A multicenter randomized clinical trial of pharmacological vitamin B1 administration to critically ill patients who develop hypophosphatemia during enteral nutrition (The THIAMINE 4 HYPOPHOSPHATEMIA trial)

Clin Nutr. 2021 Aug;40(8):5047-5052. doi: 10.1016/j.clnu.2021.07.024. Epub 2021 Jul 24.

Abstract

Background: Hypophosphatemia may be a useful biomarker to identify thiamine deficiency in critically ill enterally-fed patients. The objective was to determine whether intravenous thiamine affects blood lactate, biochemical and clinical outcomes in this group.

Method: This randomized clinical trial was conducted across 5 Intensive Care Units. Ninety critically ill adult patients with a serum phosphate ≤0.65 mmol/L within 72 h of commencing enteral nutrition were randomized to intravenous thiamine (200 mg every 12 h for up to 14 doses) or usual care (control). The primary outcome was blood lactate over time and data are median [IQR] unless specified.

Results: Baseline variables were well balanced (thiamine: lactate 1.2 [1.0, 1.6] mmol/L, phosphate 0.56 [0.44, 0.64] mmol/L vs. control: lactate 1.0 [0.8, 1.3], phosphate 0.54 [0.44, 0.61]). Patients randomized to the intervention received a median of 11 [7.5, 13.5] doses for a total of 2200 [1500, 2700] mg of thiamine. Blood lactate over the entire 7 days of treatment was similar between groups (mean difference = -0.1 (95 % CI -0.2 to 0.1) mmol/L; P = 0.55). The percentage change from lactate pre-randomization to T = 24 h was not statistically different (thiamine: -32 (-39, -26) vs. control: -24 (-31, -16) percent, P = 0.09). Clinical outcomes were not statistically different (days of vasopressor administration: thiamine 2 [1, 4] vs. control 2 [0, 5.5] days; P = 0.37, and deaths 9 (21 %) vs. 5 (11 %); P = 0.25).

Conclusions: In critically ill enterally-fed patients who developed hypophosphatemia, intravenous thiamine did not cause measurable differences in blood lactate or clinical outcomes.

Trial registration: Australian and New Zealand Clinical Trials Registry (ACTRN12619000121167).

Keywords: Critical illness; Enteral nutrition; Lactic acidosis; Phosphate; Refeeding syndrome; Thiamine.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous
  • Adult
  • Aged
  • Biomarkers / blood
  • Critical Illness / therapy
  • Enteral Nutrition / adverse effects*
  • Female
  • Humans
  • Hypophosphatemia / drug therapy*
  • Hypophosphatemia / etiology
  • Intensive Care Units
  • Lactic Acid / blood
  • Male
  • Middle Aged
  • Phosphates / blood
  • Thiamine / administration & dosage*
  • Thiamine Deficiency / etiology
  • Thiamine Deficiency / prevention & control*
  • Treatment Outcome

Substances

  • Biomarkers
  • Phosphates
  • Lactic Acid
  • Thiamine