RESUMO
Extracorporeal haemofiltration devices that selectively remove cytokines could represent an adjunctive treatment in inflammatory diseases. One such device is the "IL-6-Sieve", wherein magnetic Anti-IL-6 Beads are introduced into an extracorporeal circuit via a Bead Adapter and then removed along with any surface-bound interleukin (IL)-6 by a Filter deployed in a Magnet, before the blood is returned to the patient. We report here on a series of animal studies, and a first-in-human study, on the safety of the IL-6-Sieve. Evaluations focused on the: (a) safety of Filter and Magnet placed in an extracorporeal circuit in sheep; (b) safety of Anti-IL-6 Beads-directly infused intravenously as worst case scenario of misuse; or injected into an extracorporeal circuit using the Bead Adapter, Filter, and Magnet as intended-in sheep; (c) biodistribution of Anti-IL-6 Beads intravenously infused in mice; and (d) safety of Filter and Magnet placed in an extracorporeal circuit in healthy volunteers. No serious adverse events or significant changes in vital signs or routine laboratory parameters occurred in any of the animals or humans. Although safety of the IL-6-Sieve requires further study, these initial evaluations represent a promising start for the translation of this new blood purification modality into clinical use.
Assuntos
Hemofiltração , Interleucina-6 , Hemofiltração/instrumentação , Hemofiltração/métodos , Animais , Humanos , Ovinos , Camundongos , Interleucina-6/sangue , Feminino , Masculino , AdultoRESUMO
BACKGROUND: The use of left ventricular assist devices (LVAD) in patients with advance heart failure is still associated with an important risk of immune dysregulation and infections. The aim of this study was to determine whether extracorporeal blood purification using the CytoSorb device benefits patients after LVAD implantation in terms of complications and overall survival. MATERIALS AND METHODS: Between August 2010 and January 2020, 207 consecutive patients underwent LVAD implantation, of whom 72 underwent CytoSorb therapy and 135 did not. Overall survival, major adverse events, and laboratory parameters were compared between 112 propensity score-matched patients (CytoSorb: 72 patients; non-CytoSorb: 40 patients). RESULTS: WBC (p = .033), CRP (p = .001), and IL-6 (p < .001), significantly increased with LVAD implantation, while CytoSorb did not influence this response. In-hospital mortality and overall survival during follow-up were similar with CytoSorb. However, patients treated with CytoSorb were more likely to develop respiratory failure (54.2% vs. 30.0%, p = .024), need mechanical ventilation for longer than 6 days post-implant (50.0% vs. 27.5%, p = .035), and require tracheostomy during hospitalization (31.9% vs. 12.5%, p = .040). No other significant differences were observed with regard to major adverse events during follow-up. CONCLUSIONS: Overall, our results showed that CytoSorb might not convey a significant morbidity or mortality benefit for patients undergoing LVAD implantation.
Assuntos
Insuficiência Cardíaca/terapia , Coração Auxiliar/efeitos adversos , Hemofiltração/instrumentação , Proteína C-Reativa/análise , Feminino , Hemofiltração/métodos , Mortalidade Hospitalar , Humanos , Interleucina-6/sangue , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Respiração Artificial/estatística & dados numéricos , Insuficiência Respiratória , Estudos Retrospectivos , Traqueotomia/estatística & dados numéricos , Resultado do TratamentoRESUMO
We present the case of a patient with subarachnoid hemorrhage (SAH) secondary to a ruptured cerebral aneurysm and a refractory shock with high doses of vasopressors without a proven source of infection. This patient received therapy with high-volume hemofiltration plus adsorption, resolving the hemodynamic deterioration and with good neurological evolution. Our clinical case proposes that extracorporeal therapies may have a feasibility role in the management of complications of SAH.
Assuntos
Hemofiltração , Hemorragia Subaracnóidea/terapia , Hemofiltração/instrumentação , Humanos , Interleucina-6/sangue , Aneurisma Intracraniano/sangue , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/terapia , Masculino , Pessoa de Meia-Idade , Hemorragia Subaracnóidea/sangue , Hemorragia Subaracnóidea/complicaçõesRESUMO
Extracorporeal membrane oxygenation (ECMO) is frequently used in many centers around the globe for various indications. However, prognosis is often poor even with all supportive therapies, and in many cases, clinical deterioration is associated with inflammation. Hemoadsorption with CytoSorb is a novel approach to limit the inflammatory response, and the device can be safely and easily installed into ECMO circuits. CytoSorb has been used more than 130.000 times to date, but because randomized controlled trials are largely lacking, there is substantial debate on its use. Here, experts from critical care medicine, cardiology, cardiac surgery, and perfusion technology discuss the pros and cons of this novel therapy and outline the future aspects for its clinical application and research.
Assuntos
Oxigenação por Membrana Extracorpórea/métodos , Hemofiltração/instrumentação , Absorção Fisico-Química , Oxigenação por Membrana Extracorpórea/efeitos adversos , Hemofiltração/métodos , Humanos , InflamaçãoAssuntos
Valvopatia Aórtica/terapia , Endocardite Bacteriana/terapia , Implante de Prótese de Valva Cardíaca/métodos , Hemofiltração/instrumentação , Infecções Estafilocócicas/terapia , Adolescente , Antibacterianos/administração & dosagem , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/microbiologia , Valvopatia Aórtica/complicações , Valvopatia Aórtica/microbiologia , Terapia Combinada/métodos , Ecocardiografia Transesofagiana , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/microbiologia , Implante de Prótese de Valva Cardíaca/instrumentação , Humanos , Masculino , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação , Resultado do TratamentoRESUMO
Polyethyleneimine-coated polyacrylonitrile (AN69ST) and polymethyl methacrylate (PMMA) membranes are effective cytokine-adsorbing hemofilters; however, the cytokine-adsorption mechanism remains elusive. This study investigated the involvement of ionic interactions in cytokine adsorption to a negatively charged AN69ST membrane and neutral-charged PMMA membrane. Experimental hemofiltration was performed for 30 min in a closed-loop circulation system using AN69ST and PMMA hemofilters. Tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8 concentrations in the test solutions were measured at baseline and at 10 min and 30 min into hemofiltration. To investigate the involvement of ionic interactions in cytokine adsorption, cytokine clearance (CL) was calculated at 10 min into hemofiltration and with three types of solutions at various pH levels (7.6, 7.2, and 6.8). During AN69ST hemofiltration, the CLs of TNF-α, IL-6, and IL-8 were 38 ± 6 mL/min, 23 ± 7 mL/min, and 78 ± 3 mL/min, respectively, demonstrating a relationship with their respective isoelectric points. During PMMA hemofiltration, the CL of IL-6 peaked at 31 ± 76 mL/min, with no relationship observed between the CL and isoelectric point. When the pH of the test solution shifted from 7.6 to 6.8, the CLs of TNF-α, IL6, and IL-8 increased in the AN69ST hemofilter; whereas, no such trend was observed in the PMMA hemofilter. These results indicated that Ionic interactions play a role in cytokine adsorption by the AN69ST membrane but not the PMMA membrane and highlight the clinical relevance of this finding, as well as the potential practical applications for further hemofilter design.
Assuntos
Resinas Acrílicas , Citocinas/análise , Hemofiltração/instrumentação , Membranas Artificiais , Polietilenoimina , Polimetil Metacrilato , Adsorção , Hemofiltração/métodos , Humanos , Interleucina-6 , Modelos Biológicos , Fator de Necrose Tumoral alfaRESUMO
Convection-based renal replacement therapies (RRTs) have the potential to improve patient outcomes when compared to diffusion-based RRT such as hemodialysis (HD), but have limited clearance rates. We propose and characterize multipoint dilution hemofiltration (MPD-HF), a purely convective blood purification technology which removes the fundamental filtration limit associated with convective RRT resulting in clearance rates on par with HD. In MPD-HF, filtration of liquid and solutes occurs along the length of the hollow fibers that convey the blood, and substitution fluid is pushed into the fibers at multiple points along their length. Since multiple filtration and dilution steps are contained within one pass of the blood through the hollow fiber, the fraction of fluid that can be filtered may be increased to allow a high clearance rate that removes a wide range of toxins. In vitro tests yielded an average steady-state filtrate fraction of 68%, exceeding commercial HDF cartridge filtrate fractions by a factor of approximately 3. The molecular weights of molecules cleared spans up to the cutoff of 66 kDa for albumin.
Assuntos
Soluções para Diálise/análise , Hemofiltração/métodos , Falência Renal Crônica/terapia , Modelos Cardiovasculares , Soluções para Diálise/química , Desenho de Equipamento , Análise de Elementos Finitos , Hemofiltração/instrumentação , Humanos , Falência Renal Crônica/sangue , Peso Molecular , Toxinas Biológicas/análise , Toxinas Biológicas/sangue , Toxinas Biológicas/química , Toxinas Biológicas/farmacocinéticaRESUMO
BACKGROUND: Cardiopulmonary bypass (CPB) is often associated with degrees of complex inflammatory response mediated by various cytokines. This response can, in severe cases, lead to systemic hypotension and organ dysfunction. Cytokine removal might therefore improve outcomes of patients undergoing cardiac surgery. CytoSorb® (Cytosorbents, NJ, USA) is a recent device designed to remove cytokine from the blood using haemoadsorption (HA). This trial aims to evaluate the potential of CytoSorb® to decrease peri-operative cytokine levels in cardiac surgery. METHODS: We have conducted a single-centre pilot randomized controlled trial in 30 patients undergoing elective cardiac surgery and deemed at risk of complications. Patients were randomly allocated to either standard of care (n = 15) or CytoSorb® HA (n = 15) during cardiopulmonary bypass (CPB). Our primary outcome was the difference between the two groups in cytokines levels (IL-1a, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α, IFN-γ, MCP-1) measured at anaesthesia induction, at the end of CPB, as well as 6 and 24 h post-CPB initiation. In a consecutive subgroup of patients (10 in HA group, 11 in control group), we performed cross-adsorber as well as serial measurements of coagulation factors' activity (antithrombin, von Willebrand factor, factor II, V, VIII, IX, XI, and XII). RESULTS: Both groups were similar in terms of baseline and peri-operative characteristics. CytoSorb® HA during CPB was not associated with an increased incidence of adverse event. The procedure did not result in significant coagulation factors' adsorption but only some signs of coagulation activation. However, the intervention was associated neither with a decrease in pro- or anti-inflammatory cytokine levels nor with any improvement in relevant clinical outcomes. CONCLUSIONS: CytoSorb® HA during CPB was not associated with a decrease in pro- or anti-inflammatory cytokines nor with an improvement in relevant clinical outcomes. The procedure was feasible and safe. Further studies should evaluate the efficacy of CytoSorb® HA in other clinical contexts. TRIAL REGISTRATION: ClinicalTrials.gov NCT02775123 . Registered 17 May 2016.
Assuntos
Ponte Cardiopulmonar/efeitos adversos , Citocinas/efeitos adversos , Hemofiltração/instrumentação , Adulto , Idoso , Idoso de 80 Anos ou mais , Ponte Cardiopulmonar/métodos , Quimiocina CCL2/análise , Quimiocina CCL2/sangue , Citocinas/sangue , Citocinas/metabolismo , Feminino , Hemofiltração/métodos , Hemofiltração/normas , Humanos , Interleucina-10/análise , Interleucina-10/sangue , Interleucina-1alfa/análise , Interleucina-1alfa/sangue , Interleucina-1beta/análise , Interleucina-1beta/sangue , Interleucina-2/análise , Interleucina-2/sangue , Interleucina-4/análise , Interleucina-4/sangue , Interleucina-5/análise , Interleucina-5/sangue , Interleucina-6/análise , Interleucina-6/sangue , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Projetos Piloto , Complicações Pós-Operatórias/prevenção & controle , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/sangueRESUMO
PURPOSE: For the first time in Kazakhstan, we have used a combined extracorporeal support, by including the CytoSorb system in a continuous veno-venous hemofiltration system in an 8-month-old patient with a body weight of 5600 g. RESULTS: The CytoSorb therapy session resulted in a reduction of inflammation markers IL-6, S100, procalcitonin, and C-reactive protein. Simultaneously, the level of transaminases, creatine kinase, and troponin were normalized, by the end of the session patient hemodynamics were stable and there was no need for vasopressors, acid-base balance was maintained, and the patient was weaned from mechanical ventilation to spontaneous breathing. CONCLUSION: Treatment using the CytoSorb device was safe and well-tolerated in a pediatric patient and has proven its practical value as an adjuvant therapy for sepsis in pediatric patient populations.
Assuntos
Biomarcadores , Hemofiltração , Insuficiência de Múltiplos Órgãos , Choque Séptico , Equilíbrio Ácido-Base , Biomarcadores/análise , Biomarcadores/sangue , Proteína C-Reativa/análise , Terapia Combinada/métodos , Hemodinâmica , Hemofiltração/instrumentação , Hemofiltração/métodos , Humanos , Lactente , Interleucina-6/sangue , Cazaquistão , Masculino , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Insuficiência de Múltiplos Órgãos/terapia , Pró-Calcitonina/sangue , Diálise Renal/efeitos adversos , Respiração Artificial/métodos , Proteínas S100/sangue , Choque Séptico/sangue , Choque Séptico/fisiopatologia , Choque Séptico/terapia , Transaminases/sangue , Resultado do TratamentoRESUMO
Cytokines and high mobility group box chromosomal protein-1 (HMGB-1) play key roles in inflammatory conditions. While hemofiltration has been shown to remove cytokines, removal of cytokines and HMGB-1 by hemofiltration using a polyethersulfone membrane has not been reported. This study aimed to test the hypothesis that the polyethersulfone membrane will achieve higher removal performance for substances including inflammatory cytokines compared to other hemofilters, while retaining low albumin removal capacity. Subjects were eight healthy volunteers. We collected 400 mL each of blood samples into containers with heparin and added 30 mg of lipopolysaccharide to spike cytokines and HMGB-1. After incubation at 39ºC for 12 h, each blood sample was circulated through a hemofiltration circuit with a polyethersulfone hemofilter (2.1 m2 or 1.1 m2 ) at a filtration flow rate of 2 L/h. Measurement samples were collected from arterial, venous, and ultrafiltrate sampling points. Concentrations of cytokines (IL-1ß, IL-4, IL-6, IL-8, IL- 10, and tumor necrosis factor [TNF-a]), HMGB-1, and albumin were determined at each time point (1, 4, 8, 12, and 24h). High sieving coefficients (SCs) above 0.8 were obtained for all cytokines except for TNF-a as well as HMGB-1, whereas the SC for albumin was less than 0.04 with both hemofilters. The hemofilter with a larger membrane area achieved significantly higher clearances for TNF-a and HMGB-1, and slower decreases in SCs over time for IL-1ß, IL-6, IL-8, TNF-a, and albumin. Continuous hemofiltration with a polyethersulfone membrane achieved high efficiency removal of cytokines and HMGB-1, without excessive removal of albumin.
Assuntos
Citocinas/sangue , Proteína HMGB1/sangue , Hemofiltração/métodos , Polímeros/química , Sulfonas/química , Hemofiltração/instrumentação , Heparina/administração & dosagem , Humanos , Interleucinas/sangue , Membranas Artificiais , Albumina Sérica/metabolismo , Fator de Necrose Tumoral alfa/sangueRESUMO
Hemofilters applied in continuous renal replacement therapies (CRRTs) for the treatment of acute kidney injury must meet high standards in biocompatibility and permeability for middle and large molecules over extended treatment times. In general, cellulose-based membranes exhibit good biocompatibility and low fouling, and thus appear to be beneficial for CRRT. In this in vitro study, we compared a novel asymmetric cellulose triacetate (ATA) membrane with three synthetic membranes [polysulfone (PS), polyethersulfone (PES), and polyethylenimine-treated acrylonitrile/sodium methallyl sulfonate copolymer (AN69 ST)] regarding thrombogenicity and cytokine removal. For thrombogenicity assessment, we analyzed the thrombin-antithrombin complex (TAT) generation in human whole blood during 5 h recirculation and filtration. Sieving coefficients of interleukin-6 (IL-6), IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α) were determined using human plasma as test fluid. ATA and AN69 ST membrane permeability were determined also during long-term experiments (48.5 h). ATA exhibited the lowest TAT generation (6.3 µg/L at 5 h), while AN69 ST induced a pronounced concentration increase (152.1 µg/L) and filter clogging during 4 out of 5 experiments. ATA (IL-8: 1.053; IL-6: 1.079; IL-10: 0.898; TNF-α: 0.493) and PES (0.973; 0.846; 0.468; 0.303) had the highest sieving coefficients, while PS (0.697; 0.100; 0.014; 0.012) and AN69 ST (N/A; 0.717; 0; 0.063) exhibited lower permeability. Long-term experiments revealed stronger fouling of the AN69 ST compared to the ATA membrane. We observed the highest permeability for the tested cytokines, the lowest thrombogenicity, and the lowest fouling with the ATA membrane. In CRRT, these factors may lead to increased therapy efficacy and lower incidence of coagulation-associated events.
Assuntos
Injúria Renal Aguda/terapia , Celulose/análogos & derivados , Citocinas/sangue , Hemofiltração/instrumentação , Trombose/terapia , Injúria Renal Aguda/sangue , Injúria Renal Aguda/complicações , Coagulação Sanguínea , Desenho de Equipamento , Seguimentos , Humanos , Membranas Artificiais , Trombose/sangue , Trombose/etiologia , Fatores de TempoRESUMO
Objective Continuous renal replacement therapy (CRRT) is well suited for treating metabolic abnormalities and renal insufficiency associated with tumour lysis syndrome (TLS). However, there is controversy regarding the choice of time for CRRT, the selection of CRRT models, and methods of decreasing complications of CRRT. This study aimed to evaluate the efficacy and outcomes of daytime continuous veno-venous haemofiltration (CVVH) for treating paediatric TLS. Methods The clinical features, technique-related complications, and prognosis were prospectively analysed in eight paediatric patients with TLS who were supported by daytime CVVH in West China Second University Hospital, Sichuan University from January 2007 to July 2016. Results Seven patients were boys and one was a girl. All of the patients had hyperphosphataemia, and there were four cases of hyperkalaemia, four cases of hyperuricaemia, and two cases of hypocalcaemia. All of the patients received one to 10 CVVH treatments. Urine output, renal function, serum uric acid levels, and potassium, phosphate, and calcium levels returned to normal in all of the patients, but recovery of renal function was relatively slow. No significant adverse reactions were observed. All of the patients recovered and were discharged. Conclusion Daytime CVVH is a safe and effective treatment for paediatric TLS.
Assuntos
Hemofiltração/métodos , Síndrome de Lise Tumoral/terapia , Injúria Renal Aguda , Adolescente , Criança , Feminino , Hemofiltração/instrumentação , Humanos , Masculino , Prognóstico , Fatores de Tempo , Síndrome de Lise Tumoral/diagnóstico , Síndrome de Lise Tumoral/etiologiaRESUMO
Recently, intensive care physicians have focused on continuous hemodiafiltration with a cytokine-adsorbing hemofilter in the treatment of sepsis. We aimed to establish extracorporeal circulation in a rat sepsis model to evaluate the cytokine removal properties of mini-modules using two types of membrane materials. Rats were divided into polyester polymer alloy (PEPA) and cellulose triacetate (CTA) groups as membrane materials of mini-modules. One hour after 0.1 mg/kg of lipopolysaccharide administration, continuous hemofiltration (CHF) was started in each group. Plasma interleukin-6 (IL-6), an important mediator of sepsis, was measured over time during hemofiltration. The peak IL-6 concentration in PEPA group was approximately 13,000 pg/mL, in comparison to approximately 31,000 pg/mL in CTA group. IL-6 clearance in PEPA group was much more than CTA group. Since IL-6 was not detected in the filtrate in PEPA group, it was considered that IL-6 was adsorbed to the membrane. In conclusion, our results suggest that CHF with PEPA hemofilter can be suitable for removing IL-6 from the blood stream efficiently.
Assuntos
Hemofiltração/instrumentação , Interleucina-6/sangue , Membranas Artificiais , Sepse/terapia , Adsorção , Ligas , Animais , Celulose/análogos & derivados , Citocinas/sangue , Modelos Animais de Doenças , Humanos , Masculino , Poliésteres , Polímeros , Ratos , Ratos Sprague-Dawley , Diálise RenalRESUMO
Static cold storage is accompanied with a partial safe ischemic interval for donor hearts. In this current study, a machine perfusion system was built to provide a better preservation for the donor heart and assessment for myocardial function. Chinese mini-swine (weight 30-35 kg, n = 16) were randomly divided into HTK, Celsior, and Heartbeat groups. All donor hearts were respectively preserved for 8 hours under static cold storage or machine perfusion. The perfusion solution is aimed to maintain its homeostasis based on monitoring the Heartbeat group. The ultrastructure of myocardium suggests better myocardial protection in the Heartbeat group compared with HTK or Celsior-preserved hearts. The myocardial and coronary artery structural and functional integrity was evaluated by immunofluorescence and Western blots in the Heartbeat. In the Heartbeat group, donor hearts maintained a high adenosine triphosphate level. Bcl-2 and Beclin-1 protein demonstrates high expression in the Celsior group. The Heartbeat system can be used to preserve donor hearts, and it could guarantee the myocardial and endothelial function of hearts during machine perfusion. Translating Heartbeat into clinical practice, it is such as to impact on donor heart preservation for cardiac transplantation.
Assuntos
Oxigenação por Membrana Extracorpórea/instrumentação , Coração , Hemofiltração/instrumentação , Preservação de Órgãos/instrumentação , Perfusão/instrumentação , Animais , Isquemia Fria , Temperatura Baixa , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/ultraestrutura , Citoproteção , Dissacarídeos/farmacologia , Eletrólitos/farmacologia , Metabolismo Energético , Desenho de Equipamento , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/métodos , Glucose/farmacologia , Glutamatos/farmacologia , Glutationa/farmacologia , Coração/efeitos dos fármacos , Coração/fisiopatologia , Hemofiltração/efeitos adversos , Hemofiltração/métodos , Histidina/farmacologia , Manitol/farmacologia , Modelos Animais , Contração Miocárdica , Miocárdio/metabolismo , Miocárdio/ultraestrutura , Preservação de Órgãos/efeitos adversos , Preservação de Órgãos/métodos , Soluções para Preservação de Órgãos/farmacologia , Perfusão/efeitos adversos , Perfusão/métodos , Cloreto de Potássio/farmacologia , Procaína/farmacologia , Suínos , Porco Miniatura , Fatores de TempoRESUMO
Performing safe cardiac surgery in neonates or infants whose parents are Jehovah's Witnesses is only possible in a coordinated team approach. An unconditional prerequisite is a cardiopulmonary bypass (CPB) circuit with a very low priming volume to minimize hemodilution. In the past decade, we have developed a functional blood-sparing approach at our institution. The extracorporeal circuit was miniaturized. This had to be recently adapted, faced with a challenge associated with the switch to high-volume crystalloid cardioplegia. A filtration circuit was added. Here, we report an open heart surgery on three consecutive children of Jehovah's Witness parents with a body weight of 2.7, 4.5, and 4.8 kg, respectively. Procedures consisted of one arterial switch operation and two repairs of complete atrioventricular septal defects. Our static priming volume of less than 90 mL resulted in a nadir hematocrit during CPB of 27.7% (Hb 8.9 g/dL) in a patient which happened to have the lowest body weight of 2.7 kg. The two other patients had their lowest hematocrit at 31.4% (Hb 10.2 g/dL). The three children could be treated without any kind of transfusion of blood which had left the circulation or its extensions, in accordance with the parents' wishes, and enjoy favorable outcomes without transfusion of blood products during their entire hospital stay.
Assuntos
Procedimentos Médicos e Cirúrgicos sem Sangue/instrumentação , Procedimentos Médicos e Cirúrgicos sem Sangue/métodos , Procedimentos Cirúrgicos Cardíacos/instrumentação , Ponte Cardiopulmonar/instrumentação , Ponte Cardiopulmonar/métodos , Hemofiltração/instrumentação , Testemunhas de Jeová , Doadores de Sangue , Transfusão de Sangue , Procedimentos Cirúrgicos Cardíacos/métodos , Desenho de Equipamento , Feminino , Hemofiltração/métodos , Humanos , Lactente , Monitorização Intraoperatória/instrumentação , Monitorização Intraoperatória/métodos , Resultado do TratamentoRESUMO
INTRODUCTION: Percutaneous hepatic perfusion (PHP) with melphalan is an effective treatment for patients with hepatic metastases, but associated with high rates of bone marrow depression. To reduce systemic toxicity, improvements have been made to the filtration system. In pre-clinical studies, the Delcath System's GEN2 filter was superior to the first-generation filters. In this clinical study, we analysed the pharmacokinetics and toxicity of PHP using the new GEN2 filter. METHODS AND MATERIALS: Starting February 2014, two prospective phase II studies were initiated in patients with hepatic metastases from ocular melanoma or colorectal cancer. In 10 PHP procedures performed in the first 7 enrolled patients, blood samples were obtained to determine filter efficiency and systemic drug exposure. PHP was performed with melphalan 3 mg/kg with a maximum of 220 mg. Complications were assessed according to CTCAE v4.03. Response was assessed according to RECIST 1.1. RESULTS: Pharmacokinetic analysis of blood samples showed an overall filter efficiency of 86% (range 71.1-95.5%). The mean filter efficiency decreased from 95.4% 10 min after the start of melphalan infusion to 77.5% at the end of the procedure (p = 0.051). Bone marrow depression was seen after up to 80.0% of 10 procedures, but was self-limiting and mostly asymptomatic. No hypotension-related complications or procedure-related mortality occurred. CONCLUSION: The GEN2 filter has a higher melphalan filter efficiency compared to the first-generation filters and a more consistent performance. PHP with the GEN2 filter appears to have an acceptable safety profile, but this needs further validation in larger studies.
Assuntos
Quimioterapia do Câncer por Perfusão Regional/métodos , Hemofiltração/instrumentação , Hemofiltração/métodos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Melfalan/uso terapêutico , Adulto , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Colorretais/patologia , Neoplasias Oculares/patologia , Feminino , Humanos , Masculino , Melanoma/secundário , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
Atherosclerosis is an important predictor of mortality in patients with chronic kidney disease (CKD) and is associated with a wide inflammatory response. The aim of this study is to evaluate in vitro how different membranes can remove mediators associated with this pathology in a closed loop dialysis model. We performed experimental hemofiltration in vitro using three different membrane materials. Human plasma was preliminarily incubated with various inflammatory mediators and filtered in a closed loop circulation model for 240 min. Respective concentrations of 17 different mediators were measured over time to study the removal mechanisms of each membrane, including associated removal time course. The experiment was repeated three times for the assay of tumor necrosis factor (TNF)-α to document the model variability. Means were compared using Mann-Whitney test. Most of the investigated mediators were effectively removed with the different dialysis membranes. Adsorption mechanism was mainly at the origin of the decrease in mediators circulating concentrations and was maximized in the region 10 000-20 000 Da. Especially, the HeprAN membrane showed fast removal capacities of mediators with elevated isoelectric point including complement factors and chemokines or having basic groups located in the protein periphery, plasminogen activator inhibitor (PAI-1), and TNF-α-like. The latter was further significantly removed with HeprAN and polymethylmethacrylate (PMMA) compared to polyethersulfone (PES) material (P < 0.01). We concluded that dialysis using ionic adsorptive membrane could have a beneficial impact for CKD patients with atherosclerosis and would deserve further clinical investigations.
Assuntos
Aterosclerose/complicações , Hemofiltração/instrumentação , Mediadores da Inflamação/isolamento & purificação , Membranas Artificiais , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Adsorção , Aterosclerose/sangue , Aterosclerose/terapia , Quimiocina CCL2/sangue , Quimiocina CCL2/isolamento & purificação , Endotelina-1/sangue , Endotelina-1/isolamento & purificação , Desenho de Equipamento , Humanos , Inflamação/sangue , Inflamação/complicações , Inflamação/terapia , Mediadores da Inflamação/sangue , Projetos Piloto , Inibidor 1 de Ativador de Plasminogênio/sangue , Inibidor 1 de Ativador de Plasminogênio/isolamento & purificação , Polímeros/química , Polimetil Metacrilato/química , Insuficiência Renal Crônica/sangue , Sulfonas/química , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/isolamento & purificaçãoRESUMO
BACKGROUND: The CARdiorenal PEDIatric EMergency (CARPEDIEM) machine was originally designed to perform only continuous venovenous hemofiltration (CVVH) in neonatal and pediatric patients. In some cases, adequate convective clearance may not be reached because of a limited blood flow. In such conditions, the application of diffusive clearance [continuous venovenous hemodialysis (CVVHD)] would help optimize blood purification. In this study, the CARPEDIEM™ machine was modified to enable the circulation of dialysis through the filter allowing testing of the performance of CARPEDIEM™ machine in CVVHD. METHODS: Three different polyethersulfone hemodialyzers (surface area = 0.1 m(2), 0.2 m(2), and 0.35 m(2), respectively) were tested in vitro with a scheduled combination of plasma flow rates (Qp = 10-20-30 ml/min) and dialysis fluid flow rate (Qd = 5-10-15 ml/min). Three sessions were performed in co-current and one in counter-current configuration (as control) for each filter size. Clearance was measured from the blood and dialysate sides and results with mass balance error greater than 5 % were discarded. RESULTS: Urea and creatinine clearances for each plasma/dialysate combination are reported: clearance increase progressively for every filter proportionally to plasma flow rates. Similarly, clearances increase progressively with dialysate flow rates at a given plasma flow. The clearance curve tends to present a steep increase for small increases in plasma flow in the range below 10 ml/min, while the curve tends to plateau for values averaging 30 ml/min. As expected, the plateau is reached earlier with the smaller filter showing the effect of membrane surface-area limitation. At every plasma flow, the effect of dialysate flow increase is evident and well defined, showing that saturation of effluent was not achieved completely in any of the experimental conditions explored. No differences (p > 0.05 for all values) were obtained in experiments using whole blood instead of plasma or using co-current versus counter-current dialysate flow configuration. CONCLUSIONS: Although plasma flow and filter surface give an important contribution to the level of clearance urea and creatinine, it appears evident that dialysate flow plays an essential role in the blood purification process, justifying the use of CVVHD versus CVVH in case of high dialysis dose requirement and/or limited blood flow rate.
Assuntos
Hemofiltração/instrumentação , Injúria Renal Aguda/terapia , Criança , Creatinina/sangue , Soluções para Diálise , Desenho de Equipamento , Humanos , Polímeros , Sulfonas , Ultrafiltração , Ureia/sangueRESUMO
BACKGROUND: Providing renal support for small children is very challenging using the machinery currently available in the United States. As the extracorporeal volume (ECV) relative to blood volume increases and the state of critical illness worsens, the chance for instability during continuous renal replacement therapy (CRRT) initiation also increases. CRRT machines with smaller ECV could reduce the risks and improve outcomes. METHODS: We present a case series of small children (n = 12) who received continuous venovenous hemofiltration (CVVH) via an Aquadex™ machine (ECV = 33 ml) with 30 ml/kg/h of prereplacement fluids at Children's of Alabama between December 2013 and April 2015. We assessed in vitro fluid precision using the adapted continuous veno-venous hemofiltration (CVVH) system. RESULTS: We used 101 circuits over 261 days to provide CVVH for 12 children (median age 30 days; median weight 3.4 kg). Median CVVH duration was 14.5 days [interquartile range (IQR) = 10; 22.8 days]. Most circuits were routinely changed after 72 h. Five of 101 (5 %) initiations were associated with mild transient change in vital signs. Complications were infrequent (three transient cases of hypothermia, three puncture-site bleedings, one systemic bleed, and one right atrial thrombus). Most patients (7/12, 58 %) were discharged from the intensive care unit; six of them (50 %) were discharged home. CONCLUSIONS: CRRT machines with low ECV can enable clinicians to provide adequate, timely, safe, and efficient renal support to small, critically ill infants.
Assuntos
Injúria Renal Aguda/terapia , Hemofiltração/instrumentação , Rins Artificiais , Insuficiência Renal Crônica/terapia , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/fisiopatologia , Fatores Etários , Alabama , Tamanho Corporal , Estado Terminal , Desenho de Equipamento , Hemofiltração/efeitos adversos , Hospitais Pediátricos , Humanos , Lactente , Recém-Nascido , Miniaturização , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Equilíbrio HidroeletrolíticoRESUMO
Efficacy of autologous blood and residual blood laundering while cardiosurgical operations performance in a newborn babies for the inborn heart failures in conditions of artificial blood circulation, using a cell saver apparatus, was investigated. In accordance to the investigation data obtained, the efficacy of a free hemoglobin laundering have constituted 71.6%, proinflammatory interleukin-6--95.8%, loss of thrombocytes--85.8%.