Perioperative Metabolic and Hormonal Aspects in Major Emergency Surgery

Completed

• Conditions: Acute Illness; Gastrointestinal Disease; Stress; Surgery--Complications

• Registration Number: NCT03482830
• Lead Sponsor: Zealand University Hospital

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-02-13
• Study Start: 2018-03-05
• Study First Submitted QC: 2018-03-22
• Study First Posted: 2018-03-29
• Primary Completion: 2018-11-01
• Study Completion: 2019-11-01
• Status Verified: 2020-01
• Last Update Submitted: 2020-01-21
• Last Update Posted: 2020-01-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 98

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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 cortisol	Change from preoperative levels at postoperative day 5	Assessment of plasma cortisol (free and bound)
Changes of syndecan-1	Change from preoperative levels at postoperative day 5	Assessment of plasma syndecan-1
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 thrombomodulin	Change from preoperative levels at postoperative day 5	Assessment of plasma thrombomodulin
Changes of sVE-cadherin	Change from preoperative levels at postoperative day 5	Assessment of plasma sVE-cadherin
Changes of neuropeptides	Change from preoperative levels at postoperative day 5	Assessment of plasma neuropeptides

Secondary Outcome Measures

Name	Time	Method
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
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

Trial Locations

Locations (1)

Department of Surgery, Zealand University Hospital; 🇩🇰 Køge, Denmark