Dexmedetomidine for Postoperative Sedation in Patients Undergoing Repair of Thoracoabdominal Aortic Aneurysms

Sedation Clinical Trial

Official title:

Phase 4 Study of Dexmedetomidine for Postoperative Sedation in Patients Undergoing Repair of Thoracoabdominal Aortic Aneurysms

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00409344
• Other study ID #: 2006-P-001827
• Secondary ID: IND:74068
• Status: Terminated
• Phase: Phase 4
• First received: December 7, 2006
• Last updated: September 16, 2009
• Start date: January 2007
• Est. completion date: January 2008

Study information

• Verified date: September 2009
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to test the hypothesis that time on the ventilator and ICU length of stay will be shorter in TAA patients given postoperative sedation with dexmedetomidine compared to those given standard sedation. Secondary endpoints are: requirement for sedatives vasoactive drugs incidence of postoperative delirium and cost analysis.

Description:

Repair of thoraco-abdominal aortic aneurysms (TAA) is mostly performed in specialized centers. These centers report an operative mortality around 10%. In an analysis of 337 consecutive TAA, Cambria et al reported pulmonary (44%), cardiac, (13.8 %) renal (13.5%) and postoperative spinal cord deficit as prominent complications. Due to the extent of the surgery and the high risk of complications, all these patients require post- operative care in the Intensive Care Unit (ICU). In 2003, the operation was performed in approximately 40 patients at the Massachusetts General Hospital (MGH). The median length of stay in the ICU was 7 days (range 2-55) All patients required postoperative mechanical ventilation for greater than 48 h. During this period, a continuous intravenous infusion of propofol is normally used for sedation. Pain relief is provided by a continuous intravenous infusion of hydromorphone. This combination of sedation and analgesia is widely used at MGH and other institutions. Although very effective, it may cause respiratory depression and a deep sedative state, which may result in a prolonged requirement for mechanical ventilation. Lighter or more controllable sedation appears to be beneficial in this regard: daily wake up of intubated and sedated ICU patients decreases days on the ventilator and length of stay in the ICU.

Dexmedetomidine is a highly specific α2 agonist with prominent central nervous system (CNS) and cardiovascular effects It is FDA-approved as a postoperative sedative-hypnotic agent for intensive care patients for use up to 24 hours. The drug has hypnotic, sedative, analgesic and anxiolytic actions, and it tends to cause a mild decrease in blood pressure and heart rate. Patients or healthy volunteers sedated with dexmedetomidine alone are easily arousable and have no apparent respiratory depression. Dexmedetomidine has synergistic hypnotic and analgesic interactions with virtually all CNS depressants tested. It significantly decreases sedative and opioid requirements during and after major surgical procedures.Other potentially beneficial effects that are not as well-documented include bronchodilation and the ability to induce a more 'physiologic' sleep than other hypnotics commonly used in the ICU. Dexmedetomidine sedation may also be associated with a lower incidence of delirium.

Patients recovering from TAA surgery routinely require substantial ICU resources. If dexmedetomidine decreases the opioid and sedative requirement in these patients, it may potentially decrease the average number of days spent on the ventilator and in the ICU.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 0
• Est. completion date: January 2008
• Est. primary completion date: January 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• All Patients over age 18 undergoing non-emergent repair of type I-III TAA

Exclusion Criteria:

• Pregnancy

• Patients with hepatic impairment (increase of ALT or AST three times normal)

• Patient taking clonidine or tricyclic antidepressants.

• Patients taking opioids or benzodiazepines chronically (> 2 doses a day for > 1 month)

• Patients with second or third degree heart block without a pacer

• Patients undergoing emergency repair of TAA

• Intraoperative cardiac arrest

• Intraoperative massive blood loss (>10 l)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Aneurysm
• Aortic Aneurysm
• Aortic Aneurysm, Thoracic
• Length of Stay
• Respiration, Artificial
• Sedation

Intervention

Drug:
• Dexmedetomidine
A continuous infusion of dexmedetomidine will be started at a dose of 0.8mcg/kg/hr. This will continue for no longer than 24 hours. Four hours post extubation the study drug wii be discontinued using a standard tapering protocol: 0.6mcg/kg/hr for 4 hours then 0.4mcg/kg/hr for 4 hours, then 0.2 mcg/kg/hr for 4 hours and then 0.1mcg/kg/hr for 4 hours and then turned off.

Other:
• Normal Saline
Normal Saline will be given as the placebo and will administered at 0.8mcg/kg/hr

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	Hospira, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to a Successful Spontaneous Breathing Trial.		1/1/2008	No
Primary	Intensive Care Unit Length of Stay		1/1/2008	No
Secondary	Secondary Endpoints Include:Amount of Sedative and Opiates Given		1/1/2008	No
Secondary	Time to Extubation		1/1/2008	No
Secondary	Amount of Vasoactive Substances Used to Achieve Hemodynamic Stability		1/1/2008	No
Secondary	Pharmaco-economics		1/1/2008	No
Secondary	Incidence of Delirium; Number of Shifts During Which Delirium Was Diagnosed		1/1/2008	Yes