The use of intravenous fluids for management of mast cell disease

I get frequent consult requests from patients specifically around the use of IV fluids to treat mast cell disease. I am often asked to provide references for papers that show its use and benefit. I am not able to provide any such references because there are none. There has been no organized study for the use of intravenous fluids to manage symptoms from mast cell disease.

Despite this fact, use of intravenous fluids in mast cell disease is increasing in popularity, largely because it works, and word of effective treatments travels fast in a rare disease community. While there is no firm answer for why it helps, there is a reasonable explanation: it treats both deconditioning and POTS and many mast cell patients have one or both.  I wrote a seven part series on why exactly intravenous fluids help in these situations. I have also written in great detail about the way that mast cell disease and POTS interact.

A paper published in early 2017 reestablished the finding that use of intravenous fluids helps POTS. Treatment lengths and infusion volumes varied from person to person. Despite these variations, use of IV fluids decreased symptoms and improved quality of life for POTS patients. The link to the abstract is here.

Many mast cell mediators are vasoactive, affecting the permeability of blood vessels. This means that mast cell activation causes third spacing, the loss of fluid from the bloodstream to the tissues, where the body cannot use it. This functional dehydration can cause a lot of symptoms, not the least of which is exhaustion and difficulty standing or exercising. For obvious reasons, this will be further exacerbated in a patient that is deconditioning or who has also has POTS.

Orthostatic symptoms can be very activating to patients and managing them effectively can help significantly. I have seen IV fluids work where more traditional methods like drinking lots of fluids and consuming lots of salt, or medications like fludrocortisone have not helped. Additionally, the first line tools for managing POTS, beta blockers, are contraindicated in patients at increased risk for anaphylaxis and therefore in people with mast cell disease.

I am a fervent supporter of IV fluids (also called volume loading) in the context of mast cell disease. I have seen it stabilize patients and reduce the frequency of anaphylaxis and severe symptoms, especially orthostatic symptoms and GI symptoms.

I personally use IV fluids. If I don’t receive IV fluids at least three times a week, my orthostatic symptoms become so severe that it is difficult to stand or even move. This in turn triggers mast cell reactions. The benefits of IV fluids to my personal health are significant. Many patients report the same.

While I support the use of IV fluids in the context of mast cell disease, patients should be aware that there are infection risks associated with repeated IV access or placement of a central line. The risks are much lower for repeated IV access as central lines have a host of other risks, including blood clots, and infections have the potential to be much more serious. However, IV access can be difficult for mast cell patients. The treatment value of IV fluids should be weighed on a case by case basis and IV access on a case by case basis.

For additional reading, please visit the following posts:

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 1

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 2

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 3

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 4

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 5

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 6

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 7

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 12

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 31

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 32

Deconditioning, orthostatic intolerance, exercise and chronic illness – Part 7

A number of studies have investigated whether loading with intravenous hydration solutions (saline, etc) or with a volume expander such as dextran can ameliorate symptoms associated with deconditioning. These studies have found that volume expansion (also called fluid or volume loading) can improve a number of symptoms in deconditioned patients, but does not improve exercise capacity. Multiple studies have found the best effects from intravenous saline in conjunction with exercise.

Shibata investigated whether orthostatic intolerance could be mitigated following bed rest with exercise and/or fluid loading (Shibata 2010). This study found that OI could be dextran solution (IV fluids) given after twenty days of bed rest was insufficient to control OI symptoms, but that it was successful when used in conjunction with a daily exercise program. This finding was important, as it indicated that low blood volume was not the exclusive factor in orthostatic intolerance.

Figueroa et al looked at the relationship between blood volume and exercise capacity in POTS patients (Figueroa 2014). They found that acute volume loading with IV saline reduces heart rate and improves orthostatic tolerance and other symptoms in POTS patients. Importantly, IV saline significantly increased the stroke volume, cardiac output and reduced systemic vascular resistance. However, IV saline did not affect peak exercise capacity or improve cardiovascular markers during exercise. So while IV saline does help symptoms in these deconditioned patients, it does not improve exercise capacity. The author notes that for this purpose, acute infusion may not be sufficient and may need to undergone chronically to see benefits on exercise physiology.

Whole body heating is known to increase cardiac output, constrict the blood vessels in the abdominal cavities, increase sympathetic nerve activity in the muscles and decrease vascular resistance in the skin. Taken together, these factors stress the regulatory mechanism of the cardiovascular system. One study (Keller 2009) found that acute expansion of blood volume (with dextran) completely mitigated the impact of heat stress on orthostatic tolerance. In short, receiving an infusion that increased the blood volume allowed the cardiovascular system to function properly in the face of a known stressor.

One study looked at the effect of fluid loading on orthostatic intolerance and blood flow in the brain (Jeong 2012). They found that following bed rest, volume loading alone prevented larger reductions in cerebral blood flow, but did not prevent orthostatic intolerance. Exercise and volume loading prevented orthostatic intolerance but did not affect cerebral blood flow. Importantly, aerobic or resistance exercise before bed rest did not prevent development of decompensation.

A 2000 paper notes that POTS symptom scores improved significantly following administration of IV saline (Gordon 2000). Additionally, a 2013 study evaluated the frequency and characterization of “brain fog”, a common term for the cognitive deficits associated with this (and other) conditions (Joyner 2013). 86% (56/66) of patients reported that IV saline was the most effective treatment for brain fog.

In summary, bolus IV fluids or volume expanders have been found to improve a number of symptoms in deconditioned patients, although they have not been found to improve exercise capacity. For this metric, a graded exercise program is recommended. 

(Author’s note: I have recently been made aware that the data supporting use of graded exercise for chronic fatigue patients was hugely flawed. I retract this statement at this time. For details on this topic, please refer to this Lancet article: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60686-7/fulltext)

A 2008 paper compared POTS and deconditioning (Joyner 2008). The author pointed out that a number of parallels existed between the physiological changes seen in POTS patients and those seen in deconditioned patients. Additionally, he made note of the parallels between POTS, chronic fatigue syndrome and fibromyalgia and the fact that exercise training had seen benefits in all of them. Given the significant relationship between mast cell disease and POTS, and the large overlap in CFS, fibromyalgia and mast cell populations, it is a comfortable assumption that an effective treatment modality for CFS, POTS and fibromyalgia may also be effective for mast cell disease. It is my belief that this is the basis for the frequently discussed finding of mast cell patients that intravenous fluids ameliorate a number of symptoms.

Furthermore, there are special considerations for mast cell disease that make intravenous fluids likely to cause a positive change in symptom profile. The first is that mast cell degranulation can induce systemic effects on arterial tone, hypotension and vasodilation (Willingham 2009). The next is that hypotension is characteristic of systemic mastocytosis, and that hypotension and syncope may occur due to cerebral hypoperfusion (Ozdemir 2010). Lastly, it is well known that mast cell mediators, including histamine, serotonin and tryptase, can induce capillary leakage leading leading to edema, and that they can increase vascular permeability (He 1997). Taken together, these points indicate that a mast cell patient may lose volume from the bloodstream into the surrounding tissues, which can exacerbate an already existing tendency toward hypotension, in turn made worse by orthostatic intolerance.

Fluid loading in the form of intravenous fluids may decrease symptoms in mast cell patients due to deconditioning, orthostatic intolerance and the capillary leakage often seen as a result of mast cell disease, which is especially present following mast cell attacks and anaphylaxis.

 

References:

Gordon VM., et al. Hemodynamic and symptomatic effects of acute interventions on tilt in patients with postural tachycardia syndrome. Clin Auton Res. 2000 Feb; 10(1): 29-33.

Ross, Amanda J., et al. What is brain fog? An evaluation of the symptom in postural tachycardia syndrome. Clin Auton Res 2013 Dec; 23(6): 305-311.

Raj, Satish R., et al. Postural orthostatic tachycardia syndrome (POTS). Circulation 2013; 127: 2336-2342.

Rocío A. Figueroa, et al. Acute volume loading and exercise capacity in postural tachycardia syndrome. J Appl Physiol 117:663-668, 2014.

He, Shaoheng, Walls, Andrew F. Mast cell activation may be all that is sufficient and necessary for the rapid development of microvascular leakage and tissue edema. European Journal of Pharmacology 1997; 328(1): 89-97.

Ozdemir, D., et al. Hypotension, syncope and fever in systemic mastocytosis without skin infiltration and rapid response to corticosteroid and cyclosporine: a case report. Case Reports in Medicine, Volume 2010 (2010), Article ID 782595.

Willingham DL, et al. Unexplained and prolonged perioperative hypotension after orthotopic liver transplantation: undiagnosed systemic mastocytosis. Liver Transpl 2009 Jul; 15(7): 701-8.

Keller, David M., et al. Acute volume expansion preserves orthostatic tolerance during whole body heat stress in humans. J Physiol 2009 Mar; 587(5): 1131-1139.

Sung-Moon Jeong , Shigeki Shibata , Benjamin D. Levine , Rong Zhang. Exercise plus volume loading prevents orthostatic intolerance but not reduction in cerebral blood flow velocity after bed rest. American Journal of Physiology – Heart and Circulatory Physiology 2012 Vol. 302 no. 2.

Shizue Masuki , John H. Eisenach , William G. Schrage , Christopher P. Johnson , Niki M. Dietz , Brad W. Wilkins , Paola Sandroni , Phillip A. Low , Michael J. Joyner. Reduced stroke volume during exercise in postural tachycardia syndrome. Journal of Applied Physiology 2007 Vol. 103 no. 4, 1128-1135.

 

 

 

 

 

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 6

Exercise can be very effective in treating deconditioning due to orthostatic intolerance or other conditions. Exercise can exacerbate symptoms in deconditioned patients even when it is mild, and this effect will be more pronounced if exercising in hot weather or after eating. Recumbent exercise, rather upright, is ideal for deconditioned patients at the beginning of exercise regimens, as being upright more stress on the body.

There are some physical maneuvers that can be helpful in avoiding OI episodes or in managing them when they do occur.   A sustained hand grip will activate the sympathetic nervous system and raise blood pressure for a short time. This can be helpful when changing position or following triggering activities, such as eating a meal or exercising. Leg crossing while tensing muscles can also prevent blood from pooling in the leg veins. This is recommended when an OI episode first occurs, and for vasovagal syncope patients to prevent fainting.

One study regimen prescribed POTS patients to engage in recumbent exercise 2-4 times a week for 30-45 minute sessions. In this study, they attempted to keep heart rate at 75-85% of maximum heart rate. As patients continued and became more fit, upright exercise was added in slowly in the second or third week. The length of training sessions increased and sessions of maximum intensity was added gradually until there were two maximum sessions per week. Weight lifting started once a week as a 15-20 minute session and increased to twice weekly 30-40 minute sessions. At the end, patients were exercising 5-6 hours/week. The duration of this study was twelve weeks.

Of the 29 patients who completed this study, a number of cardiovascular markers were improved. Blood volume and plasma volume were both expanded. The peak oxygen uptake during exercise, usually low for POTS patients, was increased by 11%. The muscle in the left ventricle of the heart, often smaller than usual in POTS patients, increased by 8%. Both laying down and standing heart rates decreasing significantly. Quality of life improved significantly and at the conclusion, almost half of the patients who completed the training no longer met the criteria for POTS.

Another study had POTS patients begin exercising twice a week in recumbent exercise, such as rowing or swimming, for 30-45 minutes. They increased to four times per week. After three months, plasma and blood volumes were both increased, as well as total hemoglobin mass and red blood cell volume. Systolic and diastolic pressures were lower while standing. Standing heart rate was lower and the amount of blood pumped out of the heart was stable.

Multiple papers have noted that OI patients are motivated to exercise, but often exert themselves too much in the beginning and trigger symptoms that make it difficult to continue. Going slowly and building up your tolerance is critical here. It is the factor that will make this successful. As an example, when I was very POTSy last year after several days of bed rest, I was advised that I could only stand for 10 minutes a day for an entire week. I could increase by ten minutes every week until I got to sixty, at which point I could resume normal activity. It was incredibly frustrating and drove me crazy, but I was able to get my orthostatic symptoms under control. Gradually increasing activity for OI patients is tried and true.

For severely disabled patients, it may not be practical to begin with recumbent aerobic exercises. If this is the case, gentle stretching and very low impact moves are good to start.

Following this, short workouts preceded by 5-10 minutes of stretching can be added. Target heart rate of 75-80% has been cited as desirable in some publications. Of utmost importance is the use of recumbent exercises, like rowing, swimming or recumbent cycling. Start slow. Dysautonomia International has a great breakdown on their site for how long you should workout at this stage.

Following several weeks of success, normal weekends can be introduced. Some patients are able to recover significant capability, running marathons and so on. It is recommended that POTS patients who are significantly conditioned exercise for at least 45 minutes three times a week.

While OI is a prime example of deconditioning as so many of its patients are deconditioned (95% of POTS patients and 91% of OI patients in one study), it is not the only condition associated with deconditioning that can be significantly improved with exercise.

In various studies with chronic fatigue syndrome patients, 60-84% said they felt better or much better after a graded exercise program. A study with fibromyalgia implemented three times a week workouts of sixty minutes, which included 10 minutes of slow walking, 20 minutes of aerobic exercise at 60-70% max heart rate, 20 minutes stretching and strength training, and 10 minutes cooling down. This program was highly successful for a number of patients.

Given the variety of illnesses which produce secondary deconditioning, and the success achieved by their patient populations with graded exercise, it is reasonable to assume that graded exercise may provide conditioning benefits to the mast cell population. Mast cell patients have the addition concerns that mast cells can be mechanically degranulated by the motions associated with vigorous exercise and that heat and sweating may be triggering, so exercise should be undertaken carefully and never alone. Some patients find utility in premedicating with H1 and H2 antihistamines before exercising. Please consult with your healthcare provider prior to beginning an exercise regimen.

 

References:

De Lorenzo, H. Xiao, M. Mukherjee, J. Harcup, S. Suleiman, Z. Kadziola and V.V. Kakkar. Chronic fatigue syndrome: physical and cardiovascular deconditioning. Q J Med 1998; 91:475–481.

Hasser, E. M. And Moffitt, J. A. (2001), Regulation of Sympathetic Nervous System Function after Cardiovascular Deconditioning. Annals of the New York Academy of Sciences, 940: 454–468.

Mathias, C. J. et al. Postural tachycardia syndrome – current experience and concepts. Nat. Rev. Neurol. 8, 22–34 (2012).

Parsaik A., et al. Deconditioning in patients with orthostatic intolerance. Neurology 2012; 79; 1435.

Benarroch, Eduardo E. Postural tachycardia syndrome: a heterogeneous and multifactorial disorder. Mayo Clin Proc 2012 Dec; 87(12): 1214-1225.

Shizue Masuki , John H. Eisenach , William G. Schrage , Christopher P. Johnson , Niki M. Dietz , Brad W. Wilkins , Paola Sandroni , Phillip A. Low , Michael J. Joyner. Reduced stroke volume during exercise in postural tachycardia syndrome. Journal of Applied Physiology Published 1 October 2007 Vol. 103 no. 4, 1128-1135.

Sung-Moon Jeong , Gyu-Sam Hwang , Seon-Ok Kim , Benjamin D. Levine , Rong Zhang. Dynamic cerebral autoregulation after bed rest: effects of volume loading and exercise countermeasures. Journal of Applied Physiology 2014 Vol. 116 no. 1, 24-31.

 

 

 

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 4

Syncope, also called fainting, is the loss of consciousness caused by temporary loss of blood supply to the brain, followed by complete recovery. About 40% of people will faint in their lifetime and half of them will first faint as teenagers, around the age of 15. Fainting can be caused by orthostatic hypotension. Otherwise, it can occur for cardiac or neurologic reasons (also called reflex syncope). One type of reflex syncope is vagovagal syncope, which can be further divided into postural syncope (fainting upon standing) and emotional or phobic syncope (fainting due to unpleasant psychological stimuli).

Vagovagal syncope has been attributed to several things, but none have been definitively proven. Some patients have decreased presence of enzymes that mediate blood pressure, like norepinephrine transportase (NET). Some have insufficient circulation in the abdominal cavity. As vasovagal syncope is often preceded by lightheadedness, sweating, weakness, nausea and visual disturbances, it can be difficult to distinguish between VVS and POTS. However, VVS patients often go long periods without OI symptoms, which only occur immediately before syncope.   Postural syncope and POTS are also associated with increased rate and depth of breathing in order to meet oxygen needs during these episodes.

Ingestion of 16 ounces of water in five minutes is known to effectively treat OI episodes of all types. It begins to have effect in about twenty minutes. It is important that this water not have solutes; that is to say, it should be pure water. Effects can last for hours.

There are a number of precipitating factors that can induce OI symptoms in susceptible patients. Avoidance is a key treatment modality. These factors include large meals, sudden postural changes, laying down for extended periods of time, environmental heat, alcohol, vasodilators* and sympathomimetic drugs, such as methylphenidate. (*It is worth noting that mast cell disease is inherently vasodilatory).

For both orthostatic hypotension and neurogenic POTS patients, physical maneuvers and compression garments can decrease venous pooling of blood. Increasing both salt and water intake can be helpful to expand plasma volume; 1.5-2L is recommended for adults.

Medications that retain salt and water, such as fludrocortisone, may be tried as well. Pressor drugs with short half lives, such as midodrine and pyridostigmine, are also used in these patients. Droxidopa is used outside of the US. Other meds, such as clonidine, also see some utility. Exercise is also encouraged as a treatment option (will be detailed in a follow up post).

HyperPOTS is often treated with beta blockers. (WARNING: beta blockers interfere with the action of epinephrine and should be used cautiously in mast cell patients). Angiotensin receptor blockers like Cozaar have been used, as has droxidopa. Exercise is likewise suggested for treatment of this patient group.

Water ingestion is recommended for patients with vasovagal syncope. Additionally, physical maneuvers are advised upon the onset of OI symptoms.

 

References:

Stewart, Julian M. Update on the theory and management of orthostatic intolerance and related syndromes in adolescents and children. Expert Rev Cardiovasc Ther 2012 November; 10(11): 1387-1399.

Benarroch, Eduardo E. Postural tachycardia syndrome: a heterogenous and multifactorial disorder. Mayo Clinic Proceedings 2012; 87(12): 1214-1225.

 

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 3

POTS (postural orthostatic tachycardia syndrome) is one type of orthostatic intolerance. It is defined as the increase in heart rate of 30 beats/min or more when standing in the absence of orthostatic hypotension. There are a number of mechanisms that cause POTS.

Neuropathic POTS is caused by inefficient constriction of blood vessels in the lower limbs due to a defect in the sympathetic nervous system. In these patients , the heart does not sense the change in blood pressure correctly and does not pump out enough blood volume to accommodate the pressure change. Patients with this syndrome usually do not sweat in the feet. They have insufficient release of norepinephrine upon standing.

The orthostatic intolerance in neuropathic POTS is caused by the veins not constricting enough in the legs to maintain blood pressure upon standing. When executing the Valsalva maneuver, they are unable to raise blood pressure significantly. Blood is found to pool in the leg veins when these patients do not use pressure devices like compression stockings. These patients have “high blood flow”, meaning that the total peripheral resistance (the total pressure exerted by the blood vessels) is lower than expected when laying down or standing. This form of POTS may have an autoimmune link, but this though requires further investigation.

Hyperadrenergic POTS is caused by excessive cardiac response to stimulation by the sympathetic nervous system. In these patients, the nervous system tells the heart to beat faster and harder.  30-60% of patients have this form. These patients have serum plasma norepinephrine of 600 pg/mL or higher when standing. They have fluctuating or elevated blood pressure (both consistently or during crisis), and episodes of tachycardia, hypertension and hyperhidrosis. Of note, these episodes can be triggered by orthostatic stimuli (changing position) as well as physical or even emotional stimuli.

This category has also been referred to as “low volume” POTS, in which norepinephrine levels in serum can exceed 1000 pg/mL, and in which patients often have pale and cold skin, tachycardia while laying down, elevated blood pressure while laying down and increased neurologic signals to muscles while laying down. A genetic condition affecting the norepinephrine transporter (NET) gene is responsible for some cases of hyperadrenergic POTS. Hyperadrenergic POTS can be secondary to a number of conditions, including mast cell activation disease. One study found that 38% of patients with mast cell disease also had hyperPOTS.

POTS patients may have low plasma, red cell or total blood volumes. One study found 28.9% of POTS patients to be hypovolemic, meaning they had less volume in their blood stream than normal. In some of these patients, they have low renin activity and aldosterone when standing. Others may have high angiotensin II levels. These molecules are related to regulation of blood pressure. GI conditions that result in poor oral water intake from nausea or diarrhea can cause hypovolemia with orthostatic intolerance and tachycardia. For this population, the recommendation is to consider POTS as secondary the GI condition.

POTS patients present with persistent tachycardia, reduced stroke volume (amount of blood pushed out of the heart), loss of mass in the left ventricle (this part of the heart is smaller than normal), and reduced peak oxygen uptake when standing, during and after exercise. These markers are also present in physical deconditioning, which can also cause orthostatic intolerance regardless of why the deconditioning occurred. For this reason, POTS is often associated with conditions that provoke exercise intolerance, such as fibromyalgia, chronic fatigue syndrome and deconditioning.

 

References:

Stewart, Julian M. Update on the theory and management of orthostatic intolerance and related syndromes in adolescents and children. Expert Rev Cardiovasc Ther 2012 November; 10(11): 1387-1399.

Figueroa, Juan J., et al. Preventing and treating orthostatic hypotension: As easy as A, B, C. Cleve Clin J Med 2010 May; 77(5): 298-306.

Benarroch, Eduardo E. Postural tachycardia syndrome: a heterogenous and multifactorial disorder. Mayo Clinic Proceedings 2012; 87(12): 1214-1225.

Cheung, Ingrid, Vadas, Peter. A new disease cluster: mast cell activation syndrome, postural orthostatic tachycardia syndrome and Ehlers-Danlos syndrome. J All Clin Immunol 2015: 135(2); AB65.

Joyner, M., Masuki, S. POTS versus deconditioning: the same or different? Clin Auton Res 2008 Dec; 18(6): 300-307.

 

 

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 2

The term orthostasis means to stand up. Orthostatic intolerance is the presentation of symptoms which interfere with or prevent standing up. Orthostatic intolerance (OI) affects heart rate, blood pressure and blood distribution in the brain. This can present as a number of symptoms with multiple root causes.

The autonomic nervous system is responsible for making quick changes to the cardiovascular system based upon changes in the environment. It adjusts the circulatory system by changing heart rate, constricting blood vessels and inducing secretion from the adrenal gland to sustain a normal blood pressure.

The sympathetic nervous system is one part of the autonomic nervous system and its function is to activate the fight-or-flight response. When it malfunctions as in OI, it causes pallor, headache, high blood pressure, palpitations, sweating, tremor and anxiety. When the autonomic nervous system is unbalanced with the parasympathetic system being more active, low blood pressure, slow heart rate, cold hands and feet and constriction of the pupil may occur. This is called vagotonia. Another principle symptom of orthostatic intolerance is intolerance to exercise.

Other parts of the nervous system are involved here as well. Misbehavior in the central nervous system can cause loss of consciousness, dizziness and cognitive issues. Malfunction of the vagus nerve can cause tachycardia, abdominal pain and nausea/vomiting.

There are three common forms of orthostatic intolerance.

Orthostatic hypotension is a consistent reduction of systolic blood pressure of more than 20 mm Hg or diastolic blood pressure of more than 10 mm Hg within three minutes of standing or a head up tilt of at least 60°. Orthostatic hypotension can occur for many reasons, including dehydration, blood loss or conditions that cause acute or chronic hypovolemia. Neurogenic OH is caused by insufficient norepinephrine released from cells of the sympathetic nervous system, causing inadequate vasoconstriction. Neurogenic OH typically occurs secondary to a systemic disease.

POTS patients suffer daily OI symptoms in conjunction with excessive tachycardia when standing, but not with low blood pressure. In adults, excessive tachycardia is defined as an increase of 30 bpm when standing or over 120 bpm. In children, excessive tachycardia is an increase of 40 bpm. Tachycardia is not sufficient for diagnosis; patients must also have OI symptoms. There are multiple subcategories of POTS, which I have previously covered and will cover in more detail elsewhere.

Postural syncope can be caused by acute orthostatic intolerance, simple fainting or vagovagal syncope (VVS). Syncope, also called fainting, is the loss of consciousness due to temporarily insufficient blood supply to the brain, followed by complete recovery. In short, this means fainting upon standing up. About 40% of people will faint at some point in their lives. About half of these people have their initial episode during adolescence, most around the age of 15. Syncope can be cardiovascular, from arrhythmia or structural abnormalities, or reflex/neurologic.

Mast cell disease (both mastocytosis and MCAS) has a known propensity for causing orthostatic intolerance.

References:

Stewart, Julian M. Update on the theory and management of orthostatic intolerance and related syndromes in adolescents and children. Expert Rev Cardiovasc Ther 2012 November; 10(11): 1387-1399.

Figueroa, Juan J., et al. Preventing and treating orthostatic hypotension: As easy as A, B, C. Cleve Clin J Med 2010 May; 77(5): 298-306.

Medow MS, Stewart JM, Sanyal S, Mumtaz A, Sica D, Frishman WH. Pathophysiology, diagnosis, and treatment of orthostatic hypotension and vasovagal syncope. Cardiol. Rev. 2008; 16(1):4–20.

Bayles R, Kn H, Lambert E, et al. Epigenetic modification of the norepinephrine transporter gene in postural tachycardia syndrome. Arterioscler. Thromb. Vasc. Biol. 2012; 32(8):1910–1916.

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 1

Deconditioning (also called cardiovascular deconditioning) is the acclimation of the body to a less strenuous environment and the decreased ability to function properly under normal conditions. This basically means that when you have less physical stress on the body for a certain period of time, like seen in bed rest, the body adapts to that level of functioning, so when you want to engage again in normal physical activities, it is difficult for your body. Deconditioning makes multiple systems of your body less functional.

Bed rest is the typical situation associated with deconditioning. Patients on bed rest lose muscle mass and strength rapidly.  1-3% of muscle strength is lost per day, with 10-20% decrease in a week’s time. If completely immobilized for 3-5 weeks, a patient can lose up to 50% of their strength. Loss of muscle mass is also a problem. Upper legs can lose 3% mass within a week of bed rest. The lower back and weight bearing muscles in the legs are most affected by loss of mass.

Within 24 hours of bed rest, your cardiovascular system is changing. In this time, your blood volume decreases 5%. In less than a week, 10% is lost; in two weeks, 20%. Resting heart rate also increases 4-15 bpm within the first month of bed rest. Laying down for so long means that blood that is normally in the lower part of your body is moved to the trunk. This causes excretion of water and salt, resulting in less plasma and blood volume.

In healthy controls, when you change position, your body rapidly moves fluid from one part of the body to others. This phenomenon is called fluid shifting. Normally, when moving from a laying position to standing, 500-700 ml of blood are moved from the trunk to the legs. This movement of fluid is called “functional hemorrhage”. Special nerve clusters called baroreceptors (which measure pressure in the blood vessels) tell the nervous system that there is less blood in the chest.   Your body then increases the heart rate, the force with which your heart beats, tightens up vessels so that they are less “leaky” and tells your body not to make urine temporarily. All of these functions allow your body to keep a normal blood pressure and adequate blood supply despite this large movement of fluid.

In healthy controls, when you lay down after standing, the reverse happens. 500-700 ml of fluid is rapidly transferred from the lower body to the trunk. This is called a “central shift”. This increase in fluid in the chest results in the veins returning more blood to the heart, increasing blood pressure. When the baroreceptors feel more pressure than usual from this added fluid, the heart rate and force with which the heart beats decrease, the vessels are relaxed so that fluids can move out of them more freely and your body begins to make urine again.

When you are deconditioned, your body does not make these changes correctly when you change position. The hallmark of deconditioning is reduced orthostatic tolerance. This means that when you change position, your body does not compensate correctly to maintain necessary blood pressure and adequate blood supply to the brain. Deconditioned patients often do not have sufficient blood volume to maintain blood pressure when standing. When they stand, their heart pumps out less blood than normal, so the heart starts beating faster to compensate. When it beats too fast, it is called tachycardia.

In addition to inability to maintain blood pressure correctly when changing positions, deconditioned patients also exhibit decreased blood volume pumped out by the heart, atrophy of heart muscle and decreased maximum oxygen consumption. These patients often have other forms of vascular dysfunction, diminished neurologic reflexes and reduced ability to exercise. A number of other systems are affected by deconditioning.

Though prolonged bed rest is the model with which deconditioning is most often associated, there is significant evidence that chronically ill patients may often be deconditioned, including those with chronic lower back pain, chronic fatigue syndrome, and rheumatoid arthritis.

References:

Munsterman et al. Are persons with rheumatoid arthritis deconditioned? A review of physical activity and aerobic capacity. BMC Musculoskeletal Disorders 2012, 13:202

Eric J. Bousema, Jeanine A. Verbunt, Henk A.M. Seelen, Johan W.S. Vlaeyen, J. Andre Knottnerus. Disuse and physical deconditioning in the first year after the onset of back pain. Pain 130 (2007) 279–286.

De Lorenzo, H. Xiao, M. Mukherjee, J. Harcup, S. Suleiman, Z. Kadziola and V.V. Kakkar. Chronic fatigue syndrome: physical and cardiovascular deconditioning. Q J Med 1998; 91:475–481.

Hasser, E. M. And Moffitt, J. A. (2001), Regulation of Sympathetic Nervous System Function after Cardiovascular Deconditioning. Annals of the New York Academy of Sciences, 940: 454–468.