Vitamin D to prevent lung injury following esophagectomy: a randomized placebo controlled trial

Research output: Contribution to journalArticle

Authors

  • Phillip Howells
  • Jonathan Tang
  • Mark S. Cooper
  • William D. Fraser
  • LamChin Tan
  • Adrian R. Martineau
  • Olga Tucker
  • Gavin D. Perkins
  • David Thickett

External organisations

  • University of Sydney
  • University of East Anglia
  • University Hospitals Coventry and Warwickshire NHS Trust
  • Queen Mary University of London
  • University of Warwick
  • Heart of England NHS Foundation Trust

Abstract

Objectives: Observational studies suggest an association between vitamin D deficiency and adverse outcomes of critical illness and identify it as a potential risk factor for the development of lung injury. To determine whether pre-operative administration of oral high-dose cholecalciferol ameliorates early acute lung injury post-operatively in adults undergoing elective esophagectomy.


Design: A double-blind, randomized, placebo-controlled trial.


Setting: Three large UK university hospitals.


Patients: Seventy nine adult patients undergoing elective esophagectomy were
randomized.


Intervention: A single oral preoperative (3-14 days) dose of 7.5mg (300,000IU; 15mls) cholecalciferol or matched placebo.


Measurements and Main Results: Primary outcome was change in extravascular lung water index (EVLWI) at the end of esophagectomy. Secondary outcomes included PaO2:FiO2 ratio, development of lung injury, ventilator and organ-failure free days, 28 and 90 day survival, safety of cholecalciferol supplementation, plasma vitamin D status (25(OH)D, 1,25(OH)2D and vitamin D binding protein), pulmonary vascular permeability index (PVPI) and EVLWI day 1 postoperatively. An exploratory study measured biomarkers of alveolar-capillary inflammation and injury. Forty patients were randomized to cholecalciferol and 39 to placebo. There was no significant change in EVLWI at the end of the operation between treatment groups (placebo median 1.0[IQR 0.4 – 1.8] vs cholecalciferol median 0.4[IQR 0.4 – 1.2] ml/kg, p=0.059). Median PVPI
values were significantly lower in the cholecalciferol treatment group (placebo 0.4[IQR 0 – 0.7] vs cholecalciferol 0.1[IQR -0.15 -0.35] , p=0.027). Cholecalciferol treatment effectively increased 25(OH)D concentrations but surgery resulted in a decrease in 25(OH)D concentrations at day 3 in both arms. There was no difference in clinical outcomes.


Conclusions: High-dose preoperative treatment with oral cholecalciferol was effective at increasing 25(OH)D concentrations, and reduced changes in postoperative PVPI but not EVLWI.

Details

Original languageEnglish
Pages (from-to)e1128–e1135
JournalCritical care medicine
Volume46
Issue number12
Early online date14 Sep 2018
Publication statusPublished - Dec 2018

Keywords

  • cholecalciferol, acute respiratory distress syndrome, vitamin D, esophagectomy