determination of the effectiveness and the cost-effectiveness of simvastatin(Zocor 40 mg) plus standard therapy (SSCG)versus standard therapy alone in critically ill septic patient from the societal perspective over one year.

Prospective double blinded randomized controlled study Will be carried out at Ain-Shams university hospital Method: - After approval of the research ethics committee of Ain shams University and obtaining consent from each patient, 100 patients newly admitted to the intensive care unit (ICU) diagnosed to have sepsis/severe sepsis defined by American College of Chest Physicians (ACP) *will be randomized by the clinical pharmacist using a computer-generated randomization sequence with a block size of four into two groups.

Group I (Control group):-50 patients will be treated according to "Surviving Sepsis Campaign guidelines (SSCG) (Dellinger, et al. 2013) Group II (Intervention group):-50 patients will be treated according SSCG plus simvastatin.

Outcomes:- Primary outcome measures: 28 day ICU and hospital mortality.

Secondary Outcome Measures:

• Requirement and length of renal replacement therapy, vasoactive agent support or mechanical ventilation
• Total ICU length of stay.(LOS)
• Number of patients alive 3, 6, and 12 months
• Incremental cost effectiveness ratio

Inclusion criteria:-

1. Age >18 and less than 70
2. Sepsis for less than 24 hours from ICU admission

Exclusion criteria:-

1. Elderly (defined as older than 70).
2. Pediatrics (defined as younger than 18).
3. Pregnancy and nursing.
4. Unable to receive enteral medications.
5. History of hypersensitivity to the trial drug.
6. Are receiving drugs known to interact with simvastatin.
7. Acute liver failure and chronic liver disease (Child C).
8. High risk of rhabdomyolysis (multiple traumas, crush injuries, extensive burns(>60%), baseline creatinine kinase (CK) ≥ten-times upper limit of normal.
9. Patients with dyslipidemia or Prior statin user.
10. Sever renal impairment (defined as need for replacement therapy )and uncontrolled hypothyroidism
11. Have a history of known or suspected porphyria
12. Are unlikely to survive more than 24 hours