Optimization of prescribing in orthostatic hypotension

Contributed by:

Lesley Charles, MBChB, CCFP(COE)
(Click for bio)

Case

Mr. Howell is 81 and presenting with a six-month history of lightheadedness on standing up. His past medical history includes hypertension, dyslipidemia, diabetes, osteoporosis, diverticular disease and venous insufficiency. Current medications include bisoprolol 7.5 mg daily, furosemide 40 mg bid, atorvastatin 20 mg daily, metformin 1000 mg bid, vitamin D 1000 units daily, Calcium 500 mg daily, and risedronate 35 mg q weekly. Blood pressure measurement revealed a blood pressure of 142/88 lying, 134/80 sitting, 104/68 standing at one minute and 126/74 at three minutes.

Issue

Orthostatic hypotension (OH) and concomitant hypertension are common in elderly patients particularly the frail. Treatment of one may compound the other and it is a delicate balance. OH is a common medical condition in older adults that is associated with higher risk of falls, coronary heart disease, stroke and death.

Background

Orthostatic hypotension is defined as a drop in blood pressure (systolic ≥20 mmHg or diastolic ≥10 mmHg) from the supine to standing position within three minutes.¹ 20% of those aged over 65 years suffers from OH.² 

Evidence

OH may result if there is inadequate intravascular volume, autonomic nervous system dysfunction, decreased venous return, or inability to increase cardiac output in response to postural changes.³

The patient’s history should enquire about autonomic dysfunction: erectile dysfunction, urinary retention and urinary incontinence. It should also concentrate on timing, particularly with respect to meals. The patient’s physical exam should concentrate on cardiovascular assessment: his blood pressure and pulse rate should be measured in the supine position and repeated after he has been standing for three minutes.⁴ Newer research has shown that OH assessments collected within the first 30 seconds after standing were most closely associated with a self-reported history of orthostatic dizziness and informative as to risk of future fall, fracture, syncope and mortality.⁵ Additionally a neurological assessment for Parkinson’s and cerebellar ataxia should be done.6 Patient’s volume depletion should also be ruled out.³ Not all patients are symptomatic.

Diabetes is present in about 40% of patients, which is not unexpected given that this is the most common cause of peripheral and autonomic neuropathy. However, by far, the most common comorbidity among patients with OH is hypertension, which is present in approximately 70% of patients.⁷

Following identification of OH a cause should be sought. Examples to rule out are anemia, volume depletion, heart failure, sepsis, arrhythmia, seizure, Parkinson’s, multi system atrophy, primary autonomic failure, DM autonomic neuropathy and postprandial hypotension.⁸

The next step after identifying symptomatic OH is review of medications. Beta blockers, diuretics, calcium channel blockers, alpha-blockers among others should be reassessed.⁹ See Table 1. Medications should be decreased, discontinued or taken at night where possible. If OH persists, laboratory testing for underlying causes should include a complete blood count, lytes, creatinine, vitamin B12 level and morning cortisol.⁶

Table 1 Common medications that cause OH⁸

• Alcohol 
• Antiadrenergics 
• Antianginals 
• Antiarrhythmics 
• Anticholinergics 
• Antidepressants 
• Antihypertensives 
• Antiparkinsonian agents 
• Diuretics 
• Narcotics 
• Neuroleptics
• Sedatives

Treatment of acute OH should be directed at the underlying cause. Treatment of chronic OH involves non-pharmacological and pharmacological care. Education is first regarding maintaining adequate hydration and standing up slowly and in stages.¹⁰ Older patients should drink a minimum of 1.25 to 2.50 L of fluid per day to balance expected 24-hour urine losses (unless there is a medical condition to preclude higher volume fluid intake). Lower limb pressure gradients stockings and particularly abdominal binders can improve symptoms.¹¹ 

Pharmacological treatments should be reserved for cases resistant to non-pharmacological treatment and where the patient is at risk of falls. Sodium can be supplemented by adding extra salt to food or taking 0.5- to 1.0-g salt tablets. Fludrocortisone, a mineralocorticoid is first line but should be avoided in patients with concomitant hypertension or heart failure. It is started at 0.1 mg and titrated in 0.1 mg increments per week to effect, max 1mg or side effects of edema/weight gain. Hypokalemia, heart failure and hypertension must also be watched for.^8,12 Midodrine is a peripheral selective alpha-1-adrenergic agonist which significantly increases standing systolic blood pressure and improves symptoms. The last dose must not be taken after 18.00 to avoid supine hypertension. It is started at 2.5 mg tid and increased in 2.5 mg increments weekly to 10mg tid. It should be avoided in coronary heart disease. It can have a synergistic effect in combination with fludrocortisone. Pyridostigmine, a cholinesterase inhibitor that improves neurotransmission at acetylcholine-mediated neurons of the autonomic nervous system can also be used. It is given 30 mg bid to tid and titrated to 60mg tid. Pharmacotherapy must consider other co morbidities. 

Recommendation

The patient was counselled regarding adequate hydration, standing up slowly and in stages and pressure gradient stockings. Lasix was discontinued as it was being used for edema and replaced with the pressure gradient stockings. There was some improvement with only a 22mmHg drop in systolic blood pressure (SBP). Bisoprolol was then reduced to 5 mg and switched to qhs. This resulted in a reduction to 5mmHg SBP drop and elimination of symptoms. It is important to treat hypertension in patients with OH as there is evidence that uncontrolled hypertension worsens OH so both should be managed.¹³ Current research favors angiotensin receptor blockers and calcium channel blockers in the treatment of the hypertensive patient with OH.¹³

References

1. Freeman R, Wieling W, Axelrod F et al. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope. Auton Neurosci. 2011;161(1–2):46–8. 
2. Ooi WL, Barrett S, Hossain M, Kelley-Gagnon M, Lipsitz LA. Patterns of orthostatic blood pressure change and their clinical correlates in a frail, elderly population. JAMA. 1997;277(16):1299-1304.
3. Hollister AS. Orthostatic hypotension. Causes, evaluation, and management. West J Med. 1992;157(6):652-657.
4. Carlson JE. Assessment of orthostatic blood pressure: measurement technique and clinical applications. South Med J. 1999;92(2):167-173.
5. Juraschek S, Daya N, Rawlings A et al. Comparison of Early versus Late Orthostatic Hypotension Assessment Times in Middle-Age Adults. JAMA Intern Med. 2017 September 01; 177(9): 1316–1323. doi:10.1001/jamainternmed.2017.2937.
6. Freeman R. Clinical practice. Neurogenic orthostatic hypotension. N Engl J Med. 2008;358(6):615-624.
7. Shibao C, Grijalva CG, Raj SR, Biaggioni I, Griffin MR. Orthostatic hypotension-related hospitalizations in the United States. Am J Med 2007; 120:975–980.
8. Lanier J, Mote M & Clay E. Evaluation and Management of Orthostatic Hypotension. AFP. 2011;84(5):527-536.
9. Gupta V, Lipsitz LA. Orthostatic hypotension in the elderly: diagnosis and treatment. Am J Med. 2007;120(10):841-847.
10. Low PA, Singer W. Management of neurogenic orthostatic hypotension: an update. Lancet Neurol. 2008;7(5): 451-458.
11. Podoleanu C, Maggi R, Brignole M, et al. Lower limb and abdominal compression bandages prevent progressive orthostatic hypotension in elderly persons: a randomized single-blind controlled study. J Am Coll Cardiol. 2006;48(7):1425-1432.
12. Bradley WG. Neurology in Clinical Practice. 5th ed. Philadelphia, Pa.: Butterworth-Heinemann/Elsevier.
13. Biaggioni I. Orthostatic Hypotension in the Hypertensive Patient. Am J Hypertens. 2018 Nov 13;31(12):1255-1259. doi: 10.1093/ajh/hpy089. PMID: 29982276.