Clinical trial NCT03482830: Perioperative Metabolic and Hormonal Aspects in Major Emergency Surgery
Official title: Perioperative Metabolic and Hormonal Aspects in Major Emergency Surgery
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Surgery--Complications
Acute Illness
Gastrointestinal Disease
Stress
Keywords: Inflammation
Insulin-glucose homeostasis
Hypothalamic-pituitary-adrenal axis
Endothelial function and damage
Thyroid hormones
Lead sponsor: Zealand University Hospital
Sponsor class: OTHER
First posted: 2018-03-29
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.


Eligibility criteria: 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

Primary outcomes:
measure: Changes of immunological biomarkers
timeFrame: Change from preoperative levels at postoperative day 5
measure: Number of patients with stress induced hyperglycemia
timeFrame: Postoperative day 5
measure: Changes of plasma thyroid hormones
timeFrame: Change from preoperative levels at postoperative day 5
measure: Changes of the central endocrine stress response
timeFrame: Change from preoperative levels at postoperative day 5
measure: Changes of sE-selectin
timeFrame: Change from preoperative levels at postoperative day 5
measure: Changes of the endothelial function
timeFrame: Change from postoperative day 1 at postoperative day 5
measure: Changes of the periferal endocrine stress response
timeFrame: Change from preoperative levels at postoperative day 5
measure: Changes of cortisol
timeFrame: Change from preoperative levels at postoperative day 5
measure: Changes of neuropeptides
timeFrame: Change from preoperative levels at postoperative day 5
measure: Changes of syndecan-1
timeFrame: Change from preoperative levels at postoperative day 5
measure: Changes of thrombomodulin
timeFrame: Change from preoperative levels at postoperative day 5
measure: Changes of sVE-cadherin
timeFrame: Change from preoperative levels at postoperative day 5
Secondary outcomes:
measure: Number of patients with major adverse cardiovascular events
timeFrame: 365 days after surgery
measure: Number of patients with postoperative non-cardiovascular complications
timeFrame: 365 days after surgery
Other outcomes:
Locations:
city: Køge
country: Denmark
facility: Department of Surgery, Zealand University Hospital
Study officials:
affiliation: Zealand University Hospital
name: Jakob Burcharth, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.