Biomarkers in Acute High-risk AbdoMinAl Surgery

NCT03582631 | Completed DMC

• 1 other identifier: BAHAMAS1
• Study Type: observational
• Target: 600
• Locations: 1 country
• Sites: 1

Brief Summary

Acute high-risk abdominal surgery (AHA) is performed in hospitals worldwide. Ethiologies are heterogeneous, but it carries a high mortality rate (1)(2). In particular, emergency laparotomies performed on elderly people has a high mortality rate(3)(4). Different quality improvement programs have been suggested, but the quality of care and mortality varies between hospitals (5)(6). The use of postoperative intensive care seem to be inadequate for this high risk population (1)(7)(8). It is of paramount importance to identify the frailest and acutely deranged patients, who are in risk of poor outcome, to allocate resources for optimization postoperatively. Failure to escalate care intensity after having developed postoperative complications affect outcome. Organization, teamwork and culture is important postoperatively to be able to escalate care especially in standard care wards (9)(10). However, it is difficult to predict which patients will develop complications. Different risk assessment tools have been proposed for patients undergoing AHA (11)(12). The APACHE-II score, even though developed for critical care, seems to give the best prediction of outcome. Objective risk assessment tools support clinical decision making as subjective clinical assessment often underestimates the risk for the patients in highest risk of complications and death (13). Good clinical decision-making is likely to improve the clinical outcome by allocating appropriate resources. Prognostic tools are also useful to inform patients about what to expect in the postoperative phase and of long-term outcome. Especially in the elder population with increased risk of loss of function or independency, this can be useful to give informed consent to treatment. Furthermore, good risk assessment is important to optimize palliative care after end-of-life decisions, which is often ignored in research, but highly relevant in clinical work. Prognostic biomarkers in other high mortality populations have received much attention for risk stratification (14). An ideal biomarker should be readily available upon decision-making, easy to measure, and reliable. Furthermore, it should accurately differentiate prognosis for patients to have value in the clinical decision-making and guide the treatment. It should also be linked to the clinical outcomes. The investigators aim to identify AHA biomarkers that are prognostic or predictive for postoperative morbidity, mortality and length of hospitalization.

Conditions

General Surgery; Inflammation; Troponins; Biomarkers

Outcome Measures

Primary Outcomes (3)

• No of patients died within 30 days postoperatively

  30 day mortality after surgery

  30 days

• No of patients died within 180 days postoperatively

  180-day mortality after surgery

  180 days

• No of patients with major postoperative complications within 30 days afer surgery

  Clavien Dindo grade more than 3a

  30 days

Interventions

Emergency abdominal surgery PROCEDURE

Emergency surgery for high-risk abdominal pathology using a protocol for optimized perioperative care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Include patients with a preoperative blood sample stored in the bio bank; the patients did undergo AHA at Hvidovre Hospital, Copenhagen, Denmark, from June 1st 2013 when the AHA study protocol was initiated. In the primary study we will include the first 100 consecutive primary operations in the cohort.

You may qualify if:

• Patients aged 18 or older with the suspicion for abdominal pathology requiring immediate emergency laparotomy or laparoscopy including reoperations after elective surgery and reoperations after previous AHA surgery.

You may not qualify if:

• We excluded the following procedures: appendectomies; negative laparoscopies and laparotomies; cholecystectomies; simple herniotomies following incarceration (without intestinal resection); reoperation due to fascial separation with no other abdominal pathology; internal herniation after roux-en-y gastric bypass surgery; sub-acute surgery (planned within 48 hours) for inflammatory bowel disease; and sub-acute colorectal cancer surgery.
• We excluded, traumas, pregnant woman, uro-genital, gynaecological and vascular pathology except for mesenteric ischemia.

Sponsors & Collaborators

• University of Copenhagen: lead
• Hvidovre University Hospital: collaborator

Study Sites (1)

Hvidovre University hospital

Hvidovre, Capital Region, 2650, Denmark

Location

Related Publications (32)

• Pearse RM, Moreno RP, Bauer P, Pelosi P, Metnitz P, Spies C, Vallet B, Vincent JL, Hoeft A, Rhodes A; European Surgical Outcomes Study (EuSOS) group for the Trials groups of the European Society of Intensive Care Medicine and the European Society of Anaesthesiology. Mortality after surgery in Europe: a 7 day cohort study. Lancet. 2012 Sep 22;380(9847):1059-65. doi: 10.1016/S0140-6736(12)61148-9.

  PMID: 22998715 BACKGROUND

• Tolstrup MB, Watt SK, Gogenur I. Morbidity and mortality rates after emergency abdominal surgery: an analysis of 4346 patients scheduled for emergency laparotomy or laparoscopy. Langenbecks Arch Surg. 2017 Jun;402(4):615-623. doi: 10.1007/s00423-016-1493-1. Epub 2016 Aug 9.

  PMID: 27502400 BACKGROUND

• Stoneham M, Murray D, Foss N. Emergency surgery: the big three--abdominal aortic aneurysm, laparotomy and hip fracture. Anaesthesia. 2014 Jan;69 Suppl 1:70-80. doi: 10.1111/anae.12492.

  PMID: 24303863 BACKGROUND

• Jeppesen MH, Tolstrup MB, Kehlet Watt S, Gogenur I. Risk factors affecting morbidity and mortality following emergency laparotomy for small bowel obstruction: A retrospective cohort study. Int J Surg. 2016 Apr;28:63-8. doi: 10.1016/j.ijsu.2016.02.059. Epub 2016 Feb 18.

  PMID: 26912017 BACKGROUND

• Saunders DI, Murray D, Pichel AC, Varley S, Peden CJ; UK Emergency Laparotomy Network. Variations in mortality after emergency laparotomy: the first report of the UK Emergency Laparotomy Network. Br J Anaesth. 2012 Sep;109(3):368-75. doi: 10.1093/bja/aes165. Epub 2012 Jun 22.

  PMID: 22728205 BACKGROUND

• Symons NR, Moorthy K, Almoudaris AM, Bottle A, Aylin P, Vincent CA, Faiz OD. Mortality in high-risk emergency general surgical admissions. Br J Surg. 2013 Sep;100(10):1318-25. doi: 10.1002/bjs.9208. Epub 2013 Jul 17.

  PMID: 23864490 BACKGROUND

• Jhanji S, Thomas B, Ely A, Watson D, Hinds CJ, Pearse RM. Mortality and utilisation of critical care resources amongst high-risk surgical patients in a large NHS trust. Anaesthesia. 2008 Jul;63(7):695-700. doi: 10.1111/j.1365-2044.2008.05560.x. Epub 2008 May 16.

  PMID: 18489613 BACKGROUND

• Vester-Andersen M, Lundstrom LH, Moller MH, Waldau T, Rosenberg J, Moller AM; Danish Anaesthesia Database. Mortality and postoperative care pathways after emergency gastrointestinal surgery in 2904 patients: a population-based cohort study. Br J Anaesth. 2014 May;112(5):860-70. doi: 10.1093/bja/aet487. Epub 2014 Feb 10.

  PMID: 24520008 BACKGROUND

• Johnston MJ, Arora S, King D, Bouras G, Almoudaris AM, Davis R, Darzi A. A systematic review to identify the factors that affect failure to rescue and escalation of care in surgery. Surgery. 2015 Apr;157(4):752-63. doi: 10.1016/j.surg.2014.10.017.

  PMID: 25794627 BACKGROUND

• Ghaferi AA, Dimick JB. Importance of teamwork, communication and culture on failure-to-rescue in the elderly. Br J Surg. 2016 Jan;103(2):e47-51. doi: 10.1002/bjs.10031. Epub 2015 Nov 30.

  PMID: 26616276 BACKGROUND

• Oliver CM, Walker E, Giannaris S, Grocott MP, Moonesinghe SR. Risk assessment tools validated for patients undergoing emergency laparotomy: a systematic review. Br J Anaesth. 2015 Dec;115(6):849-60. doi: 10.1093/bja/aev350. Epub 2015 Nov 3.

  PMID: 26537629 BACKGROUND

• Al-Temimi MH, Griffee M, Enniss TM, Preston R, Vargo D, Overton S, Kimball E, Barton R, Nirula R. When is death inevitable after emergency laparotomy? Analysis of the American College of Surgeons National Surgical Quality Improvement Program database. J Am Coll Surg. 2012 Oct;215(4):503-11. doi: 10.1016/j.jamcollsurg.2012.06.004. Epub 2012 Jul 11.

  PMID: 22789546 BACKGROUND

• Hobson SA, Sutton CD, Garcea G, Thomas WM. Prospective comparison of POSSUM and P-POSSUM with clinical assessment of mortality following emergency surgery. Acta Anaesthesiol Scand. 2007 Jan;51(1):94-100. doi: 10.1111/j.1399-6576.2006.01167.x. Epub 2006 Nov 1.

  PMID: 17073858 BACKGROUND

• Sandquist M, Wong HR. Biomarkers of sepsis and their potential value in diagnosis, prognosis and treatment. Expert Rev Clin Immunol. 2014 Oct;10(10):1349-56. doi: 10.1586/1744666X.2014.949675. Epub 2014 Aug 21.

  PMID: 25142036 BACKGROUND

• Donadello K, Scolletta S, Taccone FS, Covajes C, Santonocito C, Cortes DO, Grazulyte D, Gottin L, Vincent JL. Soluble urokinase-type plasminogen activator receptor as a prognostic biomarker in critically ill patients. J Crit Care. 2014 Feb;29(1):144-9. doi: 10.1016/j.jcrc.2013.08.005. Epub 2013 Oct 9.

  PMID: 24120089 BACKGROUND

• Liu X, Shen Y, Li Z, Fei A, Wang H, Ge Q, Pan S. Prognostic significance of APACHE II score and plasma suPAR in Chinese patients with sepsis: a prospective observational study. BMC Anesthesiol. 2016 Jul 29;16(1):46. doi: 10.1186/s12871-016-0212-3.

  PMID: 27473112 BACKGROUND

• Zeng M, Chang M, Zheng H, Li B, Chen Y, He W, Huang C. Clinical value of soluble urokinase-type plasminogen activator receptor in the diagnosis, prognosis, and therapeutic guidance of sepsis. Am J Emerg Med. 2016 Mar;34(3):375-80. doi: 10.1016/j.ajem.2015.11.004. Epub 2015 Nov 9.

  PMID: 26615223 BACKGROUND

• Donadello K, Scolletta S, Covajes C, Vincent JL. suPAR as a prognostic biomarker in sepsis. BMC Med. 2012 Jan 5;10:2. doi: 10.1186/1741-7015-10-2.

  PMID: 22221662 BACKGROUND

• Hodges GW, Bang CN, Wachtell K, Eugen-Olsen J, Jeppesen JL. suPAR: A New Biomarker for Cardiovascular Disease? Can J Cardiol. 2015 Oct;31(10):1293-302. doi: 10.1016/j.cjca.2015.03.023. Epub 2015 Mar 25.

  PMID: 26118447 BACKGROUND

• Botha S, Fourie CMT, Schutte R, Eugen-Olsen J, Pretorius R, Schutte AE. Soluble urokinase plasminogen activator receptor as a prognostic marker of all-cause and cardiovascular mortality in a black population. Int J Cardiol. 2015 Apr 1;184:631-636. doi: 10.1016/j.ijcard.2015.03.041. Epub 2015 Mar 4.

  PMID: 25771228 BACKGROUND

• Sando A, Schultz M, Eugen-Olsen J, Rasmussen LS, Kober L, Kjoller E, Jensen BN, Ravn L, Lange T, Iversen K. Introduction of a prognostic biomarker to strengthen risk stratification of acutely admitted patients: rationale and design of the TRIAGE III cluster randomized interventional trial. Scand J Trauma Resusc Emerg Med. 2016 Aug 5;24:100. doi: 10.1186/s13049-016-0290-8.

  PMID: 27491822 BACKGROUND

• Lahiri R, Derwa Y, Bashir Z, Giles E, Torrance HD, Owen HC, O'Dwyer MJ, O'Brien A, Stagg AJ, Bhattacharya S, Foster GR, Alazawi W. Systemic Inflammatory Response Syndrome After Major Abdominal Surgery Predicted by Early Upregulation of TLR4 and TLR5. Ann Surg. 2016 May;263(5):1028-37. doi: 10.1097/SLA.0000000000001248.

  PMID: 26020106 BACKGROUND

• John J, Woodward DB, Wang Y, Yan SB, Fisher D, Kinasewitz GT, Heiselman D. Troponin-I as a prognosticator of mortality in severe sepsis patients. J Crit Care. 2010 Jun;25(2):270-5. doi: 10.1016/j.jcrc.2009.12.001. Epub 2010 Feb 10.

  PMID: 20149590 BACKGROUND

• Landesberg G, Jaffe AS, Gilon D, Levin PD, Goodman S, Abu-Baih A, Beeri R, Weissman C, Sprung CL, Landesberg A. Troponin elevation in severe sepsis and septic shock: the role of left ventricular diastolic dysfunction and right ventricular dilatation*. Crit Care Med. 2014 Apr;42(4):790-800. doi: 10.1097/CCM.0000000000000107.

  PMID: 24365861 BACKGROUND

• Sheyin O, Davies O, Duan W, Perez X. The prognostic significance of troponin elevation in patients with sepsis: a meta-analysis. Heart Lung. 2015 Jan-Feb;44(1):75-81. doi: 10.1016/j.hrtlng.2014.10.002. Epub 2014 Nov 18.

  PMID: 25453390 BACKGROUND

• Benz F, Roy S, Trautwein C, Roderburg C, Luedde T. Circulating MicroRNAs as Biomarkers for Sepsis. Int J Mol Sci. 2016 Jan 9;17(1):78. doi: 10.3390/ijms17010078.

  PMID: 26761003 BACKGROUND

• Johansson PI, Stensballe J, Rasmussen LS, Ostrowski SR. A high admission syndecan-1 level, a marker of endothelial glycocalyx degradation, is associated with inflammation, protein C depletion, fibrinolysis, and increased mortality in trauma patients. Ann Surg. 2011 Aug;254(2):194-200. doi: 10.1097/SLA.0b013e318226113d.

  PMID: 21772125 BACKGROUND

• Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen BK, Ganz T. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest. 2004 May;113(9):1271-6. doi: 10.1172/JCI20945.

  PMID: 15124018 BACKGROUND

• Gallo V, Egger M, McCormack V, Farmer PB, Ioannidis JP, Kirsch-Volders M, Matullo G, Phillips DH, Schoket B, Stromberg U, Vermeulen R, Wild C, Porta M, Vineis P; STROBE Statement. STrengthening the Reporting of OBservational studies in Epidemiology--Molecular Epidemiology (STROBE-ME): an extension of the STROBE Statement. PLoS Med. 2011 Oct;8(10):e1001117. doi: 10.1371/journal.pmed.1001117. Epub 2011 Oct 25.

  PMID: 22039356 BACKGROUND

• Pedersen CB. The Danish Civil Registration System. Scand J Public Health. 2011 Jul;39(7 Suppl):22-5. doi: 10.1177/1403494810387965.

  PMID: 21775345 BACKGROUND

• Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205-13. doi: 10.1097/01.sla.0000133083.54934.ae.

  PMID: 15273542 BACKGROUND

• Sankar A, Johnson SR, Beattie WS, Tait G, Wijeysundera DN. Reliability of the American Society of Anesthesiologists physical status scale in clinical practice. Br J Anaesth. 2014 Sep;113(3):424-32. doi: 10.1093/bja/aeu100. Epub 2014 Apr 11.

  PMID: 24727705 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples were collected at the time of induction of anaesthesia. For AHA-patients a pre-operative optimisation protocol was introduced in the hospital throughout the data collection period, which stated that the patient was optimized with goal directed fluid therapy before induction of anaesthesia. The blood samples were usually taken from the arterial line used for invasive blood pressure monitoring but some were obtained from venous puncture with standard preoperative tests. The blood samples were collected in tubes with EDTA as anti-coagulant for plasma and in tubes with coagulation enhancer for serum. After centrifugation for 10 mins at room temperature the plasma and serum, respectively were transferred to freezing tubes for subsequent long-term storage at -80C.

MeSH Terms

Conditions

Inflammation

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Nicolai B Foss, DMSc

  Department of Anaesthesiology, Hvidovre University Hospital, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Medical Doctor

Study Record Dates

• First Submitted: June 11, 2018
• First Posted: July 11, 2018
• Study Start: June 1, 2013
• Primary Completion: May 1, 2022
• Study Completion: May 1, 2022
• Last Updated: August 5, 2022

Record last verified: 2022-08

Locations

DK (1)