Hemoperfusion techniques using Jafron HA330 cartridge combined with BBraun Dialog+ dialysis machine in patient with coronavirus disease 2019 pneumonia and septic shock: a case report.

BACKGROUND: The use of hemoperfusion for cytokine removal and inflammatory mediators is increasingly intense, especially in coronavirus disease 2019 patients who are already known to the general public for having cytokine storms. However, we have known about these cytokine storms for a long time in the critical care world. One of the modalities to remove cytokines is to use filtration and adsorption techniques with continuous renal replacement therapy. The use of continuous renal replacement therapy is usually constrained by its very high cost compared with standard care, especially in Indonesia, where health costs are covered by national health insurance. In this case, we use hemodialysis and hemoperfusion, using a dialysis machine, which is more cost-effective and easy to use. CASE PRESENTATION: We used the Jafron HA330 cartridge, modified for the BBraun Dialog+ dialysis machine. This case report presents an 84-year-old Asian man with septic shock due to pneumonia, congestive heart failure, and acute chronic kidney disease accompanied by fluid overload. After undergoing hemodialysis and hemoperfusion separately, there was a gradual and significant clinical improvement. Clinical indicators, including the vasopressor inotropic score and infection markers, should all be considered when deciding whether to begin hemodialysis and hemoperfusion. CONCLUSION: In general, using hemoperfusion to treat septic shock patients can reduce the length of stay in the intensive care unit, and morbidity and mortality.

Recent nanoengineered diagnostic and therapeutic advancements in management of Sepsis.

COVID-19 acquired symptoms have affected the worldwide population and increased the load of Intensive care unit (ICU) patient admissions. A large number of patients admitted to ICU end with a deadly fate of mortality. A high mortality rate of patients was reported with hospital-acquired septic shock that leads to multiple organ failures and ultimately ends with death. The patients who overcome this septic shock suffer from morbidity that also affects their caretakers. To overcome these situations, scientists are exploring progressive theragnostic techniques with advanced techniques based on biosensors, biomarkers, biozymes, vesicles, and others. These advanced techniques pave the novel way for early detection of sepsis-associated symptoms and timely treatment with appropriate antibiotics and immunomodulators and prevent the undue effect on other parts of the body. There are other techniques like externally modulated electric-based devices working on the principle of piezoelectric mechanism that not only sense the endotoxin levels but also target them with a loaded antibiotic to neutralize the onset of inflammatory response. Recently researchers have developed a lipopolysaccharide (LPS) neutralizing cartridge that not only senses the LPS but also appropriately neutralizes with dual mechanistic insights of antibiotic and anti-inflammatory effects. This review will highlight recent developments in the new nanotechnology-based approaches for the diagnosis and therapeutics of sepsis that is responsible for the high number of deaths of patients suffering from this critical disease.

Rationale for sequential extracorporeal therapy (SET) in sepsis.

Sepsis and septic shock remain drivers for morbidity and mortality in critical illness. The clinical picture of patients presenting with these syndromes evolves rapidly and may be characterised by: (a) microbial host invasion, (b) establishment of an infection focus, (c) opsonisation of bacterial products (e.g. lipopolysaccharide), (d) recognition of pathogens resulting in an immune response, (e) cellular and humoral effects of circulating pathogen and pathogen products, (f) immunodysregulation and endocrine effects of cytokines, (g) endothelial and organ damage, and (h) organ crosstalk and multiple organ dysfunction. Each step may be a potential target for a specific therapeutic approach. At various stages, extracorporeal therapies may target circulating molecules for removal. In sequence, we could consider: (a) pathogen removal from the circulation with affinity binders and cartridges (specific), (b) circulating endotoxin removal by haemoperfusion with polymyxin B adsorbers (specific), (c) cytokine removal by haemoperfusion with sorbent cartridges or adsorbing membranes (non-specific), (d) extracorporeal organ support with different techniques for respiratory and cardiac support (CO2 removal or extracorporeal membrane oxygenation), and renal support (haemofiltration, haemodialysis, or ultrafiltration). The sequence of events and the use of different techniques at different points for specific targets will likely require trials with endpoints other than mortality. Instead, the primary objectives should be to achieve the desired action by using extracorporeal therapy at a specific point.

[Pathophysiology of sepsis]. / Pathophysiologie der Sepsis.

Up to now, sepsis is one of the most threatening diseases and its therapy remains challenging. Sepsis is currently defined as a severely dysregulated immune response to an infection resulting in organ dysfunction. The pathophysiology is mainly driven by exogenous PAMPs ("pathogen-associated molecular patterns") and endogenous DAMPs ("damage-associated molecular patterns"), which can activate PRRs ("pattern recognition receptors") on different cell types (mainly immune cells), leading to the initiation of manifold downstream pathways and a perpetuation of patients' immune response. Sepsis is neither an exclusive pro- nor an anti-inflammatory disease: both processes take place in parallel, resulting in an individual immunologic disease state depending on the severity of each component at different time points. Septic shock is a complex disorder of the macro- and microcirculation, provoking a severe lack of oxygenation further aggravating sepsis defining organ dysfunctions. An in-depth knowledge of the heterogeneity and the time-dependency of the septic immunopathology will be essential for the design of future sepsis trials and therapy planning in patients with sepsis. The big aim is to achieve a more individualized treatment strategy in patients suffering from sepsis or septic shock.

[Management of refractory septic shock with blood purification therapy using a special filter. Report of one case]. / COVID-19, shock séptico refractario y terapia extracorpórea de purificación sanguínea con OXIRIS®.

Sepsis is one of the leading causes of death in critically ill patients with COVID-19 and blood purification therapies have a role to immunomodulate the excessive inflammatory response and improve clinical results. One of the devices designed for these therapies is the oXiris® filter, allowing to perform renal replacement therapy combined with selective adsorption of endotoxins and cytokines. We report a 55-year-old male with COVID who developed a septic shock secondary to a sepsis caused by Pseudomona aeruginosa, refractory to the usual management. A veno-venous continuous hemofiltration was started using the oXiris® filter for 48 hours. Subsequently, there was an improvement in clinical perfusion parameters and a reduction in inflammatory markers. The patient was discharged from the intensive care one month later.

Blood purification in sepsis and systemic inflammation.

PURPOSE OF REVIEW: Sepsis and septic shock are life-threatening diseases with high mortality. Although efforts have made to improve the survivals, the outcomes are still frustrating. Blood purification was thought to be a promising adjunctive therapy to regulate the excessive cytokine storm or to reduce the endotoxin activity caused by sepsis. Critically ill COVID-19 characterized with the similar disease to sepsis may also benefit from blood purification. RECENT FINDINGS: The recent studies mainly focused on hemadsorption materials. The results of the clinical trials showed a tendency in decrease of cytokine levels and endotoxin activity and improvement in haemodynamics. However, the results were controversial. More evidence about blood purification in sepsis and COVID-19 are needed from currently ongoing trials and future well designed trials. SUMMARY: The blood purification therapy demonstrated the tendency in decrease of cytokines and endotoxin activity in different degree according to the current studies. However, the effect on mortality and haemodynamics is still in controversy. Further well designed, large sample sized studies should focus on the timing of initiating blood purification, the appropriate indications and the optimal type of blood purification membrane or cartridge to provide more evidence for clinical practice.

Extracorporeal haemoadsorption: does the evidence support its routine use in critical care?

Extracorporeal haemoadsorption is increasingly being used for the removal of endotoxin or inflammatory cytokines in patients with septic shock or other severe inflammatory states. A reduction in excessively high levels of inflammatory mediators-and mitigation of the devastating clinical impact of severe inflammation-might be a sound rationale for extracorporeal haemoadsorption in critical care, but the evidence for beneficial effects is uncertain. Few randomised controlled trials have been undertaken, and they have not provided reliable evidence for routine use in clinical practice. No study has shown a survival benefit, and only a few studies have shown a significant effect on patients' blood cytokine concentrations. Nonetheless, some clinicians have encouraged the use of haemoadsorption devices, largely on the basis of incomplete data or contentious interpretations of the available data. Further research is required, particularly well designed, prospective clinical trials assessing relevant patient-centred outcomes, including mortality, before widespread adoption of this technology can be recommended.

Therapeutic Modulation of the Host Defense by Hemoadsorption with CytoSorb®-Basics, Indications and Perspectives-A Scoping Review.

The "normal" immune response to an insult triggers a highly regulated response determined by the interaction of various immunocompetent cells with pro- and anti-inflammatory cytokines. Under pathologic conditions, the massive elevation of cytokine levels ("cytokine storm") could not be controlled until the recent development of hemoadsorption devices that are able to extract a variety of different DAMPs, PAMPs, and metabolic products from the blood. CytoSorb® has been approved for adjunctive sepsis therapy since 2011. This review aims to summarize theoretical knowledge, in vitro results, and clinical findings to provide the clinician with pragmatic guidance for daily practice. English-language and peer-reviewed literature identified by a selective literature search in PubMed and published between January 2016 and May 2021 was included. Hemoadsorption can be used successfully as adjunct to a complex therapeutic regimen for various conditions. To the contrary, this nonspecific intervention may potentially worsen patient outcomes in complex immunological processes. CytoSorb® therapy appears to be safe and useful in various diseases (e.g., rhabdomyolysis, liver failure, or intoxications) as well as in septic shock or cytokine release syndrome, although a conclusive assessment of treatment benefit is not possible and no survival benefit has yet been demonstrated in randomized controlled trials.

Therapeutic Rationale for Endotoxin Removal with Polymyxin B Immobilized Fiber Column (PMX) for Septic Shock.

Endotoxin removal therapy with polymyxin B immobilized fiber column (PMX) has been clinically applied for sepsis and septic shock patients since 1994. The effectiveness and usefulness of this therapy have been demonstrated for more than a quarter of a century. However, a documented survival benefit has not yet been demonstrable in a large, multicenter, randomized and controlled trial. Following the findings derived from a large sepsis clinical trial with PMX in North America, a new trial is ongoing to determine if PMX has a long-term survival benefit when administered to septic patients. Another approach to support a survival benefit from intervention with PMX is to utilize a detailed analysis available from a large clinical data base. The endotoxin adsorption capacity of PMX columns in vitro and the effectiveness of PMX columns can be further demonstrable in animal models. The capability of PMX and details of its mechanism of action to intervene in the sepsis cascade and impede organ dysfunction in septic patients is not fully understood. The surface antigen expression in monocytes and neutrophils are improved after PMX therapy. Immunomodulatory effects as a result of endotoxin removal and/or other mechanisms of action have been suggested. These effects and other potential immune effects may explain some of the improved effects upon organ dysfunction of sepsis and septic shock patients. Endotoxemia may be involved in the pathophysiology of other diseases than sepsis. A rapid diagnostic method to detect and target endotoxemia could allow us to practice precision medicine and expand the clinical indications of endotoxin removal therapy.

Nursing Care for the Initial Resuscitation of Severe Sepsis Patients.

Sepsis is recognized as a major health care problem worldwide. In the United States, mortality from severe sepsis and septic shock remains a serious health problem; yet, the early recognition of sepsis by nurses reduces can reduce mortality, morbidity, and long-term consequences of sepsis for patients. Improving the knowledge of nurses to first recognize the early signs of sepsis and then how to apply the most up-to-date evidence-based treatments can improve outcomes. Enhanced monitoring includes the use of computerized early warning systems to alert nurses of worrisome clinical patterns and promote the early recognition of sepsis.

Successful use of CytoSorb in a Covid-19 patient with secondary septic shock due to a sacral decubitus infection.

Septic shock is a clinical condition with high mortality (40%-70%) and morbidity. During septic shock, there is a significant release of cytokines and other inflammatory mediators that can cause damage to different organs, known as a "cytokine storm." The cytokine storm can cause hypotension, tissue damage, metabolic acidosis, and renal failure. This clinical picture also seems to be confirmed in the context of Covid-19 patients. Hemoadsorption with CytoSorb represents an adjunctive therapy to attenuate the systemic inflammatory process and helps restore a balanced immune response. We present the clinical case of a 75-year-old man, admitted to our hospital with respiratory failure due to Sars-CoV-2 infection and secondary septic shock due to a sacral decubitus. On admission the patient presented with a clinical picture of mixed acidosis with high levels of lactate and inflammatory indexes. Simultaneously along with antibiotic therapy, we started hemoadsorption treatment with CytoSorb in combination with continuous venous-venous hemodiafiltration. At the end of the treatment the patient had recovered his vital functions and the infection was successfully treated. Use of the CytoSorb device in a Covid-19 positive patient was safe and well-tolerated. Early treatment with CytoSorb decreased interleukin 6 plasma levels and inflammatory indexes, resulting in earlier stabilization of homeostasis. This case report suggests that the use of CytoSorb could be a possible adjuvant therapy in patients with septic shock even when affected by Covid-19.

[39-Year-Old Woman with Severe COVID-19 Pneumonia: Successful Weaning after Septic Shock and Forefoot Amputation after Microvascular Complications]. / 39-jährige Frau mit schwerer COVID-19-Pneumonie: Erfolgreiches Weaning nach septischem Schock und Vorfußamputation wegen mikrovaskulärer Komplikationen.

We present the case of a slightly obese 39-year-old patient with a severe course of COVID-19 pneumonia. The patient was referred from a hospital to regular care with suspected COVID-19 pneumonia. The initial clinical symptoms consisted of dysuria and fever. A bilateral infiltrate was seen in the chest x-ray. In the CT thorax, advanced COVID-19 typical changes were found on both sides. The COVID-19 infection was confirmed by a positive SARS-CoV-2 PCR from the nasopharynx smear. In the case of progressive ARDS with respiratory exhaustion, the patient was intubated and invasively ventilated. When a bacterial superinfection was suspected, we initiated empirical antibiotic therapy. In addition, a therapy with dexamethasone was applied. Therapy with ASA and weight-adapted semi-therapeutic low molecular weight heparin was also carried out. During the intensive care treatment the patient developed a fulminant septic shock with consecutive severe thrombocytopenia. A dilated tracheotomy was performed. The weaning progress was hampered by recurrent septic attacks. Necrosis in the area of ​​the right foot was identified as the cause of the septic relapses. As there was no alternative focus, surgical rehabilitation with partial amputation was carried out. The patient then remained infection-free and could be weaned from the respirator.