The Effects of Corticosteroids, Glucose Control, and Depth-of-Anesthesia on Perioperative Inflammation and Morbidity From Major Non-cardiac Surgery (Dexamethasone, Light Anesthesia and Tight Glucose Control (DeLiT Trial))

This study has been terminated.
(interim analysis)
Sponsor:
Information provided by:
Outcomes Research Consortium
ClinicalTrials.gov Identifier:
NCT00995501
First received: October 14, 2009
Last updated: May 4, 2012
Last verified: May 2012
  Purpose

Evidence thus suggests that steroid administration, tight glucose control, and avoidance of deep anesthesia may decrease perioperative morbidity by reducing the inflammatory response to surgery. Using a three-way factorial approach, the investigators thus propose to test the primary hypotheses that major perioperative morbidity is reduced by: 1) low-dose dexamethasone; 2) intensive perioperative glucose control; and 3) lighter anesthesia.

Secondary hypotheses include that each intervention reduces circulating concentrations of the inflammatory marker CRP, and that there is a correlation between C-reactive protein (CRP) and post-operative complications. Anesthetic sensitivity predicts major and minor complications, and delirium Other secondary hypotheses are that each intervention, reduces minor surgical complications, reduces postoperative nausea and vomiting (PONV), reduces postoperative delirium, speeds hospital discharge, improves quality of life (SF-12v2 Health Survey, Christensen's VAS fatigue score), and reduces all-cause one-year mortality.


Condition Intervention
Inflammation
Perioperative Morbidity
Drug: dexamethasone
Drug: glucose
Device: BIS monitor

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Supportive Care
Official Title: The Effects of Corticosteroids, Glucose Control, and Depth-of-Anesthesia on Perioperative Inflammation and Morbidity From Major Non-cardiac Surgery (Dexamethasone, Light Anesthesia and Tight Glucose Control (DeLiT Trial))

Resource links provided by NLM:


Further study details as provided by Outcomes Research Consortium:

Primary Outcome Measures:
  • major perioperative morbidity [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • postoperative delirium [ Time Frame: one year ] [ Designated as safety issue: No ]

Enrollment: 970
Study Start Date: January 2007
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: insulin therapy

Patients will be randomized to either group:

Intensive Glucose Control The target range for blood glucose will be 80-110 mg/dl or Conventional Glucose Control The target range for blood glucose will be 180-200 mg/dl

Drug: glucose
The target range for blood glucose will be 80-110 mg/dl or Conventional Glucose Control The target range for blood glucose will be 180-200 mg/dl
Active Comparator: dexamethasone
Patients will be randomized to receive either: placebo or dexamethasone administered at 8 mg given 1-2 hours before surgery (incision time), 4 mg on the first postoperative morning, and 2 mg on the second postoperative morning.
Drug: dexamethasone
8 mg given 1-2 hours before surgery (incision time), 4 mg on the first postoperative morning, and 2 mg on the second postoperative morning
Active Comparator: Lighter or deeper anesthetic management
Patients will be randomized to either: target BIS of 55 (lighter anesthesia group)or to a target BIS of 35 (deeper anesthesia group)
Device: BIS monitor
BIS of 55 (lighter anesthesia group)or to a target BIS of 35 (deeper anesthesia group)

Detailed Description:

The perioperative period is characterized by an intense inflammatory response marked by elevated concentrations of inflammatory markers like C-Reactive Protein (CRP). This response has been linked to increased perioperative morbidity and mortality. Available evidence suggests that blunting the inflammatory response to surgical trauma might improve perioperative outcomes. The putative benefits from blunting the surgical stress response are likely to be greatest in high-risk patients such as those having major non-cardiac surgery. We will study three interventions potentially modulating perioperative inflammation, corticosteroids, tight glucose control and light anesthesia and their effects on major morbidity and mortality resulting from major non-cardiac surgery.

Steroids are the most powerful routinely available anti-inflammatory drugs. They decrease perioperative concentrations of inflammatory markers and improve outcomes after cardiac and abdominal surgery.

Poorly controlled blood glucose worsens the inflammatory response to surgery. Hyperglycemia impairs wound healing, increases infection risk, increases overall hospital mortality, increases the risk of perioperative renal failure, and augments transfusion requirements. Treatment of hyperglycemia has been shown to improve outcomes and decrease mortality in cardiac patients. Also in critically ill patients, it decreased inflammatory markers, overall hospital mortality by 34%, blood stream infections by 46%, and acute renal failure by 41%.

Cumulative deep hypnotic time is associated with increased one-year all-cause mortality, possibly through aggravation of the inflammatory response to surgery. In contrast, avoidance of deep anesthesia appears to reduce postoperative CRP levels, the risk of nausea and vomiting, as well as postoperative hemodynamic, respiratory and infectious complications.

Evidence thus suggests that steroid administration, tight glucose control, and avoidance of deep anesthesia may decrease perioperative morbidity by reducing the inflammatory response to surgery. Using a three-way factorial approach, we thus propose to test the primary hypotheses that major perioperative morbidity is reduced by: 1) low-dose dexamethasone; 2) intensive perioperative glucose control; and, 3) lighter anesthesia.

Secondary hypotheses include that each intervention reduces circulating concentrations of the inflammatory marker CRP, and that there is a correlation between CRP and post-operative complications. Anesthetic sensitivity predicts major and minor complications, and delirium Other secondary hypotheses are that each intervention, reduces minor surgical complications, reduces postoperative nausea and vomiting (PONV), reduces postoperative delirium, speeds hospital discharge, improves quality of life (SF-12v2 Health Survey, Christensen's VAS fatigue score), and reduces all-cause one-year mortality.

  Eligibility

Ages Eligible for Study:   40 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥40 years old.
  2. Major non-cardiac surgical procedures scheduled to take ≥ two hours done under general anesthesia.
  3. Written informed consent

Exclusion Criteria:

  1. Recent intravenous or oral steroid therapy (within 30 days); inhaled steroids are permitted
  2. Any contraindications to the proposed interventions
  3. ASA Physical Status > 4
  4. Non English speaking patients
  5. Procedures done under regional anesthesia
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00995501

Locations
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
Outcomes Research Consortium
Investigators
Principal Investigator: Basem Abdelmalak, MD The Cleveland Clinic
  More Information

No publications provided by Outcomes Research Consortium

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Daniel Sessler, MD, Cleveland Clinic
ClinicalTrials.gov Identifier: NCT00995501     History of Changes
Obsolete Identifiers: NCT00433251
Other Study ID Numbers: 07-010
Study First Received: October 14, 2009
Last Updated: May 4, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Outcomes Research Consortium:
steroid administration
tight glucose control
light anesthesiReducing inflammatory response to surgical stress
a

Additional relevant MeSH terms:
Inflammation
Pathologic Processes
Anesthetics
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
BB 1101
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 22, 2014