A systematic review and meta-analysis on endothelial dysfunction post-shock resuscitation

Abstract Introduction Shock-induced endotheliopathy (SHINE), defined as a profound sympathoadrenal hyperactivation in shock states leading to endothelial activation, glycocalyx damage, and eventual compromise of end-organ perfusion, was first described in 2017. The aggressive resuscitation therapies utilised in treating shock states could potentially lead to further worsening endothelial activation and end-organ dysfunction. Objective This study aimed to systematically review the literature on resuscitation-associated and resuscitation-induced endothelial dysfunction. Methods A pre-determined structured search of literature published over an eleven-year period (1 January 2011 to 31 December 2022) was performed in two indexed databases (PubMed/MEDLINE and EMBASE) per PRISMA guidelines. Results Thirty studies met the inclusion criteria and were included in the final qualitative synthesis. Most of these studies (43%) reported on a combination of mediators released from endothelial cells and biomarkers of glycocalyx breakdown, while only 20% reported on microvascular flow changes. Only eight individual studies were included in the quantitative meta-analysis based on the comparability of the parameters assessed. Six studies measured syndecan-1, with a heterogeneity index, I 2 = 75.87% (pooled effect-size; z = 2.00; mean = 0.43; 95% CI 0.01 to 0.85; p = 0.05). Thrombomodulin was measured in 4 comparable studies ( I 2 = 78.93%; z = 1.57; mean = 0.41; 95% CI -0.10 to 0.92; p = 0.12). Conclusion Acute resuscitation therapies administered could exacerbate endothelial dysfunction in shock states. In the included studies, syndecan-1 had the highest frequency of assessment in the post-resuscitation period and changes in concentrations showed a statistically significant effect of the resuscitation. There are inadequate data available in this area and further research and standardisation of the ideal assessment and panel of biomarkers are urgently needed.