---
title: "Methylene blue versus hydroxocobalamin in septic shock: comparative real-world effectiveness"
id: "pubmed-42565679"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42565679"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42565679/"
doi: "10.1080/08998280.2026.2697704"
published_at: "2026-08-07T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Methylene blue versus hydroxocobalamin in septic shock: comparative real-world effectiveness
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42565679
- **Specialty:** [Critical Care](https://medichelpline.com/clinical-feed/critical-care.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42565679/)
- **DOI:** [10.1080/08998280.2026.2697704](https://doi.org/10.1080%2F08998280.2026.2697704)
- **Published At:** 2026-08-07T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- This retrospective cohort study compared adjunctive **methylene blue (MB)** and high-dose **hydroxocobalamin (HC)** in adults hospitalized with sepsis, severe sepsis, or septic shock using the TriNetX US electronic health record network covering 65 health systems. - The analysis included patients treated between 2016 and 2025 after excluding those with nitroprusside exposure, methemoglobinemia, cardiogenic shock, or who received neither therapy. - Propensity score matching (1:1) balanced 91 covariates to reduce confounding; the matched cohort comprised 732 patients (366 MB, 366 HC). - Early mortality and rates of acute kidney injury (AKI) were similar between the MB and HC groups according to the reported results. - **Hydroxocobalamin** was associated with higher initiation of **continuous renal replacement therapy (CRRT)** at 3–7 days and at 7 days after treatment (both P < 0.001). - Stroke events and prolonged vasopressor use were more frequent in the HC group during days 3–7 but these differences were not present by day 7. - Other secondary outcomes were reported as comparable between the two groups; specific secondary endpoints were not detailed in the abstract. - Authors conclude that MB and HC showed similar early mortality, but MB had advantages for lower CRRT use and fewer early strokes and prolonged vasopressor requirements. - The report emphasizes that these are observational, real-world findings and recommends prospective comparative studies to validate these results. - Keywords and focus areas include **septic shock**, adjunctive vasodilatory therapies, methylene blue, hydroxocobalamin, vasopressor requirements, and renal replacement therapy.
## Clinical Analysis & Structured Key Points
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Online ahead of print. # Methylene blue versus hydroxocobalamin for septic shock: a real-world comparative effectiveness study using TriNetX [Joshua Pei Le](https://pubmed.ncbi.nlm.nih.gov/?term=Pei+Le+J&cauthor_id=42565679)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42565679/#full-view-affiliation-1 "Medicine Institute, Allegheny Health Network, Pittsburgh, Pennsylvania, USA."), [Navneet Gupta](https://pubmed.ncbi.nlm.nih.gov/?term=Gupta+N&cauthor_id=42565679)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42565679/#full-view-affiliation-1 "Medicine Institute, Allegheny Health Network, Pittsburgh, Pennsylvania, USA."), [Sachin Singh](https://pubmed.ncbi.nlm.nih.gov/?term=Singh+S&cauthor_id=42565679)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42565679/#full-view-affiliation-2 "University of Pittsburgh, Pittsburgh, Pennsylvania, USA."), [Palwasha Zafar](https://pubmed.ncbi.nlm.nih.gov/?term=Zafar+P&cauthor_id=42565679)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42565679/#full-view-affiliation-1 "Medicine Institute, Allegheny Health Network, Pittsburgh, Pennsylvania, USA."), [Cameron McCraw](https://pubmed.ncbi.nlm.nih.gov/?term=McCraw+C&cauthor_id=42565679)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42565679/#full-view-affiliation-3 "Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico, USA."), [Rohail Gul](https://pubmed.ncbi.nlm.nih.gov/?term=Gul+R&cauthor_id=42565679)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42565679/#full-view-affiliation-4 "Department of Internal Medicine, Allegheny General Hospital, Pittsburgh, Pennsylvania, USA."), [Osama Ahmed](https://pubmed.ncbi.nlm.nih.gov/?term=Ahmed+O&cauthor_id=42565679)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42565679/#full-view-affiliation-5 "Department of Internal Medicine, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, Michigan, USA."), [Abu Baker Sheikh](https://pubmed.ncbi.nlm.nih.gov/?term=Baker+Sheikh+A&cauthor_id=42565679)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42565679/#full-view-affiliation-3 "Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico, USA."), [Dhaval Patel](https://pubmed.ncbi.nlm.nih.gov/?term=Patel+D&cauthor_id=42565679)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42565679/#full-view-affiliation-4 "Department of Internal Medicine, Allegheny General Hospital, Pittsburgh, Pennsylvania, USA."), [Adeel Nasrullah](https://pubmed.ncbi.nlm.nih.gov/?term=Nasrullah+A&cauthor_id=42565679)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42565679/#full-view-affiliation-6 "Division of Pulmonary and Critical Care, Allegheny Health Network, Pittsburgh, Pennsylvania, USA.") Affiliations Expand ### Affiliations * 1 Medicine Institute, Allegheny Health Network, Pittsburgh, Pennsylvania, USA. * 2 University of Pittsburgh, Pittsburgh, Pennsylvania, USA. * 3 Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico, USA. * 4 Department of Internal Medicine, Allegheny General Hospital, Pittsburgh, Pennsylvania, USA. * 5 Department of Internal Medicine, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, Michigan, USA. * 6 Division of Pulmonary and Critical Care, Allegheny Health Network, Pittsburgh, Pennsylvania, USA. * PMID: **42565679** * DOI: [ 10.1080/08998280.2026.2697704 ](https://doi.org/10.1080/08998280.2026.2697704) Item in Clipboard # Methylene blue versus hydroxocobalamin for septic shock: a real-world comparative effectiveness study using TriNetX Joshua Pei Le et al. Proc (Bayl Univ Med Cent). 2026. Show details Display options Display options Format Abstract PubMed PMID Proc (Bayl Univ Med Cent) Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Proc+%28Bayl+Univ+Med+Cent%29%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Proc+%28Bayl+Univ+Med+Cent%29%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42565679/) . 2026 Aug 7:1-6. doi: 10.1080/08998280.2026.2697704. Online ahead of print. ### Authors [Joshua Pei Le](https://pubmed.ncbi.nlm.nih.gov/?term=Pei+Le+J&cauthor_id=42565679)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42565679/#short-view-affiliation-1 "Medicine Institute, Allegheny Health Network, Pittsburgh, Pennsylvania, USA."), [Navneet Gupta](https://pubmed.ncbi.nlm.nih.gov/?term=Gupta+N&cauthor_id=42565679)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42565679/#short-view-affiliation-1 "Medicine Institute, Allegheny Health Network, Pittsburgh, Pennsylvania, USA."), [Sachin Singh](https://pubmed.ncbi.nlm.nih.gov/?term=Singh+S&cauthor_id=42565679)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42565679/#short-view-affiliation-2 "University of Pittsburgh, Pittsburgh, Pennsylvania, USA."), [Palwasha Zafar](https://pubmed.ncbi.nlm.nih.gov/?term=Zafar+P&cauthor_id=42565679)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42565679/#short-view-affiliation-1 "Medicine Institute, Allegheny Health Network, Pittsburgh, Pennsylvania, USA."), [Cameron McCraw](https://pubmed.ncbi.nlm.nih.gov/?term=McCraw+C&cauthor_id=42565679)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42565679/#short-view-affiliation-3 "Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico, USA."), [Rohail Gul](https://pubmed.ncbi.nlm.nih.gov/?term=Gul+R&cauthor_id=42565679)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42565679/#short-view-affiliation-4 "Department of Internal Medicine, Allegheny General Hospital, Pittsburgh, Pennsylvania, USA."), [Osama Ahmed](https://pubmed.ncbi.nlm.nih.gov/?term=Ahmed+O&cauthor_id=42565679)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42565679/#short-view-affiliation-5 "Department of Internal Medicine, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, Michigan, USA."), [Abu Baker Sheikh](https://pubmed.ncbi.nlm.nih.gov/?term=Baker+Sheikh+A&cauthor_id=42565679)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42565679/#short-view-affiliation-3 "Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico, USA."), [Dhaval Patel](https://pubmed.ncbi.nlm.nih.gov/?term=Patel+D&cauthor_id=42565679)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42565679/#short-view-affiliation-4 "Department of Internal Medicine, Allegheny General Hospital, Pittsburgh, Pennsylvania, USA."), [Adeel Nasrullah](https://pubmed.ncbi.nlm.nih.gov/?term=Nasrullah+A&cauthor_id=42565679)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42565679/#short-view-affiliation-6 "Division of Pulmonary and Critical Care, Allegheny Health Network, Pittsburgh, Pennsylvania, USA.") ### Affiliations * 1 Medicine Institute, Allegheny Health Network, Pittsburgh, Pennsylvania, USA. * 2 University of Pittsburgh, Pittsburgh, Pennsylvania, USA. * 3 Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico, USA. * 4 Department of Internal Medicine, Allegheny General Hospital, Pittsburgh, Pennsylvania, USA. * 5 Department of Internal Medicine, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, Michigan, USA. * 6 Division of Pulmonary and Critical Care, Allegheny Health Network, Pittsburgh, Pennsylvania, USA. * PMID: **42565679** * DOI: [ 10.1080/08998280.2026.2697704 ](https://doi.org/10.1080/08998280.2026.2697704) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Background:** Adjunctive therapies targeting pathologic vasodilation in septic shock are increasingly used when standard vasoactive strategies fail. Although methylene blue (MB) and high-dose hydroxocobalamin (HC) have shown potential hemodynamic benefits, comparative data in sepsis are lacking. We compared outcomes among septic patients treated with MB or HC using a large multicenter electronic health record network. **Methods:** We conducted a retrospective cohort study using the TriNetX US network (65 health systems). Adults hospitalized with sepsis, severe sepsis, or septic shock from 2016 to 2025 who received MB or HC were included. Patients with nitroprusside exposure, methemoglobinemia, cardiogenic shock, or neither therapy were excluded. Propensity score matching (1:1) balanced 91 covariates. **Results:** A total of 732 matched patients were analyzed (366 MB, 366 HC). Mortality and acute kidney injury rates were similar between groups. HC was associated with higher continuous renal replacement therapy initiation at 3-7 days and 7 days after treatment (both _P_ < 0.001). Stroke and prolonged vasopressor use were more frequent with HC during days 3-7 but not by day 7. Other secondary outcomes were comparable. **Conclusions:** MB and HC demonstrated similar early mortality, but MB was associated with lower continuous renal replacement therapy use and fewer early strokes and prolonged vasopressor requirements. These findings suggest MB may be the more favorable adjunctive therapy, although prospective comparative studies are needed to confirm these observational results. **Keywords:** Critical care; hydroxycobalamin; methylene blue; septic shock; vasopressor. 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