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))

d sessler

Status

Terminated

Conditions

Inflammation

Perioperative Morbidity

Treatments

Other: Insulin - Placebo

Drug: Dexamethasone Sodium Sulfate

Drug: anesthesia management

Drug: Insulin

Other: Anesthesia management -Placebo

Other: Dexamethasone - placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT00995501

07-010

Details and patient eligibility

About

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.

Full 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.

Enrollment

381 patients

Sex

All

Ages

40 to 90 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

Recent intravenous or oral steroid therapy (within 30 days); inhaled steroids are permitted
Any contraindications to the proposed interventions
ASA Physical Status > 4
Non English speaking patients
Procedures done under regional anesthesia

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Factorial Assignment

Masking

Double Blind

381 participants in 8 patient groups, including a placebo group

Intensive Glucose Control, Dexamethasone, light anesthesia

Active Comparator group

Description:

* 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

Treatment:

Drug: Dexamethasone Sodium Sulfate

Drug: anesthesia management

Drug: Insulin

Intensive Glucose Control, Dexamethasone, Deep anesthesia

Active Comparator group

Description:

Treatment:

Drug: Dexamethasone Sodium Sulfate

Other: Anesthesia management -Placebo

Drug: Insulin

Intensive Glucose Control, placebo, Light anesthesia

Active Comparator group

Description:

* 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

Treatment:

Other: Insulin - Placebo

Drug: Dexamethasone Sodium Sulfate

Drug: anesthesia management

Conventional Glucose Control, Dexamethasone, Light anesthesia

Active Comparator group

Description:

* 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

Treatment:

Drug: anesthesia management

Other: Dexamethasone - placebo

Drug: Insulin

Intensive Glucose Control, Placebo, Deep anesthesia

Active Comparator group

Description:

Treatment:

Other: Insulin - Placebo

Drug: Dexamethasone Sodium Sulfate

Other: Anesthesia management -Placebo

Conventional Glucose Control, Dexamethasone, Deep anesthesia

Active Comparator group

Description:

Treatment:

Other: Anesthesia management -Placebo

Other: Dexamethasone - placebo

Drug: Insulin

Conventional Glucose Control, Placebo, Light anesthesia

Active Comparator group

Description:

* 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

Treatment:

Other: Insulin - Placebo

Drug: anesthesia management

Other: Dexamethasone - placebo

Conventional Glucose Control, Placebo, Deep anesthesia

Placebo Comparator group

Description:

Treatment:

Other: Insulin - Placebo

Other: Anesthesia management -Placebo

Other: Dexamethasone - placebo