Levodopa‐induced orthostatic hypotension in parkinsonism: A red flag of autonomic failure

Abstract

Background and purposeLevodopa (LD) is the main treatment for parkinsonism, but its use may be limited by a potential hypotensive effect.MethodsWe evaluated the cardiovascular effect of LD performing head‐up tilt test (HUTT) before and 60 min after 100/25 mg LD/dopa‐decarboxylase inhibitor (pre‐LD vs. post‐LD HUTT) in 164 patients with parkinsonism on chronic LD treatment. Features predictive of LD‐induced orthostatic hypotension (OH) were assessed by logistic regression analysis.ResultsBasal supine blood pressure (BP) and heart rate (HR) decreased after LD. During post‐LD HUTT, BP drop and HR increase were significantly greater than at pre‐LD HUTT. Thirty‐eight percent of patients had OH at post‐LD HUTT compared to 22% of patients presenting OH at pre‐LD HUTT (p < 0.001). Risk factors for LD‐induced/worsened OH were pre‐LD OH (odds ratio [OR] = 36, 95% confidence interval [CI] = 10–131), absence of overshoot at Valsalva maneuver (OR = 9, 95% CI = 4–20), and pathological Valsalva ratio (OR = 6, 95% CI = 2–15).ConclusionsLD administration caused/worsened hypotension in both supine and orthostatic conditions. Patients with cardiovascular autonomic failure had a higher risk of developing LD‐induced OH. In clinical practice, LD‐induced OH could represent a red flag for cardiovascular autonomic failure.

Exploring Cardiovascular Autonomic Function before and after Chronic Deep Brain Stimulation in Parkinson's Disease

“…9 However, it's noteworthy that patients were assessed while on medication, including dopaminergic drugs that are known hypotensive agents with demonstrated capacity to cause or exacerbate OH. 3,19 We independently assessed the effect of LD, chronic stimulation and the combinations of the two treatments.…”

“…On the other hand, LD-induced OH serves as red flag for detecting autonomic failure in patients without overt OH, prompting the referral for standardized CRTs during the disease course and before surgical assessment. 3 Following DBS surgery, however, the incidence of LDinduced OH decreases perhaps because of an overall reduction of LEDD.…”

“… 9 However, it's noteworthy that patients were assessed while on medication, including dopaminergic drugs that are known hypotensive agents with demonstrated capacity to cause or exacerbate OH. 3 , 19 …”

“…On the other hand, LD‐induced OH serves as red flag for detecting autonomic failure in patients without overt OH, prompting the referral for standardized CRTs during the disease course and before surgical assessment. 3 …”

“…Recently, we documented that LD has a relevant hypotensive effect in both supine and orthostatic conditions and it induces and worsens OH in patients with parkinsonism. 3 Additionally, the direct influence of STN stimulation on cardiovascular system has been postulated due to its structural and functional connectivity to regions of the central autonomic network. 4 The medial STN limbic region receives several inputs from the prefrontal and anterior cingulate cortex, modulating autonomic responses.…”