Impact of Early Peri-operative Use of Polymyxin-B Hemoperfusion in Septic Patients Undergoing Emergent Abdominal Surgery

University Hospitals (UH)

Status: Completed

Conditions: Peritonitis; Abdominal Sepsis; Colon Perforation

Treatments: Other: Control; Other: Polymyxin-B hemoperfusion

Study type: Interventional

Funder types: Other

Identifiers

NCT01646229

NAC11-054(CC11-146)

Details and patient eligibility

About

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.

Enrollment: 28 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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28 participants in 2 patient groups

Polymyxin-B hemoperfusion

Active Comparator group

Description:

In the HEMOPERFUSION group, a veno-venous dialysis catheter type GamCath 12 F, 3 lumen will be inserted instead of a regular double or triple-lumen central venous catheter, and connected to the Toraymyxin® (PMX-20-R) device for endotoxin adsorption by hemoperfusion with the DECAPSMART pump. The length of the hemoperfusion will be a minimum of 120 min and started just before the beginning of the surgical intervention in the OR and stopped at the end of surgery.

Treatment:

Other: Polymyxin-B hemoperfusion

Control

Active Comparator group

Description:

In the CONTROL group, the administration of fluids (250 to 500ml crystalloids) and cardiovascular supportive drugs will be guided to maintain standard pressure-related parameters within a normal range: MAP \> 65mmHg, HR \< 90/min, CVP between \> 8 and 12 \< mmHg, urinary output \> 0.5 ml/kg/h. In line with the conventional approach, other physiological parameters will also be targeted: T° \> 35.5°C, Sp02 \> 95%, lactate \< 2.5 mMol/L, normalisation of the BE. At the discretion of the attending anaesthesiologist with the FMH level, a PiCCO monitoring, a transoesophageal echography, or a pulmonary artery catheter, will be inserted to complement the standard hemodynamic monitoring if deemed necessary.

Treatment:

Other: Control