Clinical trial NCT02109965: The Effect of Dexmedetomidine on Microcirculation in Severe Sepsis
Official title: The Effect of Dexmedetomidine on the Microcirculation in Patients With Severe Sepsis and Septic Shock
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Severe Sepsis
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2014-04-10
Enrollment: 12
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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

Primary outcomes:
measure: Changes of total small vessel density and perfused small vessel density
timeFrame: 6h
Secondary outcomes:
measure: Changes of total small vessel density and perfused small vessel density
timeFrame: 24h
measure: Change of microvascular flow index
timeFrame: 6h and 24h
Other outcomes:
measure: Endocan level
timeFrame: 24h
measure: Hemodynamic variables
timeFrame: 6h and 24h
measure: NGAL level
timeFrame: 6h and 24h
measure: BNP level
timeFrame: 24h
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: National Taiwan University Hospital
name: Yu-Chang Yeh, MD, PhD
role: STUDY_DIRECTOR
References: