The aim of this observational study is to investigate whether GDF-15 levels can predict clinical outcome in patients admitted to the intensive care unit with a diagnosis of septic shock.

The main question is:

• Can the level of GDF-15 levels during ICU admission predict the development of multiple organ failure in patients with septic shock? All patients will continue to receive routine treatment for sepsis and septic shock. The investigators will observe the development of multiple organ failure by the Sequential Organ Failure Assessment (SOFA) score increase

Sepsis can be defined as a disproportionate host response to infection. It has been reported that 2.8 million deaths per year in high-income countries are associated with sepsis. Excessive inflammatory response may lead to organ failure and death after multiple organ failure. After infection, pathogen-mediated molecular fragments (PAMPS) are formed and recognised by toll-like receptors and the immune system is activated. Pro- and anti-inflammatory mediators are released and levels of various cytokines increase. These changes affect neutrophil-endothelial adhesion, disrupt the coagulation cascade and increase microthrombi formation. The systemic inflammatory state may be followed by immune paralysis and secondary infections, which may lead to the loss of patients as a result of multiple organ failure.

Growth differentiation factor-15 (GDF-15), also known as macrophage inhibitory cytokine-1 (MIC-1), is a member of the transforming growth factor-β (TGFβ) superfamily. It is found in many tissues and is strongly expressed in epithelial cells and macrophages. Its level is correlated with macrophage activation. In recent years, circulating GDF-15 level has been identified as a biomarker with prognostic value in cardiopulmonary diseases such as heart failure myocardial infarction and pulmonary embolism. In addition, elevated GDF-15 levels have been shown in end-stage renal failure and acute respiratory distress syndrome and chronic inflammatory diseases.

Septic shock requires vasopressor support to maintain a mean arterial pressure of 65 mmHg despite adequate fluid replacement. Septic shock has a higher mortality rate and development of multiple organ failure is more common.

Although the correlation of elevated GDF-15 levels with organ failure has been shown, the relationship between GDF-15 levels and multiple organ failure in patients with septic shock has not yet been studied.

Primary aim in this study is to investigate the relationship between GDF-15 level measured after admission and progression to multiple organ failure in patients admitted to intensive care with septic shock.

Secondary aim is to predict mortality with GDF-15 level in patients treated in intensive care unit with septic shock.

Inclusion Criteria:

• Patients older thab 18 years of age
• Patients with septic shock
• Patients without end-stage renal failure (KDIGO G4,G5)
• Patients without chronic liver disease
• Patients with New York Heart Association (NYHA) stage 1-2
• Patients not diagnosed with active cancer
• Non-pregnant patients
• Patients without chronic immunodeficiency
• Patients without chronic inflammatory disease

Exclusion Criteria:

• Patients younger than 18 years age
• Patients not diagnosed with septic shock
• Patients with end-stage renal failure
• Patients with chronic liver disease
• Patients with New York Heart Association (NYHA) stage 3-4
• Patients diagnosed with active cancer
• Pregnant patients
• Patients with chronic immunodeficiency
• Patients with chronic inflammatory diseases

Patients admitted to the intensive care unit of Ankara Bilkent City Hospital with a diagnosis of septic shock who met the inclusion criteria

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