Circulating Inflammatory and Immunomodulatory Mediators in Critically Ill Patients
CCCF ePoster library. Loukov D. Nov 1, 2016; 150939; 60
Dessi Loukov
Dessi Loukov
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Topic: Clinical Trial

Circulating Inflammatory and Immunomodulatory Mediators in Critically Ill Patients

Verschoor CP1, Loukov D1, Novakowski KE1, Naidoo A1, Thevaranjan N1, Dorrington MG1, Malik M1, Lamarche D1, Surette M1, Clarke F1, Zytaruk N1, Hand L1, McDonald E1, Hoad N1, Wachmann KA1, Johnstone J2, 3, Meade MO1, Marshall JC3,4, Karachi T1, Charbonney E5, Ansdell D1, Cook DJ1, Bowdish DME1 for the PROSPECT Investigators and the Canadian Critical Care Trials Group
1McMaster University, Hamilton, Ontario
2Public Health Ontario, Toronto, Ontario
3University of Toronto, Toronto, Ontario
4St. Michael’s Hospital, Toronto, Ontario
5University of Montreal, Montreal, Quebec

Grant acknowledgements:
Funded by the Hamilton Academic Health Science Organization, Physicians Services Incorporated of Ontario, Canadian Frailty Network (previously Technology Evaluation in the Elderly Network) and the Canadian Institutes for Health Research.


Introduction: Circulating cytokines, acute phase proteins, and bacterial products may be associated with disease severity and the outcome of critical illness.
Objectives: We sought to test whether the levels of cytokines, acute phase proteins, and bacterial products were associated with infection upon admission to the intensive care unit (ICU) or with ICU survival. 
Methods: This was a prospective, observational sub-study nested within a multicenter pilot randomized control trial of probiotic administration.  Three tertiary care medical-surgical and neuro-trauma ICUs in Hamilton, Ontario, Canada were included. The patients were critically ill, invasively mechanically ventilated patients.  Serum cytokines (GM-CSF, IL-10, IL-12p70, IL-17A, IL-1b, IL-4, IL-23, IL-6, and TNF), C-reactive protein (CRP) and nucleic acids (cell-free, mitochondrial, and 16S bacterial DNA), and whole blood endotoxin activity (EAA) were measured on admission to ICU and thrice weekly thereafter while in the ICU.  Infections were documented on admission and throughout the ICU stay in accordance to predefined standardized definitions.  Patients were followed until death or discharge from ICU.  
Results: A total of 42 patients (26 male and 16 female) were recruited for the study and 242 biospecimens were drawn. Patient ICU stay ranged from 1 to 58 days (median 9). These results reflect 36 patients who had biospecimens drawn upon ICU admission and 29 prior to ICU discharge (whether dead or alive).  Upon ICU admission, 28 patients had an infection and 8 patients had no infection. Median levels of the following cytokines at baseline were significantly higher for patients with infection than without infection (IL-10, 17.8 vs. 7.4 pg/ml, p=0.02; IL-6, 42.5 vs. 14.7 pg/ml, p=0.03 and TNF pg/ml, 12.8 vs. 3.7, p=0.02).  No significant differences between patients with and without infection were observed for other cytokines, CRP, nucleic acids or EAA measured at baseline.  Of 29 patients with samples drawn within 3 days of death or discharge from ICU, 5 died (mortality rate 17.2%); cytokine, CRP, nucleic acid and EAA levels were similar between patients who survived and died. 
Conclusions: The baseline cytokines IL-10, IL-6 and TNF were significantly elevated in critically ill patients with infection upon admission to ICU when compared to patients without infection. Levels of cytokines, CRP, nucleic acids and EAA drawn within 72 hours of death or discharge were not associated with ICU mortality.   


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