The Neutrophil-to-Lymphocyte Ratio at the Time of Admission: A New Prognostic Indicator for Hospital Mortality of Trauma Patients
-
Hamed Fouladseresht
,
Shahram Bolandparvaz
,
Hamid Reza Abbasi
,
Hossein Abdolrahimzadeh Fard
,
Shahram Paydar
Abstract
The elevated neutrophil-to-lymphocyte ratio (NLR) is associated with poor clinical outcomes, especially in pro-inflammatory states such as surgical injuries and severe hemorrhages. Therefore, it was hypothesized whether NLR value at the time of admission could be a prognostic indicator of hospital mortality in trauma patients.
This retrospective cohort study was conducted on 865 trauma patients referred to Rajaee Hospital between April 2016 and July 2019. The NLR value was calculated at the time of admission, and receiver operating characteristics (ROC) curve analysis was used to determine the cut-off point value of admission NLR related to hospital mortality of trauma patients. Furthermore, Kaplan-Meier survival analysis and Cox regression models have been applied to determine the effectiveness and prognostic potential of the admission NLR in the hospital mortality of trauma patients.
The median age of the trauma patients was 32 years with an interquartile range (IQR) of 23 to 48 years, and most of them were male (83.9%). Also, trauma patients had a median injury severity score (ISS) of 9 (IQR=4-16) and a median Glasgow coma scale (GCS) of 14 (IQR=9-15). The cut-off value for admission NLR was 5.27 (area under the curve: 0.642, 95%CI: 0.559-0.726, p=0.001). In Kaplan-Meier survival analysis, the admission NLR>5.27 was an indicator of hospital mortality in trauma patients (p=0.001). Multivariate Cox regression models demonstrated that trauma patients with an admission NLR>5.27 had a 2.33-fold risk of hospital mortality (hazard ratio=2.33, 95%CI: 1.02-5.38, p=0.041). Furthermore, the admission NLR>5.27 was associated with a higher risk of hospital mortality in trauma patients with age≥65 years, systolic blood pressure≤90 mmHg, blood potassium>4.5 mmol/L, blood sodium>144 mEq/L, blood potential hydrogen (pH)≤7.28, GCS≤8, ISS>24 and blood base excess≤-6.1 mEq/L.
The NLR value greater than 5.27 at the time of admission was associated with poorer outcomes, and it can be considered an independent prognostic indicator of hospital mortality in trauma patients.
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5. Sobrino J, Shafi S. Timing and causes of death after injuries. Proc (Bayl Univ Med Cent). 2013;26(2):120-3.
6. Thompson KB, Krispinsky LT, Stark RJ. Late immune consequences of combat trauma: a review of trauma-related immune dysfunction and potential therapies. Mil Med Res. 2019;6(1):11.
7. Mira JC, Brakenridge SC, Moldawer LL, Moore FA. Persistent inflammation, immunosuppression and catabolism syndrome. Critical care clinics. 2017;33(2):245-58.
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11. Fouladseresht H, Safa A, Khosropanah S, Doroudchi M. Increased frequency of HLA-A* 02 in patients with atherosclerosis is associated with VZV seropositivity. Arch Physiol Biochem. 2019:1-8.
12. Siwicka-Gieroba D, Malodobry K, Biernawska J, Robba C, Bohatyrewicz R, Rola R, et al. The Neutrophil/Lymphocyte Count Ratio Predicts Mortality in Severe Traumatic Brain Injury Patients. J Clin Med. 2019;8(9):1453.
13. Duchesne JC, Tatum D, Jones G, Davis B, Robledo R, DeMoya M, et al. Multi-institutional analysis of neutrophil-to-lymphocyte ratio (NLR) in patients with severe hemorrhage: A new mortality predictor value. J Trauma Acute Care Surg. 2017;83(5):888-93.
14. Ma J, Kuzman J, Ray A, Lawson BO, Khong B, Xuan S, et al. Neutrophil-to-lymphocyte Ratio (NLR) as a predictor for recurrence in patients with stage III melanoma. Sci Rep. 2018;8(1):1-6.
15. Tanık VO, Çınar T, Velibey Y, Öz A, Kalenderoğlu K, Gümüşdağ A, et al. Neutrophil-to-lymphocyte ratio predicts contrast-induced acute kidney injury in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention. J Tehran Heart Cent. 2019;14(2):59-66.
16. Fouladseresht H, Doroudchi M, Rokhtabnak N, Abdolrahimzadehfard H, Roudgari A, Sabetian G, et al. Predictive monitoring and therapeutic immune biomarkers in the management of clinical complications of COVID-19. Cytokine Growth Factor Rev. 2020;(In Press).
17. Sauaia A, Moore FA, Moore EE, Haenel JB, Read RA, Lezotte DC. Early predictors of postinjury multiple organ failure. Arch Surg. 1994;129(1):39-45.
18. Inose H, Kobayashi Y, Yuasa M, Hirai T, Yoshii T, Okawa A. Procalcitonin and Neutrophil Lymphocyte Ratio After Spinal Instrumentation Surgery. Spine (Phila Pa 1976). 2019;44(23):e1356-61.
19. Wang F, Wang L, Jiang T-t, Xia J-j, Xu F, Shen L-j, et al. Neutrophil-to-lymphocyte ratio is an independent predictor of 30-day mortality of intracerebral hemorrhage patients: a validation cohort study. Neurotox Res. 2018;34(3):347-52.
20. Jung J, Eo E, Ahn K, Noh H, Cheon Y. Initial base deficit as predictors for mortality and transfusion requirement in the severe pediatric trauma except brain injury. Pediatr Emerg Care. 2009;25(9):579-81.
21. Alexiou GA, Lianos G, Fotakopoulos G, Michos E, Pachatouridis D, Voulgaris S. Admission glucose and coagulopathy occurrence in patients with traumatic brain injury. Brain Inj. 2014;28(4):438-41.
22. Bordbar E, Paydar S, Taghipour M, Khalili H, Jafari M. Initial GCS and laboratory findings of patients with TBI are associated with the GOSE and mortality rate at one year. Int J Res Med Sci. 2018;6(1):14-9.
23. Yadollahi M, Anvar M, Ghaem H, Bolandparvaz S, Paydar S, Izianloo F. Logistic regression modeling for evaluation of factors affecting trauma outcome in a level I trauma center in Shiraz. Iran Red Crescent Med. 2017;19(1).
24. Dilektasli E, Inaba K, Haltmeier T, Wong MD, Clark D, Benjamin ER, et al. The prognostic value of neutrophil-to-lymphocyte ratio on mortality in critically ill trauma patients. J Trauma Acute Care Surg. 2016;81(5):882-8.
25. Heffernan DS, Monaghan SF, Thakkar RK, Machan JT, Cioffi WG, Ayala A. Failure to normalize lymphopenia following trauma is associated with increased mortality, independent of the leukocytosis pattern. Crit Care. 2012;16(1):R12.
26. Keel M, Eid K, Labler L, Seifert B, Trentz O, Ertel W. Influence of injury pattern on incidence and severity of posttraumatic inflammatory complications in severely injured patients. Eur J Trauma. 2006;32(4):387-95.
27. Faist E, Kupper TS, Baker CC, Chaudry IH, Dwyer J, Baue AE. Depression of cellular immunity after major injury: its association with posttraumatic complications and its reversal with immunomodulation. Arch Surg. 1986;121(9):1000-5.
28. Kovtun A, Messerer DA, Scharffetter-Kochanek K, Huber-Lang M, Ignatius A. Neutrophils in tissue trauma of the skin, bone, and lung: two sides of the same coin. J Immunol Res. 2018;2018.
29. Manson J, Cole E, De’Ath HD, Vulliamy P, Meier U, Pennington D, et al. Early changes within the lymphocyte population are associated with the development of multiple organ dysfunction syndrome in trauma patients. Crit Care. 2016;20(1):176.
30. Zhou Z, Ren L, Zhang L, Zhong J, Xiao Y, Jia Z, et al. Heightened innate immune responses in the respiratory tract of COVID-19 patients. Cell Host Microbe. 2020;27(6):883-90.
31. Mortaz E, Alipoor SD, Adcock IM, Mumby S, Koenderman L. Update on neutrophil function in severe inflammation. Front Immunol. 2018;9:2171.
32. Lei H, Schmidt-Bleek K, Dienelt A, Reinke P, Volk H-D. Regulatory T cell-mediated anti-inflammatory effects promote successful tissue repair in both indirect and direct manners. Front Pharmacol. 2015;6: :184.
33. Talepoor AG, Fouladseresht H, Khosropanah S, Doroudchi M. Immune-Inflammation in Atherosclerosis: A New Twist in an Old Tale. Endocr Metab Immune Disord Drug Targets. 2020;20(4):525-45.
34. Ward NS, Casserly B, Ayala A. The compensatory anti-inflammatory response syndrome (CARS) in critically ill patients. Clin Chest Med. 2008;29(4):617-25.
35. Xiao W, Mindrinos MN, Seok J, Cuschieri J, Cuenca AG, Gao H, et al. A genomic storm in critically injured humans. J Exp Med. 2011;208(13):2581-90.
36. Vanzant EL, Lopez CM, Ozrazgat-Baslanti T, Ungaro R, Davis R, Cuenca AG, et al. Persistent inflammation, immunosuppression and catabolism syndrome after severe blunt trauma. J Trauma Acute Care Surg. 2014;76(1):21-9.
37. Surbatovic M, Veljovic M, Jevdjic J, Popovic N, Djordjevic D, Radakovic S. Immunoinflammatory response in critically ill patients: severe sepsis and/or trauma. Mediators Inflamm. 2013;2013.
38. Younan D, Richman J, Zaky A, Pittet J-F. An increasing neutrophil-to-lymphocyte ratio trajectory predicts organ failure in critically-ill male trauma patients. An exploratory study. Healthcare (Basel). 2019;7(1):e42.
39. Yadollahi M. A study of mortality risk factors among trauma referrals to trauma center, Shiraz, Iran, 2017. Chin J Traumatol. 2019;22(4):212-8.
40. Bolandparvaz S, Yadollahi M, Abbasi HR, Anvar M. Injury patterns among various age and gender groups of trauma patients in southern Iran: a cross-sectional study. Medicine (Baltimore). 2017;96(41):e7812.
41. McIntyre A, Mehta S, Aubut J, Dijkers M, Teasell RW. Mortality among older adults after a traumatic brain injury: a meta-analysis. Brain Inj. 2013;27(1):31-40.
42. Aiyagari V, Deibert E, Diringer MN. Hypernatremia in the neurologic intensive care unit: how high is too high? J Crit Care. 2006;21(2):163-72.
43. Brinkman JE, Sharma S. Physiology, Respiratory Alkalosis Treasure Island (FL): StatPearls Publishing LLC; [updated Jun 23, 2019 Available from: https://www.ncbi.nlm.nih.gov/books/NBK482117/.
44. Castro D, Keenaghan M. Arterial Blood Gas Treasure Island (FL): StatPearls Publishing LLC; [updated February 20, 2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK536919/.
2. Haagsma JA, Graetz N, Bolliger I, Naghavi M, Higashi H, Mullany EC, et al. The global burden of injury: incidence, mortality, disability-adjusted life years and time trends from the Global Burden of Disease study 2013. Inj Prev. 2016;22(1):3-18.
3. Azami-Aghdash S, Sadeghi-Bazargani H, Shabaninejad H, Gorji HA. Injury epidemiology in Iran: a systematic review. J Inj Violence Res. 2017;9(1):27.
4. Yadollahi M, Mokhtari AM, Malekhoseini HR. Fatality rate of trauma victims in southern Iran: a five-year survey. Trauma Mon. 2017;23(1):e42081-e.
5. Sobrino J, Shafi S. Timing and causes of death after injuries. Proc (Bayl Univ Med Cent). 2013;26(2):120-3.
6. Thompson KB, Krispinsky LT, Stark RJ. Late immune consequences of combat trauma: a review of trauma-related immune dysfunction and potential therapies. Mil Med Res. 2019;6(1):11.
7. Mira JC, Brakenridge SC, Moldawer LL, Moore FA. Persistent inflammation, immunosuppression and catabolism syndrome. Critical care clinics. 2017;33(2):245-58.
8. Binkowska AM, Michalak G, Słotwiński R. Current views on the mechanisms of immune responses to trauma and infection. Cent Eur J Immunol. 2015;40(2):206.
9. Frink M, van Griensven M, Kobbe P, Brin T, Zeckey C, Vaske B, et al. IL-6 predicts organ dysfunction and mortality in patients with multiple injuries. Scand J Trauma Resusc Emerg Med. 2009;17(1):49.
10. Fouladseresht H, Talepoor AG, Farjadian S, Khosropanah S, Doroudchi M. Anti-Varicella Zoster Virus IgG and hsCRP Levels Correlate with Progression of Coronary Artery Atherosclerosis. Iran J Allergy Asthma Immunol. 2019;18(5):543-53.
11. Fouladseresht H, Safa A, Khosropanah S, Doroudchi M. Increased frequency of HLA-A* 02 in patients with atherosclerosis is associated with VZV seropositivity. Arch Physiol Biochem. 2019:1-8.
12. Siwicka-Gieroba D, Malodobry K, Biernawska J, Robba C, Bohatyrewicz R, Rola R, et al. The Neutrophil/Lymphocyte Count Ratio Predicts Mortality in Severe Traumatic Brain Injury Patients. J Clin Med. 2019;8(9):1453.
13. Duchesne JC, Tatum D, Jones G, Davis B, Robledo R, DeMoya M, et al. Multi-institutional analysis of neutrophil-to-lymphocyte ratio (NLR) in patients with severe hemorrhage: A new mortality predictor value. J Trauma Acute Care Surg. 2017;83(5):888-93.
14. Ma J, Kuzman J, Ray A, Lawson BO, Khong B, Xuan S, et al. Neutrophil-to-lymphocyte Ratio (NLR) as a predictor for recurrence in patients with stage III melanoma. Sci Rep. 2018;8(1):1-6.
15. Tanık VO, Çınar T, Velibey Y, Öz A, Kalenderoğlu K, Gümüşdağ A, et al. Neutrophil-to-lymphocyte ratio predicts contrast-induced acute kidney injury in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention. J Tehran Heart Cent. 2019;14(2):59-66.
16. Fouladseresht H, Doroudchi M, Rokhtabnak N, Abdolrahimzadehfard H, Roudgari A, Sabetian G, et al. Predictive monitoring and therapeutic immune biomarkers in the management of clinical complications of COVID-19. Cytokine Growth Factor Rev. 2020;(In Press).
17. Sauaia A, Moore FA, Moore EE, Haenel JB, Read RA, Lezotte DC. Early predictors of postinjury multiple organ failure. Arch Surg. 1994;129(1):39-45.
18. Inose H, Kobayashi Y, Yuasa M, Hirai T, Yoshii T, Okawa A. Procalcitonin and Neutrophil Lymphocyte Ratio After Spinal Instrumentation Surgery. Spine (Phila Pa 1976). 2019;44(23):e1356-61.
19. Wang F, Wang L, Jiang T-t, Xia J-j, Xu F, Shen L-j, et al. Neutrophil-to-lymphocyte ratio is an independent predictor of 30-day mortality of intracerebral hemorrhage patients: a validation cohort study. Neurotox Res. 2018;34(3):347-52.
20. Jung J, Eo E, Ahn K, Noh H, Cheon Y. Initial base deficit as predictors for mortality and transfusion requirement in the severe pediatric trauma except brain injury. Pediatr Emerg Care. 2009;25(9):579-81.
21. Alexiou GA, Lianos G, Fotakopoulos G, Michos E, Pachatouridis D, Voulgaris S. Admission glucose and coagulopathy occurrence in patients with traumatic brain injury. Brain Inj. 2014;28(4):438-41.
22. Bordbar E, Paydar S, Taghipour M, Khalili H, Jafari M. Initial GCS and laboratory findings of patients with TBI are associated with the GOSE and mortality rate at one year. Int J Res Med Sci. 2018;6(1):14-9.
23. Yadollahi M, Anvar M, Ghaem H, Bolandparvaz S, Paydar S, Izianloo F. Logistic regression modeling for evaluation of factors affecting trauma outcome in a level I trauma center in Shiraz. Iran Red Crescent Med. 2017;19(1).
24. Dilektasli E, Inaba K, Haltmeier T, Wong MD, Clark D, Benjamin ER, et al. The prognostic value of neutrophil-to-lymphocyte ratio on mortality in critically ill trauma patients. J Trauma Acute Care Surg. 2016;81(5):882-8.
25. Heffernan DS, Monaghan SF, Thakkar RK, Machan JT, Cioffi WG, Ayala A. Failure to normalize lymphopenia following trauma is associated with increased mortality, independent of the leukocytosis pattern. Crit Care. 2012;16(1):R12.
26. Keel M, Eid K, Labler L, Seifert B, Trentz O, Ertel W. Influence of injury pattern on incidence and severity of posttraumatic inflammatory complications in severely injured patients. Eur J Trauma. 2006;32(4):387-95.
27. Faist E, Kupper TS, Baker CC, Chaudry IH, Dwyer J, Baue AE. Depression of cellular immunity after major injury: its association with posttraumatic complications and its reversal with immunomodulation. Arch Surg. 1986;121(9):1000-5.
28. Kovtun A, Messerer DA, Scharffetter-Kochanek K, Huber-Lang M, Ignatius A. Neutrophils in tissue trauma of the skin, bone, and lung: two sides of the same coin. J Immunol Res. 2018;2018.
29. Manson J, Cole E, De’Ath HD, Vulliamy P, Meier U, Pennington D, et al. Early changes within the lymphocyte population are associated with the development of multiple organ dysfunction syndrome in trauma patients. Crit Care. 2016;20(1):176.
30. Zhou Z, Ren L, Zhang L, Zhong J, Xiao Y, Jia Z, et al. Heightened innate immune responses in the respiratory tract of COVID-19 patients. Cell Host Microbe. 2020;27(6):883-90.
31. Mortaz E, Alipoor SD, Adcock IM, Mumby S, Koenderman L. Update on neutrophil function in severe inflammation. Front Immunol. 2018;9:2171.
32. Lei H, Schmidt-Bleek K, Dienelt A, Reinke P, Volk H-D. Regulatory T cell-mediated anti-inflammatory effects promote successful tissue repair in both indirect and direct manners. Front Pharmacol. 2015;6: :184.
33. Talepoor AG, Fouladseresht H, Khosropanah S, Doroudchi M. Immune-Inflammation in Atherosclerosis: A New Twist in an Old Tale. Endocr Metab Immune Disord Drug Targets. 2020;20(4):525-45.
34. Ward NS, Casserly B, Ayala A. The compensatory anti-inflammatory response syndrome (CARS) in critically ill patients. Clin Chest Med. 2008;29(4):617-25.
35. Xiao W, Mindrinos MN, Seok J, Cuschieri J, Cuenca AG, Gao H, et al. A genomic storm in critically injured humans. J Exp Med. 2011;208(13):2581-90.
36. Vanzant EL, Lopez CM, Ozrazgat-Baslanti T, Ungaro R, Davis R, Cuenca AG, et al. Persistent inflammation, immunosuppression and catabolism syndrome after severe blunt trauma. J Trauma Acute Care Surg. 2014;76(1):21-9.
37. Surbatovic M, Veljovic M, Jevdjic J, Popovic N, Djordjevic D, Radakovic S. Immunoinflammatory response in critically ill patients: severe sepsis and/or trauma. Mediators Inflamm. 2013;2013.
38. Younan D, Richman J, Zaky A, Pittet J-F. An increasing neutrophil-to-lymphocyte ratio trajectory predicts organ failure in critically-ill male trauma patients. An exploratory study. Healthcare (Basel). 2019;7(1):e42.
39. Yadollahi M. A study of mortality risk factors among trauma referrals to trauma center, Shiraz, Iran, 2017. Chin J Traumatol. 2019;22(4):212-8.
40. Bolandparvaz S, Yadollahi M, Abbasi HR, Anvar M. Injury patterns among various age and gender groups of trauma patients in southern Iran: a cross-sectional study. Medicine (Baltimore). 2017;96(41):e7812.
41. McIntyre A, Mehta S, Aubut J, Dijkers M, Teasell RW. Mortality among older adults after a traumatic brain injury: a meta-analysis. Brain Inj. 2013;27(1):31-40.
42. Aiyagari V, Deibert E, Diringer MN. Hypernatremia in the neurologic intensive care unit: how high is too high? J Crit Care. 2006;21(2):163-72.
43. Brinkman JE, Sharma S. Physiology, Respiratory Alkalosis Treasure Island (FL): StatPearls Publishing LLC; [updated Jun 23, 2019 Available from: https://www.ncbi.nlm.nih.gov/books/NBK482117/.
44. Castro D, Keenaghan M. Arterial Blood Gas Treasure Island (FL): StatPearls Publishing LLC; [updated February 20, 2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK536919/.
| Files | ||
| Issue | Vol 20 No 1 (2021) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v20i1.5411 | |
| Keywords | ||
| Inflammation Mortality Trauma | ||
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How to Cite
1.
Fouladseresht H, Bolandparvaz S, Abbasi H, Abdolrahimzadeh Fard H, Paydar S. The Neutrophil-to-Lymphocyte Ratio at the Time of Admission: A New Prognostic Indicator for Hospital Mortality of Trauma Patients. Iran J Allergy Asthma Immunol. 2021;20(1):33-45.
