All-cause mortality

Method

Death from any cause, ascertained over the follow-up horizon each trial states, pooled as a risk ratio, odds ratio or hazard ratio. The horizon is recorded on the edge and is not optional: 'short-term', ICU-period, hospital-period and longest-follow-up mortality are different denominators of person-time and their pooled estimates are not comparable. Reported throughout the trial literature as overall mortality or total mortality.

The method is part of the endpoint identity. Studies measuring the same quantity by a different method are held as separate endpoints.

Notes

Named in the trial literature as OVERALL MORTALITY as often as all-cause mortality, and that synonym is carried in `measurement` deliberately while "overall survival" is NOT. Survival is the same event at inverted polarity — a review reporting improved overall survival is reporting reduced mortality — so admitting that phrase would invite an extractor to record `increases` on a mortality node from a sentence describing a benefit. The two words differ by one and the error they produce is the worst this graph can make. Added 2026-08-26 after "overall mortality" tied against CAT:outcome/pooled-exercise-performance-composite, whose label begins with the same generic word and split the span one token each way. Cardiovascular mortality is cause-specific, adjudicated, and usually drawn from population cohorts over years; this endpoint is any-cause and frequently over days in critically ill patients. PMID 22493407 found a cardiovascular-death signal that vanished on sensitivity analysis while all-cause mortality stayed flat — merging the two would have preserved a signal that is not there. Also distinct from death before hospital discharge in preterm infants: same word 'death', but a fixed neonatal window standing in a competing-risk relationship with bronchopulmonary dysplasia, which this node's pooling assumptions do not model.

Findings

6 findings from 4 compounds, strongest first.

• methylene blue — decreases

  AWell establishedGrade A, Well established. Replicated human trial evidence, consistent direction.Finding

  “We found that MB may reduce short-term mortality in patients with septic shock (RR 0.66 [95% CI, 0.47–0.94]), based on low-certainty evidence, downgraded for imprecision and risk of bias among the included trials.”

  Study

  meta-analysis

  Participants

  260

  Population

  critically ill adults with septic shock; short-term mortality horizon, longest reported up to 60 d or in-hospital

  Effect 0.66 risk ratio, 95% CI 0.47 to 0.94

  Methylene Blue in Septic Shock: A Systematic Review and Meta-Analysis.2024PMID:38904978

• melatonin — no detected effect on

  AWell establishedGrade A, Well established. Replicated human trial evidence, consistent direction.FindingNull result

  “We found no significant difference in mortality between patients receiving melatonin and those receiving placebo (RR, 0.90; 95% CI: 0.77–1.06; I2 = 0%).”

  Study

  meta-analysis

  Participants

  2,350

  Population

  Adult ICU patients; secondary endpoint, 10 trials, longest reported follow-up

  Effect 0.9 risk ratio, 95% CI 0.77 to 1.06

  Prophylactic melatonin for delirium in critically ill patients: A systematic review and meta-analysis with trial sequential analysis.2022PMID:36316858

• coenzyme Q10 — no detected effect on

  AWell establishedGrade A, Well established. Replicated human trial evidence, consistent direction.FindingNull result

  “Moreover, no significant difference was observed in the 28-day mortality rate between the two groups (2 in the CoQ10 group vs. 3 in the placebo group) (P = 0.99).”

  Study

  RCT

  Participants

  52

  Duration

  10 days

  Dose

  100 mg three times a day after meals, total 300 mg/day

  Population

  Adults aged 18-65 with 20-60% total body surface area burns admitted to a burn ICU in Isfahan, Iran, all receiving routine burn care and the unit's standard vitamin, selenium, zinc and B-complex supplementation in both arms; secondary outcome.

  Coenzyme Q10 supplementation in burn patients: a double-blind placebo-controlled randomized clinical trial.2024PMID:38431600

• L-glutamine — no detected effect on

  AWell establishedGrade A, Well established. Replicated human trial evidence, consistent direction.FindingNull resultreplicated ×2

  “The mortality rate was insignificantly different between glutamine group and placebo group (22.7% vs. 36.4% respectively, p-value = 0.509) as presented in Table 4 and.”

  Study

  RCT

  Participants

  44

  Dose

  20 gm/100 mL intravenous N(2)-L-Alanyl-L-Glutamine Dipeptide (Dipeptiven) on the day 1-2 regimen every 2 weeks

  Population

  Stage II and III colon cancer patients, both arms receiving identical mFOLFOX-6 chemotherapy, randomised to intravenous L-alanyl L-glutamine dipeptide or placebo; mortality over the trial follow-up

  Ameliorative Potential of L-Alanyl L-Glutamine Dipeptide in Colon Cancer Patients Receiving Modified FOLFOX-6 Regarding the Incidence of Diarrhea, the Treatment Response, and Patients' Survival: A Randomized Controlled Trial.2022PMID:35334570

• L-glutamine — no detected effect on

  BLikelyGrade B, Likely. Human evidence, limited replication or design limits.FindingNull resultreplicated ×2

  “Mortality showed no significant difference between glutamine group and control group.”

  Study

  meta-analysis

  Population

  critically ill patients

  The effect of glutamine therapy on outcomes in critically ill patients: a meta-analysis of randomized controlled trials.2014PMID:24401636

• L-glutamine — no detected effect on

  BLikelyGrade B, Likely. Human evidence, limited replication or design limits.FindingNull resultreplicated ×2

  “The pooled data indicated that enteral Gln did not decrease the overall mortality (RR = 0.37; 95% CI: 0.06 − 2.37; p = 0.300), with significant heterogeneity (I 2 = 61%).”

  Study

  meta-analysis

  Participants

  1,271

  Population

  Adults with severe burns (second- or third-degree burns over 20% or more TBSA, or 15% or more with inhalation injury) given enteral glutamine; primary endpoint; 3 pooled trials

  Effect 0.37 risk ratio, 95% CI 0.06 to 2.37

  Enteral glutamine supplements for patients with severe burns: A systematic review and meta-analysis.2024PMID:37460347