What is the diagnostic accuracy of pulsus paradoxus for cardiac tamponade?

A classic Step 1 associations is: increased pulsus paradoxus=cardiac tamponade. But like everything in medicine, it’s not that simple. An abnormal pulsus paradoxus is not really sensitive or specific for cardiac tamponade. Pulsus paradoxus may also be present in patients with labored breathing, asthma attacks, pulmonary hypertension, constrictive pericarditis, PE, etc. This summary cites one report that “15% pulsus paradoxus in the face of relative hypotension was found in 97% of patients with moderate or severe tamponade and only 6% of patients with absent or mild tamponade.”

This review in Clinical Cardiology describes pulsus paradoxus as the “end of a spectrum” in cardiac tamponade, which frames it as what it is: an exam finding that if present, means that it’s more likely the patient is ALREADY in tamponade and you should act quickly…but just because it’s absent doesn’t mean the patient does NOT have tamponade.  This study reports that NHYA Class III symptoms (comfortable at rest but significant symptoms impairing function) were significantly associated the development of cardiac tamponade, which seems like it would be obvious, but can help in ambiguous cases. In my anecdotal experience, this is true, and relative hypotension, a narrow pulse pressure, and distended neck veins have been more sensitive for predicting tamponade.

NB: when trying to figure out if a pulsus paradoxus is abnormal, 20-30 mm Hg is considered high. But remember to take the pulse pressure into account! If the pulse pressure is narrow (like 110/90), then a pulsus of even 10 mm Hg might be abnormal and warrants immediate ultrasound.


What are the basics of starting hormone replacement therapy?

Hormone replacement therapy (HRT) has gotten a bad rap since the Women’s Health Initiative showed that there was a slight increase in the number of older women getting breast cancer and heart disease. However, fifteen years later, the consensus is that for women under the age of 60 who are experiencing menopausal symptoms, hormone therapy may relieve symptoms without a significant increase in risk of heart disease and cancer. It should be noted that no one thinks prescribing HRT for chronic conditions like osteoporosis is beneficial.

What women might benefit from HRT? 
Menopausal symptoms include hot flashes, joint aches/pains, and vaginal atrophy/dyspareunia. The evidence supports using HRT in women <60 years of age. The risk of adverse effects increases with age.

NB: alternative treatments for hot flashes include bedtime gabapentin and a variety of SSRI/SNRIs. Paroxetine and citalopram can be considered (paroxetine is the only SSRI/SNRI FDA approved for treatment of hot flashes, but should not be used in women taking tamoxifen due to cytochrome p450 metabolism). Bazedoxifene/conjugated estrogen is a SERM combination therapy with estrogen that has been shown to be effective but also carries increased risk of VTE. Black cohosh is NOT supported. For women with milder symptoms, simply adjusting the thermostat or changing clothes may be acceptable, or cognitive-behavioral therapy.

NB: women who only have vaginal atrophy and dyspareunia can use estrogen cream instead of taking systemic therapy like pills or patches.

What are the contraindications to prescribing HRT? 


  • history of breast cancer
  • unexplained vaginal bleeding
  • high-risk endometrial cancer
  • Cardiovascular disease risk (CVD risk) >10% by JACC calculator or known CAD
  • previous venous thromboembolic event
  • previous stroke or TIA
  • active liver disease, i.e. cirrhosis


  • hypertriglyceridemia
  • active gallbladder disease
  • hypercoagulable conditions like FVL, without known history of clot
  • migraine with aura is not a contraindication, but you might consider transdermal estrogen instead of oral (same for women with obesity)

What doses of estrogen should I prescribe? 

NB: estrogens come in creams, rings, vaginal formulations, patches, and pills. When thinking about dosing, remember to check for medication interactions as estrogen is metabolized by the liver. Women taking estrogen should also be counseled to avoid or limit alcohol intake for this reason.

  • Transdermal estrogen (the patch) can be started at 0.025 mg/day
  • Low-dose estrogen (pill) can be started at 0.5 mg/day

Check in after 1 month and titrate up for symptoms

Why the progestin, too? 

All women with a uterus should also receive progestin to prevent the increased risk of endometrial cancer from endometrial hyperplasia. (Women who have undergone hysterectomy do not need to take a progestin.) Oral micronized progesterone, which sometimes is called a “minipill.” Progesterone may cause nausea, bloating, and breakthrough bleeding that women can’t tolerate–in these cases, try continuous progesterone therapy, or consider an IUD or switching to a SERM/conjugated estrogen.


The many uses of desmopressin

Desmopressin is a vasopressin (antidiuretic hormone) analog that has some interesting and varied applications. It also comes as an oral, injectable, or intranasal formulation.

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  1. Treatment of bleeding disorders (von Willebrand disease and uremic bleeding are the most common, I think)
  2. Treatment of SIADH (it’s important to note that desmopressin doesn’t actually lower the sodium, it is given prophylactically or reactively to prevent overcorrection of sodium in hyponatremia. In fact, when desmopressin is given for DI, hyponatremia is a potential adverse effect!)
  3. Treatment of diabetes insipidus (ONLY for central DI, since in nephrogenic DI the kidneys are resistant to ADH)
  4. Treatment of nocturnal eneuresis (bed wetting)

What are the PCSK9 inhibitors?

There are two that are FDA approved: alirocumab (Praluent) and evolocumab (Repatha).

What is the biological basis of PCSK9 inhibitors?

LDL-R (for receptor) is found on the surface of hepatocytes. These receptors pick out LDL-c from the circulation, lowering the LDL level in the bloodstream. That’s a good thing!

PCSK9 is a protein that balances out the effect of LDL-R by binding to LDL-R and getting it degraded, thereby not allowing LDL-c to get reabsorbed. This means LDL levels may go up. (See this illustration and explanation) The PCSK9 inhibitors (mAbs) bind to PCSK9, which allows LDL-R to keep doing it’s job, and keep LDL-c levels low.

Are PCSK9 inhibitors effective? 

Yes. They are especially effective at reducing LDL levels when combined with statins. This review goes into exhaustive detail about trial data. However, no one knows for sure if they, like statins, reduce mortality from cardiovascular disease.

What caveats do I need to know about these drugs? 

  • Injected, not in pill form. This may be a barrier for some patients who either can’t (or won’t) inject themselves
  • These drugs are expensive! A year’s supply of evolocucamb is estimated to cost about $14,500. It’s unclear how much of that may be covered by insurance
  • The most common side effects are nasopharyngitis, congestion, and myalgia, but there are concerns about allergic reactions (it’s a monoclonal antibody) and cognitive impairment (subjective, but was reported in the phase III trials).
  • Patients with severe kidney and liver disease were excluded from studies, so if, for example, you have a patient with cirrhosis who wants to start one of these medications, talk with their hepatologist
  • Long-term studies on these drugs are lacking; there is a Cochrane review that reports that overall, follow up times for PCSK9 inhibitor studies have been short (26 months at the longest) and there have been few reported events.






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Should I be worried that this patient has a stroke mimic, and is it still safe to push tPA/thrombolytics?

When you’re called about a patient with new dysarthria, weakness, or altered mental status, stroke is one of the first and most dangerous things that probably comes to mind. Stroke, whether ischemic or hemorrhagic, can present in a variety of different ways depending on the particular insult–anything from tingling in a few fingers to full-on obtundation.

There are quite a few things that mimic stroke (see below), but you should always assume that an acute neurological deficit might be stroke unless there is a very convincing alternative explanation. Stroke is a clinical diagnosis, which means that you do NOT absolutely need brain imaging to prove it. In this “brain attack” study from Scotland, published in 2006, features associated with true strokes were: patient was well within the last week, an exact time of onset can be stated, obvious focal deficit is present, NIHSS score >10 (although some mimics did have high NIHSS scores as well). On the other hand, stroke was less likely in patients with a history of cognitive disturbance, loss of consciousness at onset of episode, witnessed seizure, lack of lateralizing deficits, and who were still able to walk. This study was observational and did have significant limitations–for example, not all patients got imaging and there was no gold standard defined for diagnosis of stroke–but these features square with what I’ve been taught.

Stroke mimics: 

  • TIA (although many high-risk TIAs are later found to be strokes)
  • Stroke recrusdescence (stroke-like symptoms in a patient with a history of stroke triggered by an acute cause)
  • Dementia or delirium (including toxic-metabolic encephalopathy)
  • Seizure
  • Space-occupying lesion (infection, tumor)
  • Syncope
  • Vestibular dysfunction
  • Migraine
  • Spinal cord lesion
  • Peripheral mononeuropathy

What if you suspect that your patient might actually have a stroke mimic, but you can’t get imaging in time (<3 hours) and they have concerning neurological symptoms and a high NIHSS? Should you withhold tPA? This meta-analysis from Greece suggests that patients who have a stroke mimic also have a lower risk of bleeding from tPA, so if there is any concern about an ischemic stroke, this study recommends giving tPA.

Can I give normal saline to a patient with hyponatremia who might have SIADH?

On the inpatient medical wards, not a month goes by without a case of a patient  with hyponatremia who gets 2 liters of normal saline, and when their sodium is rechecked, there’s no change or it’s even lower than it was before. Was giving normal saline the right thing to do?

If the patient has a good story for hypovolemia (has been taking twice the prescribed amount of diuretic, has not eaten in four days, etc.) then it makes sense that normal saline, with an osmolarity of 154 mEq/L, should help. It’s also a no-brainer that if a patient is grossly hypervolemic (has massive ascites, an acute heart failure exacerbation, etc.) then you should not give extra fluids, and diuresis will improve the sodium. The tricky one is “euvolemic hyponatremia,” and the most common cause of this is SIADH.

SIADH (syndrome of inappropriate ADH secretion) is a water problem. The body has too much water but continues to secrete ADH to retain free water (hence, inappropriate). One dictum you will hear is, “Don’t give normal saline to a patient with SIADH.” The argument is that in SIADH, salt handling is intact, so if you give a patient normal saline, all the sodium will be excreted but only half of the free water will be, which will make hyponatremia worse.

Is this true? Like so many things in medicine, it’s not an absolute rule. More important than whether someone has SIADH is how “saline responsive” they are likely to be. That is, will their sodium increase with normal saline or will it not?

How saline responsive might a patient be? The urine lytes are the key. 

  • urine osmolality: Uosm <100 is consistent with hypovolemia, whereas Uosm >200 is almost definitely not hypovolemia
  • urine Na: UNa <20 is considered consistent with hypovolemia (the body is trying to hold on on sodium to retain water) and >20 is considered fair game for a diagnosis of SIADH, although >50 seems to be the point of non-saline responsiveness. (paper here) UNa is unreliable in patients taking diuretics.
  • fractionated excretion of urea: FEurea >45% is considered to be non-saline responsive. (paper here)
UOsm <100, UNa<20
Malnutrition, beer potomania, surreptitious diuretic use, reset osmostat, hypovolemia already treated with normal saline
Uosm >300, UNa >40
SIADH, hypothyroidism, adrenal insufficiency

One review says that giving normal saline can unmask patients who are thought to be hypovolemic but actually have SIADH: “A rapid increase in FENa (>0.5% after 2 L of isotonic saline over 24 h), without correction of PNa, correlates with inappropriate ADH secretion.” This Hospitalist article recommends, “In salt depletion, plasma Na usually increases ≥5 mmol/L after 2 L saline infusion, which is not the case with SIADH.” So, a trial of normal saline can be diagnostic and therapeutic.  

The only patients you should NOT give normal saline to as a trial are those with an Na <120, as further driving down Na could put them at risk for seizures and coma. Patients with malnutrition or alcoholism are also at higher risk for overly rapid correction and osmotic demyelination, so use caution when repleting with fluids.