CLINICAL REPORT

Guidance for the Clinician in Rendering Pediatric Care

Pain Assessment and Treatment in Julie Hauer, MD, FAAP,a,​ b​ Amy J. Houtrow, MD, PhD, MPH, FAAP,c​ SECTION ON HOSPICE ChildrenAND PALLIATIVE MEDICINE, COUNCIL With ON CHILDREN Significant WITH DISABILITIES Impairment of the Central Nervous System Pain is a frequent and significant problem for children with impairment abstract of the central nervous system, with the highest frequency and severity occurring in children with the greatest impairment. Despite the significance of the problem, this population remains vulnerable to underrecognition and undertreatment of pain. Barriers to treatment may include uncertainty in identifying pain along with limited experience and fear with the use of aComplex Care Service, Division of General Pediatrics, Boston medications for pain treatment. Behavioral pain-assessment tools are Children’s Hospital, Assistant Professor, Harvard Medical School, Boston Massachusetts; bSeven Hills Pediatric Center, Groton, reviewed in this clinical report, along with other strategies for monitoring Massachusetts; and cDepartment of Physical Medicine and Rehabilitation, University of Pittsburgh, Pediatric Rehabilitation pain after an intervention. Sources of pain in this population include Medicine, Rehabilitation Institute, Children’s Hospital of Pittsburgh of acute-onset pain attributable to tissue injury or inflammation resulting UPMC, Pittsburgh, Pennsylvania in nociceptive pain, with pain then expected to resolve after treatment Dr Hauer conceptualized and drafted the initial manuscript, reviewed and responded to questions and comments from all reviewers, and directed at the source. Other sources can result in chronic intermittent pain contributed to writing the final manuscript; Dr Houtrow contributed that, for many, occurs on a weekly to daily basis, commonly attributed to to the initial drafting and editing at all stages, including the final manuscript; and all authors approved the final manuscript as gastroesophageal reflux, spasticity, and hip subluxation. Most challenging submitted. are pain sources attributable to the impaired central nervous system, This document is copyrighted and is property of the American requiring empirical medication trials directed at causes that cannot Academy of Pediatrics and its Board of Directors. All authors have filed conflict of interest statements with the American Academy be identified by diagnostic tests, such as central neuropathic pain. of Pediatrics. Any conflicts have been resolved through a process approved by the Board of Directors. The American Academy of Interventions reviewed include integrative therapies and medications, Pediatrics has neither solicited nor accepted any commercial such as gabapentinoids, tricyclic antidepressants, α-agonists, and opioids. involvement in the development of the content of this publication. This clinical report aims to address, with evidence-based guidance, the Clinical reports from the American Academy of Pediatrics benefit from expertise and resources of liaisons and internal (AAP) and external inherent challenges with the goal to improve comfort throughout life in this reviewers. However, clinical reports from the American Academy of vulnerable group of children. Pediatrics may not reflect the views of the liaisons or the organizations or government agencies that they represent.

The guidance in this report does not indicate an exclusive course of treatment or serve as a standard of medical care. Variations, taking into account individual circumstances, may be appropriate.

The identification, assessment, and treatment of pain in children with To cite: Hauer J, Houtrow AJ, AAP SECTION ON HOSPICE severe neurologic impairment (SNI) is an important goal for clinicians AND PALLIATIVE MEDICINE, COUNCIL ON CHILDREN WITH DISABILITIES. Pain Assessment and Treatment in Children involved in the care of such children. Meeting this goal is considered With Significant Impairment of the Central Nervous System. a significant1 challenge, even for clinicians with expertise in symptom Pediatrics. 2017;139(6):e20171002 treatment.

Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 139, number 6, June 2017:e20171002 FROM THE AMERICAN ACADEMY OF PEDIATRICS TABLE 1 Definitions Pain Defined by the IASP2 as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. The inability to communicate verbally does not negate the possibility that an individual is experiencing pain and is in need of appropriate pain-relieving treatment” Pain behaviors Observable features expressed by an individual in pain, with features specific to children with SNI indicated in Table 3 Nociceptive pain Defined by the IASP2 as “pain that arises from actual or threatened damage to nonneural tissue and is due to the activation of nociceptors” Indicates tissue injury or inflammation Neuropathic pain Defined by the IASP2 as “pain that arises from an alteration or disease in the somatosensory nervous system” Attributable to alterations in the peripheral nervous system or CNS, resulting in abnormal excitability Dysesthesia Defined by the IASP2 as “an unpleasant sensation, whether spontaneous or evoked” with cases including hyperalgesia and allodynia Hyperalgesia Defined by the IASP2 as “increased pain from a stimulus that normally provokes pain” Allodynia Defined by the IASP2 as “pain due to a stimulus that does not normally provoke pain” Agitation Unpleasant state of arousal manifesting as irritability, restlessness, and increased motor activity3 Features include loud speech, crying, increased movement, increased autonomic arousal, such as sweating and tachycardia, inability to relax, and disturbed sleep-rest pattern Irritability A disorder characterized by an abnormal responsiveness to stimuli or physiologic arousal; may be in response to pain, fright, a drug, an emotional situation, or a medical condition4 Neuroirritability Might best be used to indicate children with SNI who have persistent or recurrent episodes with pain behaviors after assessment and management of potential nociceptive sources, suggesting the CNS as a source of persistent pain features IASP, International Association for the Study of Pain.

“ The International Association for pain, sleep problems, and feeding that most children referenced in this the Study of Pain indicates that the difficulties, with6 symptoms often not report are unable to verbally indicate inability to communicate verbally well controlled. the presence or location of pain, yet does not negate the possibility that will have features that indicate pain. Recurrent pain can have a an individual is experiencing pain SNI will be used to refer to this group, ” significant effect on all aspects and is in need of appropriate pain- reflecting severe impairment of the 2 of daily life, including sleep and relieving treatment ‍ (Table 1). CNS. family interactions, and can lead There are many reasons why pain to distress, anxiety, depression, Pain Frequency and Severity Are can be a significant burden for irritability, insomnia, fatigue, and Significant in Children With SNI children with SNI, including their negative coping behaviors in the increased risk for sources of acute child and family members. Because pain, with symptoms expected to chronic pain can be an outcome of resolve once a problem is identified Medical tests, procedures, and many factors, a holistic approach is and treated. An even greater surgery are thought to be a frequent8 often needed to relieve pain and the challenge is recurrent or chronic pain 7 source of pain in children with SNI,​ associated problems. experienced by many children with yet in 1 study only 8% of all pain Specifying the Group of Children SNI, with risk including pain sources episodes9 were attributed to these With SNI attributable to alterations in the sources. Pain in some is chronic, central nervous system (CNS) that occurring on a weekly to daily basis cannot be identified by diagnostic and persisting despite treatment of tests. Significant impairment of the CNS problems such– as gastroesophageal can be attributable to various reflux disease9 13 (GERD) and Given the complexity of identifying etiologies and indicated by different spasticity. ‍ ‍ For example, pain and treating pain in such children, developmental descriptors (Table 2). was noted to occur weekly in pain goes unrecognized or This clinical report focuses 44% of children with moderate to inadequately treated all too often. predominantly on children with profound cognitive impairment In 1 study of children with cerebral severe to profound intellectual and almost daily in 41% to 42% of palsy who experienced pain, more disability with resulting lifelong children with severe to profound ’ than 90% had experienced ongoing limitations in verbal communication. impairment, assessed by using the – recurrent pain for more than 1 Most will have associated motor Non-Communicating Children s Pain year, yet only half were receiving5 impairment (ie, cerebral palsy). Checklist Revised9,10,​ 12​ or the Pediatric any treatment directed at pain. In This report is not specific to autism, Pain Profile. ‍ In children with children with progressive genetic, because pain in this group has not moderate to severe cerebral palsy, “ ” “ ” metabolic, or neurologic conditions been well studied, although many of pain was noted by parents to occur “ ” “ ” “ with no cure, the 3 most common the same principles may apply. The once or twice to a few times in symptoms reported by parents were use of the term nonverbal reflects 44% and fairly often to every/ Downloaded from www.aappublications.org/news by guest on September 27, 2021 e2 FROM THE AMERICAN ACADEMY OF PEDIATRICS TABLE 2 Neurodevelopmental Terminology and Causes of SNI Term Definitions and Comments SNI Used in this clinical report to indicate children with severe impairment of the CNS resulting in lifelong intellectual disability and limited verbal communication, often with coexisting motor impairment (eg, cerebral palsy) Causes include genetic, metabolic, neurodegenerative, structural malformation of the CNS, CNS infection, anoxic or traumatic brain injury, unknown Intellectual disability A disorder with onset during the developmental period that includes both intellectual and adaptive functioning deficits in conceptual, social, and practical domains Also referred to as cognitive impairment; previously called mental retardation References indicated in this report are typically of children who have severe to profound intellectual disability with associated limitations in communication Cerebral palsy Nonprogressive impairment of the CNS affecting muscle tone and control of movement Not always associated with intellectual disability especially with milder forms, whereas those with severe impairment often have both Autism Neurodevelopmental disorder characterized by impairments in social interaction and communication and a pattern of repetitive behaviors and interests

” TABLE 3 Pain Behaviors in Nonverbal Children With SNI Category Examples almost every day11 in 21% over a 4-week period. This information Vocalizations Crying, whimpering, moaning, gasping, sharp intake of breath Facial expression Grimacing, frowning, furrowed brow, squinting, eyes wide open, clenched teeth, is in marked contrast to typically teeth grinding, distressed look developing children, with only 12% Consolability Inability to be consoled and made comfortable identified in a large population-based Interaction Withdrawn, seeking comfort survey to experience pain Sleep Disturbed sleep, increased or decreased sleep 14 Movement Increase from baseline in movement of arms and legs, restless and fidgety, startles on a weekly basis. easily, pulls away when touched, twists or turns Tone Stiffening of extremities, clenching of fists, back arching, resists movement Pain intensity is also rated high in Physiologic Tachycardia, sweating, shivering, change in color, pallor, breath holding, tears children with SNI. Children with Atypical features Blunted facial expression, laughter, breath holding, self-injurious behaviors developmental and neuromuscular disorders were identified as 1 Identifying Pain in Children With of 3 subgroups with high pain SNI scores, assessed by using the with SNI have been identified in Individualized Numeric Rating Scale, studies of such children after surgery and painful procedures and by asking in a retrospective cohort analysis of The goals of pain assessment are to parents and caregivers what they more than 1.5 million documented identify the presence of pain and to observe when they believe their pain scores in a tertiary pediatric track the response to interventions child is in pain. Table 3 indicates the medical center during a 3-year for pain. To meet these goals, – 15 categories and features identified on period. In children with severe pain-assessment tools have been 10,18​ 21 pain-assessment tools. ‍ ‍ ‍ cognitive impairment, the average developed for use in children with Behavioral Pain-Assessment Tools pain intensity for all sources of SNI who cannot communicate their nonaccidental pain was 6.1 on a pain experience. Such tools can 10-point scale (0 equaling no pain educate clinicians and empower Behavioral pain-assessment– tools and 10 equaling the worst pain), parents in recognizing specific pain 9 for children with SNI are listed in behaviors in a child. When using such 10,18​ 21 with an average duration of 6 hours. Table‍ 4. ‍ ‍ ‍ Such tools assist tools, it is beneficial to recognize both In those with less impairment, with determining the presence of the information they provide and the specifically the ambulatory group pain. The use of these tools involves limitations in their use. with accidental pain, the average pain Pain Behaviors a detailed review with parents, ’ intensity was 3.8, with an9 average caregivers, and home-based nurses, duration of 46 minutes. Along with so as to determine a child s baseline pain severity, pain frequency is also Pain behaviors refer to the behaviors and changes from baseline noted to be higher in children observable features expressed by when pain occurs. As examples, some with the greatest5,9,​ 11,​ 16​neurologic an individual in pain (eg, facial children display less typical pain impairment. ‍ ‍ For example, grimacing). The observation of pain behaviors, such as laughing, a blunted pain was reported to be present in behaviors is considered a valid facial expression,10,13,​ 18,​ 22,​ 23​or self-injurious 48% of the ambulatory children with approach to pain assessment17 in behavior. ‍ ‍ ‍ cerebral palsy compared with5 79% in those unable to self-report. Pain Parents of children with SNI the nonambulatory group. behaviors that are specific to children consider pain identification to be an Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 139, number 6, June 2017 e3 TABLE 4 Pain-Assessment Tools for Nonverbal Children With Neurologic Impairment r-FLACC18 • Revised from the FLACC to include pain behaviors specific to children with cognitive impairment • Like the FLACC, a 5-item pain assessment tool with a score ranging from 0 to 10 • Allows parents to individualize by adding behaviors specific to their child • Option of indicating individualized behaviors can be beneficial for children with atypical pain behaviors and lack of other typical features, which may result in a false low score on other tools INRS19 • A personalized pain-assessment tool for nonverbal children with intellectual disability, based on the parent’s knowledge of the child, developed for use in the hospital • Parents and caregivers identify behaviors that indicate no pain to the worst possible pain on a scale ranging from 0 to 10 • Moderate to strong correlation between INRS ratings and NCCPC-PV (see below) total scores • Option of indicating individualized behaviors can be beneficial for children with atypical pain behaviors and lack of other typical features, which may result in a false low score on other tools NCCPC-PV20 • 27-item pain-assessment tool for children with severe cognitive impairment • Moderate to severe pain determined at a cutoff of ≥11 of 81 • In Breau et al,20​ this cutoff provided a sensitivity of 0.88 and specificity of 0.81 • Available for download for clinical use or use in research funded by not-for-profit agencies at http://pediatric-​ ​pain.​ca/​resources/​our-​measures/​ NCCPC-R21 • 30-item pain-assessment tool designed for nonverbal children ages 3–18 y with severe cognitive impairment • Moderate to severe pain determined at a cutoff of ≥7 of 90 • In Breau et al,21​ this cutoff provided a sensitivity of 0.84 and specificity of 0.77 • Revised from the NCCPC-PV (postoperative version) • Available for download for clinical use or use in research funded by not-for-profit agencies at http://pediatric-​ ​pain.​ca/​resources/​our-​measures/​ PPP10 • A 20-item pain-assessment tool for children with severe to profound cognitive impairment • Scores of ≥14 were generally associated, by observers, with moderate or severe pain • A cutoff of 14 provided a sensitivity of 1.0 and specificity of 0.91 • The tool is arranged to provide different scores to indicate a rating for “on a good day,”​ “most troublesome pain,”​ “second-most troublesome pain,”​ etc • Available to download from the Web, after registration at www.ppprofile.​ ​org.​uk Adapted with permission from Hauer, JM. Caring for Children Who Have Severe Neurologic Impairment: A Life with Grace. Baltimore, MD: Johns Hopkins University Press; 2013:52-53. FLACC, Face, Legs, Activity, Cry, Consolability; INRS, Individualized Numeric Rating Scale; NCCPC-PV, Non-Communicating Children’s Pain Checklist–Postoperative Version; NCCPC-R, Non- Communicating Children’s Pain Checklist–Revised; PPP, Pediatric Pain Profile.

uncertain process, although they rate on complexity, compatibility, and have sufficiently decreased after a themselves as accurate in identifying relative advantage, in a comparison medication trial. pain in their child and quickly of these tools with the Non- These pain-assessment tools (Table 4) identified pain behaviors specific Communicating Children's Pain have been studied in children to their child when given a pain- Checklist-Postoperative Version 9,23​ 24 identified as having intellectual assessment tool. ‍ (NCCPC-PV). In several studies, disability, with the majority also nurses preferred the r-FLACC for its No one tool can be recommended identified as having cerebral palsy. ease of use and pragmatic qualities, over another. Of note, the – Most of the children in these studies although not all tools were included revised Face, Legs, Activity, Cry, 24 26 have intellectual disability in the for comparison. ‍ ‍ Consolability (r-FLACC) scale and the Other Considerations When severe to profound range, with Individualized Numeric Rating Scale Assessing Pain few in the mild to moderate range. can be individualized by indicating There are limited studies assessing behaviors specific to each child, pain behaviors in children with with examples of pain behaviors autism and intellectual disability, 18,19​ In children with recurrent pain, provided. ‍ This option, not although the features identified assessment tools can be used present in other tools, is important are similar to those in children to score worst and typical pain for children with atypical pain with intellectual disability without episodes, although it is important 27,28​ behaviors. In such children, ratings autism. ‍ In children who acquire not to become overly dependent on other pain tools can then be a developmental age of 3 years on numbers. Other information deceptively low. or greater, age-appropriate pain- to review includes the frequency assessment tools, such as various Nurses and physicians rated the and duration of pain episodes. This 29 faces pain scales, can be used. r-FLACC and Nursing Assessment of information can assist in determining Pain Intensity (NAPI) as having an whether the frequency, duration, In addition to pain assessment after overall higher clinical utility based and severity of pain episodes surgery, other reasons to assess for Downloaded from www.aappublications.org/news by guest on September 27, 2021 e4 FROM THE AMERICAN ACADEMY OF PEDIATRICS “ pain behaviors and consider the use by parents who shared that their in children with SNI to describe a ” of behavioral pain assessment tools children with SNI23 had learned to sustained activated behavioral state •include• the following: live with pain. ‍ In addition, comfort associated with crying or agitation measures, such as holding and during which the child is not easily When concerns are identified rocking, can temporarily calm some consolable despite reasonable at routine comprehensive 4 “ children, with parents then assuming measures. Neuroirritability has assessments: Parents can be ’ the responsibility of maintaining also been used in the same manner asked at such visits, Do you their child s comfort, even if this as a diagnosis, although with no have concerns that your son is requires constant vigilance. Such a indication of the pathophysiologic uncomfortable or agitated at times, ” child may be viewed as not having mechanism. or is he typically calm and easily pain, even though frequent holding •• comforted? It is helpful to distinguish such to maintain comfort could indirectly descriptive terms that are When a child is identified to indicate an abnormal state of independent of etiology from the have intermittent muscle spasms excessive hyperarousal, possibly mechanisms that can cause the and changes in body position: attributable to pain. observed features. Consideration Determine whether pain behaviors “ ” Clinicians may assume that increased of language is important, because are associated with intermittent “ ” muscle spasms and movement or tone and movement are a result the use of such terms as agitation whether the child appears calm of spasticity and dystonia,– rather or irritability can inadvertently than investigating pain as a possible shift focus away from pain and •• during such movement. 9 11,33​ cause of these findings. ‍ ‍ ‍ thereby away from treatment When gastrointestinal symptoms, This assumption can occur when directed at the mechanisms of action “ ” such as vomiting or feeding pain behaviors in children with that result in pain. The use of the intolerance, are identified: SNI are not recognized to include phrase pain behaviors is likely to Nociceptive sources (ie, pain alterations in tone, bodily position, be viewed as a problem in need of attributable to tissue injury or and movement (Table 3). Descriptors treatment, whereas agitation and “ ” “ ” inflammation) include GERD and on pain-assessment tools include neuroirritability might be viewed “ ” “ ” “ ” “ cholecystitis and CNS sources stiffens or spasms,​ spastic,​ as indicating an irritable nervous ” “ include central neuropathic pain tense,​ rigid,​ tremors,​ marked system with less urgency given to ” “ ” – and autonomic dysfunction. Assumptions and Beliefs That increase in spasticity,​ twists10,18​ or21 its management. Such terms might Interfere With Identifying Pain turns,​ and arches back. ‍ ‍ ‍ also focus away from medication In a study in 22 children with SNI trials directed at pain mechanisms and persistent pain behaviors, and instead result in the use of When pain behaviors are observed, intermittent increased tone was adjuvant medications, such as beliefs and assumptions can interfere the most common pain behavior benzodiazepines, neuroleptics, or with considering pain as the cause. category, with 86% (19 of 22) other sedatives. Past beliefs that are not viewed of the children having recurrent Occasionally, concerns about pain as relevant included that some muscle spasms, although 20 of 22 raised by the parent or caregiver of children with SNI were indifferent or children were already taking one or 30 13 a child with SNI may appear to be insensitive to pain,​ more medications for spasticity. out of proportion to the observed and explanations for irritability With decades of literature focusing features. It is feasible that such in children with SNI included on spasticity treatment of this surrogate reporters may have psychiatric diagnoses such as bipolar population, it can be difficult to shift 31 emotional experiences that alter affective disorder. to a view that treatment directed their perception of pain in their ’ at pain may be of greater benefit Although some parents may bring child. Parent reporting of pain that ’ than another intervention directed concerns about a child s comfort is initially not observed in the child at spasticity. The identification of to a clinician s attention, for other should be reviewed carefully before other pain behaviors can guide parents their own beliefs can reduce considering that the child is not in consideration of an empirical pain the consideration of pain, such as pain. Parents historically have too treatment trial. the perception that the observed often been reassured that their child features are a natural 32part of the Various words are used to with SNI is not experiencing pain, underlying condition. Parents may describe children with SNI in likely reflecting the lack of studies on encounter uncertainty from clinicians distress, including irritability and pain behaviors until more recently, “ ” 3,34​ as to the source and management agitation (Table 1). ‍ The term and ongoing assumptions of what of symptoms, poignantly indicated neuroirritability has been used such features indicate. Consideration Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 139, number 6, June 2017 e5 TABLE 5 Problems of the CNS That Are Sources of Pain or Have Features That Include Pain Behaviors Problem Features and Comments Central neuropathic pain Symptoms include pain localized to the gastrointestinal tract, such as pain triggered by distention of the gastrointestinal tract (suggested by pain associated with tube feedings or intestinal gas, with relief after a bowel movement or flatus) Pain features can occur spontaneously and with no trigger, described by adults as “shock-like” Attributable to impairment of the spinothalamic tract and thalamus Visceral hyperalgesia Altered threshold to pain generation in response to a stimulus in the gastrointestinal tract Attributable to sensitization of visceral afferents as well as central sensitization in the CNS Autonomic dysfunction Features that suggest dysautonomia: skin flushing, hyperthermia, pain localized to the gastrointestinal tract, retching, bowel (dysautonomia) dysmotility, general discomfort, agitation, tachycardia, sweating, arching, stiffening Dysautonomia can be a source of discomfort, and pain can trigger the features that occur with dysautonomia Dystonia Involuntary sustained or intermittent muscle contractions cause twisting and repetitive movements, abnormal postures, or both Children with secondary dystonia attributable to severe alterations of the CNS may also be at risk of central neuropathic pain Pain can trigger and worsen features of dystonia Paroxysmal autonomic Involves features of both autonomic dysfunction and dystonia instability with dystonia Indicates altered function of the CNS areas that regulate autonomic function and movement Pain can trigger and worsen the observed features Spasticity Velocity-dependent increase in muscle tone that results in muscles that are resistant to movement Spasticity is often not painful but can result in musculoskeletal pain over time Muscle spasms Sudden involuntary contraction of a muscle or group of muscles; associated features can include arching, stiffening, tremors, and clonus Pain behaviors can indicate pain from muscle spasms or indicate pain from another source as the trigger for muscle spasms Delirium Disturbance of consciousness with an acute onset over hours to days and a fluctuating course Features include disordered thinking, change in cognition, inattention, altered sleep-wake cycle, change in arousal, and psychomotor disturbances

Nociceptive Pain Sources of parental emotional experience problems with acute onset have warrants expertise, such as from an features that include pain behaviors, New acute pain can be a result of interdisciplinary pediatric palliative such as medication toxicity and common childhood problems, such care team, rather than reassurance delirium. as otitis media, corneal abrasion, that the problem is not pain. When a child with SNI is identified hair tourniquet, testicular or ovarian Sources of Pain Behaviors as having recurrent pain behavior torsion, or appendicitis. Children episodes, it is important to consider with SNI are also at increased sources attributable to altered risk of GERD, gastric ulcer, acute The mechanisms that generate function of the CNS (Table 5). These pancreatitis (associated with pain include any cause of tissue sources, such as central neuropathic valproic acid and hypothermia), injury or inflammation (nociceptive pain and autonomic dysfunction, can cholecystitis (associated with tube pain) or abnormal transmission of either be a source of pain or have feedings), urinary tract infection, pain signals attributable to injury, features that include pain behaviors. nephrolithiasis (associated with dysfunction, or altered excitability Children with SNI are at risk of more immobility, topiramate, and the in the peripheral nervous system or than one of these problems to exist. ketogenic diet), hip subluxation, CNS (neuropathic pain). A focus on 1 problem as the source fracture (osteoporosis risk of observed pain behaviors could attributable to immobility and certain Sources of acute pain in children then limit consideration of other antiseizure drugs), and dental pain. with SNI include everyday routine treatment strategies for the problems Problems such as hip subluxation can discomfort, such as muscle spasms or indicated in Table 5. be a source of symptoms in some and an uncomfortable position, and pain an incidental finding in others. from a new nociceptive source, such New-Onset Pain Behaviors Evaluation for Nociceptive Pain as a fracture, urinary tract infection, Sources or other sources (highlighted in the following section). New-onset pain Tissue injury with resulting behaviors may also be observed with stimulation of nociceptors can be a No agreed-on standard nociceptive any acute illness that can result in source of acute pain, generally with7 evaluation exists for children with distress. As an example, pain sources resolution when the injury heals. SNI. Decisions will be guided by “ ” identified by parents of children with This section reviews sources to history and examination, the risk of “ ” SNI included chest congestion and consider when a child with SNI has missing a specific source, and the

chest infection,​ likely9,10​ reflecting an acute onset of significant pain level of invasiveness of the diagnostic respiratory distress. ‍ Some behaviors. study. History can determine when Downloaded from www.aappublications.org/news by guest on September 27, 2021 e6 FROM THE AMERICAN ACADEMY OF PEDIATRICS TABLE 6 Physical Examination as Part of Nociceptive Evaluation Physical Examination Technique Potential Nociceptive Pain Source the last dental assessment occurred, whether symptoms are associated Inspection of eyes for tears and conjunctival injection Corneal abrasion Inspection of dentition, mouth, and throat Dental caries and abscess, gingivitis, tonsillitis with movement (fracture or hip Inspection and palpation of shunt catheter site Ventriculoperitoneal shunt malfunction subluxation), whether the child Inspection and movement of gastrostomy tube Gastrostomy tube tension associated with growth has a ventriculoperitoneal shunt, Inspection and palpation of abdomen Constipation, distention and other details relevant to the Inspection of skin Hair tourniquet or pressure ulcer potential sources. Older children Inspection, palpation, and movement of extremities Occult fracture Palpation and range-of-motion of joints Subluxation (especially hips) with moderate intellectual disability may be able to point to the location of pain. A thorough physical examination involves examining the child unclothed. Details include determining whether pain behaviors are reproduced with movement of the gastrostomy tube and whether pain occurs with positioning or palpation of the extremities (Table 6). Parts of the examination should be isolated as much as possible to determine whether the pain response is consistently localized to 1 area. Allowing the child to calm down and relax when possible between areas of examination can minimize confounding information. Baseline studies that may aid in the discovery of the source of pain include blood tests (basic metabolic panel, a complete blood cell count, alanine aminotransferase, total bilirubin, alkaline phosphatase, amylase, lipase), urine (urinalysis and culture), stool guaiac, gastric pH in a patient with a gastrostomy tube, and radiography or bone35,36​ scan if a fracture is suspected. ‍ A dentist, ideally with expertise in children with special health care needs, can complete a dental assessment if specific concerns are identified or if there has been no dental examination in the past year. If the initial evaluation is negative, empirical FIGURE 1 treatment of GERD is often initiated Decisions when pain behaviors are identified in children with SNI. Abd U/S, abdominal ultrasonography; while considering other tests. alk phos, alkaline phosphatase; ALT, alanine aminotransferase; BMP, basic metabolic panel; CBC, complete blood count; t bili, total bilirubin; UA/UCx, urine analysis/urine culture. After this initial assessment of a child with no history of irritability and recurrent pain behaviors, further diagnostic evaluation would directed by history and examination. directed at the CNS sources of pain be warranted. This workup may In a child with a history of persistent behaviors while considering further include abdominal ultrasonography irritability that has increased over diagnostic studies that are invasive. or computed tomography scan, time to a level of concern for the ‍Figure 1 provides suggested upper gastrointestinal tract series, parent, it might be reasonable to guidance for this decision-making impedance study, and endoscopy, as initiate an empirical medication trial process. Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 139, number 6, June 2017 e7 Medication Toxicity and Withdrawal

SNI, with some features associated medication trials directed at CNS with pain in this group. Triggers sources (Table 5) that cannot be Many of the features associated for delirium include medications, identified by diagnostic tests. Repeat with certain medication toxicities 37,38​ pain, stress, illness, infection, and testing exposes such children to include painlike behaviors. ‍ metabolic disturbances. potential harm from invasive testing Examples include serotonin and delayed pain management. syndrome, with features including Delirium can be an important tachycardia, hypertension, sweating, consideration in children in the It is also possible to have an hyperthermia, increased muscle ICU, with assessment tools being40, 41​ abnormal finding that is not the tone, clonus, agitation,37 dilated pupils, developed for use with children. ‍ source of symptoms. Examples and diarrhea. Medications to In 1 study of delirium in the PICU, 22 include a child with persistent consider include selective serotonin of the 111 patients were identified symptoms after cholecystectomy, reuptake inhibitors (SSRIs), tricyclic as having significant developmental with improvement35 after starting antidepressants (TCAs), linezolid, delay. Use of the Cornell Assessment gabapentin,​ and 2 children tramadol, fentanyl, metoclopramide, of Pediatric Delirium tool in this identified by colonoscopy to ondansetron, dextromethorphan, group had a low specificity of 51.2%, have nonspecific colitis, with no and, in some instances, several such37 compared with a specificity of 86.5% improvement or escalation in medications used in combination. in those without delay, with40 an symptoms after antiinflammatory Another example with similar overall specificity of 79.2%. This treatment with significant features is neuroleptic malignant study highlights the challenge of improvement after42 the use of a TCA syndrome attributable to dopamine distinguishing problems that have or gabapentin. At times, empirical antagonists, such38 as metoclopramide overlapping presenting features in treatment can help avoid invasive and risperidone. Other problems children with SNI. testing and unclear findings from that can present with pain behaviors Chronic Recurrent Pain tests. include paradoxical drug reactions, Neuropathic Pain (Peripheral and including to benzodiazepines, Central) anticholinergics, SSRIs, and Chronic pain is continuous or neuroleptics. History can determine recurrent pain that may involve whether a medication was started a persistent noxious stimulus Neuropathic pain is attributable days to weeks before the onset of or persist in the absence of an to damage or dysfunction of the symptoms. identifiable pathophysiology. As peripheral nerves (peripheral Unintentional sudden cessation or a noted earlier, some children with SNI neuropathic pain) or the CNS (central rapid decrease in the dose of certain have recurrent pain episodes rather neuropathic pain). Neuropathic pain medications can also present with than acute pain episodes that resolve has some characteristics that are painlike behaviors. Medications after treatment of a nociceptive different from nociceptive pain. Pain include benzodiazepines, baclofen, source. When a child with SNI first descriptors in those able to report opioids, and TCAs. Withdrawal presents because of symptoms include burning, shocklike, shooting, symptoms include excitation of the reaching a threshold for parental prickling, or needlelike pain. Pain can CNS (agitation, muscle spasms), concern, history can identify the child be persistent or recurrent, including activation of the sympathetic nervous with long-standing irritability and pain that occurs spontaneously system (tachycardia, hypertension, agitation as potential indicators of with no known trigger. Neuropathic diaphoresis), and gastrointestinal chronic pain. pain can be difficult to treat but is often managed with nontraditional Dsymptomselirium (vomiting, diarrhea). Children with long-standing analgesic drugs, such as irritability may have had repeated antidepressants and anticonvulsants. tests and interventions for commonly Benefit from medications used Delirium is a disturbance of recognized problems, such as for neuropathic pain may provide consciousness with an acute onset, treatment directed at GERD and – indirect evidence of this chronic pain over hours to days, and a fluctuating spasticity. Chronic symptoms may 13,42​ 45 source in children with SNI. ‍ ‍ course. Features described in be attributed to these problems, adults include disordered thinking, potentially limiting consideration Neuropathic pain can result in change in cognition, inattention, of other coexisting pain sources as pain from a stimulus that does not altered sleep-wake cycle, perceptual triggers. Children with SNI are also normally result in pain (allodynia) disturbances,39 and psychomotor vulnerable to repeat testing over or an increased pain response to disturbances. Features of delirium months in the search for a cause, with a painful stimulus (hyperalgesia). are difficult to assess in children with delayed consideration of empirical Neuropathic pain is suggested in Downloaded from www.aappublications.org/news by guest on September 27, 2021 e8 FROM THE AMERICAN ACADEMY OF PEDIATRICS “ 13 children with SNI by higher baseline gastrointestinal tract and bladder, were receiving treatment of GERD. ” pain ratings when they are not described by 1 adult as feeling56 like In both studies, medications used considered to be in pain and the Vmyisceral bowels Hyperalgesia will explode. ‍ to treat visceral hyperalgesia and significant intensity and duration central neuropathic pain resulted in of symptoms that were5,9,​ 10,​ attributed23,​ 24,​ 46​ improvement in symptoms, including to routine problems. ‍ ‍ ‍ ‍ Visceral hyperalgesia is an altered decreased vomiting and retching, Examples that suggest hyperalgesia threshold to pain generation in improved feeding tolerance, weight include constipation, with an average gain, and change from jejunostomy to response to a stimulus57 in the 13,58​ intensity of 6.2 out of 10 and a gastrointestinal tract. As a gastrostomy tube feedings. duration of 24.5 hours, and teething, result, a normal stimulus, such as Nissen fundoplication and with an average intensity of 5.2 out of 9 distention and pressure within the gastrostomy tube placement may be 10 and a duration of 18.5 hours. gastrointestinal tract, or minor another risk to visceral sensitization Surgery can be a risk to the tissue injury, such as from GERD, can of the gastrointestinal tract. Higher development of neuropathic pain. result in significant pain. Injury or levels of pain in response to the Persistent pain has been reported in inflammation in the gastrointestinal same degree of gastric distention tract is believed to cause sensitization 10% to 50% of adults after common were identified61 after Nissen of visceral afferent pathways, with57,​ fundoplication. In addition, parents surgeries, becoming severe47 in 2% to 10% of these patients. One case resulting58 visceral hyperalgesia. of children with SNI have reported an ‍ Visceral hyperalgesia may also be series of 6 children with cerebral increase in pain symptoms after the62 palsy identified neuropathic pain referred to as visceral dysesthesia, placement of a gastrostomy tube. indicating an unpleasant sensation after orthopedic surgery48 of the (Table 1). Information from history can suggest lower extremities. In addition, visceral hyperalgesia and/or central some diseases of the nervous system Studies identify the gastrointestinal neuropathic pain as potential sources have associated painful peripheral tract as 1 of the most common of gastrointestinal tract symptoms neuropathy. sources of recurrent pain in children in children with SNI. Questions with SNI, despite treatment of Central neuropathic pain can – include those that suggest a lower common sources 9such11,13,​ as59,​ GERD60​ threshold to pain generation in develop when injury or– disease of and constipation. ‍ ‍ ‍ ‍ Pain the CNS involves the thalamus or the gastrointestinal tract and may 49 51 attributed to the bowels is also noted spinothalamic tract. ‍ ‍ Central include a history of pain associated to have a high pain intensity of 7.5 neuropathic pain is best studied with gastrostomy or jejunostomy out of 10, second only to pain of in adults with such problems as 9 tube feedings, bowel gas, and pain unknown cause. Such information multiple sclerosis (MS) or after before a bowel movement, with relief suggests visceral hyperalgesia and a cerebral vascular accident. after the passing of stool. Such pain central neuropathic pain as potential Thalamic MRI findings have been sources may also be suggested by a sources for recurrent pain behaviors reported with various conditions, decrease in symptoms when formula in children with SNI. including metabolic and genetic by feeding tube is substituted with an disorders (Leigh syndrome, Visceral hyperalgesia was identified electrolyte solution or tube feedings Krabbe disease, Canavan disease, as the source of gastrointestinal are held while intravenous fluids Alexander disease, gangliosidosis, symptoms in 12 of 14 medically are provided. Such information from neuronal ceroid lipofuscinosis, fragile children, most with cerebral history suggests a decrease in the Rett syndrome), infections palsy, with symptoms that persisted threshold to the generation of painful symptoms from gastrointestinal tract (cytomegalovirus, toxoplasmosis),– after medications for GERD58 and Astimulation.utonomic Dysfunction osmotic demyelination syndrome,52 55 Nissen fundoplication. Fewer and hypoxic-ischemic injury. ‍ ‍ were identified to have impaired This information suggests a risk for gastrointestinal tract motility. central neuropathic pain in children Of those, 7 had both impaired Autonomic dysfunction is another with SNI but does not indicate gastrointestinal tract motility and potential source for pain5,63​ behaviors which child may develop symptoms visceral hyperalgesia, and only 2 in children with SNI. ‍ Other terms attributable to this problem. The of the 14 children had a motility include dysautonomia, autonomic symptoms experienced with central disorder as58 the sole problem storm, sympathetic storm, thalamic neuropathic pain can be constant and identified. In another study, storm, and paroxysmal autonomic involve sudden bursts of intense pain. gastrointestinal symptoms were instability with dystonia. Features Other symptoms include visceral noted in 14 of 22 children with SNI that suggest autonomic dysfunction pain associated with distention of the and persistent pain, all of whom include altered heart rate and body Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 139, number 6, June 2017 e9 temperature; pale skin or flushing by involuntary muscle contractions principles for pain treatment can of the skin; retching, vomiting, and– that lead to repetitive twisting serve as a guide throughout this abdominal pain; sweating; and64 66 movements68 and/or abnormal process. Initial considerations increased production of saliva. ‍ postures. Like spasticity, dystonia include tailoring therapy to each Some features are the same is not typically painful, and pain from child on the basis of the severity, behaviors associated with pain, and any source can increase movements frequency, and duration of episodes Seizuresothers can contribute to discomfort. associatedHip Subluxation with dystonia. and the expected outcome after an empirical medication trial directed at potential chronic pain sources, along with close follow-up and availability For a child with persistent agitation Hip subluxation/dislocation is 7 and pain behaviors, EEG might be a potential source of chronic throughout this process. considered to determine whether nociceptive pain. Because A tool to guide medication selection, movement associated with the this problem is common in referred to as the analgesic ladder events is attributable to seizures. nonambulatory children with SNI, and originally applied to cancer

EEG warrants careful consideration, it may be an incidental finding in69 pain, was developed by the World because it is possible for a child the evaluation for a pain source. Health Organization (WHO) in 1986. to have results indicating seizure Interventions for this problem It was revised recently for children activity while simultaneously warrant consideration when from a 3-step to a 2-step ladder having a pain source that alters positioning, transferring, bathing, because of concerns7 that the previous the threshold to seizures. Seizures dressing, and diaper care are difficult second step included codeine, a in adults are67 not typically viewed to conduct because of pain or medication that is no longer routinely as painful. Discomfort can be Morelimitations Than in1 Source range of of motion. Pain May recommended given the recognized experienced in the postictal period Coexist concerns with safety and efficacy because of repeated movement or related to genetic70,71​ variability in Spasticity,injury. Muscle Spasms, and metabolism. ‍ Tramadol was also Dystonia Children with SNI are at risk of included in the second step, although several sources of pain behaviors. A the WHO suggests that the risks child may have GERD or spasticity associated with strong opioids such In children with SNI and recurrent as well as central neuropathic pain. as morphine are acceptable when pain behaviors, it can be unclear Coexisting sources of pain may only compared with the uncertainty of whether associated spasticity or be evident after symptoms improve, response and risk associated7 with dystonia are the direct cause of pain yet remain troublesome after the tramadol in children. behaviors or if a chronic pain source treatment of such problems. The The first step is used for mild pain is triggering any observed changes presence of more than 1 source and includes the use of nonopioid in tone and movement. When pain of pain may also be suspected by analgesics. The second step is used behaviors coexist with spasticity symptoms that are out of proportion for moderate to severe pain and or dystonia, children with SNI may to the problem, such as prolonged includes the use of opioid analgesics, benefit from a multimodal approach, and severe crying associated with starting with a lower dose for including interventions directed constipation in a child with central moderate pain. Adjuvant medications at chronic pain sources as well as pain. By considering more than 1 can be used at either step. These spasticity or dystonia. source, such children may experience include medications such as Spasticity is defined as hypertonia symptom improvement sooner. anticonvulsants and antidepressants in which stretching the muscle Treatment of Pain that can provide benefit for specific at increasing speed results in types of pain, such as neuropathic pain, or others that can enhance the higher tone or resistance to 68 externally imposed movement. Treatment of pain starts with a benefit of medications used for pain Spasticity is often not painful, but comprehensive evaluation, with treatment. “ over time it can result in painful an initial goal to identify and treat Other pain treatment principles ” “ ” “ musculoskeletal injury. In addition, the cause whenever possible. Some guided by the WHO include by the ” intense muscle spasms can result sources, such as pain from a fracture, clock,​ by7 the mouth,​ and by in intermittent pain. Spasticity and require temporary treatment of the child,​ ‍ which indicates that muscle spasms can be increased by pain. The greater challenge is when treatment should be scheduled when acute illness and pain. Dystonia is a pain behaviors have been identified pain is frequent, with rescue doses movement disorder characterized as recurrent or chronic. General of analgesics or other appropriate Downloaded from www.aappublications.org/news by guest on September 27, 2021 e10 FROM THE AMERICAN ACADEMY OF PEDIATRICS medications available as needed. is 1 of the greatest barriers to needed. Although physicians were Medications should be given by opioid use. Knowing the intent of aware of the benefit of opioids for the least-invasive route, such as pain treatment can assist when severe dyspnea in adults, a significant ’ enteral, buccal, or transdermal, and considering this risk. For example, gap remained between the benefit be tailored to the child s needs and opioid use after surgery involves experienced by patients and family response to treatment. Intramuscular monitoring to identify and manage caregivers and physician73 fear over injection is not an appropriate option respiratory depression, meeting the the use of opioids. for analgesia, given the other delivery intent to safely promote comfort and Parental fear of addiction can options available. avoid any harm. In contrast, when be addressed by reviewing the the intention to relieve pain is the It is unclear how well the WHO difference between physical primary and overriding goal in a analgesic ladder applies to children dependence and drug addiction. child with a life-limiting condition, with SNI, because it has not been Parents can be informed of the need accepting the low risk of respiratory studied in this population, but the to slowly taper off of a medication depression is ethically permissible, principles of its use with patients so as to avoid withdrawal symptoms along with forgoing monitoring at ’ with cancer apply. Children with SNI from a sudden stop or reduction such a time. The risk of significant may be more likely to have chronic in the medication s dose. In respiratory depression is low when pain attributable to impairment contrast, drug addiction refers to a following evidence-based dosing of the CNS (Table 5), and not all psychological desire and dependence guidelines and slow titration, from a central sources respond to opioids. on a drug. starting dose that is individualized to Medications directed at these CNS the patient. When available, expert Another commonly held fear is that sources of pain behaviors (Table consultation may be considered. effective pain treatment will mask 7) may have a preferential role in Fears should not interfere with pain from a new pain source, but children with SNI before the use adequate symptom treatment. this does not occur, as noted in a of an around-the-clock opioid. ’ Rather, access to expertise or the case series of children with SNI In recognition of these issues, an advancement of one s own expertise when, at a time of effective symptom alternative to the WHO analgesic through education can provide management of recurrent pain ladder was proposed for use in “ ” guidance on how to safely start behaviors, urinary tract infections children with SNI and recurrent opioids as well as other medications, in 3 patients were identified 13by the pain, indicated as the neuro-pain 45 monitor for effectiveness and adverse Aonsetcute ofPain new Treatment: pain behaviors Procedural. ladder. effects, adjust the dose as needed, and Postsurgical Pain Because there is no standard and consider other treatment options approach to pain and symptom43 when symptoms have not adequately treatment in children with SNI,​ improved. Pain-management techniques should empirical medication selection be used for painful procedures. for persistent pain behaviors is The association of opioid use with Strategies include medications best guided first by the safety of end-of-life care can create the along with nonpharmacologic medications, with information on assumption that opioids hasten interventions, such as music,74 their efficacy for chronic sources of death. Opioids do not hasten death distraction, and holding. Medication pain primarily guided by evidence when used appropriately and can delivery options for procedural in adults. The proposed neuro-pain enhance comfort throughout life. In pain management include– topical, ladder for children with SNI and a case series of children with SNI on enteral, intravenous, 75intranasal,77 and persistent pain behaviors takes scheduled morphine for recurrent inhaled medications. ‍ ‍ There are “ this approach, such as suggesting respiratory distress with associated numerous guidelines and policy 75 a gabapentin trial before a TCA or pain behaviors, 1 parent said, I think statements for pain management,​ Barriersmethadone. to Pain Treatment [my son] has lived this long due to yet pain during procedures for77 ” his improved comfort, [as] he used to children is often undertreated. struggle so much with each illness,​ a The management of postoperative

Fears commonly experienced when sentiment shared by72 several parents pain ideally involves an considering medications for pain, and primary nurses. Once parents interdisciplinary team of providers especially opioids, include harm, observe benefit from symptom to assess and monitor pain and drug addiction, masking pain from treatment, clinician fear may make adjustments as needed. The a new problem, and giving up too continue and interfere with ongoing family can be engaged in all phases, soon on identifying a pain source. use of medications, adjustment in from plan development through Fear of respiratory depression dosage, and additional trials when implementation and monitoring. Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 139, number 6, June 2017 e11 TABLE 7 Medications for Acute and Chronic Pain Medications Evidence for Use Comments Gabapentinoids Gabapentin, pregabalin Neuropathic pain, peripheral and Thought to inhibit excitation by binding to the α-2δ subunit of voltage-dependant Ca2+ central ion channel in the CNS Visceral hyperalgesia Side effects include sedation, nystagmus, tremor, swelling Dysautonomia Sedation can be minimized by increasing the dose gradually and then advancing more rapidly as tolerated Spasticity No significant interactions with other drugs No evidence that 1 is superior to the other for children who have SNI TCAs Nortriptyline, amitriptyline Neuropathic pain, peripheral and Reuptake inhibition or serotonin and norepinephrine in the CNS, both inhibitors of pain central visceral hyperalgesia transmission (also antagonists of 5HT-2, H-1, and Ach) Adverse effects include dry mouth, constipation, urinary retention, sedation, agitation, akathisia, and prolonged QTc syndrome (consider baseline ECG) Limit the use of other anticholinergic medications Side effects can be lessened by increasing gradually Caution when using with other medications that result in serotonin syndrome Serum level not necessary, although can document absorption Nightly lower dose may have benefit for sleep Opioids Tramadol Pain Opioid receptor agonists, including μ-receptors Tramadol should not be used in children under 12 years or in those 12 to 18 years with altered respiratory status and should be used with caution in older patients with seizures or on drugs that cause serotonin syndrome Morphine, other short-acting Pain Morphine and other opioids safe when started with a standard dose, titrated to effect, opioids Dyspnea and adjusted for renal impairment and respiratory depression, as examples Autonomic storms Methadone Neuropathic pain Methadone has benefit of longer duration of action, but requires expertise in use α2-Adrenergic receptor agonist Clonidine Dysautonomia Side effects include hypotension, bradycardia, sedation, although fewer side effects in children than in adults Spasticity Side effects can be minimized by gradual dose increase May enhance pain management Clonidine has the option of transdermal patch Nightly dose may have benefit for sleep Cannabinoids Dronabinol Central pain in adults with multiple Cannabinoid receptor agonist (C-1 and C-2) sclerosis Appetite stimulant Limited studies in children Side effects include delayed gastric emptying, dizziness, anxiety, depression, irritability, restlessness, tachycardia, and dry mouth Benzodiazepines as adjuvants Clonazepam Autonomic storms Not for pain treatment, used as adjuvants to enhance pain treatment Lorazepam Muscle spasms Increase affinity of GABA for GABAA receptors Midazolam Myoclonus Consider as-needed use for breakthrough symptoms in children on scheduled analgesics Seizures Side effects include prolonged sedation and paradoxical reactions Use cautiously in combination with opioids Midazolam has rapid onset and shorter duration Tolerance develops with scheduled use Ach, acetylcholine; C, cannabinoid; ECG, electrocardiogram; GABA, gamma-aminobutyric acid; H, histamine; 5-HT, serotonin.

The plan can include preemptive postoperative management of after surgery, as noted in79, children80​ management of constipation that can children with spasticity. For lower undergoing spinal– fusion. ‍ Epidural be made worse by anesthesia and extremity orthopedic surgery, some analgesia is also81 a83 consideration for opioids. physicians use botulinum toxin selectChronic patients Pain Treatment. ‍ Postoperative pain management, injections to help diminish the effects including the use of intravenous of postoperative spasticity, which is opioids in children with SNI, requires especially helpful in the child who78 An empirical analgesic trial can be a team with expertise in safe pain is immobilized for several weeks. considered when pain behaviors “ 17 ” management. Benzodiazepines Perioperative gabapentin may aid continue. There is no absolute may play an adjuvant role in the in reducing pain and opioid need tipping point when the severity, Downloaded from www.aappublications.org/news by guest on September 27, 2021 e12 FROM THE AMERICAN ACADEMY OF PEDIATRICS frequency, and duration of episodes recognizing that the hoped-for lung disease, which may increase the with pain behaviors warrant Ibenefitnterventions might notfor alwaysPain be achieved. risk of86 respiratory depression and an empirical medication trial death. Some individuals, because versus further diagnostic testing. of genetic variations, are ultrarapid Consideration of central sources Interventions start with daily metabolizers who convert tramadol of symptoms with parents can management of expected sources more rapidly and completely to minimize the assumption that testing of discomfort in children with O-desmethyltramadol, the active will eventually identify the source SNI, such as repositioning. The form of the opioid, resulting in this to be treated, which may facilitate ability to console the child with risk. The WHO analgesic ladder earlier initiation of a medication such interventions, along with for children recommends a strong trial directed at the chronic pain other comfort strategies, indicates opioid started at a lower dose for sources that cannot be identified moderate pain rather than the use that routine needs have been met. 7 by diagnostic tests. Initiating an In children with persistent pain of tramadol. In older patients, empirical medication trial while behaviors despite such strategies, tramadol must be used with caution considering invasive tests, such as medications (Table 7) and in those with a seizure disorder, endoscopy or impedance study, nonpharmacologic strategies can be receiving medications that are can then avoid the need for such considered and used. Experts in pain CYP2D6 and CYP3A4 inhibitors, and tests when symptoms improve. An on medications that are associated treatment, such as pain or palliative 37,87​ empirical trial can also be considered medicine specialists, can be consulted withOpioids serotonin syndrome. ‍ before surgical interventions for Nwhenonsteroidal needed. Antiinflammatory GERD and spasticity with associated Drugs and Acetaminophen pain behaviors, potentially avoiding Opioid use requires knowledge of surgery if there is adequate dosing, titration, adverse effects, and improvement in symptoms. when to consider opioid rotation, Medications used for mild pain information covered in greater include acetaminophen and 84,85​ Guiding principles for treatment of detail elsewhere. ‍ Opioid use nonsteroidal antiinflammatory recurrent pain behavior episodes in 7 in children with SNI includes the drugs. Adverse effects with children with SNI include frequency management of acute nociceptive the chronic use of nonsteroidal and duration of events. Infrequent pain, acute breakthrough pain that antiinflammatory drugs include episodes may be adequately managed occurs despite use of scheduled gastritis and gastrointestinal with a medication used as needed, medications for chronic pain sources, bleeding. Lack of benefit may along with nonpharmacologic and intermittent autonomic storms indirectly indicate a problem more 72 strategies. When episodes occur or dyspnea. weekly, a scheduled medication significant than a routine ache or can be considered, with the pain. At such a time, an empirical If an opioid is the only medication goal to minimize the frequency, trial directed at chronic pain sources being used for frequent pain, it is best duration, and severity of episodes. can be considered. There is still an scheduled around the clock on the Occasionally, a child may have a ongoing role for these medications basis of duration of benefit, typically monthly cycle of pain, such as a given the benefit when used in every 4 hours when given enterally, with a dose available as needed for male with SNI described as having Tramadolcombination. 7 daily severe symptoms for 7 to 10 breakthrough pain. Monitoring will days each month for at least 4 years, determine when the scheduled dose μ needs to be adjusted. with a significant benefit noted after The analgesic effect of tramadol several medication13 trials directed at includes weak -opioid agonist One limitation of opioid use for neuropathic pain. activity and weak reuptake inhibition84,85​ chronic pain in children with of norepinephrine and serotonin. ‍ feeding tubes is the frequency of Setting realistic goals can better The Food and Drug Administration dosing required with short-acting prepare families throughout the (FDA) recently issued a warning opioids and fewer long-acting process of treatment directed at indicating that tramadol should not options. Options of longer duration “ ” chronic pain sources, reflecting be used to treat pain in children include methadone solution or a the inability to fix the sources younger than 12 years and a warning fentanyl transdermal patch. The of chronic pain that arise from the against its use in adolescents fentanyl patch should not be used impaired nervous system. One can between 12 and 18 years who are to manage acute pain. Long-acting acknowledge the hoped-for goal of obese or have conditions such as morphine pellet-filled capsules can improved symptom control while obstructive sleep apnea or severe be given by gastrostomy tube if the Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 139, number 6, June 2017 e13 equivalent daily dose of short-acting usually transient, and urinary The analgesic mechanism is not fully morphine converts to the capsule retention. understood, although gabapentinoids doses available, by suspending the are noted to bind to presynaptic pellets in water and administering Not all children with SNI and severe voltage-gated calcium channels in in a gastrostomy tube that is 16 F pain behaviors will respond to 44,45​ the dorsal horn, reducing the release or larger, although care must be opioids, as noted in case reports. ‍ of excitatory neurotransmitters Short-acting opioids may be best taken not88,89​ to crush or dissolve the such102 as glutamate and substance pellets. ‍ This process is in contrast used in the postsurgical period, P. Pregabalin has an advantage of to long-acting tablets, which cannot when a pain source such as a fracture twice-daily dosing in older children, be opened or crushed and therefore is expected to resolve, and on an although there is less information cannot be given in a feeding tube. as-needed basis for breakthrough regarding its use compared with episodes. When needed, experts in gabapentin in children. Pregabalin Methadone is the only long-acting ’ pediatric pain and palliative care also has linear pharmacokinetics opioid available as a liquid. The μ can assist with the use of long-acting compared with gabapentin s analgesic effects of methadone N Gopioidabapentinoids forms. decreasing bioavailability at higher include -opioid agonist activity d doses, although there are no data and -methyl- -aspartate receptor to indicate whether differences in antagonist against glutamate, an absorption are clinically significant excitatory neurotransmitter in the Gabapentin and pregabalin are the in children. Both require dose CNS, providing theoretical added most commonly used anticonvulsants reductions in children with renal benefit for children with SNI and for neuropathic pain. Evidence, insufficiency and appear to be similar chronic pain. Its use requires mostly in adults, indicates benefit in their adverse-effect profiles, expertise, given its biphasic for many of the chronic pain – including no known drug-drug elimination and alterations in sources reviewed earlier, including– 93,95​ 90,91​ 92 95 interactions. ‍ metabolism with other drugs. ‍ peripheral neuropathic pain,49– 51,​ 95​‍ ‍ Potential drug interactions central neuropathic pain,58,96​ ​ 98‍ ‍ ‍ Given the limited evidence in treating include many medications used visceral hyperalgesia,​ 64,‍99​ ‍ persistent and recurrent pain commonly for children with SNI, autonomic100 dysfunction,​ ‍ and behavior episodes in children with including phenobarbital, phenytoin, spasticity. Gabapentin is approved SNI, gabapentin may be reasonable carbamazepine, ciprofloxacin, by the FDA for use in postherpetic in a first-line empirical trial on the neuralgia in adults, adjunctive diazepam, metronidazole,90,91​ and basis of its safety and theoretical erythromycin. ‍ therapy in the treatment of partial benefit for central pain sources seizures with and without secondary (Fig 2). Clinicians routinely involved When opioids are used, adverse generalization in patients over 12 in the care of children with SNI effects need to be anticipated and 84,85​ years of age with epilepsy, and can pursue knowledge in its use, managed. ‍ In children with SNI, adjunctive therapy in the treatment including starting dose, titration, the risk of respiratory depression can of partial seizures in pediatric initial goal dose, and potential be minimized by attending to patient patients 3 to 12 years of age. FDA- adverse effects (Table 8). Gabapentin details, such as the presence of severe approved indications for pregabalin dosing in children indicates that hypotonia and obstructive apnea, include postherpetic neuralgia children younger than 5 years need and determining whether other in adults and diabetic peripheral a 30% higher dose, with doses up to sedating medications were recently neuropathy. The use of gabapentin 72 mg/kg per day (3600 mg/day) started. Constipation is best managed 13,103,​ 104​ and pregabalin for the treatment of reported. ‍ In adults, doses up preemptively by initiating treatment potential pain sources in children to 3600 mg/day are used, although that includes a stimulant laxative and with SNI is off-label, as is commonly doses greater than 2400 mg/day is not limited to stool softeners or the case in pediatrics. may have incrementally less benefit. by increasing any treatment already 84 To provide an adequate empirical in use for constipation. Itching can Gabapentinoids are considered first- – trial, such information is important also occur, a problem to consider if line medications for neuropathic pain 93 95 when determining the initial dose to new agitation is noted. Management in adults. ‍ ‍ Several case reports achieve. options include opioid rotation, and 2 different case series of children TCAs ondansetron, and opioid antagonists. with SNI indicated a reduction in Antihistamines are not effective, pain behavior episodes as well as because opioid-induced itching is not an improvement in muscle spasms,– Nortriptyline and amitriptyline– histamine mediated. Other adverse feeding intolerance, and sleep13,42​ after45,101​ have been used to96 treat98 peripheral effects of opioid use include sedation, treatment with gabapentin. ‍ ‍ ‍ neuropathic pain,​ ‍‍ central Downloaded from www.aappublications.org/news by guest on September 27, 2021 e14 FROM THE AMERICAN ACADEMY OF PEDIATRICS 49,​51,95​ neuropathic pain,58,96​ ​ ‍ and visceral hyperalgesia. ‍ Their mechanisms of action include presynaptic reuptake inhibition of norepinephrine and serotonin, resulting in the modulation of95 descending inhibition from the CNS. Both also have anticholinergic properties, with subsequent adverse effects including sedation, constipation, and urinary retention, along with possible benefit because of decreased secretion production. Adverse effects can be lessened with a slow titration to the initial goal dose. Nortriptyline has a lower anticholinergic effect, FIGURE 2 45,93​ 95,​ although it is unclear whether this Suggested guidelines for pharmacologic management of recurrent pain behavior episodes. ‍ ‍–‍ 105‍–‍107 is clinically significant in children. TCAs should be used cautiously with other medications that can result TABLE 8 Analgesic Dosing Guidelines and Suggested Titration Schedules in serotonin syndrome. Other risk Gabapentin factors include potential cardiac Days 1–3: 2 mg/kg (100 mg maximum), enterally, 3 times daily dysrhythmia, including prolonged Days 4–6: 4 mg/kg, enterally, 3 times daily Increase every 2–4 days by 5–6 mg/kg per day until the following92: QT interval. For these reasons, TCAs 1. Effective analgesia reached (may be noted at 30–45 mg/kg per day) require expertise in their use. 2. Side effects experienced (nystagmus, sedation, tremor, ataxia, swelling) 3. Maximum total dose of 50–72 mg/kg per day reached (2400–3600 mg/day) Nortriptyline and amitriptyline are 4. Younger children (<5 years) may require a 30% higher mg/kg per day dosing, such as a total 13,103,​ 104​ considered– first- or second-line dose of 45–60 mg/kg per day ‍ ‍ treatment of neuropathic pain in 5. Half of the total daily dose may be given as the evening dose if symptoms occur mostly in the 93 95 evening and overnight adults. ‍‍ They have the benefit of 6. Titrate more rapidly for severe pain or as tolerated, titrate more gradually if sedation noted once- or twice-daily dosing. Given Pregabalin the lack of evidence in children with Days 1–3: 1 mg/kg (50 mg maximum), enterally, every night SNI and potential adverse effects, a Days 4–6: 1 mg/kg, enterally, twice daily TCA might be a reasonable second- Increase every 2–4 days up to 3 mg/kg per dose, enterally, given 2 or 3 times daily (maximum 6 mg/ kg per dose) line medication after a trial with a Amitriptyline or nortriptyline gabapentinoid in such children with Days 1–4: 0.2 mg/kg (10 mg maximum), enterally, every night92 recurrent pain behaviors (Fig 2). A Days 5–8: 0.4 mg/kg, orally, every night TCA can be started while continuing Increase every 4–5 days by 0.2 mg/kg per day until the following92: gabapentin, an approach supported 1. Effective analgesia, side effects (constipation, dry mouth, urinary retention, sedation), or dosing reaches 1 mg/kg per day (50 mg/day maximum) by 1 study that identified greater 2. Consider ECG before further dose escalation up to 1.5–2 mg/kg per day (100 mg/day maximum); benefit with the combination of higher rate of side effects with higher doses including anticholinergic gabapentin and nortriptyline over 3. Consider plasma level if concerns with gastrointestinal tract absorption 4. Consider twice-daily dosing of 25% 30% in the morning and 70% 75% in the evening either 1 given 105solely for neuropathic – – Medicationpain in adults. Combinations for Clonidine Neuropathic Pain Days 1–3: 0.002 mg/kg (0.1 mg maximum), enterally, every night Days 4–6: 0.002 mg/kg, enterally, twice daily Days 7–9: 0.002 mg/kg, enterally, 3 times daily Increase every 2–4 days by 0.002 mg/kg until the following: The combination of 2 or more 1. Effectiveness noted or side effects develop medications for neuropathic pain 2. Titrate more rapidly if tolerated 3. Average dose in 1 study (for spasticity): 0.02 mg/kg per day108 may improve analgesic efficacy and 4. 0.002–0.004 mg/kg every 4 hours as needed for breakthrough episodes that suggest autonomic reduce overall adverse effects if storm events (suggested by facial flushing, muscle stiffening and tremors, hyperthermia) synergistic 106,benefit107​ allows for dose Data from refs 13,‍45​ ,‍9​ 2–‍95,‍103​ ,‍104​ ,‍108.​ ECG, electrocardiogram. reductions. ‍ Combinations studied for neuropathic pain include gabapentin plus nortriptyline, Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 139, number 6, June 2017 e15 gabapentinoid plus opioid, and Studies are predominantly in statement, the American Academy of TCA plus opioid. General principles adult patients with peripheral Pediatrics opposed the use of medical when considering a combination neuropathic pain, with fewer studies marijuana outside the regulatory include selecting medications with for central pain. Studies in children process of the FDA but recognizes the following: (1) maximal efficacy, are limited to adolescent patients that marijuana may be an option the fewest adverse effects, and with depression. SNRIs include for cannabinoid administration for minimal adverse interactions with venlafaxine immediate release, which children with life-limiting or severely other drugs; (2) minimal adverse can be crushed and given by feeding debilitating conditions and for whom114 drug interaction with each other; (3) tube, and duloxetine, which cannot current therapies are inadequate. different adverse-effect profiles; (4) be crushed, because it is an extended- Although the data in adults indicate different mechanisms of action;106 and release capsule. SNRIs have a greater benefit for chronic neuropathic pain (5) different sites of action. benefit for neuropathic pain than as well as spasticity in patients with Figure 2 provides suggested SSRIs, with SSRIs indicated as fourth- MS, no studies have been performed guidelines to a stepwise approach line therapy for neuropathic pain on the use of medical marijuana in by using such evidence as well as in adults. The reuptake inhibition children. The American Academy information from the neuro-pain– of norepinephrine is thought to be of Pediatrics supports the research ladder and guidelines from45,93​ 95adults beneficial against neuropathic pain, a and development of pharmaceutical withClonidine neuropathic pain. ‍ ‍‍ property shared by SNRIs and TCAs cannabinoids and supports a review but not with SSRIs. of policies promoting research on the α Antiseizure Medications: Other 114 Benzodiazepinesmedical use of these compounds.

Clonidine is an 2-agonist used108 in the treatment of spasticity 109 Antiseizure drugs are used in adults and autonomic dysfunction. It with neuropathic pain, including Benzodiazepines are commonly used also has potential mild analgesia valproic acid, carbamazepine, in children with SNI for spasticity, through the inhibition of substance P 110 oxcarbazepine, lamotrigine, and dystonia, seizures, dysautonomia, release. Clonidine may have a role topiramate. Studies in adults agitation, and sleep. Tolerance can in symptom treatment of children with peripheral neuropathic pain develop with daily, prolonged use. with SNI when associated problems showed mixed results, and there are Increasing the dose as tolerance include significant hypertonia or few studies in adults with central develops may increase the risk when features suggest autonomic neuropathic pain. Overall, they are of adverse effects. It can become dysfunction. Clonidine also has a considered third- or fourth-line difficult to separate out potential suggested benefit in reducing pain treatment of peripheral and central sedation or paradoxical effects, perception during gastric and colonic 93,95​ 111 neuropathic pain in adults. ‍ such as agitation and irritability, distension. Adverse effects of Their role in children with SNI and from problems115, attributable116​ to the sedation and hypotension can be persistent pain behaviors is unclear. impaired CNS. ‍ lessened with a gradual increase Cannabinoids There are times when the benefit to the initial goal dose. Children of daily use of a benzodiazepine with SNI who are unable to stand δ may outweigh the disadvantage independently will not have the Dronabinol is the synthetic form of of tolerance and other concerns, risk of orthostatic hypotension and 9-tetrahydrocannabinol, an active such as the use of clonazepam for associated fall. In children with compound of the cannabis plant. certain seizure types. For other associated sleep disruption, it can be Dronabinol has been studied in adult indications, such as for intermittent used at nighttime to enhance sleep patients with MS and traumatic brain 112 muscle spasms, autonomic storms, or and to minimize problems such as injury. Benefit for central pain and prolonged seizures, benzodiazepines muscle spasms that can disrupt sleep. spasticity has been shown in patients 95,112​ might be ideally used as needed. Clonidine should not be discontinued with MS. ‍ Other cannabinoid abruptly because of the risk of therapies used in adults include Other considerations include drug- reboundSerotonin- hypertension.Norepinephrine Reuptake nabilone, a synthetic cannabinoid, drug interactions with midazolam, Inhibitors and nabiximols, a cannabis extract diazepam, and clonazepam– as a

that is available in the United result of metabolism117 119 by the P450 Kingdom and other countries95,113​ but enzyme system. ‍ ‍ In contrast, Serotonin-norepinephrine reuptake not in the United States. Such lorazepam is metabolized by inhibitors (SNRIs) are considered– therapies are suggested as third- conjugation. Children started on first- or second-line therapy for93 95 line treatment95,113​ of neuropathic pain clonazepam should be monitored adults with neuropathic pain. ‍ ‍ in adults. ‍ In a recent policy for the development of significant Downloaded from www.aappublications.org/news by guest on September 27, 2021 e16 FROM THE AMERICAN ACADEMY OF PEDIATRICS saliva production and bronchial trigger for 127,observed128​ self-injurious Medications include baclofen, secretions, possibly120, a121​ greater risk in behaviors. ‍ Medications trihexyphenidyl, and carbidopa/ younger children. Midazolam directed at central sources of pain are levodopa, yet only baclofen has137 FDA- is highly fat soluble, which can options to consider before the use of approved dosing for children. result in accumulation over time. Managementantipsychotics of and Chronic SSRIs. Problems: Benzodiazepines, neuroleptics, Continuous use in the hospital can Spasticity, Dystonia, Hip muscle relaxants, and presynaptic Subluxation, and Visceral Distention result in accumulation122 and prolonged dopamine-depleting medications sedation. These considerations have all 138been used with varying for midazolam are relevant to γ success. Intramuscular botulinum children with SNI, given the The treatment of spasticity includes toxin and intrathecal baclofen are greater 123,percentage124​ of fat for body baclofen,108, a 129​ -aminobutyric acid also options. A randomized trial of weight. ‍ agonist. ‍ The major adverse intrathecal baclofen for dystonic effect of sedation can be minimized cerebral palsy, including its impact Sudden cessation should be 139 by titrating the dose slowly. There on pain, is ongoing. In a subset of avoided, because withdrawal can is also concern that baclofen can patients with significant dystonia, occur. Withdrawal can result in potentiate seizures in children with implantation of a deep-brain such symptoms as jitteriness, 130 cerebral palsy. Other medications stimulator into the globus pallidus agitation, anxiety, increased heart 137 for spasticity include tizanidine, can be considered. rate, muscle cramps, disrupted 108,129​ clonidine, and dantrolene. sleep, gastrointestinal upset, and Nonpharmacologic strategies to Benzodiazepines for spasticity may heightened sensitivity to light and lessen the effects of spasticity best be reserved for intermittent or sound. One review of benzodiazepine 129 and dystonia include brace and short-term use. tapering after long-term use positioning, passive stretching, suggested a taper over 8 to 12 weeks, Intramuscular injections of massage, and warm baths. When such as decreasing by 10%125 of the botulinum toxin for focal spasticity pain behaviors are associated with original dose every 7 days. If can have benefit for associated spasticity and dystonia, medication persistent pain behaviors in a child pain in131, some132​ children with cerebral trials for chronic pain sources can be palsy. ‍ In studies in adults, with SNI are successfully managed considered before13,138​ pursuing surgical after other medication trials, botulinum toxin had some efficacy interventions. ‍ tapering of a benzodiazepine can be for neuropathic pain with localized 133 Interventions for hip subluxation/ considered. symptoms. Antipsychotics dislocation that results in pain The placement of an intrathecal or limitations in movement baclofen pump allows for the include botulinum toxin injections Used for agitation and delirium, it delivery of continuous and/ around the hip joint to improve132 is unclear what role antipsychotics, or pulse doses. The reduction range of motion and comfort– . including atypical antipsychotics in spasticity with intrathecal Surgical interventions can140 also143 such as risperidone, have in the baclofen is well documented, provide symptom relief. ‍ The management of persistent pain with limited134 evidence regarding consideration for surgery ideally behaviors in children with SNI. pain relief. Complications involves an interdisciplinary team Evidence in adults is lacking, with with intrathecal baclofen include of providers and shared goal setting adverse effects needing to be malfunction, infection,135 overdose, with the family, given the potential considered before126 use as an add-on and withdrawal. Selective dorsal risks and lengthy recovery period for therapy for pain. Antipsychotics rhizotomy is another surgical option some children,141 including pain for up should not be used as the sole for spasticity, although it is best toManagement 6 months. of Symptoms therapy when children with SNI suited for children with spastic Attributable to Visceral Distention have persistent pain behaviors. diplegia who are ambulatory136 and When used, adverse effects are an cognitively intact. important consideration. Interventions for dystonia include Children with SNI may be noted to Antipsychotics, as well as SSRIs, medications and surgically placed have symptom escalation before a have been used in children with self- devices. Such interventions are less bowel movement or with urinary injurious behaviors with variable effective in children with secondary retention. As discussed in the benefit. Self-injurious behaviors are dystonia than those with primary sections on central neuropathic also identified as pain behaviors dystonia, likely reflecting the pain and visceral hyperalgesia, this

(Table 3). Recent literature has coexistence137, of138​ other problems symptom escalation may reflect suggested neuropathic pain as a of the CNS. ‍ an altered threshold to symptom Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 139, number 6, June 2017 e17 generation at times of visceral ginseng, and tryptophan, when used to intermittent hyperthermia, distention. Some children will have in combination with other drugs. sweating, or a tracheostomy, is also a adequate symptom benefit from consideration when estimating fluid Vibratory stimulation is reported interventions that lessen distention, – Specificneeds. Considerations With as being beneficial for some with including the management of 147 149 Different Neurodevelopmental chronic pain. ‍ ‍ Products constipation that results in a Disorders available include vibrating mats and daily bowel movement, the use pillows. Parents may also observe of a suppository during times of their child appearing relaxed and persistent symptoms to determine This report focuses on children with comfortable when using high- whether colonic distention is a severe intellectual disability who lack frequency chest-wall oscillation vest trigger (ie, resolution of symptoms verbal communication, but there are therapy for mucous mobilization. after a bowel movement), and some specific conditions that warrant Other sensory techniques include the use of intermittent urinary mention. Children with cerebral palsy transcutaneous electrical nerve catheterization. Bowel medications and pain will often have worsening stimulation when neuropathic for consideration include 150 muscle tensing and spasms during pain can be well localized. The polyethylene glycol, lactulose, pain episodes. In contrast, children 144 potential benefit of vibratory senna, suppositories, and enemas. with intellectual disability and autism stimulation and transcutaneous The nonpharmacologic strategies would not be expected to have electrical nerve stimulation is based reviewed next can also be beneficial. pronounced muscle spasms with on the gate-control theory of pain When symptoms associated with pain. These differences can affect the in which a nonpainful stimulus can visceral distention occur weekly utility of different pain-assessment enhance the inhibition of nociceptive after such interventions, the use of 149,150​ tools. In addition, there have been transmission. ‍ a scheduled medication directed few studies specifically looking at at neuropathic pain/visceral Distention of the gastrointestinal pain assessment in children with hyperalgesia may lessen the tract is an important consideration, autism. Such children may have frequency, severity, and duration of given the lower– threshold to behavioral features that complicate associatedNonpharmacologic symptoms. Strategies That symptom13, generation56​ 58,61​ in some the process of pain assessment. Improve Comfort children. ‍ ‍‍ Strategies In general, the same principles of for symptoms triggered by pain assessment will apply to all gastrointestinal tract distention children with intellectual disability, Nonpharmacologic interventions include gastrostomy tube venting, with or without cerebral palsy or are an important part of symptom equipment that allows venting autism. Pain assessment includes management for all children with during feedings, and a decrease identifying individual baseline SNI. Simple strategies include in the total volume of fluids and characteristics as well as features tight swaddling, cuddling, rocking,84 nutrition given by feeding tube, that suggest pain, as noted by those repositioning, and massage. which is important given the risk of most familiar with the child. In such Supportive equipment, such as overestimating metabolism and fluid children with chronic recurrent seating systems and supportive needs. The greatest risk factors for pain behaviors, pain treatment will pillows, can minimize positional pain. overestimating energy expenditure require an empirical trial along Other interventions include warm by 30% or greater in children with with use of nonpharmacologic baths, weighted blankets, and music. SNI include chronic hypothermia, strategies (Figs 1 and 2). Children Audiotherapy has also been shown limited movement of extremities, with less impairment of the CNS to decrease pain postoperatively145 in placement of an intrathecal baclofen (eg, mild intellectual disability pediatric patients. Complementary pump, successful pain treatment with without cerebral palsy) likely have and integrative therapies can include a reduction in intermittent– muscle a lower incidence of pain sources essential oils, Reiki, and acupuncture, spasms, and declining13,123,​ health151​ 155 with attributable to the CNS. In children with evidence of efficacy being 146 declining activity. ‍ ‍ ‍ ‍ Fluid with autism, nonanalgesic medication notably limited in this population. needs can also be overestimated, categories have been studied for the A trusting relationship with families given that metabolic expenditure management of distressing behaviors can enhance the disclosure of accounts for more than half of fluid that overlap with pain behaviors, alternative medicines being used, estimation, with fluid estimation including SSRIs, antipsychotics, which can be relevant to drug based on weight then overestimating naltrexone, and clonidine. As noted interactions or sources of symptoms. what is required to maintain earlier, neuropathic pain has been ’ An example is the risk of serotonin hydration. Increased insensible suggested as a trigger for self- syndrome with St John s wort, fluid loss, such as that attributable injurious behaviors, a feature more Downloaded from www.aappublications.org/news by guest on September 27, 2021 e18 FROM THE AMERICAN ACADEMY OF PEDIATRICS commonly seen in those with effects, (5) the minimal initial dose the following information, with •• autism and127, severe128​ intellectual and time frame 156of the trial, and (6) examples provided in the Appendix: disability. ‍ Other considerations adverse effects. Table 8 provides ’ presenting symptoms (describe the and interventions, including a guidelines that use this information •• child s specific pain behaviors); search for triggers and behavioral and can be individualized. Monitoring management strategies, are clearly will determine whether there is initial routine interventions (check warranted for this complex problem. adequate benefit and, if not, if a •• for wet diaper, reposition); In children with intellectual disability second medication with a different initial nonpharmacologic and pain, these subgroups are mechanism of action directed at strategies (considerations include important considerations with the chronic pain sources will be added removing orthotics that may assessment and treatment of pain as (Fig 2). If a medication will be cause temporary discomfort, well as with future studies. discontinued, those to be tapered swaddling, rocking, using a fan, Broader Pain-Management before discontinuing include placing headphones with favorite Strategies and Considerations gabapentinoids, TCAs, opioids, music, massaging legs, placing benzodiazepines, and baclofen. on a vibratory mat, and other Ideally, when several medications are strategies that have been identified Although pain can often be improved to be tapered, 1 is tapered at •• as effective); by implementing the interventions a time. interventions for triggers such as discussed previously, the optimal Monitoring requires the availability gastrointestinal tract distention treatment of pain in children with of a team with adequate expertise to (use as-needed suppository or SNI often requires considerable time answer questions and to address new enema if no stool in 1 day, vent and effort to achieve and is most changes in pain episodes. As new gastrostomy feeding tube, hold likely accomplished if the overall symptoms occur, consideration of feedings for 2 hours, hold feedings treatment of pain for the child is new nociceptive pain sources can be and give electrolyte replacement guided by some broader management balanced with a review of medication overnight, reduce total feedings/ strategies and considerations. dosing and additional medication •• fluids); Optimal pain treatment includes ’ trials directed at sources of chronic care coordination with various use of as-needed medications pain. This team can also oversee providers involved with the child s (options include as-needed other important aspects of care, medical home. Specialty involvement antacid, acetaminophen, such as encouraging a family to store regarding potential sources and ibuprofen, morphine, clonidine, or medications such as opioids in a safe pain-management strategies may •• benzodiazepine); and location, ideally in a locked cabinet, include neurology, physical medicine to reduce the risk of accidental when to call (call the clinic during and rehabilitation, complex care, overdose by other children and to the day or the on-call clinician after gastroenterology, orthopedics, pain, discourage the diversion of opioids hours if symptoms persist despite palliative care, and hospice teams. for illicit use. Diversion might also use of the interventions outlined, Individualized pain-assessment tools be considered if the expected benefit provide numbers to call). and care plans can be made available does not occur with escalating doses. across different locations of care. Care Plans in the Home for Care plans can empower families One clearly designated team, ideally Breakthrough Pain Episodes with home-based options while with pain-management expertise, retaining the option for direct can oversee this process and can assessment in the clinic, emergency serve as the contact for questions and Chronic symptoms attributable to department, or hospital. If the Iconcernsnitiating asand they Monitoring arise. Empirical the impaired CNS can be modified frequency and severity of events Trials but not eliminated. Breakthrough increase, the dose of scheduled pain episodes should be anticipated, medications can be reviewed and with care plans developed to assist options for additional empirical Initiating a medication trial and families and home nurses in the Imedicationntractable trialsSymptoms can be considered. monitoring the outcome benefit from moment. Families, caregivers, and a rigorous process. Information to nurses are integral to this process, consider includes the following: (1) including monitoring the benefit Many children with SNI and response to previous medications, (2) of such plans. Care plans can be recurrent pain will have interaction with other medications, tailored through trial and error as improvement in symptoms after (3) initial dose, (4) the need for interventions that are beneficial are medication trials. The hoped-for titration to minimize adverse identified. A care plan may include benefit can be acknowledged with Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 139, number 6, June 2017 e19 Symptom Treatment Throughout Life families while also preparing them 5. Pain-management strategies for the possibility that some will should be used for painful Children with SNI deserve symptom have less benefit than desired. procedures. identification and treatment Case reports also suggest a risk of throughout life. Waiting until a child 6. Postsurgical pain a return of symptoms without a is thought to be dying often delays management benefits from an source, speculated to indicate further 35 symptom treatment, because it is interdisciplinary team approach. neuronal apoptosis in the CNS. “ often not possible to predict when 7. Children with SNI and acute pain Language at such times can include, a child with SNI is dying. It is also have an increased risk of certain I hope for as much benefit from this possible that a child with SNI will nociceptive pain sources. The next trial, although I also want you do better than expected if pain is goal is to identify and treat the to be prepared that we might not significantly lessened, reflecting cause of pain when possible. have the hoped-for benefit. What the harmful effect from the chronic ” 8. Pain that reaches a threshold is important to you as157 we consider release of stress hormones. Some these possibilities? ‍ children may also have improved of concern for a parent may respiratory function and a decrease reflect long-standing discomfort without a source, with the child Many of the sources of chronic in metabolic expenditure when often referred to as agitated or symptoms cannot be fixed; rather, muscle spasms triggered by pain irritable. Chronic pain sources medications can modify the are lessened, given the potential for attributable to the impaired CNS symptoms that are generated by altered position or respiratory72 effort attributable to muscle tensing. can be considered while also altering the imbalance of inhibition assessing for a new acute pain and excitation in the CNS. There Palliative care and hospice teams can assist with complex symptom source as a reason for escalating is also a balance between further symptoms. testing along with seeking a better management, including at the end of life. 9. Recurrent pain behavior outcome from multiple medication episodes in children are trials, with consideration that the Summary typically best treated by using problems and associated symptoms an empirical approach, with the are intractable, analogous to goal to lessen the frequency, intractable epilepsy. Although not Available evidence supports the duration, and severity of studied in children with SNI and following points for consideration: episodes. chronic pain behavior episodes, 1. Children with severe impairment 10. Lack of benefit from a decreasing benefit may occur from of the CNS, often referred to medication trial should not be more than 3 medication trials as children with SNI, have a viewed as evidence that pain is directed at chronic pain sources. significantly elevated frequency not present. and severity of pain episodes These considerations are compared with typically 11. Benefit from an empirical trial important for parents so as to developing children. directed at central causes of pain minimize overtesting at a time of behaviors can lessen the need 2. Features that are observed when diminishing benefit. Palliative care for invasive testing in search of a a nonverbal child with SNI is and hospice teams can provide nociceptive source. experiencing pain are referred to support and guidance throughout 12. Most evidence for treating “ 158 as pain behaviors. These features this process. Suggested language are summarized in Table 3. chronic pain sources in children includes, I know that comfort is with SNI is derived from the an important goal. I worry that it 3. These features are well adult literature. High-level has been difficult to meet this goal established, with pain- evidence exists for the treatment or that it will only be possible with assessment tools (Table 4) of central neuropathic pain in ” available to assist with pain adults, a source for consideration increased sedation.157 What are your thoughts? ‍ Discussions may monitoring in the hospital, such in children with SNI and result in a shared conclusion to as after surgery, as well as to persistent pain. First- and redirect goals and decisions, such as track response to interventions second-line trials (Fig 2) include for chronic pain. accepting sedation to meet the goal gabapentinoids and TCAs. of comfort and reconsidering the role 4. Nonpharmacologic interventions 13. Case series and reports of of further testing, resuscitation, and are an important part of routine children with SNI and persistent hospitalization. symptom management. pain behavior episodes suggest Downloaded from www.aappublications.org/news by guest on September 27, 2021 e20 FROM THE AMERICAN ACADEMY OF PEDIATRICS Lynn F. Davidson, MD, FAAP Beth Ellen Davis, MD, MPH, FAAP benefit from medications 21. Breakthrough symptoms can Sandra L. Friedman, MD, MPH, FAAP directed at central neuropathic be anticipated, with care plans Amy J. Houtrow, MD, PhD, MPH, FAAP pain, visceral hyperalgesia, and developed to assist families and Susan L. Hyman, MD, FAAP autonomic dysfunction, including home nurses in the moment and Dennis Z. Kuo, MD, MHS, FAAP Garey H. Noritz, MD, FAAP gabapentin and TCAs. tailored through trial and error Larry Yin, MD, MSPH, FAAP as beneficial interventions are 14. Neuropathic pain that persists Nancy A. Murphy, MD, FAAP, Immediate Past identified. after 1 medication trial can Chairperson 22. Potential CNS sources, such as benefit from medication Liaisons combinations with different central neuropathic pain and Jennifer Bolden Pitre, MA, JD Family Voices mechanisms of action. autonomic dysfunction, cannot – be eliminated. Medications Marie Mann, MD, MPH, FAAP – Maternal and Child Health Bureau 15. Other medications include can decrease symptoms acetaminophen and nonsteroidal Georgina Peacock, MD, MPH, FAAP – Centers for by increasing inhibition or Disease Control and Prevention antiinflammatory drugs for mild decreasing excitation in the Edwin Simpser, MD, FAAP – Section on Home Care pain and opioids for moderate to CNS. Many children will have a Peter J. Smith, MD, MA, FAAP – Section on severe pain. Not all children with decrease in symptoms with drug Developmental and Behavioral Pediatrics SNI and chronic pain behaviors trials, some will not experience Staff will respond to opioids. the degree of benefit desired, Stephanie Mucha, MPH 16. Pain behaviors often include and symptoms originating from alterations in tone, body the CNS can return or persist. position, and movement. When 23. Palliative care teams can bring Appendix: Home Care Plan a child with muscle spasms or interdisciplinary expertise Examples for Breakthrough dystonia is also identified to to assist with symptom Symptoms have pain behaviors, a chronic management and family support, Example 1: Child With Benefit From pain source can be the trigger for especially when symptoms Morphine When Symptoms Persist intermittent changes in tone and remain intractable after first-line After Other Interventions position. Some children will have Lead interventions.Authors improvement after a medication Julie Hauer, MD, FAAP directed at potential central Amy Houtrow, MD, PhD, MPH, FAAP Features that suggest pain/ sources of pain. discomfort in the child include Section on Hospice and Palliative crying, tears, stiffening of extremities, 17. Management of coexisting Medicine Executive Committee, problems, such as medications tremors, facial flushing (redness), 2015–2016 directed at spasticity and sweating, and facial grimacing. Chris Feudtner, MD, PhD, MPH, FAAP, Chairperson Actions when such features are dystonia, can also improve Julie Hauer, MD, FAAP comfort. Scott Klein, MD, MHSA, FAAP noted: Jeffrey Klick, MD, FAAP 1. Routine comfort measures: 18. If symptoms persist after Jennifer Linebarger, MD, MPH, FAAP such medication trials, some reposition, check diaper, etc children may benefit from Former Executive Committee Member 2. Remove ankle foot orthotics invasive interventions, including Kelly Komatz, MD, MPH, FAAP 3. Vibrating mat or pulmonary vest botulinum toxin injections and (when features persist) an intrathecal baclofen pump. Parent Affiliate Members Blyth Lord 4. Use fan if warm to the touch or 19. Bowel distention can trigger Stacy Parker facial flushing noted pain attributable to central neuropathic pain or visceral Staff 5. If pain considered mild, give as needed ibuprofen hyperalgesia. Management of Madra Guinn-Jones, MPH constipation can lessen this 6. If no improvement or if moderate trigger. Council on Children With Disabilities, to severe pain noted, give as 2015–2016 needed morphine sulfate 20. Overestimation of feeding and Kenneth W. Norwood Jr, MD, FAAP, Chairperson fluid requirements can be a 7. If no improvement within 20 to 30 Richard C. Adams, MD, FAAP trigger for symptoms in some, Timothy J. Brei, MD, FAAP minutes with 1 medication, give especially those with limited other medication (ie, if ibuprofen energy expenditure. given and no improvement within Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 139, number 6, June 2017 e21 Example 4: Younger Child Receiving Gabapentin and Clonidine, With 20 to 30 minutes, then give rate versus discomfort as a trigger Benefit From Vibratory Mat and morphine) for muscle tremors); allow judgment Clonazepam for Breakthrough Symptoms E8.xample Call team 2: C ifhild symptoms With Symptoms persist and experience to guide the order Attributable to Gastrointestinal Tract of medication use when it is not Distension and With Movement That possible to know with certainty while Is Not Always a Seizure considering and eliminating sources Interventions for persistent crying or that can trigger such events. toning: Example 3: Child With Symptom 1. Use the following 3 interventions, Protocol for events with back arching Relief From Gut Rest ⚬in⚬ no particular order: and/or muscle tremors: consider ≥ Swaddling: use large bath towel triggers for these events in addition or blanket, flex legs up toward to considering a seizure. For pain of 4 on pain scale: ⚬⚬abdomen, swaddle tightly 1. Start with the following 1. Give clonidine 0.2 mg via Vibratory mat, maximum of ⚬interventions:⚬ gastrostomy tube 15 minutes on followed by ⚬⚬ Reposition 2. If no stool that day, give milk ⚬⚬minimum of 15 minutes off ⚬⚬ of magnesia, 30 mL (used as an Vent gastrostomy tube Weighted blanket, 30 minutes antacid and for constipation) ⚬⚬If no stool during the day on followed by minimum of 30 3. If no stool in 1 day, give fleet minutes off Give scheduled suppository if not enema ⚬⚬yet given that day 2. If no benefit from the above, use 4. If no improvement, give morphine as-needed dose of clonazepam Give as needed enema if sulfate, 0.5 mL (10 mg) buccal (suggested starting dose of 0.005- suppository already given 0.01 mg/kg) Other interventions at times of Abbreviations 2. Give ibuprofen if not already given discomfort and pain: 3. Consider giving antacid if not 1. Bath for comfort already given 2. Vent gastrostomy tube if any CNS: central nervous system 4. Place in calm, dark environment abdominal distention, gagging, or FDA: Food and Drug Administration 5. If event includes facial flushing retching GERD: gastroesophageal reflex ⚬⚬ disease (redness) and appearing agitated 3. Other options include as-needed MS: multiple sclerosis Give as needed clonidine milk of magnesia, acetaminophen, r-FLACC: revised Face, Legs, and ibuprofen as ordered 6. If event involves rhythmic Activity, Cry, Consolability movement of extremities to For persistent pain despite as-needed SNI: severe neurologic ⚬suggest⚬ seizure medications (notify team the next impairment Give rectal diazepam; repeat if day): SNRI: serotonin-norepinephrine seizure activity persists for >15 1. Give electrolyte solution at 50 mL/ reuptake inhibitor × minutes hour in place of regular formula SSRI: selective serotonin “ ” reuptake inhibitor It is not critical to determine the feedings 24 hours × TCA: tricyclic antidepressant chicken and the egg (eg, is the 2. Give acetaminophen scheduled WHO: World Health Organization event a seizure with increased heart every 6 hours 24 hours

All clinical reports from the American Academy of Pediatrics automatically expire 5 years after publication unless reaffirmed, revised, or retired at or before that time.

DOI: https://​doi.​org/​10.​1542/​peds.​2017-​1002

Address correspondence to Julie Hauer, MD, FAAP. E-mail: [email protected]

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2017 by the American Academy of Pediatrics FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.

FUNDING: No external funding.

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

Downloaded from www.aappublications.org/news by guest on September 27, 2021 e22 FROM THE AMERICAN ACADEMY OF PEDIATRICS References 1. McCluggage HL. Symptoms suffered by 11. Houlihan CM, O’Donnell M, Conaway M, non-communicating children’s pain life-limited children that cause anxiety Stevenson RD. Bodily pain and health- checklist-postoperative version. to UK children’s hospice staff. Int J related quality of life in children with Anesthesiology. 2002;96(3):528–535 Palliat Nurs. 2006;12(6):254 258 cerebral palsy. Dev Med Child Neurol. – 21. Breau LM, McGrath PJ, Camfield CS, 2004;46(5):305 310 2. International Association for the Study – Finley GA. Psychometric properties of of Pain. IASP taxonomy. Available 12. Stallard P, Williams L, Velleman R, the Non-Communicating Children’s at: www.​iasp-​pain.​org/​Taxonomy. Lenton S, McGrath PJ. Brief report: Pain Checklist-Revised. Pain. Accessed June 15, 2016 behaviors identified by caregivers 2002;99(1–2):349–357 to detect pain in noncommunicating 22. Hadden KL, von Baeyer CL. Pain in 3. US Department of Health and Human children. J Pediatr Psychol. Services; National Institutes of Health; children with cerebral palsy: common 2002;27(2):209–214 National Cancer Institute. Common triggers and expressive behaviors. Terminology Criteria for Adverse 13. Hauer JM, Solodiuk JC. Gabapentin Pain. 2002;99(1–2):281–288 for management of recurrent Events (CTCAE). Available at: www.​hrc.​ 23. Car ter B, McArthur E, Cunliffe M. pain in 22 nonverbal children with govt.​nz/​sites/​default/​files/​CTCAE%20​ Dealing with uncertainty: parental severe neurological impairment: a manual%20​-​%20​DMCC.​pdf. Accessed assessment of pain in their children retrospective analysis. J Palliat Med. June 15, 2016 with profound special needs. J Adv 2015;18(5):453–456 4. Gilles EE. “Neuro-irritability” in Nurs. 2002;38(5):449–457 14. Per quin CW, Hazebroek-Kampschreur children with developmental 24. Voepel-Lewis T, Malviya S, Tait AR, disabilities: the role of autonomic AA, Hunfeld JA, et al. Pain in children and adolescents: a common et al. A comparison of the clinical nervous system dysregulation. utility of pain assessment tools for experience. Pain. 2000;87(1):51–58 Neuropadiatrie. 2011;10(1):15–19 children with cognitive impairment. 15. Solodiuk JC, Brighton H, McHale J, 5. Svedber g LE, Englund E, Malker H, Anesth Analg. 2008;106(1):72–78 et al. Documented electronic medical Stener-Victorin E. Parental perception record-based pain intensity scores at 25. Crosta QR, Ward TM, Walker AJ, Peters of cold extremities and other a tertiary pediatric medical center: LM. A review of pain measures for accompanying symptoms in children a cohort analysis. J Pain Symptom hospitalized children with cognitive with cerebral palsy. Eur J Paediatr impairment. J Spec Pediatr Nurs. Manage. 2014;48(5):924–933 Neurol. 2008;12(2):89–96 2014;19(2):109–118 16. Hunt A, Wisbeach A, Seers K, et al. 6. Steele R, Siden H, Cadell S, et al. Development of the Paediatric Pain 26. Chen-Lim ML, Zarnowsky C, Green R, Charting the territory: symptoms and Profile: role of video analysis and Shaffer S, Holtzer B, Ely E. Optimizing functional assessment in children with saliva cortisol in validating a tool to the assessment of pain in children progressive, non-curable conditions. assess pain in children with severe who are cognitively impaired through Arch Dis Child. 2014;99(8):754 762 – neurological disability. J Pain Symptom the quality improvement process. J Pediatr Nurs. 2012;27(6):750 759 7. World Health Organization. WHO Manage. 2007;33(3):276–289 – guidelines on the pharmacological 17. Herr K, Coyne PJ, McCaffery M, 27. Rattaz C, Dubois A, Michelon C, treatment of persisting pain in Manworren R, Merkel S. Pain Viellard M, Poinso F, Baghdadli A. How children with medical illnesses. assessment in the patient unable to do children with autism spectrum Available at: www.​who.​int/​medicines/​ self-report: position statement with disorders express pain? A comparison areas/​quality_​safety/​guide_​ clinical practice recommendations. with developmentally delayed and perspainchild/en/​ ​. Accessed June 15, Pain Manag Nurs. 2011;12(4):230–250 typically developing children. Pain. 2016 2013;154(10):2007–2013 18. Malviya S, Voepel-Lewis T, Burke C, 8. Oberlander TF, O’Donnell ME. Beliefs Merkel S, Tait AR. The revised FLACC 28. Nader R, Oberlander TF, Chambers about pain among professionals observational pain tool: improved CT, Craig KD. Expression of pain in working with children with significant reliability and validity for pain children with autism. Clin J Pain. neurologic impairment. Dev Med Child assessment in children with cognitive 2004;20(2):88–97 Neurol. 2001;43(2):138 140 – impairment. Paediatr Anaesth. 29. Tomlinson D, von Baeyer CL, Stinson 9. Breau LM, Camfield CS, McGrath 2006;16(3):258–265 JN, Sung L. A systematic review of PJ, Finley GA. The incidence of pain 19. Solodiuk JC, Scott-Sutherland J, FACES scales for the self-report of in children with severe cognitive Meyers M, et al. Validation of the pain intensity in children. Pediatrics. impairments. Arch Pediatr Adolesc Individualized Numeric Rating Scale 2010;126(5). Available at: www.​ Med. 2003;157(12):1219–1226 (INRS): a pain assessment tool for pediatrics.​org/​cgi/​content/​full/​126/​5/​ e1168 10. Hunt A, Goldman A, Seers K, et al. nonverbal children with intellectual Clinical validation of the paediatric disability. Pain. 2010;150(2):231–236 30. Biersdorff KK. Incidence of significantly pain profile. Dev Med Child Neurol. 20. Breau LM, Finley GA, McGrath PJ, altered pain experience among 2004;46(1):9–18 Camfield CS. Validation of the individuals with developmental

Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 139, number 6, June 2017 e23 disabilities. Am J Ment Retard. 41. Smith HA, Boyd J, Fuchs DC, et al. 53. Rieger D, Auerbach S, Robinson P, 1994;98(5):619–631 Diagnosing delirium in critically ill Gropman A. Neuroimaging of lipid children: validity and reliability of storage disorders. Dev Disabil Res Rev. 31. Jan JE, Abroms IF, Freeman RD, Brown the pediatric Confusion Assessment 2013;17(3):269 282 GM, Espezel H, Connolly MB. Rapid – Method for the Intensive Care Unit. Crit cycling in severely multidisabled 54. Dunn HG. Neurons and neuronal Care Med. 2011;39(1):150 157 children: a form of bipolar – systems involved in the affective disorder? Pediatr Neurol. 42. Hauer JM, Wical BS, Charnas L. pathophysiologies of Rett syndrome. 1994;10(1):34–39 Gabapentin successfully manages Brain Dev. 2001;23(suppl 1):S99–S100 chronic unexplained irritability in 32. St hle-Oberg L, Fjellman-Wiklund A. 55. Huang BY, Castillo M. Hypoxic-ischemic å children with severe neurologic Parents experience of pain in children brain injury: imaging findings from ’ impairment. Pediatrics. 2007;119(2). with cerebral palsy and multiple birth to adulthood. Radiographics. Available at: www.​pediatrics.​org/​cgi/​ disabilities: an interview study. Adv 2008;28(2):417 439, quiz 617 content/​full/​119/​2/​e519 – Physiother. 2009;11(3):137–144 43. Siden HB, Carleton BC, Oberlander TF. 56. Canavero S, Bonicalzi V. Central Pain 33. Penner M, Xie WY, Binepal N, Switzer L, Physician variability in treating pain Syndrome: Pathophysiology, Diagnosis, Fehlings D. Characteristics of pain in and irritability of unknown origin in and Management. New York, NY: children and youth with cerebral palsy. children with severe neurological Cambridge University Press; 2007:48 Pediatrics. 2013;132(2). Available at: impairment. Pain Res Manag. www.​pediatrics.​org/​cgi/​content/​full/​ 57. Delgado-Aros S, Camilleri M. Visceral 2013;18(5):243 248 132/​2/​e407 – hypersensitivity. J Clin Gastroenterol. 44. Haney AL, Garner SS, Cox TH. 2005;39(5 suppl 3):S194–S203; 34. Wusthoff CJ, Shellhaas RA, Licht DJ. Gabapentin therapy for pain and discussion: S210 Management of common neurologic irritability in a neurologically symptoms in pediatric palliative care: 58. Zangen T, Ciarla C, Zangen S, et al. impaired infant. Pharmacotherapy. seizures, agitation, and spasticity. Gastrointestinal motility and sensory 2009;29(8):997–1001 abnormalities may contribute to Pediatr Clin North Am. 2007;54(5):709– 733, xi 45. Hauer J. Improving comfort in children food refusal in medically fragile with severe neurological impairment. toddlers. J Pediatr Gastroenterol Nutr. 35. Hauer JM. Pain: evaluation and Prog Palliat Care. 2012;20(6):349–356 2003;37(3):287–293 treatment. In: Caring for Children Who Have Severe Neurological Impairment: 46. Defrin R, Lotan M, Pick CG. The 59. Hunt A, Mastroyannopoulou K, Goldman A Life With Grace. Baltimore, MD: Johns evaluation of acute pain in individuals A, Seers K. Not knowing—the problem Hopkins University Press; 2013: with cognitive impairment: a of pain in children with severe 81–130 differential effect of the level of neurological impairment. Int J Nurs impairment. Pain. 2006;124(3):312–320 Stud. 2003;40(2):171–183 36. Siden H, Oberlander TF. Pain management for children with 47. Kehlet H, Jensen TS, Woolf CJ. 60. Breau LM, Camfield CS, McGrath a developmental disability in a Persistent postsurgical pain: risk PJ, Finley GA. Risk factors for pain primary care setting. In: Walco factors and prevention. Lancet. in children with severe cognitive GA, Goldschneider KR, eds. Pain in 2006;367(9522):1618–1625 impairments. Dev Med Child Neurol. Children: A Practical Guide for Primary 48. Lauder GR, White MC. Neuropathic 2004;46(6):364–371 Care. Totowa, NJ: Humana Press; pain following multilevel surgery in 61. Mousa H, Caniano DA, Alhajj M, Gibson 2008:32 children with cerebral palsy: a case L, Di Lorenzo C, Binkowitz L. Effect 37. Boyer EW, Shannon M. The series and review. Paediatr Anaesth. of Nissen fundoplication on gastric serotonin syndrome. N Engl J Med. 2005;15(5):412–420 motor and sensory functions. J Pediatr 2005;352(11):1112–1120 49. Nicholson BD. Evaluation and Gastroenterol Nutr. 2006;43(2):185–189 38. Jackson N, Doherty J, Coulter S. treatment of central pain syndromes. 62. Agrawal S. Neuro-crying, neuro- Neuropsychiatric complications of Neurology. 2004;62(5 suppl 2):S30–S36 irritability, or pain? A personal commonly used palliative care drugs. 50. Frese A, Husstedt IW, Ringelstein EB, account. Complex Child E-Magazine. Postgrad Med J. 2008;84(989):121–126, Evers S. Pharmacologic treatment of Available at: www.​articles.​ quiz 125 central post-stroke pain. Clin J Pain. complexchild.​com/​nov2009/​00166.​html. Accessed June 15, 2016 39. Del Fabbro E, Dalal S, Bruera E. 2006;22(3):252–260 Symptom control in palliative care— 51. Klit H, Finnerup NB, Jensen TS. 63. Park ES, Park CI, Cho SR, Lee JW, part III: dyspnea and delirium. J Palliat Central post-stroke pain: clinical Kim EJ. Assessment of autonomic Med. 2006;9(2):422–436 characteristics, pathophysiology, nervous system with analysis of and management. Lancet Neurol. 40. T raube C, Silver G, Kearney J, et al. heart rate variability in children with 2009;8(9):857 868 Cornell assessment of pediatric – spastic cerebral palsy. Yonsei Med J. delirium: a valid, rapid, observational 52. Renard D, Castelnovo G, Campello C, 2002;43(1):65–72 tool for screening delirium in the PICU. et al. Thalamic lesions: a radiological 64. Axelrod FB, Berlin D. Pregabalin: a Crit Care Med. 2014;42(3):656–663 review. Behav Neurol. 2014;2014:154631 new approach to treatment of the

Downloaded from www.aappublications.org/news by guest on September 27, 2021 e24 FROM THE AMERICAN ACADEMY OF PEDIATRICS dysautonomic crisis. Pediatrics. pain: a systematic review. Pediatrics. Available at: https://​www.​fda.​gov/​ 2009;124(2):743–746 2014;133(3):500–515 Drugs/​DrugSafety/​ucm549679.​htm. 65. Chelimsky G, Chelimsky T. Familial 76. Zier JL, Rivard PF, Krach LE, Wendorf Accessed April 23, 2017 association of autonomic and HR. Effectiveness of sedation using 87. Gardner JS, Blough D, Drinkard gastrointestinal symptoms. Clin Auton nitrous oxide compared with enteral CR, et al. Tramadol and seizures: a Res. 2001;11(6):383–386 midazolam for botulinum toxin A surveillance study in a managed 66. Chelimsky G, Hupertz VF, Chelimsky injections in children. Dev Med Child care population. Pharmacotherapy. TC. Abdominal pain as the presenting Neurol. 2008;50(11):854–858 2000;20(12):1423–1431 symptom of autonomic dysfunction 77. Cramton RE, Gruchala NE. Managing 88. Nicholson B. Morphine sulfate in a child. Clin Pediatr (Phila). procedural pain in pediatric patients. extended-release capsules for the 1999;38(12):725–729 Curr Opin Pediatr. 2012;24(4):530–538 treatment of chronic, moderate- 67. Foster -Barber A. Pain and 78. Bar wood S, Baillieu C, Boyd R, et al. to-severe pain. Expert Opin suffering from epileptic seizures Analgesic effects of botulinum toxin Pharmacother. 2008;9(9):1585–1594 in the noncommunicative patient. A: a randomized, placebo-controlled 89. Center to Advance Palliative Care. Neuropadiatrie. 2011;10(1):20–25 clinical trial. Dev Med Child Neurol. Once-daily oral morphine formulations. 68. Sanger TD, Delgado MR, Gaebler- 2000;42(2):116–121 Available at: https://​www.​capc.​org/​fast-​ Spira D, Hallett M, Mink JW; Task 79. Rusy LM, Hainsworth KR, Nelson TJ, facts/​166-​once-​daily-​oral-​morphine-​ Force on Childhood Motor Disorders. et al. Gabapentin use in pediatric formulations/​. Accessed June 15, 2016 Classification and definition of spinal fusion patients: a randomized, 90. Bruera E, Sweeney C. Methadone use in disorders causing hypertonia in double-blind, controlled trial. Anesth cancer patients with pain: a review. childhood. Pediatrics. 2003;111(1). Analg. 2010;110(5):1393–1398 J Palliat Med. 2002;5(1):127–138 Available at: www.​pediatrics.​org/​cgi/​ 80. Mayell A, Srinivasan I, Campbell 91. Strouse TB. Pharmacokinetic drug content/​full/​111/​1/​e89 F, Peliowski A. Analgesic effects interactions in palliative care: 69. Valencia FG. Management of hip of gabapentin after scoliosis focus on opioids. J Palliat Med. deformities in cerebral palsy. Orthop surgery in children: a randomized 2009;12(11):1043–1050 Clin North Am. 2010;41(4):549–559 controlled trial. Paediatr Anaesth. 92. Berde CB, Lebel AA, Olsson G. 70. Williams DG, Patel A, Howard RF. 2014;24(12):1239–1244 Neuropathic pain in children. In: Pharmacogenetics of codeine 81. Gauger VT, Voepel-Lewis TD, Burke CN, Schechter NL, Berde CB, Yaster metabolism in an urban population et al. Epidural analgesia compared M, eds. Pain in Infants, Children, of children and its implications for with intravenous analgesia after and Adolescents. Philadelphia, PA: analgesic reliability. Br J Anaesth. pediatric posterior spinal fusion. Lippincott Williams and Wilkins; 2002;89(6):839–845 J Pediatr Orthop. 2009;29(6):588–593 2003:620–641 71. Ciszkowski C, Madadi P, Phillips 82. Nolan J, Chalkiadis GA, Low J, Olesch 93. Finnerup NB, Otto M, McQuay HJ, MS, Lauwers AE, Koren G. Codeine, CA, Brown TC. Anaesthesia and pain Jensen TS, Sindrup SH. Algorithm ultrarapid-metabolism genotype, and management in cerebral palsy. for neuropathic pain treatment: postoperative death. N Engl J Med. Anaesthesia. 2000;55(1):32–41 an evidence based proposal. Pain. 2009;361(8):827–828 83. Taenzer AH, Clark C. Efficacy of 2005;118(3):289–305 72. Hauer JM. Treating dyspnea with postoperative epidural analgesia 94. Dworkin RH, O’Connor AB, Backonja morphine sulfate in nonverbal children in adolescent scoliosis surgery: a M, et al. Pharmacologic management with neurological impairment. Pediatr meta-analysis. Paediatr Anaesth. of neuropathic pain: evidence- Pulmonol. 2015;50(4):E9–E12 2010;20(2):135–143 based recommendations. Pain. 73. Rocker G, Young J, Donahue M, 84. Friedrichsdorf SJ, Kang TI. The 2007;132(3):237–251 Farquhar M, Simpson C. Perspectives management of pain in children with 95. Moulin D, Boulanger A, Clark of patients, family caregivers and life-limiting illnesses. Pediatr Clin AJ, et al; Canadian Pain Society. physicians about the use of opioids North Am. 2007;54(5):645–672, x Pharmacological management of for refractory dyspnea in advanced 85. Zernikow B, Michel E, Craig F, Anderson chronic neuropathic pain: revised chronic obstructive pulmonary BJ. Pediatric palliative care: use of consensus statement from the disease. CMAJ. 2012;184(9):E497–E504 opioids for the management of pain. Canadian Pain Society. Pain Res Manag. 2014;19(6):328 335 74. Koller D, Goldman RD. Distraction Paediatr Drugs. 2009;11(2):129–151 – techniques for children undergoing 86. Food and Drug Administration. 96. Hasler WL. Pharmacotherapy for procedures: a critical review of FDA Drug Safety Communication: intestinal motor and sensory pediatric research. J Pediatr Nurs. FDA restricts use of prescription disorders. Gastroenterol Clin North 2012;27(6):652–681 codeine pain and cough medicines Am. 2003;32(2):707–732, viii–ix 75. Lee GY, Yamada J, Kyololo O, Shorkey and tramadol pain medicines in 97. Lee KJ, Kim JH, Cho SW. Gabapentin A, Stevens B. Pediatric clinical practice children; recommends against use in reduces rectal mechanosensitivity guidelines for acute procedural breastfeeding women. April 20, 2017. and increases rectal compliance in

Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 139, number 6, June 2017 e25 patients with diarrhoea-predominant bench to bedside. Lancet Neurol. 117. Devlin JW, Roberts RJ. Pharmacology irritable bowel syndrome. Aliment 2013;12(11):1084–1095 of commonly used analgesics and Pharmacol Ther. 2005;22(10): 107. Chaparro LE, Wiffen PJ, Moore RA, sedatives in the ICU: benzodiazepines, 981–988 Gilron I. Combination pharmacotherapy propofol, and opioids. Crit Care Clin. 2009;25(3):431 449, vii 98. Houghton LA, Fell C, Whorwell PJ, for the treatment of neuropathic pain – Jones I, Sudworth DP, Gale JD. Effect in adults. Cochrane Database Syst Rev. 118. Riss J, Cloyd J, Gates J, Collins of a second-generation alpha2delta 2012;(7):CD008943 S. Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. ligand (pregabalin) on visceral 108. Lubsch L, Habersang R, Haase M, Acta Neurol Scand. 2008;118(2):69 86 sensation in hypersensitive patients Luedtke S. Oral baclofen and clonidine – with irritable bowel syndrome. Gut. for treatment of spasticity in children. 119. Tanaka E. Clinically significant 2007;56(9):1218 1225 – J Child Neurol. 2006;21(12):1090–1092 pharmacokinetic drug interactions with benzodiazepines. J Clin Pharm 99. Baguley IJ, Heriseanu RE, Gurka 109. Baguley IJ, Cameron ID, Green AM, Ther. 1999;24(5):347 355 JA, Nordenbo A, Cameron ID. Slewa-Younan S, Marosszeky JE, Gurka – Gabapentin in the management JA. Pharmacological management 120. Browne TR. Clonazepam: a review of a of dysautonomia following severe of dysautonomia following new anticonvulsant drug. Arch Neurol. traumatic brain injury: a case series. traumatic brain injury. Brain Inj. 1976;33(5):326–332 J Neurol Neurosurg Psychiatry. 2004;18(5):409–417 121. Browne TR. Clonazepam. N Engl J Med. 2007;78(5):539–541 110. Smith H, Elliott J. Alpha(2) 1978;299(15):812–816 100. Cutter NC, Scott DD, Johnson JC, receptors and agonists in pain 122. Gan TJ. Pharmacokinetic and Whiteneck G. Gabapentin effect on management. Curr Opin Anaesthesiol. pharmacodynamic characteristics spasticity in multiple sclerosis: a 2001;14(5):513–518 of medications used for moderate placebo-controlled, randomized sedation. Clin Pharmacokinet. trial. Arch Phys Med Rehabil. 111. Kuiken SD, Tytgat GN, Boeckxstaens GE. Review article: drugs interfering with 2006;45(9):855–869 2000;81(2):164–169 visceral sensitivity for the treatment 123. Kuperminc MN, Gurka MJ, Bennis JA, 101. Cappuccio G, Brunetti-Pierri N, Terrone of functional gastrointestinal et al. Anthropometric measures: poor G, Romano A, Andria G, Del Giudice disorders—the clinical evidence. predictors of body fat in children with E. Low-dose amitriptyline-induced Aliment Pharmacol Ther. moderate to severe cerebral palsy. Dev acute dystonia in a patient with 2005;21(6):633–651 Med Child Neurol. 2010;52(9): metachromatic leukodystrophy. JIMD 112. Croxford JL. Therapeutic potential 824–830 Rep. 2013;9:113–116 of cannabinoids in CNS disease. CNS 124. Kong CK, Wong HS. Weight-for-height 102. Taylor CP. The biology and Drugs. 2003;17(3):179–202 values and limb anthropometric pharmacology of calcium channel 113. Collin C, Davies P, Mutiboko IK, Ratcliffe composition of tube-fed children alpha2-delta proteins. Pfizer Satellite with quadriplegic cerebral palsy. Symposium to the 2003 Society for S; Sativex Spasticity in MS Study Group. Randomized controlled trial of Pediatrics. 2005;116(6). Available at: Neuroscience Meeting; New Orleans, www.​pediatrics.​org/​cgi/​content/​full/​ LA; November 10, 2003. CNS Drug Rev. cannabis-based medicine in spasticity caused by multiple sclerosis. Eur J 116/​6/​e839 2004;10(2):183–188 Neurol. 2007;14(3):290–296 125. Lader M, Tylee A, Donoghue J. 103. Korn-Merker E, Borusiak P, Boenigk HE. 114. Ammerman S, Ryan S, Adelman WP; Withdrawing benzodiazepines Gabapentin in childhood epilepsy: a Committee on Substance Abuse; in primary care. CNS Drugs. prospective evaluation of efficacy and Committee on Adolescence. The impact 2009;23(1):19–34 safety. Epilepsy Res. 2000;38(1):27–32 of marijuana policies on youth: clinical, 126. Seidel S, Aigner M, Ossege M, Pernicka 104. Haig GM, Bockbrader HN, Wesche research, and legal update. Pediatrics. E, Wildner B, Sycha T. Antipsychotics DL, et al. Single-dose gabapentin 2015;135(3). Available at: www.​ for acute and chronic pain in pharmacokinetics and safety in healthy pediatrics.​org/​cgi/​content/​full/​135/​3/​ adults. Cochrane Database Syst Rev. infants and children. J Clin Pharmacol. e769 2013;(8):CD004844 2001;41(5):507–514 115. Kalachnik JE, Hanzel TE, Sevenich R, 127. Symons FJ. Self-injurious behavior 105. Gilron I, Bailey JM, Tu D, Holden Harder SR. Benzodiazepine behavioral in neurodevelopmental disorders: RR, Jackson AC, Houlden RL. side effects: review and implications relevance of nociceptive and immune Nortriptyline and gabapentin, alone for individuals with mental retardation. mechanisms. Neurosci Biobehav Rev. and in combination for neuropathic Am J Ment Retard. 2002;107(5):376–410 2011;35(5):1266–1274 pain: a double-blind, randomised 116. Kalachnik JE, Hanzel TE, Sevenich R, 128. Peebles KA, Price TJ. Self-injurious controlled crossover trial. Lancet. Harder SR. Brief report: clonazepam behaviour in intellectual disability 2009;374(9697):1252 1261 – behavioral side effects with an syndromes: evidence for aberrant 106. Gilron I, Jensen TS, Dickenson AH. individual with mental retardation. pain signalling as a contributing Combination pharmacotherapy for J Autism Dev Disord. 2003;33(3): factor. J Intellect Disabil Res. management of chronic pain: from 349–354 2012;56(5):441–452

Downloaded from www.aappublications.org/news by guest on September 27, 2021 e26 FROM THE AMERICAN ACADEMY OF PEDIATRICS 129. Delgado MR, Hirtz D, Aisen M, et al; 138. Rouber tie A, Mariani LL, Fernandez- alleviation of pain. Scand J Rehabil Quality Standards Subcommittee of Alvarez E, Doummar D, Roze E. Med. 1987;19(4):153–158 the American Academy of Neurology; Treatment for dystonia in childhood. 150. DeSantana JM, Walsh DM, Vance C, Practice Committee of the Child Eur J Neurol. 2012;19(10):1292–1299 Rakel BA, Sluka KA. Effectiveness Neurology Society. Practice parameter: 139. Bonouvrié LA, Becher JG, Vles JS, of transcutaneous electrical pharmacologic treatment of spasticity et al. Intrathecal baclofen treatment in nerve stimulation for treatment of in children and adolescents with dystonic cerebral palsy: a randomized hyperalgesia and pain. Curr Rheumatol cerebral palsy (an evidence-based clinical trial: the IDYS trial. BMC Rep. 2008;10(6):492–499 review): report of the Quality Pediatr. 2013;13:175 Standards Subcommittee of the 151. Dickerson RN, Brown RO, Hanna DL, American Academy of Neurology 140. Hogan KA, Blake M, Gross RH. Williams JE. Effect of upper extremity and the Practice Committee of the Subtrochanteric valgus osteotomy posturing on measured resting Child Neurology Society. Neurology. for chronically dislocated, painful energy expenditure of nonambulatory spastic hips. J Bone Joint Surg Am. tube-fed adult patients with severe 2010;74(4):336–343 2006;88(12):2624–2631 neurodevelopmental disabilities. 130. Hansel DE, Hansel CR, Shindle MK, JPEN J Parenter Enteral Nutr. et al. Oral baclofen in cerebral palsy: 141. Knaus A, Terjesen T. Proximal femoral 2002;26(5):278–284 possible seizure potentiation? Pediatr resection arthroplasty for patients with cerebral palsy and dislocated 152. Dickerson RN, Brown RO, Hanna DL, Neurol. 2003;29(3):203–206 hips: 20 patients followed for 1-6 years. Williams JE. Energy requirements 131. Rivard PF, Nugent AC, Symons FJ. Acta Orthop. 2009;80(1):32–36 of non-ambulatory, tube-fed adult Parent-proxy ratings of pain before 142. Raphael BS, Dines JS, Akerman M, patients with cerebral palsy and and after botulinum toxin type A chronic hypothermia. Nutrition. treatment for children with spasticity Root L. Long-term followup of total 2003;19(9):741–746 and cerebral palsy. Clin J Pain. hip arthroplasty in patients with cerebral palsy. Clin Orthop Relat Res. 153. Gale R, Namestnic J, Singer P, Kagan 2009;25(5):413–417 2010;468(7):1845–1854 I. Caloric requirements of patients 132. Lundy CT, Doherty GM, Fairhurst CB. with brain impairment and cerebral 143. Boldingh EJ, Bouwhuis CB, van der Botulinum toxin type A injections can palsy who are dependent on chronic Heijden-Maessen HC, Bos CF, Lankhorst be an effective treatment for pain ventilation [published online ahead GJ. Palliative hip surgery in severe in children with hip spasms and of print August 15, 2016]. JPEN J cerebral palsy: a systematic review. cerebral palsy. Dev Med Child Neurol. Parenter Enteral Nutr. doi:​10.​1177/​ J Pediatr Orthop B. 2014;23(1): 2009;51(9):705–710 0148607116662970 86–92 133. Intiso D, Basciani M, Santamato A, 154. McCoy AA, Fox MA, Schaubel DE, 144. Elawad MA, Sullivan PB. Management Intiso M, Di Rienzo F. Botulinum toxin Ayyangar RN. Weight gain in children of constipation in children with type A for the treatment of neuropathic with hypertonia of cerebral origin disabilities. Dev Med Child Neurol. pain in neuro-rehabilitation. receiving intrathecal baclofen 2001;43(12):829 832 Toxins (Basel). 2015;7(7): – therapy. Arch Phys Med Rehabil. 2454–2480 145. Sunitha Suresh BS, De Oliveira GS 2006;87(11):1503–1508 Jr, Suresh S. The effect of audio 134. Hoving MA, van Raak EP, Spincemaille 155. Vernon-Rober ts A, Wells J, Grant H, therapy to treat postoperative pain in GH, et al; Dutch Study Group on Child et al. Gastrostomy feeding in cerebral children undergoing major surgery: a Spasticity. Safety and one-year efficacy palsy: enough and no more. Dev Med randomized controlled trial. Pediatr of intrathecal baclofen therapy in Child Neurol. 2010;52(12):1099–1105 children with intractable spastic Surg Int. 2015;31(2):197–201 156. Hauer JM. Treating pain and other cerebral palsy. Eur J Paediatr Neurol. 146. Liptak GS. Complementary and distressing symptoms. In: Caring 2009;13(3):247 256 alternative therapies for cerebral – for Children Who Have Severe palsy. Ment Retard Dev Disabil Res Rev. 135. Albright AL, Gilmartin R, Swift D, Krach Neurological Impairment: A Life With 2005;11(2):156 163 LE, Ivanhoe CB, McLaughlin JF. Long- – Grace. Baltimore, MD: Johns Hopkins term intrathecal baclofen therapy for 147. Vibration for pain control and calming. University Press; 2013:65–77 severe spasticity of cerebral origin. Complex Child E-Magazine. Available 157. Hauer JM, Wolfe J. Supportive and J Neurosurg. 2003;98(2): at: www.​articles.​complexchild.​com/​ palliative care of children with 291 295 – sept2009/​00152.​html. Accessed June metabolic and neurological diseases. 136. Sgouros S. Surgical management 15, 2016 Curr Opin Support Palliat Care. of spasticity of cerebral origin in 148. Lundeber g T. Long-term results 2014;8(3):296–302 children. Acta Neurochir Suppl (Wien). of vibratory stimulation as a pain 158. Section on Hospice and Palliative 2007;97(pt 1):193–203 relieving measure for chronic pain. Medicine; Committee on Hospital 137. Mink JW. Special concerns in Pain. 1984;20(1):13–23 Care. Pediatric palliative care and defining, studying, and treating 149. Lundeber g T, Abrahamsson P, hospice care commitments, guidelines, dystonia in children. Mov Disord. Bondesson L, Haker E. Vibratory and recommendations. Pediatrics. 2013;28(7):921–925 stimulation compared to placebo in 2013;132(5):966–972

Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 139, number 6, June 2017 e27 Pain Assessment and Treatment in Children With Significant Impairment of the Central Nervous System Julie Hauer, Amy J. Houtrow and SECTION ON HOSPICE AND PALLIATIVE MEDICINE, COUNCIL ON CHILDREN WITH DISABILITIES Pediatrics 2017;139; DOI: 10.1542/peds.2017-1002 originally published online May 22, 2017;

Updated Information & including high resolution figures, can be found at: Services http://pediatrics.aappublications.org/content/139/6/e20171002 References This article cites 146 articles, 15 of which you can access for free at: http://pediatrics.aappublications.org/content/139/6/e20171002#BIBL Subspecialty Collections This article, along with others on similar topics, appears in the following collection(s): Current Policy http://www.aappublications.org/cgi/collection/current_policy Council on Children with Disabilities http://www.aappublications.org/cgi/collection/council_on_children_ with_disabilities Section on Gastroenterology, Hepatology and Nutrition http://www.aappublications.org/cgi/collection/section_on_gastroente rology_hepatology_and_nutrition Section on Hospice and Palliative Medicine http://www.aappublications.org/cgi/collection/section-hospice-palliat ive-medicine Hospice/Palliative Medicine http://www.aappublications.org/cgi/collection/hospice:palliative_me dicine_sub Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.aappublications.org/site/misc/Permissions.xhtml Reprints Information about ordering reprints can be found online: http://www.aappublications.org/site/misc/reprints.xhtml

Downloaded from www.aappublications.org/news by guest on September 27, 2021 Pain Assessment and Treatment in Children With Significant Impairment of the Central Nervous System Julie Hauer, Amy J. Houtrow and SECTION ON HOSPICE AND PALLIATIVE MEDICINE, COUNCIL ON CHILDREN WITH DISABILITIES Pediatrics 2017;139; DOI: 10.1542/peds.2017-1002 originally published online May 22, 2017;

The online version of this article, along with updated information and services, is located on the World Wide Web at: http://pediatrics.aappublications.org/content/139/6/e20171002

Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. Pediatrics is owned, published, and trademarked by the American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 2017 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.

Downloaded from www.aappublications.org/news by guest on September 27, 2021