• Dhruv Parekh, DancerRachel C ARCABirmingham Acute Care Research Group, Institute of Inflammation and Aging, University of Birmingham, Birmingham, United Kingdom.Academic Department of Anaesthesia, Critical Care, Resuscitation and Pain, Heartlands Hospital, University H, Aaron Scott, Vijay K D'Souza, Phillip A Howells, Rahul Y Mahida, Jonathan C Y Tang, Mark S Cooper, William D Fraser, LamChin Tan, Fang Gao, Adrian R Martineau, Olga Tucker, Gavin D Perkins, and David R Thickett.
• Warwick Clinical Trials Unit, Warwick Medical School, University of Warwick, Coventry, United Kingdom.
• Crit. Care Med. 2018 Dec 1; 46 (12): e1128e1135e1128-e1135.

ObjectivesObservational 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 preoperative administration of oral high-dose cholecalciferol ameliorates early acute lung injury postoperatively in adults undergoing elective esophagectomy.DesignA double-blind, randomized, placebo-controlled trial.SettingThree large U.K. university hospitals.PatientsSeventy-nine adult patients undergoing elective esophagectomy were randomized.InterventionsA single oral preoperative (3-14 d) dose of 7.5 mg (300,000 IU; 15 mL) cholecalciferol or matched placebo.Measurements And Main ResultsPrimary outcome was change in extravascular lung water index 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, and extravascular lung water index 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 extravascular lung water index at the end of the operation between treatment groups (placebo median 1.0 [interquartile range, 0.4-1.8] vs cholecalciferol median 0.4 mL/kg [interquartile range, 0.4-1.2 mL/kg]; p = 0.059). Median pulmonary vascular permeability index values were significantly lower in the cholecalciferol treatment group (placebo 0.4 [interquartile range, 0-0.7] vs cholecalciferol 0.1 [interquartile range, -0.15 to -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.ConclusionsHigh-dose preoperative treatment with oral cholecalciferol was effective at increasing 25(OH)D concentrations and reduced changes in postoperative pulmonary vascular permeability index, but not extravascular lung water index.

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