fludrocortisone for vasovagal syncope

vasovagal syncope is pretty common, but there are no documented effective treatments. Fludrocortisone has potential by improving venous return: its efficacy was evaluated in the Prevention of Syncope Trial 2 -- POST 2 trial (see syncope fludrocortisone jacc2016​ in dropbox, or Sheldon R. JACC 2016; 68: 1). details:

--210 patients (71% female, median age 30, BMI 24, HR 70 bpm, BP 112/70) with a mean of 15 syncopal episodes over 9 years

--randomized to fludrocortisone at the highest tolerated doses (from 0.05-0.2 mg/d, titrated over 2 weeks, with most achieving the 0.2  mg dose) vs placebo and followed for 1 year

--inclusion criteria: >13 yo, >2 lifetime syncopal episodes; exclusions: diabetes, hepatic disease BP>135/85, "significant comorbidities", or if when standing 5 minutes they had postural tachycardia of >30 bpm, or orthostatic hypotension of >20/10 mmHg.

--results

    --96 patients had at least 1 syncopal episode

    --overall there was a 31% marginally non-significant reduction in syncope in those on fludrocortisone [HR 0.69 (0.46-1.03), p=0.069]: 44.0% vs 60.5%. the most benefit was in those with systolic BP<110, BMI>20, and syncope frequency >7/yr

    ​--but, in multivariable model, fludrocortisone conferred a significant 37% decrease [HR 0.63 (0.42-0.94), p=0.024]

    --and, when analysis was restricted to being on the fludrocorisone after dose stabilization, there was an even more significant 49% decrease [HR 0.51 (0.28-0.89), p=0.019]: approx 60% vs 30% in those achieving the 0.2 mg dose

commentary:

--there are a myriad of etiologies for syncope to consider, especially cardiac or neurologic (all excluded in the above study). And the preferred treatment for the syncope is to treat the underlying condition.

--the above applies to those with classic "fainting" episodes: vasovagal syncope, which can happen even in patients with underlying cardiac or neuro morbidities, often triggered by stress, noxious stimuli, anxiety (including venipuncture, blood donation), prolonged standing or sitting, heat exposure, exertion, orthostasis, etc (and in older people can be associated with micturition, defecation, cough), and clinically associated with the typical prodrome of light-headedness, along with vagal symptoms of nausea, pallor, diaphoresis. symptoms typically gets better with lying down, though there can be some residual fatigue. and there can be brief episodes of myoclonic/involuntary esp limb movements. but there should be no post-ictal state

--fludrocortisone seemed pretty effective when at the 0.2 mg dose, and likely more effective than midodrine (a few small studies finding effectiveness but less impressively)

--fludrocortisone has been used effectively in those with autonomic failure and orthostatic hypotension, presumably from its increased renal sodium absorption and plasma volume expansion.

--In my experience, fludrocortisone is very well-tolerated in fragile patients with multiple comorbidities: I have prescribed fludrocortisone (sometimes with midodrine) very effectively in my reasonably large group of older patients with orthostatic hypotension, presumably from autonomic dysfunction (workup otherwise negative, or perhaps some diabetes, but often just from aging...). In this young group in the study above, without comorbidities and with just vasovagal syncope, there were no serious adverse events. and for those with orthostatic hypotension, of course, caffeine helps (1-3 cups of coffee/d, or 2-5 cups of tea). and, though I have not used them, NSAIDs can also help when used with fludrocortisone.

--so, bottom line: vasovagal syncope is common (overall about 20-35% of syncope causes), a pretty high % (up to 34% in one study) have no warning symptoms prior to syncope, and can be associated with bad accidents (eg, car crashes), so the above study may really prove to be clinically useful. One wonders if using the max dose of 0.3 mg might be even more useful, and I do have several elderly patients tolerating this dose well)