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

Nina Rittgerodt, Thorben Pape, Markus Busch, Lena S Becker, Andrea Schneider, Heiner Wedemeyer, Benjamin Seeliger, Julius Schmidt, Anna Maria Hunkemöller, Jan Fuge, Wolfgang Knitsch, Christine Fegbeutel, Hans-Jörg Gillmann, Bernhard C Meyer, Marius M Hoeper, Jan B Hinrichs, Sascha David, Klaus Stahl, Nina Rittgerodt, Thorben Pape, Markus Busch, Lena S Becker, Andrea Schneider, Heiner Wedemeyer, Benjamin Seeliger, Julius Schmidt, Anna Maria Hunkemöller, Jan Fuge, Wolfgang Knitsch, Christine Fegbeutel, Hans-Jörg Gillmann, Bernhard C Meyer, Marius M Hoeper, Jan B Hinrichs, Sascha David, Klaus Stahl

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://ichgcp.net/clinical-trials-registry/NCT04235634?cond=NOMI&draw=2&rank=1 .

Keywords: Intestinal failure; Non-occlusive mesenteric ischemia; Sepsis; Shock.

Conflict of interest statement

The authors declare that they have no competing interest.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Flowchart of study participants. Flowchart demonstrates inclusion of patients into the observational study. ICU intensive care unit, CT computed tomography, NOMI non-occlusive mesenteric ischemia
Fig. 2
Fig. 2
Primary and key secondary outcomes. Kaplan–Meier graphs showing the 28-day survival course in the overall cohort (primary outcome (A) and in patients stratified for lactate reduction > 2 mmol/l (B). Violine plots showing time course of lactate concentration 48, 24, 12 and 6 h before inclusion, at inclusion as well as after 6, 12 and 24 h (key secondary outcome) following inclusion (C). Violine plots demonstrating reduction of lactate concentration in relation to baseline at 6, 12 and 24 h following inclusion (D)

References

    1. Ende N. Infarction of the bowel in cardiac failure. N Engl J Med. 1958;258(18):879–881. doi: 10.1056/NEJM195805012581804.
    1. Stahl K, Busch M, Maschke SK, Schneider A, Manns MP, Fuge J, et al. A retrospective analysis of nonocclusive mesenteric ischemia in medical and surgical ICU patients: clinical data on demography, clinical signs, and survival. J Intensive Care Med. 2020;35(11):1162–1172. doi: 10.1177/0885066619837911.
    1. Soussi S, Taccori M, De Tymowski C, Depret F, Chaussard M, Fratani A, et al. Risk factors for acute mesenteric ischemia in critically ill burns patients-a matched case-control study. Shock. 2019;51(2):153–160. doi: 10.1097/SHK.0000000000001140.
    1. Stahl K, Rittgerodt N, Busch M, Maschke SK, Schneider A, Manns MP, et al. Nonocclusive mesenteric ischemia and interventional local vasodilatory therapy: a meta-analysis and systematic review of the literature. J Intensive Care Med. 2020;35(2):128–139. doi: 10.1177/0885066619879884.
    1. Clair DG, Beach JM. Mesenteric ischemia. N Engl J Med. 2016;374(10):959–968. doi: 10.1056/NEJMra1503884.
    1. Samel S, Keese M, Kleczka M, Lanig S, Gretz N, Hafner M, et al. Microscopy of bacterial translocation during small bowel obstruction and ischemia in vivo—a new animal model. BMC Surg. 2002;2:6. doi: 10.1186/1471-2482-2-6.
    1. Piton G, Capellier G. Biomarkers of gut barrier failure in the ICU. Curr Opin Crit Care. 2016;22(2):152–160.
    1. Kramer SC, Gorich J, Oertel F, Scheld H, Heindel W. Non-occlusive mesenteric ischemia. Rofo. 2003;175(9):1177–1183. doi: 10.1055/s-2003-41923.
    1. Trompeter M, Brazda T, Remy CT, Vestring T, Reimer P. Non-occlusive mesenteric ischemia: etiology, diagnosis, and interventional therapy. Eur Radiol. 2002;12(5):1179–1187. doi: 10.1007/s00330-001-1220-2.
    1. Tilsed JV, Casamassima A, Kurihara H, Mariani D, Martinez I, Pereira J, et al. ESTES guidelines: acute mesenteric ischaemia. Eur J Trauma Emerg Surg. 2016;42(2):253–270. doi: 10.1007/s00068-016-0634-0.
    1. Stockmann H, Roblick UJ, Kluge N, Kunze U, Schimmelpenning H, Kujath P, et al. Diagnosis and therapy of non-occlusive mesenteric ischemia (NOMI) Zentralbl Chir. 2000;125(2):144–151.
    1. Ernst S, Luther B, Zimmermann N, Bohner H, Wilke R, Feindt P, et al. Current diagnosis and therapy of non-occlusive mesenteric ischemia. Rofo. 2003;175(4):515–523. doi: 10.1055/s-2003-38441.
    1. Schindler G, Bruch HP. The current status of the diagnosis and therapy of nonocclusive intestinal ischemia (NII) RoFo: Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin. 1991;155(2):123–127. doi: 10.1055/s-2008-1033232.
    1. Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22(7):707–10.
    1. Murray T, Rodt T, Lee MJ. Two-dimensional perfusion angiography of the foot: technical considerations and initial analysis. J Endovasc Ther. 2016;23(1):58–64. doi: 10.1177/1526602815621289.
    1. Minko P, Groesdonk H, Stroeder J, Miodek J, Graeber S, Bucker A, et al. A scoring system for the assessment of angiographic findings in non-occlusive mesenteric ischemia (NOMI) Rofo. 2012;184(9):805–809. doi: 10.1055/s-0032-1312750.
    1. Minko P, Stroeder J, Groesdonk HV, Graeber S, Klingele M, Buecker A, et al. A scoring-system for angiographic findings in nonocclusive mesenteric ischemia (NOMI): correlation with clinical risk factors and its predictive value. Cardiovasc Intervent Radiol. 2014;37(3):657–663. doi: 10.1007/s00270-014-0844-y.
    1. Thuijls G, van Wijck K, Grootjans J, Derikx JP, van Bijnen AA, Heineman E, et al. Early diagnosis of intestinal ischemia using urinary and plasma fatty acid binding proteins. Ann Surg. 2011;253(2):303–308. doi: 10.1097/SLA.0b013e318207a767.
    1. Schellekens D, Reisinger KW, Lenaerts K, Hadfoune M, Olde Damink SW, Buurman WA, et al. SM22 a plasma biomarker for human transmural intestinal ischemia. Ann Surg. 2018;268(1):120–126. doi: 10.1097/SLA.0000000000002278.
    1. Fujiwara S, Sekine Y, Nishimura R, Tadasa K, Miyazaki S. Treatment of nonocclusive mesenteric ischemia with type B aortic dissection using intra-arterial catheterization after trauma surgery: case report. Surg Case Rep. 2018;4(1):5. doi: 10.1186/s40792-017-0412-1.
    1. Winzer R, Fedders D, Backes M, Ittermann T, Grundling M, Mensel B, et al. Local intra-arterial vasodilator infusion in non-occlusive mesenteric ischemia significantly increases survival rate. Cardiovasc Intervent Radiol. 2020;43(8):1148–1155. doi: 10.1007/s00270-020-02515-4.
    1. Vincent JL, de Mendonca A, Cantraine F, Moreno R, Takala J, Suter PM, et al. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on "sepsis-related problems" of the European Society of Intensive Care Medicine. Crit Care Med. 1998;26(11):1793–800.
    1. Ferreira FL, Bota DP, Bross A, Melot C, Vincent JL. Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA. 2001;286(14):1754–1758. doi: 10.1001/jama.286.14.1754.
    1. Al-Diery H, Phillips A, Evennett N, Pandanaboyana S, Gilham M, Windsor JA. The pathogenesis of nonocclusive mesenteric ischemia: implications for research and clinical practice. J Intensive Care Med. 2019;34(10):771–781. doi: 10.1177/0885066618788827.
    1. Calame P, Nuzzo A, Ronot M. Local intra-arterial vasodilator infusion in non-occlusive mesenteric ischemia: Dealing with one consequence hoping to affect the cause? Cardiovasc Intervent Radiol. 2021;44(3):507–508. doi: 10.1007/s00270-020-02696-y.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다