Early adjunctive methylene blue in patients with septic shock: a randomized controlled trial.

Ibarra-Estrada M, Kattan E, Aguilera-González P, Sandoval-Plascencia L, Rico-Jauregui U, Gómez-Partida CA, Ortiz-Macías IX, López-Pulgarín JA, Chávez-Peña Q, Mijangos-Méndez JC, Aguirre-Avalos G, Hernández G

Critical care (London, England)13 Mar 2023Cited by 69 (Europe PMC)

PMID36915146PMCIDPMC10010212DOI10.1186/s13054-023-04397-7PepBankPUB-36915146

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Summary

PurposeMethylene blue (MB) has been tested as a rescue therapy for patients with refractory septic shock. However, there is a lack of evidence on MB as an adjuvant therapy, its' optimal timing, dosing and safety profile. We aimed to assess whether early adjunctive MB can reduce time to vasopressor discontinuation in patients with septic shock.MethodsIn this single-center randomized controlled trial, we assigned patients with septic shock according to Sepsis-3 criteria to MB or placebo. Primary outcome was time to vasopressor discontinuation at 28 days. Secondary outcomes included vasopressor-free days at 28 days, days on mechanical ventilator, length of stay in ICU and hospital, and mortality at 28 days.ResultsAmong 91 randomized patients, forty-five were assigned to MB and 46 to placebo. The MB group had a shorter time to vasopressor discontinuation (69 h [IQR 59-83] vs 94 h [IQR 74-141]; p < 0.001), one more day of vasopressor-free days at day 28 (p = 0.008), a shorter ICU length of stay by 1.5 days (p = 0.039) and shorter hospital length of stay by 2.7 days (p = 0.027) compared to patients in the control group. Days on mechanical ventilator and mortality were similar. There were no serious adverse effects related to MB administration.ConclusionIn patients with septic shock, MB initiated within 24 h reduced time to vasopressor discontinuation and increased vasopressor-free days at 28 days. It also reduced length of stay in ICU and hospital without adverse effects. Our study supports further research regarding MB in larger randomized clinical trials. Trial registration ClinicalTrials.gov registration number NCT04446871 , June 25, 2020, retrospectively registered.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

7 results from studies that gave the peptide. 7 results from people.

01HumanRandomized controlled trialEfficacy outcome
In septic shock, methylene blue shortened time to vasopressor discontinuation versus placebo.
In plain wordsIn septic shock, methylene blue shortened time to stop vasopressors compared with placebo.
Peptide
Methylene blue
Outcome
DecreaseTime to vasopressor discontinuation
Study
n = 91
Comparator
Placebo
Analysis
Primary
Outcome group
Blood pressure · Cardiovascular
Studied dose
Dose not stated
Measurements
Time to vasopressor discontinuation
69 h
MB
Time to vasopressor discontinuation
94 h
placebo
Source sentences
Summary
The MB group had a shorter time to vasopressor discontinuation (69 h [IQR 59-83] vs 94 h [IQR 74-141]; p < 0.001), one more day of vasopressor-free days at day 28 (p = 0.008), a shorter ICU length of stay by 1.5 days (p = 0.039) and shorter hospital length of stay by 2.7 days (p = 0.027) compared to patients in the control group.
2 context sentences(design, population, supporting numbers)
Summary · context
In this single-center randomized controlled trial, we assigned patients with septic shock according to Sepsis-3 criteria to MB or placebo.
Summary · context
Among 91 randomized patients, forty-five were assigned to MB and 46 to placebo.
Show in the study text Report a problemFND-3691514601
02HumanRandomized controlled trialEfficacy outcome
In septic shock, methylene blue increased vasopressor-free days at day 28 versus placebo.
In plain wordsIn septic shock, methylene blue increased days without vasopressors compared with placebo.
Peptide
Methylene blue
Outcome
IncreaseVasopressor-free days
Study
n = 91
Comparator
Placebo
Analysis
Secondary
Outcome group
Blood pressure · Cardiovascular
Studied dose
Dose not stated
Measurements
Additional vasopressor-free days, MB versus placebo
1 days
MB versus placebo at day 28
Source sentences
Summary
The MB group had a shorter time to vasopressor discontinuation (69 h [IQR 59-83] vs 94 h [IQR 74-141]; p < 0.001), one more day of vasopressor-free days at day 28 (p = 0.008), a shorter ICU length of stay by 1.5 days (p = 0.039) and shorter hospital length of stay by 2.7 days (p = 0.027) compared to patients in the control group.
2 context sentences(design, population, supporting numbers)
Summary · context
In this single-center randomized controlled trial, we assigned patients with septic shock according to Sepsis-3 criteria to MB or placebo.
Summary · context
Among 91 randomized patients, forty-five were assigned to MB and 46 to placebo.
Show in the study text Report a problemFND-3691514602
03HumanRandomized controlled trialEfficacy outcome
In septic shock, methylene blue shortened ICU stay by 1.5 days versus placebo.
In plain wordsIn septic shock, methylene blue shortened ICU stay by 1.5 days compared with placebo.
Peptide
Methylene blue
Outcome
DecreaseICU length of stay
Study
n = 91
Comparator
Placebo
Analysis
Secondary
Outcome group
Intensive care and hospital outcomes · Whole body
Studied dose
Dose not stated
Measurements
ICU length of stay reduction, MB versus placebo
1.5 days
MB shorter than placebo
Source sentences
Summary
The MB group had a shorter time to vasopressor discontinuation (69 h [IQR 59-83] vs 94 h [IQR 74-141]; p < 0.001), one more day of vasopressor-free days at day 28 (p = 0.008), a shorter ICU length of stay by 1.5 days (p = 0.039) and shorter hospital length of stay by 2.7 days (p = 0.027) compared to patients in the control group.
2 context sentences(design, population, supporting numbers)
Summary · context
In this single-center randomized controlled trial, we assigned patients with septic shock according to Sepsis-3 criteria to MB or placebo.
Summary · context
Among 91 randomized patients, forty-five were assigned to MB and 46 to placebo.
Show in the study text Report a problemFND-3691514603
04HumanRandomized controlled trialEfficacy outcome
In septic shock, methylene blue shortened hospital stay by 2.7 days versus placebo.
In plain wordsIn septic shock, methylene blue shortened hospital stay by 2.7 days compared with placebo.
Peptide
Methylene blue
Outcome
DecreaseHospital length of stay
Study
n = 91
Comparator
Placebo
Analysis
Secondary
Outcome group
Intensive care and hospital outcomes · Whole body
Studied dose
Dose not stated
Measurements
Reduction in hospital length of stay
2.7 days
MB vs control
Source sentences
Summary
The MB group had a shorter time to vasopressor discontinuation (69 h [IQR 59-83] vs 94 h [IQR 74-141]; p < 0.001), one more day of vasopressor-free days at day 28 (p = 0.008), a shorter ICU length of stay by 1.5 days (p = 0.039) and shorter hospital length of stay by 2.7 days (p = 0.027) compared to patients in the control group.
2 context sentences(design, population, supporting numbers)
Summary · context
In this single-center randomized controlled trial, we assigned patients with septic shock according to Sepsis-3 criteria to MB or placebo.
Summary · context
Among 91 randomized patients, forty-five were assigned to MB and 46 to placebo.
Show in the study text Report a problemFND-3691514604
05HumanRandomized controlled trialEfficacy outcome
In septic shock, mechanical ventilation days were similar with methylene blue and placebo.
In plain wordsIn septic shock, ventilation days were similar with methylene blue and placebo.
Peptide
Methylene blue
Outcome
No significant changeDays on mechanical ventilation
Study
n = 91
Comparator
Placebo
Analysis
Secondary
Outcome group
Respiratory function · Respiratory
Studied dose
Dose not stated
Source sentences
Summary
Days on mechanical ventilator and mortality were similar.
2 context sentences(design, population, supporting numbers)
Summary · context
In this single-center randomized controlled trial, we assigned patients with septic shock according to Sepsis-3 criteria to MB or placebo.
Summary · context
Among 91 randomized patients, forty-five were assigned to MB and 46 to placebo.
Show in the study text Report a problemFND-3691514605
06HumanRandomized controlled trialSafety outcome
In septic shock, mortality was similar with methylene blue and placebo.
In plain wordsIn septic shock, death rates were similar with methylene blue and placebo.
Peptide
Methylene blue
Outcome
No significant changeMortality
Study
n = 91
Comparator
Placebo
Analysis
Secondary
Outcome group
Mortality · Whole body
Studied dose
Dose not stated
Source sentences
Summary
Days on mechanical ventilator and mortality were similar.
2 context sentences(design, population, supporting numbers)
Summary · context
In this single-center randomized controlled trial, we assigned patients with septic shock according to Sepsis-3 criteria to MB or placebo.
Summary · context
Among 91 randomized patients, forty-five were assigned to MB and 46 to placebo.
Show in the study text Report a problemFND-3691514606
07HumanRandomized controlled trialSafety outcome
In septic shock, no serious adverse effects were related to methylene blue administration.
In plain wordsIn septic shock, no serious adverse effects were related to methylene blue.
Peptide
Methylene blue
Outcome
Not applicableSerious adverse effects
Study
n = 45
Outcome group
Adverse events · Whole body
Studied dose
Dose not stated
Source sentences
Summary
There were no serious adverse effects related to MB administration.
2 context sentences(design, population, supporting numbers)
Summary · context
In this single-center randomized controlled trial, we assigned patients with septic shock according to Sepsis-3 criteria to MB or placebo.
Summary · context
Among 91 randomized patients, forty-five were assigned to MB and 46 to placebo.
Show in the study text Report a problemFND-3691514607

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials2

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

2 trials · 1 not yet recruiting · 1 completed · source ClinicalTrials.gov (opens in a new tab)

Not yet recruitingPhase 2/3NCT06306001

Intravenous Methylene Blue for Treating Refractory Neonatal Septic Shock

Post Graduate Institute of Medical Education and Research, Chandigarhn = 130est. 15 Mar 2024 to est. Feb 2027

Neonatal Sepsis · Shock, Septic

Trial page ClinicalTrials.govUpdated 12 Mar 2024

CompletedPhase 2/3NCT04446871

Methylene Blue in Early Septic Shock

Hospital Civil de Guadalajaran = 9117 Mar 2017 to 25 Jan 2021

Septic Shock

Trial page ClinicalTrials.govUpdated 4 Nov 2022

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
14 Oct 2026, 05:02 UTC
Study results updated
Version 1
14 Oct 2026, 01:46 UTC
First added · source update from Europe PMC

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