Midodrine initiation criteria, dose titration, and adverse effects when administered to treat shock: A systematic review and semi-quantitative analysis

Puissant, Madeleine M.; Armstrong, Kaitlin J; Riker, Richard R; Haydar, Samir; Strout, Tania D; Smith, Kathryn E; Seder, David B; Gagnon, David J

doi:10.2478/jccm-2025-0007

Figures & Tables

Preferred reporting items for systematic reviews and meta-analyses (PRISMA) flow diagram

Patient characteristics and outcomes of included studies

Study	Subjects	Illness Severity^*	Shock Type	*Renal Function^ (SCr in mg/dL)**	Level of Care	ICU LOS, d Hospital LOS, d	ICU Mortality, n (%) Hospital Mortality, n (%)
Ahmed Ali 2022	TICU n=30 MID n=30 Control	NR	Spinal	MID first day SCr 0.72 ± 0.39 Control first day SCr 1.02 ± 0.59 p=0.005 MID last day SCr 1.04 ± 0.62 Control last day SCr 1.39 ± 1.27 p=0.276	ICU	ICU MID 5.13 ± 1.83 Control 9.03 ± 3.74 p<0.001 Hospital—NR	NR
Costa-Pinto 2022	MICU n=32 MID n=30 Control	APACHE III MID 49.5 (41, 56.25) Control 48.5 (38.25, 58) p=0.76	Septic; post-op	MID SCr 0.82 (0.66, 1.17) Control SCr 0.83 (0.64, 1.00) p=0.53	ICU	ICU MID 2.08 (1.06, 3.08) Control 2.46 (1.6, 3.89) p=0.14 Hospital MID 9 (5.75, 25.25) Control 7.5 (6, 14.5) p=0.92	ICU MID 1 (3.1%) Control 0 (0%) p>0.99 Hospital MID 3 (9.4%) Control 2 (6.7%) p>0.99
Davoudi-Monfared 2021	General ICU n=15 MID n=13 Control	APACHE II MID 17.06 ± 3.15 Control 16.15 ± 4.01 p=0.10 SOFA MID 7.5 ± 2.17 Control 8.3 ± 2.25 p=0.99	Septic	MID SCr 1.2 (0.9,1.7) Control SCr 1.3 (0.85, 1.95) p=0.95	ICU	ICU MID 8 (4, 15) Control 12 (4.5, 20) p=0.55 Hospital—NR	ICU—NR Hospital (28-d) MID 8 (55.4%) Control 9 (69.2%) p=0.32
Hussein El Adly 2022	General ICU n=30 MID n=30 Control	APACHE II^ MID 24 (13–39) Control 21.5 (7–39) SOFA^ MID 11.5 (13–39) Control 9 (3–20)	Septic	NR	ICU	ICU Control 11.9 ± 7 MID 11.5 ± 6.8 p=0.876 Hospital—NR	ICU Control 22 (73.3%) MID 13 (43.4%) p=0.018 Hospital—NR
Kim 2021	ICU to Floor n=19 MID n=132 Control	NR	NR	NR	Floor (post-ICU)	ICU MID 4.1 ± 3.8 Hospital MID 13.3 ± 12.2	ICU—NR Hospital Association between MID and mortality: OR 7.5 (1.3–44.5); p=0.03
Lal 2021	MICU n=17 MID n=15 Placebo	SOFA MID 6.8 ± 3.3 Placebo 6.3 ± 2.6 p=0.64	Septic	MID SCr 2.0 ± 0.9 Placebo SCr 1.4 ± 0.6 p=0.03	ICU	ICU MID 2.29 (1.5, 3.9) Placebo 2.45 (1.6, 3.2) p=0.36 Hospital MID 7 (3.5, 10.5) Placebo 7 (4, 12) p=0.41	NR
Levine 2013	SICU n=20 MID	APACHE II MID 18 ± 6	Post-op	MID SCr 0.74 ± 0.28	ICU	ICU time from MID initiation to discharge 4 (3, 6) Hospital time from MID initiation to discharge 8.5 (5, 16)	ICU 1 (5%) Hospital 1 (5%)
Macielak 2021	General ICU n=33 MID Floor n=11 MID	NR	NR	MID SCr 1.56 (0.85, 2.33)	Any	ICU 12 (5, 27) Hospital—NR	ICU—NR Hospital 13 (29.5%)
Poveromo 2016	MICU, SICU, CVICU, NICU, TICU n=94 MID n= 94 Control	APACHE IV MID 59 (44, 83) Control 82 (66, 93) p=0.02	Cardiogenic; Spinal; Post-op; Septic	NR	ICU	ICU MID 5.5 (3, 14.8) Control 5 (3, 10) p=0.29 Hospital MID 12 (8, 21.8) Control 9.5 (5, 16) p<0.01	ICU—NR Hospital MID 8 (8.5%) Control 21 (22.3%) P=0.01
Rizvi 2018	MICU, SICU, CTICU, TICU, NICU, CICU n=1119 MID n=456 no IVP n=663 yes IVP	APACHE III MID (no IVP) 76 (62, 93) MID (yes IVP) 78 (62, 96)	Cardiogenic; Spinal; Septic	SCr before MID: 1.96 SCr 24 h after MID: 1.94 p=0.3	ICU	ICU MID (no IVP) 4 (2, 9) MID (yes IVP) 6 (3, 14) Hospital MID (no IVP) 15 (8, 31) MID (yes IVP) 18 (8, 37)	ICU MID (no IVP) 35 (8%) MID (yes IVP) 74 (11%) Hospital MID (no IVP) 77 (17%) MID (yes IVP) 129 (19%)
Rizvi 2019	MICU, SICU, CTICU, TICU, NICU, CICU n=1010 MID	APACHE III MID 78 ± 25.6	Cardiogenic; Septic	NR	ICU	ICU MID continued at ICU discharge 8.5d ± 10.7 MID stopped at ICU discharge 10.6 ± 13.4 Hospital—NR	ICU—NR Hospital MID continued at ICU discharge HR 0.45 (0.30–0.68), p<0.001 1-year MID continued at ICU discharge HR 1.56 (1.23–1.99) p<0.001
Santer 2020	SICU, MICU n=66 MID n=66 Placebo	APACHE II MID 14.7 ± 5.5 Placebo 14.8 ± 5.9	Septic; Post-op; Other	MID SCr 0.8 (0.6, 1.0) Placebo SCr 0.9 (0.6, 1.3)	ICU	ICU MID 6 (5, 8) Placebo 6 (4, 8) p=0.46 Hospital MID 11 (9, 21) Placebo 14 (9, 22) p=0.45	NR
Tremblay 2020	CTICU n=74 MID n=74 Control	Euroscore II MID 1.94 (1, 2.91) Control 2.08 (1.31, 4) p=0.088	Vasoplegia after cardiac surgery	Acute kidney injury: MID 11 (14.9%) Control 10 (13.5%) p=0.462	ICU	ICU MID 4.13 (2.83, 6.08) Control 2.83 (2, 4.13) p=0.001 Hospital—NR	ICU—NR Hospital MID 10 (13.5%) Control 1 (1.4%) p=0.036
Whitson 2016	MICU n=135 MID n=140 Control	APACHE IV MID 82.6 ± 26.4 Control 84.3 ± 26.8 p=0.55	Septic	Change in SCr: MID 0.5 ± 1.3 Control 0.8 ± 1.6 p=0.048	ICU	ICU MID 7.5 ± 5.9 Control 9.4 ± 6.7 p=0.017 Hospital MID 21.9 ± 14.4 Control 24.2 ± 14.3 p=0.3	ICU MID 15 (11.1%) Control 26 (18.6%) p=0.08 Hospital MID 31 (23%) Control 32 (25.7%) p=0.6
Wood 2022	SICU, MICU n=19 MID n=42 Control	APACHE II MID 15 (12, 17) Control 18.5 (17, 25)	Septic, Post-op, Other	NR	ICU or step down unit	ICU MID 7 (6, 13) Control 6 (5, 6) p=0.0058 Hospital MID 26 (14, 51) Control 14 (10, 17) p=0.022	NR

Design of included studies

Study	Design	Country	Inclusion Criteria	Exclusion Criteria	Primary Outcome
Ahmed Ali 2022	RCT; blinding unclear; single center	Egypt	Spinal shock in the ICU; age ≥18 years; hemodynamically stable on low-dose NE (<8 mcg/min) monotherapy	Anuric or oliguric; CKD; allergy	Total duration of IVP
Costa-Pinto 2022	Pilot RCT; open-label; multicenter	Australia and New Zealand	Admitted to the ICU; age ≥18 years; clinically stable with hypotension for >24 hours requiring low-dose IVP (≤10 mcg/min of NE or ≤100 mcg/min of metaraminol) monotherapy	Lactate >4 mmol/L; renal failure; hemorrhagic, obstructive, or cardiogenic shock; liver failure; severe heart disease; acute brain pathology; pregnancy; thyrotoxicosis; bradycardia (HR <50 bpm), NPO or fed via jejunal tube; allergy	Time from randomization to discontinuation of IVP
Davoudi-Monfared 2021	Pilot RCT; open-label, single-center	Iran	Septic shock (MAP <65 mmHg and lactate ≥2 mg/dL despite fluid resuscitation) in the ICU; age ≥18 years; requiring IVP	≥24 hours since septic shock onset; CKD (GFR <30 mL/min); neurogenic bladder and urination disorders; PAD; scleroderma, bradycardia (HR <60 bpm); MID PTA	Lactate clearance at 4, 24 and 48 hours
Hussein El Adly 2022	RCT; open label; single-center	Egypt	Septic shock in the ICU; age 18–80 years; hypotension (SBP <90 mmHg and MAP <65 mmHg) for >24 hours requiring IVP	Hypovolemic shock; HF (EF <30%); CKD (SCr >2 mg/dL); thyrotoxicosis; pheochromocytoma; CMO; DDI (MAOIs, alpha-1 blockers, TCAs); orthostatic hypotension; bradycardia (HR <50 bpm); MID PTA; NPO; allergy	Total duration of IVP; duration of IVP wean; cumulative dose of IVP
Kim 2021	Retrospective cohort study; single center	USA	Patients admitted to ICU from ED then transferred to floor	ICU mortality; admitted to ICU due to diabetic ketoacidosis or tissue plasminogen activator administration	ICU readmission; rapid response team activation; hospital LOS; in-hospital mortality; 30 day hospital readmission
Lal 2021	Pilot RCT; double-blinded; multicenter	USA; United Arab Emirates	Septic shock (MAP <70 mmHg and SBP <130 mmHg despite antibiotics and fluids 30 mL/kg) in the ICU; age ≥18 years	ACS or EF <30%; GIB; obstructive or cardiogenic shock; lactate > 4 mmol/L; acute intraabdominal process; transferred from outside facility; cardiac arrest; child-bearing age; thyrotoxicosis; pheochromocytoma; PAD or ischemic bowel; CMO; DDI (MAOIs); bradycardia (HR <40 bpm); MID PTA; NPO; allergy	Duration of IVP in the first 24 hours
Levine 2013	Prospective cohort study; single-center	USA	Admitted to the SICU; age ≥18 years; clinically stable (otherwise discharge ready) with hypotension for >24 hours requiring low-dose IVP (phenylephrine <150 mcg/min or NE <8 mcg/min)	Hypovolemic shock; adrenal insufficiency; <3 doses of MID; orthostatic hypotension; MID PTA	Time from MID initiation to discontinuation of IVP; Change in IVP rate before/after MID initiation
Macielak 2021	Retrospective cohort study; single center	USA	Age ≥18 years; receiving MID dosed “four times daily” or “every six hours”	Incarcerated; pregnancy	Characterization of patients receiving MID “four times daily” or “every six hours”
Poveromo 2016	Retrospective cohort study; single-center	USA	Admitted to the ICU with diagnosis related to cardiovascular, trauma, or sepsis; age ≥18 years; requiring ≥1 IVP	ICU mortality within 24 hours; duration of IVP <2 hours; <3 doses of MID; MID for indication other than IVP weaning	Time from MID initiation to discontinuation of IVP
Rizvi 2018	Retrospective case series; single-center	USA	Admitted to the ICU; age ≥18 years; initiated on MID	MID PTA	Cumulative dose of IVP at MID initiation and 24 hours; MAP at MID initiation and 24 hours
Rizvi 2019	Retrospective case series; single-center	USA	Admitted to the ICU; age ≥18 years; initiated on MID	ICU mortality; MID PTA	Incidence of MID continuation after ICU discharge
Santer 2020	RCT; double-blinded; multicenter	USA, Australia	Admitted to the ICU or step-down unit; age ≥18 years; clinically stable with hypotension for >24 hours requiring low-dose (<100 mcg/min phenylephrine, <8 mcg/min of NE, or <60 mcg/min of metaraminol) IVP monotherapy	Clinical evidence of inadequate tissue oxygenation; adrenal insufficiency; liver failure; CKD (SCr >2 mg/dL); HF (EF <30%); acute urinary retention; pheochromocytoma; thyrotoxicosis; pregnancy; bradycardia (HR <50 bpm); MID PTA; NPO; allergy	Time from randomization to discontinuation of IVP
Tremblay 2020	Retrospective propensity matched cohort study; single center	Canada	Admitted to the ICU following cardiac surgery requiring CPB; age ≥18 years; hypotension requiring IVP for >12 hours post-surgery	MID before surgery; mechanical circulatory support before surgery; emergency surgery; transplantation; cirrhosis	Number of days alive and free from ICU at 30 days
Whitson 2016	Retrospective cohort study; single-center	USA	Septic shock in the ICU; clinically stable with hypotension for >24 hours requiring IVP	NR	Total duration of IVP; ICU LOS
Wood 2022	Retrospective case-control; single center	Australia	Admitted to ICU or step-down unit; age ≥18; clinically stable with hypotension for >24 hours requiring low-dose (<8 mcg/min of NE or <60 mcg/min of metaraminol) IVP monotherapy	Clinical evidence of inadequate tissue oxygenation; adrenal insufficiency; liver failure; CKD (SCr >2 mg/dL); HF (EF <30%); acute urinary retention; pheochromocytoma; thyrotoxicosis; pregnancy; bradycardia (HR <50 bpm); NPO; allergy	Time from intervention to discontinuation of IVP

Midodrine Use

Study	Protocol	Protocol details	Initial Dose/Frequency	Max Dose/Frequency	Titration vs. Fixed Dose	Start Before, With or After Pressors	Duration of Midodrine (d)	Route of Admin	Continued at ICU Discharge n (%)	Continued at Hospital Discharge n (%)
Ahmed Ali 2022	Yes	4 doses of MID, then IVP weaning initiated	10 mg every 8 h	10 mg every 8 h	Fixed	After	NR	PO	No	No
Costa-Pinto 2022	Yes	MID administered until off IVP for at least 24 h Wean: 7.5 mg every 8 h for 24 h, then 5 mg every 8 h for 24 h, then DC	10 mg every 8 h	10 mg every 8 h	Fixed	After	NR	NR	Yes	NR
Davoudi-Monfared 2021	Yes	Randomly assigned to adjunctive MID to facilitate IVP wean	10 mg TID	10 mg TID	Fixed	With	Up to 5 d	If conscious, PO; if not, via NGT	NR	NR
Hussein El Adly 2022	Yes	Randomly assigned to adjunctive midodrine to facilitate IVP wean	10 mg TID	10 mg TID	Fixed	After	NR	PO tablet or crushed (via Ryle)	NR	NR
Kim 2021	No	No protocol	NR	NR	NR	NR	NR	NR	19 (12.6)	NR
Lal 2021	Yes	If septic shock without response to antibiotics and fluids, randomized to MID or placebo	10 mg every 8 h	10 mg every 8 h	Fixed	After or monotherapy	3 doses	PO	No	No
Levine 2013	No	No protocol	NR	20 mg TID	Titration; no details	After	4 (3–7)	PO	NR	NR
Macielak 2021	No	No protocol	NR	20 mg every 6 h	Titration	After n=23 (52.3%) Continued from home n=18 (40.9%) Monotherapy n=3 (6.8%)	NR	NR	Yes	Yes
Poveromo 2016	No	No protocol	NR	10 mg every 4 h	Titration	After	4.4 (3.2, 7.8)	NR	NR	NR
Rizvi 2018	No	No protocol	NR	30 mg every 8 h	Titration	After (59%); Before (41%)	NR	PO	NR	NR
Rizvi 2019	No	No protocol	NR	40 mg every 8 h	Titration	After: 58% Before or monotherapy: 42%	11.8 ± 20.9	PO	672 (67)	311 (34)
Santer 2020	Yes	Randomized to MID or placebo until ICU discharge. DC’ed with stable at goal blood pressure at discretion of clinical team per a standardized weaning protocol (decrease dose every 1–2 d from 20 mg to 10 mg every 8 h, then 5 mg every 8 h, then DC)	20 mg every 8 h	20 mg every 8 h	Fixed	After at least 24 h of IVP	1.77 (0.98, 2.97)	PO	NR	No
Tremblay 2020	No	No protocol	10 mg TID (for n=61, 82.4%)	Only n=2 with doses >10 mg; All TID	Majority fixed. Progressive tapering for n=19 (26%)	After at least 12 h of IVP	1.67 (0.96, 3.04)	NR	17 (23)	NR
Whitson 2016	No	No protocol	10 mg every 8 h	40 mg every 8 h	Titration	After at least 24 h of IVP	6.15 For patients who were not discharged on MID (n=117, 86.7%)	NR	Yes	18 (13.3)
Wood 2022	No	Started on MID at discretion of treatment team. If enrolled, MID administered until at least 24 h after DC of IVP	20 mg every 8 h	20 mg every 8 h	Fixed	After	NR	PO	NR	NR

Intravenous Vasopressor Use

Study	Percent of patients on IVP at MID initiation, n (%)	Number of IVP at MID initiation	NEE at MID initiation	Time to IVP discontinuation (h)	Need to restart IVP, n (%)
Ahmed Ali 2022	MID 30 (100) Control 30 (100)	1 (NE only)	NR; inclusion criteria <8 mcg/min NE	MID 79.2 ± 31.7 Control 166.3 ± 55.7 p<0.001	NR
Costa-Pinto 2022	MID 32 (100) Control 30 (100)	1 (NE or metaraminol)	NR; inclusion criteria <10 mcg/min NE or <100 mcg/min metaraminol	MID 16.5 (7.2, 27.5) Control 19 (12.2, 38.5) p=0.32	MID 6 (18.8) Control 4 (13.3) p=0.73
Davoudi-Monfared 2021	MID 15 (100) Control 13 (100)	1 (NE only)	Midodrine median NEE 0.14 mcg/kg/min Control median NEE 0.13 mcg/kg/min	MID 96 (48, 192) Control 120 (72, 264) p=0.36	MID 4 (26.7) Control 5 (38.5) p=0.39
Hussein El Adly 2022	MID 30 (100) Control 30 (100)	1 (NE only)	Midodrine median NEE 0.08, range 0.04–0.21 mcg/kg/min Control median NEE 0.11, range 0.02–0.35 mcg/kg/min	MID 26 (14, 106) Control 78.5 (32, 280) p<0.001	MID 3 (10%) Control 3 (10%)
Kim 2021	All 73 (48.3)	NR	NR	NR	NR
Lal 2021	MID 11 (52.4) Placebo 10 (47.6)	NR	NR	Requiring IVP at 12 h: MID 41.2% vs Control 60% p=0.29	NR
Levine 2013	MID 20 (100)	1 (NE or PE)	Midodrine mean NEE 4.1 mcg/min	MID 17 (7, 38.4)	NR
Macielak 2021	MID 23 (52.3)	NR	Midodrine mean NEE 0.1 mcg/kg/min	NR	NR
Poveromo 2016	MID 94 (100) Control 94 (100)	MID: 1 (40.4%), 2 (41.5%), 3+ (18.1%) Control: 1 (62.8%), 2 (24.4%), 3+ (12.8%)	Midodrine median NEE 0.05 (0.03, 0.08) mcg/kg/min Control median NEE 0.05 (0.03, 0.08) mcg/kg/min	MID 28.8 (12, 67.2) Control: NR	MID 42 (44.7) Control: NR
Rizvi 2018	MID 663 (59.0)	NR	Midodrine median NEE 0.24 mcg/kg/min	Requiring IVP at 24 h: 48%	NR
Rizvi 2019	MID 587 (58.1)	NR	Midodrine median NEE 0.19 mcg/kg/min	NR	NR
Santer 2020	MID 66 (100) Placebo 66 (100)	1 (NE, PE, or metaraminol)	Midodrine median NEE 0.03 (0.02, 0.06) mcg/kg/min Control median NEE 0.03 (0.02, 0.06) mcg/kg/min	MID 23.5 (10.4, 44) Control 22.5 (10.4, 40) p=0.62	NR
Tremblay 2020	MID 74 (100) Control 74 (100)	MID: 1 (85.1%), 2 (13.5%), 3 (1.4%) Control: NR	All patients median NEE 0.05 (0.03, 0.09) mcg/kg/min	MID 19 (4, 44)	MID 16 (21.6)
Whitson 2016	MID 135 (100) Control 140 (100)	1 (NE or PE)	Midodrine mean NEE 0.09 mcg/kg/min Control mean NEE NR	MID 69.6 ± NR Control 91.2 ± NR p<0.001	MID 7 (5.2) Control 21 (15) p=0.007
Wood 2022	MID 19 (100) Control 42 (100)	1 (NE or metaraminol)	Midodrine median NEE 0.05 mcg/kg/min Control median NEE 0.08 mcg/kg/min	MID 26 (22, 36) Control 24 (17, 93) p=0.511	NR

Quality appraisal for included studies by study design

Randomized controlled trials
Study	Randomization	Allocation concealment	Groups similar at baseline	Participants blinded	Staff delivering treatment blinded	Groups treated the same except intervention	Blinded outcomes assessors	Standardized outcomes measurement	Complete follow-up or differences described, analyzed	Participants analyzed in randomization group	Appropriate statistics	Design appropriate and deviations from standard accounted for
Ahmed Ali 2022	Yes	No	No	Unclear	No	Yes	Unclear	Yes	Yes	Yes	Yes	Yes
Costa-Pinto 2022	Yes	Yes	Yes	Unclear	No	Yes	Unclear	Yes	Yes	Yes	Yes	Yes
Davoudi-Monfared 2021	Yes	Unclear	Yes	Unclear	Unclear	Yes	Unclear	Yes	Yes	Yes	Yes	Yes
Hussein El Adly 2022	Yes	Yes	Yes	No	No	Yes	Unclear	Yes	Yes	Yes	Yes	Yes
Lal 2021	Yes	Yes	No	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Santer 2020	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes

Reported Side Effects

Study	Bradycardia Definition	Bradycardia Incidence, n (%)	Heart Rate Change (bpm)	Bradycardia Interventions	Bowel Ischemia n (%)	Peripheral Ischemia n (%)	Cerebral Ischemia n (%)	Allergy n (%)
Ahmed Ali 2022	No definition	NA	MID Day 1: 117 ± 14.2, MID Mid-study: 103.77 ± 16.65, MID Last Day: 79 ± 16.9 Control Day 1: 120.43 ± 14.64 Control Mid-study: 97.1 ± 16.65 Control Last Day: 96.73 ± 18.75	NA	NR	NR	NR	NR
Costa-Pinto 2022	Bradycardia: ≤50 bpm; Severe bradycardia: <40 bpm	Bradycardia within 24 h: MID 10 (31.2) Control 2 (6.7) p=0.02	Baseline MID HR: 76 (70, 85) Baseline Control HR: 77.5 (65.5, 85) p=0.61 MID HR over 24 h: 69 (62, 82) Control HR over 24 h: 74 (67, 83) p=0.21	None; episodes of bradycardia, except one, were transient and deemed clinically insignificant	NR	NR	NR	NO
Davoudi-Monfared 2021	<60 bpm	NO	NR	NA	NR	NR	NR	NR
Hussein El Adly 2022	<50 bpm	NR	NR	NA	NR	NR	NR	NR
Kim 2021	NR	NR	NR	NA	NR	NR	NR	NR
Lal 2021	<40 bpm and symptomatic	NO	NR	NA	NO	NO	NO	NO
Levine 2013	No definition	NR	Before MID HR 82 ± 13 After MID HR 81 ± 15 p=0.66	NA	NR	NR	NR	NR
Macielak 2021	<50 bpm	NO	NR	NA	1 (2.3)	NO	NR	NR
Poveromo 2016	<60 bpm for two consecutive readings	MID: 12 (12.8) Control: NR	NR	NR	NR	NR	NR	NR
Rizvi 2018	≤50 bpm; ≤40 bpm	≤50 bpm: 172 (15.4) ≤40 bpm: 100 (9) Lowest HR: 39 (33, 44) bpm	NR	None	2 (0.18)	NR	NO	NR
Rizvi 2019	NR	NR	NR	NA	NR	NR	NR	NR
Santer 2020	<40 bpm or ≥20% decrease from a pre-specified goal	MID: 5 (7.6) Control: 0 (0) p=0.02	NR	NR	NR	NR	NR	NR
Tremblay 2020	No definition	NR	NR	NA	2 (2.7)	NR	NR	NR
Whitson 2016	No definition	MID: 1 (0.7) Control: NO	NR	MID discontinued and bradycardia resolved.	NR	NR	NR	NR
Wood 2022	<40 bpm or ≥20% decrease from a pre-specified goal	MID: 4 (22) Control: 1 (2.4) p=0.025	No significant change	NR	NR	NR	NR	NR

Where midodrine may be consider and avoided

Some Experience – Likely Safe	Limited Experience – Use Caution	No Experience – Avoid Use	Contraindications for Use
Orthostatic hypotension	Vasopressor sparing	Cardiogenic shock	Pheochromocytoma
Hemodialysis hypotension	Mixed shock	Cerebral vasospasm	Thyrotoxicosis
Septic Shock	Renal failure	Unknown enteral absorption	Urinary retention
Vasopressor weaning	Lactate clearance	Mechanical circulatory support
Hepatorenal syndrome	Bradycardia	Daily dose >120 mg
Fixed dosing regimen	Dosing every four hours
	Hepatic impairment
	Titrated dosing regimen

Midodrine initiation criteria, dose titration, and adverse effects when administered to treat shock: A systematic review and semi-quantitative analysis

Figures & Tables

Fig. 1.

Patient characteristics and outcomes of included studies

Design of included studies

Midodrine Use

Intravenous Vasopressor Use

Quality appraisal for included studies by study design

Reported Side Effects

Where midodrine may be consider and avoided

Paradigm

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