Combined extracorporeal CO2 removal and renal replacement therapy in a pregnant patient with COVID-19: a case report.

Background. Pregnant women are at high risk of Coronavirus disease 2019 (COVID-19) complications, including acute respiratory distress syndrome. Currently, one of the cornerstones in the treatment of this condition is lung-protective ventilation (LPV) with low tidal volumes. However, the occurrence of hypercapnia may limit this ventilatory strategy. So, different extracorporeal CO2 removal (ECCO2R) procedures have been developed. ECCO2R comprises a variety of techniques, including low-flow and high-flow systems, that may be performed with dedicated devices or combined with continuous renal replacement therapy (CRRT). Case description. Here, we report a unique case of a pregnant patient affected by COVID-19 who required extracorporeal support for multiorgan failure. While on LPV, because of the concomitant hypercapnia and acute kidney injury, the patient was treated with an ECCO2R membrane inserted in series after a hemofilter in a CRRT platform. This combined treatment reducing hypercapnia allowed LPV maintenance at the same time while providing kidney replacement and ensuring maternal and fetal hemodynamic stability. Adverse effects consisted of minor bleeding episodes due to the anticoagulation required to maintain the extracorporeal circuit patency. The patient's pulmonary and kidney function progressively recovered, permitting the withdrawal of any extracorporeal treatment. At the 25th gestational week, the patient underwent spontaneous premature vaginal delivery because of placental abruption. She gave birth to an 800-gram female baby, who three days later died because of multiorgan failure related to extreme prematurity. Conclusions. This case supports using ECCO2R-CRRT combined treatment as a suitable approach in the management of complex conditions, such as pregnancy, even in the case of severe COVID-19.

Therapeutic plasma exchange and continuous renal replacement therapy in pediatric dengue-associated acute liver failure: A case series from Vietnam.

BACKGROUND AND OBJECTIVES: Paediatric dengue-associated acute liver failure (PALF) is a rare and fatal complication. To date, clinical data regarding the combination of therapeutic plasma exchange (TPE) and continuous renal replacement therapy (CRRT) for the treatment of dengue-associated PALF are limited. METHODS: We conducted a single-center, retrospective study of all children with dengue-associated PALF admitted to the paediatric intensive care unit of Children Hospital No.2, Vietnam, who were treated with TPE+CRRT between January 2021 and March 2022. The main study outcomes were in-hospital survival, normalisation of hepatic function, and hepatic encephalopathy improvement. RESULTS: Twelve patients aged from 06 to 12 years underwent TPE+CRRT procedures. Among them, three (25 %) patients died of severe sepsis and septic shock confirmed by Enterobacteriaceae spp. haemocultures (stable on maintenance treatment of COVID-19-associated MIS-C with low dose of oral steroids on hospital admission), acute respiratory distress syndrome (ARDS), and clinically apparent intracranial haemorrhage. Nine patients (75 %) survived. The paediatric mortality risk score improved significantly at discharge compared with PICU admission (P < 0.01). Markedly, all twelve patients were diagnosed with hepatoencephalopathy of grades III and IV on PICU admission. After the combined TPE+CRRT interventions, there were substantial improvements in liver transaminases levels, coagulation profiles, and metabolic biomarkers. Normal neurological functions were observed in nine alive patients at hospital discharge. Only one patient experienced an adverse event of slightly low blood pressure, which rapidly self-resolved. INTERPRETATION AND CONCLUSIONS: Combined TPE+CRRT significantly improved survival outcome, neurological status, and rapid normalisation of liver functions in dengue-associated PALF.

Target attainment and population pharmacokinetics of flucloxacillin in critically ill patients: a multicenter study.

PURPOSE: Insufficient antimicrobial exposure has been associated with worse clinical outcomes. Reportedly, flucloxacillin target attainment in critically ill patients was heterogeneous considering the study population selection and reported target attainment percentages. Therefore, we assessed flucloxacillin population pharmacokinetics (PK) and target attainment in critically ill patients. METHODS: This prospective, multicenter, observational study was conducted from May 2017 to October 2019 and included adult, critically ill patients administered flucloxacillin intravenously. Patients with renal replacement therapy or liver cirrhosis were excluded. We developed and qualified an integrated PK model for total and unbound serum flucloxacillin concentrations. Monte Carlo dosing simulations were performed to assess target attainment. The unbound target serum concentration was four times the minimum inhibitory concentration (MIC) for ≥ 50% of the dosing interval (ƒT>4xMIC ≥ 50%). RESULTS: We analyzed 163 blood samples from 31 patients. A one-compartment model with linear plasma protein binding was selected as most appropriate. Dosing simulations revealed 26% ƒT>2 mg/L ≥ 50% following continuous infusion of 12 g flucloxacillin and 51% ƒT>2 mg/L ≥ 50% for 24 g. CONCLUSION: Based on our dosing simulations, standard flucloxacillin daily doses of up to 12 g may substantially enhance the risk of underdosing in critically ill patients. Prospective validation of these model predictions is needed.

CVVHD results in longer filter life than pre-filter CVVH: Results of a quasi-randomized clinical trial.

BACKGROUND: Filter clotting is a major issue in continuous kidney replacement therapy (CKRT) that interrupts treatment, reduces delivered effluent dose, and increases cost of care. While a number of variables are involved in filter life, treatment modality is an understudied factor. We hypothesized that filters in pre-filter continuous venovenous hemofiltration (CVVH) would have shorter lifespans than in continuous venovenous hemodialysis (CVVHD). METHODS: This was a single center, pragmatic, unblinded, quasi-randomized cluster trial conducted in critically ill adult patients with severe acute kidney injury (AKI) at the University of Iowa Hospitals and Clinics (UIHC) between March 2020 and December 2020. Patients were quasi-randomized by time block to receive pre-filter CVVH (convection) or CVVHD (diffusion). The primary outcome was filter life, and secondary outcomes were number of filters used, number of filters reaching 72 hours, and in-hospital mortality. RESULTS: In the intention-to-treat analysis, filter life in pre-filter CVVH was 79% of that observed in CVVHD (mean ratio 0.79, 95% CI 0.65-0.97, p = 0.02). Median filter life (with interquartile range) in pre-filter CVVH was 21.8 (11.4-45.3) and was 26.6 (13.0-63.5) for CVVHD. In addition, 11.8% of filters in pre-filter CVVH were active for >72 hours, versus 21.2% in the CVVHD group. Finally, filter clotting accounted for the loss of 26.7% of filters in the CVVH group compared to 17.5% in the CVVHD group. There were no differences in overall numbers of filters used or mortality between groups. CONCLUSIONS: Among critically patients with severe AKI requiring CKRT, use of pre-filter CVVH resulted in significantly shorter filter life compared to CVVHD. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04762524. Registered 02/21/21-Retroactively registered, https://clinicaltrials.gov/ct2/show/NCT04762524?cond=The+Impact+of+CRRT+Modality+on+Filter+Life&draw=2&rank=1.

The Sequential Use of Extracorporeal Cytokine Removal Devices in an Adolescent With COVID-19 Receiving Continuous Renal Replacement Therapy.

A 14-year-old male developed multisystem inflammatory syndrome in children (MIS-C) after acquiring the SARS-CoV-2 infection. He deteriorated rapidly requiring inotropic and ventilatory support as well as continuous renal replacement therapy (CRRT) due to rhabdomyolysis-associated acute kidney injury. A hemoadsoprtion column Cytosorb® was first incorporated into the CRRT circuit for myoglobin and cytokines removal, which was followed by sequential use of another type of cytokine-removing hemofilter (Oxiris®) (altogether 100 hours of extracorporeal blood purification [EBP] therapy). There was no major complication related to the EBP therapy. Cytokine profile revealed a marked reduction of levels of several cytokines including tumor necrosis factor-α, interleukin (IL)-6, IL-8, and IL-10 after the EBP therapy. It was noted that both pro-inflammatory and anti-inflammatory cytokines were removed, and the removal efficacy varied between different devices. His condition improved and the serum ferritin, C-reactive protein, and procalcitonin levels also dropped gradually, which correlated well with his clinical progress and the trend of cytokine levels. Our case demonstrated that extracorporeal cytokine removal can be safely applied in children with MIS-C and can be considered as adjunctive therapy in selected patients with critically ill conditions.

Fluid balance neutralization secured by hemodynamic monitoring versus protocolized standard of care in critically ill patients requiring continuous renal replacement therapy: study protocol of the GO NEUTRAL randomized controlled trial.

BACKGROUND: Fluid overload is associated with worse outcome in critically ill patients requiring continuous renal replacement therapy (CRRT). Net ultrafiltration (UFNET) allows precise control of the fluid removal but is frequently ceased due to hemodynamic instability episodes. However, approximately 50% of the hemodynamic instability episodes in ICU patients treated with CRRT are not associated with preload dependence (i.e., are not related to a decrease in cardiac preload), suggesting that volume removal is not responsible for these episodes of hemodynamic impairment. The use of advanced hemodynamic monitoring, comprising continuous cardiac output monitoring to repeatedly assess preload dependency, could allow securing UFNET to allow fluid balance control and prevent fluid overload. METHODS: The GO NEUTRAL trial is a multicenter, open-labeled, randomized, controlled, superiority trial with parallel groups and balanced randomization with a 1:1 ratio. The trial will enroll adult patients with acute circulatory failure treated with vasopressors and severe acute kidney injury requiring CRRT who already have been equipped with a continuous cardiac output monitoring device. After informed consent, patients will be randomized into two groups. The control group will receive protocolized fluid removal with an UFNET rate set to 0-25 ml h-1 between inclusion and H72 of inclusion. The intervention group will be treated with an UFNET rate set on the CRRT of at least 100 ml h-1 between inclusion and H72 of inclusion if hemodynamically tolerated based on a protocolized hemodynamic protocol aiming to adjust UFNET based on cardiac output, arterial lactate concentration, and preload dependence assessment by postural maneuvers, performed regularly during nursing rounds, and in case of a hemodynamic instability episode. The primary outcome of the study will be the cumulative fluid balance between inclusion and H72 of inclusion. Randomization will be generated using random block sizes and stratified based on fluid overload status at inclusion. The main outcome will be analyzed in the modified intention-to-treat population, defined as all alive patients at H72 of inclusion, based on their initial allocation group. DISCUSSION: We present in the present protocol all study procedures in regard to the achievement of the GO NEUTRAL trial, to prevent biased analysis of trial outcomes and improve the transparency of the trial result report. Enrollment of patients in the GO NEUTRAL trial has started on June 31, 2021, and is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov NCT04801784. Registered on March 12, 2021, before the start of inclusion.

Maintenance of the critical care system during the pandemic in non-COVID-19 patients requiring continuous renal replacement therapy: a single center experience.

BACKGROUND: During the COVID-19 pandemic, maintenance of essential healthcare systems became very challenging. We describe the triage system of our institute, and assess the quality of care provided to critically ill non-COVID-19 patients requiring continuous renal replacement therapy (CRRT) during the pandemic. METHODS: We introduced an emergency triage pathway early in the pandemic. We retrospectively reviewed the medical records of patients who received CRRT in our hospital from January 2016 to March 2021. We excluded end-stage kidney disease patients on maintenance dialysis. Patients were stratified as medical and surgical patients. The time from hospital arrival to intensive care unit (ICU) admission, the time from hospital arrival to intervention/operation, and the in-hospital mortality rate were compared before (January 2016 to December 2019) and during (January 2021 to March 2021) the pandemic. RESULTS: The mean number of critically ill patients who received CRRT annually in the surgical department significantly decreased during the pandemic in (2016-2019: 76.5 ± 3.1; 2020: 56; p < 0.010). Age, sex, and the severity of disease at admission did not change, whereas the proportions of medical patients with diabetes (before: 44.4%; after: 56.5; p < 0.005) and cancer (before: 19.4%; after: 32.3%; p < 0.001) increased during the pandemic. The time from hospital arrival to ICU admission and the time from hospital arrival to intervention/operation did not change. During the pandemic, 59.6% of surgical patients received interventions/operations within 6 hours of hospital arrival. In Cox's proportional hazard modeling, the hazard ratio associated with the pandemic was 1.002 (0.778-1.292) for medical patients and 1.178 (0.783-1.772) for surgical patients. CONCLUSION: Our triage system maintained the care required by critically ill non-COVID-19 patients undergoing CRRT at our institution.

Mortality and renal long-term outcome of critically ill COVID-19 patients with acute kidney failure, continuous renal replacement therapy and invasive mechanical ventilation. / Mortalidad y función renal a largo plazo en pacientes ingresados en la UCI por COVID-19 con fracaso renal agudo, terapia continua de reemplazo renal y ventilación mecánica invasiva.

BACKGROUND: There are limited data describing the long-term renal outcomes of critically ill COVID-19 patients with acute kidney injury (AKI) and continuous renal replacement therapy (CRRT) and invasive mechanical ventilation. METHODS: In this retrospective observational study we analyzed the long-term clinical course and outcomes of 30 critically ill patients hospitalized with COVID-19 during the peak of highest incidence in the first wave, with acute respiratory distress syndrome (ARDS) and AKI that required CRRT. Baseline features, clinical course, laboratory data, therapies and filters used in CRRT were compared between survivors and non-survivors to identify risk factors associated with in-hospital death. Renal parameters: glomerular filtration rate, proteinuria and microhematuria were collected at 6months after discharge. RESULTS: 19 patients (63%) died and 11 were discharged. Mean time to death was 48days (7-206) after admission. Patients with worse baseline renal function had higher mortality (P=.009). Patients were treated with CRRT for an average of 18.4days. Filters with adsorptive capacity (43%) did not offer survival benefits. Regarding long-term renal outcomes, survivor patients did not receive any additional dialysis, but 9 out of 11 patients had an important loss of renal function (median of eGF of 44 (13-76)ml/min/1.73m2) after 6months. CONCLUSION: Mortality among critically ill hospitalized patients diagnosed with COVID-19 on CRRT is extremely high (63%). Baseline renal function is a predictor factor of mortality. Filters with adsorption capacity did not modify survival. None survivor patients required long-term dialysis, but an important loss of renal function occurred after AKI episode related to COVID-19 infection.

Protocol for Local On-Site Dialysate Production for Continuous Renal Replacement Therapy during the COVID-19 Pandemic.

AKI frequently occurs in patients with COVID-19, and kidney injury severe enough to require RRT is a common complication among patients who are critically ill. During the surge of the pandemic, there was a high demand for dialysate for continuous RRT, and this increase in demand, coupled with vulnerabilities in the supply chain, necessitated alternative approaches, including internal production of dialysate. Using a standard hemodialysis machine and off-the-shelf supplies, as per Food and Drug Administration guidelines, we developed a method for on-site dialysate production that is adaptable and can be used to fill multiple bags at once. The use of a central reverse osmosis unit, dedicated hemodialysis machine, sterile bags with separate ports for fill and use, and frequent testing will ensure stability, sterility, and-therefore-safety of the produced dialysate. The dialysate made in house was tested and it showed both stability and sterility for at least 30 hours. This detailed description of our process for generating dialysate can serve as a guide for other programs experiencing similar vulnerabilities in the demand versus supply of dialysate.

Regional citrate and systemic heparin are adequate to maintain filter half-life for COVID-19 patients on continuous renal replacement therapy.

INTRODUCTION: The aim of our study is to compare clotting of CRRT filters in patients with COVID-19-associated AKI versus septic shock-associated AKI. METHODS: Retrospective study of adult ICU patients with COVID-19 compared to those with septic shock admitted to a tertiary hospital April-October 2020. Independent t test and chi-square test used to determine statistical significance of CRRT filter clotting between the two groups. Time-to-event data analyzed with Kaplan-Meier curves. Analyses performed on Microsoft Excel and MedCalc. RESULTS: Twenty-seven ICU patients with AKI requiring CRRT were included, 13 with COVID-19 and 14 non-COVID-19 patients with septic shock. The mean half-life of CRRT hemofilter was similar in COVID-19 patients compared to non-COVID-19 patients (27.4 vs. 27.5 h, p = 0.79). The number of CRRT hemofilter changes per day was similar in both groups (0.6 filter changes per day, p = 0.84). However, significantly more patients with COVID-19 were on systemic heparin (69% vs. 13%, p = 0.02). CONCLUSION: We found that COVID-19 patients with AKI requiring CRRT had similar CRRT hemofilter half-life compared with sepsis-associated AKI patients with use of regional citrate and systemic heparin. Further studies are needed to find which methods of anticoagulation are optimal in patients with COVID-19 infection with AKI requiring CRRT.

Renal Tubular Acidosis in Critically Ill Patients with Coronavirus Disease 2019 Acute Respiratory Distress Syndrome.

The coronavirus disease 2019 (COVID-19) infection associated with multisystemic involvement including renal manifestations has been described in the literature. The recent data show a high mortality rate of 60%-90% once renal function begins to deteriorate. We report on three patients who were admitted to intensive care unit due to severe COVID-19 acute respiratory distress syndrome and developed distal renal tubular acidosis. The three COVID-19 patients had hyperchloremic acidosis which was investigated thoroughly through a biochemical analysis of arterial blood gases and urine test as well as serological tests for autoimmune diseases and chronic infections, in addition to renal ultrasound. Metabolic acidosis was managed through repeated doses of intravenous sodium bicarbonate therapy; however, continuous renal replacement therapy was initiated for two refractory cases. We found that severe COVID-19 infection may be accompanied by hyperchloremic acidosis due to the cytopathic damage of the distal renal tubules, making the buffering system nonefficient and if not managed adequately, it may lead to poor prognosis.

Hemodialysis during Lockdown Due to Coronavirus Disease 2019 Pandemic in Eastern Saudi Arabia.

The first case of Coronavirus disease-2019 (COVID-19) in the Kingdom of Saudi Arabia was confirmed in the city of Qatif in March 2020. As a result, Qatif was placed under lockdown for two months in an attempt to prevent the widespread of COVID-19. Doing hemodialysis (HD) during lockdown was a new and challenging experience that we recently have faced. Swift arrangements were made to accommodate patients with end-stage renal disease in need for HD. The challenges to healthcare facilities, healthcare providers, and patients are discussed with the hope that this experience would help mitigate some of the difficulties healthcare providers may face in a similar situation.

Efficacy and complications of regional citrate anticoagulation during continuous renal replacement therapy in critically ill patients with COVID-19.

BACKGROUND: We compared filter survival and citrate-induced complications during continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) in COVID-19 and Non-COVID-19 patients. METHODS: In this retrospective study we included all consecutive adult patients (n = 97) treated with RCA-CRRT. Efficacy and complications of RCA-CRRT were compared between COVID-19 and Non-COVID-19 patients. RESULTS: Mean filter run-time was significantly higher in COVID-19 patients compared to Non-COVID-19 patients (68.4 (95%CI 67.0-69.9) vs. 65.2 (95%CI 63.2-67.2) hours, respectively; log-rank 0.014). COVID-19 patients showed significantly higher activated partial thromboplastin time (aPTT) throughout the CRRT due to intensified systemic anticoagulation compared to Non-COVID-19 patients (54 (IQR 45-61) vs. 47 (IQR 41-58) seconds, respectively; p < 0.001). A significantly higher incidence of metabolic alkalosis, hypercalcemia and hypernatremia, consistent with reduced filter patency and citrate overload, was observed in COVID-19 patients compared to Non-COVID-19 patients (19.1% vs. 12.7%, respectively; p = 0.04). These metabolic disarrangements were resistant to per-protocol adjustments and disappeared after replacement of the CRRT-filter. CONCLUSIONS: RCA-CRRT in COVID-19 patients with intensified systemic anticoagulation provides an adequate filter lifespan. However, close monitoring of the acid-base balance appears warranted, as these patients tend to develop reduced filter patency leading to a higher incidence of citrate overload and metabolic disturbances. TRIAL REGISTRATION (LOCAL AUTHORITY): EA1/285/20 (Ethikkommission der Charité - Universitätsmedizin Berlin); date of registration 08.10.2020.

Continuous Renal Replacement Therapy among Patients with COVID-19 and Acute Kidney Injury.

BACKGROUND AND OBJECTIVES: Acute kidney injury (AKI) is a common complication among patients with COVID-19 and acute respiratory distress syndrome. Reports suggest that COVID-19 confers a pro-thrombotic state, which presents challenges in maintaining hemofilter patency and delivering continuous renal replacement therapy (CRRT). We present our initial experience with CRRT in critically ill patients with COVID-19, emphasizing circuit patency and the association between fluid balance during CRRT and respiratory parameters. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Retrospective chart review of 32 consecutive patients with COVID-19 and AKI managed with continuous venovenous hemodiafiltration with regional citrate anticoagulation (CVVHDF-RCA) according to the University of Michigan protocol. Primary outcome was mean CRRT circuit life per patient during the first 7 days of CRRT. We used simple linear regression to assess the relationship between patient characteristics and filter life. We also explored the relationship between fluid balance on CRRT and respiratory parameters using repeated measures modeling. RESULTS: Patients' mean age was 54.8 years and majority were Black (75%). Comorbidities included hypertension (90.6%), obesity (70.9%) diabetes (56.2%), and chronic kidney disease (40.6%). Median CRRT circuit life was 53.5 [interquartile range 39.1-77.6] hours. There was no association between circuit life and inflammatory or pro-thrombotic laboratory values (ferritin p = 0.92, C-reactive protein p = 0.29, D-dimer p = 0.24), or with systemic anticoagulation (p = 0.37). Net daily fluid removal during the first 7 days of CRRT was not associated with daily (closest recorded values to 20:00) PaO2/FIO2 ratio (p = 0.21) or positive end-expiratory pressure requirements (p = 0.47). CONCLUSIONS: We achieved adequate CRRT circuit life in COVID-19 patients using an established CVVHDF-RCA protocol. During the first 7 days of CRRT therapy, cumulative fluid balance was not associated with improvements in respiratory parameters, even after accounting for baseline fluid balance.

Continuous renal replacement therapy under special conditions like sepsis, burn, cardiac failure, neurotrauma, and liver failure.

Continuous renal replacement therapy (CRRT) in sepsis does have a role in removing excessive fluid, and also role in removal of mediators although not proven today, and to allow fluid space in order to feed. In these conditions, continuous renal replacement therapy can improve morbidity but never mortality so far. Regarding sepsis, timing has become a more important issue after decades and is currently more discussed than dosing. Rationale of blood purification has evolved a lot in the last years regarding sepsis with the discovery of many types of sorbent allowing ideas from science fiction to become reality in 2021. Undoubtedly, COVID-19 has reactivated the interest of blood purification in sepsis but also in COVID-19. Burn is even more dependent about removal of excessive fluid as compared to sepsis. Regarding cardiac failure, ultrafiltration can improve the quality of life and morbidity when diuretics are becoming inefficient but can never improve mortality. Regarding brain injury, CRRTs have several advantages as compared to intermittent hemodialysis. In liver failure, there have been no randomized controlled trials to examine whether single-pass albumin dialysis offers advantages over standard supportive care, and there is always the cost of albumin.