Preoperative High-dose Dexamethasone and Emergency Laparotomy

Phase 4

Completed

• Conditions: Sepsis; Pathophysiology; Inflammatory Response; Intestinal Obstruction and Ileus; Perforated Viscus
• Interventions: Drug: Dexamethasone 1 mg/kg; Drug: Physiologic saline

• Registration Number: NCT04791566
• Lead Sponsor: Mirjana Cihoric

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.

Study Timeline

• Study Start: 2021-03-01
• Study First Submitted: 2021-03-03
• Study First Submitted QC: 2021-03-08
• Study First Posted: 2021-03-10
• Primary Completion: 2022-10-09
• Status Verified: 2022-12
• Study Completion: 2022-12-09
• Last Update Submitted: 2022-12-13
• Last Update Posted: 2022-12-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 120

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intestinal obstruction, Dexamethasone 1 mg/kg	Dexamethasone 1 mg/kg	Dexamethasone 1 mg/kg administered preoperatively as an i.v. infusion over 10-15 minutes
Intestinal obstruction, PLACEBO	Physiologic saline	Physiologic saline, administered preoperatively as an i.v. infusion over 10-15 minutes
Perforated viscus, Dexamethasone 1 mg/kg	Dexamethasone 1 mg/kg	Dexamethasone 1 mg/kg administered preoperatively as an i.v. infusion over 10-15 minutes
Perforated viscus, PLACEBO	Physiologic saline	Physiologic saline, administered preoperatively as an i.v. infusion over 10-15 minutes

Primary Outcome Measures

Name	Time	Method
plasma C-reactive protein	24* hours (*+/- 6 hours) after surgery.

Secondary Outcome Measures

Name	Time	Method
changes in plasma C-reactive protein	Preoperatively, 6 hours postoperatively, as well as postoperative day 3 and 5

Trial Locations

Locations (1)

Mirjana Cihoric; 🇩🇰 Hvidovre, Denmark