Evaluation of high C -

reactive protein and low

cholesterol levels as prognostic values of
survival in critically ill patients with severe
sepsis
Protocol of thesis
Submitted for partial fulfilment of Master degree of Critical care medicine
By
Ahmed Gebriel Basioni
M.B.B.Ch
Supervised by

Prof /Dr Saad Ibrahim Saad

Professor of anaesthesia and intensive care
Faculty of medicine-Benha University
Dr/Eman Shafik AbdelHamid
Lecturer of Critical care medicine
Faculty of medicine-Benha University
Faculty of medicine
Benha University
2022
 Introduction

Patients with severe, life-threatening, infectious diseases account for a

significant number of those admitted to intensive care units (ICU). Sepsis
is not a homogeneous disease; rather, it is a complex clinical syndrome
with distinct immunologic features[1,2] .The deleterious effects of
bacterial invasion of body tissues result from the combined actions of
enzymes and toxins produced by the microorganisms themselves, and
by endogenous cells in response to the infectious process. In spite of
advances made in supportive care, the mortality rate in patients with
severe sepsis continues to exceed 30%. The ambiguity of clinical findings
and unclear risk stratification in sepsis have been major problems in
sepsis intervention trials [3]. Thus, the prognosis of a septic patient may
contribute significantly to the success of any intervention. Within this
context, there is a need for biomarkers to tackle the challenges of sepsis
monitoring and treatment [4].
In 1994, Dunham and co-workers [5] showed that patients with severe
trauma had a sudden reduction in total serum cholesterol
concentration. Hypocholesterolaemia has been observed in patients
undergoing surgical interventions [6], and in those with multiple-organ
dysfunction syndrome [7-9] and burns [10]. There is also the theory that
serum cholesterol correlates with organ failure and sepsis [5].Proposed
explanations for the development of hypocholesterolaemia include
down-regulation of hepatic synthesis [9], dilutional effects with
resuscitation [11], loss of apo proteins in burns after blister formation,
and metabolic use [5,12]. The use of serum cholesterol as a prognostic
indicator of infection and multiple organ dysfunction syndrome, and as
 a biologic marker for resolution of systemic inflammation, is less well
defined.
A number of inflammatory cells and mediators involved in the
inflammatory response have been assessed for their role as potential
markers of the presence and severity of the inflammatory response and
organ failure [13-15]. Serum levels of C-reactive protein (CRP), an acute-
phase protein synthesized by the liver after stimulus by various
cytokines including tumour necrosis factor and interleukin (IL)-6,
markedly increase within hours of infection or inflammation [16].
Numerous studies have shown increased CRP levels in patients with
sepsis [17], but their relation to multiple-organ dysfunction and failure,
to date, has not been well evaluated.
In the present study, we aimed to evaluate the prognostic value of
cholesterol levels in a well-defined cohort of ICU patients as compared
with those of other biomarkers (CRP and physiologic score [acute
physiology and chronic health evaluation, APACHE] II).
 Aim of the study

 Evaluation of serum C-reactive protein and cholesterol as a

prognostic factor for survival in patients with severe sepsis.
 Patients and methods

Patients and settings:

The study is a prospective randomized controlled study .The study would

be conducted on 60 resuscitated patients in whom severe sepsis was
diagnosed within 4 hours of clinical onset, would be enrolled
consecutively in the study.
Administrative and Ethical design:
 An official permission will be obtained from the Dean of Benha
Faculty of Medicine and the administrators of Benha University
Hospitals.

 An informed written consent will be obtained from all participants; it

will include data about aim of the work, study design, site, time,
subject and measures, confidentiality.

 An approval from Research Ethics Committee in Benha faculty of

medicine will be obtained.
Inclusion criteria:

I. Patients with age greater than 18 years.

II. Patients satisfying the criteria for sepsis.

III. SOFA (sepsis-related organ failure assessment) score.

Exclusion criteria:

I. Patients with burns, those receiving coronary care, or with trauma

were excluded from the study.

II. Patients with an immunosuppressed state (i.e., receiving treatment

with steroids; or bone marrow or organ transplant recipients,
leukopenia [white blood cell count, b1000/lL] or neutropenia
[polymorph nuclear granulocyte count, b500/lL], hematologic
malignancy ,SLE and AIDS).

III. A medical condition considered to be irreversible or lethal within 24

hours of admission, would be also excluded from the study.

Methodology:
After getting written informed consent from the patients or immediate
relatives, a detailed clinical examination was done in all patients. After
the diagnosis of sepsis was made in patients with the help of examination
and laboratory investigations, blood sample would be collected on day of
admission, on day 4 and on the day of discharge from the ICU or on the day of
death to determine serum total cholesterol and CRP levels. The increase
or decrease in cholesterol and CRP values would be compared with
outcome of the disease.

Data collection
Critically ill patients with bacteriologically documented infections would be
included in the study as soon as they meet at least two of the following criteria of
sepsis, defined by the American College of Chest Physicians/Society of Critical Care
Medicine Consensus Conference Committee : temperature higher than 38 °C or
lower than 36°C; heart rate (HR) greater than 90 beats per minute (bpm);
respiratory rate (RR) greater than 20 breaths per minute (breaths/min); arterial
carbon dioxide tension (PaCO2) lower than 32 mmHg; leukocyte count of greater
than 12 109 cells/L or less than 4 109 cells/L. In addition, at least one of the
following conditions would be required: hypoxemia (arterial oxygen
tension/inspired oxygen concentration [PaCO2/FIO2], b250); oliguria (urine output,
b0.5 mL/kg body weight for two h); lactic acidosis (lactate concentration, N2
mmol/L); thrombocytopenia,
(Platelet count, b100 109/L); or a recent change in mental status without sedation.

Data management and statistical analysis:

 The collected data would be statistically presented and analyzed using the
Statistical Package for Social Science (SPSS).

 Categorical data would be expressed as number and percentage.

 Continuous data would be expressed as mean and standard deviation.

 Suitable tests of significance would be used.

 References

1. Cohen J. The immunopathogenesis of sepsis. Nature 2002; 420: 885-.19

2. Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med
2003;348:138-.05

3. Riedemann NC, Guo RF, Ward PA. The enigma of sepsis. J Clin Invest
2003;112:460-
.7

4. Dunham CM, Frankenfield D, Belzberg H, et al. Inflammatory markers:

superior predictors of adverse outcome in blunt trauma patients? Crit Care Med
1994;22:667-72.

5. Coombes EJ, Shakespeare PG, Batstone GF. Lipoprotein changes after burn injury
in man. J Trauma 1980;20:971-5.

6. Sun X, Oberlander D, Huang J, Weissman C. Fluid resuscitation, nutritional

support, and cholesterol in critically ill postsurgical patients. J Clin Anesth 1998;10:302-
8.

7. Smith RP, Lipworth BJ, Cree IA, et al. C-reactive protein: a clinical marker in
community-acquired pneumonia. Chest 1995;108:1288-91.

8. Chien JY, Jerng JS, Jen Yu C, Yang PC. Low serum level of high density lipoprotein
cholesterol is a poor prognostic factor for severe sepsis. Crit Care Med 2005;33:1688-93
9. Vesy CJ, Kitchens RL, Wolfbauer G, Albers JJ, Munford RS.
Lipopolysaccharidebinding protein and phospholipid transfer protein release
lipopolysaccharides from gramnegative bacterial membranes. Infect Immune
2000;68:2410-7.

10.Eichacker PQ, Parent C, Kalil A, et al. Risk and the efficacy of anti-inflammatory
agents: retrospective and confirmatory studies of sepsis. Am J Respir Crit Care Med
2002;166:1197-205.

11.Gui D, Spada PL, De Gaetano A, Pacelli F . Hypocholesterolaemia and risk of death

in the critically ill surgical patient. Intensive Care Med 1996;22:790-4.

12.Eichacker PQ, Parent C, Kalil A, et al . Risk and the efficacy of anti-inflammatory

agents: retrospective and confirmatory studies of sepsis. Am J Respir Crit Care Med
2002;166:1197-205.

13.Levels JH, Abraham PR, van Barreveld EP, Meijers JC, van Deventer SJ.
Distribution and kinetics of lipoprotein-bound lipoteichoic acid. Infect Immun
2003;71:3280-4.

14.Albert MA, Ridker PM (2006) C-reactive protein as a risk predictor: do race/ ethnicity
and gender make a difference? Circulation 114: e67–74.

15.Schmit X, Vincent JL (2008) The time course of blood C-reactive protein

concentrations in relation to the response to initial antimicrobial therapy in patients
with sepsis. Infection 36: 213–219.

16.Gaddam BK, Narayanan M. Study of serum HDL cholesterol levels in sepsis patients
and its prognostic significance. Int J Adv Med. 2019; 6:312-7.

17.Seymour CW, Angus DC. Sepsis and Septic Shock. Harrison's Principles of Internal
Medicine.20th ed. McGraw Hill, 2018, 2044-2052.
 ‫بروتوكول‬
‫توطئة للحصول على درجة الماجستير في طب ورعاية الحاالت) الحرجة‬
‫من الطبيب‬
‫احمد جبريل بسيونى‬
‫بكالوريوس الطب والجراحة‬

‫تحت إشراف‬

‫أ‪.‬د‪/‬سعد ابراهيم سعد‬

 ‫أستاذ التخدير والعناية المركزة‬
‫كلية الطب‪-‬جامعة بنها‬

‫د‪/‬ايمان شفيق‬
‫مدرس طب ورعاية الحاالت الحرجة‬
‫كلية الطب‪-‬جامعة بنها‬

‫قسم طب ورعاية الحاالت الحرجة‬

‫كلية الطب‪-‬جامعة بنها‬
‫‪2022‬‬