Dexmedetomidine vs Midazolam on Resting Energy Expenditure in Critically Ill Patients

NCT ID: NCT03030911

Last Updated: 2018-03-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-01
• Study Completion Date: 2018-03-15

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.

Conditions

Mechanical Ventilation; Dexmedetomidine; Midazolam; Sedation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Dexmedetomidine

Intervention Type: DRUG

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

Fentanyl

Intervention Type: DRUG

The drug will be administered in both groups

Indirect calorimetry

Intervention Type: DEVICE

The device will be used for measurement of basal metabolic rate

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

Group Type: PLACEBO_COMPARATOR

Midazolam

Intervention Type: DRUG

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

Fentanyl

Intervention Type: DRUG

The drug will be administered in both groups

Indirect calorimetry

Intervention Type: DEVICE

The device will be used for measurement of basal metabolic rate

Interventions

Dexmedetomidine

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

Intervention Type: DRUG

Midazolam

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

Intervention Type: DRUG

Fentanyl

The drug will be administered in both groups

Intervention Type: DRUG

Indirect calorimetry

The device will be used for measurement of basal metabolic rate

Intervention Type: DEVICE

Other Intervention Names

Precedex; dormicum; Calorimetry

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cairo University

OTHER

Sponsor Role: lead

Responsible Party

Ahmed Hasanin

Lecturer of anesthesia and critical care medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mohamed Abdulatif, Professor

Role: STUDY_CHAIR

Professor and member of research committee of anesthesia department

Locations

Cairo University

Cairo, , Egypt

Countries

Egypt

References

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

Reference Type: BACKGROUND

PMID: 19327188 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 14758147 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 6794409 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11288413 (View on PubMed)

Other Identifiers

N-26-2016

Identifier Type: -

Identifier Source: org_study_id