Continuous renal replacement therapy with the addition of CytoSorb cartridge in critically ill patients with COVID‐19 plus acute kidney injury: A case‐series

Alharthy, Abdulrahman; Faqihi, Fahad; Memish, Ziad A.; Balhamar, Abdullah; Nasim, Nasir; Ahmad, Shazaad; Tamim, Hani; Alqahtani, Saleh A.; Brindley, Peter G.; Karakitsos, Dimitrios

doi:10.1111/aor.13864

Cited by 65 publications

(88 citation statements)

References 83 publications

(275 reference statements)

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“…In 14 articles, including three case series, norepinephrine was weaned off after treatment with Cytosorb. Norepinephrine dosage was higher than 0.5 µg/kg/min at the end of the treatment with Cytosorb in one case report [74], and in two case series [12,78]. The median dosage of norepinephrine required decreased by a full order of magnitude at the end of Cytosorb therapy.…”

Section: Resultsmentioning

confidence: 87%

The Potential Role of Extracorporeal Cytokine Removal in Hemodynamic Stabilization in Hyperinflammatory Shock

et al. 2021

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Hemodynamic instability due to dysregulated host response is a life-threatening condition requiring vasopressors and vital organ support. Hemoadsorption with Cytosorb has proven to be effective in reducing cytokines and possibly in attenuating the devastating effects of the cytokine storm originating from the immune over-response to the initial insult. We reviewed the PubMed database to assess evidence of the impact of Cytosorb on norepinephrine needs in the critically ill. We further analyzed those studies including data on control cohorts in a comparative pooled analysis, defining a treatment effect as the standardized mean differences in relative reductions in vasopressor dosage at 24 h. The literature search returned 33 eligible studies. We found evidence of a significant reduction in norepinephrine requirement after treatment: median before, 0.55 (IQR: 0.39–0.90); after, 0.09 (0.00–0.25) μg/kg/min, p <0.001. The pooled effect size at 24 h was large, though characterized by high heterogeneity. In light of the importance of a quick resolution of hemodynamic instability in the critically ill, further research is encouraged to enrich knowledge on the potentials of the therapy.

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Section: Resultsmentioning

confidence: 87%

The Potential Role of Extracorporeal Cytokine Removal in Hemodynamic Stabilization in Hyperinflammatory Shock

et al. 2021

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“…To evaluate TPE's ability to remove the inflammatory mediators associated with COVID-19 patients [ 12 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ] we measured serum C-reactive protein (CRP), D-dimer, lactate dehydrogenase (LDH), ferritin, and interleukin-6 (IL‐6) prior to initiation, and within 24 hours after the last TPE session. CRP was defined as elevated if it was > 5.0 mg/L and IL‐6 if > 7.0 pg/mL [50] . To determine thromboinflammation risk, we also measured the levels of ADAMTS-13 activity (TECHNOZYM®ELISA) at the same time points in all enrolled patients [ 26 , 51 ].…”

Section: Methodsmentioning

confidence: 99%

Therapeutic plasma exchange in patients with life-threatening COVID-19: a randomised controlled clinical trial

Faqihi

Alharthy

Abdulaziz

et al. 2021

International Journal of Antimicrobial Agents

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134

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Objective To assess the efficacy of therapeutic plasma exchange (TPE) following life-threatening COVID-19. Design, setting, and participants Open-label, randomized clinical trial of intensive care unit (ICU) patients with life-threatening COVID-19 [positive real-time-polymerase-chain-reaction test, plus acute respiratory distress syndrome (ARDS), sepsis, organ failure, hyperinflammation]. The study was terminated after 87/120 patients were enrolled. Intervention and randomization Standard treatment plus TPE (n = 43) versus standard treatment (n = 44), and stratified by peripheral arterial oxygen saturation/fraction of inspired oxygen (PaO 2 /FiO 2 ) ratio (> 150 versus ≤ 150). Main Outcomes and measures Primary outcomes were 35-day mortality and TPE safety. Secondary outcomes were association between TPE and mortality, improvement in Sequential Organ Function Assessment (SOFA) score, change in inflammatory biomarkers, days on mechanical ventilation (MV), and ICU length-of-stay. Results Eighty-seven patients [median years of age 49 (IQR: 34-63); 72 males (82.8%)] were randomized [44 to standard care; 43 to standard care plus TPE]. Days on MV (p=0.007) and ICU length-of-stay (p=0.02) were lower in the TPE group versus controls. Thirty-five-day mortality was lower in the TPE group (20.9% vs. 34.1% in controls), but this did not reach statistical significance [Kaplan-Meir analysis: p=0.582). TPE was associated with increased lymphocytes and ADAMTS-13 activity; plus decreased serum lactate, lactate dehydrogenase, ferritin, D-dimers, and interleukin-6. Multivariable regression analysis provided several predictors of 35-day mortality: PaO 2 /FiO 2 ratio [hazard ratio (HR): 0.98, 95% CI: 0.96-1.00, p=0.02], ADAMTS-13 activity (HR: 0.89, 95% CI: 0.82-0.98, p=0.01), and PE (HR: 3.57, 95% CI: 1.43-8.92, p=0.007). Post-hoc analysis revealed a significant reduction in SOFA score for TPE patients (p<0.05) compared to controls. Conclusion In critically ill COVID-19 patients the addition of TPE to standard ICU therapy was associated with faster clinical recovery and no increased 35-day mortality.

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“…Hemadsorption techniques targeting circulating in ammatory mediators may lead to a re-balancing of the internal cytokine milieu. Several case series and small studies in patients with COVID-19 or septic shock have shown promising results using hemadsorption (18,20,34,35). Although initial reports suggested uncontrolled cytokine response in patients with COVID-19, cytokine levels have been reported to be not as high as compared to other causes of ARDS (10,11,36).…”

Section: Analysis Of Endpoints and Outcomesmentioning

confidence: 99%

Effect of Hemadsorption in Critically Ill Patients with COVID-19 (CYTOCOV-19): A Prospective Randomized Controlled Pilot Trial

Jarczak

Roedl

Fischer

et al. 2021

Preprint

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Purpose: Immunomodulatory therapies have shown beneficial effects in patients with severe COVID-19. Patients with hypercytokinemia might benefit from removal of inflammatory mediators via hemadsorption.Methods: Single-center prospective randomized trial at the University Medical Center Hamburg-Eppendorf (Germany). Patients with confirmed COVID-19, refractory shock (norepinephrine ≥0.2 μg/kg/min to maintain a mean arterial pressure ≥ 65 mmHg), IL-6≥500 ng/l and an indication for renal replacement therapy (RRT) or extracorporeal membrane oxygenation (ECMO) were included. Patients received either hemadsorption therapy (HT) or standard medical therapy (SMT). For HT, a CytoSorb® adsorber was used for up to 5 days and was replaced every 18–24 hours. The primary endpoint was sustained hemodynamic improvement (norepinephrine ≤0.05 µg/kg/min≥24h). Secondary endpoints included 28-day mortality, SOFA, and reduction of IL-6, PCT, and MR-proADM. Results: Of 242 screened patients, 24 were randomized and assigned to either HT (N=12) or SMT (N=12). Both groups had similar severity as assessed by SAPS II (median 75 points HT group vs. 79 SMT group, p=0.590) and SOFA (17 vs. 16, p=0.551). At randomization, 22 (92%) patients were on RRT and 11 (46%) had vv-ECMO. Median IL-6 levels were 2269 (IQR 948–3679) and 3747 (1301–5415) ng/l in the HT and SMT group at baseline, respectively (p=0.378). Serum IL-6 reduction in the first 24h of treatment compared between both groups was 83% vs. 46% (p=0.235). Shock resolution (primary endpoint) was reached in 33% (4/12) vs. 17% (2/12) in the HT and SMT group, respectively (p=0.640). 28-day mortality was 58% (7/12) in the HT compared to 67% (8/12) in the SMT group (p=1.0).Conclusion: HT was associated with a non-significant trend towards clinical improvement within the intervention period including reduction of IL-6 levels and shock resolution. In selected patients, HT might therefore be an option for stabilization and bridge to transfer and decision. (Trial registration: ClinicalTrials.gov: NCT04344080, https://clinicaltrials.gov/ct2/show/NCT04344080, trial registration date 04/14/2020)]

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Continuous renal replacement therapy with the addition of CytoSorb cartridge in critically ill patients with COVID‐19 plus acute kidney injury: A case‐series

Cited by 65 publications

References 83 publications

The Potential Role of Extracorporeal Cytokine Removal in Hemodynamic Stabilization in Hyperinflammatory Shock

The Potential Role of Extracorporeal Cytokine Removal in Hemodynamic Stabilization in Hyperinflammatory Shock

Therapeutic plasma exchange in patients with life-threatening COVID-19: a randomised controlled clinical trial

Effect of Hemadsorption in Critically Ill Patients with COVID-19 (CYTOCOV-19): A Prospective Randomized Controlled Pilot Trial

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