Preserving the endothelial glycocalyx in patients undergoing cardiopulmonary bypass: a prospective randomised interventional pilot study of lidocaine and doxycycline (LiDEG trial)

Background: During major surgery, particularly heart surgery, an element of the lining of blood vessels, known as the endothelial glycocalyx (EG), can be damaged. This can lead to swelling, low oxygen levels, kidney failure and other problems, which delay recovery. There are laboratory studies that show lidocaine (a local anaesthetic) and doxycycline (an antibiotic) may help protect this lining. The study agents are widely available, cheap and safe drugs. Trial design and objective: This is a phase IV, single centre, prospective, unblinded, randomised, parallel-group trial. The objectives of the trial are to investigate the role of doxycycline and lidocaine as potential agents to reduce EG shedding and correlate with early postoperative outcomes. Methods: : 60 adult patients undergoing heart surgery requiring cardiopulmonary bypass (CPB) will be randomly assigned to one of three groups: doxycycline group (oral doxycycline, 200mg preoperatively); lidocaine group (perioperative intravenous lidocaine, 1.5mg/kg bolus at induction followed by 2mg/kg/hr infusion for the duration of surgery); and control group (standard care). The randomisation will be undertaken using a sealed opaque envelope method. The primary outcome will be the relative difference in the biochemical marker of EG injury, syndecan-1, at different timepoints in the intraoperative and early post-operative period. Secondary endpoints include vasopressor requirements, markers of organ dysfunction (lung, kidney, brain, arrhythmia), coagulation and inflammation. Discussion: EG injury is ubiquitous in patients undergoing CPB. Maintaining homeostasis of this delicate layer would appear to be a valuable therapeutic target.  To date no agents have been shown to be effective in protecting the EG. Our study agents have shown some promise in the preclinical setting and would represent a novel therapeutic approach should they show a protective effect. Trial registration: Australian New Zealand Clinical Trials Registry, ACTRN12619000621112 (26 th April 2019).