Why the study?
Endothelial glycocalyx damage during cardiopulmonary bypass leads to adverse outcomes, but no clinical agents have been shown to protect it despite promising preclinical data for lidocaine and doxycycline.
Does doxycycline or lidocaine reduce endothelial glycocalyx shedding in adult patients undergoing cardiopulmonary bypass?
Does doxycycline or lidocaine reduce endothelial glycocalyx shedding in adult patients undergoing cardiopulmonary bypass?
This study protocol outlines a randomized trial to evaluate whether prophylactic doxycycline or lidocaine can preserve the endothelial glycocalyx and improve early postoperative outcomes in patients undergoing cardiopulmonary bypass.
Supports testing lidocaine/doxycycline for glycocalyx protection during CPB; leaves open efficacy in larger trials.
<ns3:p> <ns3:bold>Background:</ns3:bold> 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. </ns3:p> <ns3:p> <ns3:bold>Trial design and objective:</ns3:bold> 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. </ns3:p> <ns3:p> <ns3:bold>Methods:</ns3:bold> 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. </ns3:p> <ns3:p> <ns3:bold>Discussion:</ns3:bold> 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. </ns3:p> <ns3:p> <ns3:bold>Trial registration:</ns3:bold> Australian New Zealand Clinical Trials Registry, <ns3:ext-link xmlns:ns4="http://www.w3.org/1999/xlink" ext-link-type="uri" ns4:href="https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376584&showOriginal=true&isReview=true">ACTRN12619000621112</ns3:ext-link> (26 <ns3:sup>th</ns3:sup> April 2019). </ns3:p>
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Pannekoek et al. (2020) studied this question.
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