Acute Illness, Gastrointestinal Disease, Stress, Surgery--Complications
Conditions
Keywords
Inflammation, Insulin-glucose homeostasis, Hypothalamic-pituitary-adrenal axis, Endothelial function and damage, Thyroid hormones
Brief summary
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.
Interventions
PROCEDUREMajor 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
Sponsors
Zealand University Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes of sVE-cadherin | Change from preoperative levels at postoperative day 5 | Assessment of plasma sVE-cadherin |
| Changes of syndecan-1 | Change from preoperative levels at postoperative day 5 | Assessment of plasma syndecan-1 |
| Changes of thrombomodulin | Change from preoperative levels at postoperative day 5 | Assessment of plasma thrombomodulin |
| Changes of immunological biomarkers | Change from preoperative levels at postoperative day 5 | Assessment of: * plasma inflammatory interleukines incl. IL-1-alfa, IL-1beta, IL-6, IL-10 * plasma TNF-alfa * plasma TGF-beta |
| Number of patients with stress induced hyperglycemia | Postoperative day 5 | Assessment of: * Blood glucose, plasma c-peptide, HbA1C * plasma Glucagon-like peptide 1 (GLP-1) |
| Changes of plasma thyroid hormones | Change from preoperative levels at postoperative day 5 | Assessment of: * Thyropin-releasing hormone (TRH) * Thyroid-stimulating hormone (TSH) * Thyroid hormones (fT3, fT4, rT3) |
| Changes of the central endocrine stress response | Change from preoperative levels at postoperative day 5 | Assessment of plasma corticotropin releasing hormone (CRH) |
| Changes of sE-selectin | Change from preoperative levels at postoperative day 5 | Assessment of plasma sE-selectine * sE-selectin * syndecan-1 * thrombomodulin * sVE-cadherin |
| Changes of the endothelial function | Change from postoperative day 1 at postoperative day 5 | Assessed with the non-invasive EndoPAT and expressed as the reactive hyperemia index |
| Changes of the periferal endocrine stress response | Change from preoperative levels at postoperative day 5 | Assessment of plasma adrenocorticotropic hormone (ACTH) |
| Changes of cortisol | Change from preoperative levels at postoperative day 5 | Assessment of plasma cortisol (free and bound) |
| Changes of neuropeptides | Change from preoperative levels at postoperative day 5 | Assessment of plasma neuropeptides |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with postoperative non-cardiovascular complications | 365 days after surgery | 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 |
| Number of patients with major adverse cardiovascular events | 365 days after surgery | 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 |
Countries
Denmark
Outcome results
None listed