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Time Stamps

• 00:05 Case Presentation: Urinary Retention → Lightheadedness
• 02:37 Defining Orthostatic Hypotension & Prevalence
• 04:10 Why Diagnosis Is Harder Than It Seems
• 06:20 How (and When) to Measure Orthostatic Vitals
• 10:06 Role of Heart Rate in Narrowing the Differential
• 14:41 Rethinking Treatment Goals: Function > Numbers
• 17:52 Recognizing Orthostatic Intolerance Symptoms
• 22:14 Non-Pharmacologic Strategies in the Hospital

Show Notes

Orthostatic hypotension (OH) is very common, seen in 20% of those over 60 years old and 50% in nursing homes.

The NORMAL Physiology of Standing

• FIRST: Stand up–> 300-800cc of blood pools in the legs and splanchnic vasculature! → Drop in blood pressure (lowest point in BP within 30 seconds of standing)
• SECOND: Baroreceptors in the carotid arteries and aortic arch detect this fall in blood pressure →sympathetic nervous system reflex → doubles norepinephrine levels in 5 minutes
• THIRD: Cerebral vasculature changes increases vascular tone to maintain a consistent cerebral perfusion pressures
• Fourth: Muscles inthe legs promote venous return while we’re moving

The Pathophysiology of ORTHOSTATIC Hypotension

• Normal responses (above) fails → mean arterial pressure (MAP) so low that the cerebral vasculature cannot maintain cerebral pressure
  • Result is cerebral hypoperfusion.
  • The exact MAP where this occurs differs between individuals
    • Since cerebral vasculature adapts to patient’s baseline blood pressure.
• Causes:
  • Decreased venous return
    • Hypovolemia
    • Vasodilators
    • Third spacing, such as immediately after a meal
  • Failure of cardiovascular system to respond to normal reflex arc & increase in sympathetic tone when standing
    • Issues with the heart (severe valvular disease, conduction system disease)
    • Issues with vessels (calcified vessels, vasodilatory medications, anti-adrenergic medications).
      • NOTE: Hypertension can lead to the heart and vessels becoming stiffer and the baroreceptors becoming less sensitive → decreasing responsiveness to the increase of sympathetic tone seen with standing
  • Failure of neurologic reflex arc (aka neurogenic orthostatic hypotension)
    • Neurodegenerative disease (Parkinson’s, multiple system atrophy, or pure autonomic failure)
    • Neuropathies (diabetes, amyloidosis, vitamin B12 deficiency)
    • Aging
      • Both from decreased responsiveness of nerves and vasculature on standing
    • NOTE: About a third of patients have a neurogenic cause
      • Key to identify!

Deep Dive 1: Measurement of Orthostatic Hypotension

Definition

• Orthostatic hypotension is defined as a sustained reduction of systolic blood pressure of at least 20 mmHg or diastolic blood pressure of 10 mmHg
  • within either 3 minutes of standing or
  • 3 minutes of assuming a head-up position of at least 60 degrees on a tilt table
• Where do these cutoffs comes from?
  • Associated with worse outcomes
  • OH increase risk of:
    • lightheadedness and falls
    • cardiovascular disease (1, 2, 3),
    • cognitive decline (1, 2),
    • mortality (1, 2, 3, 4, 5, 6)

How to Measure

• Blood pressure measurements vary significantly based on
  • technique
  • positioning and time of day
  • NOTE: This variation is more pronounced at higher blood pressures
    • Always make note of blood pressure, heart rate, and any symptoms at each time point of measurement
• How do you measure orthostatic blood pressure?
  • use a properly sized cuff
  • measure at the level of the heart with the arm supported
    • have the blood pressure at the patient’s side of in their lap can overestimate blood pressure
  • Steps:
    • ONE: Have the patient lie down for at least 5 minutes
      • Measure at least 2x to ensure your readings are consistent and you have a reliable baseline
    • TWO: If a patient is safe to stand and able to do so, consider moving directly from lying to standing vital sign measurements (bypassing the seated measurement).
      • More accurately simulates how patients rise to stand
      • Lying → standing blood pressure changes have a higher correlation with falls and symptoms (when compared to changes when moving from lying to seated)
    • Once the patient stands, measure (1) BP, (2) HR, (3) Symptoms at
      • One minute of standing (to assess for immediate OH)
      • Three minutes of standing (to assess for standard OH)
      • And (if the patient can tolerate) another measurement or two after five minutes of standing.

When To Measure

• Check after the same situation of the patients reported symptoms (ex: after a meal)
  • If no clear trigger exists > check at same time each day
    • Allows for comparison overtime and increase consistency of measurements
    • Consider first thing in the AM
      • particularly high risk time of day for OH to become symptomatic (as patients are often dehydrated in the morning and the lack of mobility while sleeping!)

What to Look For

• Timing of OH
  • Some patients have immediate symptoms, while others have delayed
    • Immediate symptoms → higher fall risk
    • “delayed” OH (measurement after 5 minutes): can be seen in early neurogenic disease (1,2).
  • Heart rate
    • Typically heart rate increases by 1 beat per minute for every 2mmHg drop in systolic blood pressure with standing.
      • NORMAL: typical ratio of change in heart rate to change in blood pressure (ΔHR/ΔSBP) is >0.5.
      • ABNORMAL: A ratio of < 0.5 suggests an insufficient heart rate response
        • Likely neurogenic cause of OH
          • Unless beta-blockers or a primary electrophysiologic issue
        • One study found a ratio of 0.492 had a sensitivity of 91% and specificity of 88% to distinguish between patients with neurogenic and non-neurogenic OH
• Symptoms
  • Remember that they may be subtle! (see below)

Buckets to Diagnosis OH

• Neurogenic vs Non-neurogenic:
  • Signs of neurogenic:
    • insufficient heart rate response upon standing,
    • comes on after a delay of five minutes or more (seen in earlier disease)
    • comes suddenly (seen in more advanced disease),
    • concomitant symptoms of neurogenic/autonomic disease (neurogenic bladder, sensory polyneuropathy, Parkinsonian symptoms)

Deep Dive 2: Treatment Goals of Orthostatic Hypotension

• Treatment Goal: Focus on symptom management and functionality (1, 2, 3)
  • Regardless, it can still be helpful to aim for a standing systolic blood pressure >100mmHg, which lowers the risk of falls and other complications
  • Individualize treatment for:
    • High risk patients
      • history of falls
      • neurogenic OH
      • cardiovascular disease (especially hypertension!)
      • those who fall with no warning signs/symptoms
• Approach to Treatment:
  • Working with physical therapy to ensure the patient is moving safely.
  • Look out for any positional symptoms and actively ask your patient for symptoms and monitor them for signs that may indicate hypoperfusion.
    • Vision changes
    • Fatigue
    • Dyspnea or chest pain, or
    • Pain in muscular groups such as the back, legs, or the upper back/between the shoulder blades (this symptom, called “coathangar pain” is due to hypoperfusion of the trapezius muscle).
    • Keep an eye out for signs the patient may not report, such as cognitive changes, which can indicate hypoperfusion
  • NOTE: In advanced neurogenic OH, sensation and recognition of symptoms as well as protective responses to symptoms (such as putting up one’s hands to break a fall) may be impaired.
    • Falling without symptoms should raise concern for neurogenic OH, and extra precaution should be taken when measuring orthostatic vital signs in those with known neurogenic OH to ensure safety and proper support if OH does occur.
      • Consider starting with seated vital signs in such patients!
• Patients with positive orthostatic vital signs but no symptoms are still at risks of falls in the future as asymptomatic OH often progresses (1, 2). These patients benefit from close monitoring and non-pharmacologic interventions below.

Deep Dive 3: Non-Pharmacologic Management of Orthostatic Hypotension

Mobility is the most important aspect of prevention and treatment

• Immobility
  • Decreased muscle activity → decreased venous return f
  • Decreased sensitivity to baroreceptors → harder to respond to standing!
  • Laying flat also increases natriuresis and can contribute to volume depletion.
    • One study found 9 hours of bed rest doubled the incidence of morning orthostatic hypotension in hospitalized patients.
• Encourage patients in the hospital to move! But move safely…
  • They often think that they can’t move. (Lines and tubes may subtly reinforce this message)
    • Remove any unnecessary objects keeping a patient in bed
      • Ex: foley catheter
  • Getting up slowly and with support when standing.
• Exercises! They can even be in bed…
  • Physical therapists adjust a patient to being upright slowly
    • raising the head of the bed, in bed-exercises, and lift-offs (sitting on the side of the bed and lifting up without fully standing before sitting again).
  • In-bed exercises can be prescribed by physical therapy
    • lower extremity exercises including bicycle exercises or elastic bands.
    • sometimes used as a preventative measure (before getting out of bed) or as a rescue measure (if patients feel symptoms and then sit down again).
  • Remind your patient to do these exercises when PT isn’t around!
    • Talk to your local physical therapist, but can ask patients to do 5-10 repetitions of these exercises 2-3 times per day

Triggers

• Dehydration
  • Very common in the hospital and nursing homes.
    • Patients are often not eating or drinking for long periods of time, either intentionally (when NPO) or not (when waiting in the ER or due to having less access to food and water than usual).
• Meals
  • High in carbohydrates, are a common trigger.
    • High carb meals lead to a lot of third-spacing into the splanchnic vessels and increased parasympathetic tone
      • Don’t forget post-prandial orthostatic hypertension!
  • Consider suggesting smaller and lower-carbohydrate meals to curb this effect
  • Remind patients to wait some time before getting up after meals

• Medications
  • Be careful not to stop all anti-hypertensives indiscriminately
    • While some patients may need all held, these medications have different relative risks for worsening orthostatic hypotension
  • Higher risk medications
    • Loop diuretics (dehydrate)
    • Hydralazine and nitrates (block normal reflex to stand)
    • prazosin, doxazosin, tamsulosin and tricyclic anti-depressants AND metoprolol, carvedilol (block adrenergic receptors – alpha 1, beta blockers)
    • clonidine and tizanidine(block adrenergic receptors – alpha 2)
  • Other triggers:
    • Heat (hot showers)
    • Exercise (especially in heat)
    • Alcohol

Assess your patient’s water and salt intake.

• Water intake
  • If not at risk for volume overload should be counseled to ensure they are taking in sufficient fluids (at least 2-3 liters per day)
    • 16 ounces of COLD tap water quickly (in 3-4 minutes) can be effective in treating orthostatic hypotension
      • rescue measure to treat symptoms or as a preventative measure first thing in the morning.
      • In these small studies, this caused an increase in norepinephrine similar to ~250mg of caffeine (2-3 cups of coffee) (1, 2) and increased standing SBP by an average of 12mmHg.
• Salt intake
  • Higher salt intake has been shown to be effective in treating orthostatic hypotension.
    • However higher amounts are generally needed (6-10 grams per day!)
      • this should NOT be prescribed indiscriminately due to risk of fluid retention and exacerbating hypertension. Choose your patient carefully! (1, 2)

Consider compression treatment

• No consensus on if you need BOTH abdominal and leg compression; versus just one
  • Leg compression
    • The most effective compression is with hip/thigh-high compression stockings of at least 20-30mmHg of pressure, but these can be hard to apply.
      • Try at least 15-20mmHg of pressure and/or knee high compression if these adjustments increase adherence. (1)
    • Just be sure to avoid bunching of stockings at the knee as this will decrease venous return
  • Abdominal compression
    • Effective in those that can tolerate it
      • One study found it similar in efficacy to midodrine!
    • Be sure to advise patients to only use this when out of bed

Transcript

Dr. Nick Villano: Welcome to Gray Matters, where we unpack how medical management is rarely black or white.

Dr. Shreya Trivedi: And go on deep dives along the way.

Dr. Nick Villano: I’m Dr. Nick Villano.

Dr. Shreya Trivedi: And I’m Dr. Shreya Trivedi.

Dr. Nick Villano: So Shreya, it’s been a while. I’m looking forward to jumping back into the fog of uncertainty with you.

Dr. Shreya Trivedi: The fog of uncertainty sounds really dreadful, but I do think it’s easier to cut through fog with some help and some friends.

Dr. Nick Villano: So I had this patient on the inpatient wards recently. He’s 72. He has a history of hypertension and mild diabetes and he comes in with syncope. Turns out he had severe urinary retention. I mean they placed a catheter in the ED and over a liter of urine came out

Dr. Shreya Trivedi: A liter. Gosh, that makes me so uncomfortable to even think about.

Dr. Nick Villano: I know it’s one of those things you can just feel, but to figure out why he had severe urinary retention, we got an MRI that showed that his prostate wasn’t too big and there was no cord compression, but eventually we did find out that his hemoglobin A1C was 12.5%, so we start insulin.

Dr. Shreya Trivedi: I was still thinking about that urinary attention. I bet he had a pretty gnarly a KI from that,

Dr. Nick Villano: But thankfully the AKI did resolve with the catheter, he did have some post obstructive diuresis. He got a little lightheaded since he was peeing a ton, but we gave him fluids and eventually his polyuria resolved.

Dr. Shreya Trivedi: What happened next?

Dr. Nick Villano: So here’s the thing. His polyuria resolved but his lightheadedness did not resolve. I had been giving him a lot of fluids. He had been net positive for a few days. Now like I said, his sugars were looking better, so I was like, there’s no way this patient can still be dehydrated and then I realize I’m facing my old nemesis.

Dr. Shreya Trivedi: Oh no, don’t say it. The biggest discharge blocker of them all

Dr. Nick Villano: Afraid. So orthostatic hypotension.

Dr. Shreya Trivedi: Yeah, sympathy though I will say, Nick, I’m glad we’re talking about this. I feel like our patients are so complex in the hospital and often slips my radar until I get a message from a nurse the day before discharge saying, oh, this patient almost passed out when they stood up or their blood pressure was this when they stood up?

Dr. Nick Villano: Yeah, I mean if it’s not on the problem list, we sometimes forget about it, but it’s surprisingly common. I found that one in five patients over the age of 60 actually deal with orthostatic hypertension and some studies actually documented it in half of nursing home residents

Dr. Shreya Trivedi: Half. It’s humbling to even think, but we might even catch more people if we actually diagnosed it correctly. So why don’t we start there?

Dr. Nick Villano: Yes, that is exactly where I want to take us for our first deep dive because I learned that it’s a lot more than just having someone stand up and check their blood pressure.

Deep Dive 1

Dr. Shreya Trivedi: I think we’ve all learned that orthostatic hypotension is a consequence of changing position. We stand up, blood pulls in the leg and the gut and so venous return drops and so does our cardiac output and then normally our nervous system detects that and ramps up our sympathetic tone and we’re fine. We just go about our day. But if our nervous system or our heart can’t respond normally, then the blood pressure stays low, our cerebral perfusion drops and then we pass out or just feel awful and we’re looking for that drop in the blood pressure when standing to make the diagnosis.

Dr. Nick Villano: Exactly. And more precisely the official diagnosis would be a drop in systolic blood pressure by 20 millimeters of mercury or a drop in diastolic blood pressure by 10 millimeters of mercury when standing.

Dr. Shreya Trivedi: I’m curious, where are we getting those numbers from? Why is it 20 millimeters mercury and 10 millimeters mercury? Do those numbers have any real significance?

Dr. Lewis Lipsitz: Ultimately, what’s important is what level of blood pressure change results in bad outcomes. So studies have looked at that and the reason that we come up with a number like 20 millimeters of systolic pressure is because a drop of 20 or more millimeters pressure and systolic pressure is associated with bad outcomes such as dizziness, falls, syncope.

Dr. Shreya Trivedi: That’s Dr.Lewis Lipsitz, our first consultant.

Dr. Lewis Lipsitz: I am Lewis Lipsitz, a geriatrician. I’m currently a professor of medicine at Harvard Medical School and director of the Marcus Institute for Aging Research at Hebrews Senior life

Dr. Lewis Lipsitz: Syncope falls myocardial infarction cognitive impairment. So that’s why we use those parameters as sort of guidelines as to what might be significant.

Dr. Shreya Trivedi: Wow. I did not think about how orthostatic hypotension could be related to heart attacks, but now that I think about it, it makes sense that the coronaries fill during diastole and that diastolic blood pressure can get pretty low in orthostatic hypotension.

Dr. Nick Villano: Yeah, it sure can. I mean some people even consider orthostatic hypotension an independent risk factor for cardiovascular disease. I saw studies where it was associated with mortality and cognitive decline, but I mean, what’s the takeaway here? Catching this disease is important and the measurements unfortunately aren’t always consistent. I mean blood pressure measurements have actually been shown to be way more variable than we’d like to think. Sometimes by 10 to 20 millimeters of mercury between measurements and that gets even worse at higher blood pressures, which is why diagnosis is even trickier in patients with hypertension.

Dr. Shreya Trivedi: Wait a minute, variations are like 10 to 20 millimeters per mercury. That’s basically the difference between calling so of the orthostatic hypotension or not. Literally those are the numbers and the definition. I think that definitely makes me feel more compelled to know then how exactly who should measure that blood pressure as accurately as possible, I think is making sure we have the right size cuff and then second, making sure that arm is supported and at the heart level,

Dr. Nick Villano: And I didn’t know this, but actually a third thing is to have them lay flat for about five minutes to allow the blood pressure to stabilize and most guidelines actually suggest checking the blood pressure at least twice to get a good baseline to compare our standing vital signs to. I mean if you can find time to do that in the hospital.

Dr. Shreya Trivedi: Wait, Nick, I have seen some technicians and nurses just compare blood pressures from sitting to standing. Is that right?

Dr. Lewis Lipsitz: They’re going to equilibrate when they’re sitting and you’re not going to really know what happens under the maximal stress of supine to standing, which is what most people do when they faint.

Dr. Nick Villano: So yeah, some advocates skipping sitting since blood pressure management’s going from laying to standing, actually have a higher correlation with falls and symptoms and also it’s more realistic with how people get out of bed. I

Dr. Cyndya Shibao: Have to check the blood pressure after the patient is laying down for at least five minutes and then you ask the patient to stand up and you try to collect the blood pressure as 1, 3, 5, 10 minutes if the patient tolerates it and you also have to measure the heart rate.

Dr. Nick Villano: That’s Dr. Cyndya Shibao, our second consultant.

Dr. Cyndya Shibao: My name is Cyndya Shibao and I am a tenured professor of medicine at Vanderbilt University Medical Center and the associate director of the Autonomic Dysfunction Center.

Dr. Shreya Trivedi: Wait a minute, let me just make sure I heard that correctly, Nick. They want us to check a blood pressure after standing at one minute, three minutes, five minutes and 10 minutes.

Dr. Nick Villano: Yeah, I know it’s going to be tricky to get all these different data points in a busy hospital or clinic setting, but the point here is that if we only check the blood pressure one minute after standing, we may miss people who get symptoms at two minutes or three minutes. It’s not that uncommon.

Dr. Shreya Trivedi: Yeah, fair. I mean I guess waiting longer will increase their sensitivity in patients who we have a higher index suspicion for

Dr. Nick Villano: Patients who have early neurogenic disease actually tend to have a delay in their symptoms withstanding. They may not get symptoms where stasis for three minutes after standing.

Dr. Shreya Trivedi: Oh, interesting. That’s good to know. So this is all about how to take a blood pressure in an ideal world where you have time and the patient is also patient with it. But I’m curious, does it matter when we check that orthostatic blood pressure? I mean most of us just order AM orthostatic vital signs, right, but is that the right thing to do?

Dr. Lewis Lipsitz: What you want to do is put them through the exact same situation in which they faint. Did it occur after a meal? Did it occur an hour after taking a medicine? Did it occur while standing up first thing in the morning when they’re dehydrated? So first part of it, the answer is test them under the exact same circumstances in which the event, whatever it is occurred.

Dr. Nick Villano: So you can time your orthostatic vital signs around the triggers for the patient’s symptoms like were they eating lunch when they stood up and fell? Did they get lightheaded after walking around doing light chores? If you don’t have those triggers the early morning before medications is a good place to start.

Dr. Cyndya Shibao: We encouraged not to just rely on one measurement but try to do multiple measurements, particularly in the morning and before the patient takes the medication because the periods of time where patients are very, very symptomatic and it’s more reliable because blood pressure in these patients they change dramatically throughout the day.

Dr. Shreya Trivedi: Okay, got it. So what did you do for your patient who had that severe urinary obstruction now status PO catheter has this post obstructive diuresis that’s now resolved but is still lightheaded and uses his spec test orthostatic hypotension.

Dr. Nick Villano: So he didn’t have any clear triggers, so we just tried measuring his orthostatic vital signs first thing in the morning. We got a good cuff. We measure his blood pressure twice while laying down. Luckily we could find the time and then we stood him right up. He could only stand for about three minutes before a symptoms set in, but if you compare a systolic blood pressure we’re laying down to the blood pressure when standing at one and three minutes, it went from 140 to 80 to 75 points. So it definitely dropped and while that happened his heart rate went from 70 to 85 beats per minute.

Dr. Shreya Trivedi: Wow. Nick, that systolic blood pressure dropped to 75, not good. You also reminded me about checking the heart rate. I mean I remember somewhere along the way learning something about an increase in heart rate like 30 or 20 can signal orthostatic hypertension.

Dr. Nick Villano: Yeah, I’m glad you brought that up. I thought the same thing but I found out we really just use blood pressure to diagnose orthostatic hypertension.

Dr. Shreya Trivedi: So if we don’t need heart rate for the diagnosis, why are we measuring it?

Dr. Nick Villano: So what I found out is that we want to see if the heart rate is doing what we expect it to do basically is it going up by enough? Because if it doesn’t, it could mean that there’s something wrong with the normal reflex arc to standing, meaning there could be some kind of neurogenic process driving the orthostatic hypotension.

Dr. Cyndya Shibao: We cannot tested this new index, so we take the blood pressure supine and standing at one minute as well as the heart rate. So you calculate the difference in terms of how much the heart rate goes up from the supine to the upper posture at one minute and how low the blood pressure drop. And then you have these deltas delta of the heart rate divided by the delta of the systolic blood pressure and if this index is less than 0.5, then there’s much high likelihood the is probably an anomic neuropathy compared to blood volume depletion or disorder factors of which is discussed.

Dr. Nick Villano: And we will link to the ratio of the change in heart rate to the change in systolic blood pressure at one minute in our show notes. But another way to put it is that if the autonomic reflexes are intact, that is if they’re not being affected by neurogenic disease or a medication like a beta blocker, then for every two points that your systolic blood pressure drops when you stand, your heart rate should go up by one. So the change in heart rate over the change in systolic blood pressure should be at least 0.5 or higher.

Dr. Shreya Trivedi: And so if you do see that change being greater than 0.5, then we’re good and autonomic neuropathy is less likely on the table

Dr. Nick Villano: If you see that the change in heart rate over the change in systolic blood pressure is standing is over 1.5 AKA you’re getting that heart rate response of at least one for every two-point drop in systolic blood pressure. That’s pretty suggestive of a non-neurogenic cause of orthostatic hypertension. In fact, it has a sensitivity of 91% and a specificity of 88%.

Dr. Shreya Trivedi: Nice. This is all great learning. Let’s summarize our best practices we learned on orthostatic hypotension and making that diagnosis. I think one, we want to make sure we have a good size cuff if we can try to have a patient lay supine for at least five minutes, get a couple baseline reads and heart rate reads if we can have them stand right up, and then document the blood pressure and heart rate and symptoms at one minute, three minutes and then longer. If we really want to increase the sensitivity, we want to make sure that it’s not neurogenic and we’re going to look at the heart rate response and see if it’s blunted or not. And then it could be helpful to do all of this around the same time the patient initially fell or was showing symptoms or if not, just check it in the morning each day to standardize our readings.

Dr. Shreya Trivedi: Okay. Nick, you said your patient’s systolic blood pressure dropped from 140 to 80 at minute one. That’s a change of 60 millimeters per mercury and so you’d expect that heart rate to go up by at least 0.5 or half, so at least 30 beats per minute, but your patient’s heart rate just went from 70 to 85. Nick, what do you make of that?

Dr. Nick Villano: Yeah, I mean I went back and I found that he did have some signs that he might have lost some fine touch and proprioception in the toes. So I was thinking that maybe his uncontrolled diabetes was causing peripheral autonomic dysfunction and maybe that contributed to his urinary retention in the first place and now is contributing to his orthostatic hypotension.

Dr. Shreya Trivedi: Yeah. Real quick Nick, we throw around the term neurogenic causes often, but clear is kind. Why don’t we talk a little bit more about what exactly you put in that bucket versus other causes?

Dr. Nick Villano: Absolutely. The causes of OH is a whole big topic. But in the simplest terms, we can think two major buckets. The first bucket is the “neurogenic” causes- anything that impairs that normal baroreceptor reflex of sensing a low BP and the brain doubling norepinephrine levels in response. This could be a neurodegnerative issue like Parkinsons+ disorders or pure autonomic failure, or neuropathy like diabetes or amyloidosis.

The second bucket is the non-neurogenic causes – things that will impact venous return like dehydration or impact cardiac output like valvular disease. I did put in the show notes for a deeper breakdown of causes for those interested, just remember a neurology referral can be helpful esp since some disease fall in both buckets!

Dr. Shreya Trivedi: Interesting. I’m glad we’re talking about neuro versus not because I think they do have big implications in terms of treatment goals and speaking of which I feel like most people put for treatment goal, like free check AM orthostatic blood pressure and discharge when not orthostatic.

Dr. Nick Villano: Yeah, I mean I like making look numbers look nice as much as the next internal medicine doctor, but that can be really hard for patients with hypertension and these patients aren’t all the same. I mean they come in different flavors. So what are our treatment goals and how does that depend on the specific patient we’re treating?

So I always thought that our treatment goal was going to be just making the standing blood pressure better. I mean that makes sense. But this one circulation review article flipped my whole approach to treating orthostatic hypertension. It said that the goal is improvement in symptoms and functionality rather than correction of the orthostatic hypertension and recommendations from other societies are in line with this.

Dr. Shreya Trivedi: So improving symptoms and functionality, that feels like a realistic goal Nick and probably a lot more patient friendly, but it’s also not very specific. How do we actually do this?

Dr. Nick Villano: I mean first off, yeah, we’re not focusing on a particular number, but there are two somewhat nuanced caveats to that. The first is we do want to try keeping the standing blood pressure out of the danger zone,

Dr. Shreya Trivedi: But what exactly is a blood pressure target? That’s not a danger zone for patient. I mean your patient’s blood pressure dropped to like 75 milligrams for mercury at one point, right? It’s pretty low.

Dr. Nick Villano: Yeah, I agree that is pretty low, but what’s out of the danger zone can get a little bit gray. I mean the brain adjusts its blood flow separate from the mean arterial pressure AKA, the MAP and it does that to keep the brain fed and happy at different blood pressures, but everyone’s brain does this differently. So how low can a patient’s MAP yet before it affects the cerebral blood flow is hard to say, but our consultants did have some guidance here.

Dr. Lewis Lipsitz: I will also try to just keep that systolic above a hundred because that’s really I think a critical, an easily observed value that is sort of a critical point between perfusion and not.

Dr. Nick Villano: So for many patients a systolic above nineties to hundreds is a reasonable goal to make sure the brain and coronaries are perfusing and they’re able to do their daily activities. But the other caveat we wanted to talk about here are patients with true severe neurogenic disease.

Dr. Cyndya Shibao: Now if the patient has an autonomic failure, they’re always going to have orthostatic hypotension. I mean you are not going to cure that because the problem with these patients is the cardiovascular anomic reflexes are impaired

Dr. Lewis Lipsitz: And I don’t care so much whether it’s a 90 millimeter systolic or not, as long as they’re able to do their activities, I know their risk of falling. I mean I already know that. The question is how long can I have them stand up?

Dr. Shreya Trivedi: Yeah, I’ve definitely had neurology consults have different thresholds for patients with severe neurogenic orthostatic hypertension. I think it’s just a different group of patients where it gets even more gray and the number cutoffs that are dangerous for them is just a different ballgame.

Dr. Nick Villano: Blood pressure goals can be so hard, especially in this population. So I want to take a step back towards our main goal of reducing or stopping any symptoms that affect functionality. When I think about symptoms that come with orthostatic hypertension, I really like using this term orthostatic intolerant symptoms to remind myself to not just anchor on lightheadedness. That reminds me to think of any symptom that can come with standing.

Dr. Sharon Gorman: Sometimes patients won’t describe it necessarily as lightheadedness or dizziness. They might just say they feel weak or they feel a little unsteady or even if you kind of dive into it, watch their face, it looks like you are not feeling well right now. So there’s quite a bit of me looking right at them when they’re doing this to make sure I’m not seeing anything.

Dr. Nick Villano: That’s our third consultant physical therapist, Sharon Gorman.

Dr. Sharon Gorman: So my name is Sharon Gorman. I am a licensed physical therapist. I’ve been a physical therapist for more than 20 years.

Dr. Nick Villano: So you can get vision issues, you can get chest pain from poor coronary flow. One interesting symptom is called coat hanger pain that comes from decreased blood flow to the trapezius. Symptoms can also be subtle. I wonder how many times I’ve written asymptomatic orthostatic hypertension as a diagnosis when my patient actually did have something like maybe mild confusion when they stood up.

Dr. Shreya Trivedi: I think the other flip side of all this Nick, is what if we have a patient who doesn’t have truly any warning symptoms? They just fell before they could respond.

Dr. Lewis Lipsitz: Most people will be able to experience symptoms when they have a reduction in blood flow, but not everyone, particularly if they’re older and have dementia or other conditions, may not be able to experience that.

Dr. Nick Villano: Yeah, that’s a super high-risk group. I mean, patients who have severe dysautonomia or dementia, where they may not be able to sense their orthostasis before falling, ugh, that really worries me.

Dr. Shreya Trivedi: And I think in some sense falling with no warning signs, people just assume like, oh, maybe it’s cargenic and that’s what they only worry about. But I think the other thing to keep in mind on the differential is maybe they have really bad orthostatic hypertension.

Dr. Nick Villano: I feel like sometimes when we think that the fall was caused by orthostatic hypotension, we’re almost reassured, but it can still be really dangerous, especially in these patients with no warning.

Dr. Shreya Trivedi: Yeah, definitely. The other patient scenario to think about is person we see in clinic who has actually positive orthostatic vitals, but they’re doing fine. They have no symptoms, they haven’t fell, they’re tolerating it. This drop in blood pressure just fine. So what do we do about that?

Dr. Nick Villano: Yeah, there are some patients who can physically tolerate a slightly lower blood pressure like their cerebral blood folk can adapt. But as much as I hate to find a problem with someone being fine, even if they’re truly asymptomatic right now, studies show that asymptomatic orthostatic hypertension will often progress in one study of older adults, the risk of unexplained falls doubled in these patients after six years.

Dr. Shreya Trivedi: Man, I just want to point out a double edged I guess nuance here. We said earlier that our treatment goal is symptoms and functionality, but at the same time it seems like we just can’t ignore that low blood pressure number when they stand. I think it seems like consistently throughout this episode it’s shown as it does carry a poor prognostic sign for bad to come later.

Dr. Nick Villano: Definitely. To summarize the bigger point here, our treatment goal should be to focus on functionality and symptoms and on the point of symptoms we really want to investigate if there are any symptoms at all of orthostatic intolerance when the patient stands up, signs of poor organ perfusion like chest pain vision or mental status changes or even neck pain.

Dr. Shreya Trivedi: Yeah and while we don’t want to focus on the number entirely in terms of our treatment goal, we do want to make sure that standing blood pressure is out of that danger zone. So for most people it’s going to be trying to getting them up to at least a systolic blood pressure of nineties to a hundreds when they stand. And of course it’s going to be challenging and the thresholds are so different and treatment goals are so different when it comes to severe dysautonomia, the neurogenic patient’s neurology will just have some different individualized treatment goals. So let’s try to apply some of these treatment goals to your patient. When you are treating this patient, what are you hoping to achieve?

Dr. Nick Villano: Definitely, that’s a great question. So when he stood up, he did report lightheadedness as well as feeling like his thoughts were kind of foggy. So I thought, okay, that’s what I want to get better with treatment and hopefully get a systolic blood pressure to the nineties or hundreds while we do it.

Dr. Shreya Trivedi: Yeah, man, I hope this doesn’t mean that we’re going to put him on three new medications.

Dr. Nick Villano: Yeah, I know medications are an important important avenue, but I love that you’re driving at the question of how we can intervene without medications right now. And this led me down a road with a lot of different pit stops. I learned that different people need different kinds of fuel.

Dr. Shreya Trivedi: Oh man, what a clunky analogy, but do appreciate so me levity.

Dr. Nick Villano: So let’s open the hood on how to prevent or treat orthostatic hypertension in the hospital without medications.

Dr. Shreya Trivedi: Okay, yes. I love thinking about non-pharmacological treatment. I don’t know why, but it just makes me feel like such a good medicine doctor not using actual medicines.

Dr. Nick Villano: I totally get that. That circulation paper recommended four big non-pharmacologic interventions for everyone with orthostatic hypertension regardless of symptoms. And that starts with the oldest medicine known to man. Your body staying upright depends on your body continuing to move otherwise gravity wins.

Dr. Lewis Lipsitz: Interestingly, if you take the most healthy fit astronaut and send ’em up to space for 24 hours, when they get back down on earth, they can’t stand. They have orthostatic hypotension and that’s because we are so dependent on our leg muscles to pump blood.

Dr. Nick Villano: So one study of elderly inpatients found that daily bedrest of at least nine hours more than doubled orthostatic hyportension. When you rest, you retain less fluids. You aren’t working the leg muscle pump in your bar

Dr. Lewis Lipsitz: Risk unusual that less to the hospital and lo and behold, orthostatic hypertension to try to stand up after parole and bedrest.

Dr. Nick Villano: Yeah, so one study of elderly inpatients found that daily bedrest of at least nine hours more than doubled morning orthostatic. When you rest, you retain less fluids. You aren’t working your leg muscle pump and those barrow receptors that help you stay vertical actually get less sensitive with time. And then lo and behold, orthostatic hypertension develops.

Dr. Sharon Gorman: A lot of patients think they can’t get up. They have lines and tubes on them. There was actually great study out of Australia with really healthy people who had no restrictions when they were in the hospital and the number one reason they said they didn’t get up was they had a fully catheter, which is the easiest thing to take with you and walk. But they thought because they had that and it hangs on the bed, I can’t go anywhere. I’m just such the big person who pushes everyone who can do whatever they can to encourage mobility and even if that’s you as the physician asking the patient when you come in the room, did you get up today? How often have you gotten up today? Why are you getting up? Oh, what’s stopping you from getting up? How can we help you get up more? Even if you just ask those questions, that’s giving the message to the patient that they need to move around.

Dr. Nick Villano: But one thing is that my patient already has orthostatic hypertension. I mean, I still want to encourage exercise, but I can’t exactly tell my patient who almost passes out when they stand up to go walk lap around the unit. I mean, I was honestly kind of worrying that maybe it’s too late to promote mobility, but our experts assured me that we can still get these patients moving even if that doesn’t mean standing.

Dr. Sharon Gorman: If I have somebody who I know has a really big problem with orthostasis, I may put the head of the bed up, let them start adjusting to that. Do some lower extremity exercises in bed first to try and boost that venous return, get those muscle pumps helping.

Dr. Nick Villano: : Sharon said that as a rule of thumb she recommends patients do at least 5-10 reps of in bed, 2-3 times a day especially as a warm up to get blood moving before they get up and move.

Dr. Lewis Lipsitz: And you might want to start with supine bicycle exercises, which are great because you’re not standing upright but you’re semi supine and you’re using your leg muscles. There was a nice study number of years ago that showed that people with severe orthostatic hypertension could lie in bed and take these TheraBands, these stretchy rubber bands and put them around their feet and extend their feet 10 on one side, 10 on the other side, and then stand up and they actually ameliorated much of the orthostatic hypotension and enabled them to do their activities that they needed to do in the morning.

Dr. Shreya Trivedi: Wow. Can we get our patients TheraBands? That sounds so cool, Nick. I have to say I do love telling them I want you to do knee bends and arm raises every hour. And I’m sure our physical therapy colleagues have even better exercises. Some of the ones they just mentioned, like the semi supine bicycle movements, even seasoned liftoffs can be helpful in terms of getting muscle pumping without having them actually stand.

Dr. Nick Villano: Okay, so the first non-pharmacologic treatment is to get patients moving. The second is that you want to look for anything that’s clearly treatable or reversible that contributes to the orthostatic hypertension. Think here about dehydration to start. Many patients have poor appetite at baseline as they get older. Then in the hospital they face long emergency room stays without food or fluids. NPO status, restrictive diets, aggressive diuresis. I mean we are kind of pros at dehydration

Dr. Shreya Trivedi: Yeah, and I think we’ve already touched on some causes. We thought about if dehydration is contributing, if there’s some autonomic dysfunction at play. I think the one we’ve left out is a really big offender, which is medications.

Dr. Nick Villano: What caught my eye on my patient’s medication list was this isosorbide mononitrate and his lisinopril.

Dr. Cyndya Shibao: So one of the things that we usually do is we look at what medications these patients are taking. Sometimes you can find hidden agents. For example, tizanitine is a big problem in the south. There is overuse of that medication. People don’t know that it’s similar to cloning, for example. So you have to stop the medication. When we look at the type of medication that really produce a lot of problems with orthostatic hypotension, for example, beta blockers, one of the culprit, diuretics, that’s another called culprit, you know, vasodilators like nifedipine, for example, that can cause orthostatic hypotension. So what we ask is, don’t stop everything. Just, you know, stop the medications that has been a associated with orthostatic hypotension.

Dr. Nick Villano: So focus on holding or reducing high risk medications. Being dehydrated is a risk for falls. So be careful with loop diuretics and think about anything that will block the adrenergic response to standing. Things like beta blockers, alpha blockers, like doxazosin or tamsulosin, or even tricyclic antidepressants or alpha two agonists like tizanadine or clonidine. Finally, if your blood vessels dilate as you stand up, you’re gonna be at higher risk for falls. So primary vasodilators, like nitrates, can also be high risk.

Dr. Shreya Trivedi: Nice, nice. Let me just reiterate that in a way my brain can understand. So maybe I’ll just make it like alphabetical to just chunk it out a little bit more. So big offenders, high risk beds are gonna be a alpha blockers like tamsulosin, alpha two agonists like clonidine or tazanidine, beta blockers, nitrates that vasodilate and then tricyclic antidepressants. You also said that the ACE inhibitor caught your eye, but that was not on the high risk category. So maybe I’m guessing the ACE and ARBs are lower risk.

Dr. Nick Villano: Yeah, they’re relatively lower risk. I mean you may still need to hold them if patients remain orthostatic on them, but it may not need to be your first move. Check the shownotes for our graphic on the relative risk of different antihypertensive medications on causing orthostatic hypertension. But basically to that effect, we held the patient’s isosorbide mononitrate, but continued his lisinopril

Dr. Shreya Trivedi: Great. I think here’s the part where I get stuck, Nick is a third bucket of non-pharm things to try, which is compression stockings. I think I’ve ordered compression stocking so many times by abdominal binder so many times and I don’t know if it’s really doing anything and more so I’m like, is this the right fit for my patient?

Dr. Nick Villano: Okay, so when we start talking about compression, things are going to get a lot more gray. For instance, some clinicians say that you need to compress the entire leg and the abdomen to squeeze blood all the way back to the heart

Dr. Shreya Trivedi: Like a tube of toothpaste,

Dr. Nick Villano: Like a tube of toothpaste. But talking to Dr. Shibao, she actually made a good case that abdominal binders could be effective on their own.

Dr. Cyndya Shibao: So what we did is we took a lot of graduate students, we put them electrodes all over the body and then we tilt them and then we try to estimate where the fluid goes. When you are tilted up the majority of the fluids sequester in abdominal area, not in the thighs, not in the cough, and definitely not in the feet. It goes really to the abdominal area. We have shown that just using an abdominal binder is as often as using midodrine when we did a comparison between the midodrine and the inflatable abdominal binder.

Dr. Shreya Trivedi: Wow, what a great headliner. Abdominal binders are as good as midodrine in these healthy graduate students. I love this. Cause we know fluid sequesters in the abdomen, and so when you stand up, this is where the money is. And I love when the science pans out. An abdominal binder is as potent as a midodrine

Dr. Cyndya Shibao: So what we usually do is we encourage our patients to wear any of the commercial abdominal binder, all the lumbar support and see if with that they’re able to have some symptomatic improvement and also adhere to the therapy. And so far for us has been very useful because patient like the fact that they’re able to put it on, put it out or take it out fast.

Dr. Shreya Trivedi: I love how the focus here is super practical, right? Because abdominal binders are just easier for a patient to use on their own and most of our patients are on their own at home. I feel kind of guilty when we’re treating a patient with compression stockings and they need all this help in the hospital with nursing. It’s a whole production to get these compression stocking on. And so how are they going to really manage this at home?

Dr. Nick Villano: But then again, just because abdominal binders can be effective, don’t totally discount leg compression. Remember we said it’s gray. Our older patients with venous pooling in their legs aren’t the healthy graduate students in Dr. Shibao’s study that benefited so much from abdominal binders.

Dr. Shreya Trivedi: How do we give helpful instructions for our older patients who might need leg compression too?

Dr. Lewis Lipsitz: If we use compression stockings, bunching ’em up below the knee actually prevents venous return rather than promotes venous return. And I’ve always, it’s funny, as a younger attending, I would always say, oh, they’ve got to be thigh high because obviously we don’t want to bunch ’em up below the knee, but nobody can get the thigh high ones on. Absolutely. So I have sort of modified my view and said at least if you can get up to the knee and try not to bunch ’em up underneath, that’s probably the best.

Dr. Nick Villano:And what specifically do we recommend our patients get? Well compression stockings generally list how much pressure they apply on the packaging, and Dr. Lipsitz suggested looking for ones that can provide at least 20-30mmHg of pressure, If those are too hard to get on you can try ones that give 15-20mmhg of pressure.

Dr. Nick Villano: So yeah, I mean this is obviously super situational. In our case, we didn’t have fitted thigh high compression stockings for my patient and the ones that we did give him just kept bunching up around the knee. Kind of like Dr. Lipsitz said, we were worried about blocking venous return, so we just stopped using the compression stockings altogether.

Dr. Shreya Trivedi: So I guess for some people compression stocks can work and some like your patient, it might not.

Dr. Nick Villano: So for the last thing in the non-pharmacologic toolkit, I want to look at behavioral changes that patients can make. And to start, I want to talk about something that really surprised me and that’s that the way patients drink their water can actually help to treat orthostatic hypotension.

Dr. Cyndya Shibao: The other thing is drinking water as fast as you can. So a lot of these patients when they drink 16 oz of water as fast as they can, the blood pressure increase in about 30 minutes and it’s a very good rescue measure to increase the blood pressure when a patient doesn’t have access to their medication or they’re in a place where they cannot sit down or lay down because they have symptoms.

Dr. Nick Villano: Yeah this is really interesting, rapidly drinking about one water bottle’s worth of cool water in 3-4 minutes is, like, unexpectedly effective. Get this. In a study of older adults, it increased standing SBP by average of 12mmhg. Another study of those with dysautonomia showed it increased norepinephrine levels in patients with neurogenic disease similar to 2-3 cups of coffee!

Dr. Shreya Trivedi: Wait, chucking water did this?

Dr. Nick Villano: Yeah, I know The thought is that this works because water’s hypotonic, so don’t add anything. But having patients drink this bolus of water in the morning or before exercise can actually really help.

Dr. Shreya Trivedi: What a clutch hack if there was a medicine hack. I think the other behavioral thing I’ve seen people recommend is stay hydrated, not just with that morning chug of cold water, but throughout the day I think people have also been told to eat salt. I think Nick, you were saying you had an attending who used to tell people to have soy sauce in the morning.

Dr. Nick Villano: Right? I mean for patients that aren’t at risk for volume overload, recommending at least two liters per day of fluids can help. So that’s definitely something to keep in mind. I found out that you need five to 10 grams of sodium per day to really affect your orthostatic blood pressure.

Dr. Shreya Trivedi: Yeah, definitely. With salt, we are all constantly worried about the edema, the hypertension. I think it has to be right for that patient.

Dr. Nick Villano: I just want to move on to think about things we can recommend that our patients avoid triggers for orthostatic hypotension.

Dr. Cyndya Shibao: So of course triggers are a big important part of management, right? We ask them not to take hot showers, not to take a hot bath because that produces a violation. We ask them try to limit the amount of caffeine because that produces diuresis and volume depletion. We ask them to wear abdominal binders that compress the splenic circulation to prevent the significant drop in blood pressure after you trap blood in the splenic once blood vessels. And we ask the patient if eating particularly large meal reaching carbs a trigger, a worsening of their symptom because some of these patients have postprandial hypertension.

Dr. Nick Villano: So changing the patient to more smaller meals to lower those big carbohydrate boluses can actually really help also tell them to try to avoid heat because remember, sweating is a sympathetic activity and patients with autonomic dysfunction may not be able to do that to cool themselves off.

Dr. Shreya Trivedi: So why don’t we summarize all the things in the non-pharmacological buckets that we talked about? First is really promoting exercise mobility, get those muscles pumping. Second is really to assess any treatable causes for orthostatic hypotension, like stopping any of those high-risk medications. And if orthostatic hypertension persists, despite all this, we can consider compression like abdominal binders or thigh high compression stockings that don’t bunch up behind the knee. And then in terms of behavioral changes, we learned about a really cool trick about having patients chug cold water first thing in the morning as fast as possible, and that could help with some orthostatic hypotension and avoid triggers like heat or high carb meals.

Dr. Shreya Trivedi: All right, stay tuned for our next episode, where we’re going to learn more about what happened to Nick’s patients. Did these non-pharmacological interventions help? And if so, by how much and did he have to reach for some medications? And if so, what was the right approach?

Dr. Nick Villano: That’s a wrap for today. As much as we love going through this case, we also love going through other cases. So if you have one that you want to bring to us, please email us at [email protected]. And if you found this episode helpful, please share with your team and colleagues and give it a rating on Apple Podcasts or whatever podcast app you use. It really does help people find us.

Dr. Shreya Trivedi: Thank you to our reviewers, Dr. Adam Straus. At Dr. Jason Yoon, and as always, opinions expressed our own and do not represent the opinions of any affiliate institutions. Thank you. Take care.

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