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

NCT ID: NCT00409344

Last Updated: 2009-09-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2008-01-31

Brief 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.

Detailed 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.

Conditions

Sedation; Respiration, Artificial; Length of Stay

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

1

Normal Saline

Group Type: PLACEBO_COMPARATOR

Normal Saline

Intervention Type: OTHER

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

Dexmedetomidine

Dexmedetomidine is a highly specific a2 agonist with prominent central nervous system and cardiovascular effects. A postoperative sedative-hypnotic agent for intensive care patients for use up to 24 hours.

Group Type: ACTIVE_COMPARATOR

Dexmedetomidine

Intervention Type: DRUG

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.

Normal Saline

Intervention Type: OTHER

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

Interventions

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.

Intervention Type: DRUG

Normal Saline

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

Intervention Type: OTHER

Other Intervention Names

No other names have been specified; No other names have been specified

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Hospira, now a wholly owned subsidiary of Pfizer

INDUSTRY

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Massachusetts General Hospital

Principal Investigators

Ulrich Schmidt, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

IND:74068

Identifier Type: -

Identifier Source: secondary_id

2006-P-001827

Identifier Type: -

Identifier Source: org_study_id