C-Reactive Protein (CRP) as a Biomarker in the Management of Sepsis Ne Myo Aung, Kaung Myat, Mar Mar Kyi, Myo Lwin Nyein Department of Medicine, University of Medicine 2, Yangon

Department of Medical Research FUNDING External Grant from Department of Medical Research Myanmar

BACKGROUND SEPSIS is fatal! National In-hospital Death – Leading cause of mortality ICD 10 Code 41 – Sepsis & Septicemia ICD 10 Code A41 2012 2013 2014 2015 2016 Mortality 6.1% 6% 7.4% 8% 6.6% Leading Cause 1 MOHS, Hospital Statistics Report 2018

BACKGROUND Appropriate and timely management could change the outcome of sepsis. Biomarker guided therapy could help change of intensity of treatment. C-Reactive Protein (CRP) could be the potential candidate as CRP level reacts to sepsis drastically.

OBJECTIVES This study aimed to determine the usefulness of C-Reactive Protein (CRP) as biomarker for sepsis management.

MATERIALS & METHODS The study was hospital based observational study. The study was conducted in Medical Ward of Insein General Hospital. The study population was those over 18 years with severe sepsis.

MATERIALS & METHODS The inclusion criteria were fever plus any two of qSOFA parameters - Respiratory rate  22/min - Glasgow Coma Scale < 15 - Systolic Blood Pressure  100 mmHg And Informed Consent qSOFA – quick sequential organ failure assessment score

MATERIALS & METHODS Fever plus Any 2 qSOFA Entry Point (Time of Admission) Record Clinical Parameters Blood culture CRP determination (1st Time) Serial Observation of Organ Damage CRP determination (2nd Time) at 48 hours after Admission Observe for Endpoints

MATERIALS & METHODS Primary Endpoint – In-hospital Death Secondary Endpoints - Hospital Stay - Development of Shock - Multi-organ Failure - Bacteraemia

MATERIALS & METHODS C-Reactive Protein was measured quantitatively by ELISA. The study was ethically approved by Ethic Review Committee of University of Medicine 2, Yangon.

RESULTS One hundred and fifty six (156) sepsis cases met the study criteria. Mean age of study population was 46. Male to female ratio was nearly 1:1.

RESULTS Ninety nine percent of cases (154/156) had high CRP (>10mg/L) on admission.

RESULTS Primary Endpoint – In-Hospital Death 29 Cases died in hospital.

8 deaths within 24 hours of admission RESULTS Primary Endpoint – In-Hospital Death 156 cases included 8 deaths within 24 hours of admission 21 deaths after 24 hours 127 cases survived

RESULTS Primary Endpoint – In-Hospital Death All cases that died within 24 hours of hospital admission were found to have very high CRP level (> 100mg/L).

Secondary Endpoints – for CRP level at admission RESULTS Secondary Endpoints – for CRP level at admission Very High CRP on Admission (>100 mg/L) N = 131 High and normal CRP on Admission (<100 mg/L) N = 25 p value Development of Shock (percent) 55 68 0.11 Multi-organ failure (percent) 23 16 0.16 Bacteremia 8 0.29 Hospital Stay (Mean) (days) 7.7 (SD 5.2) 6.3 (SD 3) 0.001

RESULTS CRP after 48 hours of treatment (post-admission) Thirty percent (61/156) of cases had rising CRP value after 48 hours of treatment.

CRP after 48 hours of treatment (post-admission) RESULTS CRP after 48 hours of treatment (post-admission) CRP rise N = 61 CRP fall N = 87 p value Death after 48 hours (percent) 28 4.6 < 0.00001 Multi-organ failure (percent) 46 3 Hospital Stay (Mean) (days) 8.2 (SD 4.4) 7.6 (SD 5.1) 0.88

CONCLUSION Very high CRP (>100mg/dL) on admission strongly predicted immediate mortality (within 24 hours). It also predicts longer hospital stay. However, very high CRP on admission did not predict development of shock or multi-organ failure or bacteraemia.

CONCLUSION Rise of CRP after treatment strongly predicts in-hospital death and development of multi-organ failure.

CONCLUSION Therefore it can be concluded that C-Reactive Protein level is a useful biomarker in the management of sepsis!

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