Dexmedetomidine vs Midazolam on Resting Energy Expenditure in Critically Ill Patients

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Effect of Dexmedetomidine vs Midazolam on Resting Energy Expenditure in Critically Ill Patients: Randomized Controlled Study

Conditions
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Mechanical Ventilation, Dexmedetomidine, Midazolam, Sedation

Intervention / Treatment
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* Drug: Dexmedetomidine
* Drug: Midazolam
* Drug: Fentanyl
* Device: Indirect calorimetry


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dexmedetomidine group<br>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 | Drug: Dexmedetomidine<br>* The drug will be administered for sedation and its effect on basal metabolic rate will be investigated<br>* Other names: Precedex;Drug: Fentanyl<br>* The drug will be administered in both groups<br>Device: Indirect calorimetry<br>* The device will be used for measurement of basal metabolic rate<br>* Other names: Calorimetry;|
| Placebo Comparator: midazolam group<br>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 | Drug: Midazolam<br>* The drug will be administered for sedation and its effect on basal metabolic rate will be investigated<br>* Other names: dormicum;Drug: Fentanyl<br>* The drug will be administered in both groups<br>Device: Indirect calorimetry<br>* The device will be used for measurement of basal metabolic rate<br>* Other names: Calorimetry;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Resting energy expenditure after drug administration | Resting energy expenditure will be measured using indirect calorimetry via metabolic module on General Electric ventilator | The first baseline measurement will be taken before drug administration. The second measurement will be taken 24 hours after drug infusion. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart rate | number of heart beats per minute | 24 hours | 
| arterial blood pressure | arterial blood pressure measured in mmHg | 24 hours | 
| Richmond agitation and sedation scale | range from -5 (unarousable) to +4 (combative) | 24 hours | 
| Plasma interleukin-1β level | determined by ELISA using a quantitative sandwich enzyme immunoassay technique | 24 hours | 
| Tumor necrosis factor-α plasma concentration | Enzyme immunoassay | 24 hours | 
| partial pressure of oxygen in arterial blood | the partial pressure of oxygen in arterial blood measured in mmHg | 24 hours | 
| VO2 | the oxygen consumption measured in mL/Kg/min | 24 hours | 
| VCO2 | carbon dioxide production measured in mL/Kg/min | 24 hours | 
| end-tidal co2 | the pressure of carbon dioxide in expired air measured in mmHg | 24 hours | 
| cardiac output | the amount of blood pumped by the heart during one minute | 24 hours |