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

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

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.

Study Overview

• Status: Terminated
• Conditions: Sedation; Respiration, Artificial; Length of Stay
• Intervention / Treatment: Other: Normal Saline; Drug: Dexmedetomidine

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.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: 1; Normal Saline	Other: Normal Saline; Normal Saline will be given as the placebo and will administered at 0.8mcg/kg/hr; Other Names: No other names have been specified
ACTIVE_COMPARATOR: 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.	Other: Normal Saline; Normal Saline will be given as the placebo and will administered at 0.8mcg/kg/hr; Other Names: No other names have been specified; 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 Names: No other names have been specified

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to a Successful Spontaneous Breathing Trial.	Did not achieve this primary outcome due to no enrollment of participants. Unable to measure this outcome.	1/1/2008
Intensive Care Unit Length of Stay	The number of days each patient was in the Intensive Care Unit. Unable to measure this outcome due to no enrollment of participnats.	1/1/2008

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Endpoints Include:Amount of Sedative and Opiates Given	Did not achieve this outcome due to no enrollment of participants	1/1/2008
Time to Extubation	Did not achieve this outcome due to no enrollment of participants	1/1/2008
Amount of Vasoactive Substances Used to Achieve Hemodynamic Stability	Did not achieve this outcome due to no enrollment of participants, unable to measure this outcome	1/1/2008
Pharmaco-economics	Did not achieve this outcome due to no enrollment of participants	1/1/2008
Incidence of Delirium; Number of Shifts During Which Delirium Was Diagnosed	Did not achieve this outcome due to no enrollment of participants. Was unable to measure this outcome.	1/1/2008

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Hospira, now a wholly owned subsidiary of Pfizer
• Investigators: Principal Investigator: Ulrich Schmidt, MD,PhD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (ACTUAL): January 1, 2008
• Study Completion (ACTUAL): January 1, 2008

Study Registration Dates

• First Submitted: December 7, 2006
• First Submitted That Met QC Criteria: December 7, 2006
• First Posted (ESTIMATE): December 8, 2006

Study Record Updates

• Last Update Posted (ESTIMATE): September 22, 2009
• Last Update Submitted That Met QC Criteria: September 16, 2009
• Last Verified: September 1, 2009

More Information

Terms related to this study

• Keywords: Dexmedetomidine; Mechanical ventilation; Thoracoabdominal Aortic Aneurysm
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Aortic Diseases; Aneurysm; Aortic Aneurysm; Aortic Aneurysm, Thoracic; 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; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: 2006-P-001827; IND:74068