Medical Aspects of Chemical Warfare (2008) - The Black Vault

Medical Aspects of Chemical Warfarechemicals may tend to have a larger volume of distributionin newborns and infants because of theirrelatively large water content. On the other hand, toxiclipophilic agents, such as nerve agents, are decreased intheir partitioning to fat because of the lower body lipidcontent in young children compared to older childrenand adults. 52,53,55 Lower fat stores may cause lipophilicagents to reach higher concentrations in children’splasma than they would in adults’.Organ size relative to body weight is another factoraffecting the tissue distribution of chemicals inchildren. Young children’s brains are disproportionatelylarge and their blood-brain barriers are relativelypermeable, which leads to higher concentrations ofsome chemicals in the brain. 56 Liver mass relative tobody weight is greatest in the early postnatal period,and other tissues (eg, liver, kidney, lung, and brain)undergo rapid growth during the first 2 years of life; 57these organs are all at increased risk from toxicitybecause of children’s disproportionately larger sizerelative to body weight.Renal clearance is particularly diminished in childrencompared to adults. Glomerular filtration rateand transporter (secretory) systems in the proximalconvoluted tubule are decreased at birth. 52,55 In addition,although cardiac output is higher in children thanin adults, a lower percentage of the output reaches thekidneys, 54 decreasing renal clearance even further andleading to greater plasma levels of toxic agent. Theparental forms of nerve agents and their metabolitesundergo hydrolysis with predominantly renal elimination;however, renal clearance is faster in childrencompared to adults because of allometric scalingdifferences. According to the rules of allometric scaling,smaller organisms have greater respiratory rates,cardiac output, nutrient and oxygen demands, andbasal metabolic rates compared to larger organisms.This appears to be true for children, although fastermetabolic rates are not seen in neonates because ofhepatic enzyme immaturity and reduced hepatic clearance(which lead to a prolonged toxic agent half-lifeand duration of action).Metabolic VulnerabilityChildren are unable to detoxify as efficiently asadults because they have less mature metabolic systems.33 In particular, phase I oxidative systems, phase IIconjugating systems, and other systems (eg, serum esterases,hydrolases, dehydrogenases) are all immaturein children compared to adults. Neonates and childrenup to 1 year old are most affected in their maturingenzymatic function, with the greatest effect seen in thefirst 2 months of life. This leads to slower metabolicclearance of many drugs, toxic chemicals, and activatedmetabolites. 54 In addition, several authors havereported a reduced activity of acetylcholinesterases(AChEs), pseudocholinesterases, and arylesterases(eg, paraoxonase, the enzyme that detoxifies OP pesticides)in premature and full–term newborns. 55–61 Theselevels do not reach adult levels until a child is about1 year old. 62 Newborns possess half the paraoxonasefound in an average adult. 33 Other studies suggest thatnewborns have paraoxonase levels 4-fold lower andactivities 3-fold lower than their mothers. 63Traumatic Injury VulnerabilityBecause chemical agents are often dispersedthrough explosive devices, trauma and injury frequentlyaccompany chemical attacks. 64 Traumaticinjury patterns differ in children compared to adults;because of their smaller size, multiple trauma occursmore frequently in children than in adults after achemical attack. Children often sustain more headtrauma because of their relatively larger head sizeand weaker supportive musculature, and their morecompliant skeletal systems provide less protection tointernal organs, leading to greater internal injurieswithout overlying fractures.Neurobehavioral VulnerabilityImmature cognitive function can also put childrenat risk during a chemical attack. 33 Children often lackthe ability to discern threat and to protect themselves,and infants, toddlers, and young children do not havethe motor skills to flee from incident sites. 32 This canadversely impact their avoidance of a contaminatedarea and can interrupt decontamination in the eventof exposure. During decontamination, healthcareworkers and emergency personnel must have a planfor dealing with children who have been separatedfrom their caregivers. Children may need to be guidedthrough the decontamination process. 65Psychological VulnerabilityChildren have fewer coping skills when sustainingor witnessing injury that can produce short- or longtermpsychological trauma, such as parental or siblingdeath. 66 Children involved in attacks often suffer fromposttraumatic stress disorder (PTSD). 32 Adult reactionsto a chemical event can also make managing childrendifficult. Children are often influenced by the emotionalstates of their caregivers, so providers must try to remaincalm. Also, fear or discomfort may cause children todisobey or act out against care providers (Table 21-2). 31660