Preoperative High-dose Dexamethasone and Emergency Laparotomy

Sepsis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04791566
• Other study ID #: H-20038432
• Status: Completed
• Phase: Phase 4
• Start date: March 1, 2021
• Est. completion date: December 9, 2022

Study information

• Verified date: December 2022
• Source: Copenhagen University Hospital, Hvidovre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: December 9, 2022
• Est. primary completion date: October 9, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 -

Related Conditions & MeSH terms

• Emergencies
• Inflammatory Response
• Intestinal Obstruction
• Intestinal Obstruction and Ileus
• Pathophysiology
• Perforated Viscus
• Sepsis

Intervention

Drug:
• Dexamethasone 1 mg/kg
Dexamethasone 1 mg/kg administered as a single preoperative i.v. infusion over 10-15 min prior to general anaesthesia
• Physiologic saline
100 mL Physiologic saline administered as a single preoperative i.v., infusion over 10-15 min prior to general anaesthesia

Locations

Country	Name	City	State
Denmark	Mirjana Cihoric	Hvidovre

Sponsors (1)

Lead Sponsor	Collaborator
Mirjana Cihoric

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	changes in postoperative inflammatory responses (IL-6, TNF alfa)		Preoperatively, 6 hours postoperatively, as well as postoperative day 1,3 and 5
Other	Change in plasma Syndecain-1sE-Selectin (CD62E)		Preoperatively, 6 hours postoperatively, as well as postoperative day 1,3 and 5
Other	Change in plasma soluble thrombomodulin (sTM)(CD141)		Preoperatively, 6 hours postoperatively, as well as postoperative day 1,3 and 5
Other	Change in plasma sE-Selectin (CD62E)		Preoperatively, 6 hours postoperatively, as well as postoperative day 1,3 and 5
Other	Change in vascular endothelial growth factor (VEGF)	0 to 1 point: Not high risk; 2 to 3 points: High risk	Preoperatively, 6 hours postoperatively, as well as postoperative day 1,3 and 5
Other	quick Sequential Organ Failure Assessment score, qSOFA		Assessed once preoperatively and 4 times daily during the first 5 postoperative days
Other	Preload dependency via stroke volume(SV) guided resuscitation		Preoperatively, 6 hours postoperatively, as well as postoperative day 1,3 and 5
Other	Fluid distribution, full body water via bioelectrical impedance vector analysis		Preoperatively, 6 hours postoperatively, as well as postoperative day 1,3 and 5
Other	Peak flow measurements		Once a day on postoperative day 1,3 and 5
Other	Postoperative need for antiemetic and analgesic beyond standard course		Once a day during the the first 5 postoperative days
Other	Mobilization, The Cumulated Ambulation Score (CAS)	The CAS describes the patient's independence with regard to three activities (getting in and out of bed, sit-to-stand-to-sit from a chair, and walking). Each activity is assessed on a three-point ordinal scale from 0-2 (0 = Not able to, despite human assistance and verbal cueing, 1 = Able to, with human assistance and/or verbal cueing from one or more persons, 2 = Able to safely, without human assistance or verbal cueing, use of a walking aid allowed) resulting in a total daily CAS score ranging from zero to six	Once a day on postoperative day 1,3 and 5
Other	Postoperative delirium via Confusion Assessment method scale	1.a: Acute onset; 1b: Fluctuating course, 2: inattention 3: disorganized thinking 4: altered level of conciosness At least one criterion must be met for a positive result	Once a day during the the first 5 postoperative days
Other	Postoperative resting pain measured according to Numeric Rating Scale (NRS)	0-10 where 0 is no pain and 10 is the worst pain imaginable	6 hours after surgery as well as once a day one postoperative day 1,3 and 5
Other	Postoperative pain during mobilization, measured according to Numeric Rating Scale (NRS)	0-10 where 0 is no pain and 10 is the worst pain imaginable	6 hours after surgery as well as once one postoperative day 1,3 and 5
Other	30-day postoperative mortality		30 days
Other	90-day postoperative mortality		90 days
Other	30-day postoperative complications		30 days
Other	Length of ICU stay		30 days
Other	Overall hospital stay		30 days
Other	Plasma NO-bioavailability (L-arginine, asymmetric dimethylarginine)		preoperatively, 6 hours after surgery as well as once one postoperative day 1,3 and 5
Primary	plasma C-reactive protein		24* hours (*+/- 6 hours) after surgery.
Secondary	changes in plasma C-reactive protein		Preoperatively, 6 hours postoperatively, as well as postoperative day 3 and 5