Mellon, RD, Simone, A, Woodcock, J. Defining safe use of anesthesia in children. N Engl J Med. 2011;364:1387–90.Google Scholar
Rappaport, BA, Suresh, S, Hertz, S, Evers, AS, Orser, BA. Anesthetic neurotoxicity—clinical implications of animal models. N Engl J Med. 2015;372:796–7.Google Scholar
US Food and Drug Administration. FDA Drug Safety Communication: FDA approves label changes for use of general anesthetic and sedation drugs in young children. 2017. Available at www.fda.gov/Drugs/DrugSafety/ucm554634.htm.Google Scholar
van der Griend, BF, Lister, NA, McKenzie, IM, Martin, N, Ragg, PG, Sheppard, SJ, et al. Postoperative mortality in children after 101,885 anesthetics at a tertiary pediatric hospital. Anesth Analg. 2011;112:1440–7.Google Scholar

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