Intestinal Oxygenotherapy of Critical Conditions

The latent or mist diagnosed dysfunction of the small intestine is a common disorder in critically ill patients. Intestinal oxygenotherapy is one of the alternative ways to normalize the coordinated activity of the smooth muscles of the digestive tract.

Purpose of the study. To determine the effect of intestinal oxygenotherapy in patients with enteropathies of critical conditions on the dynamics of biomarkers of the intestinal wall permeability and ischemia.

Materials and methods. An open prospective descriptive study of 12 critically ill patients (7 adults, 5 children) with multiple organ failure and evident or saspected dysfunction of the gastrointestinal tract. Pediatric patients included children with congenital heart disease who underwent open-heart surgery for the purpose of radical or palliative correction.

Results. Complications related to the intestinal oxygenotherapy were not observed. On the contrary, its use in children coincided with the positive clinical dynamics: elimination of intestinal paresis, normalization of digestion of enteral nutrition. However, it is difficult to interpret the results unambiguously. Serum citrulline concentration in children is an objective marker of the functional state of the gastrointestinal tract: in the vast majority of the control points its level was <20 μmol/l; it means a very severe intestinal damage. Serum I-FABP concentration was<100 pg/ml in a significant number of control points, which, by contrast, does not allow to talk about the intestinal wall severe ischemic disturbances. In adults, the initial serum citrulline concentration was <20 μmol/l in the vast majority of control points; but by days 5—6 after the onset of intestinal oxygenation, in the majority of patients the citrulline levels exceeded >20 μmol/l (up to 80 μmol/l). No correlation between serum citrulline and I-FABP concentrations in adults was found.

Conclusion. Intestinal oxygenotherapy is a promising therapeutic technique for prevention and correction of enteropathies. The method may appear especially effective in treatment of anaerobic (i.e. Cl. defficile-assosiated colitis) infection. The diagnostic value of plasma citrulline and I-FABP concentrations needs further confirmation.

1. Reintam A., Parm P., Kitus R., Kern H., Starkopf J. Gastrointestinal symptoms in intensive care patients. Acta Anaesthesiol. Scand. 2009; 53 (3): 318-324. DOI: 10.1111/j.1399-6576.2008.01.860.x. PMID: 19243317

2. Oldenburg W.A., Lau L.L., Rodenberg T.J., Edmonds H.J., Burger C.D. Acute mesenteric ischemia: a clinical review. Arch. Intern. Med. 2004; 164 (10): 1054-1062. DOI: 10.1001/archinte.164.10.1054. PMID: 15159262

3. Kougias P., Lau D., El Sayed H.F., Zhou W., Huynh T.T., Lin P.H. Determinants of mortality and treatment outcome following surgical interventions for acute mesenteric ischemia. J. Vasc. Surg. 2007; 46 (3): 467-474. DOI: 10.1016/j.jvs.2007.04.045. PMID: 17681712

4. Evennett N.J., Petrov M.S., Mittal A., Windsor J.A. Systematic review and pooled estimates for the diagnostic accuracy of serological markers for intestinal ischemia. World J. Surg. 2009; 33 (7): 1374-1383. DOI: 10.1007/s00268-009-0074-7. PMID: 19424744

5. Angelelli G., Scardapane A., Memeo M., Stabile Ianora A.A., Rotondo A. Acute bowel ischemia: CT findings. Eur. J. Radiol. 2004; 50 (1): 37-47. DOI: 10.1016/j.ejrad.2003.11.013. PMID: 15093234

6. Furukawa A., Kanasaki S., Kono N., Wakamiya M., Tanaka T., Takahashi M., Murata K. CT diagnosis of acute mesenteric ischemia from various causes. AJR Am. J. Roentgenol. 2009; 192 (2): 408-416. DOI: 10.2214/AJR.08.1138. PMID: 19155403

7. Kozuch P.L., Brandt L.J. Review article: diagnosis and management of mesenteric ischaemia with an emphasis on pharmacotherapy. Aliment. Pharmacol. Ther. 2005; 21 (3): 201-215. DOI: 10.1111/j.1365-2036.2005.02269.x. PMID: 15691294

8. Kanda T., Fujii H., Tani T., Murakami H., Suda T., Sakai Y., Ono T., Hatakeyama K.Intestinal fatty acid-binding protein is a useful diagnostic marker for mesenteric infarction in humans. Gastroenterology. 1996; 110 (2): 339-343. DOI: 10.1053/gast.1996.v110.pm8566578. PMID: 8566578

9. Lieberman J.M., Sacchettini J., Marks C., Marks W.H. Human intestinal fatty acid binding protein: report of an assay with studies in normal volunteers and intestinal ischemia. Surgery. 1997; 121 (3): 335-342. DOI: 10.1016/S0039-6060(97)90363-9. PMID: 9068676

10. Gollin G., Marks C., Marks W.H. Intestinal fatty acid binding protein in serum and urine reflects early ischemic injury to the small bowel. Surgery. 1993; 113 (5): 545-551. PMID: 8488474

11. Crenn P., Hanachi M., Neveux N., Cynober L.La citrullinemie: un biomar-queur de la fonctionnalite intestinale. Ann. Biol. Clin. (Paris). 2011; 69 (5) : 513-521. DOI: 10.1684/abc.2011.0609. PMID: 22008130

12. Curis E., Nicolis I., Moinard C., Osowska S., Zerrouk N., Benazeth S., Cynober L. Almost all about citrulline in mammals. Amino Acids. 2005; 29 (3): 177-205. DOI: 10.1007/s00726-005-0235-4. PMID: 16082501

13. Crenn P., Messing B., Cynober L. Citrulline as a biomarker of intestinal failure due to enterocyte mass reduction. Clin. Nutr. 2008; 27 (3): 328339. DOI: 10.1016/j.clnu.2008.02.005. PMID: 18440672

14. Crenn P., Coudray-Lucas C., Thuillier F., Cynober L., Messing B. Postabsorptive plasma citrulline concentration is a marker of absorptive ente-rocyte mass and intestinal failure in humans. Gastroenterology.2000; 119 (6) : 1496-1505. DOI: 10.1053/gast.2000.20227. PMID: 11113071

15. Ruiz P., Tryphonopoulos P., Island E., Selvaggi G., Nishida S., Moon J., Berlanga A., Defranc T., Levi D., Tekin A., Tzakis A.G. Citrulline evaluation in bowel transplantation. Transplant. Proc. 2010; 42 (1): 54-56. DOI: 10.1016/j.transproceed.2009.12.029. PMID: 20172280

16. Crenn P., Vahedi K., Lavergne-Slove A., Cynober L., Matuchansky C., Messing B. Plasma citrulline: a marker of enterocyte mass in villous atrophy-associated small bowel disease. Gastroenterology. 2003; 124 (5): 1209-1210. DOI: 10.1016/S0016-5085(03)00170-7. PMID: 12730862

17. Papadia C., Sherwood R. A., Kalantzis C., Wallis K., Volta U., Fiorini E., Forbes A. Plasma citrulline concentration: a reliable marker of small bowel absorptive capacity independent of intestinal inflammation. Am. J. Gastroenterol. 2007; 102 (7): 1474-1482. DOI: 10.1111/j.1572-0241.2007.01239.x. PMID: 17459021

18. Herbers A.H., Blijlevens N.M., Donnelly J.P., de Witte T.J.Bacteraemia coincides with low citrulline concentrations after high-dose melphalan in autologous HSCT recipients. Bone Marrow Transplant. 2008; 42 (5): 345349. DOI: 10.1038/bmt.2008.170. PMID: 18587437

19. Pan L., Wang X., Li W., Li N., Li J.The intestinal fatty acid binding protein diagnosing gut dysfunction in acute pancreatitis: a pilot study. Pancreas. 2010; 39 (5): 633-638. DOI: 10.1097/MPA.0b013e3181c79654. PMID: 20575163

20. Dillon Ya.G. A simple way of oxygen therapy. Sovetskaya Meditsina.1940; 21: 35-39. [In Russ.]

21. Charnyi A.M. Pathophysiology of hypoxic conditions. Moscow: Medgiz; 1961: 343. [In Russ.]

22. Gelman S.I. The effect of enteral oxygen administration on the hepatic circulation during halothane anaesthesia: experimental investigations. Br. J. Anaesth. 1975; 47 (12): 1253-1259. DOI: 10.1093/bja/47.12.1253. PMID: 1218163

23. Gelman S.I. The effect of enteral oxygen administration on the hepatic circulation during halothane anaesthesia: clinical observations. Br. J. Anaesth. 1975; 47 (12): 1261-1264. DOI: 10.1093/bja/47.12.1261. PMID: 1218164

24. Gelman S., Paz M., Levy E. Influence of enteral oxygen administration on the slow electrical activity of the intestine and stomach. Arch. Surg. 1976; 111 (5): 566-574. DOI: 10.1001/archsurg.1976.01360230066014. PMID: 1267607

25. Gross B.D., Sacristan E., Peura R.A., Shahnarian A., Devereaux D., Wang H.L., Fiddian-Green R. Supplemental systemic oxygen support using an intestinal intraluminal membrane oxygenator. Artif. Organs.2000; 24 (11): 864-869. DOI: 10.1046/j.1525-1594.2000.06563.x. PMID: 11119073

26. Belikov V.L., Zavoiskikh E.V., Mazurok V.A., Pchelnikov A.A., Saturnov A.V., Slivin O.A., Sulima D.L., Khantalina G.M. Enteral oxygenation in complextreatmentofanaerobicsepticshockinpostpartumwoman(case report). Anesteziologiya i Reanimatologiya. 2014; 59 (5): 74-77. PMID: 25844478. [In Russ.]

27. Belikov V.L., Mazurok V.A., Slivin O.A., Zavoiskikh E.V. Anatomical and physiological justification of enteral oxygenotherapy. Anesteziologiya i Reanimatologiya. 2015; 60 (6): 16-21. PMID: 27025127. [In Russ.]

28. Belikov V.L., Mazurok V.A., Slivin O.A., Makarenko A.M. Intestinal insufflation of oxygen to increase systemic oxygenation. Vestnik Intensivnoi Terapii. 2013; Suppl 5: 8-9. [In Russ.]

29. Mazurok V.A., Belikov V.L., Slivin O.A., Lobach S.M. Extra-pulmonary oxygenation: modern view on the old ideas. Vestnik SZGMU Imeni I.I. Mechnikova. 2013; 5 (3): 119-127. [In Russ.]

30. Mazurok V.A., Golovkin A.S., Bautin A.E., Gorelov I.I., Belikov V.L., Slivin O.A. Gastrointestinal tract in critical illness: the first who suffers, and the last who recieves the attention. Vestnik Intensivnoi Terapii. 2016; 2: 28-36. [In Russ.]

31. Shifrin G.A., Gorenshtein M.L. Recovery of biostability in sepsis. Zaporozhye; 2004: 300. [In Russ.]

32. Mazurok V.A., Antonova I.V., Golovkin A.S., Bautin A.E., Gorelov I.I., Belikov V.L., Slivin O.A. Gut insufficiency in critical illness: clinico-mor-phological forms, ways of correction. Translyatsionnaya Meditsina.2016; 3 (5): 42-52. [In Russ.]

33. BurchJ.M., Moore E.E., Moore F.A., Franciose R. The abdominal compartment syndrome. Surg. Clin. North Am. 1996; 76 (4): 833-842. DOI: 10.1016/S0039-6109(05)70483-7. PMID: 8782476

34. Norms of physiological needs in energy and nutrients for different population groups in the Russian Federation. Guidelines. Federal Center for Hygiene and Epidemiology (Rospotrebnadzor); 2009: 36. [In Russ.]

35. Piton G., Manzon C., Cypriani B., Carbonnel F., Capellier G. Acute intestinal failure in critically ill patients: is plasma citrulline the right marker? Intensive Care Med. 2011; 37 (6): 911-917. DOI: 10.1007/s00134-011-2172-x. PMID: 21400011

36. Papadia C., Fonaroli F., Lanzarotto F., Salemme M., Sabatino A. Di, Villanacci V., Corazza G.R., Forbes A. PTU-187 is plasma citrulline concentration a reliable marker for diagnosis and clinical management of coeliac disease? Gut.2013; 62 (Suppl 1): A125. DOI: 10.1136/gutjnl-2013-304907.277

37. Poole A., Deane A., Summers M., FletcherJ., Chapman M. The relationship between fasting plasma citrulline concentration and small intestinal function in the critically ill. Crit. Care. 2015; 19: 16. DOI: 10.1186/s13054-014-0725-4. PMID: 25599966

38. Lepage N., McDonald N., Dallaire L., Lambert M. Age-specific distribution of plasma amino acid concentrations in a healthy pediatric population. Clin. Chem. 1997; 43 (12): 2397-2402. PMID: 9439460

39. Thuijls G., van Wijck K., Grootjans J., DerikxJ.P., van Bijnen A.A., Heine-man E., Dejong C.H., Buurman W.A., Poeze M. 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. PMID: 21245670

40. Rahman S.H., Ammori BJ., HolmfieldJ., Larvin M., McMahon MJ. Intestinal hypoperfusion contributes to gut barrier failure in severe acute pancreatitis. J. Gastrointest. Surg. 2003; 7 (1): 26-35. DOI: 10.1016/S1091-255X(02) 00090-2. PMID: 12559182

41. van Waardenburg D.A., de Betue C.T., Luiking Y.C., Engel M., Deutz N.E. Plasma arginine and citrulline concentrations in critically ill children: strong relation with inflammation. Am. J. Clin. Nutr. 2007; 86 (5): 14381444. PMID: 17991657

42. Grimaldi D., Guivarch E., Neveux N., FichetJ., Pene F., MarxJ.S., Chiche J.D., CynoberL., MiraJ.P., Cariou A. Markers of intestinal injury are associated with endotoxemia in successfully resuscitated patients. Resuscitation. 2013; 84 (1): 60-65. DOI: 10.1016/j.resuscitation.2012.06.010. PMID: 22743354

43. Peters J.H., Wierdsma NJ., Teerlink T., van Leeuwen PA., Mulder CJ., van Bodegraven A.A. Poor diagnostic accuracy of a single fasting plasma cit-rulline concentration to assess intestinal energy absorption capacity. Am. J. Gastroenterol. 2007; 102 (12): 2814-2819. DOI: 10.1111/j.1572-0241.2007.01513.x. PMID: 17764491

44. Tizianello A., De Ferrari G., Garibotto G., Gurreri G., Robaudo C. Renal metabolism of amino acids and ammonia in subjects with normal renalfunction and in patients with chronic renal insufficiency. J. Clin. Invest. 1980; 65 (5): 1162-1173. DOI: 10.1172/JCI109771. PMID: 7364943

45. Fragkos K.C., Forbes A. PP228-Sun is citrulline a marker of small intestinal absorption? A systematic review and meta-analysis. Clin. Nutr. Suppl.2011; 6 (1): 110. DOI: 10.1016/S1744-1161(11)70281-2

46. Santarpia L., Catanzano F., Ruoppolo M., Alfonsi L., Vitale D.F., Pecce R., Pasanisi F., Contaldo F., Salvatore F. Citrulline blood levels as indicators of residual intestinal absorption in patients with short bowel syndrome. Ann. Nutr. Metab. 2008; 53 (2): 137-142. DOI: 10.1159/000170888. PMID: 18997462

47. Cynober L. Citrulline: just a biomarker or a conditionally essential amino acid and a pharmaconutrient in critically ill patients? Crit. Care. 2013; 17 (2): 122. DOI: 10.1186/cc12534. PMID: 23509945

48. Hanssen S.J., Derikx J.P., Vermeulen Windsant I.C., Heijmans J.H., Koeppel T.A., Schurink G.W., Buurman W.A., Jacobs M.J. Visceral injury and systemic inflammation in patients undergoing extracorporeal circulation during aortic surgery. Ann. Surg. 2008; 248 (1): 117-125. DOI: 10.1097/SLA.0b013e3181784cc5. PMID: 18580215

49. Derikx J.P., Evennett N.J., Degraeuwe P.L., Mulder T.L., van Bijnen A.A., van Heurn L.W., Buurman W.A., Heineman E. Urine based detection of intestinal mucosal cell damage in neonates with suspected necrotising enterocolitis. Gut. 2007; 56 (10): 1473-1475. DOI: 10.1136/gut.2007.128934. PMID: 17872576

50. van de Poll M.C., Derikx J.P., Buurman W.A., Peters W.H., Roelofs H.M., Wigmore S.J., Dejong C.H. Liver manipulation causes hepatocyte injury and precedes systemic inflammation in patients undergoing liver resection. World J. Surg.2007; 31 (10): 2033-2038. DOI: 10.1007/s00268-007-9182-4. PMID: 17668263

51. van der Voort P.H., Westra B., Wester J.P., Bosman R.J., van Stijn I., Haagen I.A., Loupatty F.J., Rijkenberg S. Can serum L-lactate. D-lactate. creatine kinase and I-FABP be used as diagnostic markers in critically ill patients suspected for bowel ischemia. BMC Anesthesiol. 2014; 14: 111. DOI: 10.1186/1471-2253-14-111. PMID: 25844063

52. Barr F.E., Beverley H., VanHook K., Cermak E., Christian K., Drinkwater D., Dyer K., Raggio N.T., Moore J.H., Christman B., Summar M. Effect of cardiopulmonary bypass on urea cycle i ntermediates and nitric oxide levels after congenital heart surgery. J. Pediatr. 2003; 142 (1): 26-30. DOI: 10.1067/mpd.2003.mpd0311. PMID: 12520250

53. Piton G., Manzon C., Monnet E., Cypriani B., Barbot O., Navellou J.C., Car-bonnel F., Capellier G. Plasma citrulline kinetics and prognostic value in critically ill patients. Intensive Care Med. 2010; 36 (4): 702-706. DOI: 10.1007/s00134-010-1751-6. PMID: 20084502

54. Hersch M., Scott J.A., Izbicki G., McCormack D., Cepinkas G., Ostermann M., Sibbald W.J. Differential inducible nitric oxide synthase activity in circulating neutrophils vs. mononuclears of septic shock patients. Intensive Care Med. 2005; 31 (8): 1132-1135. DOI: 10.1007/s00134-005-2680-7. PMID: 15959762

55. Kao C.C., Bandi V., Guntupalli K.K., Wu M., Castillo L., Jahoor F. Arginine. citrulline and nitric oxide metabolism in sepsis. Clin. Sci. (Lond.). 2009; 117 (1): 23-30. DOI: 10.1042/CS20080444. PMID: 19105791

56. Luiking Y.C., Poeze M., Ramsay G., Deutz N.E. Reduced citrulline production in sepsis is related to diminished de novo arginine and nitric oxide production. Am. J. Clin. Nutr. 2009; 89 (1): 142-152. DOI: 10.3945/ajcn.2007.25765. PMID: 19056593

57. Noordally S.O., Sohawon S., Semlali H., Michely D., Devriendt J., Gottignies P. Is there a correlation between circulating levels of citrulline and intestinal dysfunction in the critically ill? Nutr. Clin. Pract. 2012; 27 (4): 527-532. DOI: 10.1177/0884533612449360. PMID: 22706681

58. Ware L.B., Magarik J.A., Wickersham N., Cunningham G., Rice T.W., Christman B.W., Wheeler A.P., Bernard G.R., Summar M.L. Low plasma citrulline levels are associated with acute respiratory distress syndrome in patients with severe sepsis. Crit. Care. 2013; 17 (1): R10. DOI: 10.1186/cc11934. PMID: 23327349

59. Freund H., Atamian S., Holroyde J., Fischer J.E. Plasma amino acids as predictors of the severity and outcome of sepsis. Ann. Surg. 1979; 190 (5): 571-576. DOI: 10.1097/00000658-197911000-00003. PMID: 389183

60. Luiking Y.C., Deutz N.E. Exogenous arginine in sepsis. Crit. Care Med. 2007; 35 (9 Suppl): S557-S563. DOI: 10.1097/01.CCM.0000279191.44730.A2. PMID: 17713409

61. Van Eijk H.M., Dejong C.H., Deutz N.E., Soeters P.B. Influence of storage conditions on normal plasma amino-acid concentrations. Clin. Nutr. 1994; 13 (6): 374-380. DOI: 10.1016/0261-5614(94)90028-0. PMID: 16843417

62. Coste J., Pouchot J. A grey zone for quantitative diagnostic and screening tests. Int. J. Epidemiol. 2003; 32 (2): 304-313. DOI: 10.1093/ije/dyg054. PMID: 12714554

63. Le Boucher J., Charret C., Coudray-Lucas C., Giboudeau J., Cynober L. Amino acid determination in biological fluids by automated ion-exchange chromatography: performance of Hitachi L-8500A. Clin. Chem. 1997; 43 (8 Pt 1): 1421-1428. PMID: 9267323

64. Demacker P.N., Beijers A.M., van Daal H., Donnelly J.P., Blijlevens N.M., van den Ouweland J.M. Plasma citrulline measurement using UPLC tandem mass-spectrometry to determine small intestinal enterocyte pathology. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2009; 877 (4): 387-392. DOI: 10.1016/j.jchromb.2008.12.041. PMID: 19144577