Diagnosis and treatment of orthostatic hypotension

Abstract

Orthostatic hypotension is an unusually large decrease in blood pressure on standing that increases the risk of adverse outcomes even when asymptomatic. Improvements in haemodynamic profiling with continuous blood pressure measurements have uncovered four major subtypes: initial orthostatic hypotension, delayed blood pressure recovery, classic orthostatic hypotension, and delayed orthostatic hypotension. Clinical presentations are varied and range from cognitive slowing with hypotensive unawareness or unexplained falls to classic presyncope and syncope. Establishing whether symptoms are due to orthostatic hypotension requires careful history taking, a thorough physical examination, and supine and upright blood pressure measurements. Management and prognosis vary according to the underlying cause, with the main distinction being whether orthostatic hypotension is neurogenic or non-neurogenic. Neurogenic orthostatic hypotension might be the earliest clinical manifestation of Parkinson's disease or related synucleinopathies, and often coincides with supine hypertension. The emerging variety of clinical presentations advocates a stepwise, individualised, and primarily non-pharmacological approach to the management of orthostatic hypotension. Such an approach could include the cessation of blood pressure lowering drugs, adoption of lifestyle measures (eg, counterpressure manoeuvres), and treatment with pharmacological agents in selected cases.

Figure 1:. Steady-state circulatory adjustments to the upright posture

Orthostatic stress results in a shift of blood from the chest to the distensible venous capacitance system below the diaphragm. This venous pooling rapidly reduces central blood volume, and this reduction is compounded by increased capillary filtration of plasma secondary to the increased hydrostatic pressure in the legs. The reduction in central blood volume decreases cardiac filling and stroke volume (the volume pumped by each heartbeat). In healthy individuals, heart rate increases on standing, but not enough to compensate for the reduction in stroke volume, and so cardiac output (the product of stroke volume and heart rate) decreases. The key circulatory adjustments to the upright posture (large arrow) are arterial baroreflex-mediated constriction of arterioles and splanchnic venous capacitance vessels, with a subsequent increase in systemic vascular resistance that compensates for the decrease in cardiac output, therefore maintaining normotension (mean arterial pressure=cardiac output × systemic vascular resistance). This response is augmented by increased skeletal and abdominal muscle tone, which increases venous return through the skeletal muscle pump. In healthy individuals, mean blood pressure changes little, systolic blood pressure decreases only slightly, if at all, and diastolic blood pressure increases. Humoral activation, particularly increases in plasma renin activity and vasopressin release, also supports the circulation during standing for long durations. Cerebral autoregulation helps to maintain cerebral blood flow over various perfusion pressures. CBV=central blood volume.

Figure 2:. Four major subtypes of orthostatic hypotension

Schematics of continuous blood pressure curves showing normal recovery and the diagnostic criteria for initial orthostatic hypotension, delayed blood pressure recovery, classic orthostatic hypotension, and delayed orthostatic hypotension. Because around 95% of patients with orthostatic intolerance and unexplained syncope can be identified as having orthostatic hypotension by systolic blood pressure criteria alone, we display only the systolic blood pressure criteria. Individual blood pressure tracings were revised from ref . Note that a reduction in systolic blood pressure of ≥30 mm Hg is commonly used to define classic orthostatic hypotension in patients who have supine hypertension.^,,,

Figure 3:. Proposed flowchart for diagnostic investigation

We propose that diagnosis is based on clinical presentation and whether orthostatic hypotension is reproduced during bedside testing, and if so, whether it is associated with symptoms.^, If a patient presents with symptoms that could relate to orthostatic hypotension, a detailed medical history and physical examination should be taken: to establish the circumstances of the events; to identify accompanying symptoms of autonomic failure or signs of neurological conditions that can present with orthostatic hypotension; to identify comorbidities associated with orthostatic hypotension; and to identify any drugs that might induce orthostatic hypotension. If the medical history supports possible orthostatic hypotension, a bedside active standing test should be done. If this test identifies orthostatic hypotension and the patient has their typical symptoms, a definitive diagnosis of symptomatic orthostatic hypotension can be made. If the standing test reveals orthostatic hypotension but the patient is asymptomatic on that occasion, the diagnosis is still likely to be orthostatic hypotension, particularly in patients with neurodegenerative conditions associated with hypotensive unawareness. If orthostatic hypotension is found but the presenting symptoms are not entirely consistent with orthostatic hypotension, alternative causes of orthostatic intolerance, syncope, transient loss of consciousness, and falls should be considered. If bedside screening does not show orthostatic hypotension despite a typical presentation, repeated measurements after meals or exercise and at different times of day, or ambulatory blood pressure monitoring, could be useful. If the clinical evaluation is inconclusive, referral to a specialised centre could be considered. For all patients with orthostatic hypotension, it is important to identify the probable mechanism (neurogenic or non-neurogenic) and to consider autonomic function testing.^,,

Figure 4:. Physical countermanoeuvres to increase blood pressure in patients with orthostatic hypotension

Red lines show the effects of crossing the legs, placing a foot on a chair, squatting when standing, and crossing the legs while seated on beat-to-beat arterial pressure measured at the finger in a middle-aged patient with pure autonomic failure and incapacitating neurogenic classic orthostatic hypotension. The arrows indicate the duration of the manoeuvres. Note the increase in blood pressure and pulse pressure. Blood pressure tracings are adapted from ref .