Risk factors and prevention of nosocomial pneumonia in polytrauma

Nosocomial pneumonia (NK) is one of the most frequent complications of polytrauma leading to death. Meanwhile, the recommendations on prevention of NK in case of polytrauma have not been specified so far. This is due in large part to the lack of study of the pathophysiology of severe combined trauma. The review presents the results of modern experimental and clinical studies of the effect of shock, immune distress syndrome, posttraumatic immunosuppression, the phenomenon of mutual aggravation of lesions, age, sex, concomitant pathology on the risk of NK in polytrauma. The role of iatrogenic risk factors for NK in polytrauma – intubation of trachea and artificial lung ventilation (AVL), massive hemotransfusions, immobilization, the phenomenon of “second strike” after multiple surgeries has been determined. The most effective measures of NK prevention are reduction of the duration of AVL, prevention of oropharyngeal colonization and aspiration in case of AVL, use of inhalation antibacterial drugs, antishock measures, early mobilization of the patient, the earliest possible stable functional osteosynthesis by minimally traumatic methods. The data on the effectiveness of selective decontamination of intestines, probiotics and glucocorticosteroids for the prevention of NK in polytrauma are inconsistent. A promising area of NK prophylaxis may be the development of agents that regulate the complex mechanisms of immune response to polytrauma and prevent secondary acute lung injury and post-traumatic immunosuppression.

1. Pfeifer R., Pape H.C. [Diagnostics and treatment strategies for multiple trauma patients]. Chirurg. 2016; 87 (2): 165–175. DOI: 10.1007/s00104-015-0139-0 (in German).

2. Agadzhanyan V.V., Kravtsov S.A., Shatalin A.V., Levchenko T.V. [Hospital mortality in polytrauma and main directions for its decrease]. Politravma. 2015; (1): 6–15 (in Russian).

3. Negrin L.L., Halat G., Kettner S. et al. Club cell protein 16 and cytokeratin fragment 21-1 as early predictors of pulmonary complications in polytraumatized patients with severe chest trauma. PLoS One. 2017; 12 (4): e0175303. DOI: 10.1371/journal.pone.0175303.

4. Gel'fand B.R., ed. [Nosocomial Pneumonia in Adult: Russian National Guidelines]. Moscow: Meditsinskoe informatsionnoe agentstvo; 2016 (in Russian).

5. Arumugam S.K., Mudali I., Strandvik G. et al. Risk factors for ventilator-associated pneumonia in trauma patients: a descriptive analysis. World J. Emerg. Med. 2018; 9 (3): 203–210. DOI: 10.5847/wjem.j.1920-8642.2018.03.007.

6. Chaari A., Zribi E., Dammak H. et al. Does selective digestive decontamination prevent ventilator-associated pneumonia in trauma patients? Am. J. Ther. 2014; 21 (6): 470–476. DOI: 10.1097/MJT.0b013e31825e7a8f.

7. Chaari A., El Habib M., Ghdhoun H. et al. Does low-dose hydrocortisone therapy prevent ventilator-associated pneumonia in trauma patients? Am. J. Ther. 2015; 22 (1): 22–28. DOI: 10.1097/MJT.0b013e3182691af0.

8. Mangram A.J., Sohn J., Zhou N. et al. Trauma-associated pneumonia: time to redefine ventilator-associated pneumonia in trauma patients. Am. J. Surg. 2015; 210 (6): 1056–1062. DOI: 10.1016/j.amjsurg.2015.06.029.

9. Hamill M.E., Reed C.R., Fogel S.L. et al. Contact isolation precautions in trauma patients: an analysis of infectious complications. Surg. Infect. (Larchmt). 2017; 18 (3): 273– 281. DOI: 10.1089/sur.2015.094.

10. Huber-Lang M., Lambris J.D., Ward P.A. Innate immune responses to trauma. Nat. Immunol. 2018; 19 (4): 327–341. DOI: 10.1038/s41590-018-0064-8.

11. Simmons J.D., Freno D.R., Muscat C.A. et al. Mitochondrial DNA damage associated molecular patterns in ventilator-associated pneumonia: Prevention and reversal by intratracheal DNase I. J. Trauma Acute Care Surg. 2017; 82 (1): 120–125. DOI: 10.1097/TA.0000000000001269.

12. Thacker S., Moran A., Lionakis M. et al. Restoration of lung surfactant protein D by IL-6 protects against secondary pneumonia following hemorrhagic shock. J. Infect. 2014; 68 (3): 231–241. DOI: 10.1016/j.jinf.2013.11.010.

13. Ding N., Dahlke K., Janze A.K. et al. Role of p38 mitogenactivated protein kinase in posttraumatic immunosuppression in mice. J. Trauma Acute Care Surg. 2012; 73 (4): 861–868. DOI: 10.1097/TA.0b013e31825ab11f.

14. Roquilly A., Broquet A., Jacqueline C. et al. Hydro - cortisone prevents immunosuppression by interleukin-10+ na tu ral killer cells after trauma-hemorrhage. Crit. Care Med. 2014; 42 (12): e752–761. DOI: 10.1097/CCM.0000000000000658.

15. Kojima M., Gimenes-Junior J.A., Chan T.W. et al. Exosomes in postshock mesenteric lymph are key mediators of acute lung injury triggering the macrophage activation via Toll-like receptor 4. FASEB J. 2018; 32 (1): 97–110. DOI: 10.1096/fj.201700488R.

16. Xu J., Guardado J., Hoffman R. et al. IL33-mediated ILC2 activation and neutrophil IL5 production in the lung response after severe trauma: A reverse translation study from a human cohort to a mouse trauma model. PLoS Med. 2017; 14 (7): e1002365. DOI: 10.1371/journal.pmed.1002365.

17. Relja B., Taraki R., Teuben M.P. et al. Sera from severe trauma patients with pneumonia and without infectious complications have differential effects on neutrophil biology. BMC Pulm. Med. 2016; 16 (1): 171. DOI: 10.1186/s12890-016-0329-7.

18. Prokhorov A.V., Prokhorova N.D., Khalimov Yu. Sh. еt аl. [The role of biomarkers in nosocomial pneumonia diagnostics in polytraumatized patients]. Sovremennye problemy nauki i obrazovaniya. 2018; (3): 20 (in Russian).

19. Shabanov A.K., Khubutiya M.Sh., Bulava G.V. et al. [Time course of changes in the level of procalcitonin in the development of nosocomial pneumonia in victims with severe concomitant injury in an intensive care unit]. Obshchaya reanimatologiya. 2013; 9 (5): 11–17 (in Russian).

20. Dunham C.M., Chirichella T.J. Attenuated hypocholesterolemia following severe trauma signals risk for late ventilator-associated pneumonia, ventilator dependency, and death: a retrospective study of consecutive patients. Lipids Health Dis. 2011; 10: 42. DOI: 10.1186/1476-511X-10-42.

21. Cook K.M., Sifri Z.C., Baranski G.M. et al. The role of plasma granulocyte colony stimulating factor and bone marrow dysfunction after severe trauma. J. Am. Coll. Surg. 2013; 216 (1): 57–64. DOI: 10.1016/j.jamcollsurg.2012.08.028.

22. Cohen M., Call M., Nelson M. et al. Critical role of activated protein C in early coagulopathy and later organ failure, infection and death in trauma patients. Ann. Surg. 2012; 255 (2): 379–385. DOI: 10.1097/SLA.0b013e318235d9e6.

23. Relja B., Lustenberger T., Puttkammer B. et al. Thrombinactivatable fibrinolysis inhibitor (TAFI) is enhanced in major trauma patients without infectious complications. Immunobiology. 2013; 218 (4): 470–476. DOI: 10.1016/j.imbio.2012.06.002.

24. Swanson J.M., Wood G.C., Xu L. et al. Developing a gene expression model for predicting ventilator-associated pneumonia in trauma patients: a pilot study. PLoS One. 2012; 7(8): e42065. DOI: 10.1371/journal.pone.0042065.

25. Jovanovic B., Milan Z., Markovic-Denic L. et al. Risk factors for ventilator-associated pneumonia in patients with severe traumatic brain injury in a Serbian trauma centre. Int. J. Infect. Dis. 2015; 38: 46–51. DOI: 10.1016/j.ijid.2015.07.005.

26. Weinberg D.S., Narayanan A.S., Moore T.A., Vallier H.A. Assessment of resuscitation as measured by markers of metabolic acidosis and features of injury. Bone Joint J. 2017; 99-B (1): 122–127. DOI: 10.1302/0301-620X.99B1.BJJ2016-0418.R2.

27. Shabanov A.K., Bulava G.V., Kislukhina E.V., Khubu - tiya M.Sh. [Criteria of high risk infection pulmonary complications in severe polytrauma patients]. Anesteziologiya i reanimatologiya. 2015; 60 (2): 16–20 (in Russian).

28. Hu P.J., Pittet J.F., Kerby J.D. et al. Acute brain trauma, lung injury, and pneumonia: more than just altered mental status and decreased airway protection. Am. J. Physiol. Lung. Cell. Mol. Physiol. 2017; 313 (1): L1–L15. DOI: 10.1152/ajplung.00485.2016.

29. Lustenberger T., Kern M., Relja B. et al. The effect of brain injury on the inflammatory response following severe trauma. Immunobiology. 2016; 221 (3): 427–431. DOI: 10.1016/j.imbio.2015.11.011.

30. Xiang L., Lu S., Mittwede P.N. et al. Inhibition of NADPH oxidase prevents acute lung injury in obese rats following severe trauma. Am. J. Physiol. Heart. Circ. Physiol. 2014; 306 (5): H684–689. DOI: 10.1152/ajpheart.00868.2013.

31. Dai H., Xu L., Tang Y. et al. Treatment with a neutralising anti-rat interleukin-17 antibody after multiple-trauma reduces lung inflammation. Injury. 2015; 46 (8): 1465–1470. DOI: 10.1016/j.injury.2015.05.016.

32. Li H., Itagaki K., Sandler N. et al. Mitochondrial damageassociated molecular patterns from fractures suppress pulmonary immune responses via formyl peptide receptors 1 and 2. J. Trauma Acute Care Surg. 2015; 78 (2): 272–281. DOI: 10.1097/TA.0000000000000509.

33. Chen X., Song Y., Liu Z. et al. Ultrastructural lung pathology following brain injury combined with femur shaft fracture in a rat model. J. Trauma Acute Care Surg. 2015; 78 (3): 558–564. DOI: 10.1097/TA.0000000000000538.

34. Chrysou K., Halat G., Hoksch B. et al. Lessons from a large trauma center: impact of blunt chest trauma in polytrauma patients-still a relevant problem? Scand. J. Trauma Resusc. Emerg. Med. 2017; 25 (1): 42. DOI: 10.1186/s13049-017-0384-y.

35. Strumwasser A., Chu E., Yeung L. et al. A novel CT volume index score correlates with outcomes in polytrauma patients with pulmonary contusion. J. Surg. Res. 2011; 170 (2): 280–285. DOI: 10.1016/j.jss.2011.03.022.

36. Hoth J.J., Wells J.D., Jones S.E. et al. Complement mediates a primed inflammatory response after traumatic lung injury. J. Trauma Acute Care Surg. 2014; 76 (3): 601–608. DOI: 10.1097/TA.0000000000000129.

37. Neunaber C., Oestern S., Andruszkow H. et al. Cytokine productive capacity of alveolar macrophages and Kupffer cells after femoral fracture and blunt chest trauma in a murine trauma model. Immunol. Lett. 2013; 152 (2): 159–166. DOI: 10.1016/j.imlet.2013.05.012.

38. Weckbach S., Hohmann C., Braumueller S. et al. Inflammatory and apoptotic alterations in serum and injured tissue after experimental polytrauma in mice: distinct early response compared with single trauma or “double-hit” injury. J. Trauma Acute Care Surg. 2013; 74 (2): 489–498. DOI: 10.1097/TA.0b013e31827d5f1b.

39. Denk S., Wiegner R., Hönes F.M. et al. Early detection of junctional adhesion molecule-1 (JAM-1) in the circulation after experimental and clinical polytrauma. Mediators Inflamm. 2015; 2015: 463950. DOI: 10.1155/2015/463950.

40. Ayan E., Koksel O., Polat A. et al. The role of thoracic trauma in inflammatory responses, apoptosis and bacterial translocation following multiple traumas. Ulus. Travma Acil. Cerr. Derg. 2013; 19 (6): 491–499. DOI: 10.5505/tjtes.2013.29660.

41. Turnbull I.R., Ghosh S., Fuchs A. et al. Polytrauma increases susceptibility to Pseudomonas pneumonia in mature mice. Shock. 2016; 45 (5): 555–563. DOI: 10.1097/SHK.0000000000000538.

42. Itagaki K., Kaczmarek E., Lee Y.T. et al. Mitochondrial DNA released by trauma induces neutrophil extracellular traps. PLoS One. 2015; 10 (3): e0120549. DOI: 10.1371/journal.pone.0120549.

43. Firsov S. A., Matveev R.P., Sinkevich D.I., Vereshchagin N.A. [Manifestations of apoptosis in patients with craniocerebral trauma if alcohol problems in history]. Sovremennye problemy nauki i obrazovaniya. 2016; (2): 93 (in Russian).

44. Mica L., Keller C., Vomela J. et al. Obesity and overweight as a risk factor for pneumonia in polytrauma patients: a retrospective cohort study. J. Trauma Acute Care Surg. 2013; 75 (4): 693–698. DOI: 10.1097/TA.0b013e31829a0bdd.

45. American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am. J. Respir. Crit. Care Med. 2005; 171 (4): 388–416. DOI: 10.1164/rccm.200405-644ST.

46. Chaari A., Kssibi H., Zribi W. et al. Ventilator-associated pneumonia in trauma patients with open tracheotomy: Predictive factors and prognosis impact. J. Emerg. Trauma Shock. 2013; 6 (4): 246–251. DOI: 10.4103/0974-2700.120364.

47. Poole D., Chieregato A., Langer M. et al. Systematic review of the literature and evidence-based recommendations for antibiotic prophylaxis in trauma: results from an Italian consensus of experts. PLoS One. 2014; 9 (11): e113676. DOI: 10.1371/journal.pone.0113676.

48. Righy C., do Brasil P.E.A., Vallés J. et al. Systemic antibiotics for preventing ventilator-associated pneumonia in comatose patients: a systematic review and meta-analysis. Ann. Intensive Care. 2017; 7 (1): 67. DOI: 10.1186/s13613-017-0291-4.

49. Póvoa F.C.C., Cardinal-Fernandez P., Maia I.S. et al. Effect of antibiotics administered via the respiratory tract in the prevention of ventilator-associated pneumonia: a systematic review and meta-analysis. J. Crit. Care. 2018; 43: 240–245. DOI: 10.1016/j.jcrc.2017.09.019.

50. Vitko H.A., Sekula L.K., Schreiber M.A. Probiotics for trauma patients: should we be taking a precautionary approach? J. Trauma Nurs. 2017; 24 (1): 46–52. DOI: 10.1097/JTN.0000000000000263.

51. Stueber T., Karsten J., Voigt N., Wilhelmi M. Influence of intraoperative positive end-expiratory pressure level on pulmonary complications in emergency major trauma surgery. Arch. Med. Sci. 2017; 13 (2): 396–403. DOI: 10.5114/aoms.2016.59868.

52. Iqbal H.J., Alsousou J., Shah S. et al. Early surgical stabilization of complex chest wall injuries improves short-term patient outcomes. J. Bone Joint. Surg. 2018; 100 (15): 1298– 1308. DOI: 10.2106/JBJS.17.01215.

53. Sír M., Pleva L., Procházka V. [Multiple trauma – treatment of skeletal injuries with damage control orthopaedics]. Rozhl. Chir. 2014; 93 (5): 287–291 (in Czech).

54. Sangkomkamhang T., Thinkhamrop W., Thinkhamrop B., Laohasiriwong W. Incidence and risk factors for complications after definitive skeletal fixation of lower extremity in multiple injury patients: a retrospective chart review. F1000Res. 2018; 7: 612. DOI: 10.12688/f1000research.14825.1.

55. Zhu T.F., Zhao W.G., Zheng H.L., Wu J.X. [Application of damage control orthopedics for the treatment of severe multiple fractures]. Zhongguo Gu Shang. 2018; 31 (2): 145–149. DOI: 10.3969/j.issn.1003-0034.2018.02.010 (in Chinese).

56. Wu X., Dubick M.A., Schwacha M.G. et al. Tranexamic acid attenuates the loss of lung barrier function in a rat model of polytrauma and hemorrhage with resuscitation. Shock. 2017; 47 (4): 500–505. DOI: 10.1097/SHK.0000000000000758.

57. Song Z., Zhao X., Liu M. et al. Recombinant human brain natriuretic peptide attenuates trauma-/haemorrhagic shockinduced acute lung injury through inhibiting oxidative stress and the NF-κB-dependent inflammatory/MMP-9 pathway. Int. J. Exp. Pathol. 2015; 96 (6): 406–413. DOI: 10.1111/iep.12160.

58. Li D., Pan X., Zhao J. et al. Bone marrow mesenchymal stem cells suppress acute lung injury induced by lipopolysaccharide through inhibiting the TLR2, 4/NF-κB pathway in rats with multiple trauma. Shock. 2016; 45 (6): 641–646. DOI: 10.1097/SHK.0000000000000548.

59. Ruan X., Darwiche S.S., Cai C. et al. Anti-HMGB1 monoclonal antibody ameliorates immunosuppression after peripheral tissue trauma: attenuated T-lymphocyte response and increased splenic CD11b (+) Gr-1 (+) myeloid-derived suppressor cells require HMGB1. Mediators Inflamm. 2015; 2015: 458626. DOI: 10.1155/2015/458626.

60. Itagaki K., Riça I., Zhang J. et al. Intratracheal instillation of neutrophils rescues bacterial overgrowth initiated by trauma damage-associated molecular patterns. J. Trauma Acute Care Surg. 2017; 82 (5): 853–860. DOI: 10.1097/TA.0000000000001413.