Predictors of Response To Intra-Arterial Vasodilatory Therapy of Non-Occlusive Mesenteric Ischemia In Patients With Severe Shock - Results From A Prospective Observational Study
Authors: Rittgerodt Nina , Pape Thorben , Busch Markus , Becker Lena S. , Schneider Andrea , Wedemeyer Heiner , Seeliger Benjamin , Schmidt Julius J. , Hunkemöller Anna M. , Fuge Jan , Knitsch Wolfgang , Fegbeutel Christine , Gillmann Hans-Jörg , Meyer Bernhard C. , Hoeper Marius M. , Hinrichs Jan B. , David Sascha , Stahl Klaus 
Published: January 2022

Abstract
Background: Non-occlusive mesenteric ischemia (NOMI) is a life-threatening condition occurring in patients with shock and is characterized by vasoconstriction of the mesenteric arteries leading to intestinal ischemia and multi-organ failure. Although minimal invasive local intra-arterial infusion of vasodilators into the mesenteric circulation has been suggested as a therapeutic option in NOMI, current knowledge is based on retrospective case series and it remains unclear which patients might benefit. Here, we prospectively analyzed predictors of response to intra-arterial therapy in patients with NOMI.Methods: Prospective single-center observational study to analyze 28-day mortality (primary outcome) and reduction of blood lactate > 2mmol/l from baseline after 24 hours (key secondary endpoint) in patients with NOMI undergoing intra-arterial vasodilatory therapy. Predictors of response to therapy concerning primary and key secondary endpoint were identified using a) clinical parameters as well as b) data from 2D-perfusion angiography and c) experimental biomarkers of intestinal injury.Results: A total of 42 patients were included into this study. At inclusion patients had severe shock, indicated by high doses of norepinephrine (NE) (median (Interquartile Range (IQR)) 0.37 (0.21-0.60) μg/kg/min), elevated lactate concentrations (9.2 (5.2-13) mmol/l), and multi-organ failure. Median intestinal fatty-acid binding protein (i-FABP) (p<0.001) and smooth muscle protein 22 (SM-22) (p<0.0001) plasma concentrations were increased compared to healthy controls indicating significant mucosal and transmural intestinal ischemia at inclusion. 28-day mortality was 71% and higher NE dose and lactate as well as lower thrombocytes, bicarbonate and pH 24 hours following intervention were associated with higher mortality. Patients showed a continuous reduction of lactate following intra-arterial prostaglandin infusion (baseline: (9.2 (5.2-13) mmol/l vs. 24 hours: 4.4 (2.5-9.1) mmol/l, p<0.001). 28-day mortality was 59% in patients with a reduction of lactate > 2 mmol/l 24 hours after inclusion (n=22), while it was 85% in all other patients (n=20) (Hazard Ratio 0.409; 95% CI, 0.14-0.631, p=0.005). Conclusions: A reduction of lactate concentrations was observed following implementation of intra-arterial therapy and lactate reduction was associated with better survival. Our findings concerning outcome predictors in NOMI patients undergoing intra-arterial prostaglandin therapy might help designing a randomized controlled trial to further investigate this therapeutic approach. Trial registration: Retrospectively registered January 22th 2020 at clinicaltrials.gov (REPERFUSE, NCT04235634), https://clinicaltrials.gov/ct2/show/NCT04235634?cond=NOMI&draw=2&rank=1