Prospects for Monitoring Aromatic and Mitochondrial Metabolites Using Gas Chromatography–Mass Spectrometry during Extracorporeal Blood Purification in Patients with Sepsis

Перспективы мониторинга ароматических и митохондриальных метаболитов методом газовой хроматомасс-спектрометрии при экстракорпоральном очищении крови у пациентов с сепсисом

Severe liver failure is common in Low-and-Medium Income Countries (LMIC) and is associated with a high morbidity, mortality and represents an important burden to the healthcare system. In its most severe state, liver failure is a medical emergency, that requires supportive care until either the liver recovers or a liver transplant is performed. Frequently the patient requires intensive support until their liver recovers or they receive a liver transplant. Extracorporeal blood purification techniques can be employed as a strategy for bridging to transplantation or recovery. The most common type of extracorporeal support provided to these patients is kidney replacement therapy (KRT), as acute kidney injury is very common in these patients and KRT devices more readily available. However, because most of the substances that the liver clears are lipophilic and albumin-bound, they are not cleared effectively by KRT. Hence, there has been much effort in developing devices that more closely resemble the clearance function of the liver. This article provides a review of various non-biologic extracorporeal liver support devices that can be used to support these patients, and our perspective keeping in mind the needs and unique challenges present in the LMIC of Latin America.

Objective To investigate the application and the effect of TNF-α,IL-6 in plasm of continuous blood purification in patients with multiple organ disorder syndrome （MODS）. Methods Twenty-six patients with MODS were treated by CBP. Blood markers of biochemistry, blood routine and TNF-α, IL-6 in plasm were checked before and after treatment. Results Blood levels of Scr,BUN, WBC,CRP, TNF-α, IL-6 after treatment were significandy lower than those before treatment of CBP （ P 〈 0.05, P 〈 0.01 ）, and blood levels of pH and HCO2^- after treatment were significantly higher than those before treatment of CBP（P 〈 0.05, P 〈 0.01 ）. 8 patients survived in the 26 patients and the survival rate was 31% . Conclusion In the patients with MODS,CBP can efficiendy treat the water-electrolyte disturbance,keep the acid-base balance,clear the inflammatory mediator and protect organs injured further,improve the patients＇ condkion and increase the survival rate. Key words: Continuous blood purification; Multiple organ disorder syndrome; Cytokines

Objective To evaluate the effects of continuous blood purification in patients with septic shock during perioperative period. Methods Forty-seven patients with infectious shock during perioperative period were enrolled and randomly divided into experimental group(group D, n=23) and control group(group F, n=24). Patients in group D received continuous venous hemofiltration starting before surgery till 72 hours after surgery. Patients in group F were treated with blood purification for 72 hours postoperatively. The blood oxygenation index, pH, HCO, base excess(BE), BUN, serum creatinine(SCr), SBP, DBP and HR were recorded in the two groups before surgery (T0), by the end of operation (T1), and 24 h (T2), and 48 h (T3), and 72 h (T4) after operation. The duration of operation, the perioperative doses of dopamine and metaraminol, and the recovery rate of patients were recorded, as well. Results Doses of dopamine and alamin in group D were significantly lower than those in group F (P 0.05), there was significant difference in oxygenation index at T2-T4 (P 0.05). There were no significant difference in biochemical indexes between group F and group D at T0 (P>0.05). Conclusions Continuous blood purification for perioperative patients with septic shock improved patients′ outcome: stabilizing homeostasis, maintaining the hemodynamics, reducing the doses of vasoactive drugs, improving patients′ tolerance and recovery rate. Key words: Perioperative period; Septic shock; Continuous blood purification

Objective To discuss the rationale, hypothesis, modality of extracorporeal blood purification (EBP) techniques for the critically ill animal models or patients, and to summarize the experimental and clinical studies with inconsistent data which explored the EBP's efficacy in the areas of critical care medicine. Data sources Articles referred in this review were collected from the database of PubMed published in English up to June 2014. Study selection We had done a literature search by using the term “(sepsis OR acute lung injury OR acute respiratory distress syndrome) AND (extracorporeal blood purification OR hemofiltration OR hemoperfusion OR plasma exchange OR plasmapheresis OR adsorpiton)”. Related original or review articles were included and carefully analyzed. Results Acute cellular and humoral immune disturbances occur in both sepsis and acute respiratory distress syndrome (ARDS). Treatments aimed at targeting one single pro-/anti-inflammatory mediator have largely failed with no proven clinical benefits. Such failure shifts the therapeutic rationale to the nonspecific, broad-spectrum methods for modulating the over-activated inflammatory and anti-inflammatory response. Therefore, EBP techniques have become the potential weapons with high promise for removing the circulating pro-/anti-inflammatory mediators and promoting immune reconstitution. Over the years, multiple extracorporeal techniques for the critically ill animal models or patients have been developed, including hemofiltration (HF), high-volume hemofiltration (HVHF), high-cutoff hemofiltration (HCO-HF), hemo-perfusion or -adsorption (HP/HA), coupled plasma filtration adsorption (CPFA), and plasma exchange (PE). These previous studies showed that EBP therapy was feasible and safe for the critically ill animal models or patients. However, data on their efficacy (especially on the clinical benefits, such as mortality) were inconsistent. Conclusions It is not now to conclude that EBP intervention can purify septic or ARDS patients with high clinical efficacy from current experimental and clinical practice. Prospective, randomized controlled, and well-designed clinical or experimental studies and most suitable EBP modalities should be further developed.

ABSTRACTIntroductionReflecting on recent reports suggesting the efficacy of extracorporeal blood purification, including hemodialysis, for severe caffeine poisoning, we conducted a retrospective 5‐year follow‐up study on acute caffeine poisoning in Japan particularly focusing on extracorporeal blood purification.MethodsPatients transported to emergency facilities between April 2016 and March 2021 after consuming large or excessive amounts of over‐the‐counter drugs and energy drinks containing caffeine as a primary ingredient were included. We collected information on demographic characteristics, medical history, the caffeine‐containing products consumed, clinical and laboratory findings, treatments, and outcomes using a questionnaire. We compared the data of patients who were treated with and without extracorporeal blood purification (blood purification vs. nonblood purification group). We also compared our findings with those of a previous related study.FindingsSeventy‐six patients were included. Patients in the blood purification group (n = 22) were significantly older (p = 0.02), ingested higher estimated doses of caffeine (p < 0.01), demonstrated higher pulse rates (p = 0.01), respiratory rates (p = 0.03), and serum glucose levels (p = 0.05) on admission, resulting in longer hospital stays (p < 0.01) than those in the nonblood purification group (n = 54). However, their backgrounds, clinical features on arrival, and clinical signs and symptoms during the clinical course were similar between this and the previous study. Compared to the previous study, this study had a higher percentage of patients who underwent extracorporeal blood purification (16.8% vs. 28.9%; p = 0.07), including hemodialysis (10.9% vs. 22.4%; p = 0.06); nevertheless, no statistically significant differences were observed in the prognoses between the studies.ConclusionsCurrently, the use of extracorporeal blood purification including hemodialysis for the treatment of caffeine poisoning is being promoted in Japan; however, the decision to administer it mostly depends on the patients' ingested doses or vital signs, and not on the serum caffeine levels. Further studies are warranted to confirm whether extracorporeal blood purification improves the prognoses of patients with severe caffeine poisoning.

Cardiac surgery-associated acute kidney injury (CSA-AKI) remains a significant problem following cardiopulmonary bypass (CPB). Various strategies are proposed to attenuate CSA-AKI, including extracorporeal blood purification (EBP), but little is known about the effect of EBP through an acrylonitrile-sodium methallylsulfonate/polyethyleneimine membrane during CPB. To determine whether the use of an EBP device in a nonemergent cardiac surgery population reduces CSA-AKI after CPB. This double-blind, randomized clinical trial was conducted in 2 tertiary hospitals in Spain. Patients 18 years or older undergoing nonemergent cardiac surgery who were at high risk for CSA-AKI were enrolled from June 15, 2016, through November 5, 2021, with follow-up data through February 5, 2022. Of 1156 patients assessed, 343 patients were randomized (1:1) to either receive EBP or standard care. Nonselective EBP device connected to the CPB circuit. The primary outcome was the rate of CSA-AKI in the 7 days after randomization. Among 343 patients randomized (169 to receive EBP and 174 to receive usual care), the mean (SD) age was 69 (9) years and 119 were females. The rate of CSA-AKI was 28.4% (95% CI, 21.7%-35.8%) in the EBP group vs 39.7% (95% CI, 32.3%-47.3%) in the standard care group (P = .03), with an adjusted difference of 10.4% (95% CI, 2.3%-18.5%) using a log-binomial model (P = .01). No significant differences (P > .05) were observed in most of the predefined clinical secondary end points or post hoc exploratory end points. In a sensitivity analysis, EBP was found to be more effective in terms of CSA-AKI reduction in patients with chronic kidney disease, diabetes, hypertension, low left ventricular ejection fraction (<40%), and lower body mass index (<30). No differences were observed between the groups in adverse events tracking. The use of a nonselective EBP device connected to the CPB circuit in a nonemergent population of patients undergoing cardiac surgery was associated with a significant reduction of CSA-AKI in the first 7 days after surgery. ClinicalTrials.gov Identifier: NCT02518087.

Background : Systemic inflammatory states such as severe sepsis and septic shock result in immunologic disturbances with the release of numerous inflammatory mediators. The systemic inflammatory response, though a result of innate immunity, can become deleterious when excessive or uncontrolled, leading to the development of multi-organ failure syndrome and death. Extracorporeal blood purification therapies have been proposed to improve outcomes for patients with severe sepsis. These therapies are based on the principle that removal of inflammatory mediators or bacterial toxins (or both) from the blood will favorably modulate the host inflammatory response. Recently, significant technological progress has greatly broadened the spectrum of techniques available for blood purification. However, these techniques have not entered into mainstream clinical practice around the world. Hemoadsorption places sorbents in direct contact with blood via an extracorporeal circuit. Polymyxin B is a cyclic basic polypeptide that disrupts the permeability of the cell membrane of Gram-negative bacteria. Polymyxin B-immobilized polystyrene-derived fibres (Toramyxin, Toray Industries, Inc., Tokyo, Japan) have been developed for use in extracoporeal therapy as a means to remove endotoxin from the blood. There are not many studies showing the efficacy of extracorporeal blood purification in paediatric population in India or around the world. Methods : A six years old girl with Salmonella typhi sepsis was retrieved on day 6 of illness in a state of fluid refractory shock on ventilatory support with oxygenation index (OI) of 16.2 and Vasoactive Inotropic Score (VIS) after 2 hours of admission was 50 with a diastolic blood pressure (DBP) of 35mmHg. She had multi-organ dysfunction with SGOT 3745U/L, SGPT 1353U/L, Arterial Lactate 11mmol/L, Creatinine 1.0mg/dl, CRP 108mg/ dl, Bicytopenia - Platelet 56000/cu.mm, WBC 2200/cu.mm (with 76% Neutrophils). She was on appropriate antibiotics since past 2 days at the referral centre. Over a period of 24 hours, her VIS increased to 53 with Fluid Overload percent (FO%) reaching 12% and her kidney injury progressed to AKIN Stage 3. We started her on Continuous Veno-venous Hemo-diafiltration (CVVHDF) which resulted in improvement in her renal parameters, Creatinine 0.4mg/dl, but she continued to have very low DBP (30 -35mmHg) despite high VIS and her inflammatory markers increased CRP 132mg/dl, with persistent Bicytopenia - Platelet 23000/cu.mm, WBC 2700/cu.mm (with 80% Neutrophils). As the child was already on CRRT, a decision to start the child on extracorporeal blood purification using Toramyxin cartridge was made and initiated at 40 hours after admission and continued for 36 hours. Results : With this, the child showed improvement with VIS decreasing to 35 after twelve hours, 25 after thirty six hours and 11 after twelve hours of stopping extracorporeal blood purification. Her inflammatory markers decreased with CRP 90mg/L after twelve hours and 54mg/L twenty four hours later. Blood counts also improved with WBC rising to 9100 (80% Neutrophils) forty eight hours of starting hemoadsorption, while she received platelet transfusion for thrombocytopenia. Her OI also improved to 8.7 after forty eight hours. The patient was off inotropes within 72 hours of starting extracorporeal blood purification and was extubated within 96 hours. Conclusion : We conclude that the use of an extracorporeal blood purification device (Toramyxin) may have helped in the removal of circulating endotoxin by adsorption, thus preventing progression of the biological cascade of sepsis and resulted in improvement in our patient’s hemodynamic status and decrease in inflammatory response leading to clinical improvement. The major limitation of our report is our inability to measure endotoxin levels of our patient to demonstrate decrease in their level pre- and post- hemoadsorption. We also cannot comment on the efficacy of extracorporeal blood purification devices based on this single case. But we wish to emphasise that many new modalities exist in treatment of septic shock and can be considered when dealing with refractory septic shock.

This study tried to investigate the impact of oXiris filter on both clinical and laboratory parameters in critically‐ill COVID‐19 intensive care unit (ICU) patients receiving extracorporeal blood purification and the clinical setting for the initiation of therapy. A consecutive sample of 15 ICU patients with COVID‐19 was treated with oXiris membrane for blood purification or for support of renal function due to acute kidney injury. We have included 19 non treated ICU COVID‐19 patients as a control group. Two chest x‐rays were analyzed for determining the chest x‐ray severity score. We have found a significant decrease of SOFA score, respiratory status improved and the chest x‐ray severity score was significantly decreased after 72 h of treatment. IL‐6 significantly decreased after 72 h of treatment while other inflammatory markers did not. Respiratory status in the control group worsened as well as increase in SOFA score and chest x‐ray severity score. Survived patients have shorter time from the onset of symptoms before starting with extracorporeal blood purification treatment and shorter time on vasoactive therapy and invasive respiratory support than deceased patients. Critically‐ill patients with COVID‐19 treated with extracorporeal blood purification survived significantly longer than other ICU COVID‐19 patients. Treatment with oXiris membrane provides significant reduction of IL‐6, leads to improvement in respiratory status, chest x‐ray severity score, and reduction of SOFA score severity. Our results can suggest that ICU COVID‐19 patients in an early course of a disease could be potentially a target group for earlier initiation of extracorporeal blood purification.

Critically ill patients often require complex extracorporeal treatments, such as extracorporeal blood purification (EBP). At the bedside, there can be reluctance or uncertainty about when to initiate EBP, and there is no standard agreement on which goals to pursue, what prescriptions to use to achieve those goals, or which recommendations to follow to prevent complications. Furthermore, an accurate analysis of why clinical goals are not achieved or how often the patient should be reassessed to readjust the EBP prescription is not currently standardized. This narrative review describes the main actions characterizing a quality improvement program for EBP in the ICU, which took place at the University of Florence and was subsequently adopted at the national level. The pillars of this program were: (1) definition, implementation, and dissemination of information and communication technology tools aimed at objectively measuring results at the bedside, supporting dynamic prescribing and precision medicine, and promoting advances in knowledge in this field; (2) creation of a national multi-professional network of clinical users and researchers in EBP; (3) promotion and maintenance of technical and non-technical skills in EBP based on the reformulation of advanced academic training in this field.

To investigate the clinical outcome and complications associated with extracorporeal blood purification (EBP) using either hemodialysis (HD), hemodialysis and hemoperfusion (HD+HP), or therapeutic plasma exchange (TPE) for the management of acute toxin ingestion in small animals. Retrospective, multicenter study from January 2011 to July 2018. One university teaching hospital and one private specialty hospital. Fifty-one dogs and 3 cats with a history of acute toxin exposure that could lead to severe morbidity and mortality, managed with different EBP techniques. Nonsteroidal anti-inflammatory drugs (38/54, 52%), baclofen (8/54, 15%), and ethylene glycol (7/54, 13%) were the most common toxicities treated with EBP. Membrane-based TPE was used most commonly (22/54, 40.7%), followed by HD (17/54, 31.5%) and then HD+HP (15/54, 27.8%). There was an 83.3% (45/54) overall survival, with 88.9% (8/9) of nonsurvivors having clinical signs prior to therapy. One third (18/54) of the patients never developed clinical signs of toxicity. Treatment complications occurred in 44.4% (24/54) of the animals, although only 18.5% (10/54) of these complications, such as mild hypotension, thrombocytopenia secondary to the HP cartridge, facial swelling after plasma transfusion for TPE, bleeding from catheter size secondary to heparinization, or clotting of the system, could be attributed to the EBP treatment. None of the nonsurvivors died because of EBP complications. Early initiation of EBP therapy might be considered as an alternative route of decontamination in severe acute toxicities with high potential for significant morbidity and mortality. The survival rate in small animals undergoing EBP is high despite exposure to potential lethal doses of toxins, and survival appears to be more likely if clinical signs of toxicity are not present at the time of EBP. Continued research is warranted with randomized controlled clinical trials to further evaluate the clinical efficacy and benefit of EBP.

Acrylamide in food was determined by gas chromatography - mass spectrometry (GC-MS) after bromination of acrylamide and underivatized acrylamide was quantified by ultra performance liquid chromatography -mass spectrometry (UPLC-MS). Two different sample preparation methods were used and optimised. The GC-MS method was used for various food matrices like breads, potato crisps, potato crackers, french fries. The UPLC-MS method was used for analysis of coffee. The limit of detection and limit of quantification for acrylamide were 7 µg.kg-1 and 20 µg.kg-1 by GC-MS, 9 µg.kg-1 and 30 µg.kg-1 by UPLC-MS. For both methods the reproducibility, given as relative standard deviation was &lt; 5% , and the recovery was close to 100 %.

The role of peritoneal dialysis in the management of AKI is not well defined, although it remains frequently used, especially in low-resource settings. A systematic review was performed to describe outcomes in AKI treated with peritoneal dialysis and compare peritoneal dialysis with extracorporeal blood purification, such as continuous or intermittent hemodialysis. MEDLINE, CINAHL, and Central Register of Controlled Trials were searched in July of 2012. Eligible studies selected were observational cohort or randomized adult population studies on peritoneal dialysis in the setting of AKI. The primary outcome of interest was all-cause mortality. Summary estimates of odds ratio were obtained using a random effects model. Of 982 citations, 24 studies (n=1556 patients) were identified. The overall methodological quality was low. Thirteen studies described patients (n=597) treated with peritoneal dialysis only; pooled mortality was 39.3%. In 11 studies (7 cohort studies and 4 randomized trials), patients received peritoneal dialysis (n=392, pooled mortality=58.0%) or extracorporeal blood purification (n=567, pooled mortality=56.1%). In the cohort studies, there was no difference in mortality between peritoneal dialysis and extracorporeal blood purification (odds ratio, 0.96; 95% confidence interval, 0.53 to 1.71). In four randomized trials, there was also no difference in mortality (odds ratio, 1.50; 95% confidence interval, 0.46 to 4.86); however, heterogeneity was significant (I(2)=73%, P=0.03). There is currently no evidence to suggest significant differences in mortality between peritoneal dialysis and extracorporeal blood purification in AKI. There is a need for good-quality evidence in this important area.

BackgroundExtracorporeal blood-purification techniques are frequently needed in the pediatric intensive care unit (PICU), yet data on their clinical application are lacking. This study aims to review the indications, rate of application, clinical characteristics, complications, and outcomes of patients undergoing extracorporeal blood purification (i.e., by continuous renal replacement therapy [CRRT] or therapeutic plasma exchange [TPE]) in our PICU, including before the coronavirus disease 2019 (COVID-19) pandemic in 2019 and during the pandemic from 2020 to 2022.MethodsThis study included children admitted for extracorporeal blood-purification therapy in the PICU. The indications for TPE were analyzed and compared to the American Society for Apheresis categories.ResultsIn 82 children, 380 TPE sessions and 37 CRRT sessions were carried out children, with 65 patients (79%) receiving TPE, 17 (20.7%) receiving CRRT, and four (4.8%) receiving both therapies. The most common indications for TPE were neurological diseases (39/82, 47.5%), followed by hematological diseases (18/82, 21.9%). CRRT was mainly performed for patients suffering from acute kidney injury. Patients with neurological diseases received the greatest number of TPE sessions (295, 77.6%). Also, the year 2022 contained the greatest number of patients receiving extracorporeal blood-purification therapy (either CRRT or TPE).ConclusionsThe use of extracorporeal blood-purification techniques increased from 2019 through 2022 due to mainly autoimmune dysregulation among affected patients. TPE can be safely used in an experienced PICU. No serious adverse events were observed in the patients that received TPE, and overall survival over the 4 years was 86.5%.

Introduction: Coronavirus disease 2019 (COVID-19) is characterized by hyperinflammation and coagulopathy. Severe cases often develop respiratory distress, requiring mechanical ventilation and with critical cases progressing to acute respiratory distress syndrome. Control of hyperinflammation has been proposed as a possible therapeutic avenue for COVID-19; extracorporeal blood purification (EBP) modalities offer an attractive mean to ameliorate maladaptive inflammation. With this work, we evaluated the longitudinal changes of systemic inflammatory markers in critically ill COVID-19 patients treated with blood purification using AN69ST (oXiris®) haemofilter. Methods: We performed a time-series analysis of 44 consecutive COVID-19 cases treated with the AN69ST (oXiris®) cytokine adsorbing haemofilter (CAH) according to local practice; we visualize longitudinal results of biochemical, inflammatory, blood gas, and vital sign parameters focussing on systemic levels of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin. Results: All patients were treated with ≥1 cycle extracorporeal continuous venovenous haemofiltration (CVVH) with CAH; of these, 30 severe patients received CVVH-CAH within 4–12 h of admission after recognizing a hyper-inflammatory state. Another 14 patients admitted with mild-to-moderate symptoms progressed to severe disease and were placed on EBP during hospitalization. The treatment was associated with a reduction of ferritin, CRP, fibrinogen, several inflammatory markers, and a resolution of numerous cytopenias. The observed mortality across the cohort was 36.3%. Conclusion: EBP with CAH was associated with a decrease in CRP, and control of IL-6 and procalcitonin.