Midodrine as Novel Treatment of Post-Cardiopulmonary Bypass Vasoplegic Syndrome

Study Overview
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Brief Summary
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Vasoplegic syndrome (VS) is a common and serious complication of cardiopulmonary bypass (CPB) procedures associated with a significant increase in morbidity and mortality. VS is defined as significant hypotension, high or normal cardiac outputs, low systemic vascular resistance, low cardiac filling pressures, and vasopressor requirement despite adequate fluid resuscitation following CPB. Extensive research has been performed regarding the pathophysiologic response to CPB and risk factors associated with VS. No safe and effective preventive strategy has gained widespread use. Supportive care with intravenous (IV) vasopressors has thus been adopted as standard of care. The use of these medications, while effective in the majority of patients, generally necessitates close monitoring in an intensive care unit (ICU) setting. These patients are subject to prolonged ICU and hospital stays, as well as the potential complications of prolonged use of central venous lines (CVL) required to give these medications. Recent studies suggest midodrine, a generic oral vasopressor, may accelerate the decline in IV vasopressor requirements in select ICU patients. At our institution, the addition of midodrine to IV vasopressors for the treatment of VS has been observed to be effective in reducing IV vasopressor duration. No literature exists describing the use of midodrine in this patient population. The goal of this study is to investigate the novel use of midodrine in CPB surgery complicated by VS. Ultimately, we hope to produce literature supporting its use that may be applied on a global scale to improve patient care

Official Title
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Midodrine as Novel Treatment of Post-Cardiopulmonary Bypass Vasoplegic Syndrome

Conditions
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Use of Midodrine in Post-cardiopulmonary Bypass Vasoplegic Syndrome

Intervention / Treatment
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* Drug: Midodrine
* Drug: Methylcellulose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: post-cardiopulmonary bypass surgery vasoplegic syndrome criteria MAP < 65mmHg Cardiac index>/=2.4 L/min/m^2, as determined by Swan- systemic vascular resistance index </=1400 dynes s/cm^5/m^2 adequate fluid resuscitation as determined by treating critical care team vasopressor requirement norepinephrine 0.05-0.5 mcg/kg/min WITH/WITHOUT vasopressin any dose Exclusion Criteria: allergy to midodrine pregnancy midodrine or cardiac glycoside as preadmission medication history of orthostatic hypotension, thyrotoxicosis, or pheochromocytoma severe organic heart disease (endocarditis, untreated congenital or rheumatic heart disease) liver failure/cirrhosis chronic kidney disease (GFR <30mL/hr) ventricular assist device implantation procedure, intra-aortic balloon pump placement, or heart transplantion unresolved post-operative acute kidney injury (rise in serum creatinine by >/= 0.5mg/dl from baseline inadequate tissue oxygenation (lactate > 2 mmol/L) inability to take oral medications

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Midodrine Arm<br>Patients will receive the drug Midodrine | Drug: Midodrine<br>* Oral vasoactive that is metabolized by the liver an peripheral tissues into desglymidodrine, an active metabolite. It produces arteriolar and venous constriction with a subsequent elevation in blood pressure.<br>|
| Placebo Comparator: Placebo Arm<br>Patients will receive placebo. | Drug: Methylcellulose<br>* Placebo will consist of inert methylcellulose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from procedure end until discontinuation of IV vasopressors |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of decline in IV vasopressor dose |  | 12 months | 
| Time until CVL removal |  | 12 mothns | 
| ICU length of stay |  | 12 months | 
| Hospital length of stay |  | 12 months | 
| Rate of major infections/complications |  | 12 months | 
| Rate of in-hospital and 30-day mortality |  | 12 months |