e1 References 1 Narang SK, Estrada C, Greenberg S, et al Acceptance of shaken baby syndrome and abusive head trauma as medical diagnoses J Pediatr 2016;177 273 278 2 Christian CW, Block R Committee on[.]
e1 References Narang SK, Estrada C, Greenberg S, et al Acceptance of shaken baby syndrome and abusive head trauma as medical diagnoses J Pediatr 2016;177:273-278 Christian CW, Block R Committee on Child Abuse and Neglect, American Academy of Pediatrics Abusive head trauma in infants and children Pediatrics 2009;123:1409-1411 Lindberg DM, Dubowitz H, Alexander RC, Reece RM The “new science” of abusive head trauma Int J Child Maltreat 2019;2:1-16 U.S Department of Health and Human Services, Administration for Children and Families, Administration on Children, Youth and Families, Children’s Bureau Child Maltreatment 2016 2018 Available at: https://www.acf.hhs.gov/sites/default/files/cb/cm2016.pdf Ward A, Iocono JA, Brown S, Ashley P, Draus JM Non-accidental trauma injury patterns and outcomes: a single institutional experience Am Surg 2015;81:835-838 Leventhal JM, Gaither JR Incidence of serious injuries due to physical abuse in the United States: 1997 to 2009 Pediatrics 2012; 130:e847-e852 Sheets LK, Leach ME, Koszewski IJ, Lessmeier AM, Nugent M, Simpson P Sentinel injuries in infants evaluated for child physical abuse Pediatrics 2013;131:701-707 Sugar NF, Taylor JA, Feldman KW Bruises in infants and toddlers: those who don’t cruise rarely bruise Arch Pediatr Adolesc Med 1999;153:399-403 Deans KJ, Minneci PC, Lowell W, Groner J Increased morbidity and mortality of traumatic brain injury in victims of nonaccidental trauma J Trauma Acute Care Surg 2013;75(1):157-160 10 Estroff JM, Foglia RP, Fuchs JR A comparison of accidental and nonaccidental trauma: it is worse than you think J of Emerg Med 2015; 48(3):274-279 11 Raghupathi R, Margulies SS Traumatic axonal injury after closed head injury in the neonatal pig J Neurotrauma 2002;19:843-885 12 Barr RG Preventing abusive head trauma resulting from a failure of normal interaction between infants and their caregivers Proc Natl Acad Sci USA 2012;109(suppl 2):17294-17301 13 Caffey J On the theory and practice of shaking infants Its potential residual effects of permanent brain damage and mental retardation Am J Dis Child 1972;124:161-169 14 Caffey J The whiplash shaken infant syndrome: manual shaking by the extremities with whiplash-induced intracranial and intraocular bleedings, linked with residual permanent brain damage and mental retardation Pediatrics 1974;54:396-403 15 Berkowitz C Physical abuse of children N Engl J Med 2017;376: 1659-1666 16 Levin AV, Christian CW, Committee on Child Abuse and Neglect, Section on Ophthalmology The eye examination in the evaluation of child abuse Pediatrics 2010;126:376-380 17 Kochanek PM, Tasker RC, Bell MJ, et al Management of Pediatric Severe Traumatic Brain Injury: 2019 Consensus and guidelinesbased algorithm for first and second tier therapies Pediatr Crit Care Med 2019;20(3):269-279 18 Hettler J, Greenes DS Can the initial history predict whether a child with a head injury has been abused? Pediatrics 2003;111:602-607 19 Jenny C, Hymel KP, Ritzen A, et al Analysis of missed cases of abusive head trauma JAMA 1999;281:621-626 20 Chadwick DL, Bertocci G, Castillo E, et al Annual risk of death resulting from short falls among young children: less than in million Pediatrics 2008;121:1213-1224 21 Maguire SA, Watts PO, Shaw AD, et al Retinal haemorrhages and related findings in abusive and21 non-abusive head trauma: a systematic review Eye (Lond) 2013;27:28-36 22 Binenbaum G, Chen W, Huang J, et al The natural history of retinal hemorrhage in pediatric head trauma J AAPOS 2016;20:131-135 23 Case ME Distinguishing accidental from inflicted head trauma at autopsy Pediatr Radiol 2014;44 (suppl 4):S632-S640 24 Wright JN CNS Injuries in Abusive Head Trauma AJR 2017;208: 991-1001 25 Geddes JF, Hackshaw AK, Vowles GH, et al Neuropathology of inflicted head injury in children I Patterns of brain damage Brain 2001;124:1290-1298 26 Choudhary AK, Ishak R, Zacharia TT, Dias MS Imaging of spinal injury in abusive head trauma: a retrospective study Pediatr Radiol 2014;44:1130-1140 27 Barber I, Perez-Rossello JM, Wilson CR, et al Prevalence and relevance of pediatric spinal fractures in suspected child abuse Pediatr Radiol 2013;43:1507-1515 28 Sieswerda-Hoogendoorn T, Postema FA, Verbaan D, et al Age determination of subdural hematomas with CT and MRI: a systematic review Eur J Radiol 2014;83:1257-1268 29 Vázquez E, Delgado I, Sánchez-Montañez A, et al Imaging abusive head trauma: why use both computed tomography and magnetic resonance imaging? Pediatr Radiol 2014;44(suppl 4):S589-S603 30 Bradford R, Choudhary AK, Dias MS Serial neuroimaging in infants with abusive head trauma: timing abusive injuries J Neurosurg Pediatr 2013;12(2):110-119 31 Adamsbaum C, Morel B, Ducot B, Antoni G, Rey-Salmon C Dating the abusive head trauma episode and perpetrator statements: key points for imaging Pediatr Radiol 2014;44(suppl 4):S578-S588 32 Barnes PM, Norton CM, Dunstan FD, et al Abdominal injury due to child abuse Lancet 2005;366:234-235 33 Gwirtzman Lanea W, Dubowitz H, Langenberg P, Dischinger P Epidemiology of abusive abdominal trauma hospitalizations in United States children Child Abuse Negl 2012;(36):142-148 34 Huntimer CM, Muret-Wagstaff S, Leland NL Can falls on stairs result in small intestine perforations? Pediatrics 2000;106(2 Pt 1): 301-305 35 Maguire SA, Upadhyaya M, Evans A, et al A systematic review of abusive visceral injuries in childhood—Their range and recognition Child Abuse Negl 2013;37(7):430-445 36 DeRidder, CA, Berkowitz CD A toddler with vomiting, abdominal pain, and alopecia Pediatr Emerg Care 2013;29(10):1114-1115 37 Rooks VJ, Eaton JP, Ruess L, et al Prevalence and evolution of intracranial hemorrhage in asymptomatic term infants AJNR Am J Neuroradiol 2008;29:1082-1089 38 Whitby EH, Griffiths PD, Rutter S, et al Frequency and natural history of subdural haemorrhages in babies and relation to obstetric factors Lancet 2004;363:846-851 39 Cherry JD Pertussis vaccine encephalopathy”: it is time to recognize it as the myth that it is JAMA 1990;263(12):1679-1680 40 Curcoy AI, Trenchs V, Morales M, et al Is pertussis in infants a potential cause of retinal haemorrhages? Arch Dis Child 2012;97: 239-240 41 Raoof N, Pereira S, Dai S, et al Retinal haemorrhage in infants with pertussis Arch Dis Child 2017;102:1158-1160 42 Curcoy AI, Trenchs V, Morales M, et al Retinal hemorrhages and apparent life-threatening events Pediatr Emerg Care 2010;26: 118-120 43 Herr S, Pierce MC, Berger RP, et al Does Valsalva retinopathy occur in infants? An initial investigation in infants with vomiting caused by pyloric stenosis Pediatrics 2004;113:1658-1661 44 Bonkowsky JL, Guenther E, Filloux FM, et al Death, child abuse and adverse neurological outcome of infants after an apparent lifethreatening event Pediatrics 2008;122:125-131 45 Hansen JB, Frazier T, Moffatt M, et al Evaluation of the hypothesis that choking/ALTE may mimic abusive head trauma Acad Pediatr 2017;17:362-367 46 Heller C, Heinecke A, Junker R, et al Childhood Stroke Study Group Cerebral venous thrombosis in children: a multifactorial origin Circulation 2003;108:1362-1367 47 McLean LA, Frasier LD, Hedlund GL Does intracranial venous thrombosis cause subdural hemorrhage in the pediatric population? AJNR Am J Neuroradiol 2012;33:1281-1284 e2 48 Choudhary AK, Servaes S, Slovis TL, et al Consensus statement on abusive head trauma in infants and young children Pediatr Radiol 2018;48:1048-1065 49 Binenbaum G, Christian CW, Guttmann K, et al Evaluation of temporal association between vaccinations and retinal hemorrhage in children JAMA Opthalmol 2015;133(11):1261-1265 50 Mendelson KL Critical review of “temporary brittle bone disease.” Pediatr Radiol 2005;35:1036-1040 e3 Abstract: The intensivist should be knowledgeable about the difference between a medical and forensic evaluation, the significance of sentinel injuries, the scope of findings as related to accidental versus abusive trauma, and the importance of a multidisciplinary approach when developing a comprehensive assessment of critically ill and injured children This chapter reviews common abuse syndromes, provides guidance on recognizing signs or patterns of abuse, and reviews obligations for information sharing Key words: child abuse, inflicted trauma, nonaccidental trauma, abusive head injury, forensic assessment, mandated reporter SECTION XIII Pediatric Critical Care: Pharmacology and Toxicology 122 Principles of Drug Disposition, 1426 123 Molecular Mechanisms of Drug Actions, 1446 124 Adverse Drug Reactions and DrugDrug Interactions, 1464 125 Principles of Toxin Assessment and Screening, 1486 126 Toxidromes and Their Treatment, 1496 1425 122 Principles of Drug Disposition NICOLE R ZANE AND ATHENA F ZUPPA • Approximately 25% of the worldwide population is younger than 15 years, meaning that a quarter of the world’s population is classified as pediatric.1 Pediatric studies were not required by the US Food and Drug Administration or other regulatory agencies prior to the late 1990s, leaving a lack of dosing guidance for children Throughout the early 19th and 20th centuries, federal regulations for medications did not exist; most medications lacked efficacy while others were blatantly toxic Some of the high-profile toxicity cases involved the disfigurement, harm, and death of children, including the tragedies of Mrs Winslow’s soothing syrup, sulfanilamide containing diethylene glycol, and thalidomide.2–4 Today, regulatory agencies require pediatric-specific clinical trials before approval of new drug entities Even with these requirements, pediatric patients, especially those who are critically ill, are undoubtedly a vulnerable population who exhibit significant physiologic differences that affect drug disposition compared with healthy children.5,6 The basics of drug disposition are governed by pharmacokinetics and pharmacodynamics There are many factors that affect the pharmacokinetics and pharmacodynamics of drugs, including, but not limited to, age and organ dysfunction Maturation and development affect every system in the body—changes occur from gestation through the newborn and infant period throughout childhood and into adulthood Some of these developmental changes have been well characterized, while others have limited data Critical illness can impact all of the major organ systems, such as the immune, cardiac, hepatic, renal, and circulatory systems, which can lead to multiorgan dysfunction.7,8 Changes in blood pH, hypoproteinemia, increased hydrostatic pressure, 1426 • • Studies of drug disposition in critically ill children are limited Effective pharmacologic therapeutic interventions should focus on choosing the right drug, right time, right dose, right duration, and right route Age-dependent and pathophysiologic changes affect the pharmacokinetics and pharmacodynamics of drugs Drug disposition is controlled by pharmacokinetics, which describes the changes in drug or metabolite concentration in the body over time Drug effect is governed through pharmacodynamics, which describes the response that is effected by the drug in the body • • • • • PEARLS A comprehensive understanding of both pharmacokinetics and pharmacodynamics allows for rational therapeutic choices based on targeting the correct drug exposure to achieve the targeted response Pharmacokinetic processes that influence drug disposition include absorption, distribution, metabolism, and elimination Pharmacotherapeutic strategies in the critically ill must incorporate developmental and disease-dependent changes for effective therapy concomitant medications, and increased capillary permeability8–10 are all aspects of critical illness that can have profound effects on drug disposition, which will be described in greater detail later in this chapter Clinical Pharmacokinetics Pharmacokinetics—the movement of compounds in, within, and out of the body—can be described using mathematical equations In simple terms, it is what the body does to the drug over time The most basic and important pharmacokinetic (PK) parameters are clearance (CL), volume of distribution (Vd), and half-life (t1/2) For drugs not administered through the intravenous route (e.g., oral, transdermal, inhaled) bioavailability (F) must also be taken into account All of these parameters influence the total concentration of drug in the body over time, also known as the area under the concentration-time curve (AUC) Clearance Clearance is defined as the volume of blood from which the drug is removed over time (e.g., mL/min or L/h) CL is often weight normalized and represented per kilogram of body weight (e.g., mL/min per kg or L/h per kg) Given a patient profile, clearance is calculated by multiplying the volume of distribution of the compartment that contains the drug by the elimination rate constant (ke) from that compartment, or the rate of drug eliminated from the body, using the following equation: CL Vd ke However, in the clinical setting, estimating the value of ke is not ... which will be described in greater detail later in this chapter Clinical Pharmacokinetics Pharmacokinetics—the movement of compounds in, within, and out of the body—can be described using mathematical... involved the disfigurement, harm, and death of children, including the tragedies of Mrs Winslow’s soothing syrup, sulfanilamide containing diethylene glycol, and thalidomide.2–4 Today, regulatory agencies... multidisciplinary approach when developing a comprehensive assessment of critically ill and injured children This chapter reviews common abuse syndromes, provides guidance on recognizing signs or patterns