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

Study Overview

• Status: Completed
• Conditions: Sedation; Dexmedetomidine; Mechanical Ventilation; Midazolam
• Intervention / Treatment: Drug: Dexmedetomidine; Drug: Fentanyl; Device: Indirect calorimetry; Drug: Midazolam

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Cairo University

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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Cairo University
• Investigators: Study Chair: Mohamed Abdulatif, Professor, Professor and member of research committee of anesthesia department

Publications and helpful links

General Publications

• Walker RN, Heuberger RA. Predictive equations for energy needs for the critically ill. Respir Care. 2009 Apr;54(4):509-21.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): March 10, 2018
• Study Completion (Actual): March 15, 2018

Study Registration Dates

• First Submitted: January 19, 2017
• First Submitted That Met QC Criteria: January 23, 2017
• First Posted (Estimate): January 25, 2017

Study Record Updates

• Last Update Posted (Actual): March 27, 2018
• Last Update Submitted That Met QC Criteria: March 24, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Analgesics, Opioid; Narcotics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Fentanyl; Midazolam; Dexmedetomidine
• Other Study ID Numbers: N-26-2016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No