Clinical trial NCT00995501: 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))
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))
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Inflammation
Perioperative Morbidity
Keywords: steroid administration
tight glucose control
light anesthesiReducing inflammatory response to surgical stress
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Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
First posted: 2009-10-15
Enrollment: 381
Sex: ALL
Minimum age (years): 40
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Major Perioperative Morbidity
timeFrame: 30 day after surgery
Secondary outcomes:
measure: 1 Year Mortality
timeFrame: 1 year after surgery
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Basem Abdelmalak, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.