Clinical trial NCT04791566: Preoperative High-dose Dexamethasone and Emergency Laparotomy
Official title: The Effects of Preoperative High-dose Dexamethasone on Inflammatory Response and Recovery After Emergency Laparotomy, a Randomized, Double-blind, Placebo-controlled Clinical Trial - AHA STEROID TRIAL
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Intestinal Obstruction and Ileus
Perforated Viscus
Sepsis
Pathophysiology
Inflammatory Response
Lead sponsor: Copenhagen University Hospital, Hvidovre
Sponsor class: OTHER
First posted: 2021-03-10
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this trial is to evaluate the effect of high-dose glucocorticoid on inflammatory response and recovery after emergency laparotomy in participants with intestinal obstruction and perforated viscus.

Primary outcome is the reduction of C-reactive protein on postoperative day 1. Secondary outcomes are organ specific complications in the post anaesthesia phase, endothel and inflammatory markers, fluid status, preload dependency, pain, lung function, nausea and mobilization during the first 5 days after surgery, .

The investigators hypothesize, that a preoperative single high dose of glucocorticoid reduces systemic inflammatory response after emergency laparotomy.

Detailed description: Surgical trauma and accompanying inflammation results in increased capillary permeability leading to tissue edema. Since the vascular endothelium contributes to homeostasis, endothelial damage may increase the risk of cardiovascular and hemodynamic complications.

Pre-operative high-dose glucocorticoids provide reduction in the inflammatory response after surgery, effective pain relief in several major surgical procedures, as well as reducing fatigue, impairing endothelial dysfunction, potentially amend fluid extravasation, edema and dyscoagulation and vasodilation.

However, glucocorticoids have not been assessed in patients with peritonitis or intestinal obstruction, specifically, the impact on pain, fluid dynamics, respiratory as well as endothelial function and mobilization in both obstruction and perforation.

In this study, patients will be randomized to either high dose dexamethason (1 mg /kg) or placebo (0,9% NaCl), administered as a single dose preoperatively. The investigatoris hypothesize that a preoperative single high dose of glucocorticoid reduces systemic inflammatory response after emergency laparotomy.

Eligibility criteria: Inclusion Criteria:

1. Adults (18 years or over) undergoing emergency laparotomy (laparotomy or laparoscopy) for following abdominal pathology:

   1. Primary perforated viscus (perforated ulcer, small intestine or colon)
   2. Primary intestinal obstruction ( small intestine or colon)
2. Provided verbal and written informed consent
3. Must speak and understand the Danish language

Exclusion Criteria:

1. Appendectomies, cholecystectomies, negative diagnostic laparoscopies/laparotomies, herniotomies without bowel resections, sub-acute internal hernias after gastric bypass surgery, sub-acute surgery for inflammatory bowel diseases.
2. Emergency re-operations after elective surgery owing to paralytic/obstructive ileus, perforated viscus, anastomotic leakage
3. Reoperation owing to fascial separation with no other abdominal pathology identified and sub-acute colorectal cancer-surgery will be excluded from the cohort. Sub-acute surgery is defined as surgery planned within 48 hours.
4. Intestinal Ischemia
5. intraabdominal bleeding
6. Traumas, gynecological, urogenital and other vascular pathology, pregnant participants.
7. Dementia and/or cognitive dysfunction (diagnosed).
8. Participants not oriented in time, place and person
9. Insuline treatment for diabetes mellitus type I and II
10. Current treatment with systemic glucocorticoids or immune suppressive treatment ( apart from inhalation steroids)
11. Allergies to trial medicine

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Primary outcomes:
measure: plasma C-reactive protein
timeFrame: 24* hours (*+/- 6 hours) after surgery.
Secondary outcomes:
measure: changes in plasma C-reactive protein
timeFrame: Preoperatively, 6 hours postoperatively, as well as postoperative day 3 and 5
Other outcomes:
measure: changes in postoperative inflammatory responses (IL-6, TNF alfa)
timeFrame: Preoperatively, 6 hours postoperatively, as well as postoperative day 1,3 and 5
measure: Change in plasma Syndecain-1sE-Selectin (CD62E)
timeFrame: Preoperatively, 6 hours postoperatively, as well as postoperative day 1,3 and 5
measure: Change in plasma soluble thrombomodulin (sTM)(CD141)
timeFrame: Preoperatively, 6 hours postoperatively, as well as postoperative day 1,3 and 5
measure: Change in plasma sE-Selectin (CD62E)
timeFrame: Preoperatively, 6 hours postoperatively, as well as postoperative day 1,3 and 5
measure: Change in vascular endothelial growth factor (VEGF)
timeFrame: Preoperatively, 6 hours postoperatively, as well as postoperative day 1,3 and 5
measure: quick Sequential Organ Failure Assessment score, qSOFA
timeFrame: Assessed once preoperatively and 4 times daily during the first 5 postoperative days
measure: Preload dependency via stroke volume(SV) guided resuscitation
timeFrame: Preoperatively, 6 hours postoperatively, as well as postoperative day 1,3 and 5
measure: Fluid distribution, full body water via bioelectrical impedance vector analysis
timeFrame: Preoperatively, 6 hours postoperatively, as well as postoperative day 1,3 and 5
measure: Peak flow measurements
timeFrame: Once a day on postoperative day 1,3 and 5
measure: Postoperative need for antiemetic and analgesic beyond standard course
timeFrame: Once a day during the the first 5 postoperative days
measure: Mobilization, The Cumulated Ambulation Score (CAS)
timeFrame: Once a day on postoperative day 1,3 and 5
measure: Postoperative delirium via Confusion Assessment method scale
timeFrame: Once a day during the the first 5 postoperative days
measure: Postoperative resting pain measured according to Numeric Rating Scale (NRS)
timeFrame: 6 hours after surgery as well as once a day one postoperative day 1,3 and 5
measure: Postoperative pain during mobilization, measured according to Numeric Rating Scale (NRS)
timeFrame: 6 hours after surgery as well as once one postoperative day 1,3 and 5
measure: 30-day postoperative mortality
timeFrame: 30 days
measure: 90-day postoperative mortality
timeFrame: 90 days
measure: 30-day postoperative complications
timeFrame: 30 days
measure: Length of ICU stay
timeFrame: 30 days
measure: Overall hospital stay
timeFrame: 30 days
measure: Plasma NO-bioavailability (L-arginine, asymmetric dimethylarginine)
timeFrame: preoperatively, 6 hours after surgery as well as once one postoperative day 1,3 and 5
Locations:
city: Hvidovre
country: Denmark
facility: Mirjana Cihoric
Study officials:
affiliation: Dept. of Anaesthesiology and Intensive Care
name: Nicolai Bang Foss, Professor
role: STUDY_DIRECTOR
References: