Comments on the REDOX Trial

Submitted by Dr. Luisito Llido, Clinical Nutrition Service, St. Luke's Medical Center, Quezon City, Philippines (May 4, 2015)

  1. Glutamine was given to patients with renal problems (dysfunction or failure) (=20% of 1,218 patients) > is glutamine to be given to patients with renal problems? (=this looks like expanding the indication of glutamine – patients with renal dysfunction/failure, thus the study has an indication bias)
  2. There were more renal problem patients given glutamine compared to those who were not given glutamine (20% vs. 17% = +3%)
  3. Glutamine was given to patients with 3 to 4 failed organs (=15%)
  4. There were more patients with 3 to 4 failed organs who were given glutamine than those not given glutamine (15% vs. 12% = +3%)
  5. Since there were more patients in the glutamine group who had 3 to 4 organ failures – we expect more mortality in the glutamine group > this is not due to the glutamine, but to the assignment of patients to this group (= assignment error)
  6. Glutamine was given to patients with cardiogenic shock, this means microcirculation failure > glutamine should not be given to this group of patients, but 9% of patients with cardiogenic shock were given glutamine, another expanded indication for glutamine?
  7. Calorie intake of all patients was only 50% of the computed (=there was inadequate intake of calories)
  8. Protein intake of all patients was only 50% of the computed (=there was inadequate intake of protein)
  9. The main factor for the inadequate intake was focusing only on enteral nutrition as the main delivery route (=80%); supplemental parenteral nutrition was not implemented (=choice of delivery bias and failure in achieving adequacy not only in calories, but also in protein)
  10. This inability to achieve adequacy in the gut is an indication of gut dysfunction or failure, which are indications of severely ill status (= was glutamine indicated in this inadequately fed, enterally delivered, gut dysfunction patients?)
  11.  The study period was only for 28 days; the 6 month outcomes were based on the Kaplan-Meier estimate (=not so accurate, only an estimate = estimate bias?)
  12. The dose of glutamine was high:
    1. Intravenous glutamine (20% Dipeptiven) 0.35 g/kg/IBW (=20 to 25 gm/day) PLUS Enteral glutamine at 0.45 g/kg IBW/day (=30 gm/day)
    2. This is on top of the prescribed protein intake per day
    3. Total glutamine per patient/day = at least 55 gm/day
  1. Glutamine indication was expanded and not for the usual indications
    1. Renal failure
    2. Gut dysfunction
    3. 3 to 4 organ failures
    4. Patients in shock (specifically cardiogenic)
  2. A lot of patients who should not be given glutamine were assigned to the glutamine group (=patients with 3 to 4 organ failures, where the mortality rate is expected to be higher)
  3. Glutamine dose was very high
  4. Intake of protein and calorie was inadequate (<70% of requirements)