| Objective: |
Primary endpoint
• Comparing peritonitis related complications and Comprehensive Complication Index between Vacuum-assisted closure (VAC) and relaparotomy “on-demand” (ROD) after 30, 90 days and 1 year
Secondary endpoints
• Mortality and peritonitis related complications
• Quality of life after 3 and 12 months assessed by the SF-36 questionnaire
• Ventral hernia rate after 3 and 12 months assessed via clinical examination and computed tomography scan of the abdomen
• Cost-effective analysis
Definition of diffuse fecal peritonitis
Diffuse fecal peritonitis is defined as contamination of 2 out of the 4 abdominal quadrants with fecal contamination starting from the small intestine, colon or rectum.
Peritonitis related complications:
Incisional hernia + obstruction
Incisional hernia - obstruction
Postoperative ileus due to intra-abdominal adherences or abscess
Fascial dehiscence
Failure of closuring the patient's own fascia
Abdominal compartment syndrome
Intraabdominal bleeding or hematoma
Perforation of intra-abdominal organ confirmed by surgery
Anastomotic leakage (confirmed by CT and relaparotomy)
Ischemia or necrosis of intra-abdominal organ
Enterostomy dysfunction due to prolapse, stenosis or failure
VAC treatment longer than 8 days
VAC change sooner than scheduled at 48-hour intervals
On-demand relaparotomy
Intraperitoneal abscess
Entero-atmospheric fistula
Entero-enteric fistula
Fistula between hollow organ and other and other
Fistula between hollow organs and cutis or between two hollow organs
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| Aim: |
With this research project, we want to compare the two current treatments for peritonitis caused by intestinal perforation. VAC has been gained increased clinical practice the last three decades, concurrently the technique of the equipment has developed. In spite of this there has never been made a randomized controlled trial examining potential benefits and risks with the second most commonly used treatment regimen, primary closure with ROD. The study will help us answer many important questions will potentially be of great benefit for our patients world-wide. |
| Methods: |
A multicenter non-blinded randomized controlled trial on Vacuum assisted closure versus on-demand relaparotomy in patients with diffuse feculent peritonitis. A total of 340 patients must be included in order to obtain sufficient evidence of which method is best. Several hospitals in Denmark and other Nordic countries are participating in the study.
Inclusion criteria
Patients eligible for enrolment are 18+ years of age, who are scheduled for acute laparotomy and with a suspected diffuse peritonitis from intestinal perforation originating from the small bowel, colon or rectum, with purulent or faecal contamination in minimum 2 out of 4 quadrants.
Exclusion criteria
• Diffuse peritonitis originating from a focus other than the small intestine, colon or rectum, such as: Perforated ventricle and duodenal ulcer, perforated gallbladder, necrotizing pancreatitis, salpingitis, peritoneal dialysis
• Primary peritonitis; Immunocompromised patients, chronic parenchymal liver disease, patients on hemodialysis
• Pregnancy
• The patient who is expected to die shortly after surgery due to their condition in the operating room, and there is no intention to continue with life-prolonging treatment where the only appropriate treatment for the patient is “good and loving care”; (an example of where this may occur would be complete transmural small bowel ischemia /necrosis)
• Planned Laparoscopic surgery (not laparotomy)
• Acute occlusion of superior mesenteric artery as primary pathology
• Peritoneal carcinomatosis
• Uncontrollable bleeding
• Abdominal trauma
• Lack of consent
• Perioperatively not detecting diffuse / fecal peritonitis or contamination in 1 quadrant
Randomisation
The study has been approved by the Danish Medical Ethics committee with the permission to include patients by a surgical equipoise, followed by informed consent after recovery. The permission to include patients in the following manner was chosen due to; Subjects requiring immediate surgical intervention, partial or complete incapacitation due to the condition, mortality increasing by each hour, third-party authorization cannot be secured in time, the treatment regimens are accepted, safe and widely used for this patient group and have similar known risks, hence why it would be reasonable to randomly allocated patients to either.
The project manager will be contacted by phone and randomize the patients web-based via RedCap/OPEN in blocks of 2, 4 and 6 for primary closure with ROD or application of VAC. Stratification will be carried out for each centre and age above or below 65 years. Patients who cannot be treated according to randomization will be analysed according to intention-to-treat and per protocol principles in the arm they are randomized to.
Surgical technique
(VAC) with the narrowing technique
the VAC® Abdominal Dressing System (KCI Vacuum Assisted Closure, San Antonio, TX, USA) will be used. Intestines, including lateral aspects, is covered by the visceral protective layer. The first layer of foam is placed flat in the wound immediately below the fascia at a distance of 5 cm around the wound edge. A minimum of one piece of foam is folded and placed in the laparostoma above the first layer of foam. Thereafter there will be applied an occlusive drape loosely in 10–15 cm wide strips. An opening of approximately 5 cm is cut out in the drape for the connection to the negative pressure pump. Simultaneously as the negative pressure is applied; the facial edges are approximated manually towards the midline. This is done to make the laparostoma as narrow as possible, with the intention to prevent lateralisation of the fascia. A standard negative pressure of −125 mmHg will be applied. The dressing is changed with an interval of 48 hours depending on the clinical condition, with earlier changes as an option. Each dressing change is performed at the operation theatre, while the patient is under general anesthesia at maximum relaxation. When the patient’s general condition is improving judged by gastrointestinal, renal function and a decline in inflammatory parameters, the fascia was either completely or gradually closed.
How to do primary closure
The abdominal wall is closed according to the Isreaelsson principle where it is sewn continuously in the fascia at a distance between the sutures of 5 mm and the distance to the facade edge of 5-10 mm. Monofilament PDS 0-0 (Ethicon) (or equivalent) is used. The suturing is started cranially and caudally, and the sutures are tied at the end of the continuous thread with self-locking knots. 4 times as much suture material as the length of the wound must be consumed.
How the fascia is closed after VAC treatment
The fascia can be closed according to the Israelssons principle as described above. However, the method of closure is decided by the surgeon. If the laparastoma cannot be completely closed, we recommend closing the fascia cranially and distally as much as possible successively and placing a new VAC-system until the laparastoma is fully closed, if possible.
When to make relaparotomy-on demand
Relaparotomy should be performed in patients with clinical deterioration or lack of clinical improvement with a probable intra-abdominal cause and/or after exclusion of other infectious foci (e.g., pneumonia) in blood tests and relevant imaging or in surgical emergencies.
• Clinical deterioration is defined as:
o Increase of SOFA score ≥2 after last operative intervention
• Lack of clinical improvement is defined as the following:
o Signs of persistent sepsis
o SOFA score unchanged for at least 48 hours after the index laparotomy or previous relaparotomy or VAC shift
• Surgical emergencies are defined as:
o Abdominal compartment syndrome
o Intra-abdominal bleeding with sustained decrease in hemoglobin despite replacement or hemodynamic instability
o Peritoneal reaction
o Perforation of a hollow organ in the abdomen
o Anastomotic leakage
o Intra-abdominal abscess that cannot drain percutaneously
o Ischemia or necrosis of a visceral organ.
The clinician should only be guided by the scoring systems. The final decision lies with the attending clinicians.
Immediately after the operation the surgeon completes Baseline, Postoperative record and Björck's classification. All patients should be transferred post-operatively to the intensive care unit. Upon arrival to the intensive care unit (ICU) patients will be APACHE II and SOFA scored by the anesthesiologist on call. Routine blood sampling and SOFA scoring in the ICU is registered the first 7 days after index operation. When an intensive care doctor assesses that there no need for further intensive care, the patient is transferred to the ward.
As soon as the patient is transferred to the ward, blood tests should be ordered daily (CRP, creatinine, bilirubin, platelets). At daily rounds the patients must be GCS scored. The nurses will register oxygen saturation and amount of oxygen given via the nose or mask, if given and MAP. All the above mentioned paraclinical parameters should be recorded in the patient’s electronical journal. Patients will be SOFA scored daily for the first 7 days after the index operation. This should be done by the responsible physician and filled out in the SOFA score sheet, which can be found in the patient’s project folder (applies to both the intensive care unit and the surgical ward).
Patients randomized to VAC treatment are booked for VAC change after 48 hours by a specialist, where the following events can happen:
o VAC is changed
o VAC is changed and closure is started
o The abdomen is closed
o The peritoneal fluid should be cultured at index operation and at closure
Patients randomized to primary closure with the ROD of the abdomen will be assessed at the department / intensive care unit of the project manager and a specialist in surgery before the 48-hour surgery, where the following events can happen
o No operation
o Re-operation with closure of the abdomen
o Re-operation with establishment of VAC treatment
o The peritoneal fluid should be cultured upon closure
Follow up
All patients are booked for follow-up after 12 months in the outpatient clinic. The abdomen is examined clinically with palpation in upright and supine position. Prior to the outpatient follow-up, CT will be performed with intravenous contrast with and without Valsalva manoeuvre. Above mentioned procedures are made in order to detect incisional hernias. The SF-36 questionnaire will be sent out to the patient’s electronic mailbox or via standard post after 3 and 12 months.
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| Reason for International Trial: |
• The numbers of patients matching the inclusion criteria are few in Denmark, although many centres are participating, many more are needed in order to include 340 patients
• The more centres that are participating helps us getting a greater understanding of the actual outcome on a widespread scale
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