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))

NCT ID: NCT00995501

Last Updated: 2017-04-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 381 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2015-12-31

Brief Summary

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.

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.

Conditions

Inflammation; Perioperative Morbidity

Study Design

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

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Dexamethasone Sodium Sulfate

Intervention Type: DRUG

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

Insulin

Intervention Type: DRUG

Insulin to maintain blood glucose 80-110 mg/dl.

anesthesia management

Intervention Type: DRUG

Light anesthesia to maintain BIS about 55

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

Group Type: ACTIVE_COMPARATOR

Dexamethasone Sodium Sulfate

Intervention Type: DRUG

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

Insulin

Intervention Type: DRUG

Insulin to maintain blood glucose 80-110 mg/dl.

Anesthesia management -Placebo

Intervention Type: OTHER

Deep anesthesia to maintain BIS about 35

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

Group Type: ACTIVE_COMPARATOR

Dexamethasone Sodium Sulfate

Intervention Type: DRUG

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

anesthesia management

Intervention Type: DRUG

Light anesthesia to maintain BIS about 55

Insulin - Placebo

Intervention Type: OTHER

Insulin to maintain blood glucose 180-200 mg/dl.

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

Group Type: ACTIVE_COMPARATOR

Insulin

Intervention Type: DRUG

Insulin to maintain blood glucose 80-110 mg/dl.

anesthesia management

Intervention Type: DRUG

Light anesthesia to maintain BIS about 55

Dexamethasone - placebo

Intervention Type: OTHER

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

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

Group Type: ACTIVE_COMPARATOR

Dexamethasone Sodium Sulfate

Intervention Type: DRUG

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

Insulin - Placebo

Intervention Type: OTHER

Insulin to maintain blood glucose 180-200 mg/dl.

Anesthesia management -Placebo

Intervention Type: OTHER

Deep anesthesia to maintain BIS about 35

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

Group Type: ACTIVE_COMPARATOR

Insulin

Intervention Type: DRUG

Insulin to maintain blood glucose 80-110 mg/dl.

Dexamethasone - placebo

Intervention Type: OTHER

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

Anesthesia management -Placebo

Intervention Type: OTHER

Deep anesthesia to maintain BIS about 35

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

Group Type: ACTIVE_COMPARATOR

anesthesia management

Intervention Type: DRUG

Light anesthesia to maintain BIS about 55

Dexamethasone - placebo

Intervention Type: OTHER

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

Insulin - Placebo

Intervention Type: OTHER

Insulin to maintain blood glucose 180-200 mg/dl.

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

Group Type: PLACEBO_COMPARATOR

Dexamethasone - placebo

Intervention Type: OTHER

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

Insulin - Placebo

Intervention Type: OTHER

Insulin to maintain blood glucose 180-200 mg/dl.

Anesthesia management -Placebo

Intervention Type: OTHER

Deep anesthesia to maintain BIS about 35

Interventions

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

Intervention Type: DRUG

Insulin

Insulin to maintain blood glucose 80-110 mg/dl.

Intervention Type: DRUG

anesthesia management

Light anesthesia to maintain BIS about 55

Intervention Type: DRUG

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

Intervention Type: OTHER

Insulin - Placebo

Insulin to maintain blood glucose 180-200 mg/dl.

Intervention Type: OTHER

Anesthesia management -Placebo

Deep anesthesia to maintain BIS about 35

Intervention Type: OTHER

Eligibility 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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

d sessler

OTHER

Sponsor Role: lead

Responsible Party

d sessler

MD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Basem Abdelmalak, MD

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

Cleveland Clinic

Cleveland, Ohio, United States

Countries

United States

References

Bellon F, Sola I, Gimenez-Perez G, Hernandez M, Metzendorf MI, Rubinat E, Mauricio D. Perioperative glycaemic control for people with diabetes undergoing surgery. Cochrane Database Syst Rev. 2023 Aug 1;8(8):CD007315. doi: 10.1002/14651858.CD007315.pub3.

Reference Type: DERIVED

PMID: 37526194 (View on PubMed)

Abdelmalak BB, Duncan AE, Bonilla A, Yang D, Parra-Sanchez I, Fergany A, Irefin SA, Sessler DI. The intraoperative glycemic response to intravenous insulin during noncardiac surgery: a subanalysis of the DeLiT randomized trial. J Clin Anesth. 2016 Mar;29:19-29. doi: 10.1016/j.jclinane.2015.10.005. Epub 2016 Feb 2.

Reference Type: DERIVED

PMID: 26897443 (View on PubMed)

Abdelmalak BB, Bonilla A, Mascha EJ, Maheshwari A, Tang WH, You J, Ramachandran M, Kirkova Y, Clair D, Walsh RM, Kurz A, Sessler DI. Dexamethasone, light anaesthesia, and tight glucose control (DeLiT) randomized controlled trial. Br J Anaesth. 2013 Aug;111(2):209-21. doi: 10.1093/bja/aet050. Epub 2013 Mar 28.

Reference Type: DERIVED

PMID: 23539236 (View on PubMed)

Abdelmalak B, Maheshwari A, Kovaci B, Mascha EJ, Cywinski JB, Kurz A, Kashyap VS, Sessler DI. Validation of the DeLiT Trial intravenous insulin infusion algorithm for intraoperative glucose control in noncardiac surgery: a randomized controlled trial. Can J Anaesth. 2011 Jul;58(7):606-616. doi: 10.1007/s12630-011-9509-3. Epub 2011 May 20.

Reference Type: DERIVED

PMID: 21598057 (View on PubMed)

Other Identifiers

07-010

Identifier Type: -

Identifier Source: org_study_id

NCT00433251

Identifier Type: -

Identifier Source: nct_alias