Clinical trial NCT00995501
Conditions: Inflammation Perioperative Morbidity
Keywords: steroid administration tight glucose control light anesthesiReducing inflammatory response to surgical stress a
Sponsor: d sessler
Start date: 2007-01-01; Completion date: 2015-12-01
Enrollment: 381 participants; Allocation: RANDOMIZED; Intervention model: FACTORIAL

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.

Arms: arm 1: * 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 arm 2: * 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 arm 3: * 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 arm 4: * 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 arm 5: * 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 arm 6: * 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 arm 7: * 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 arm 8: * 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
Interventions: intervention 1: Dexamethasone Sodium Sulfate intervention 2: Insulin intervention 3: anesthesia management intervention 4: Dexamethasone - placebo intervention 5: Insulin - Placebo intervention 6: Anesthesia management -Placebo
Intervention descriptions: intervention 1: 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 2: Insulin to maintain blood glucose 80-110 mg/dl. intervention 3: Light anesthesia to maintain BIS about 55 intervention 4: 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 5: Insulin to maintain blood glucose 180-200 mg/dl. intervention 6: Deep anesthesia to maintain BIS about 35

Protocol documents: