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

• ClinicalTrials.gov Identifier: NCT00409344
• Recruitment Status: Terminated
• First Posted: December 8, 2006
• Results First Posted: September 16, 2009
• Last Update Posted: September 22, 2009
• Sponsor: Massachusetts General Hospital
• Collaborator: Hospira, now a wholly owned subsidiary of Pfizer
• Information provided by: Massachusetts General Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Sedation; Respiration, Artificial; Length of Stay	Drug: Dexmedetomidine; Other: Normal Saline	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: Phase 4 Study of Dexmedetomidine for Postoperative Sedation in Patients Undergoing Repair of Thoracoabdominal Aortic Aneurysms
• Study Start Date: January 2007
• Actual Primary Completion Date: January 2008
• Actual Study Completion Date: January 2008

Arms and Interventions

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 Name: 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.	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 Name: No other names have been specified; Other: Normal Saline; Normal Saline will be given as the placebo and will administered at 0.8mcg/kg/hr; Other Name: No other names have been specified

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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)

Contacts and Locations

Locations

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Massachusetts General Hospital

Hospira, now a wholly owned subsidiary of Pfizer

Investigators

• Principal Investigator: Ulrich Schmidt, MD,PhD; Massachusetts General Hospital

More Information

• Responsible Party: Ulrich Schmidt, MD PhD, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00409344
• Other Study ID Numbers: 2006-P-001827; IND:74068
• First Posted: December 8, 2006
• Results First Posted: September 16, 2009
• Last Update Posted: September 22, 2009
• Last Verified: September 2009

Keywords provided by Massachusetts General Hospital:

Thoracoabdominal Aortic Aneurysm; Dexmedetomidine; Mechanical ventilation

Additional relevant MeSH terms:

Aneurysm; Aortic Aneurysm; Aortic Aneurysm, Thoracic; Vascular Diseases; Cardiovascular Diseases; Aortic Diseases; Dexmedetomidine; Hypnotics and Sedatives; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action