Hemodynamic and Inflammatory Effects of Abrupt Versus Tapered Corticosteroid Discontinuation in Septic Shock
Condition: Septic Shock
MeSH terms: Shock, Septic; Shock
Intervention: hydrocortisone; Normal Saline
Intervention description: 1) Hydrocortisone 50 mg IV every 12 hours x 4 doses (2 days), followed by Hydrocortisone 50 mg IV every 24 hours x 2 doses (2 days); 0.9% sodium chloride (equal volume to hydrocortisone) IV every 12 hours x 4 doses (2-days), followed by 0.9% sodium chloride (equal volume to hydrocortisone) IV every 24 hours x 2 doses (2-days)
Intervention MeSH terms: Hydrocortisone
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: Sepsis; hydrocortisone

Summary:

      The proposed study will evaluate the potential benefit of a tapered course of hydrocortisone
      compared to abrupt cessation in patients initiated on hydrocortisone for septic shock. The
      study will include adult patients in the medical intensive care unit (MICU) who meet criteria
      for corticosteroid therapy for septic shock according to the current MICU protocol.All
      patients will receive 7 days of hydrocortisone (50mg/Q6hrs) as part of the routine management
      of septic shock, before being randomly assigned to receive hydrocortisone taper versus no
      taper. The primary study endpoint is the incidence of hypotension within 7 days after
      randomization. Secondary endpoints will include incidence of adrenal insufficiency, and
      changes in the inflammatory status (assessed by cytokine measurements) before, during, and
      after corticosteroid discontinuation. The cytokines to be measured include IL-1, IL-6, IL-9,
      IL-10, and TNF. Since there has not been a randomized clinical trial to investigate the
      potential benefit of weaning septic patients off low-dose hydrocortisone as opposed to
      stopping abruptly, this study has potential to change clinical practice by leading to a
      consistent approach of corticosteroid discontinuation and to a better understanding of their
      impact on the inflammatory modulation in septic shock.
    

Eligibility criteria:

        Inclusion Criteria:Patients who meet the following criteria will be enrolled in the study:

          -  suspected septic shock

          -  initiation of hydrocortisone 50mg IV Q6H (per MICU protocol)

          -  written informed consent signed by patient or legal surrogate

          -  Septic shock is defined by meeting all of the following requirements:

          -  Clinical evidence of infection. Clinical evidence of infection is defined as the
             presence of a known or probable source of infection that has necessitated the
             initiation of systemic antimicrobial therapy. Clinical evidence of infection could
             include (but is not limited to) one or more of the following:

               1. presence of increased number of PMNs (neutrophils) in normally sterile body fluid

               2. positive culture or gram stain of blood, sputum, urine, or normally sterile body
                  for a pathogenic microorganism

               3. chest radiograph consistent with a diagnosis of pneumonia with a positive
                  culture, gram stain, diagnostic bronchoalveolar lavage, or protected specimen
                  brush for a respiratory tract pathogen

               4. focus of infection identified by visual inspection (e.g., ruptured bowel found at
                  surgery, wound with purulent drainage, radiographic or Computed tomographic
                  evidence of an abscess or osteomyelitis, etc.) and

               5. patient has an underlying disease or condition that is highly likely to be
                  associated with infection (e.g., ascending cholangitis, ischemic bowel, etc.)

          -  Two of the following:

               1. Core temperature either > 38°C (> 100.4°F) or < 36°C (< 96.8°F)

               2. Tachycardia. Heart rate greater > 90 beats/minute

               3. Respiratory rate > 20 b/min or PaCO2 < 32 torr, or need for mechanical
                  ventilation due to sepsis

               4. WBC > 12 or < 4 K/mm3

          -  End-organ cardiovascular dysfunction defined as hypotension unresponsive to fluid
             replacement necessitating vasopressor therapy, or lactate ≥4 mmol/L

        Exclusion Criteria:

          -  age less than 18

          -  previous systemic corticosteroid therapy in the past 90 days (prednisone >5 mg/d or
             equivalent)

          -  pregnancy

          -  Acquired Immune Deficiency Syndrome (AIDS)

          -  hematological malignancies

          -  advanced form of cancer with less than 30-day life expectancy

          -  patients who receive fludrocortisone

          -  evidence of prior acute myocardial infarction