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))

March 15, 2017 updated by: d sessler

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

381

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 90 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Intensive Glucose Control, Dexamethasone, light anesthesia
  • Intensive Glucose Control The target range for blood glucose will be 80-110 mg/dl
  • Dexamethasone 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.
  • Light anesthesia target BIS of 55
Drug: Dexamethasone Sodium Sulfate
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: Insulin
Insulin to maintain blood glucose 80-110 mg/dl.
Drug: anesthesia management
Light anesthesia to maintain BIS about 55
ACTIVE_COMPARATOR: Intensive Glucose Control, Dexamethasone, Deep anesthesia
  • Intensive Glucose Control The target range for blood glucose will be 80-110 mg/dl
  • Dexamethasone 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.
  • Deep anesthesia target BIS of 35
Drug: Dexamethasone Sodium Sulfate
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: Insulin
Insulin to maintain blood glucose 80-110 mg/dl.
Other: Anesthesia management -Placebo
Deep anesthesia to maintain BIS about 35
ACTIVE_COMPARATOR: Intensive Glucose Control, placebo, Light anesthesia
  • Intensive Glucose Control The target range for blood glucose will be 80-110 mg/dl
  • Placebo Placebo 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.
  • Light anesthesia target BIS of 55
Drug: Dexamethasone Sodium Sulfate
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: anesthesia management
Light anesthesia to maintain BIS about 55
Other: Insulin - Placebo
Insulin to maintain blood glucose 180-200 mg/dl.
ACTIVE_COMPARATOR: Conventional Glucose Control, Dexamethasone, Light anesthesia
  • Conventional Glucose Control The target range for blood glucose will be 180-200 mg/dl
  • Dexamethasone 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.
  • Light anesthesia target BIS of 55
Drug: Insulin
Insulin to maintain blood glucose 80-110 mg/dl.
Drug: anesthesia management
Light anesthesia to maintain BIS about 55
Other: Dexamethasone - placebo
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: Intensive Glucose Control, Placebo, Deep anesthesia
  • Intensive Glucose Control The target range for blood glucose will be 80-110 mg/dl
  • Placebo Placebo 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.
  • Deep anesthesia target BIS of 35
Drug: Dexamethasone Sodium Sulfate
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
Other: Anesthesia management -Placebo
Deep anesthesia to maintain BIS about 35
Other: Insulin - Placebo
Insulin to maintain blood glucose 180-200 mg/dl.
ACTIVE_COMPARATOR: Conventional Glucose Control, Dexamethasone, Deep anesthesia
  • Conventional Glucose Control The target range for blood glucose will be 180-200 mg/dl
  • Dexamethasone 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.
  • Deep anesthesia target BIS of 35
Drug: Insulin
Insulin to maintain blood glucose 80-110 mg/dl.
Other: Anesthesia management -Placebo
Deep anesthesia to maintain BIS about 35
Other: Dexamethasone - placebo
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: Conventional Glucose Control, Placebo, Light anesthesia
  • Conventional Glucose Control The target range for blood glucose will be 180-200 mg/dl
  • Placebo Placebo 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.
  • Light anesthesia target BIS of 55
Drug: anesthesia management
Light anesthesia to maintain BIS about 55
Other: Insulin - Placebo
Insulin to maintain blood glucose 180-200 mg/dl.
Other: Dexamethasone - placebo
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
PLACEBO_COMPARATOR: Conventional Glucose Control, Placebo, Deep anesthesia
  • Conventional Glucose Control The target range for blood glucose will be 180-200 mg/dl
  • Placebo Placebo 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.
  • Deep anesthesia target BIS of 35
Other: Anesthesia management -Placebo
Deep anesthesia to maintain BIS about 35
Other: Insulin - Placebo
Insulin to maintain blood glucose 180-200 mg/dl.
Other: Dexamethasone - placebo
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Major Perioperative Morbidity
Time Frame: 30 day after surgery
Our primary outcome was a collapsed composite endpoint (any versus none) defined as the occurrence of at least one of sixteen major complications before hospital discharge, including sepsis, severe surgical site infection, myocardial infarction, heart failure, stroke, unstable ventricular arrhythmias, pulmonary embolism, pneumonia, respiratory failure, dialysis dependent renal failure, large pleural or peritoneal effusions, major bleeding, major wound and surgical site healing complications, vascular graft thrombosis, and 30-day mortality.
30 day after surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
1 Year Mortality
Time Frame: 1 year after surgery
All-cause mortality
1 year after surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

d sessler

Investigators

  • Principal Investigator: Basem Abdelmalak, MD, The Cleveland Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2007

Primary Completion (ACTUAL)

December 1, 2015

Study Completion (ACTUAL)

December 1, 2015

Study Registration Dates

First Submitted

October 14, 2009

First Submitted That Met QC Criteria

October 14, 2009

First Posted (ESTIMATE)

October 15, 2009

Study Record Updates

Last Update Posted (ACTUAL)

April 25, 2017

Last Update Submitted That Met QC Criteria

March 15, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 07-010 (Sponsor's Code)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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