Early experience of using regional citrate anticoagulation for continuous renal replacement therapy in critically ill patients in a resource-limited setting.

AIM: Despite the superiority of regional citrate anticoagulation (RCA) in continuous renal replacement therapy (CRRT), its application is limited in resource-limited settings. We aim to explore the cost and safety of RCA for CRRT in critically ill patients, compared to usual care. METHODS: This prospective observational study included patients requiring CRRT in a tertiary intensive care unit (ICU) from February 2022 to January 2023. They were classified to either the RCA or usual care groups based on the anticoagulation technique chosen by the treating physician, considering contraindications. The CRRT prescription follows the institutional protocol. All relevant data were obtained from the ICU CRRT-RCA charts and electronic medical records. A cost analysis was performed. RESULTS: A total of 54 patients (27 per group) were included, with no demographic differences. Sequential Organ Failure Assessment score and lactate levels were significantly higher in the usual care group. The number of filters used were comparable (p = .108). The median filter duration in the RCA group was numerically longer (35.00 [15.50-56.00] vs. 23.00 [17.00-29.00] h), but not statistically significant (p = .253). The duration of mechanical ventilation, vasopressor requirement, and mortality were similar, but the RCA group had a significantly longer ICU stay. The rate of adverse events was similar, with four severe metabolic alkalosis cases in the RCA group. The RCA group had higher total cost per patient per day (USD 611 vs. 408; p = .013). CONCLUSION: In this resource-limited setting, RCA for CRRT appeared safe and had clinically longer filter lifespan compared with usual care, albeit the increased cost.

Outcomes of extracorporeal blood purification with oXiris® membrane in critically ill patients: A systematic review and meta-analysis.

PURPOSE: To evaluate the efficacy of the novel oXiris® membrane in critically ill adult patients. METHODS: We systematically searched MEDLINE, EMBASE, and CENTRAL from inception to 01/06/2023 for relevant randomised controlled trials (RCTs) and non-randomised studies of intervention (NRSI). The primary outcome was overall mortality. Random effect meta-analyses were conducted in RevMan 5.4.1. Study quality was evaluated using Cochrane's risk of bias tool. (PROSPERO: CRD42023389198). RESULTS: Ten studies (2 RCTs and 8 NRSIs) with 481 patients were included. None had low risk of bias. Treatment using oXiris® was associated with reduced overall mortality (RR 0.78, 95%CI 0.62-0.98; p = 0.03; 6 NRSI). One RCT reported 28-day mortality, finding no significant difference between groups. Besides, pooled NRSIs results showed significant reductions in SOFA scores, norepinephrine dosage, and several inflammatory biomarkers (C-reactive protein [CRP], lactate, and interleukin-6 [IL-6]) post oXiris® treatment. However, other clinical outcomes (ICU and hospital length of stay, mechanical ventilation duration) were similar between groups. CONCLUSION: In critically ill patients, the use of oXiris® membrane was associated with reduced overall mortality, norepinephrine dosage, CRP, IL-6, lactate levels, along with improved organ function. However, the certainty of evidence was very low, necessitating high-quality RCTs to further evaluate its efficacy in this population.

Prone ventilation in intubated COVID-19 patients: a systematic review and meta-analysis

Abstract Background The efficacy and safety profiles of prone ventilation among intubated Coronavirus Disease 2019 (COVID-19) patients remain unclear. The primary objective was to examine the effect of prone ventilation on the ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) in intubated COVID-19 patients. Methods Databases of MEDLINE, EMBASE and CENTRAL were systematically searched from inception until March 2021. Case reports and case series were excluded. Results Eleven studies (n = 606 patients) were eligible. Prone ventilation significantly improved PaO2/FiO2 ratio (studies: 8, n = 579, mean difference 46.75, 95% CI 33.35‒60.15, p < 0.00001; evidence: very low) and peripheral oxygen saturation (SpO2) (studies: 3, n = 432, mean difference 1.67, 95% CI 1.08‒2.26, p < 0.00001; evidence: ow), but not the arterial partial pressure of carbon dioxide (PaCO2) (studies: 5, n = 396, mean difference 2.45, 95% CI 2.39‒7.30, p= 0.32; evidence: very low), mortality rate (studies: 1, n = 215, Odds Ratio 0.66, 95% CI 0.32‒1.33, p= 0.24; evidence: very low), or number of patients discharged alive (studies: 1, n = 43, Odds Ratio 1.49, 95% CI 0.72‒3.08, p= 0.28; evidence: very low). Conclusion Prone ventilation improved PaO2/FiO2 ratio and SpO2 in intubated COVID-19 patients. Given the substantial heterogeneity and low level of evidence, more randomized- controlled trials are warranted to improve the certainty of evidence, and to examine the adverse events of prone ventilation.

A double whammy: The association between comorbidities and severe dengue among adult patients-A matched case-control study.

BACKGROUND: Dengue infection is the most prevalent mosquito-borne viral infection globally. Concurrently, there has also been an upsurge of non-communicable comorbidities. We aimed to investigate the association between these comorbidities and the development of severe dengue. METHODS: We performed a retrospective, case-control study involving 117 cases with severe dengue and 351 controls with non-severe dengue; matched according to gender, age (+/- 5 years old), and admission date (+/- 2 weeks). We analyzed the data using conditional odds ratio (cOR) and adjusted conditional odds ratio (AcOR) using univariate and multivariable conditional logistic regression respectively. RESULTS: Six main comorbidities namely obesity, diabetes mellitus, hypertension, hyperlipidemia, chronic pulmonary disease, and ischemic heart disease were observed among cases and controls. Multivariable conditional logistic regression model found only hypertension to be independently associated with the development of severe dengue (ACOR 2.46; 95% CI:1.09-5.53). Among symptoms at presentation, lethargy, vomiting, bleeding manifestations, and abdominal pain were associated with increased odds of severe dengue, although the associations were not statistically significant. Headache (ACOR: 0:32; 95% CI: 0.21-0.51) and skin rash (ACOR: 0.42; 95% CI: 0.22-0.81) were associated with significantly lower odds of severe dengue. Severe dengue patients were also found to have significantly higher white cell count, urea, creatinine, alanine aminotransferase, aspartate aminotransferase, creatine kinase, and lactate dehydrogenase on admission, while platelet and albumin were significantly lower compared to non-severe dengue patients. CONCLUSIONS: Our study found a significant association between hypertension and the development of severe dengue in adult patients. For clinical practice, this finding suggests that dengue patients with underlying hypertension warrant closer clinical monitoring for deterioration. The association between significant derangement in various laboratory parameters and severe dengue as shown in this study is in keeping with previous reports. While further substantiation by larger prospective studies will be desirable, this association may serve to inform the dengue triaging process.

Prone ventilation in intubated COVID-19 patients: a systematic review and meta-analysis.

BACKGROUND: The efficacy and safety profiles of prone ventilation among intubated Coronavirus Disease 2019 (COVID-19) patients remain unclear. The primary objective was to examine the effect of prone ventilation on the ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) in intubated COVID-19 patients. METHODS: Databases of MEDLINE, EMBASE and CENTRAL were systematically searched from inception until March 2021. Case reports and case series were excluded. RESULTS: Eleven studies (n = 606 patients) were eligible. Prone ventilation significantly improved PaO2/FiO2 ratio (studies: 8, n = 579, mean difference 46.75, 95% CI 33.35‒60.15, p < 0.00001; evidence: very low) and peripheral oxygen saturation (SpO2) (studies: 3, n = 432, mean difference 1.67, 95% CI 1.08‒2.26, p < 0.00001; evidence: ow), but not the arterial partial pressure of carbon dioxide (PaCO2) (studies: 5, n = 396, mean difference 2.45, 95% CI 2.39‒7.30, p = 0.32; evidence: very low), mortality rate (studies: 1, n = 215, Odds Ratio 0.66, 95% CI 0.32‒1.33, p = 0.24; evidence: very low), or number of patients discharged alive (studies: 1, n = 43, Odds Ratio 1.49, 95% CI 0.72‒3.08, p = 0.28; evidence: very low). CONCLUSION: Prone ventilation improved PaO2/FiO2 ratio and SpO2 in intubated COVID-19 patients. Given the substantial heterogeneity and low level of evidence, more randomized- controlled trials are warranted to improve the certainty of evidence, and to examine the adverse events of prone ventilation.

High-Dose versus Low-Dose Corticosteroids in COVID-19 Patients: a Systematic Review and Meta-analysis.

OBJECTIVES: The clinical efficacy of corticosteroids remains unclear. The primary aim of this systematic review and meta-analysis was to evaluate the use of high-dose versus low- dose corticosteroids on the mortality rate of COVID-19 patients. DESIGN: Systematic review and meta-analysis. SETTING: Electronic search for randomized controlled trials and observational studies (MEDLINE, EMBASE, CENTRAL). PARTICIPANTS: Hospitalized adults ≥ 18 years old who were SARS-CoV-2 PCR positive. INTERVENTIONS: High-dose and low-dose corticosteroids. MEASUREMENTS AND MAIN RESULTS: A total of twelve studies (n=2759 patients) were included in this review. The pooled analysis demonstrated no significant difference in mortality rate between the high-dose and low-dose corticosteroids groups (n=2632; OR: 1.07 [95%CI 0.67, 1.72], p=0.77, I2=76%, trial sequential analysis=inconclusive). No significant differences were observed in the incidence of intensive care unit (ICU) admission rate (n=1544; OR: 0.77[95%CI 0.43, 1.37], p=0.37, I2= 72%), duration of hospital stay (n=1615; MD: 0.53[95%CI -1.36, 2.41], p=0.58, I2=87%), respiratory support (n=1694; OR: 1.51[95%CI 0.77, 2.96], p=0.23, I2=84%), duration of mechanical ventilation (n=419; MD: -1.44[95%CI -4.27, 1.40], p=0.32, I2=93%), incidence of hyperglycemia (n=516, OR: 0.91[95%CI 0.58, 1.43], p=0.68, I2=0%) and infection rate (n=1485, OR: 0.86[95%CI 0.64, 1.16], p=0.33, I2=29%). CONCLUSION: The meta-analysis demonstrated high-dose corticosteroids did not reduce mortality rate. However, high-dose corticosteroids did not pose higher risk of hyperglycemia and infection rate for COVID-19 patients. Due to the inconclusive trial sequential analysis, substantial heterogeneity and low level of evidence, future large-scale randomized clinical trials are warranted to improve the certainty of evidence for the use of high-dose compared to low-dose corticosteroids in COVID-19 patients.

Clinical characteristics and outcomes of critically ill coronavirus disease 2019 patients in Malaysia during the first wave: A multi-center observational study (COVIDICU-MY).

Background: Coronavirus disease 2019 (COVID-19) emerged with a wide range of clinical presentations; Malaysia was not spared from its impact. This study describes the clinical characteristics of COVID-19 patients admitted to intensive care unit, their clinical course, management, and hospital outcomes. Methods: COVIDICU-MY is a retrospective analysis of COVID-19 patients from 19 intensive care units (ICU) across Malaysia from 1 March 2020 to 31 May 2020. We collected epidemiological history, demographics, clinical comorbidities, laboratory investigations, respiratory and hemodynamic values, management, length of stay and survival status. We compared these variables between survival and non-survival groups. Results: A total of 170 critically ill patients were included, with 77% above 50 years of age [median age 60, IQR (51-66)] and 75.3% male. Hypertension, diabetes mellitus, hyperlipidemia, chronic cardiac disease, and chronic kidney disease were most common among patients. A high Simplified Acute Physiology Score (SAPS) II score [median 45, IQR (34-49)] and Sequential Organ Failure Assessment (SOFA) score [median 8, IQR (6-11)] were associated with mortality. Patients were profoundly hypoxic with a median lowest PaO2/FiO2 ratio of 150 (IQR 99-220) at admission. 91 patients (53.5%) required intubation on their first day of admission, out of which 38 died (73.1% of the hospital non-survivors). Our sample had more patients with moderate Acute Respiratory Distress Syndrome (ARDS), 58 patients (43.9%), compared to severe ARDS, 33 patients (25%); with both ARDS classification groups contributing to 25 patients (54.4%) and 11 patients (23.9%) of the non-survival group, respectively. Cumulative fluid balance over 24 h was higher in the non-survival group with significant differences on Day 3 (1,953 vs. 622 ml, p < 0.05) and Day 7 of ICU (3,485 vs. 830 ml, p < 0.05). Patients with high serum creatinine, urea, lactate dehydrogenase, aspartate aminotransferase and d-dimer, and low lymphocyte count throughout the stay also had a higher risk of mortality. The hospital mortality rate was 30.6% in our sample. Conclusion: We report high mortality amongst critically ill patients in intensive care units in Malaysia, at 30.6%, during the March to May 2020 period. High admission SAPS II and SOFA, and severe hypoxemia and high cumulative fluid balance were associated with mortality. Higher creatinine, urea, lactate dehydrogenase, aspartate aminotransferase and d-dimer, and lymphopenia were observed in the non-survival group.

Randomized clinical trial comparing helmet continuous positive airway pressure (hCPAP) to facemask continuous positive airway pressure (fCPAP) for the treatment of acute respiratory failure in the emergency department.

STUDY OBJECTIVE: To determine whether non-invasive ventilation (NIV) delivered by helmet continuous positive airway pressure (hCPAP) is non-inferior to facemask continuous positive airway pressure (fCPAP) in patients with acute respiratory failure in the emergency department (ED). METHODS: Non-inferiority randomized, clinical trial involving patients presenting with acute respiratory failure conducted in the ED of a local hospital. Participants were randomly allocated to receive either hCPAP or fCPAP as per the trial protocol. The primary endpoint was respiratory rate reduction. Secondary endpoints included discomfort, improvement in Dyspnea and Likert scales, heart rate reduction, arterial blood oxygenation, partial pressure of carbon dioxide (PaCO2), dryness of mucosa and intubation rate. RESULTS: 224 patients were included and randomized (113 patients to hCPAP, 111 to fCPAP). Both techniques reduced respiratory rate (hCPAP: from 33.56 ± 3.07 to 25.43 ± 3.11 bpm and fCPAP: from 33.46 ± 3.35 to 27.01 ± 3.19 bpm), heart rate (hCPAP: from 114.76 ± 15.5 to 96.17 ± 16.50 bpm and fCPAP: from 115.07 ± 14.13 to 101.19 ± 16.92 bpm), and improved dyspnea measured by both the Visual Analogue Scale (hCPAP: from 16.36 ± 12.13 to 83.72 ± 12.91 and fCPAP: from 16.01 ± 11.76 to 76.62 ± 13.91) and the Likert scale. Both CPAP techniques improved arterial oxygenation (PaO2 from 67.72 ± 8.06 mmHg to 166.38 ± 30.17 mmHg in hCPAP and 68.99 ± 7.68 mmHg to 184.49 ± 36.38 mmHg in fCPAP) and the PaO2:FiO2 (Partial pressure of arterial oxygen: Fraction of inspired oxygen) ratio from 113.6 ± 13.4 to 273.4 ± 49.5 in hCPAP and 115.0 ± 12.9 to 307.7 ± 60.9 in fCPAP. The intubation rate was lower with hCPAP (4.4% for hCPAP versus 18% for fCPAP, absolute difference -13.6%, p = 0.003). Discomfort and dryness of mucosa were also lower with hCPAP. CONCLUSION: In patients presenting to the ED with acute cardiogenic pulmonary edema or decompensated COPD, hCPAP was non-inferior to fCPAP and resulted in greater comfort levels and lower intubation rate.

A Double-Blind Randomized Controlled Trial of High Cutoff Versus Standard Hemofiltration in Critically Ill Patients With Acute Kidney Injury.

OBJECTIVES: In critically ill patients with acute kidney injury receiving vasopressors, high cytokine levels may sustain the shock state. High cutoff hemofiltration achieves greater cytokine removal in ex vivo and in animal models and may reduce the duration of shock but may also increase albumin losses. DESIGN: This was a single-center double-blind randomized controlled trial comparing continuous venovenous hemofiltration-high cutoff to continuous venovenous hemofiltration-standard. SETTING: Tertiary care hospital in Australia. PATIENTS: Vasopressor-dependent patients in acute kidney injury who were admitted to the ICU. INTERVENTIONS: Norepinephrine-free time were calculated in critically ill vasopressor-dependent patients in acute kidney injury, randomized to either continuous venovenous hemofiltration-high cutoff or continuous venovenous hemofiltration-standard. MEASUREMENT AND MAIN RESULTS: A total of 76 patients were randomized with the following characteristics (continuous venovenous hemofiltration-high cutoff vs continuous venovenous hemofiltration-standard); median age of 65 versus 70 year, percentage of males 47% versus 68%, and median Acute Physiology and Chronic Health Evaluation scores of 25 versus 23.5. The median hours of norepinephrine-free time at day 7 were 32 (0-110.8) for continuous venovenous hemofiltration-high cutoff and 56 hours (0-109.3 hr) (p = 0.520) for continuous venovenous hemofiltration-standard. Inhospital mortality was 55.6% with continuous venovenous hemofiltration-high cutoff versus 34.2% with continuous venovenous hemofiltration-standard (adjusted odds ratio, 2.49; 95% CI, 0.81-7.66; p = 0.191). There was no significant difference in time to cessation of norepinephrine (p = 0.358), time to cessation of hemofiltration (p = 0.563), and filter life (p = 0.21). Serum albumin levels (p = 0.192) were similar and the median dose of IV albumin given was 90 grams (20-212 g) for continuous venovenous hemofiltration-high cutoff and 80 grams (15-132 g) for continuous venovenous hemofiltration-standard (p = 0.252). CONCLUSIONS: In critically ill patients with acute kidney injury, continuous venovenous hemofiltration-high cutoff did not reduce the duration of vasopressor support or mortality or change albumin levels compared with continuous venovenous hemofiltration-standard.

High cut-off hemofiltration versus standard hemofiltration: effect on plasma cytokines.

PURPOSE: To study the effects of continuous veno-venous hemofiltration (CVVH) with high cut-off filters (CVVH-HCO) on plasma cytokine levels, sieving coefficient and clearance compared to CVVH using standard filters (CVVH-Std) in a nested cohort within a double-blind randomized controlled trial in severe acute kidney injury (AKI) patients. METHODS: We measured plasma and post-filter levels of IL-6, TNF-alpha, IL-8, IL-1 beta, RANTES, IL-10, IFN-gamma and IFN-alpha in both study groups. We also measured cytokine levels in the ultrafiltrate and calculated sieving coefficients and clearances. RESULTS: By 72 hours of treatment, IL-6 had decreased during both treatments (p = 0.009 and 0.005 respectively). In contrast, IL-10 had decreased with CVVH-Std (p = 0.03) but not CVVH-HCO (p = 0.135). None of the other cytokines showed changes over time. There were also no significant between group differences in plasma levels for each cytokine over the 72-hour treatment period. For all cytokines combined, however, the median sieving coefficient was higher for CVVH-HCO (0.31 vs. 0.16; p = 0.042) as was the mass removal rate by ultrafiltration (p = 0.027). While overall combined cytokine levels had fallen to 62.2% of baseline at 72 hours for CVVH-HCO (p<0.0001) and to 75.9% of baseline with CVVH-Std (p = 0.008) there were no between group differences. CONCLUSIONS: CVVH-HCO achieved greater combined sieving coefficient and mass removal rate by ultrafiltration for a group of key cytokines than CVVH-Std. However, this effect did not differentially lower their plasma level over the first 72 hours. Our study does not support the use of CVVH-HCO to lower cytokines in critically ill patients with AKI.

Nucleosome levels and toll-like receptor expression during high cut-off haemofiltration: a pilot assessment.

OBJECTIVES: To measure plasma nucleosome levels and expression of toll-like receptors (TLRs) in a pilot cohort of patients with severe acute kidney injury (AKI) within a randomised controlled trial of continuous venovenous haemofiltration with high cut-off filters (CVVH-HCO) v standard filters (CVVH-std). METHODS: We measured plasma nucleosome levels using the Cell Death Detection ELISA PLUS (10X) assay kit. We analysed plasma levels for correlation with disease severity and compared the effects of CVVH-HCO and CVVH-std on plasma nucleosome levels over the first 72 hours. We studied cell surface TLR expression on CD14-positive monocytes in a subcohort of CVVH-HCO patients. RESULTS: We did not detect nucleosomes in normal human plasma, but found elevated nucleosome levels in patients with severe AKI. Nucleosome levels at randomisation correlated weakly with Acute Physiology and Chronic Health Evaluation III scores (Pearson ρ=0.475, P=0.016). Treatment with CVVH-HCO or CVVH-std had no effect on nucleosome levels over 72 hours. The mean fluorescence intensity (MFI) ratios of TLR2 and TLR4 expression were elevated throughout the 72-hour period (range for TLR2, 0.97-3.98; range for TLR4, 0.91-10.18) and did not appear to decrease as a result of treatment with CVVH-HCO. CONCLUSIONS: Nucleosome concentration was elevated in the plasma of patients with severe AKI and mildly correlated with disease severity, but was not affected by treatment with CVVH-HCO or CVVH-std. Similarly, levels of TLR2 and TLR4 expression did not decrease over time during CVVHCrit HCO treatment.

High cut-off hemofiltration versus standard hemofiltration: a pilot assessment of effects on indices of apoptosis.

OBJECTIVES: To measure plasma pro-apoptotic and pro-necrotic activity in severe acute kidney injury (AKI) patients within a randomized controlled trial of continuous veno-venous hemofiltration with high cut-off filters (CVVH-HCO) versus standard filters (CVVH-Std). METHODS: We measured pro-apoptotic and pro-necrotic plasma activity by trypan blue exclusion cell viability assay, detection of DNA fragmentation, and by determination of caspase-3 activity and annexin V-based apoptosis and necrosis detection assay. RESULTS: Compared to no apoptosis or necrosis after incubation with healthy plasma, 14-18% of cells showed apoptosis and 4-8% showed necrosis after incubation with plasma from AKI patients. When comparing different measures of pro-apoptotic or pro-necrotic activity, CVVH-HCO and CVVH-Std showed no differential effects on such activity, which remained high over the first 3 days of treatment. However, using annexin V-FITC, there was a significant drop in pro-apoptotic activity across the filter for the CVVH-HCO group (p = 0.043) but not for the CVVH-Std group (p = 0.327) and a significant difference between the two groups (CVVH-HCO vs. CVVH-Std p = 0.006). CONCLUSIONS: Patients with severe AKI have increased pro-apoptotic and pro-necrotic activity. Although on single-pass effect assessment, CVVH-HCO was superior to CVVH-Std in decreasing annexin V-FITC-assessed pro-apoptotic activity, there was no overall attenuation of such activity during the first 3 days of treatment.

Techniques of extracorporeal cytokine removal: a systematic review of human studies.

BACKGROUND AND AIMS: Hypercytokinemia is believed to be harmful and reducing cytokine levels is considered beneficial. Extracorporeal blood purification (EBP) techniques have been studied for the purpose of cytokine reduction. We aimed to study the efficacy of various EBP techniques for cytokine removal as defined by technical measures. METHOD: We conducted a systematic search for human clinical trials which focused on technical measures of cytokine removal by EBP techniques. We identified 41 articles and analyzed cytokine removal according to clearance (CL), sieving coefficient (SC), ultrafiltrate (UF) concentration and percentage removed. RESULTS: We identified the following techniques for cytokine removal: standard hemofiltration, high volume hemofiltration (HVHF), high cut-off (HCO) hemofiltration, plasma filtration techniques, and adsorption techniques, ultrafiltration (UF) techniques relating to cardiopulmonary bypass (CPB), extracorporeal liver support systems and hybrid techniques including combined plasma filtration adsorption. Standard filtration techniques and UF techniques during CPB were generally poor at removing cytokines (median CL for interleukin 6 [IL-6]: 1.09 mL/min, TNF-alpha 0.74 mL/min). High cut-off techniques consistently offered moderate cytokine removal (median CL for IL-6: 26.5 mL/min, interleukin 1 receptor antagonist [IL-1RA]: 40.2 mL/min). Plasma filtration and extracorporeal liver support appear promising but data are few. Only one paper studied combined plasma filtration and adsorption and found low rates of removal. The clinical significance of the cytokine removal achieved with more efficacious techniques is unknown. CONCLUSION: Human clinical trials indicate that high cut-off hemofiltration techniques, and perhaps plasma filtration and extracorporeal liver support techniques are likely more efficient in removing cytokines than standard techniques.

Techniques of extracorporeal cytokine removal: a systematic review of the literature on animal experimental studies.

BACKGROUND AND AIMS: Extracorporeal cytokine removal may be desirable. We sought to assess extracorporeal blood purification (EBP) techniques for cytokine removal in experimental animal studies.
 METHODS: We conducted a targeted, systematic search and identified 17 articles. We analyzed cytokine clearance, sieving coefficient (SC), ultrafiltrate (UF) concentration, and percentage removal. As this review concerns technical appraisal of EBP techniques, we made no attempts to appraise the methodology of the studies included. Results are in descriptive terms only.
 RESULTS: Applying predicted clearance for 80 kg human, high volume hemofiltration (HVHF) techniques and plasmafiltration (PF) showed the highest rates of cytokine removal. High cutoff (HCO)/HF and PF techniques showed modest ability to clear cytokines using low to medium flows. Standard hemofiltration had little efficacy. At higher flows, HCO/HF achieved clearances between 30 and 70 ml/min for IL-6 and IL-10. There was essentially no removal of tumor necrosis factor (TNF)-alpha outside of PF.
 CONCLUSIONS: Experimental animal studies indicate that HVHF (especially with HCO filters) and plasmafiltration have the potential to achieve appreciable IL-6 and IL-10 clearances. However, only PF can remove TNF-alpha reliably.

Techniques of extracorporeal cytokine removal: a systematic review of the literature.

BACKGROUND AND AIMS: Attempts at achieving cytokine homeostasis include blood purification to deliver cytokine removal. Assessment of ex vivo studies for optimal operating conditions is a vital step. METHODS: We conducted a systematic search for ex vivo studies on cytokine removal using known modalities of extracorporeal circulation. We selected 29 articles and analyzed data according to clearance, sieving coefficient, ultrafiltrate concentration and percentage removal. RESULTS: We identified four main techniques for cytokine removal: standard techniques, high cut-off (HCO) techniques, adsorption techniques and combined plasma filtration adsorption. HCO hemofiltration (HCO/HF) showed greatest consistency in cytokine removal among all approaches. Mean albumin clearance with HCO filters was 3.74 ml/min. CONCLUSION: Ex vivo data support the view that HCO/HF is the most consistently effective approach in terms of sieving and clearance. Further investigation of HCO/HF in randomized controlled trials in animal models and humans seems desirable.