Study Overview

Details

NCTId: NCT02109965

Status: Terminated

Condition: Severe Sepsis

Study Type: Interventional

Sponsor: National Taiwan University Hospital

Study Description

Brief

Despite early goal-directed maintenance of normal macrocirculation, the reduction of 60-day mortality of patients with severe sepsis and septic shock remained unsatisfied (56.9% to 44.3%). One of the major causes of high mortality is microcirculatory dysfunction. Delayed diagnosis and treatment of microcirculatory dysfunction may cause tissue hypoperfusion and resulted in multiple organ dysfunction and death. Dexmedetomidine is a highly selective α2-adrenoreceptor agonist which exhibits sedative and analgesic effects. Recent studies suggest that dexmedetomidine also has anti-coagulation and anti-inflammatory effects, and it can reduce the mortality of endotoxemic rats and patients with severe sepsis. The investigators will conduct two animal studies and one clinical trial to investigate the effect of dexmedetomidine on microcirculatory dysfunction and organ injury in rat with endotoxemia and patients with severe sepsis and septic shock.

Sixty patients with severe sepsis and septic shock will be enrolled and randomized to control group or dexmedetomidine group. In the control group, the patients will be treated according to the clinical practice guideline. If sedation is required, non-dexmedetomidine sedative agents will be used. In the dexmedetomidine group, the patients will be treated according to the clinical practice guideline, and they will also receive continuous infusion of dexmedetomidine (infusion rate ranged from 0.1 to 0.7 mcg/kg/h) for 24 hours as needed. The sublingual microcirculation, serum level of Endocan, NGAL(Neutrophil Gelatinase-Associated Lipocalin), and BNP(B-type natriuretic peptide) will be examined at preset time points up to 24 hours. The vital signs, hemodynamic parameters, and survival of 28-day and 90-day will be recorded and analyzed.

Eligibility

Criteria:

Inclusion Criteria:

ICU patients who require sedation
Patients who have diagnosis of severe sepsis / septic shock
meet 2 or more of the 4 SIRS criteria
with one organ dysfunction according the definition of Surviving Sepsis Campaign

Exclusion Criteria:

less than 20 y/o
refractory bradycardia (heart rate slower than 60 bpm despite of adequate treatment)
2nd and 3rd degree of AV-block
the onset of severe sepsis/septic shock is more than 24h before enrollment
APACHE II > 30 at enrollment
Severe liver cirrhosis (Child B or C)
New onset of myocardial infarction within 30 days or heart failure (NYHA 4)
attend other trial in ICU within one month
patient who is pregnant
receive organ transplantation within one year
expected survival is less than 30 days by attending physician
receive cardiopulmonary resuscitation within 4 weeks
patients who have signed consent of refusal of cardiopulmonary resuscitation and invasive therapy
have allergic history to dexmedetomidine
receive renal replacement therapy within 24 hours before enrollment
patient with HIV infection
non-native speaker
other factors not eligible for enrollment concerned by attending physician

Healthy Volunteers: No

Gender: All

Min Age: 20 Years

Contacts

National Taiwan University Hospital

Taipei

100

Taiwan

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