Effects of Dexmedetomidine vs Midazolam on Microcirculation in Septic Shock Patients

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

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.

Study Overview

• Status: Unknown
• Conditions: Septic Shock
• Intervention / Treatment: Device: Microdialysis Probe (Muscle microdialysis); Drug: remifentanyl

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 Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Tunisia
  • Tunis, Tunisia, 1008
    • Recruiting
    • Military Hopital of Tunis
  • Mont Fleury
    • Tunis, Mont Fleury, Tunisia, 1008
      • Recruiting
      • Military Hospital of Tunis
      • Contact: zied hajjej, Dr; Phone Number: +21620358907; Email: hajjej_zied@hotmail.com
      • Principal Investigator: zied hajjej, dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DEX group; 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); 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.; Drug: remifentanyl; 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.
Active Comparator: MDZ group; 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); 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.; Drug: remifentanyl; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Military Hospital of Tunis
• Investigators: Study Director: Mustapha Ferjani, Department of C ritical C are Medicine and Anesthesiology, Military Hospital of Tunis, Tunisia, Tunis, Tunisia

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2018
• Primary Completion (Anticipated): November 30, 2018
• Study Completion (Anticipated): December 31, 2018

Study Registration Dates

• First Submitted: February 8, 2018
• First Submitted That Met QC Criteria: February 13, 2018
• First Posted (Actual): February 15, 2018

Study Record Updates

• Last Update Posted (Actual): February 15, 2018
• Last Update Submitted That Met QC Criteria: February 13, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Remifentanil
• Other Study ID Numbers: DEX03/06

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No