Julian M. Stewart, MD, PhD, a Jeffrey R. Boris, MD, b Gisela Chelimsky, MD, c Phillip R. Fischer, MD, d PediatricJohn E. Fortunato, MD, e Blair P.Disorders Grubb, MD,f Geoffrey L. Heyer, MD,of g Imad T. Jarjour, MD, h Marvin S. Medow, PhD, a Mohammed T. Numan, MD, i Paolo T. Pianosi, MD, d Wolfgang Singer, MD, d Sally Tarbell, PhD, j OrthostaticThomas C. Chelimsky, MD,c The Pediatric Intolerance Writing Group of the American Autonomic Society abstract Orthostatic intolerance (OI), having difficulty tolerating an upright posture ∼ NIH because of symptoms or signs that abate when returned to supine, is common in pediatrics.‍ For example, 40% of people faint during their lives, half of whom faint during adolescence, and the peak age for first faint is 15 years.‍ Because of this, we describe the most common forms of OI in pediatrics and distinguish between chronic and acute OI.‍ These common forms of OI include initial orthostatic hypotension (which is a frequently Disclaimer: The guidelines/recommendations in this article are not American Acaemy of Pediatrics seen benign condition in youngsters), true orthostatic hypotension policy, and publication herein does not imply (both neurogenic and nonneurogenic), vasovagal syncope, and postural endorsement. tachycardia syndrome.‍ We also describe the influences of chronic bed rest and rapid weight loss as aggravating factors and causes of OI.‍ Presenting aNew York Medical College, Valhalla, New York; bChildren’s signs and symptoms are discussed as well as patient evaluation and Hospital of Philadelphia, Philadelphia, Pennsylvania; c testing modalities.‍ Putative causes of OI, such as gravitational and exercise Medical College of Wisconsin, Milwaukee, Wisconsin; dMayo Clinic, Rochester, Michigan; eAnn and Robert H. Lurie deconditioning, immune-mediated disease, mast cell activation, and Children’s Hospital of Chicago, Chicago, Illinois; fUniversity central hypovolemia, are described as well as frequent comorbidities, such of Toledo Medical Center, Toledo, Ohio; gNationwide Children’s Hospital, Columbus, Ohio; hTexas Children’s as joint hypermobility, anxiety, and gastrointestinal issues.‍ The medical Hospital, Houston, Texas; iUniversity of Texas Houston, management of OI is considered, which includes both nonpharmacologic and Houston, Texas; and jChildren’s Hospital of Colorado, Aurora, Colorado pharmacologic approaches.‍ Finally, we discuss the prognosis and long-term implications of OI and indicate future directions for research and patient Dr Stewart introduced the idea of the article, outlined sections, edited drafts and the final management.‍ manuscript, contributed directly to the first draft of the manuscript, and extensively redacted the draft; Dr T. Chelimsky introduced the idea of the Consensus guidelines define to build a better understanding of article, outlined sections, edited drafts and the final manuscript, contributed directly to the first draft of orthostatic disorders in adults on– pathophysiology and treatment.‍ the manuscript, and consolidated and secondarily the basis of expert opinion and 1 3 THE CHALLENGE OF ORTHOSTASIS edited the draft; Drs Boris, G. Chelimsky, Fischer, randomized controlled studies.‍ (STANDING UPRIGHT) Fortunato, Grubb, Heyer, Jarjour, Numan, Pianosi, These conclusions incompletely extend Singer, and Tarbell contributed directly to the first to children, for whom large trials draft of the manuscript; Dr Medow contributed directly to the first draft of the manuscript, and even small controlled studies Humans are bipedal.‍ While upright, extensively redacted the draft, and did the bulk of are sparse.‍ Pediatric orthostatic our brain is above our heart, whereas the revision and response to comments; and all intolerance (OI) has drawn increasing 70% of our blood volume is below authors commented on the draft, approved the final manuscript as submitted, and agree to be attention in recent– publications the heart.‍ If not for autonomic accountable for all aspects of the work. from different4 groups7 with different and cardiovascular compensatory perspectives.‍ The high and possibly mechanisms, hypotension and loss DOI: https:// doi. org/ 10. 1542/ peds. 2017- 1673 increasing prevalence of orthostatic of consciousness would ensue after Accepted for publication Sep 6, 2017 disorders in teenagers prompted orthostasisOrthostatic.‍ Intolerance the American Autonomic Society to To cite: Stewart JM, Boris JR, Chelimsky G, et al. convene member experts to draft Pediatric Disorders of Orthostatic Intolerance. an evidence-based State of the Art OI can be defined as having difficulty Pediatrics. 2018;141(1):e20171673 document.‍ This document is intended tolerating the upright posture to provide common ground on which because of symptoms that abate Downloaded from www.aappublications.org/news by guest on September 26, 2021 PEDIATRICS Volume 141, number 1, January 2018:e20171673 STATE-OF-THE-ART REVIEW ARTICLE when returned to supine.‍ Typical prognosis, and future directions for symptoms include a sense of research and therapy.‍ impending loss of consciousness, INDIVIDUAL ENTITIES cognitive deficits (memory loss and decreased reasoning and Initial Orthostatic Hypotension concentration), visual difficulties, lightheadedness, headache, fatigue, weakness, nausea, abdominal On standing, there is symptomatic discomfort, tremulousness, exercise hypotension because of the caudal intolerance, and reported signs such transference of blood because as pallor, diaphoresis, tachycardia, of gravity and a time delay8 in bradycardia, or hypotension.‍ sympathetic activation.‍ Blood pressure (BP) can decrease by >30%, This definition encompasses all reaching a nadir at 10 to 15 seconds FIGURE 1 forms of orthostatic disorders, such after standing.‍ Lightheadedness A standing test of IOH is shown. The upper panel shows HR in beats per minute, and the as postural faint and orthostatic and reflex tachycardia occur.‍ BP lower panel shows BP in mm Hg. The vertical hypotension (OH), but not others, is restored within –30 seconds, but line indicates standing. BP decreases, and HR increases briefly. Hypotension resolves within such as a broken leg or overt muscle cerebral blood flow9 11 and heart rate disease.‍ The definition is sufficiently (HR) take longer.‍ Clinically 30 seconds. HR stabilizes gradually to its upright, steady-state value. broad to encompass postural vertigo, significant initial orthostatic balance issues, and positional hypotension (IOH) is defined as a headache.‍ decrease in systolic BP of >40 mmHg or a decrease in diastolic BP of >20 Chronic OI is defined as OI that 10 mmHg.‍ The fall in BP is enhanced is present for at least 3 months, by the duration of the previous although symptoms may wax and supine position.‍ A history of transient wane.‍ An example is postural lightheadedness dissipating in <1 tachycardia syndrome (POTS).‍ minute7, 10, should 12 be considered as Acute and subacute OI are defined as IOH.‍ Syncope is uncommonly OI that has been present for <1 week reported with IOH.‍ Countermeasures and <3 months, respectively, or is to obviate symptoms include active restricted to recurrent episodes, such contraction of lower-body9, 10 muscles as with postural vasovagal syncope or recumbence.‍ IOH is 9,the 12,13 (VVS).‍ most common form of OI.‍ A FIGURE 2 representative standing test in which A tilt table test shows true OH. The upper panel Some OI represents an extension of IOH is experienced is shown in Fig 1.‍ shows HR in beats per minute, and the lower normal physiology, such as transient panel shows BP in mm Hg. The vertical line OH is defined by the steady decrease indicates tilt. There is a monotonic decrease lightheadedness immediately on in BP exceeding 20 mmHg systolic in BP and a compensatory increase in HR, standing.‍ Some consider infrequent which can often exceed 40 beats per minute in or 10 mmHg diastolic within 3 VVS to be a normal response to 1,7, 14 youngsters. central hypovolemia because its minutes of standing from supine.‍ lifetime incidence approaches The associated compromise 40%, and it can be universally in brain blood flow may cause syncope.‍ OH may be nonneurogenic occurs in familial dysautonomia induced with sufficient orthostatic 18, 19 2 from severe central hypovolemia provocation.‍ However, OI that 15 and autoimmune disorders.‍ or pharmaceutical vasodilation.‍ importantly diminishes quality of life There may be little postural deserves treatment.‍ There is supine tachycardia, which increases markedly when HR increase in adults because of frequent, associated cardiac In what follows, we more specifically upright.‍ OH may be neurogenic 1, 18 define individual entities comprising (nOH) because of an inadequate denervation.‍ In contrast, children OI and discuss how best to test for release of norepinephrine1 from typically mount a compensatory and diagnose OI.‍ We review the sympathetic neurons.‍ nOH results tachycardia, suggesting intact cardiac epidemiology, predisposing factors, from primary autonomic failure– or 6 parasympathetic efferents.‍ A putative causes, and frequent secondary autonomic failure,14, 16 as18 in comorbidities of OI and focus on diabetes and amyloidosis.‍ representative tilt table test in which POTS.‍ We discuss management, nOH is uncommon in pediatrics but OH is experienced is shown in Fig 2.‍ Downloaded from www.aappublications.org/news by guest on September 26, 2021 2 STEWART et al Postural Vasovagal Syncope Syncope is defined by a transient loss of consciousness and postural tone because of global cerebral