evaluation of the role of hydrocortisone either alone or combined with fludrocortisone in the outcome of septic shock in adults

Conditions: Septic Shock

Summary: during infection, oflfending microbes interact with the host immune system producing a downstream inflammatory cascade involving cytokines and other mediators, which in turn triggers a systemic response. the resultant effects linclude vasodilation, increased vascular permeability, myocardial depression, and impairment of the coagulation cascade, resulting in global imbalance of systemic oxygen supply and demand. during the late stage of sepsis, immunosuppression predominates, leading to multi-organ dysfunction and further clinical deterioration . sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection with two or three on quick sepsis-related organ failure assessment score (qsofa). septic shock is defined as the presence of sepsis and refractory hypotension to fluid management. vasopressors are needed to maintain systolic blood pressure more than 90mmhg or mean blood pressure more than 65 mmhg . experimental and clinical evidence suggests that sepsis is associated with dysregulated response of hypothalamic-pituitary-adrenal axis that may involve any of the steps from cortisol production to cortisol use by cells . glucocorticoid therapy for the treatment of septic shock remains controversial, with conflicting evidence regarding a mortality benefit. it has been used in patients with septic shock who remained hypotensive after fluid and vasopressor resuscitation. fludrocortisone is a corticosteroid and acts as a powerful mineralocorticoid along with some additional but comparatively very weak glucocorticoid activity. relative to cortisol, it is to 10 times the glucocorticoid potency but 250 to 800 times the mineralocorticoid potency . fludrocortisone is added to hydrocortisone to provide additional mineralocorticoid potency. the rationale for adding mineralocorticoid treatment is that an experimental sepsis study showed marked nuclear factor nf-κb mediated down regulation of vascular mineralocorticoid receptors . corticosteroids attenuate inflammation in various organs an effect partly related to inhibition of nuclear factor nf-κb. improve cardiovascular function by restoring effective blood volume through increased mineralocorticoid activity and by increasing systemic vascular resistance through vascular α-adrenergic responsiveness and reduces inflammation-mediated vasodilation .


Eligibility criteria:
inclusion criteria: * this study will be conducted on patients between 18-80 years old, both sexes who are suffering from septic shock and have any of the following any of 1, 2, or 3 criteria * clinical evidence of infection within the previous 72 hours of icu admission (any of a, b, or c) 1. presence of polymorphonuclear cells in a normally sterile body fluid. 2. culture or gram stain of blood, sputum, urine or normally sterile body fluid positive for a pathogenic micro-organism. 3. focus of infection identified by visual inspection (e.g. ruptured bowel with the presence of free air or bowel contents in the abdomen found at the time of surgery, wound with purulent drainage). * sepsis-related organ failure assessment (sofa) score of 3 or 4 (on a scale of 0 to 4 for each of six organ systems) for at least 2 organs and at least 6 hours (singer et al., 2016). * vasopressors therapy ( norepinephrine , epinephrine , or any other vasopressors at a dose of ≥ 0.25 µg / kg / minute ) for at least 6 hours to maintain a systolic blood pressure of at least 90 mm hg or mean blood pressure of at least 65 mm hg (singer et al., 2016). exclusion criteria: * refusal of patient or legal guardian to consent to participate in the study. * pregnancy and lactation. * gastrointestinal bleeding