Prospective Comparison of Primary Abdominal Closure and Vacuum Assisted Laparostomy in Treatment of Severe Peritonitis
Condition: Peritonitis
MeSH terms: Peritonitis
Study type: Interventional
Phase: Phase 4

Summary: 
      The aim of the project was to optimalize the process in severe peritonitis which is generally
      inflicted with high mortality and morbidity with long term costly therapy. Therapy of severe
      intraabdominal infection consist of treatment of the infection site and following closure of
      the abdominal cavity with possibility of re-laparotomy and in treatment of complications when
      needed; or closure introduction of laparostomy with intention to control complications
      prevention however with risk of tertiary peritonitis. Modern process is laparostomy with
      active suction (VAC) method which reduces the risk of tertiary peritonitis. It efficacy is
      however approved especially in therapy of complications. Based on the investigators
      experiences the investigators use this method even in case of primary treatment of severe
      peritonitis which led to protocol processing (VAC in case of primary closure of the abdominal
      cavity; VAC exchange according to scoring system; secondary closure of the abdominal cavity
      or early coverage with collagen mesh). The aim of this project is to prove reduced mortality,
      morbidity and hospitalization length (cost reduction) in prospective randomized study in
      patients treated due to severe peritonitis using VAC method in comparison to classical
      approach (primary closure of the abdominal cavity; secondary solution of complications).
    

Detailed description: 
      Introduction Severe peritonitis belongs among severe diseases with mortality 20-60%. Causes
      are number of primary surgical diseases (inflammatory acute abdomen syndromes - perforated
      diverticulitis, perforated tumor, colon ischemia and other) or complications after abdominal
      surgeries in frequency 12-16%.

      Secondary and tertiary peritonitis can be in insult causing system inflammatory response
      (SIRS) with subsequent sepsis and multi-organ failure; it is serious state of patient who
      requires long term and costly intensive care and despite of that it often ends with permanent
      disability. Basic therapy of severe peritonitis is surgical treatment of origin of abdominal
      sepsis, contamination elimination and prevention of postoperative complications. The
      insufficient capability to manage postoperative complications (polymorbidity, diabetes,
      inveterate peritonitis, immunosuppressed patient) is often the cause of organ and mutli-organ
      failure. In case of primary closure of the abdominal cavity and after correct surgical
      treatment; solution is the early diagnosis of the complications and their urgent sanitation.
      Mostly from objective reasons there is delay in complication diagnosis and thus adequate
      treatment. Other negative consequence of primary closure of the abdominal cavity in case of
      development of intraabdominal complicated healing is the development of intraabaominal
      hypertension and even compartment syndrome with all negative influences to organ functions.
      Alternative is to introduce laparostomy which enables simple abdominal cavity control (second
      look method) using repeated interventions. Classical laparostomy is however continual
      continuation of the tertiary contamination. According to known literal sources there is no
      recommendation for means of abdominal cavity closure in the above given surgical disease
      which is therapeutically more efficient.

      One of the modern laparostomy methods is closure of the abdominal cavity using VAC. Method
      principle is the active suction which is continual and it drains effusion from the abdominal
      cavity and thus reduces intraabdominal bacterial contamination and also supports blood
      circulation and vitality of the wound edges. It is a method which fulfills advantages of
      laparotomy including expansion of the abdominal cavity, effusion drainage quality of which
      can be controlled; it is a closed system in which there is no risk of external contamination
      as in case of common laparostomy. Use of VAC method was verified in various wound types with
      copious secretion (sternotomy, diabetic foot or fascitis). Method of VAC laparostomy was
      described; however prospective and randomized use in peritonitis has not bee evaluated yet.

      Aim of the project: The aim of this project is to prove reduced mortality, morbidity and
      hospitalization length (cost reduction) in prospective randomized study in patients treated
      due to severe peritonitis using VAC method in comparison to classical approach (primary
      closure of the abdominal cavity; secondary solution of complications). Secondary aim is to
      validate scoring systems and early sepsis markers (cytokines) in algorithm of assessment of
      severance of severe peritonitis in our conditions and their inclusion in indication for
      surgical revision. Tertiary aim is to determine group of patient who would profit the most
      from the method.

      Further aim is to compare costs and socio-economic implications of both therapy options.

      Hypothesis: Primary introduction for surgical revision due to severe peritonitis reduces
      postoperative morbidity and mortality in comparison with primary closure of the abdominal
      cavity.

      Indications for repeated intervention improves combination of scoring systems and
      immunohistochemistry markers.

      Methodology

      1- assessment of preoperative stave of patient - APACHE II (Acute Physiology and Chronic
      Health Evaluation, ASA, BMI), severity of clinical and surgical finding.

      2 - Assessment of influence of selected method primary treatment of the abdominal cavity on
      the postoperative morbidity which is expressed by monitoring basic vital functions, SOFA
      (Sequential Organ Failure Assessment), intraabdominal pressure monitoring, serum level of
      cytokines monitoring, postoperative complications, surgical revision and length of
      hospitalization.

      3 - long term and socioeconomic consequence (30 days of follow up after discharge -
      questionnaire, assessment of life quality), cost analysis expended for hospitalization
      including medication, surgery as well as postoperative outpatient control visits.

      Patient with severe peritonitis will be enrolled in study according to Mannheim Peritonitis
      Index (MPI) - more than 20-25 according to sex; APACHE II more than 10. Expected sample size
      is total of 50 patients (25 treated using VAC method) versus 25 in control group). Screening
      will include all patients designer fulfilling SIRS criteria prior abdominal approach and/or
      displaying symptoms of peritonitis. If patient fulfills these criteria and agrees with
      inclusion in study, his/her ID is entered in the electronic database which generates
      inclusion in one out of two groups according randomization scheme - surgery termination using
      VAC method or primary suture. Excluded patients: young patients younger than 18 years; mental
      state of patients which does not enable proper information and signature of informed consent
      form (see bellow) with inclusion in study; further patients who cannot be assume to live
      longer than 48 hours after surgery (APACHE II, Karnofski, SOFA).

      Preoperative care and actual surgical procedure is not the direct subject of study and will
      be conducted according to so far known procedures. Surgeon will closed the abdominal cavity
      according randomization at the end of procedure and this fact is in no way affected by actual
      surgery procedure.

      Patient will be treated at the surgical ICU. First exchange of VAC dressing will be conducted
      after 24-48 hours and subsequently so called on demand (patient health state aggravation
      defined as score SOFA increase by 4 and more points; elevation of inflammatory markers and
      interleukins). After complete sanitation of the origin the investigators close the
      laparostomy (only serous exudate) If it is not technically possible to suture abdominal
      cavity according to layers, the investigators will close it using following alternatives:
      single skin cover, mesh plasty, covering with celless skin implant (permacol surgical
      implant) so the abdominal cavity was closed as soon as possible.

      Patient with primary closed abdominal cavity (control group) will be treated according to so
      far known procedure. In case of inflammation signs the investigators will search and treat
      this focus. Cytokine inflammatory markers will be also monitored and including finding. In
      case of surgical complication the investigators will proceed in standard manner (SSI). VAC
      method will not be used in cases of those patients.

      Hospitalization will be terminated after criteria compliance which are: oral intake higher
      than 2 liters tolerance; sufficient oral analgesics; patient does not display infection
      signs; agrees with hospitalization; surgical wound is treatable in outpatient clinic.

      Means of data collection

      Preoperative examination will monitor apart from basic data such as age, diagnosis,
      co-morbidity score ASA, BMI, level of inflammatory parameters (CRP, blood count, other
      biochemistry examination). Patient must fulfill criteria SIRS to be enrolled in the study and
      display signs of peritonitis. Precise indication to surgery will be recorded. After
      introduction of anesthesia the investigators will perform examination of arterial blood
      (ASTRUP) and will calculate APACHE

      Extent of inflammation (MPI) will be evaluated and source of infection (confirmation or
      exclusion of preoperative diagnosis). Performed surgical procedure will be described, the
      investigators will monitor duration of surgery; blood loss; monitoring whether sufficient
      control of primary source (insufficient treatment of source is sufficient exclusion
      criterion).

      Daily the investigators will monitor IL-1, 6, 8, 10 and TNF alpha while at ICU (during first
      5 days), SOFA score will be calculated and IAP will be measured. The investigators will
      further monitor frequency of VAC exchanges; number of administrated transfusions; duration of
      UPV; days without oral intake and without possibility of physiotherapy - walking (parameters
      of recovery. Conscious patients will be submitted form for assessment of life quality (SF-36)
      on the 7th postoperative day. The investigators will further monitor pain using VAS.

      Entry values are: hospitalization length, number of ICU days; mean of wound closure (primary
      suture, delayed suture after VAC; skin cover and other). Incidence and severity of SSI (I-III
      grade) and further nosocomial infection (health care - associated infection - HAI). Patient
      again completes from assessing life quality (SF-36) prior discharge. Active follow up will be
      in terms of study conducted via telephone every 30th day after discharge. Patient will
      subsequently complete mailed questionnaire with assessing life quality (SF-36). Outpatient
      controls will be necessary and repeated hospitalization in complicated patients. After
      completion of patient monitoring the analysis of cost for hospitalization including
      medication, surgery and postoperative outpatient control will be conducted using the hospital
      information system.

      Statistical processing

      Sample size is estimated based on expected percentage indicator according to Fleisse. Other
      sample size estimates were estimated using standard method. Each sample must contain 26 -47
      patients for mortality estimated between 30-40% and in case of statistically significant
      difference 20-30% when 5% level of significance and test power 70% in case of one sided test.
      Morbidity estimated to 60% and clinically significant difference 30-40% requires sample size
      of 19-32 subjects providing the same significance level and one sided test. Statistical
      evaluation of results will be included based on pair tests. Difference of individual
      variables between both groups will be evaluated using Student pair test or its non-parametric
      variant (Wilcoxon test). SOFA, APACHE II scores and life quality assessment results (SF-36)
      will be evaluated using Hotelling test as multi directional generalization of Student test.

      Time schedule:

        1. year of the project: design of randomization program; personal education with study
           protocol; software design; inclusion of 18 patients. Data processing. Results will be
           evaluated at the end of the year; statistician will evaluate homogeneity of groups.

        2. year of the project: inclusion of further 18 patients. Data analysis will be performed
           and subgroup analysis and partial results will be processed and presented.

        3. year of the project: inclusion of the last 14 patients. Follow up termination. Definite
           data collection, analysis, results evaluation including financial analysis. Standard
           proposal. Presentation in national and international forums, publications.

      Discussion Surgical treatment is inseparable part of patient care with severe peritonitis.
      Advance monitoring is important for identification of risk patients but also for possible
      surgical revision indication. Generally used sepsis markers including scoring systems (APACHE
      II, MOSF - Multiple Organ System Failure, MODS - Multiple Organ Dysfunction Score) however
      react with certain delay. Possible or on demand re-laparotomy is performed afterwards in
      patient in severe conditions with MODS. On the other hand planned re-laparotomies are
      conducted excessively. Not even met-analysis of clinical studies proved clear preference of
      one procedure (23). New method VAC however has not been evaluated in prospective randomized
      study in this indication. Inclusion of early markers of septic state - IL-1, 6, 8, 10 a TNF
      alpha - in indication for re-laparotomy or VAC exchange could have large clinical benefit.
      Further controversial indication parameter commonly measured at ICU is size and development
      of IAP which can present important correlation with laboratory signs of inflammation and it
      can lead for design of special index. VAC method use has its advantages - active and closed
      intraabdominal secretion restricts possibilities of spreading HAI. Significant and reduced
      frequency of dressing; enables simple physiotherapy of patients; condition of anabolic phase
      which is necessary for any healing (24). Analysis of patient number which benefit from this
      method (intention-to treat) against general costs is necessary.

      Designer's working site has treated 19 patients over the last 18 months using this method.
      Mortality was 15.8% and average hospitalization length 59.2 days which is in compliance of so
      far published results. However it has not been prospective randomized study and VAC method
      was however used as the last therapeutic option.

      Information Working site has needed surgical equipment including equipment for performing of
      VAC; VAC is used as method for 5 years; apart from purchase of consumption material he is the
      only owner of the pump. This method has been used to treat different wounds. Principal
      investigator and all co-workers has experience with this method. Co-investigator has even
      numerous experiences with clinical studies and he published his results in journals. Other
      specific equipment is not necessary for study procedure.

      Conclusion Detected results will background for verification of efficacy of VAC introduction
      into laparostomy in patients after surgical revision due to severe peritonitis. Efficacy of
      new and standard laboratory and clinical markers of septic state.

      Expected results, aims, priorities and significance of the project Study output will consist
      of data usable for design of recommended procedure for surgical patient care with severe
      peritonitis. Standardized protocol will be introduced for ICU patients which reflect only
      those laboratory methods and clinical parameters which clinically influence therapy. Detailed
      analysis for both groups will enable precise indication single surgical interventions which
      will ensure efficient and thus cost wise preferable therapy. Simple universal software will
      be created in terms of study which manages patient database and thus enables rapid concurrent
      assessment of health care quality.

      With regard that similar complex prospective study has not been published in national and
      international magazines, publication in impact journal; socioeconomic analysis will be
      published especially in national medical journals so it would be easily accessible.
    

Intervention name(s): V.A.C.- Vacuum assisted closure laparostomy (KCI)
Intervention type(s): Device
Intervention description(s): Primary Vacuum Assisted Closure (V.A.C.)laparostomy was indicated after surgery in patients with severe peritonitis. VAC laparostomy was performed using sandwich technique (semi-permeable foil - intraabdominal foam - dynamic sutura of the fascia - foam inserted subcutaneously - non-permeable foil) and connected to the active suction of 125mmHg.
Other intervention name(s): Vacuum Assisted Closure (V.A.C.) - KCI, USA
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Vacuum Assisted Closure (VAC); Laparostomy; Severe peritonitis