Perioperative Metabolic and Hormonal Aspects in Major Emergency Surgery

Study Overview
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Brief Summary
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Emergency laparotomies, which most often is performed due to high risk disease (bowel obstruction, ischemia, perforation, etc.), make up 11 % of surgical procedures in emergency surgical departments, however, give rise to 80 % of all postoperative complications. The 30-day mortality rates in relation to these emergent procedures have been reported between 14-30 %, with even higher numbers for frail and older patients. The specific reasons for these outcomes are not yet known, however, a combination of preexisting comorbidities, acute illness, sepsis, and the surgical stress response that arise during- and after the surgical procedure due to the activation of the immunological and humoral system, is most likely to blame. The complex endocrinological response and consequences of this response to emergency surgery are sparsely reported in the literature. The aim of this PHASE project is to evaluate and describe the temporal endocrine, endothelial and immunological changes after major emergency abdominal surgery, and to associate these changes with clinical postoperative outcomes.

Official Title
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Perioperative Metabolic and Hormonal Aspects in Major Emergency Surgery

Conditions
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Surgery--Complications, Acute Illness, Gastrointestinal Disease, Stress

Intervention / Treatment
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* Procedure: Major emergency gastrointestinal surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Surgery within 72 hours of an acute admission to the Department of Surgery or an acute reoperation. Major gastrointestinal surgery on the gastrointestinal tract (see intervention definition) Exclusion Criteria: Not capable of giving informed consent after oral and written information Previously included in the trial Elective laparoscopy Diagnostic laparotomy/laparoscopy where no subsequent procedure is performed (NB, if no procedure is performed because of inoperable pathology, then include) Appendectomy +/- drainage or Cholecystectomy +/- drainage of localized collection unless the procedure is incidental to a non-elective procedure on the GI tract Non-elective hernia repair without bowel resection. Minor abdominal wound dehiscence unless this causes bowel complications requiring resection Ruptured ectopic pregnancy, or pelvic abscesses due to pelvic inflammatory disease Laparotomy/laparoscopy for pathology caused by blunt or penetrating trauma, esophageal pathology, pathology of the spleen, renal tract, kidneys, liver, gall bladder and biliary tree, pancreas or urinary tract

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Procedure: Major emergency gastrointestinal surgery|Open, laparoscopic, or laparoscopically-assisted procedures Procedures involving the stomach, small or large bowel, or rectum for conditions such as perforation, ischaemia, abdominal abscess, bleeding or obstruction|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of immunological biomarkers | Assessment of: plasma inflammatory interleukines incl. IL-1-alfa, IL-1beta, IL-6, IL-10 plasma TNF-alfa plasma TGF-beta | Change from preoperative levels at postoperative day 5 | 
| Number of patients with stress induced hyperglycemia | Assessment of: Blood glucose, plasma c-peptide, HbA1C plasma Glucagon-like peptide 1 (GLP-1) | Postoperative day 5 | 
| Changes of plasma thyroid hormones | Assessment of: Thyropin-releasing hormone (TRH) Thyroid-stimulating hormone (TSH) Thyroid hormones (fT3, fT4, rT3) | Change from preoperative levels at postoperative day 5 | 
| Changes of the central endocrine stress response | Assessment of plasma corticotropin releasing hormone (CRH) | Change from preoperative levels at postoperative day 5 | 
| Changes of sE-selectin | Assessment of plasma sE-selectine sE-selectin syndecan-1 thrombomodulin sVE-cadherin | Change from preoperative levels at postoperative day 5 | 
| Changes of the endothelial function | Assessed with the non-invasive EndoPAT and expressed as the reactive hyperemia index | Change from postoperative day 1 at postoperative day 5 | 
| Changes of the periferal endocrine stress response | Assessment of plasma adrenocorticotropic hormone (ACTH) | Change from preoperative levels at postoperative day 5 | 
| Changes of cortisol | Assessment of plasma cortisol (free and bound) | Change from preoperative levels at postoperative day 5 | 
| Changes of neuropeptides | Assessment of plasma neuropeptides | Change from preoperative levels at postoperative day 5 | 
| Changes of syndecan-1 | Assessment of plasma syndecan-1 | Change from preoperative levels at postoperative day 5 | 
| Changes of thrombomodulin | Assessment of plasma thrombomodulin | Change from preoperative levels at postoperative day 5 | 
| Changes of sVE-cadherin | Assessment of plasma sVE-cadherin | Change from preoperative levels at postoperative day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with major adverse cardiovascular events | Defined as: Cardiovascular death Myocardial injury within postoperative day 4 (definition: peak plasma cardiac troponin-I ≥ 45ng/L (99th percentile URL, 10% CV at 40ng/L)) Acute coronary syndrome (unstable angina pectoris, NSTEMI, STEMI) Congestive heart failure Stroke Nonfatal cardiac arrest New clinically important cardiac arrhythmia Coronary revascularization procedure (PCI or CABG) Sudden unexpected death | 365 days after surgery | 
| Number of patients with postoperative non-cardiovascular complications | Defined as: Non-cardiovascular death with other defined reason for death Sepsis (sepsis - severe sepsis - septic shock) Pneumonia Respiratory failure Surgical complications (Clavien-Dindo stage 3) Any non-cardiovascular life-threatening complication (Clavien-Dindo stage 4) Readmission due to a non-cardiovascular complication | 365 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Inflammation, Insulin-glucose homeostasis, Hypothalamic-pituitary-adrenal axis, Endothelial function and damage, Thyroid hormones