Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT01473979 |
| Other study ID # |
SternumStudy-CHUV-CCV-1 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
July 11, 2011 |
| Last updated |
January 24, 2012 |
| Start date |
January 2012 |
| Est. completion date |
July 2014 |
Study information
| Verified date |
January 2012 |
| Source |
University of Lausanne Hospitals |
| Contact |
Denis Berdajs, MD |
| Phone |
21 314 2695 |
| Email |
denis.berdajs[@]chuv.ch |
| Is FDA regulated |
No |
| Health authority |
Switzerland: Ethikkommission |
| Study type |
Interventional
|
Clinical Trial Summary
Sternal osteomyelitis and poststernotomy mediastinitis is a severe and life-treating
complication after the cardiac surgery. The incidence of sternal osteomyelitis ranges from
1% to 3% with a high mortality rate from 19% to 29% .
The most devastating complication of the open sternum is the laceration of the right
ventricle which has a very high mortality. Additionally destabilizations of the thoracic
cage, prolonged immobilization, or substantial surgical trauma are further complications of
the conventional strategy (4). In addition, postoperative infections after sternotomy are
associated with prolonged hospital stay, increased healthcare costs and impaired quality of
patient life, representing an economic and social burden. The emergence of increasing
antimicrobial resistant bacteria augments the importance of postsurgical infections since
the antimicrobial choices are becoming limited. Furthermore, the incidence of infection is
an indicator for the quality of patient care in the international benchmark studies.
Although several therapy strategies are nowadays present in clinical practice, there is a
lack of evidence based surgical consensus for treatment of this surgical complication. In
most case the poststernotomy mediastinitis is involving surgical revision with debridement,
open dressing and/or vacuum assisted therapy. After the granulation tissue on open chest
wound was achieved secondary closure and/or reconstruction with vascularized soft tissue
flaps such as omentum or pectoral muscle is performed.
It seems there is a need for more effective surgical treatment of poststernotomy wound
infections, which may address the prolonged hospitalization and reduce number of surgical
interventions and with this also perioperative morbidity. In light of this we propose a
randomized study comparing new delay primary closure of the sternum to the secondary vacuum
assisted closure.
Description:
1. Background
1.1. Problem of surgical site infection after sternotomy Sternal osteomyelitis and
poststernotomy mediastinitis is a severe and life-treating complication after the
cardiac surgery. The incidence of sternal osteomyelitis ranges from 1% to 3% (1, 2)
with a high mortality rate from 19% to 29% (1, 3).
The most devastating complication of the open sternum is the laceration of the right
ventricle which has a very high mortality. Additionally destabilizations of the
thoracic cage, prolonged immobilization, or substantial surgical trauma are further
complications of the conventional strategy (4). In addition, postoperative infections
after sternotomy are associated with prolonged hospital stay, increased healthcare
costs and impaired quality of patient life, representing an economic and social burden.
The emergence of increasing antimicrobial resistant bacteria augments the importance of
postsurgical infections since the antimicrobial choices are becoming limited.
Furthermore, the incidence of infection is an indicator for the quality of patient care
in the international benchmark studies.
Although several therapy strategies are nowadays there is a lack of evidence based
surgical consensus for treatment of this surgical complication. In most case the
poststernotomy mediastinitis is involving surgical revision with debridement, open
dressing, vacuum assisted therapy or closed irrigation. After the granulation tissue on
open chest wound was achieved secondary closure and/or reconstruction with vascularized
soft tissue flaps such as omentum or pectoral muscle is performed. Both open therapy
and the flap implantations may be used as a single-line therapy or as a combination of
procedures.
1.2. Etiology of poststernotomy infections Many mechanisms have been proposed to
explain the development of sternal wound infection. These theories include inadequate
sternal fixation leading to instability and dehiscence of the overlying skin incision
and inadequate surgical drainage. Further theories suggest a localized ischemic
osteomyelitis. This theory suggests that sternal wires become loose, leading to sternal
instability, which ultimately leads to skin dehiscence and osteomyelitic infection. The
most commonly cultured organism is Staphylococcus Aureus.
Several retrospective and prospective studies have identified factors relating to
increasing risk of sternal dehiscence. Patient risk factors include obesity, diabetes
mellitus, chronic obstructive lung disease (COPD), chronic cough from tobacco abuse,
steroid therapy, hypertension, immunosuppression, and advanced age. Operative risk
factors include single or bilateral internal mammary artery (IMA) harvesting
(significantly decreases blood supply to ipsilateral hemithorax), prolonged operation,
excessive hemorrhage, reoperation, break in sterile technique, and the use of an
intra-aortic balloon pump.
2. Objectives
2.1. Study hypothesis The optimal treatment of sternum osteomyelitis has not yet been
defined. The aim of this randomized study is to compare the treatment outcome of the delayed
primary closure with short-term VAC-therapy (48-72 h) with the late secondary closure with
long-term VAC therapy (>14 days).
We hypothesize that the delayed primary closure will have a better outcome than late
secondary closure regarding parameters:
- Cure rate (>80% versus <60%)
- Length of hospitalization (≤6 weeks versus >6 weeks)
- Number of surgical interventions (≤4 versus >5)
- In-hospital mortality (5 versus 15%) This combined surgical and active approach has an
economic advantage compared to the conventional therapy.
2.2. Aims Primary
1. To compare the treatment outcome (hospital stay, morbidity, mortality and surgical
stress load) of the delayed primary closure approach with the late secondary closure
Secondary
2. To evaluate side effects of both treatment approaches, and treatment expenses.
3. Study population
3.1. Ethical aspects The permission from the local Ethical Committee will be obtained
before beginning the study. This study will be also registered with
www.ClinicalTrials.gov. Patients will be enrolled before randomization 1:1 into each
study arm; in each group we will randomly include 40 patients. The randomization is not
blind and will be performed by one of the principal investigators. In absence of the
principal investigators this may be performed by co-investigators. Surgical procedures
in both arms should be standardized. In this way is essential that all the
interventions will be performed by main investigator and the co-investigator.
Arm A) In this group the patients will be treated with the standard surgical treatment.
In details the procedure is described under 4.4.
Arm B) I s the group the patients are treated according to the new concept of the
delayed primary sternal closure. The procedure id described under 4.5.
4. Procedures and methods 4.1. Definition of the sternal infection Median sternotomy wound
complications vary from sterile wound dehiscence to suppurative mediastinitis. Sternal
bone infection, mediastinitis, wound complication, and wound infection have been used
synonymously to denote deep sternal wound infection. For the sake of consistency in
comparing data from various reports, definitions of sternal wound complications are as
follows (8,9,10).
Ad 1) Mediastinal dehiscence: median sternotomy wound breakdown in the absence of clinical
or microbiologic evidence of infection.
Ad 2) Mediastinal wound infection: clinical or microbiologic evidence of infected presternal
tissue and sternal osteomyelitis, with or without mediastinal sepsis and with or without
unstable sternum. Subtypes include:
A) superficial wound infection: wound infection confined to the subcutaneous tissue B) deep
wound infection (mediastinitis): wound infection associated with sternal osteomyelitis with
or without infected retrosternal space. Deep sternal wound infections, or mediastinitis, is
classified into four subtypes based on the time of first presentation, the presence or
absence of risk factors, and whether previous attempts at treating the condition have failed
(Table 1).
Sternal wound infection will be considered:
The definition of mediastinitis has been established by the Center for Disease Control and
Prevention in the USA (11). According to these guidelines, diagnosis of mediastinitis
requires at least one of the following:
Ad 1) an organism isolated from culture of mediastinal tissue or fluid; Ad 2) evidence of
mediastinitis seen during operation; Ad 3) one of the following conditions: chest pain,
sternal instability, or fever (>38 8C), in combination with either purulent discharge from
the mediastinum or an organism isolated from blood culture or culture of mediastinal
drainage.
4.2. Outline of the surgical procedures Patients with suspected sternal osteomyelitis will
be hospitalized and the following diagnostic procedures will be performed: laboratory blood
tests (leukocytes, CRP, creatinin, AST, ALT, CK), computed tomography (CT) of the sternum,
wound swab.
After the diagnosis is secured the patients will receive an information consent form of the
study. Subsequently they will be randomly included in one of the surgical arms.
4.3. Current treatment strategy of poststernotomy infections During the past years,
vacuum-assisted closure (VAC) wound therapy has emerged as a treatment for open septic
wounds. It is a non-invasive system that helps promote wound healing by delivering negative
pressure the application of this subatmospheric form of treatment has, several advantageous
as compared to the conventional treatment. VAC therapy allows open drainage that
continuously absorbs exudate with simultaneous stabilization of the chest and isolation of
the wound. This therapy induces the building of the granulation tissue which in majority is
a result of the reduced oedema and increased blood flow in the adjacent tissue. Furthermore,
VAC therapy approximates the wound edges and provides a mass filling effect with a low
degree of surgical trauma, without establishing a new wound (e.g., abdominal wound in
omental flaps) (5,6). In the recent literature the mean hospitalization of the patients
being treated with the VAC therapy was 25 ± 20 days with overall mortality of 15%.
4.4. Arm A) Secondary closure with the vacuum-assisted system (VAC) Nowadays after the
diagnosis of the poststernotomy wound infection is established the clinical procedure is
obtained as follows: firstly the empiric antibiotic therapy with vancomycin is induced. The
lab samples including bacteriology test are obtained. The initial surgical revision is done
within 24 hours. Intraoperatively from the surgical field again tissue samples are sent for
bacteriology investigation to determine the antibiotic pattern resistance. All sternal wires
are removed. Surgical debridement is made until occurrence of tissue bleeding. Careful and
extensive cleaning of the wound is performed using saline solution at 37°C degrees Celsius
and the solution of 50% betadine and saline solution (1:1 Betadine:H20). Finally VAC sponge
is implanted with negative suction pressure of 75 mmHg. Postoperatively chest X-ray is
obtained, in the first 24 hours the lab samples with CRP and whit blood cell count is
performed. The first revision with second look and debridement is usually made in 48 hours.
Subsequently in the following days the wound is stepwise revised during VAC changes (every
48/72 hours) a sharp spoon and necrotic bone is removed when necessary, but extensive
sternectomy is avoided. At each revision tissue samples are obtained for microbiological
investigations.
According to the patients general situation they are extubated immediately after VAC therapy
initiation and are staying on the intensive care unit for about 24 hours. The patients are
obtained 5 to 7 times to the surgical procedures in time intervals of 48/72 hours.
Subsequently when the last three bacteriology samples are negative a delayed primary closure
by usage of Kryptonite biocompatible adhesive glue (Doctors Research Group Inc, Southbury,
CT)- if needed for sternal stabilization- or rectus abdominal muscle flap may be done. As
far the antibiogram is known, the specific antibiotic therapy is induced.
4.5. Arm B) Surgical procedure by delayed primary closure As compared to the previous
therapy modalities mentioned under 2.2 and 1.3 the new method has an advantage of the
surgical wound healing by delayed primary intention.
In the first step, after the diagnosis of the infection was done, and the empiric antibiotic
therapy is induced with vancomycin in the first surgical intervention the sternal wires will
be removed, the mediastinum is explored and extensive surgical debridement is performed
until occurrence of tissue bleeding. Careful and extensive cleaning of the wound was
performed using saline solution at 37°C degrees Celsius and the solution of 50% betadine and
saline solution (1:1 Betadine:H20), at least 3 samples (tissue biopsies) are taken for
microbiology. The patients will receive treatment delivered through the VAC system in the
first 48 hours following the first surgical intervention. Subsequently the wound is closed.
We begin with dissection and elevation of the pectoralis major muscle and corresponding
subcutaneous flap through diathermy. Dissection is performed from the median line along the
costal grid, up to two thirds of the anterior chest wall, preserving the humeral insertion,
thoracoacromial vascular bundle and pectoralis minor muscle. Note at this area are very
important vascular connections areas between the internal thoracic artery, acromial artery
and the lateral thoracic artery which should be preserved. At inferior plane, the pectoralis
major muscle will be raised - including the anterior rectus fascia - and down up to the
xiphoid process. The upper segment of the anterior rectum will be raised with the pectoralis
major muscle. The intercostal perforating arterial branches will be preserved also. A
silicon drain tube is placed in the retrosternal space if this is possible. In patients with
fracture or asymmetry of the sternum incision, osteosynthesis is performed using the
"Robiscek" technique. Then two suction drains were placed below the muscular plane upon the
costal grid for drainage of the large area of detachment of the musculoaponeurotic layer The
suture of the pectoral fascia should be tension free, continuous suture with resorbable
material (Vicryl 3-0). The subcutaneous tissue is closed over the drainage, with separate
subcutaneous suture. The skin is closed with non-resorbable suture analog to the "Allgöver"
suture. These sutures are removed between the 12 and 14 postoperative days.
Thus the results of the bacteriology are known in most cases after the first 48 hours the
specific antibiotic therapy, according to the results of the bacteriology results may be
introduced.
4.6 General considerations
Contraindication for closure of the chest:
Wounds with active purulence require extensive debridement prior to flap coverage and/or
rigid fixation. Additional contraindications for sternal reconstruction are found in
patients who are unstable for surgery, including those with poor pulmonary function, poor
cardiac reserve, or terminal illness. Hemodynamic stability is required for surgical
intervention in patients with sternal dehiscence.
4.7. Early perioperative management in the 48 hours
Transfer to the ICU:
After each definitive sternal closure the patients will be transferred to the ICU for the
hemodynamical observation in the first 24 hours. Beside the followings are considered as
indications to transfer on ICU.:
Preoperative sepsis, intraoperative hemodynamical instability or/and need for
catecholamines, intraoperative need for massive transfusion, rupture of the ventricular
cavities (left or right), need for emergency cardiopulmonary bypass.
Transfer to the intermediate car Hemodynamical and pulmonary stable patients will be
extubated in the operating room, and will be transferred to the intermediate care unit of
the department of cardiovascular surgery.
General considerations Independently in both investigation groups Arm A) and Arm B)
postoperatively X-ray of the thorax will be obtained after the transfer. In the first 24
hours, the lab samples will be obtained (CRP, anticoagulation, white blood cell cont,
hemoglobin, hematocrit, ASAT, ALAT, yGT, Creatinine, Urea, and anticoagulation tests PTT,
TP). Respiratory physiotherapy will be obtained 24 hours after the surgical revision.
Open chest patients should not be mobilized out of the bed, however the chest elevation and
mobilization of 45 to 90° is aloud.
After definitive closure of the chest the patient may be fully mobilized after the first 48
hours, or after the transfer to the ward.
