Predictors of response to intra-arterial vasodilatory therapy of non-occlusive mesenteric ischemia in patients with severe shock: results from a prospective observational study

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 This is a prospective single-center observational study to analyze improvement of ischemia (indicated by reduction of blood lactate > 2 mmol/l from baseline after 24 h, primary endpoint) and 28-day mortality (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. Patients showed a continuous reduction of lactate following intra-arterial prostaglandin infusion (baseline: (9.2 (5.2–13) mmol/l vs. 24 h: 4.4 (2.5–9.1) mmol/l, p < 0.001) with 22 patients (52.4%) reaching a lactate reduction > 2 mmol/l at 24 h following intervention. Initial higher lactate concentrations and lower NE doses at baseline were independent predictors of an improvement of ischemia. 28-day mortality was 59% in patients with a reduction of lactate > 2 mmol/l 24 h after inclusion, while it was 85% in all other patients (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 on January 22, 2020, at clinicaltrials.gov (REPERFUSE, NCT04235634), https://clinicaltrials.gov/ct2/show/NCT04235634?cond=NOMI&draw=2&rank=1.

Elevated pulsatility index of the superior mesenteric artery indicated prolonged mechanical ventilation in patients after cardiac valve surgery

“…This result reinforces the need for SMA blood flow monitoring and the need to pay attention to the negative effects of vasopressors on intestinal blood flow (12). Recent studies on critically ill patients with non-obstructive mesenteric ischemia showed that the vasopressor dose affects the diastolic effect of prostacyclin E1 on the SMA (17). This is precisely because blood flow in the SMA is the result of the influence of many factors, and blood flow monitoring of the SMA is of greater significance in patients after cardiac surgery.…”

Acute mesenteric ischaemia

“…Angiography can also be useful if a stenosis of the superior mesenteric artery is identified, since stenting of a previously asymptomatic stenosis in a patient with NOMI may be life saving [7]. In a study of 42 patients with severe shock and potentially reversible NOMI, lactate reduction > 2 mmol/ 24 h following intra-arterial prostaglandin infusion was shown to be associated with better survival, whereas the angiography criteria did not show a clear effect of vasodilator treatment [35].…”

Exosomal circEZH2_005, an intestinal injury biomarker, alleviates intestinal ischemia/reperfusion injury by mediating hnRNPA1/Gprc5a signaling

“…Although it is associated with a high mortality and complication rate, acute intestinal ischemia can usually be reversed if diagnosed and treated in time 2,3 . To improve its early diagnosis, several studies have suggested measuring different biomarkers, including intestinal fatty acid binding protein (IFABP), diamine oxidase, glutathione S-transferase, citrulline, and smooth muscle protein [4][5][6] . Although most of these biomarkers have proven valuable in preclinical studies, their use in the clinical setting is limited by several shortcomings, including low sensitivity and specificity and poor reliability and accuracy 7,8 .…”