Evaluation of the Role of Hydrocortisone Either Alone or Combined With Fludrocortisone in the Outcome of Septic Shock in Adults
Condition: Septic Shock
MeSH terms: Shock, Septic; Shock
Study type: Interventional
Phase: Phase 4

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 .
    


Intervention name(s): Hydrocortisone
Intervention type(s): Drug
Intervention description(s): After approval of the ethical committee of faculty of Medicine Ain Shams University and obtaining a written informed consent from all patients or their legal guardians, the study will be conducted on 66 patients subdivided randomly via computer closed envelopes method into 3 equal groups, 22 patients for each group; group HF (hydrocortisone & fludrocortisone), group H (hydrocortisone) and group C (control group).
Other intervention name(s): Fludrocortisone
Intervention MeSH terms: Hydrocortisone; Fludrocortisone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Prevention