ABSTRACT
BACKGROUND: Endotoxin adsorption is a promising but controversial therapy in severe, refractory septic shock and conflicting results exist on the effective capacity of available devices to reduce circulating endotoxin and inflammatory cytokine levels. METHODS: Multiarm, randomized, controlled trial in two Swiss intensive care units, with a 1:1:1 randomization of patients suffering severe, refractory septic shock with high levels of endotoxemia, defined as an endotoxin activity ≥ 0.6, a vasopressor dependency index ≥ 3, volume resuscitation of at least 30 ml/kg/24 h and at least single organ failure, to a haemoadsorption (Toraymyxin), an enhanced adsorption haemofiltration (oXiris) or a control intervention. Primary endpoint was the difference in endotoxin activity at 72-h post-intervention to baseline. In addition, inflammatory cytokine, vasopressor dependency index and SOFA-Score dynamics over the initial 72 h were assessed inter alia. RESULTS: In the 30, out of 437 screened, randomized patients (10 Standard of care, 10 oXiris, 10 Toraymyxin), endotoxin reduction at 72-h post-intervention-start did not differ among interventions (Standard of Care: 12 [1-42]%, oXiris: 21 [10-51]%, Toraymyxin: 23 [10-36]%, p = 0.82). Furthermore, no difference between groups could be observed neither for reduction of inflammatory cytokine levels (p = 0.58), nor for vasopressor weaning (p = 0.95) or reversal of organ injury (p = 0.22). CONCLUSIONS: In a highly endotoxemic, severe, refractory septic shock population neither the Toraymyxin adsorber nor the oXiris membrane could show a reduction in circulating endotoxin or cytokine levels over standard of care. Trial registration ClinicalTrials.gov. NCT01948778. Registered August 30, 2013. https://clinicaltrials.gov/study/NCT01948778.
Subject(s)
Hemoperfusion , Shock, Septic , Shock , Adsorption , Cytokines , Humans , Shock, Septic/therapyABSTRACT
BACKGROUND: Ventilation with low tidal volume and airway pressure results in a survival benefit in ARDS patients. Previous research suggests that avoiding mechanical ventilation altogether may be beneficial in some cases of respiratory failure. Our hypothesis was that low flow veno-venous extracorporeal CO2 removal (ECCO2R) enables maintenance of a lung protective ventilation strategy or awake spontaneous ventilation despite severe hypercapnic respiratory failure (HRF). METHODS: Twenty patients with HRF were investigated while mechanically ventilated (N.=14) or breathing spontaneously close to respiratory exhaustion (N.=6). Low flow ECCO2R was performed using a hemoperfusion device with a polypropylene gas-exchanger. RESULTS: Causes of HRF were severe ARDS (N.=11), COPD (N.=4), chronic lung transplant rejection (N.=3) and cystic fibrosis (N.=2). During the first 8h of ECCO2R, PaCO2 decreased from 10.6 (9.3-12.9) to 7.9 (7.3-9.3) kPa (P<0.001) and pH increased from 7.23 (7.09-7.40) to 7.36 (7.27-7.41) (P<0.05). Thereafter, steady state was achieved while maintaining lung protective tidal volume (4.7 (3.8-6.5) mL/kg) and peak ventilator pressure (28 (27-30) mbar at 24 h). During the first 48 h, thrombocyte count decreased by 52% (P<0.01), Fibrinogen by 38% (P<0.05). Intubation could be avoided in all spontaneously breathing patients. In 4/6 high blood flow extracorporeal circulation was required due to increased oxygen demand. 6/14 mechanically ventilated patients recovered from respiratory support. CONCLUSIONS: Our results suggest that in mechanically ventilated patients with HRF, low flow ECCO2R supports the maintenance of lung protective tidal volume and peak ventilator pressure. In selected awake patients with acute HRF, it may be a novel treatment approach to avoid mechanical ventilation, hence preventing ventilator- and sedation-associated morbidity and mortality.
