Clinical trial NCT01646229: Impact of Early Peri-operative Use of Polymyxin-B Hemoperfusion in Septic Patients Undergoing Emergent Abdominal Surgery
Official title: Impact of Early Per-operative Use of Polymyxin-B Hemoperfusion in Septic Patients Undergoing Emergent Abdominal Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Abdominal Sepsis
Peritonitis
Colon Perforation
Keywords: Hemoperfusion
Polymyxin-B
Emergency abdominal surgery
Sepsis
Endotoxin
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
First posted: 2012-07-20
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Septic shock of intra-abdominal origin is likely due to Gram-negative bacteria or mixed pathogens and associated with high levels of endotoxin. The injury to the endothelium results in an increase of endothelial permeability, interstitial edema and release of nitric oxide (NO) that is a very potent vasodilatator. \[6\] Polymyxins obtained from the Gram-positive bacterium Bacillus polymyxa are antibiotics known for their ability to bind LPS in the outer membrane of the Gram-negative bacterial cell wall as well as free endotoxins with high affinity. Polymyxin-B has been shown to block the activation of cells by a wide variety of LPS. Studies converged to show an improvement in the treatment of septic shock by removing circulating endotoxin.Starting Polymyxin-B hemoperfusion during the operative time is to block the initiation of various deleterious biological cascades induced by endotoxemia such as systemic inflammation, disseminated coagulation disorders, and shock, leading to organ dysfunction and death.


Eligibility criteria: Inclusion Criteria:

* Adults \> 18 years
* Severe sepsis\*or septic shock as define by the ACCCP/SCCM consensus conference, of abdominal origin
* Need for emergent abdominal surgery procedure under general anesthesia with expected duration of ≥ 120 min (in and out patients) for bowel perforation, ileus or peritonitis

Exclusion Criteria:

* Patients younger than 18 years
* Organ transplantation in the last year
* Terminally ill patients: do-not-resuscitate order, perceived to die within 48 hrs of admission
* Known pregnancy or diagnosed by US or Ct-scan (\>14 weeks)
* History of sensitivity to polymyxin-B or to anticoagulant ( heparin)
* Uncontrolled hemorrhage within the last 24h
* Severe granulocytopenia ( leukocyte count of \< 500/µL)
* Severe thrombocytopenia ( platelets count of \< 30'000/µL)
* Need for CPR pre-operatively

Primary outcomes:
measure: The primary endpoint will be requirement of vasopressors during the first 72 hrs after the beginning of the PMX hemoperfusion using the "inotropic score"
timeFrame: The inotropic score is assessed at the following specific time points: Time 0 - baseline measurements at the beginning of surgery, second time point at the end of surgery, Time 0 +6 hours, Time 0 + 24 hours, Time 0 + 48 hours, Time 0 + 72 hours.
Secondary outcomes:
measure: The secondary endpoint will be the variation of MAP, during the first 72 hrs after the beginning of the PMX hemoperfusion
timeFrame: The inotropic score is assessed at the following specific time points: Time 0 - baseline measurements at the beginning of surgery, second time point at the end of surgery, Time 0 +6 hours, Time 0 + 24 hours, Time 0 + 48 hours, Time 0 + 72 hours.
measure: The secondary endpoint will be the variation of "vasopressor dependency index", during the first 72 hrs after the beginning of the PMX hemoperfusion
timeFrame: The variation of the "vasopressor dependency index" is assessed at: Time 0 - baseline measurements at the beginning of surgery, second time point at the end of surgery, Time 0 +6 hours, Time 0 + 24 hours, Time 0 + 48 hours, Time 0 + 72 hours.
measure: The secondary endpoint will be the variation of Pa02/Fi02, during the first 72 hrs after the beginning of the PMX hemoperfusion
timeFrame: The variation of Pa02/Fi02 is assessed at the following specific time points: Time 0 - baseline measurements at the beginning of surgery, second time point at the end of surgery, Time 0 +6 hours, Time 0 + 24 hours, Time 0 + 48 hours, Time 0 + 72 hours.
measure: The secondary endpoint will be the variations of the total SOFA score during the first 7 days after the beginning of the PMX hemoperfusion
timeFrame: The variations of the total SOFA score will be assessed once a day from day 1, till discharge of the ICU, and this maximaly 7 days after the beginning of the PMX hemoperfusion
measure: The secondary endpoint will be the 28-days mortality
timeFrame: The 28-days mortality will be assessed on the 28th day post PMX hemoperfusion
measure: The secondary endpoint will be the 90-days mortality
timeFrame: The 90-days mortality will be assessed on day 90 post PMX hemoperfusion
Other outcomes:
Locations:
city: Geneva
country: Switzerland
facility: Emergency operating room, Geneva Cantonal Hospital
Study officials:
affiliation: University Hospital, Geneva
name: Jerome Pugin, Professor
role: STUDY_DIRECTOR
References: