Systematic Reviews
Copyright ©The Author(s) 2023.
World J Crit Care Med. Mar 9, 2023; 12(2): 71-88
Published online Mar 9, 2023. doi: 10.5492/wjccm.v12.i2.71
Table 1 Studies showing efficacy of different devices for cytokine and endotoxin removal
Ref.Study typePopulationModalityInterventionOutcomes
Tapia et al[28], 2012Prospective cohort study31 severe septic shock patientsHVHF, Cytokine removalHVHF – single short term – 6 h at 40 mL/kg/h25/31 responded to HVHF. Decrease in NE dose and improvement in hemodynamic, metabolic and respiratory parameters were significantly improved by 4 h
Joannes-Boyau et al[29], 2013Prospective, randomized, open multicentre trial137 septic shock patients (AKI < 24 h)HVHF, Cytokine removalHVHF – 70 mL/kg/h vs standard volume hemofiltration at 35 mL/kg/h No difference in hemodynamic stability, severity scores, 28-d mortality, length of stay and vasopressor free days
Livigni et al[30], 2014Prospective, randomized, multicentre parallel group trial192 septic shock patientsCPFA, Cytokine & endotoxin removalConventional therapy (n = 93) vs CPFA (n = 91)Decreased mortality in patients receiving high dose of CPFA. No difference in length of ICU stay and new organ failures in 30 d
Atan et al[31], 2018Randomized controlled trial76 critically ill patients with AKICVVH -HCOCytokine removalCVVH-HCO (n = 38) – cut off point 100 kDa vs CVVH -Std (n = 38) – cut off point 30 kDaNo difference was observed in mortality, duration of hemofiltration, norepinephrine dose, serum albumin levels and filter life
Dellinger et al[32], 2018Randomized, multicentre trial449 septic shock patientsPolymyxin B hemoperfusion; Endotoxin removalPolymyxin B hemoperfusion + Standard therapy vs Sham hemoperfusion + Standard therapyNo significant difference in 28 d mortality in overall population or in patients with MODS score of > 9
Kaçar et al[33], 2020Prospective observational study23 septic shock patients with AKIHA 330 Cytokine removalHA 330 hemoperfusion + CVVH for 2 h once daily for 3 dIncrease in pH was observed after 1st application HA330 hemoperfusion; CRP and PCT levels decreased significantly after 2nd application
Table 2 Multiple logistic regression analysis to predict 30 d mortality
Ref.
Study design
Population
Intervention
Outcomes
Friesecke et al[62], 2017 Prospective, single center study20 septic shock patientsCytoSorb hemoperfusionNorepinephrinedose reduced after 6 and 12 h; Improved lactate clearance; SOFA scores unchanged; Shock reversal achieved in 65% of patients; 28-d survival – 45%
Kogelmann et al[63], 2017Case series26 septic shock patientsCytoSorb+CVVHDRapid hemodynamic stabilization; Reduction in Vasopressor dose by 67%; Decrease in blood lactate by 26.4%; Shock reversal in 38.5% patients; Decreased mortality than predicted by APACHE II; No adverse events reported
Friesecke et al[52], 2017International registry135 septic shock patientsCytoSorb hemoperfusionReduced observed mortality of 65% than predicted by APACHE II of 78%; Marked reduction in IL6 levels; No significant reduction in SOFA scores; Safe and well tolerated without any adverse events
Brouwer et al[59], 2019Retrospective, investigator-initiated study116 septic shock patientsCytoSorb +CRRTIn CytoSorb group, the mean predicted mortality rate was 74.5%, while 28 d mortality rate was 47.8%; In CRRT group, the mean predicted mortality rate was 67.9%, while 28-d mortality was 51.0%; CytoSorb group was associated with a reduced 28-d mortality in comparison to CRRT (53% vs 72.3%)
CRRT alone
Brouwer et al[60], 2021Long term follows up116 septic shock patientsCytoSorb +CRRTCytoSorb was significantly associated with long term outcome compared to CRRT
Retrospective cohort studyCRRT alone
Mehta et al[53], 2020Retrospective, observational study40 septic shock patientsCytoSorb hemoperfusion (Survivor group vs non survivor group)Improvement in MAP (62.82 ± 9.73mmHg); Reduction in vasopressor dose; Reduction IL-6 levels (87%) and TNF levels (24%); Decrease in SOFA scores by 16.2%
Paul et al[68], 2021Prospective, real time, observational multicentre study45 septic shock patientsCytoSorb+ Standard therapy26 patients survived post therapy; Reduction in vasopressor dose (NE- 51.4%, Epinephrine – 69.4% and Vasopressin -13.9%); 52.3% reduction in IL-6 levels; Reduction in APACHE II and SOFA scores, 20.1 ± 2.47 and 9.04 ± 3.00 respectively
(Survivor vs non survivor group)
Akil et al[69], 202020 patients with pneumogenic sepsis and ARDSCytoSorb + Combined high flow veno-venous ECMO (CytoSorb group); ECMO therapy alone (Control group)The 30-d mortality rate was 0% in CytoSorb group, whereas 57% was observed in control group; Significant reduction in procalcitonin and C-reactive levels were observed in CytoSorb group in comparison to control group
Rugg et al[61], 2020Retrospective single center study42 septic shock patients compared to 42 matched controlsCytosorb +RRTCatecholamines requirements decreased to 0.26 µg/kg/min within 24 h of therapy with CytoSorb; In hospital mortality was significantly lower in CytoSorb group as compared to controls (35.7% vs 61.9%); Risk factors in CytoSorb group were high lactate levels and low thrombocyte counts proior to therapy. Lactate value of 7.5 mmol/L, predicted mortality with high specificicty (88.9%)
Table 3 Studies determining efficacy of CytoSorb in coronavirus disease 2019 infection
Ref.Study typePopulationInterventionOutcomes
Alharthy et al[70], 2020Retrospective case series50 COVID-19 patients with AKI, ARDS, Sepsis and hyperinflammationCytoSorb + CRRT [Survivors (n = 35) vs non survivors (n = 15)]Decreased SOFA score, lactate levels, ferritin, D-dimers, CRP and IL-6 levels in th survivor group after 2 ± 1 sessions of CRRT + CytoSorb
Mehta et al[64], 2021Case series3 critically ill COVID-19 patientsCytoSorb hemoperfusion other prescribed medications (tocilizumab, antivirals, hydroxychloroquine, azithromycin)Significant improvement in biochemical parameters and clinical outcomes post CytoSorb therapy; Reduction in CRP levels by 91.5%, 97.4% and 55.75%, respectively; Improvement in MAP by 18%, 23% and 17% by 7th day post therapy
Nassiri et al[71], 2021Retrospective case series26 COVID-19 patients with ARDSCytoSorb hemadsorption therapy21 patients survived; Significant decrease in NE requirement; PCT, CRP and ferritin reduced post therapy; Significant improvement in SOFA scores; Therapy was well tolerated
Paisey et al[72], 2021Retrospective case series15 severely ill COVID-19 patientsCytoSorb hemadsorption therapyAdjunctive treatment with CytoSorb lead to reduction in ferritin, CRP, PCT and lactate levels
Song et al[73], 2021Multicenter observational study52 ICU COVID -19 patients on ECMOECMO + CytoSorb hemadsorption therapyICU mortality was 17.3% on day 30, 26.9% on day 90, and 30.8% at final follow up of 143 d; Lower baseline D-Dimer levels were observed among survivors (2.3 ± 2.5 vs 19.8 ± 32.2 µg/mL) compared to non survivors; Borderline association observed between baseline D-Dimer levels and mortality with a 32% increase in risk of death per 1 µg/mL increase
Table 4 Multiple logistic regression analysis to predict 30 d mortality
Feature
CytoSorb 300[84,85,86]
Jafron HA-series (80, 130, 180, 230, 280, 330, 380)[87]
Biosky MG-Series[88]
ManufacturerCytoSorbents™ Inc, United StatesJafron Biomedical Co., Ltd. No. 98, Technology Sixth Road, High-tech Zone, Zhuhai City, 519085, Guangdong, ChinaBiosun Medical Technology Co. Ltd, China
IFU versionOctober 1, 2021[87]11-Sep-191-Aug-18
AdsorbentCrosslinked DivinylbenzeneNeutral Macroporous ResinMedical Neutral Macroporous Synthetic Resin
Coating PolyvinylpyrollidoneCollodionNo data
Adsorbent Surface> 45000 m2 100000m2 No data
Storage fluidIsotonic salineWater for injectionSterile water
Use time/cartridge24 h, Can be administered up to 7 consecutive daysDepending on mode of operation: Hemoperfusion 100-250 mL/ min; Dialysis < 320 ml/ min with use upto 4 h; CRRT 150-250 mL/min with use upto 12 h; CPB up to 700 mL/ min with use upto 2.5 h120-180 min, Not suggested to use more than 3 times within 24 h
Blood flow100-700 mL/min, Recommended > 150 mL/min100-700 mL/min100-400 mL/min; Highest rate is 250 mL/min
Pmax760 mmHg750 mmHg750 mmHg
Mode of operation coveredHemoperfusion, Intermittent hemodialysis, CRRT, Cardiopulmonary bypass (CPB) ECMOHemoperfusion; Hemodialysis; CRRT; CPBHemoperfusion; Hemodialysis; CRRT; CPB only as comment in anticoagulation, not in setup
Shelf life3 yr2 yr2 yr
Safety report statusAs of 2021: > 162000 treatments distributed without confirmed serious device related eventsNo dataNo data
Table 5 Studies determing oxiris efficacy for removal of endotoxins and cytokines
Ref.Study typePopulationIntervention Outcomes
Shum et al[98], 2013Prospective case series with historical controls6 patients with septic AKIoXiris + CVVHSignificant reduction in SOFA scores by 37% after 48 h of therapy
Ugurov et al[96], 2020Single centre case series15 COVID -19 patientsoXiris hemofilterEarly initiation of oXiris was associated with stable or reducing levels of IL-6,8,10 and TNFα
Zhang et al[49], 2021Case series5 COVID-19 patients CRRT followed by oXiris hemofilter therapyReduced levels of cytokines, haemodynamic stabilization and improvement of organ function was observed with oXiris.
Rosalia et al[100], 2020Prospective cohort study44 COVID 19 casesCVVH + oXirisReduction in CRP, ferritin, fibrinogen and other inflammatory mediators were observed