Droxidopa or Atomoxetine for Refractory Hypotension in Critically Ill Cardiothoracic Surgery Patients
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Design
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Single-center, retrospective, cohort study
N= 45
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Objective
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To evaluate the effects of droxidopa or atomoxetine on intravenous (IV) vasoactive agent discontinuation in cardiothoracic intensive care unit (ICU) patients with hypotension refractory to midodrine
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Study Groups
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Atomoxetine (n= 18)
Droxidopa (n= 17)
Both (n= 10)
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Inclusion Criteria
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Age 18 years or older, experienced hypotension refractory to midodrine therapy during the index encounter, continued to receive midodrine with the study medication, received at least 4 consecutive doses of the initially administered study medication
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Exclusion Criteria
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Patients experiencing clinical deterioration after study medication initiation requiring vasoactive agent addition or IV vasoactive agent dosage escalation for at least 12 hours
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Methods
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Patient data were collected from a single cardiothoracic intensive care unit (CTICU). The starting dose for droxidopa was 300 mg daily dose, and the median maximum daily dose was 1200 mg (interquartile range [IQR] 600, 1800 mg). Hypotension was defined as inadequate blood pressure or mean arterial pressure requiring the addition of any vasoactive agent.
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Duration
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Data collection: January 2017 to August 2022 |
Outcome Measures
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Primary: Time from study medication initiation to discontinuation of IV vasoactive agents |
Baseline Characteristics
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Atomoxetine (n= 18)
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Droxidopa (n= 17)
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Both (n= 10) |
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Age, years
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66 |
64 |
65 |
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Male
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55.6% |
70.6% |
60% |
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Midodrine total daily dose, mg
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45 |
60 |
15 |
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Index surgery
CABG and valve replacement/repair
Heart transplant
Thoracic surgery, general
Isolated valve replacement/repair
Lung transplant
Other
Isolated CABG
LVAD
Thoracic aortic surgery
None
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16.7%
16.7%
16.7%
11.1%
11.1%
11.1%
5.6%
5.6%
5.6%
0
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11.8%
17.6%
11.8%
0
35.3%
5.9%
0
11.8%
0
5.9%
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30%
30%
0
0
10%
0
0
20%
10%
0
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Other vasoactive agents
Corticosteroids
Fludrocortisone
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55.6%
11.1%
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58.8%
47.1%
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50%
40%
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Starting study dose, total daily dose, mg (IQR)
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10 (10, 20)
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300 (300, 300)
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10 (10, 20) atomoxetine
300 (300, 300) droxidopa
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Maximum study dose, total daily dose, mg (IQR)
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20 (10, 22.5) |
1200 (600, 1800) |
40 (20, 40) atomoxetine
300 (300, 1,800) droxidopa
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Study medication duration, days
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12 |
17 |
24.5 atomoxetine
15 droxidopa
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Results
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Endpoint
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Atomoxetine (n= 18)
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Droxidopa (n= 17)
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Both (n= 10)
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p-Value
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Time to IV vasopressor cessation, days
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21.9
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8
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13.9
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0.259
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ICU length of stay, days
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30 (14.8, 58.8)
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18 (8.5, 50.5)
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35 (24.3, 48.8)
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0.466 |
Hospital length of stay, days
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64.5 (37, 120.3) |
57 (42, 119.5) |
64.5 (52, 87.3) |
0.893 |
ICU readmission
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0 |
0 |
0 |
N/A |
Discharged from hospital on midodrine
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1 (5.6%) |
6 (35.3%) |
4 (40%) |
0.053 |
Discharged from hospital on study medication
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2 (11.1%) |
2 (11.8%) |
2 (20%) atomoxetine |
0.780 |
Alive at hospital discharge
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8 (44.4%) |
13 (76.5%) |
9 (90%) |
0.028 |
Adverse Events
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No stroke or heart attack events occurred in any treatment groups. The most common adverse event was new cardiac arrhythmias, which occurred in 3 patients receiving atomoxetine, 2 patients receiving droxidopa, and 1 patient receiving both, but these differences were not statistically significant.
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Study Author Conclusions
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Droxidopa and atomoxetine are oral vasoactive agents with potential mechanisms to facilitate IV vasopressor weaning for patients in the ICU with hypotension refractory to midodrine, but further prospective research is needed. |
InpharmD Researcher Critique
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This study had several limitations as it was a single-center retrospective study with a small population size, and critically ill patients have many confounding factors that could influence clinical outcomes. Additionally, treatment decisions were based on provider discretion and the study population involved cardiothoracic surgery patients, so findings may not be generalizable to non-surgical ICU patients.
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