Effects of Dexmedetomidine vs Midazolam on Microcirculation in Septic Shock Patients

Not Applicable

• Conditions: Septic Shock
• Interventions: Device: Microdialysis Probe (Muscle microdialysis); Drug: remifentanyl

• Registration Number: NCT03434691
• Lead Sponsor: Military Hospital of Tunis

Brief Summary

To investigate changes in the concentration of glucose, lactate, pyruvate and glycerol in the extracellular fluid of the skeletal muscle following Dexmedetomidine administration in patients with septic shock.

Detailed Description

Prospective randomized double blinded study. Investigators planned to enroll 60 cases diagnosed with septic shock All patients will be sedated with Midazolam and remifentanyl in accordance with a local unit protocol.

After a period of six hours of hemodynamic stability, patients were randomized to receive either continuous infusion of Dexmedetomidine at 0.4 μg/kg per hour and remifentanyl (DEX group) or a continuous infusion of a Midazolam and remifentanyl (MDZ Group).

Study Timeline

• Status Verified: 2018-02
• Study Start: 2018-02-08
• Study First Submitted: 2018-02-08
• Study First Submitted QC: 2018-02-13
• Last Update Submitted: 2018-02-13
• Study First Posted: 2018-02-15
• Last Update Posted: 2018-02-15
• Primary Completion: 2018-11-30
• Study Completion: 2018-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Patients aged over 18 years
• Septic shock requiring norepinephrine (NE) to maintain a mean arterial pressure (MAP) of at least 65mm Hg despite appropriate volume resuscitation (fluid challenge of 20 mL/kg-40 mL/kg)
• Septic shock criteria were defined according to the new Sepsis-3 definition

Exclusion Criteria

• pregnancy
• uncontrolled hemorrhage
• terminal heart failure
• significant valvular heart disease
• documented or suspected acute coronary syndrome, and limitations on the use of inotropes: left ventricle outflow obstruction, systolic anterior motion of the mitral valve
• refractory bradycardia (heart rate slower than 60 bpm despite of adequate treatment)
• 2nd and 3rd degree of AV-block ,the onset of septic shock more than 24 h 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)
• attending other trial in ICU within one month
• allergic history to dexmedetomidine

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
DEX group	Microdialysis Probe (Muscle microdialysis)	continuous infusion of Dexmedetomidine at 0.4 μg/kg per hour and remifentanyl A microdialysis probe was placed into the femoral quadriceps. An initial set of measurements will be obtained during the sedation with Midazolam and remifentanyl (before randomization). This set of measurements will be considered as baseline. Then samples were collected every 6 hours for 3 days. The changes in the energy-related metabolites lactate, the lactate/pyruvate ratio, glucose and glycerol were analyzed. Concomitantly with dialysate sampling, the effects on global haemodynamics, were assessed. Lactate and L/P clearances were also calculated.
DEX group	remifentanyl	continuous infusion of Dexmedetomidine at 0.4 μg/kg per hour and remifentanyl A microdialysis probe was placed into the femoral quadriceps. An initial set of measurements will be obtained during the sedation with Midazolam and remifentanyl (before randomization). This set of measurements will be considered as baseline. Then samples were collected every 6 hours for 3 days. The changes in the energy-related metabolites lactate, the lactate/pyruvate ratio, glucose and glycerol were analyzed. Concomitantly with dialysate sampling, the effects on global haemodynamics, were assessed. Lactate and L/P clearances were also calculated.
MDZ group	remifentanyl	continuous infusion of a Midazolam at 0,1 mg/kg/h and remifentanyl A microdialysis probe was placed into the femoral quadriceps. An initial set of measurements will be obtained during the sedation with Midazolam and remifentanyl (before randomization). This set of measurements will be considered as baseline. Then samples were collected every 6 hours for 3 days. The changes in the energy-related metabolites lactate, the lactate/pyruvate ratio, glucose and glycerol were analyzed. Concomitantly with dialysate sampling, the effects on global haemodynamics, were assessed. Lactate and L/P clearances were also calculated.
MDZ group	Microdialysis Probe (Muscle microdialysis)	continuous infusion of a Midazolam at 0,1 mg/kg/h and remifentanyl A microdialysis probe was placed into the femoral quadriceps. An initial set of measurements will be obtained during the sedation with Midazolam and remifentanyl (before randomization). This set of measurements will be considered as baseline. Then samples were collected every 6 hours for 3 days. The changes in the energy-related metabolites lactate, the lactate/pyruvate ratio, glucose and glycerol were analyzed. Concomitantly with dialysate sampling, the effects on global haemodynamics, were assessed. Lactate and L/P clearances were also calculated.

Primary Outcome Measures

Name	Time	Method
changes in the concentration of glucose(mmol/l) in the extracellular fluid of the skeletal muscle	Time Frame: At baseline and then every six hours for the following 72 hours after randomization	collected every 6 hours for 3 days
changes in the concentration of lactate(mmol/l) in the extracellular fluid of the skeletal muscle	Time Frame: At baseline and then every six hours for the following 72 hours after randomization	collected every 6 hours for 3 days
changes in the concentration of pyruvate (µmol/l) in the extracellular fluid of the skeletal muscle	Time Frame: At baseline and then every six hours for the following 72 hours after randomization	collected every 6 hours for 3 days
changes in the concentration of glycerol (µmol/l) in the extracellular fluid of the skeletal muscle	Time Frame: At baseline and then every six hours for the following 72 hours after randomization	collected every 6 hours for 3 days

Trial Locations

Locations (2)

Military hospital of tunis; 🇹🇳 Tunis, Mont Fleury, Tunisia

Military Hopital of Tunis; 🇹🇳 Tunis, Tunisia