Perioperative Metabolic and Hormonal Aspects in Major Emergency Surgery

Stress Clinical Trial

— PHASE  

Official title:

Perioperative Metabolic and Hormonal Aspects in Major Emergency Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03482830
• Other study ID #: PHASE
• Status: Completed
• Start date: March 5, 2018
• Est. completion date: November 1, 2019

Study information

• Verified date: January 2020
• Source: Zealand University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 98
• Est. completion date: November 1, 2019
• Est. primary completion date: November 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Illness
• Digestive System Diseases
• Emergencies
• Gastrointestinal Disease
• Gastrointestinal Diseases
• Stress
• Surgery--Complications

Intervention

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

Locations

Country	Name	City	State
Denmark	Department of Surgery, Zealand University Hospital	Køge

Sponsors (1)

Lead Sponsor	Collaborator
Zealand University Hospital

Country where clinical trial is conducted

Denmark, 

References & Publications (9)

Ekeloef S, Larsen MH, Schou-Pedersen AM, Lykkesfeldt J, Rosenberg J, Gögenür 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. — View 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. Review. — View 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. Review. — View 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. — View 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. Review. — View 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. — View 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. — View Citation

Münzel 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. Review. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	Changes of the central endocrine stress response	Assessment of plasma corticotropin releasing hormone (CRH)	Change from preoperative levels at postoperative day 5
Primary	Changes of sE-selectin	Assessment of plasma sE-selectine; sE-selectin; syndecan-1; thrombomodulin; sVE-cadherin	Change from preoperative levels at postoperative day 5
Primary	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
Primary	Changes of the periferal endocrine stress response	Assessment of plasma adrenocorticotropic hormone (ACTH)	Change from preoperative levels at postoperative day 5
Primary	Changes of cortisol	Assessment of plasma cortisol (free and bound)	Change from preoperative levels at postoperative day 5
Primary	Changes of neuropeptides	Assessment of plasma neuropeptides	Change from preoperative levels at postoperative day 5
Primary	Changes of syndecan-1	Assessment of plasma syndecan-1	Change from preoperative levels at postoperative day 5
Primary	Changes of thrombomodulin	Assessment of plasma thrombomodulin	Change from preoperative levels at postoperative day 5
Primary	Changes of sVE-cadherin	Assessment of plasma sVE-cadherin	Change from preoperative levels at postoperative day 5
Secondary	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
Secondary	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

External Links

•   Center for Surgical Science