scholarly journals Pharmacometabolomics identifies candidate predictor metabolites of an L‐carnitine treatment mortality benefit in septic shock

2021 ◽  
Author(s):  
Michael A. Puskarich ◽  
Theodore S. Jennaro ◽  
Christopher E. Gillies ◽  
Charles R. Evans ◽  
Alla Karnovsky ◽  
...  
Keyword(s):  
Septic Shock ◽  
Mortality Benefit ◽  
Candidate Predictor ◽  
Treatment Mortality

scholarly journals Pharmacometabolomics Identifies Candidate Predictor Metabolites of an L-carnitine Treatment Mortality Benefit in Septic Shock

2021 ◽  
Author(s):  
Michael A. Puskarich ◽  
Theodore S. Jennaro ◽  
Christopher E. Gillies ◽  
Charles R. Evans ◽  
Alla Karnovsky ◽  
...  
Keyword(s):  
Septic Shock ◽  
Drug Response ◽  
Clinical Trial Design ◽  
Threshold Concentration ◽  
Rank Test ◽  
Metabolic Dysfunction ◽  
Grid Search ◽  
Mortality Benefit ◽  
Candidate Predictor ◽  
Pre Treatment

AbstractBackgroundSepsis-induced metabolic dysfunction contributes to organ failure and death. L-carnitine has shown promise for septic shock, but a recent study demonstrated a non-significant reduction in mortality.MethodsA pharmacometabolomics study of patients (n=250) in a Phase II trial of L-carnitine to identify metabolic profiles predictive of a 90-day mortality benefit from L-carnitine. The independent predictive value of each pre-treatment metabolite concentration, adjusted for L-carnitine dose, on 90-day mortality was determined by logistic regression. A grid-search analysis maximizing the Z-statistic from a binomial proportion test identified specific metabolite threshold levels that discriminated L-carnitine responsive patients. Threshold concentrations were further assessed by hazard-ratio and Kaplan-Meier estimate.FindingsAccounting for L-carnitine treatment and dose, 11 1H-NMR metabolites and 12 acylcarnitines were independent predictors of 90-day mortality. Based on the grid-search analysis numerous acylcarnitines and valine were identified as candidate metabolites of drug response. Acetylcarnitine emerged as highly viable for the prediction of an L-carnitine mortality benefit due to its abundance and biological relevance. Using its most statistically significant threshold concentration, patients with acetylcarnitine ≥35µM were less likely to die at 90 days if treated with L-carnitine (18 g) versus placebo (p=0.01 by log rank test).InterpretationMetabolomics identified independent predictors of 90-day sepsis mortality. Our proof-of-concept approach shows how pharmacometabolomics may be useful for tackling the heterogeneity of sepsis and informing clinical trial design. Also, metabolomics can help understand mechanisms of sepsis heterogeneity and variable drug response, since sepsis induces alterations in numerous metabolite concentrations.

1271: A Meta-Analysis of Early Administration of Vasopressor in Septic Shock: Is There Mortality Benefit?

2020 ◽  
Vol 49 (1) ◽  
pp. 641-641
Author(s):  
David Gordon ◽  
Caleb Chan ◽  
Quincy Tran ◽  
Vera Bzhilyanskaya ◽  
Alexander Bracey ◽  
...  
Keyword(s):  
Septic Shock ◽  
Meta Analysis ◽  
Mortality Benefit ◽  
Early Administration

IN HOSPITAL MORTALITY BENEFIT WITH COMBINED LOW DOSE VITAMIN C AND HYDROCORTISONE IN SEVERE SEPSIS AND SEPTIC SHOCK

CHEST Journal ◽  
2019 ◽  
Vol 156 (4) ◽  
pp. A1645-A1646
Author(s):  
Elyana Matayeva ◽  
Theresa Henson ◽  
Nashreen Anderson ◽  
Donald Brown ◽  
Raghavendra Sanivarapu ◽  
...  
Keyword(s):  
Septic Shock ◽  
Severe Sepsis ◽  
Vitamin C ◽  
Hospital Mortality ◽  
Low Dose ◽  
Mortality Benefit ◽  
Sepsis And Septic Shock

Rapid Source-Control Laparotomy: Is There a Mortality Benefit in Septic Shock?

2018 ◽  
Vol 19 (2) ◽  
pp. 225-229 ◽  
Author(s):  
James Vogler ◽  
Leslie Hart ◽  
Sharon Holmes ◽  
Jason D. Sciarretta ◽  
John Mihran Davis
Keyword(s):  
Septic Shock ◽  
Source Control ◽  
Mortality Benefit

scholarly journals Anaerobic Metabolism Markers as a Guide of Resuscitation Effort and Mortality Benefit in Septic Shock Among Egyptian Population

2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Walid Mohamed Kamel Ahmed ◽  
Ramy Mohamed El Sayed Ibrahim Kishk ◽  
Dalia Mohamed Ragab ◽  
Mohamed Ibrahim Desouky
Keyword(s):  
Septic Shock ◽  
Anaerobic Metabolism ◽  
Mortality Benefit ◽  
Egyptian Population ◽  
Resuscitation Effort

Low-Dose Steroids Cut Mortality in Septic Shock

2006 ◽  
Vol 36 (19) ◽  
pp. 24
Author(s):  
BRUCE JANCIN
Keyword(s):  
Septic Shock ◽  
Low Dose

Septic shock patient and ultrasound in the emergency room

2016 ◽  
Vol 37 (S 01) ◽  
Author(s):  
M Algaba Montes ◽  
AÁ Oviedo García ◽  
M Patricio Bordomás
Keyword(s):  
Septic Shock ◽  
Emergency Room ◽  
Septic Shock Patient
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