Continuous renal replacement therapy in COVID-19-associated AKI: adding heparin to citrate to extend filter life-a retrospective cohort study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) may predispose patients to thrombotic events. The best anticoagulation strategy for continuous renal replacement therapy (CRRT) in such patients is still under debate. The purpose of this study was to evaluate the impact that different anticoagulation protocols have on filter clotting risk. METHODS: This was a retrospective observational study comparing two different anticoagulation strategies (citrate only and citrate plus intravenous infusion of unfractionated heparin) in patients with acute kidney injury (AKI), associated or not with COVID-19 (COV + AKI and COV - AKI, respectively), who were submitted to CRRT. Filter clotting risks were compared among groups. RESULTS: Between January 2019 and July 2020, 238 patients were evaluated: 188 in the COV + AKI group and 50 in the COV - AKI group. Filter clotting during the first filter use occurred in 111 patients (46.6%). Heparin use conferred protection against filter clotting (HR = 0.37, 95% CI 0.25-0.55), resulting in longer filter survival. Bleeding events and the need for blood transfusion were similar between the citrate only and citrate plus unfractionated heparin strategies. In-hospital mortality was higher among the COV + AKI patients than among the COV - AKI patients, although it was similar between the COV + AKI patients who received heparin and those who did not. Filter clotting was more common in patients with D-dimer levels above the median (5990 ng/ml). In the multivariate analysis, heparin was associated with a lower risk of filter clotting (HR = 0.28, 95% CI 0.18-0.43), whereas an elevated D-dimer level and high hemoglobin were found to be risk factors for circuit clotting. A diagnosis of COVID-19 was marginally associated with an increased risk of circuit clotting (HR = 2.15, 95% CI 0.99-4.68). CONCLUSIONS: In COV + AKI patients, adding systemic heparin to standard regional citrate anticoagulation may prolong CRRT filter patency by reducing clotting risk with a low risk of complications.

Continuous venous hemodialysis integrated to the ECMO circuit in critically ill patient with COVID-19, a case report in Morocco.

Novel coronavirus 2019 (COVID-19) is a severe respiratory infection leading to acute respiratory distress syndrome [ARDS] accounting for thousands of cases and deaths across the world. Several alternatives in treatment options have been assessed and used in this patient population. However, when mechanical ventilation and prone positioning are unsuccessful, venovenous extracorporeal membrane oxygenation [VV-ECMO] may be used. We present a case of a 62-year-old female, diabetic, admitted to the intensive care unit with fever, flu-like symptoms and a positive COVID-19 test. Ultimately, she worsened on mechanical ventilation and prone positioning and required VV-ECMO. The use of VV-ECMO in COVID-19 infected patients is still controversial. While some studies have shown a high mortality rate despite aggressive treatment, such as in our case, the lack of large sample size studies and treatment alternatives places healthcare providers against a wall without options in patients with severe refractory ARDS due to COVID-19.

Provision of acute renal replacement therapy, using three separate modalities, in critically ill patients during the COVID-19 pandemic. An after action review from a UK tertiary critical care centre.

PURPOSE: The aim of this study is to describe the incidence of Acute Kidney Injury (AKI) amongst patients admitted to the Intensive Care Unit (ICU) with COVID-19. In addition we aim to detail the range of Renal Replacement Therapy (RRT) modalities offered to these patients (including peritoneal dialysis - PD - and intermittent haemodialysis - IHD) in order to meet demand during pandemic conditions. MATERIALS AND METHODS: Single-centre retrospective case note review of adult patients with confirmed COVID-19 admitted to ICU. RESULTS: Amongst 136 patients without a prior history of End Stage Kidney Disease (ESKD), 108 (79%) developed AKI and 63% of admitted patients received RRT. Due to resource limitations the range of RRT options were expanded from solely Continuous Veno-Venous HaemoDiaFiltration (CVVHDF - our usual standard of care) to include PD (in 35 patients) and IHD (in 15 patients). During the study period the proportion of RRT provided within ICU as CVVHDF fell from 100% to a nadir of 39%. There were no significant complications of either PD or IHD. CONCLUSIONS: During periods of resource limitations PD and IHD can safely be used to reduce dependence on CVVHDF in select patients with AKI secondary to COVID-19.

Deployment of a New CRRT/PIRRT Device during the COVID-19 Pandemic Emergency: Organizational Challenges and Implementation Results.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic led to increased demand nationwide for dialysis equipment, including supplies and machines. To meet the demand in our institution, our surge plan included rapid mobilization of a novel continuous renal replacement treatment (CRRT) machine named SAMI. The SAMI is a push-pull filtration enhanced dialysis machine that can conjugate extremely high single-pass solute removal efficiency with very precise fluid balance control. MATERIAL AND METHODS: Machine assembly was conducted on-site by local biomedical engineers with remote assistance by the vendor. One 3-h virtual training session of 3 dialysis nurses was conducted before SAMI deployment. The SAMI was deployed in prolonged intermittent replacement therapy (PIRRT) mode to maximize patients covered per machine per day. Live on-demand vendor support was provided to troubleshoot any issues for the first few cases. After 4 weeks of the SAMI implementation, data on treatments with the SAMI were collected, and a questionnaire was provided to the nurse trainees to assess device usability. RESULTS: On-site installation of the SAMI was accomplished with remote assistance. Delivery of remote training was successfully achieved. 23 PIRRT treatments were conducted in 10 patients. 7/10 of patients had CO-VID-19. The median PIRRT dose was 50 mL/kg/h (IQR [interquartile range] 44 - 62 mL/kg/h), and duration of the treatment was 8 h (IQR 6.3 - 8 h). Solute control was adequate. The user response was favorable to the set of usability questions involving user interface, on-screen instructions, machine setup, troubleshooting, and the ease of moving the machine. CONCLUSION: Assembly of the SAMI and training of nurses remotely are possible when access to vendor employees is restricted during states of emergency. The successful deployment of the SAMI in our institution during the pandemic with only 3-h virtual training supports that operating the SAMI is simple and safe.

Filter clotting with continuous renal replacement therapy in COVID-19.

Coronavirus disease 2019 (COVID-19) appears to be associated with increased arterial and venous thromboembolic disease. These presumed abnormalities in hemostasis have been associated with filter clotting during continuous renal replacement therapy (CRRT). We aimed to characterize the burden of CRRT filter clotting in COVID-19 infection and to describe a CRRT anticoagulation protocol that used anti-factor Xa levels for systemic heparin dosing. Multi-center study of consecutive patients with COVID-19 receiving CRRT. Primary outcome was CRRT filter loss. Sixty-five patients were analyzed, including 17 using an anti-factor Xa protocol to guide systemic heparin dosing. Fifty-four out of 65 patients (83%) lost at least one filter. Median first filter survival time was 6.5 [2.5, 33.5] h. There was no difference in first or second filter loss between the anti-Xa protocol and standard of care anticoagulation groups, however fewer patients lost their third filter in the protocolized group (55% vs. 93%) resulting in a longer median third filter survival time (24 [15.1, 54.2] vs. 17.3 [9.5, 35.1] h, p = 0.04). The rate of CRRT filter loss is high in COVID-19 infection. An anticoagulation protocol using systemic unfractionated heparin, dosed by anti-factor Xa levels is reasonable approach to anticoagulation in this population.

Management of Acute Kidney Injury in Coronavirus Disease 2019.

Acute kidney injury is a common complication in hospitalized patients with coronavirus disease 2019. Similar to acute kidney injury associated with other conditions such as sepsis and cardiac surgery, morbidity and mortality are much higher in patients with coronavirus disease 2019 who develop acute kidney injury, especially in the intensive care unit. Management of coronavirus disease 2019-associated acute kidney injury with kidney replacement therapy should follow existing recommendations regarding modality, dose, and timing of initiation. However, patients with coronavirus disease 2019 are very hypercoagulable, and close vigilance to anticoagulation strategies is necessary to prevent circuit clotting. During situations of acute surge, where demand for kidney replacement therapy outweighs supplies, conservative measures have to be implemented to safely delay kidney replacement therapy. A collaborative effort and careful planning is needed to conserve dialysis supplies, to ensure that treatment can be safely delivered to every patient who will benefit for kidney replacement therapy.

Estimating Shortages in Capacity to Deliver Continuous Kidney Replacement Therapy During the COVID-19 Pandemic in the United States.

RATIONALE & OBJECTIVE: During the coronavirus disease 2019 (COVID-19) pandemic, New York encountered shortages in continuous kidney replacement therapy (CKRT) capacity for critically ill patients with acute kidney injury stage 3 requiring dialysis. To inform planning for current and future crises, we estimated CKRT demand and capacity during the initial wave of the US COVID-19 pandemic. STUDY DESIGN: We developed mathematical models to project nationwide and statewide CKRT demand and capacity. Data sources included the Institute for Health Metrics and Evaluation model, the Harvard Global Health Institute model, and published literature. SETTING & POPULATION: US patients hospitalized during the initial wave of the COVID-19 pandemic (February 6, 2020, to August 4, 2020). INTERVENTION: CKRT. OUTCOMES: CKRT demand and capacity at peak resource use; number of states projected to encounter CKRT shortages. MODEL, PERSPECTIVE, & TIMEFRAME: Health sector perspective with a 6-month time horizon. RESULTS: Under base-case model assumptions, there was a nationwide CKRT capacity of 7,032 machines, an estimated shortage of 1,088 (95% uncertainty interval, 910-1,568) machines, and shortages in 6 states at peak resource use. In sensitivity analyses, varying assumptions around: (1) the number of pre-COVID-19 surplus CKRT machines available and (2) the incidence of acute kidney injury stage 3 requiring dialysis requiring CKRT among hospitalized patients with COVID-19 resulted in projected shortages in 3 to 8 states (933-1,282 machines) and 4 to 8 states (945-1,723 machines), respectively. In the best- and worst-case scenarios, there were shortages in 3 and 26 states (614 and 4,540 machines). LIMITATIONS: Parameter estimates are influenced by assumptions made in the absence of published data for CKRT capacity and by the Institute for Health Metrics and Evaluation model's limitations. CONCLUSIONS: Several US states are projected to encounter CKRT shortages during the COVID-19 pandemic. These findings, although based on limited data for CKRT demand and capacity, suggest there being value during health care crises such as the COVID-19 pandemic in establishing an inpatient kidney replacement therapy national registry and maintaining a national stockpile of CKRT equipment.

Acute Kidney Injury and Special Considerations during Renal Replacement Therapy in Children with Coronavirus Disease-19: Perspective from the Critical Care Nephrology Section of the European Society of Paediatric and Neonatal Intensive Care.

Children seem to be less severely affected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) as compared to adults. Little is known about the prevalence and pathogenesis of acute kidney injury (AKI) in children affected by SARS-CoV-2. Dehydration seems to be the most common trigger factor, and meticulous attention to fluid status is imperative. The principles of initiation, prescription, and complications related to renal replacement therapy are the same for coronavirus disease (COVID) patients as for non-COVID patients. Continuous renal replacement therapy (CRRT) remains the most common modality of treatment. When to initiate and what modality to use are dependent on the available resources. Though children are less often and less severely affected, diversion of all hospital resources to manage the adult surge might lead to limited CRRT resources. We describe how these shortages might be mitigated. Where machines are limited, one CRRT machine can be used for multiple patients, providing a limited number of hours of CRRT per day. In this case, increased exchange rates can be used to compensate for the decreased duration of CRRT. If consumables are limited, lower doses of CRRT (15-20 mL/kg/h) for 24 h may be feasible. Hypercoagulability leading to frequent filter clotting is an important issue in these children. Increased doses of unfractionated heparin, combination of heparin and regional citrate anticoagulation, or combination of prostacyclin and heparin might be used. If infusion pumps to deliver anticoagulants are limited, the administration of low-molecular-weight heparin might be considered. Alternatively in children, acute peritoneal dialysis can successfully control both fluid and metabolic disturbances. Intermittent hemodialysis can also be used in patients who are hemodynamically stable. The keys to successfully managing pediatric AKI in a pandemic are flexible use of resources, good understanding of dialysis techniques, and teamwork.

Continuous Renal Replacement Therapy for a Patient with Severe COVID-19.

The outbreak of coronavirus disease 2019 (COVID-19) is a global health threat. It is a respiratory disease, and acute kidney injury (AKI) is rare; however, if a patient develops severe AKI, renal replacement therapy (RRT) should be considered. Recently, we had a critically ill COVID-19 patient who developed severe AKI and needed continuous RRT (CRRT). To avoid the potential risk of infection from CRRT effluents, we measured severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genetic material in the effluents by qRT-PCR, and low copy numbers of the viral genome were detected. Due to unstable hemodynamic status in critically ill patients, CRRT should be the first choice for severe AKI in COVID-19 patients. We suggest prevention of clinical infection and control during administration of RRT in the acute phase of COVID-19 patients with AKI or multiple organ failure.

Extracorporeal Blood Purification and Organ Support in the Critically Ill Patient during COVID-19 Pandemic: Expert Review and Recommendation.

Critically ill COVID-19 patients are generally admitted to the ICU for respiratory insufficiency which can evolve into a multiple-organ dysfunction syndrome requiring extracorporeal organ support. Ongoing advances in technology and science and progress in information technology support the development of integrated multi-organ support platforms for personalized treatment according to the changing needs of the patient. Based on pathophysiological derangements observed in COVID-19 patients, a rationale emerges for sequential extracorporeal therapies designed to remove inflammatory mediators and support different organ systems. In the absence of vaccines or direct therapy for COVID-19, extracorporeal therapies could represent an option to prevent organ failure and improve survival. The enormous demand in care for COVID-19 patients requires an immediate response from the scientific community. Thus, a detailed review of the available technology is provided by experts followed by a series of recommendation based on current experience and opinions, while waiting for generation of robust evidence from trials.

Cytokine storm intervention in the early stages of COVID-19 pneumonia.

Clinical intervention in patients with corona virus disease 2019 (COVID-19) has demonstrated a strong upregulation of cytokine production in patients who are critically ill with SARS-CoV2-induced pneumonia. In a retrospective study of 41 patients with COVID-19, most patients with SARS-CoV-2 infection developed mild symptoms, whereas some patients later developed aggravated disease symptoms, and eventually passed away because of multiple organ dysfunction syndrome (MODS), as a consequence of a severe cytokine storm. Guidelines for the diagnosis and treatment of SARS-CoV-2 infected pneumonia were first published January 30th, 2020; these guidelines recommended for the first time that cytokine monitoring should be applied in severely ill patients to reduce pneumonia related mortality. The cytokine storm observed in COVID-19 illness is also an important component of mortality in other viral diseases, including SARS, MERS and influenza. In view of the severe morbidity and mortality of COVID-19 pneumonia, we review the current understanding of treatment of human coronavirus infections from the perspective of a dysregulated cytokine and immune response.