Dysautonomia: Getting a Handle on POTS

Home , Livedo reticularis, Orthostatic intolerance

patho puzzler

Dysautonomia: Getting a handle on POTS

By Christine A. Varner, DNP(c), MSN, RN, CSN

Orthostatic intolerance is a disorder that misdiagnosed and may be given mislead- causes symptoms in patients when they ing information. Currently, there are only stand up, which are relieved when they five academic centers that offer POTS lay back down. A form of dysautonomia fellowships for providers. This lack of (autonomic nervous system [ANS] dys- education causes only a small number function), postural orthostatic tachycardia of physicians to be well versed in POTS syndrome (POTS) is a disorder of chronic management. It’s been estimated that orthostatic intolerance. In dysautonomia, patients will wait more than 4 years and there’s a problem that involves the sym- see more than seven providers before pathetic or parasympathetic components receiving the correct diagnosis, with 76% of the ANS. In POTS, there’s an overreac- of them being misdiagnosed during this tion of the ANS, causing excessive tachy- time. Timely and accurate diagnosis is the cardia upon standing. key to providing the appropriate educa- Patients with POTS experience a collec- tion for patients with POTS to help them tion of symptoms that can have a signifi- understand and cope with this disorder. cant impact on their daily lives. POTS affects women at a 5:1 ratio to men and How does it happen? the average age of diagnosis is between 20 The ANS is responsible for the regulation and 40, usually due to misdiagnosis in the of body functions that are automatic, such teenage years. Studies suggest that POTS as heartbeat, breathing, digestion, BP, and effects one in 100 teens, but only about temperature control. These functions are half of patients with POTS have an adult automatically controlled and fluctuate onset of the disorder. depending on a patient’s circumstances. Diagnosing and treating POTS can If there’s a change in position, our ANS be frustrating. Patients are frequently maintains our BP and heart rate by con- stricting the blood vessels in our lower body to compensate for the change. Our heart rate increases when we stand up, with the heart beating harder and faster due to the release of norepinephrine (the primary neurotransmitter in the sympathetic nervous system [SNS]). This increase in norepinephrine compensates for gravity that typically displaces blood downward. The brain will sense that it needs more blood flow due to the change in body position and signal the release of norepinephrine, increasing the heart rate and telling the blood vessels to tighten in the legs to push the blood back to the

brain to prevent us from passing out (see SVETIKD / SHUTTERSTOCK LISA DISCHERT

16 Nursing made Incredibly Easy! July/August 2020 www.NursingMadeIncrediblyEasy.com

Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. The orthostatic reflex). It’s estimated that about one-third of our total blood volume The orthostatic reflex is in our abdomen, buttocks, and lower extremities when standing. In POTS, this regulation of the ANS is abnormal. The blood will pool in the lower extremities, causing orthostatic intolerance. These patients have an exag- gerated orthostatic tachycardic response, but they have an absence of orthostatic hypotension, which we normally think of in the case of hypovolemia. Patients with POTS will maintain or even increase their BP when standing. However, their heart rate increases too much, causing multiple symptoms that occur upon standing but improve when lying back down. The literature suggests that dysautonomia is either disease-based or syndromic. Disease-based dysautonomia can affect the ANS either centrally, such as in Par- kinson disease and multiple body system atrophy, or peripherally in the case of pure autonomic failure or in small fiber neurop- athies (for example, with diabetes or other Source: Preston RR, Wilson T. Lippincott Illustrated Reviews: Physiology. Philadelphia, PA: Lippincott genetic, inflammatory, and immune sys- Williams & Wilkins; 2012. tem disorders). Syndromic dysautonomia includes POTS, reflex syncope, chronic fatigue syndrome, fibromyalgia, irritable half of patients with POTS have a post bowel syndrome, gastroparesis, and inter- viral onset, and mast cell abnormalities stitial cystitis. are known to occur in the early phases of Studies have shown that although many autoimmune diseases. Mast cell POTS is considered a syndromic dysauto- activation syndrome is an immunologic nomia, about half of these patients also condition in which mast cells inappropri- have small fiber neuropathy. There are ately release chemical mediators in exces- different types of small fiber nerves, sive amounts. Common triggers include including sensory, sudomotor, and vaso- foods containing high levels of hista- motor. The small fiber vasomotor nerves mines, temperature extremes, exercise, help regulate blood vessel constriction. exertion, stress, and hormone changes. It’s When these nerves are damaged, the important to stick to foods that haven’t blood vessels can’t constrict. About half of been fermented; fresh, unprocessed foods patients with POTS have dysfunction of have the lowest levels of histamines (see the sudomotor nerves, making this syn- Histamine-rich foods to avoid). drome still not completely understood. Some factors suggest that autoimmuni- Primary or secondary ty plays a role in POTS. The disorder POTS has been classified as either primary occurs predominantly in female patients or secondary. Primary subtypes include and those who have an increased rate of neuropathic POTS, hyperadrenergic POTS, estrogen-dependent comorbidities. About and hypovolemic POTS. www.NursingMadeIncrediblyEasy.com July/August 2020 Nursing made Incredibly Easy! 17

Neuropathic POTS is associated with signs include swollen lower limbs after small fiber neuropathy. This peripheral upright activity or a delay in capillary denervation causes a less-than-normal refill. Patients may have acrocyanotic norepinephrine release and less sympa- legs after being in a dependent position thetic activation in the lower extremities. caused by small blood vessel constric- In hyperadrenergic POTS, there’s exces- tion, decreased blood flow to the skin, sive SNS activity and increased levels of and possibly abnormalities in nitric ox- norepinephrine. These patients may have a ide activity that lead to the legs having a significant elevation in BP upon standing, dark reddish-blue color. They may have suggesting that the baroreflex is impaired. livedo reticularis—a mottled reticulated In hypovolemic POTS, the plasma and vascular pattern described as a lace- red blood cells (RBCs) are both low. The like purple discoloration of the skin— plasma volume is controlled by aldoste- possibly due to blood vessel spasms or rone and there may be a partial loss of an abnormality of the circulation near sympathetic nerves in the kidneys, which the skin surface. Bier spots—a benign may be the reason for low aldosterone. vascular abnormality characterized by All of these primary types have connec- white spots on the skin surrounded by tions to the peripheral nervous system, pale halo erythema—may occur due to including impaired volume control and raised pressure caused by the small vein irregular SNS activity. constriction. Secondary POTS is related to another Patients may experience cardiovascular illness. Hypermobile Ehlers Danlos syn- symptoms, such as palpitations, shortness drome (hEDS) patients have been found of breath, flushing, and lightheadedness or to have more autonomic symptoms than they may feel like they’re going to pass other EDS types. In a few recent studies, it out. They can have problems with gastro- was found that 49% of hEDS patients intestinal motility being either too fast, were diagnosed with POTS and another causing irritable bowel symptoms such as 31% had orthostatic intolerance. Other abdominal pain, cramping, and diarrhea, diseases known to cause autonomic neu- or too slow, with symptoms such as bloat- ropathy and potentially secondary POTS ing, constipation, and even gastroparesis. include diabetes, Lyme disease, and auto- They may be sensitive to heat or cold due immune disorders such as lupus and to poor temperature regulation of the skin, Sjögren syndrome. resulting in increased or decreased sweat- ing. Due to decreased cerebral perfusion, Signs and symptoms patients may have profound fatigue, brain POTS is often considered an “invis- fog, blurred vision, impaired memory, ible illness.” Some of the more obvious weakness, exercise intolerance, poor sleep quality, and migraines. Histamine-rich foods to avoid Gynecologic problems have also been noted in patients with POTS. Studies • • Smoked meats and those with Salted or canned fish, such as have shown that patients may experience high levels of preservatives, tuna or sardines endometriosis, uterine fibroids, ovarian such as bacon, ham, and • Fermented grain in sourdough cysts, and dysfunctional bleeding at a salami bread • Pickled or canned foods, • Nuts, such as peanuts, higher rate when compared with control such as sauerkraut and cashews, and walnuts patients. kimchi • Fermented soy products, such As you can see, POTS presents with • Shellfish as miso and soy sauce diverse symptoms that may limit a patient’s • Eggplant • Alcohol ability to care for his or her family, work, or attend school.

18 Nursing made Incredibly Easy! July/August 2020 www.NursingMadeIncrediblyEasy.com

Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. Diagnosis to expand blood volume. Desmopressin The diagnostic criteria for POTs are as and erythropoietin are also used to follows: increase blood volume. Desmopressin has • heart rate increase of greater than or been shown to reduce tachycardia but may equal to 30 beats/minute from supine to cause hyponatremia. Erythropoietin is standing within 10 minutes (greater than or used to increase RBC mass and may also equal to 40 beats/minute for ages 12 to 19) stimulate vasoconstriction in patients with • the absence of orthostatic hypotension POTS. Outside of the potential vascular (defined as greater than or equal to a complications, such as stroke and myocar- 20/10 mm Hg drop in BP within 3 min- dial infarction, erythropoietin is costly and utes of standing) requires injection, which makes its use less • symptoms of orthostatic intolerance last- attractive. Intermittent I.V. saline infusion ing 6 months or more is another option, but again involves can- • symptoms exacerbated by standing and nulation and infusion, making it cumber- improved with recumbency some for patients. It may be effective with • absence of other overt causes of ortho- acute symptoms to prevent hospitalization. static symptoms or tachycardia. Vasoconstrictors such as midodrine Although several phenotypes of POTS may improve venous return and decrease have been found, it’s important to keep in reflex tachycardia. Octreotide is a soma- mind that these subtypes aren’t distinct tostatin analog that works by causing diagnoses but more characteristics of the vasoconstriction in mainly the splanchnic syndrome. Many patients with POTS have circulation. It may help maintain venous several or all of these characteristics, and return in patients with POTS when stand- there’s considerable subtype overlap. A sim- ing, as well as prevent the compensatory ple test to categorize patients doesn’t exist. increase in heart rate. The tilt table test, which measures heart The beta-blocker propranolol is helpful rate and BP during posture and position in lower doses for symptom control by changes, is considered the gold standard of decreasing the heart rate and reducing acute testing for POTS. Blood and urine tests can symptoms. However, adverse reactions of help rule out other causes that may mimic beta-blockers include an increase in fatigue POTS. Blood volume studies to determine and dizziness. A less-is-more approach is hemodynamic status and an autonomic better tolerated by patients with POTS. breathing test to measure how the heart The use of the extended-cycle birth rate and BP respond during exercise may control pill ethinyl estradiol and levonorg- also assist in diagnosis. Lastly, a quantita- estrel has shown promise in teenagers with tive sudomotor axon reflex test is a ther- gynecologic comorbidities by limiting their moregulatory sweat test that can be used to periods and estrogen fluctuation to just determine if autonomic neuropathy exists. four times a year.

Pharmacologic management Nonpharmacologic management Currently, there are no FDA-approved Several treatment measures exist to man- treatments specifically for POTS. How- age POTS without medication, such as ever, several medications can be used to increasing fluid intake to 2 to 3 L/day of decrease symptoms. nonsugary, caffeine-free drinks. Increas- Blood volume expanders have been ing salt intake to an average of 10 g/day used with reasonable success in patients is also helpful because many patients with POTS. Fludrocortisone is a mineralo- have low urinary sodium levels. Salt corticoid that enhances renal sodium reab- and fluid will increase circulatory volume sorption in the distal tubules of the kidneys and BP. www.NursingMadeIncrediblyEasy.com July/August 2020 Nursing made Incredibly Easy! 19

POTS. Help your patients with POTS by on the web educating them about their illness. POTS Dysautonomia International: can be scary, and most patients become www.dysautonomiainternational.org/page. hypervigilant when symptomatic. This php?ID=30 increased stress and anxiety, along with Genetic and Rare Diseases Information Center: their overall symptoms, can affect their https://rarediseases.info.nih.gov/diseases/ quality of life. Remember that some pa- 9597/postural-orthostatic-tachycardia-syndrome tients have spent years trying to find the POTS UK: reason behind their symptoms. Early www.potsuk.org identification is key to the successful Vanderbilt Autonomic Dysfunction Center: management of POTS. ■ www.vumc.org/adc/38847 REFERENCES AbdelRazek M, Low P, Rocca W, Singer W. Epidemiology of postural tachycardia syndrome. The use of medical compression devic- Neurology. 2019;92(15 suppl):S18.005. Arnold AC, Ng J, Raj SR. Postural tachycardia syndrome— es, such as abdominal binders or those diagnosis, physiology, and prognosis. Auton Neurosci. 2018; that cause compression in the calf and 215:3-11. thighs, is helpful to decrease blood pool- Boris JR, Bernadzikowski T. Utilisation of medications to reduce symptoms in children with postural orthostatic ing in the lower extremities. Also, instruct tachycardia syndrome. Cardiol Young. 2018;28(12):1386-1392. patients to avoid sudden movements and Celletti C, Camerota F, Castori M, et al. Orthostatic intolerance and postural orthostatic tachycardia syndrome in prolonged periods of standing that cause joint hypermobility syndrome/Ehlers-Danlos syndrome, lower extremity blood pooling and aggra- hypermobility type: neurovegetative dysregulation or vate POTS symptoms. autonomic failure? Biomed Res Int. 2017;2017:1-7. Cheng JL, Au JS, Guzman JC, Morillo CA, MacDonald Seated or supine exercises, such as row- MJ. Cardiovascular profile in postural orthostatic tachy- ing machines, recumbent cycling, and cardia syndrome and Ehlers-Danlos syndrome type III. Clin Auton Res. 2017;27(2):113-116. swimming, three times per week can help Hakim A, O’Callaghan C, De Wandele I, Stiles L, Pocinki A, improve stroke volume and decrease tachy- Rowe P. Cardiovascular autonomic dysfunction in Ehlers- cardia. Patients with POTS need frequent Danlos syndrome-hypermobile type. Am J Med Genet C Semin Med Genet. 2017;175(1):168-174. rest periods and should gradually increase Raj V, Opie M, Arnold AC. Cognitive and psychological their exercise intensity. Also, limiting activi- issues in postural tachycardia syndrome. Auton Neurosci. ties that require the arms to be raised above 2018;215:46-55. Revlock MM. Postural orthostatic tachycardia syndrome. the head may help reduce tachycardia. Am Nurse Today. 2018;13(12):18-21. Avoiding triggers is beneficial for symp- Russek LN. Is it really fibromyalgia? Recognizing mast tom management. The use of cooling vests cell activation, orthostatic tachycardia, and hypermobility. Orthop Phys Ther Pract. 2018;30(3):187-193. and avoiding heat and hot showers are sug- Stiles L. Ehlers-Danlos syndrome and dysautonomia. gested to limit vasodilation. Large meals New York Institute of Technology. 2017. www.nyit.edu/ files/events/content/171208_EDSSymposium_Stiles- may increase symptoms as blood flow is Dysautonomia.pdf. diverted to the gut, causing nausea and Stiles LE, Cinnamon J, Balan I. The patient perspective: anxiety related to SNS activity. Smaller, what postural orthostatic tachycardia syndrome patients want physicians to know. Auton Neurosci. 2018;215:121-125. more frequent low-carb, high-protein meals Urlich AE, Hartung SQ. “Doesn’t anyone believe how I are suggested. Good sleep habits can make feel?”: postural orthostatic tachycardia syndrome (POTS). a significant difference in overall fatigue NASN Sch Nurse. 2015;30(2):106-115. Vernino S, Stiles LE. Autoimmunity in postural ortho- levels. Symptoms of orthostatic intolerance static tachycardia syndrome: current understanding. tend to be more severe in the morning, so Auton Neurosci. 2018;215:78-82. getting a good night’s rest may help. Christine A. Varner is an Assistant Professor of Nursing at Mansfield (Pa.) University and a DNP student at Clarion and Edinboro (Pa.) A helping hand University. The author has disclosed no financial relationships related to this You can have a significant impact by article. increasing your own knowledge about DOI-10.1097/01.NME.0000658220.96438.17

20 Nursing made Incredibly Easy! July/August 2020 www.NursingMadeIncrediblyEasy.com