Combined Hemoperfusion and Continuous Veno-Venous Hemofiltration for Carbamazepine Intoxication

<b><i>Introduction:</i></b> Carbamazepine (CBZ) is a widely used anticonvulsant with a low molecular weight that allows for extracorporeal removal of free drug by both dialytic and hemoperfusion techniques, particularly in a massive overdose where serum protein binding is saturated. This report presents a case of CBZ intoxication where we were able to compare the mass removal of CBZ using hemoperfusion, with the mass removal of CBZ achieved with continuous renal replacement therapy (CRRT) during combined treatment. <b><i>Methods:</i></b> The Jafron HA230 resin hemoperfusion cartridge was applied in series with the continuous veno-venous hemofiltration (CVVH) circuit. Baseline and ongoing serum drug levels along with further samples from pre- and post-hemoperfusion cartridges and from CVVH effluent were collected. <b><i>Results:</i></b> Combined CVVH and resin hemoperfusion therapy in series was associated with a 50% reduction in the CBZ level from 16 mg/L to 8 mg/L over 3 h, far more rapid than that observed with CVVH alone or in the absence of extracorporeal drug clearance in the preceding hours. The combination therapy removed close to 35 mg/h of CBZ. <b><i>Conclusion:</i></b> The combination of CRRT and hemoperfusion can be easily deployed, appears safe, and is able to combine the CBZ mass removal achieved with each technique, thus to maximize CBZ extraction.

Successful Treatment of Severe Lamotrigine Intoxication with CytoSorb Hemoadsorption

Severe intoxication with the anti-epileptic drug, lamotrigine can cause cardiovascular collapse, neurotoxicity – expressed as intractable seizures, and even death. As there is currently no known specific antidote, extracorporeal removal therapies such as CytoSorb hemoadsorption might represent a promising therapeutic option. We report on a deeply comatosed 60-year-old woman who was treated in our intensive care unit with severe lamotrigine intoxication. To support removal from the blood, combined treatment with continuous veno-venous hemodialysis and CytoSorb hemoadsorption was started. Pre- and post-adsorber drug level measurements showed the rapid elimination of lamotrigine accompanied by an impressive clinical improvement in the patient. Two days after treatment discontinuation, there were no more clinical signs of intoxication and the patient could be extubated, followed by transfer to the stroke unit in a stable condition the following day. In the absence of a viable antidote, for the efficient short-term removal of lamotrigine, hemoadsorption with the CytoSorb device could represent a feasible treatment option for patients with severe lamotrigine intoxication.

Large paracetamol overdose -- higher dose NAC is required - CON

Paracetamol overdose is common in developed countries but less than 10% involve large ingestions exceeding 30g or 500mg/kg. High dose acetylcysteine (NAC) has been proposed in patients taking large paracetamol overdoses based on reports of hepatotoxicity despite early initiation of NAC treatment with the commonly used 300 mg/kg intravenous acetylcysteine regimen. The evidence from cohorts of patients treated with the standard NAC regimen after large paracetamol overdoses shows that it is effective in most patients. Small studies in patients whose paracetamol concentration are above the 300mg/L nomogram line show that modification of the standard NAC regimen to provide a total of 400-500 mg/kg NAC over 21-22h may reduce the risk of hepatotoxicity (peak ALT>1000 IU/L) but the impact on development of hepatic failure, liver transplantation and mortality with this approach is presently unknown. Better risk stratification of patients taking paracetamol overdose may allow higher dose NAC and adjunctive treatments such as CYP2E1 inhibition and extracorporeal removal of paracetamol to be targeted to those patients at the highest risk of hepatotoxicity after a large paracetamol overdose.

Successful Treatment of a Critically Ill COVID-19 Patient Using Continuous Renal Replacement Therapy With Enhanced Cytokine Removal and Tocilizumab: A Case Report

The COVID-19 pandemic has caused multiple deaths worldwide. Since no specific therapies are currently available, treatment for critically ill patients with COVID-19 is supportive. The most severe patients need sustained life support for recovery. We herein describe the course of a critically ill COVID-19 patient with multi-organ failure, including acute respiratory failure, acute kidney injury, and fulminant cytokine release syndrome (CRS), who required mechanical ventilation and extracorporeal membrane oxygenation support. This patient with a predicted high mortality risk was successfully managed with a careful strategy of oxygenation, uremic toxin removal, hemodynamic support, and most importantly, cytokine-targeted intervention for CRS, including cytokine/endotoxin removal, anti-cytokine therapy, and immune modulation. Comprehensive cytokine data, CRS parameters, and biochemical data of extracorporeal removal were provided to strengthen the rationale of this strategy. In this report, we demonstrate that timely combined hemoperfusion with cytokine adsorptive capacity and anti-cytokine therapy can successfully treat COVID-19 patients with fulminant CRS. It also highlights the importance of implementing cytokine-targeted therapy for severe COVID-19 guided by the precise measurement of disease activity.

THE USE OF ANTI-CYTOKINE PROPERTIES OF THE DOMESTIC HEMOSORBENT HEMO-PROTEASOSORB IN CYTOKINE STORM IN PATIENTS WITH SEVERE COVID-19

Background: The urgency of the problem of treating a severe form of COVID-19 is due to the high mortality rate among patients in intensive care units (more than 25.8%). One of the main contributors to the severe course of the disease is the cytokine storm caused by the release of a large concentration of pro-inflammatory cytokines into the bloodstream. In addition to the drug-induced blockade of this condition, extracorporeal elimination can also be considered as an effective method for suppressing the clinical manifestations of cytokine aggression. Purpose: To assess the possibility of extracorporeal removal of cytokines by hemosorption through the Hemoproteasosorb sorbent in patients with severe COVID-19 accompanied by cytokine storm. Material and methods: A clinical and laboratory assessment of the course of the disease was made in 12 patients with a severe form of COVID-19 who developed the cytokine storm associated with hemosorption. Results: After hemosorption, a statistically significant decrease in the level of IL-6, neutrophils, procalcitonin and D-dimers was established. There was also observed an improvement in the oxygen transport function of the blood represented by an increase in the respiratory index. Conclusion: Hemisorption through the Hemo-proteasosorb sorbent can be effectively used to suppress the cytokine storm in patients with severe COVID-19.

LDL apheresis as an alternate method for plasma LPS purification in healthy volunteers and dyslipidemic and septic patients

Lipopolysaccharide (LPS) is a key player for innate immunity activation. It is therefore a prime target for sepsis treatment, as antibiotics are not sufficient to improve outcome during septic shock. An extracorporeal removal method by polymyxin (PMX) B direct hemoperfusion (PMX-DHP) is used in Japan, but recent trials failed to show a significant lowering of circulating LPS levels after PMX-DHP therapy. PMX-DHP has a direct effect on LPS molecules. However, LPS is not present in a free form in the circulation, as it is mainly carried by lipoproteins, including LDLs. Lipoproteins are critical for physiological LPS clearance, as LPSs are carried by LDLs to the liver for elimination. We hypothesized that LDL apheresis could be an alternate method for LPS removal. First, we demonstrated in vitro that LDL apheresis microbeads are almost as efficient as PMX beads to reduce LPS concentration in LPS-spiked human plasma, whereas it is not active in PBS. We found that PMX was also adsorbing lipoproteins, although less specifically. Then, we found that endogenous LPS of patients treated by LDL apheresis for familial hypercholesterolemia is also removed during their LDL apheresis sessions, with both electrostatic-based devices and filtration devices. Finally, LPS circulating in the plasma of septic shock and severe sepsis patients with gram-negative bacteremia was also removed in vitro by LDL adsorption. Overall, these results underline the importance of lipoproteins for LPS clearance, making them a prime target to study and treat endotoxemia-related conditions.

BLOCKADE OF THE CYTOKINE STORM IN SEVERE SARS-COV-2 INFECTION: DRUG SUPPRESSION OR EXTRACORPOREAL ELIMINATION?

Background: The urgency of the treatment of severe COVID-19 is due to high mortality rate both in general patient population (6.4%) and in patients in intensive care units (25.8%). The cytokine storm is a pathological condition leading to high mortality. There are 2 approaches to reducing inflammatory cytokines in blood: blocking their production by drugs and extracorporeal removal. However, the choice is rather challenging.Purpose: A literature analysis was carried out to study modern approaches to prescribing medications and using extracorporeal detoxification for the blockade of the cytokine storm in severe COVID-19 patients.Material and methods: A total of 47 literature sources were analyzed.Results: The obtained information on modern methods of blocking the cytokine storm in severe COVID-19 infection indicates the effectiveness of both tocilizumab and selective anticytokine hemosorption as well as plasmapheresis and methods of renal replacement therapy.Conclusion: Based on our clinical observations, it was found out that not only drug suppression of inflammatory cytokines but also methods of extracorporeal blood purification can be effective in the treatment of severe COVID-19 pneumonia.

Extracorporeal Removal of Poisons and Toxins

Extracorporeal therapies have been used to remove toxins from the body for over 50 years and have a greater role than ever before in the treatment of poisonings. Improvements in technology have resulted in increased efficacy of removing drugs and other toxins with hemodialysis, and newer extracorporeal therapy modalities have expanded the role of extracorporeal supportive care of poisoned patients. However, despite these changes, for at least the past three decades the most frequently dialyzed poisons remain salicylates, toxic alcohols, and lithium; in addition, the extracorporeal treatment of choice for therapeutic removal of nearly all poisonings remains intermittent hemodialysis. For the clinician, consideration of extracorporeal therapy in the treatment of a poisoning depends upon the characteristics of toxins amenable to extracorporeal removal (e.g., molecular mass, volume of distribution, protein binding), choice of extracorporeal treatment modality for a given poisoning, and when the benefit of the procedure justifies additive risk. Given the relative rarity of poisonings treated with extracorporeal therapies, the level of evidence for extracorporeal treatment of poisoning is not robust; however, extracorporeal treatment of a number of individual toxins have been systematically reviewed within the current decade by the Extracorporeal Treatment in Poisoning workgroup, which has published treatment recommendations with an improved evidence base. Some of these recommendations are discussed, as well as management of a small number of relevant poisonings where extracorporeal therapy use may be considered.