Dexmedetomidine vs Midazolam on Resting Energy Expenditure in Critically Ill Patients

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

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

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.

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

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

The drug will be administered for sedation and its effect on basal metabolic rate will be investigated

The drug will be administered for sedation and its effect on basal metabolic rate will be investigated

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.

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

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