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.
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.
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.
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.
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.
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.
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.