Dexmedetomidine vs Midazolam on Resting Energy Expenditure in Critically Ill Patients
- Conditions
- Mechanical VentilationMidazolamSedationDexmedetomidine
- Interventions
- Registration Number
- NCT03030911
- Lead Sponsor
- Cairo University
- Brief Summary
The aim of this study is to compare the effect of dexmedetomidine on resting energy expenditure in relation to the midazolam in critically ill patients using indirect calorimetry
- Detailed Description
Caloric needs in critically-ill patients fluctuate significantly over the course of the disease which might expose patients to either malnutrition or overfeeding. Malnutrition is associated with deterioration of lean body mass, poor wound healing, increased risk of nosocomial infection, and weakened respiratory muscles. On the other hand overfeeding in medically compromised patients can promote lipogenesis, hyperglycemia, and exacerbation of respiratory failure. Many factors may affect the resting energy expenditure (REE) through manipulation of oxygen consumption (VO2).
Sedatives are important contributors to reduction of REE. The postulated mechanism of sedative-induced reduction of VO2 is inhibition of circulating catecholamine and pro-inflammatory cytokines.
Dexmedetomidine is a highly selective α2-adrenoceptor agonist. Stimulation of the α2-adrenoceptor in the central nervous system causes a 60-80% reduction in sympathetic outflow and endogenous catecholamine levels. It was found that perioperative use of α2 agonists decreased sympathetic activity with subsequent reduction of VO2 and REE. Moreover, dexmedetomidine, has some anti-inflammatory effect by inhibiting the pro-inflammatory cytokines which may cause additional reduction of REE in critically ill patient.
Midazolam is another important sedative that is frequently used in critically-ill patient. Terao et al. found that increasing the depth of sedation using midazolam, decreased oxygen consumption and REE. However, it remains unclear whether the effect of midazolam on REE is related to the drug itself or to the depth of sedation.
There is no direct comparison in the literature between dexmedetomidine and midazolam on REE.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 30
- The study will be designed to recruit 30 critically-ill patients who will be admitted to the surgical ICU for ventilatory support and will be expected to continue for 2 days or longer.
- Age < 18 years old.
- Pregnant patient.
- Serious central nervous system pathologies (traumatic brain injury, acute stroke, uncontrolled seizures).
- Patient who will require fraction of inspired oxygen more than 0.6.
- Air leak from the chest tube.
- Patient with body temperature > 39 Celsius.
- Acute hepatitis or severe liver disease (Child-Pugh class C).
- Left ventricular ejection fraction less than 30%.
- Heart rate less than 50 beats/min.
- Second or third degree heart block.
- Systolic pressure < 90 mmHg despite of infusion of 2 vasopressors.
- Patients with known endocrine dysfunction.
- Patient with hypothermia
- Patient on Positive end expiratory pressure more than 14 cmH2o
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description midazolam group Indirect calorimetry * Patients will receive analgesia with fentanyl at a fixed dose of 1 µg.kg.hr-1. Each patient will receive the study drug within 24 hours after intubation. Sedatives used before study enrolment will be discontinued 6 hours prior to the initiation of study drug. * Group II patients will have midazolam (0.5 mg.mL-1). Midazolam will be started at 1 mg.h-1 (2 mL.hr-1) and adjusted by 1 mg.h-1 to a maximum of 5 mg.h-1 (10 mL.h-1). All infusions will be adjusted by increments of 2 mL.hr-1 to maintain blinding. Patients in either group not adequately sedated by the maximum infusion rate of the study medication will receive a bolus dose of fentanyl 0.5 µg.kg-1. * Intervention: indirect calorimetry Dexmedetomidine group Indirect calorimetry * Patients will receive analgesia with fentanyl at a fixed dose of 1 µg.kg.hr-1. Each patient will receive the study drug within 24 hours after intubation. Sedatives used before study enrolment will be discontinued 6 hours prior to the initiation of study drug. * Group I patients will have dexmedetomidine (0.075 µg.kg-1.mL-1). Dexmedetomidine infusion will be started at 0.15 µg.kg-1.hr-1 (2 mL.hr-1) and will be adjusted by 0.15 µg.kg-1.h-1 increments to a maximum of 0.75 µg/kg/h (10 ml.h-1) * Intervention: indirect calorimetry Dexmedetomidine group Dexmedetomidine * Patients will receive analgesia with fentanyl at a fixed dose of 1 µg.kg.hr-1. Each patient will receive the study drug within 24 hours after intubation. Sedatives used before study enrolment will be discontinued 6 hours prior to the initiation of study drug. * Group I patients will have dexmedetomidine (0.075 µg.kg-1.mL-1). Dexmedetomidine infusion will be started at 0.15 µg.kg-1.hr-1 (2 mL.hr-1) and will be adjusted by 0.15 µg.kg-1.h-1 increments to a maximum of 0.75 µg/kg/h (10 ml.h-1) * Intervention: indirect calorimetry Dexmedetomidine group Fentanyl * Patients will receive analgesia with fentanyl at a fixed dose of 1 µg.kg.hr-1. Each patient will receive the study drug within 24 hours after intubation. Sedatives used before study enrolment will be discontinued 6 hours prior to the initiation of study drug. * Group I patients will have dexmedetomidine (0.075 µg.kg-1.mL-1). Dexmedetomidine infusion will be started at 0.15 µg.kg-1.hr-1 (2 mL.hr-1) and will be adjusted by 0.15 µg.kg-1.h-1 increments to a maximum of 0.75 µg/kg/h (10 ml.h-1) * Intervention: indirect calorimetry midazolam group Midazolam * Patients will receive analgesia with fentanyl at a fixed dose of 1 µg.kg.hr-1. Each patient will receive the study drug within 24 hours after intubation. Sedatives used before study enrolment will be discontinued 6 hours prior to the initiation of study drug. * Group II patients will have midazolam (0.5 mg.mL-1). Midazolam will be started at 1 mg.h-1 (2 mL.hr-1) and adjusted by 1 mg.h-1 to a maximum of 5 mg.h-1 (10 mL.h-1). All infusions will be adjusted by increments of 2 mL.hr-1 to maintain blinding. Patients in either group not adequately sedated by the maximum infusion rate of the study medication will receive a bolus dose of fentanyl 0.5 µg.kg-1. * Intervention: indirect calorimetry midazolam group Fentanyl * Patients will receive analgesia with fentanyl at a fixed dose of 1 µg.kg.hr-1. Each patient will receive the study drug within 24 hours after intubation. Sedatives used before study enrolment will be discontinued 6 hours prior to the initiation of study drug. * Group II patients will have midazolam (0.5 mg.mL-1). Midazolam will be started at 1 mg.h-1 (2 mL.hr-1) and adjusted by 1 mg.h-1 to a maximum of 5 mg.h-1 (10 mL.h-1). All infusions will be adjusted by increments of 2 mL.hr-1 to maintain blinding. Patients in either group not adequately sedated by the maximum infusion rate of the study medication will receive a bolus dose of fentanyl 0.5 µg.kg-1. * Intervention: indirect calorimetry
- Primary Outcome Measures
Name Time Method Change in Resting energy expenditure after drug administration The first baseline measurement will be taken before drug administration. The second measurement will be taken 24 hours after drug infusion. Resting energy expenditure will be measured using indirect calorimetry via metabolic module on General Electric ventilator
- Secondary Outcome Measures
Name Time Method Heart rate 24 hours number of heart beats per minute
arterial blood pressure 24 hours arterial blood pressure measured in mmHg
Richmond agitation and sedation scale 24 hours range from -5 (unarousable) to +4 (combative)
Plasma interleukin-1β level 24 hours determined by ELISA using a quantitative sandwich enzyme immunoassay technique
Tumor necrosis factor-α plasma concentration 24 hours Enzyme immunoassay
partial pressure of oxygen in arterial blood 24 hours the partial pressure of oxygen in arterial blood measured in mmHg
VO2 24 hours the oxygen consumption measured in mL/Kg/min
VCO2 24 hours carbon dioxide production measured in mL/Kg/min
end-tidal co2 24 hours the pressure of carbon dioxide in expired air measured in mmHg
cardiac output 24 hours the amount of blood pumped by the heart during one minute
Trial Locations
- Locations (1)
Cairo University
🇪🇬Cairo, Egypt