Yoğun Bakım Hastalarında Yoğun İnsülin Tedavisi İle Kan Șekerinin Sıkı Kontrolünün Mortalite Ve Morbiditeye Etkileri

Abstract

Aim: This study was planned in order to search the effect of tight blood glucose level control with continuing insulin infusion on mortality, morbidity and immune paralysis among critically ill patients. Material and Method: This prospective randomized study was conducted on 20 patients after approval from all patients or first-degree relatives were obtained on admission to intensive care unit (ICU). On admission, the patients were randomly assigned to Intensive Insulin Therapy (IIT) or Conventional Insulin Therapy (CIT) Groups. Each group involved 10 patients. In IIT Group, we tried to maintain blood glucose levels between 80-110 mg/dL via continuous insulin infusion; whereas blood glucose level was maintained between 180-200 mg/dL in CIT Group. After admission, APACHE II (Acute Physiology and Chronic Health Evaluation II) and TISS 28 (Therapeutic Intervention Scoring System) scores were calculated daily. Complete blood count, blood chemistry analyzes CRP (C-reaktive protein) levels and monocytic HLA-DR levels were determined on admission, 5th, 14th and 28th days. The length of stay in intensive care unit and in hospital were also recorded in addition to the possible cause and time of mortalities. Were performed for statistical analyzes Mann Whitney U and Chi-Square Test. The p values less than 0.05 were considered as statistically significant. Results: The tranfusion requirement, blood glucose levels at 6 a.m. and daily minimal and maximal glucose levels were found to be lower in the IIT Group (p0.05). Although intensive insulin therapy reduced intensive care unit mortality by 20% and hospital mortality by 30%, these variables were not considered to be statistically significant. In addition, this study showed that intensive insulin therapy reduced lengths of intensive care unit and hospital stay, inotropic treatment, renal replacement therapy requirement, hyperbilirubinemia and blood stream infection; however these differences were not statistically insignificant. We could not show important effect of intensive insulin therapy upon monocyte HLA-DR and CRP levels. Conclusion: There were no difference between IIT or CIT Groups in terms of mortality and immun paralysis. The tranfusion requirement, blood glucose levels at 6 a.m. and daily minimal and maximal glucose levels were significantly lower in IIT Group (p<0.05)

Keywords

• Criticall illness, Stress response, Hyperglycemia, İntensive insulin therapy, Tight glucose control

Yoğun Bakım Hastalarında Yoğun İnsülin Tedavisi İle Kan Șekerinin Sıkı Kontrolünün Mortalite ve Morbiditeye Etkileri

Abstract

Amaç: Bu çalıșma, yoğun bakım (YB) hastalarında sürekli insülin infüzyonu ile kan șekerinin sıkı kontrolünün mortalite, morbidite ve immün paraliziye etkilerini araștırmak amacı ile planlandı. Materyal ve Metod: Bu prospektif, randomize ve kontrollü çalıșmaya YB’a kabul edilen hasta veya birinci derece yakınlarından onam alınan toplam 20 hasta dahil edildi. Hastalar YB’ye kabulden sonra randomize olarak, Yoğun İnsülin Tedavisi (YİT) veya Geleneksel İnsülin Tedavisi (GİT) gruplarından birine alındı. Her iki gruba 10’ar hasta dahil edildi. Sürekli insülin infüzyonu ile YİT grubunda kan șekeri 80-110 mg/dL, GİT grubunda 180-200 mg/dL arasında tutuldu. Hastalar YB’ye kabul edildikten sonra günlük APACHE II (Acute Physiology and Chronic Health Evaluation II, Akut Fizyoloji ve Kronik Sağlık Değerlendirmesi) ve TISS 28 (Therapeutic Intervention Scoring System, Tedavi Amaçlı Girișim Skorlama Sistemi) skorlamaları yapıldı. Kabul, 5, 14 ve 28’inci günde tam kan ve biyokimyasal analizler yapıldı, C-reaktif protein (CRP) ve akım sitometri yöntemi ile monositik HLA-DR düzeyi saptandı. Yoğun bakım ve hastanede kalma süreleri ile olası mortalite nedeni ve zamanı kaydedildi. İstatiksel analizde Mann Whitney U Testi ve Chi-Square Testi kullanıldı ve p

Keywords

• Kritik hastalık, Stres yanıt, Hiperglisemi, Yoğun insülin tedavisi, Sıkı glukoz kontrolü

References

1. 1. Takala J, Ruokonen E, Webster NR, et al. Increased mortality associated with growth hormone treatment in critically ill. N Eng J Med 1999;341:785-792.
2. 2. Weber DJ, Raasch R, Rutala WA. Nosocomial infections in ICU. The growing importance of antibioticresistanst pathogens. Chest 1999;115:34- 41
3. 3. Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Eng J Med 2001;345:1359-1367.
4. 4. McCowen KC, Malhotra A, Bistrian BR.Stress-induced hyperglycemia. Crit Care Clin 2001;17:107-124.
5. 5. Gearhart MM, Parbhoo SK. Hyperglycemia in the critically ill patient. AACN Clin Issues. 2006;17:50- 55.
6. 6. Robinson LE, van Soeren MH. Insulin resistance and hyperglycemia in critical illness:role of insulin in glycemic control. AACN Clin Issues. 2004;15:45-62.
7. 7. Van den Berghe G, Wilmer A, Hermans G, et al. Intensive insulin therapy in the medical ICU. N Engl J Med 2006;354:449-461.
8. 8. Brunkhorst FM, Engel C, Bloos F, et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. German Competence Network Sepsis (SepNet). N Engl J Med 2008;358:125-139.

9. 9. Preiser JC, Devos P, Ruiz-Santana S, et al. A prospective randomised multicentre controlled trial on tight glucose control by intensive insulin therapy in adult intensive care units:the Glucontrol study. Intensive Care Med. 2009;35:1738- 1748.
10. 10. Finfer S, Chittock DR, Su SY, et al. Intensive versus conventional glucose control in critically ill patients. NICESUGAR Study Investigators. N Engl J Med 2009 ;360:1283-1297.
11. 11. Griesdale DE, de Souza RJ, van Dam RM, et al. Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data. CMAJ 2009;180:821-827.
12. 12. Wiener RS, Wiener DC, Larson RJ. Benefits and risks of tight glucose control in critically ill adults: a metaanalysis. JAMA 2008;300:933-944
13. 13. Finfer S, Liu B, Chittock DR, et al. NICE-SUGAR Study Investigators. Hypoglycemia and risk of death in critically ill patients. N Engl J Med 2012;367:1108-1118.
14. 14. Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med 2003;348:138-150.
15. 15. Gao F, Gao E, Yue TL, et al. Nitric oxide mediates the antiapoptotic effect of insulin in myocardial ischemiareperfusion: the roles of PI-kinase, Akt, and endothelial nitrix oxide synthase phosphorylation. Circulation 2002;105:1497-1502.
16. 16. Gunst J, Van den Berghe G. Blood glucose control in the intensive care unit: benefits and risks. Semin Dial 2010;23:157-162.
17. 17. Bone RC, Balk RA, Cerra FB, et al. American College of Chest Physicians Society of Critical Care Medicine Concencus Conference: Definitions for sepsis and organ failure and guidelines for the use innovative therapies in sepsis. Crit Care Med 1992;20:864-874.
18. 18. Tulunay M. Yoğun Bakım Ünitesi. İliçin G, Ünal S, Biberoğlu K, Akalın S, Süleymanlar G (eds): Temel İç Hastalıkları. Güneş Kitabevi, Ankara 1996;605-681.
19. 19. Kox WJ, Volk T, Kox SN, Volk HD. Immunomodulatory therapies in sepsis. Intensive Care Med 2000;26:124-28. 20. Bone RC. Sir Isaac Newton, sepsis, SIRS, and CARS. Crit Care Med 1996;24:1125- 1128.
20. 21. Tulunay M. Sistemik inflamatuvar yanıt sendromu, sepsis, çoklu organ işlev bozukluğu sendromu: terminoloji, insidans, mortalite, risk faktörleri. Türkiye Klinikleri Cerrahi Dergisi. Yoğun Bakım Özel Sayısı 2002;7:113-23.
21. 22. Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med 2003;348:138-50.
22. 23. Satah A. Human leukocyte antigen-DR expression on perpheral monocytes as a marker of sepsis during acute pancreatitis. Pancreas 2002;25:245-250.
23. 24. Nierhaus A. Reversal of immunparalysis by recombinant granulocyte-macrophage colony stimulating factor in patients with severe sepsis. Intensive Care Med 2003;29:646-651.
24. 25. Hynninen M. Predictive value of monocyte histocompatibility leukocyte antigen-DR expression and plasma interleukin 4-10 levels in critically ill patients with sepsis. Shock 2000;20:1-4.
25. 26. Chang RWS, Jacobs S, Lee B. Predicting outcome among intensive care unit patients using computerized trend analysis of daily APACHE II scores corrected for organ system failure. Intensive Care Med 1988;14:558-566.
26. 27. Rogers J, Fuller HD. Use of daily APACHE II scores to predict individual patient survival rate. Crit Care Med 1994, 22:1402-1405.
27. 28. Wagner DP, Knaus WA, Harell FE. Daily prognostic estimates for critically ill adults in critical care units. Crit Care Med 1994;22:1359-1372.
28. 29. Knaus WA, Zimmerman JE, Wagner DP, et al. APACHE II-acute phsiology and chronic health evalution: A phsiologically based classification system. Crit Care Med 1981;9:591-597.
29. 30. Knaus WA, Zimmerman JE, Wagner DP, et al. APACHE II: a severity of disease classification system. Crit Care Med 1985;13:818-829.
30. 31. Egi M, Bellomo R. Reducing glycemic variability in intensive care unit patients: a new therapeutic target? J Diabetes Sci Technol. 2009 1;3:1302-1308.
31. 32. Monnier L, Mas E, Ginet C, et al. Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA. 2006;295:1681-1687.
32. 33. Hebert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled trial of transfusion requirements in critical care. Transfusion Recquierements in Critical Care Investigators, Canadian Critical Care Trials Group. New Engl Med 1999;340:409-417.
33. 34. Tshoikowsky K, Geissing MH, Schile A, et al. Coincedence of pro and antiiflammatory responses in early phase of severe sepsis: Longitudinal study of mononucleer histocompatibility leukocyte antigen-DR expression, procalcitonin, C-reactive protein and changes in T-cell subsets in septic and postoperative patients. Crit Care Med 2002;30:224-231.
34. 35. Le HT, Harris NS, Estilong AJ, Olson A, Rice MJ. Blood glucose measurement in the intensive care unit: what is the best method? J Diabetes Sci Technol 2013 1;7:489-499.
35. 36. Desachy A, Vuagnat AC, Ghazali AD et al. Accuracy of bedside glucometry in critically ill patients: influence of clinical characteristics and perfusion index. Mayo Clin Proc 2008;83:400-405.
36. 37. American Diabetes Association. Standards of Medical Care in Diabetes— 2012. Diabetes Care 2012;35:S11-S63.
37. 38. Dellinger RP, Levy MM, Rhodes A et al. Surviving Sepsis Campaign Guidelines Committee; Pediatric Subgroup. Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012. Crit Care Med 2013;41:580-637.