Use of Dexmedetomidine to Facilitate Extubation in Surgical ICU Patients Who Failed Previous Weaning Attempts

NCT ID: NCT00464490

Last Updated: 2014-10-31

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-30
• Study Completion Date: 2012-12-31

Brief Summary

Mechanical ventilation commonly is associated with patient agitation requiring sedation to alleviate discomfort and reduce excessive central respiratory drive. Upon recovery from acute respiratory failure, sedation is reduced to facilitate the withdrawal of ventilatory support. In some patients, abrupt reduction in sedation provokes severe agitation that causes catecholamine release resulting in severe hypertension, tachycardia and tachypnea. This requires increased sedation to bring hemodynamic and respiratory function under control.

Dexmedetomidine is an alpha-2 receptor agonist with both sedative and analgesic properties that allows for the reduction in the anesthetic and analgesic requirements in the perioperative setting. In addition to its sedative effects, alpha-2 receptor stimulation in the central nervous system inhibits sympathetic activity and reduces plasma epinephrine and norepinephrine levels, thereby lowering both arterial blood pressure and heart rate. Because alpha-2 receptor stimulation does not cause respiratory depression, dexmedetomidine may facilitate the transition to unassisted breathing in profoundly agitated patients. The investigators will prospectively evaluate dexmedetomidine in 30 patients who could not be extubated because of agitation with hemodynamic instability and tachypnea.

The purpose of this study is to test if a larger prospective randomized controlled pilot study can show that dexmedetomidine facilitates weaning and extubation in patients who have failed previous attempts because of agitation and hyperdynamic cardiopulmonary response.

Detailed Description

Sixty patients who are admitted to the surgical intensive care unit (ICU) at San Francisco General Hospital will be referred to the investigators for enrollment into a prospective, unblinded, randomized study of dexmedetomidine. Each patient will be considered by the critical care team as a suitable candidate for weaning and extubation based on inclusion/ exclusion criteria. Pregnant patients will not be enrolled and this will be determined by a negative urine or serum pregnancy test from admission. If none is available a pregnancy test will be performed prior to enrollment. Patients considered difficult to wean will be based on the following criteria:

Eligible patients will be randomized to either the control arm or the dexmedetomidine arm in a 1:1 ratio by using sealed envelopes.

Patient randomized to the control arm will be extubated per standard hospital protocol. This arm of the study will be observational and these patients will be extubated by the attending physician for that patient whenever they are hemodynamically stable enough to tolerate another weaning trial. The study team will collect the same data points for the control arm as in the dexmedetomidine arm. This includes ABGs, heart rate, mean blood pressure, respiratory rate and RASS scores (see description below of data points and collection time points.) Arterial blood gases will be drawn for the control arm of the study.

Patients on the dexmedetomidine arm will be started on dexmedetomidine at either 0.5 mcg/kg/hr or 0.7 mcg/kg/hr 1 hour prior to extubation. The drug calculation was based upon an average taken between the patient's measured and predicted body weight. Background sedation will be generally facilitated with lorazepam, midazolam or propofol, while analgesia will be maintained with either fentanyl or hydromorphine. After starting dexmedetomidine background sedation and analgesia will be titrated down and discontinued if possible. Analgesia levels also will be reduced if tolerated. Dexmedetomidine will be titrated according to blood pressure, RASS and heart rate response and the dose will be lowered only after sedation is discontinued or markedly reduced. Aerosolized lidocaine (20 mg) therapy will be initiated prior to the weaning trial to prevent excessive coughing in all patients.

Shortly after the dexmedetomidine infusion is started, PSV will be commenced at 5 cm H2O above 5 cm H2O of continuous positive airway pressure (CPAP). Patients will be weaned to CPAP and evaluated for extubation.

1.) Arterial blood gases will be obtained in all patients with an arterial line at three points in time: just prior to dexmedetomidine infusion, during the CPAP trial, and approximately 30 minutes after extubation.

3.) Heart rate, mean blood pressure, RASS, and respiratory rate will be collected at fifteen minute intervals 1 hour prior to dexmedetomidine infusion, during the 1 hour infusion of dexmedetomidine prior to the extubation then 5, 15, 30, 45, 60, 90 and 120 minutes after extubation for a total of 4 hours of data collection.

Conditions

Intubation; Difficult; Respiration Disorders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard Hospital Ventilation Weaning Protocol

Control. Hospital weaning protocol

Group Type: NO_INTERVENTION

No interventions assigned to this group

Dexmedetomidine for Extubation

Dexmedomidine infusion to facilitate extubation

Group Type: EXPERIMENTAL

Dexmedetomidine

Intervention Type: DRUG

Dexmedetomidine .5mcg/kg/hr-.7mcg/kg/hr 1hour prior to extubation. Dexmedetomidine will be titrated according to blood pressure, RASS and heart rate response and the dose will be lowered only after sedation is discontinued or markedly reduced.

Interventions

Dexmedetomidine

Dexmedetomidine .5mcg/kg/hr-.7mcg/kg/hr 1hour prior to extubation. Dexmedetomidine will be titrated according to blood pressure, RASS and heart rate response and the dose will be lowered only after sedation is discontinued or markedly reduced.

Intervention Type: DRUG

Other Intervention Names

Precedex

Eligibility Criteria

Inclusion Criteria

1. Age less than 70 years old

2. Normothermia (36.5 degrees centigrade)

3. Normal sinus rhythm

4. Hemodynamically stable (systolic blood pressure [SBP] > 110 mmHg)

5. Ejection fraction (EF) > 40%/absence of congestive heart failure (CHF)

6. Cardiac index > 2.5 L/min/m2

7. Minimal inotropic support (< 3 mcg/kg/min dobutamine)

8. Adequate coagulation profile

9. Adequate urine output (> 100 ml/hr)

10. Primary service and critical care physician agreement

Exclusion Criteria

1. Prior use of clonidine or alpha-antagonists

2. Prior history of intravenous drug abuse (IVDA) or alcohol abuse (ETOH)

3. Evidence of heart block

4. Difficulty with oxygenation/ventilation

5. Renal or hepatic insufficiency

6. Pregnant (positive urine or serum pregnancy test upon admission)

7. Patient received dexmedetomidine > 24 hours

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Julin F Tang, M.D., M.S.

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

University of California, San Francisco

San Francisco, California, United States

Countries

United States

Other Identifiers

0703054

Identifier Type: -

Identifier Source: org_study_id