Midodrine for the Treatment of Refractory Hypotension

Persistent hypotension in critically ill patients remains a major barrier to discharging patients from the intensive care unit (ICU). In our hospital, in patients with adequate tissue perfusion, midodrine has been observed to treat hypotension in order to wean continuous intravenous (IV) vasopressors and therefore promote ICU discharge. There are several possible etiologies of hypotension in the ICU. The most frequently seen causes include septic shock, hypovolemia, adrenal insufficiency, and idiosyncratic reactions from medications. For patients whose reversible causes of hypotension have been addressed but still require vasopressors, midodrine may prove to be a useful adjunctive medication to successfully increase blood pressure. No previous studies have examined the use of midodrine for the treatment of hypotension in an ICU setting. Therefore, we are investigating a new indication for midodrine as the treatment of hypotension in critically ill patients.

• Midodrine (Drug): Patients will be randomized to blinded to 20 mg of midodrine
• Placebo (Drug): Patients will be randomized to blinded placebo control

Primary outcomes

• Time Until Discontinuation of IV Vasopressors [From initiation of the study drug until discontinuation of IV vasopressors, assessed up to 400 hours]: Measured hours from initiation of midodrine until discontinuation of IV vasopressors

Secondary outcomes

• ICU Length of Stay [From initiation of midodrine until ICU discharge, assessed up to 45 days]: Measured number of days from initiation of midodrine until discharge ready from the ICU
• Hospital Length of Stay [From initiation of midodrine until hospital discharge, assessed up to 90 days]: Measured number of days from initiation of midodrine until discharged from hospital
• Rates of ICU Readmission [Up to 2 months after ICU discharge]: Number of patients initiated on midodrine that are readmitted back to ICU after being discharged to floor
• Rates of Hypertension, Bradycardia, and Hemodynamically Significant Tacharrythmias [From initiation of the study drug until discontinuation of the study drug, an average of 59 hours.]: Measured rates of hypertension (increase in systolic blood pressure to values higher than those set by the primary team or greater than 160 mmg), bradycardia (decrease in heart rate to values lower than those set by the primary team or less than 40 BPM), hemodynamically significant tachyarrythmias (greater than 20 mmhg decrease in systolic blood pressure).

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* At least 18 years of age
* Admitted to the SICU
* Requiring IV vasopressors at a rate of less than 100 mcg/min of phenylephrine, or 8 mcg/min of norepinephrine, or 60 mcg/min of metaraminol; and unable to wean for more than 24 hours while still maintaining desired blood pressure goal

Exclusion Criteria:

* Inadequate tissue oxygenation
* Liver failure
* Renal failure
* Hypovolemic shock or hypotension due to adrenal insufficiency
* Pregnancy
* Severe organic heart disease
* Urinary retention
* Pheochromocytoma
* Thyrotoxicosis
* Midodrine as pre-admission medication
* Any known allergies to midodrine
* Enrollment in another clinical trial

Participant flow

Outcome results

• Time Until Discontinuation of IV Vasopressors (Primary), Median, hours: Midodrine 23.5 (10.0 to 54.0); Placebo 22.5 (10.4 to 40.0)
• ICU Length of Stay (Secondary), Median, days: Midodrine 6.0 (5.0 to 8.0); Placebo 6.0 (4.0 to 8.0)
• Hospital Length of Stay (Secondary), Median, days: Midodrine 11.0 (9.0 to 21.0); Placebo 14.0 (9.0 to 22.0)
• Rates of ICU Readmission (Secondary), Count of participants, Participants: Midodrine 1; Placebo 3
• Rates of Hypertension, Bradycardia, and Hemodynamically Significant Tacharrythmias (Secondary), Count of participants, Participants: Midodrine 12; Placebo 3

Adverse events

Time frame: Adverse events were collected daily from medical records for the period of study drug administration, an average of 59 hours.

Serious adverse events by term

Other adverse events by term

• Results publication: Anstey MH, Wibrow B, Thevathasan T, Roberts B, Chhangani K, Ng PY, Levine A, DiBiasio A, Sarge T, Eikermann M. Midodrine as adjunctive support for treatment of refractory hypotension in the intensive care unit: a multicenter, randomized, placebo controlled trial (the MIDAS trial). BMC Anesthesiol. 2017 Mar 21;17(1):47. doi: 10.1186/s12871-017-0339-x. PMID 28327122

• Study Protocol and Statistical Analysis Plan (PDF, 2020-03-27)

• Matthias Eikermann, MD, PhD, Principal investigator, Beth Israel Deaconess Medical Center