Clinical trial NCT03030911: Dexmedetomidine vs Midazolam on Resting Energy Expenditure in Critically Ill Patients
Official title: The Effect of Dexmedetomidine vs Midazolam on Resting Energy Expenditure in Critically Ill Patients: Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Mechanical Ventilation
Dexmedetomidine
Midazolam
Sedation
Lead sponsor: Cairo University
Sponsor class: OTHER
First posted: 2017-01-25
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Resting energy expenditure after drug administration
timeFrame: The first baseline measurement will be taken before drug administration. The second measurement will be taken 24 hours after drug infusion.
Secondary outcomes:
measure: Heart rate
timeFrame: 24 hours
measure: arterial blood pressure
timeFrame: 24 hours
measure: Richmond agitation and sedation scale
timeFrame: 24 hours
measure: Plasma interleukin-1β level
timeFrame: 24 hours
measure: Tumor necrosis factor-α plasma concentration
timeFrame: 24 hours
measure: partial pressure of oxygen in arterial blood
timeFrame: 24 hours
measure: VO2
timeFrame: 24 hours
measure: VCO2
timeFrame: 24 hours
measure: end-tidal co2
timeFrame: 24 hours
measure: cardiac output
timeFrame: 24 hours
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Cairo University
Study officials:
affiliation: Professor and member of research committee of anesthesia department
name: Mohamed Abdulatif, Professor
role: STUDY_CHAIR
References:
citation: Walker RN, Heuberger RA. Predictive equations for energy needs for the critically ill. Respir Care. 2009 Apr;54(4):509-21.
citation: Rubinson L, Diette GB, Song X, Brower RG, Krishnan JA. Low caloric intake is associated with nosocomial bloodstream infections in patients in the medical intensive care unit. Crit Care Med. 2004 Feb;32(2):350-7. doi: 10.1097/01.CCM.0000089641.06306.68.
citation: Covelli HD, Black JW, Olsen MS, Beekman JF. Respiratory failure precipitated by high carbohydrate loads. Ann Intern Med. 1981 Nov;95(5):579-81. doi: 10.7326/0003-4819-95-5-579.
citation: Fung EB. Estimating energy expenditure in critically ill adults and children. AACN Clin Issues. 2000 Nov;11(4):480-97. doi: 10.1097/00044067-200011000-00002.