Effects of Dexmedetomidine vs Midazolam on Microcirculation in Septic Shock Patients

Study Overview
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Brief Summary
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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
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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).

Official Title
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Effects of Dexmedetomidine vs Midazolam on Microcirculation in Septic Shock Patients: a Muscle Microdialysis Study

Conditions
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Septic Shock

Intervention / Treatment
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* Device: Microdialysis Probe (Muscle microdialysis)
* Drug: remifentanyl


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DEX group<br>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. | Device: Microdialysis Probe (Muscle microdialysis)<br>* Interstitial tissue concentrations of lactate, pyruvate, glucose and glycerol were determined at baseline and then every six hours for the following 72 hours after randomization. During the study period, conventional treatment was continued as per usual practice. Fluid challenges were performed, and repeated as necessary, to maintain central venous pressure (CVP) ≥8 and pulmonary arterial occlusion pressure (PAOP) ≥12 mmHg. Norepinephrine was titrated to maintain mean arterial pressure (MAP) ≥65 mmHg. Packed red blood cells were transfused when Hemoglobin (Hb) concentrations decreased below 7 g/dL, or if the patient exhibited clinical signs of inadequate systemic oxygen supply.<br>Drug: remifentanyl<br>* Only the dose of remifentanyl (initial infusion of 6 µg/kg/h) can be changed to achieve a Goal of sedation: Richmond agitation-sedation scale 0 to -2.<br>|
| Active Comparator: MDZ group<br>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. | Device: Microdialysis Probe (Muscle microdialysis)<br>* Interstitial tissue concentrations of lactate, pyruvate, glucose and glycerol were determined at baseline and then every six hours for the following 72 hours after randomization. During the study period, conventional treatment was continued as per usual practice. Fluid challenges were performed, and repeated as necessary, to maintain central venous pressure (CVP) ≥8 and pulmonary arterial occlusion pressure (PAOP) ≥12 mmHg. Norepinephrine was titrated to maintain mean arterial pressure (MAP) ≥65 mmHg. Packed red blood cells were transfused when Hemoglobin (Hb) concentrations decreased below 7 g/dL, or if the patient exhibited clinical signs of inadequate systemic oxygen supply.<br>Drug: remifentanyl<br>* Only the dose of remifentanyl (initial infusion of 6 µg/kg/h) can be changed to achieve a Goal of sedation: Richmond agitation-sedation scale 0 to -2.<br>|

What is the study measuring?
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Primary Outcome Measures

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