Perioperative Metabolic and Hormonal Aspects in Major Emergency Surgery

NCT03482830 | Completed

• 1 other identifier: PHASE
• Study Type: observational
• Target: 98
• Locations: 1 country
• Sites: 1

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.

Conditions

Surgery--Complications; Acute Illness; Gastrointestinal Disease; Stress

Keywords

Inflammation; Insulin-glucose homeostasis; Hypothalamic-pituitary-adrenal axis; Endothelial function and damage; Thyroid hormones

Outcome Measures

Primary Outcomes (12)

• 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 Outcomes (2)

• Number of patients with major adverse cardiovascular events

  365 days after surgery

• Number of patients with postoperative non-cardiovascular complications

  365 days after surgery

Interventions

Major emergency gastrointestinal surgery PROCEDURE

* 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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients ≥ 18 years old undergoing acute major gastrointestinal surgery within 72 hours of their admission to the Department of Surgery or an acute reoperation. Major gastrointestinal surgery are defined as procedures involving the stomach, small or large bowel, or rectum for conditions such as perforation, ischaemia, abdominal abscess, bleeding or obstruction. Patients will be consecutively screened for inclusion.

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Zealand University Hospital: lead

Study Sites (1)

Department of Surgery, Zealand University Hospital

Køge, 2300, Denmark

Location

Related Publications (9)

• Huddart S, Peden CJ, Swart M, McCormick B, Dickinson M, Mohammed MA, Quiney N; ELPQuiC Collaborator Group; ELPQuiC Collaborator Group. Use of a pathway quality improvement care bundle to reduce mortality after emergency laparotomy. Br J Surg. 2015 Jan;102(1):57-66. doi: 10.1002/bjs.9658. Epub 2014 Nov 10.

  PMID: 25384994 BACKGROUND

• Lord JM, Midwinter MJ, Chen YF, Belli A, Brohi K, Kovacs EJ, Koenderman L, Kubes P, Lilford RJ. The systemic immune response to trauma: an overview of pathophysiology and treatment. Lancet. 2014 Oct 18;384(9952):1455-65. doi: 10.1016/S0140-6736(14)60687-5. Epub 2014 Oct 17.

  PMID: 25390327 BACKGROUND

• Preiser JC, Ichai C, Orban JC, Groeneveld AB. Metabolic response to the stress of critical illness. Br J Anaesth. 2014 Dec;113(6):945-54. doi: 10.1093/bja/aeu187. Epub 2014 Jun 26.

  PMID: 24970271 BACKGROUND

• Marik PE, Bellomo R. Stress hyperglycemia: an essential survival response! Crit Care Med. 2013 Jun;41(6):e93-4. doi: 10.1097/CCM.0b013e318283d124. No abstract available.

  PMID: 23685597 BACKGROUND

• Hassan-Smith Z, Cooper MS. Overview of the endocrine response to critical illness: how to measure it and when to treat. Best Pract Res Clin Endocrinol Metab. 2011 Oct;25(5):705-17. doi: 10.1016/j.beem.2011.04.002.

  PMID: 21925072 BACKGROUND

• Gibbison B, Angelini GD, Lightman SL. Dynamic output and control of the hypothalamic-pituitary-adrenal axis in critical illness and major surgery. Br J Anaesth. 2013 Sep;111(3):347-60. doi: 10.1093/bja/aet077. Epub 2013 May 9.

  PMID: 23661405 BACKGROUND

• Munzel T, Sinning C, Post F, Warnholtz A, Schulz E. Pathophysiology, diagnosis and prognostic implications of endothelial dysfunction. Ann Med. 2008;40(3):180-96. doi: 10.1080/07853890701854702.

  PMID: 18382884 BACKGROUND

• Ekeloef S, Larsen MH, Schou-Pedersen AM, Lykkesfeldt J, Rosenberg J, Gogenur I. Endothelial dysfunction in the early postoperative period after major colon cancer surgery. Br J Anaesth. 2017 Feb;118(2):200-206. doi: 10.1093/bja/aew410.

  PMID: 28100523 BACKGROUND

• McIlroy DR, Chan MT, Wallace SK, Symons JA, Koo EG, Chu LC, Myles PS. Automated preoperative assessment of endothelial dysfunction and risk stratification for perioperative myocardial injury in patients undergoing non-cardiac surgery. Br J Anaesth. 2014 Jan;112(1):47-56. doi: 10.1093/bja/aet354. Epub 2013 Oct 29.

  PMID: 24172055 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Plasma, whole blood

MeSH Terms

Conditions

Gastrointestinal Diseases; Inflammation

Condition Hierarchy (Ancestors)

Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jakob Burcharth, MD, PhD

  Zealand University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2018
• First Posted: March 29, 2018
• Study Start: March 5, 2018
• Primary Completion: November 1, 2018
• Study Completion: November 1, 2019
• Last Updated: January 22, 2020

Record last verified: 2020-01

Locations

DK (1)