The Influence of High-Dose Parenteral Vitamin C on the Incidence and Severity of Postoperative Pulmonary Complications in Cardiac Surgery with Extracorporeal Circulation: A Randomized Controlled Trial.

Cardiac surgery (CS) with extracorporeal circulation (ECC), induces intense oxidative stress (OS) and systemic inflammatory response (SIR), which may seriously affect postoperative lung function. We aimed to test if high parenteral (200 mg/kg/24 h) daily doses of Vitamin C (VitC), given within 48 h after the beginning of the operation, may reduce the incidence and severity of postoperative pulmonary complications (PPCs) in CS patients. This single-center, prospective, randomized, single-blinded, interventional trial included 150 patients, assigned to control Group A (n = 75) and interventional Group B (n = 75). Group B intraoperatively received one-fourth (i.e., 50 mg/kg) of the planned daily Vit C dose, divided into three equal parts and diluted in 10 mL of normal saline, while Group A received an equal volume of normal saline at the same time frames (i.e., the induction of anesthesia, aortic cross-clamp release, and sternal closure). After 6 h from the first intraoperative dose, the following regimen was applied: Group B: 50 mg/kg, 30 min i.v. infusion of VitC in 50 mL of normal saline, every 6 h, for the next 48 h, and Group A: 30 min i.v. infusion of an equal volume of normal saline every 6 h, for the next 48 h. Modified Kroenke's score was used to determine the incidence and severity of PPCs. The overall incidence of PPCs was 36.7% and was significantly lower in Group B (13.3% vs. 60.0%, p < 0.001). The PPCs severity score was also significantly lower in Group B (1 vs. 3, p < 0.001). In addition, patients from Group B had significantly less damaged lungs, better postoperative renal function, shorter ICU stays, fewer ICU re-admissions, and lower hospital mortality. No VitC-related adverse effects were recorded. High parenteral daily VitC doses given within 48 h after the beginning of CS are safe and effective in reducing the incidence and severity of PPCs. A multicenter RCT is needed to confirm these results.

Custodiol-MP for ex vivo lung perfusion - A comparison in a porcine model of donation after circulatory determination of death.

INTRODUCTION: Ex vivo lung perfusion (EVLP) is an established technique to evaluate and eventually recondition lungs prior to transplantation. Custodiol-MP (C-MP) solution is a new solution, designed for clinical machine perfusion, that has been used for kidneys. The aim of this study was to compare the effects of EVLP with Custodiol-MP on lung functional outcomes to the gold standard of EVLP with Steen Solution™. MATERIAL AND METHODS: In a porcine EVLP model of DCDD (Donation after Circulatory Determination of Death), lungs were perfused with Steen Solution™ (SS, n = 7) or Custodiol-MP solution supplemented with 55 g/l albumin (C-MP, n = 8). Lungs were stored cold for 4 h in low potassium dextran solution and subsequently perfused ex vivo for 4 h. During EVLP pulmonary gas exchange, activities of lactate dehydrogenase (LDH) and alkaline phosphatase (AP) as well as levels of lactate in the perfusate were recorded hourly. RESULTS: Oxygenation capacity differed significantly between groups (averaged over 4 h: SS 274 ± 178 mmHg; C-MP 284 ± 151 mmHg p = 0.025). Lactate dehydrogenase activities and lactate concentrations were significantly lower in Custodiol-MP perfused lungs.In a porcine model of DCDD with 4 h of EVLP the use of modified Custodiol-MP as perfusion solution was feasible. The use of C-MP showed at least comparable lung functional outcomes to the use of Steen SolutionTM. Furthermore C-MP perfusion resulted in significantly lower lactate dehydrogenase activity and lactate levels in the perfusate and higher oxygenation capacity.

Potential impacts of a novel integrated extracorporeal-CPR workflow using an interventional radiology and immediate whole-body computed tomography system in the emergency department.

Extracorporeal cardiopulmonary resuscitation (ECPR) can be associated with increased survival and neurologic benefits in selected patients with out-of-hospital cardiac arrest (OHCA). However, there remains insufficient evidence to recommend the routine use of ECPR for patients with OHCA. A novel integrated trauma workflow concept that utilizes a sliding computed tomography (CT) scanner and interventional radiology (IR) system, named a hybrid emergency room system (HERS), allowing emergency therapeutic interventions and CT examination without relocating trauma patients, has recently evolved in Japan. HERS can drastically shorten the ECPR implementation time and more quickly facilitate definitive interventions than the conventional advanced cardiovascular life support workflow. Herein, we discuss our novel workflow concept using HERS on ECPR for patients with OHCA.

Real-world use of extracorporeal photopheresis for patients with cutaneous T-cell lymphoma in the United States: 2010-2015.

Introduction: The National Comprehensive Cancer Network and the European Organization for Research and Treatment of Cancer recommend extracorporeal photopheresis (ECP) as systemic therapy for cutaneous T-cell lymphoma (CTCL).Objective: To investigate real-world use of ECP in CTCL patients in the US.Methods: Data from the Truven MarketScan® database (2010-2015) were used to create a cohort of CTCL patients receiving systemic treatment. Multivariable regressions were performed to compare health care resource utilization between ECP and propensity score-matched non-ECP patients.Results: Of the 1106 eligible patients, 117 (10.6%) received ECP, with an average treatment duration of 13.6 months. Psoriasis, organ transplant, graft versus host disease, and scleroderma were the most common comorbidities. ECP was used as monotherapy in 76 patients (65.0%) and combination in 41 patients (35.0%), mostly with interferon and/or a retinoid. Higher Charlson Comorbidity Index (2.6 vs 2.2, p < .05), rates of organ transplant (49.6% vs 7.8%, p < .001), and graft vs host disease (41.9% vs 3.4%, p < .001) were observed in ECP versus non-ECP patients. Post-matching analyses showed that ECP patients had shorter all-cause inpatient stay (6.67 vs 11.80 days, p = .001).Conclusions: Approximately 1 out of 10 CTCL patients receiving systemic treatment were on ECP treatment in the US. Post-matching analysis showed ECP was associated with a shorter hospital stay.

Bacteremia in the red blood cells obtained from the cell saver in patients submitted to heart surgery / Bacteremia nos glóbulos vermelhos obtidos do "cell saver" em pacientes submetidos a cirurgia cardíaca / Bacteriemia en los glóbulos rojos obtenidos del "cell saver" en pacientes intervenidos de cirugía cardíaca

Objective: to determine the microbiological characteristics of the red blood cells obtained with the cell saver in heart surgery patients on an extra-body circuit. Method: a cross-sectional and descriptive study conducted with 358 patients scheduled for heart surgery where the saver was used. Sociodemographic variables were collected, as well as from the saver and of the microbial identification in the re-infusion bag proceeding from the cell saver. Informed consent performed. Results: of the 170 GRAM+ bacteria isolations, the most frequent species were Staphylococcus epidermidis in 69% (n=138) of the cases and Streptococcus sanguinis with a report of 10% (n=20). Significant differences were found in the Staphylococcus epidermidis strain in patients with a Body Mass Index ≥25 (p=0.002) submitted to valve surgery (p=0.001). Vancomycin was the antimicrobial which resisted the Staphylococcus epidermidis strain with a minimum inhibitory concentration of >16 µg/ml. Conclusion: the microbiological characteristics of the red blood cells obtained after processing autologic blood recovered with the cell saver during heart surgery are of GRAM+ bacterial origin, the most isolated species being Staphylococcus epidermidis. Consequently, in order to reduce the presence of these GRAM+ cocci, an antibiotic should be added to the cell saver reservoir, according to a previously established protocol.

Objetivo: determinar as características microbiológicas dos glóbulos vermelhos obtidos com o "cell saver" em pacientes submetidos à cirurgia cardíaca em circuito extracorpóreo. Método: estudo descritivo transversal com 358 pacientes de cirurgia cardíaca em que o "cell saver" foi utilizado. Foram coletadas variáveis sociodemográficas e identificação microbiana da bolsa de reinfusão do "cell saver". Foi confirmado o Termo de Consentimento. Resultados: das 170 baterias isoladas GRAM+, as mais frequentes foram Staphylococcus epidermidis em 69% (n=138) dos casos e Streptococcus sanguinis com um registro de 10% (n=20). Diferenças significativas foram encontradas na cepa Staphylococcus epidermidis em pacientes com índice de massa corporal ≥25 (p=0,002) submetidos a cirurgia valvular (p=0,001). A vancomicina foi o antimicrobiano resistente à cepa Staphylococcus epidermidis com uma concentração inibitória mínima >16 µg/ml. Conclusão: as características microbiológicas dos glóbulos vermelhos obtidas após o processamento do sangue autólogo recuperado com o "cell saver" em cirurgia cardíaca são de origem bacteriana GRAM+, sendo a espécie mais isolada o Staphylococcus epidermidis. Portanto, para reduzir a presença desses cocos GRAM+, um antibiótico deve ser adicionado ao "cell saver", de acordo com um protocolo previamente estabelecido.

Objetivo: determinar las características microbiológicas de los glóbulos rojos obtenidos con el "cell saver" en el paciente de cirugía cardíaca bajo un circuito extracorpóreo. Método: estudio descriptivo transversal con 358 pacientes programados para cirugía cardíaca donde se utilizó el "cell saver". Se recogieron variables sociodemográficas e identificación microbiana de la bolsa de reinfusión procedente del "cell saver". Consentimiento informado realizado. Resultados: de 170 aislamientos de bacterias GRAM+, las especies más frecuentes fueron el Staphylococcus epidermidis en el 69% (n=138) de los casos y el Streptococcus sanguinis con un reporte del 10% (n=20). Se encontraron diferencias significativas en la cepa Staphylococcus epidermidis en pacientes con índice de masa corporal ≥25 (p=0,002) sometidos a cirugía valvular (p=0,001). La vancomicina fue el antimicrobiano resistente a la cepa Staphylococcus epidermidis con una concentración mínima inhibitoria >16 ug/ml. Conclusión: las características microbiológicas de los glóbulos rojos obtenidos tras el procesamiento de sangre autóloga recuperada con el "cell saver" en cirugía cardíaca son de origen bacteriano GRAM+ siendo la especie más aislada el Staphylococcus epidermidis. Por ello, con el fin de reducir la presencia de estos cocos GRAM+ se debería añadir un antibiótico en el reservorio del "cell saver", según un protocolo previamente establecido.

2019 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research.

Total parenteral nutrition in ex vivo lung perfusion: Addressing metabolism improves both inflammation and oxygenation.

Ex vivo lung perfusion (EVLP) protocols generally limit metabolic supplementation to insulin and glucose. We sought to determine whether the addition of total parenteral nutrition (TPN) would improve lung function in EVLP. Ten porcine lungs were perfused using EVLP for 24 hours and supplemented with insulin and glucose. In the treatment group (n = 5), the perfusate was also supplemented with a continuous infusion of TPN containing lipids, amino acids, essential vitamins, and cofactors. Physiologic parameters and perfusate electrolytes were continuously evaluated. Perfusate lactate, lipid and branch chain amino acid (BCAA) concentrations were also analyzed to elucidate how substrates were being utilized over time. Lungs in the TPN group exhibited significantly better oxygenation. Perfusate sodium was more stable in the TPN group. In the control group, free fatty acids (FFA) were quickly depleted, reaching negligible levels early in the perfusion. Alternatively, BCAA in the control group rose continually over the perfusion demonstrating a shift toward proteolysis for energy substrate. In the TPN group, both FFA and BCAA concentrations remained stable at in vivo levels after initial stabilization. TNF-α concentrations were lower in the TPN group. The addition of TPN in EVLP allows for better electrolyte composition, decreased inflammation, and improved graft performance.

Improvement of Normothermic Ex Vivo Machine Perfusion of Rat Liver Grafts by Dialysis and Kupffer Cell Inhibition With Glycine.

Normothermic ex vivo liver machine perfusion might be a superior preservation strategy for liver grafts from extended criteria donors. However, standardized small animal models are not available for basic research on machine perfusion of liver grafts. A laboratory-scaled perfusion system was developed consisting of a custom-made perfusion chamber, a pressure-controlled roller pump, and an oxygenator. Male Wistar rat livers were perfused via the portal vein for 6 hours using oxygenated culture medium supplemented with rat erythrocytes. A separate circuit was connected via a dialysis membrane to the main circuit for plasma volume expansion. Glycine was added to the flush solution, the perfusate, and the perfusion circuit. Portal pressure and transaminase release were stable over the perfusion period. Dialysis significantly decreased the potassium concentration of the perfusate and led to significantly higher bile and total urea production. Hematoxylin-eosin staining and immunostaining for single-stranded DNA and activated caspase 3 showed less sinusoidal dilatation and tissue damage in livers treated with dialysis and glycine. Although Kupffer cells were preserved, tumor necrosis factor α messenger RNA levels were significantly decreased by both treatments. For proof of concept, the optimized perfusion protocol was tested with donation after circulatory death (DCD) grafts, resulting in significantly lower transaminase release into the perfusate and preserved liver architecture compared with baseline perfusion. In conclusion, our laboratory-scaled normothermic portovenous ex vivo liver perfusion system enables rat liver preservation for 6 hours. Both dialysis and glycine treatment were shown to be synergistic for preservation of the integrity of normal and DCD liver grafts.

Low-level light therapy reduces platelet destruction during extracorporeal circulation.

Extracorporeal circulation causes many deleterious effects on blood cells. Low-level light therapy (LLLT) in the red/near-infrared spectral range is known for its cytoprotective properties but its use during cardiopulmonary bypass (CPB) has not yet been studied. We aimed to assess whether LLLT protects platelets during CPB. 24 pigs were connected to 1-hour-CPB and observed for the next 23 hours. In 12 animals, blood circulating through the oxygenator was treated with LLLT. Platelet count and function were monitored throughout the experiment. The decrease in platelet count was greater in the control group, especially during CPB and after 24 hours. In LLLT group CD62P expression remained quite stable up to the 12th hour of the experiment, whereas in the control group it continuously decreased till the end of observation. Platelets in the control group were more prone to aggregation in the postoperative period than at the beginning of the experiment, whereas platelets in the LLLT group aggregated similarly or less intense. Limitation of platelet loss, pattern of aggregation and CD62P expression suggest that LLLT may stabilize platelet function during CPB and diminish the negative effects associated with the interaction of cells with an artificial surface.

Positive impact of retrograde autologous priming in adult patients undergoing cardiac surgery: a randomized clinical trial.

BACKGROUND: Adult cardiac surgery with extracorporeal circulation is known to be associated with increased risk of blood transfusion leading to adverse outcomes. Procedures like retrograde autologous priming (RAP) may reduce these negative side effects. This randomized prospective study was initiated to assess whether RAP using specifically designed RAP bag (Terumo) has immediate effects on patient outcome. METHODS: One hundred eighteen adults undergoing elective CABG or elective aortic valve replacement were randomly assigned by a computer program into two groups: the RAP group (n = 54) in which the retrograde autologous priming was applied and the non-RAP (n = 64) group in which the same setting was used without the possibility to save priming volume. Patient demographics, preoperative characteristics and postoperative outcomes were analyzed for both groups. RESULTS: The primary endpoint defined as rate of intraoperative blood transfusion was significantly reduced in the RAP-group (p = 0.04). The absolute risk reduction for RAP managed patients was 13.5 percent points. There were no significant differences in operation time and blood loss. No deaths and no myocardial infarctions were observed. The number of patients needed to treat to prevent at least one red blood cell transfusion was around 8 (NNT = 7.42). CONCLUSIONS: Retrograde autologous priming is a safe and less invasive procedure which achieves clear benefits for adult cardiac surgery patients. In the light of increasing red blood cell transfusion risks and costs and the wish of patients to avoid a transfusion implementation of retrograde autologous priming is an interesting option. TRIAL REGISTRATION: German Clinical Trials Register ID: DRKS00013512 , registered 04 December 2017.

Oral glutamine reduces myocardial damage after coronary revascularization under cardiopulmonary bypass. A randomized clinical trial / La glutamina oral reduce el daño miocárdico tras revascularización coronaria bajo derivación cardiopulmonar. Un ensayo clínico aleatorizado

Background: Glutamine is the most abundant free amino acid in the body. It modulates immune cell function and is an important energy substrate for cells in critically ill patients. Reduction of injury cardiac markers had been observed in patients receiving intravenous glutamine and in a pilot study with oral glutamine. The aim of this study was to analyze the effect of preoperative oral supplementation of glutamine on postoperative serum levels of cardiac injury markers. Methods: A randomized clinical trial was performed in 28 Mexican patients with ischemic heart disease who underwent cardiopulmonary bypass with extracorporeal circulation. Patients were randomly assigned to receive oral glutamine (0.5 g/kg/day) or maltodextrin 3 days before surgery. Cardiac injury markers as troponin-I, creatine phosphokinase, and creatine phosphokinase-Mb were measured at 1, 12, and 24 hours postoperatively. Results: At 12 and 24 hours serum markers levels were significantly lower in the glutamine group compared with controls (p = 0.01 and p = 0.001, respectively) (p = 0.004 and p < 0.001, respectively). Overall, complications were significantly lower in the glutamine group (p = 0.01, RR = 0.54, 95% CI 0.31-0.93). Mortality was observed with 2 cases of multiple organ failure in control group and 1 case of pulmonary embolism in glutamine group (p = 0.50). Conclusion: Preoperative oral glutamine standardized at a dose of 0.5 g/kg/day in our study group showed a significant reduction in postoperative myocardial damage. Lower cardiac injury markers levels, morbidity and mortality were observed in patients receiving glutamine (AU)

Introducción: la glutamina es el aminoácido libre más abundante en el cuerpo. Modula funciones celulares inmunológicas y es un sustrato importante de energía. Se observó reducción de los marcadores de daño cardiaco en pacientes que recibieron tanto glutamina intravenosa como oral en un estudio piloto. Nuestro objetivo fue analizar el efecto preoperatorio con suplementación de glutamina oral sobre los niveles postoperatorios de los marcadores de lesión cardiaca. Métodos: ensayo clínico aleatorizado con 28 pacientes mexicanos con cardiopatía isquémica y sometidos a bypass cardiopulmonar con circulación extracorpórea. Los pacientes fueron asignados al azar para recibir glutamina oral (0,5 g/kg/día) o maltodextrina 3 días antes de ser operados. La troponina-I, creatinina fosfoquinasa y creatinina fosfoquinasa-Mb fueron medidas a la hora, 12 y 24 horas postoperatorias. Resultados: a las 12 y 24 horas los niveles séricos de marcadores fueron menores en el grupo de glutamina comparado con los controles (p = 0,01 y p = 0,001, respectivamente) (p = 0,004 y p < 0,001, respectivamente). Las complicaciones fueron menores en el grupo de glutamina (p = 0,01, RR = 0,54, 95% IC 0,31-0,93). La mortalidad ocurrió en 2 casos con dos falla orgánica múltiple en el grupo control y 1 caso de tromboembolia pulmonar en el grupo de glutamina (p = 0,50). Conclusión: la administración estandarizada de glutamina oral de manera preoperatoria (0,5 g/kg/día) en nuestro estudio demostró una reducción significativa del daño miocárdico postoperatorio. Los niveles séricos de marcadores cardiacos, la morbilidad y mortalidad fueron menores en los pacientes que recibieron glutamina (AU)

Pediatric Multiple Organ Dysfunction Syndrome: Promising Therapies.

OBJECTIVE: To describe the state of the science, identify knowledge gaps, and offer potential future research questions regarding promising therapies for children with multiple organ dysfunction syndrome presented during the Eunice Kennedy Shriver National Institute of Child Health and Human Development Workshop on Pediatric Multiple Organ Dysfunction Syndrome (March 26-27, 2015). DATA SOURCES: Literature review, research data, and expert opinion. STUDY SELECTION: Not applicable. DATA EXTRACTION: Moderated by an expert from the field, issues relevant to the association of multiple organ dysfunction syndrome with a variety of conditions were presented, discussed, and debated with a focus on identifying knowledge gaps and research priorities. DATA SYNTHESIS: Summary of presentations and discussion supported and supplemented by relevant literature. CONCLUSIONS: Among critically ill children, multiple organ dysfunction syndrome is relatively common and associated with significant morbidity and mortality. For outcomes to improve, effective therapies aimed at preventing and treating this condition must be discovered and rigorously evaluated. In this article, a number of potential opportunities to enhance current care are highlighted including the need for a better understanding of the pharmacokinetics and pharmacodynamics of medications, the effect of early and optimized nutrition, and the impact of effective glucose control in the setting of multiple organ dysfunction syndrome. Additionally, a handful of the promising therapies either currently being implemented or developed are described. These include extracorporeal therapies, anticytokine therapies, antitoxin treatments, antioxidant approaches, and multiple forms of exogenous steroids. For the field to advance, promising therapies and other therapies must be assessed in rigorous manner and implemented accordingly.

The effects of polyunsaturated fatty acids and antioxidant vitamins on atrial oxidative stress, nitrotyrosine residues, and connexins following extracorporeal circulation in patients undergoing cardiac surgery.

Cardiac surgery with extracorporeal circulation is characterized by different degrees of myocardial ischemia/reperfusion, which is often associated with postoperative atrial fibrillation (POAF). We have previously shown that a novel preventive therapy based on the reinforcement of the antioxidant system using omega-3 fatty acids plus antioxidant vitamin supplementation applied to patients undergoing cardiac surgery reduces POAF occurrence. We hypothesized that oxidative stress and nitrosative stress are involved in the development of an arrhythmogenic substrate by their effect on connexins (Cx40, Cx43 and Cx45) abundance and distribution pattern. Therefore, we have assessed the effect of redox status on atrial tissue in patients undergoing cardiac surgery. Placebo/POAF and supplemented/POAF patients showed 276 and 170% higher reactive oxygen species (ROS) levels and 223 and 96% higher nitrotyrosine residues levels, respectively, compared to sinus rhythm (SR). In POAF tissue, antioxidant supplementation prevented Cx40 and Cx43 lateralization on cardiomyocyte sarcolemma, keeping them at the intercalated disks. POAF samples showed Cx40 heterogeneous distribution pattern, presenting tissue areas lacking this protein (49 and 55% lower levels in placebo/POAF and supplemented/POAF groups, respectively, compared to SR). Of note, Cx45 overexpression occurred in POAF, being 211 and 167% higher in placebo/POAF and supplemented/POAF groups, respectively, compared to SR. It is concluded that treatment with omega-3 fatty acids and antioxidant vitamins reduces oxidative and nitrosative stress and prevents Cx40/Cx43 lateralization in atrial tissue likely contributing to POAF prevention. However, it failed to fully prevent POAF occurrence because these compounds have no effects on the normalization of Cx40 down-regulation and Cx45 up-regulation, which may promote POAF.

Emerging therapies for the treatment of sepsis.

PURPOSE OF REVIEW: Sepsis affects patients of all ages with multiple comorbidities and underlying diagnoses, and is the result of infection by many potential pathogens infecting various organs or sites. Many molecules have been clinically tested in recent years for their potential immunomodulatory effects, but have been shown to have no beneficial effects on outcomes in heterogeneous populations of patients with sepsis. There are, therefore, no specific antisepsis therapies and mortality and morbidity rates remain high despite improved overall management of these patients. This review covers promising agents currently used in clinical trials. RECENT FINDINGS: There are several candidates currently undergoing early and later phase of clinical testing, including thrombomodulin, alkaline phosphatase, interferon-beta, and selepressin. Other approaches including immunoglobulins, extracorporeal therapies, and pharmaconutrients will also be discussed. SUMMARY: Despite multiple trials of potential therapies for sepsis, no strategies have yet been persistently shown to have beneficial effects on outcomes. The main reason for the disappointing results is that patient populations in these studies have been too heterogeneous. Selecting patients on the basis of general symptoms is not enough. Rather patients should be selected according to the likely action of the drug in question. To achieve this, improved biomarkers of sepsis and of the immune response are needed and the activities of the individual agents need to be carefully characterized. New candidates are being developed and the results of ongoing and recent clinical trials of immunomodulatory therapies are eagerly awaited as new therapies for sepsis are urgently needed.

Oxigenoterapia hiperbárica no acidente aeroembólico no pós-operatóriode cirurgia cardíaca / Hyperbaric oxygen therapy for treating an aeroembolic accident after heart surgery

A embolia aérea sistêmica pode ter várias etiologias. Durante a circulação extracorpórea (CEC) é estimadaem 0,1 %, entretanto a grande maioria das intercorrências não é relatada ou é imperceptível, dependendo do grau de comprometimento neurológico e do tempo em que ocorreu após a cirurgia. Em geral, a embolia aérea pode causar distúrbios cognitivos, danos focais, coma e morte. O presente trabalho relataa experiência do Instituto Estadual de Cardiologia Aloysio de Castro com acidentes semelhantes no pósoperatório,que foram tratados com oxigenoterapiahiperbárica, com recuperação total.

Estimated at 0.1% during extracorporeal circulation, systemic air embolisms may have different etiologies. However, the vast majority ofcomplications are not reported or are imperceptible, depending on neurological involvement and the length of time after surgery. In general, air embolisms may cause cognitive disorders, focal damage, coma and death. This paper reports on the experience of the Aloysio de Castro State Cardiology Institute, treating these accidents during the postoperativeperiod with hyperbaric oxygen therapy,with full recovery.

Venovenous perfusion-induced systemic hyperthermia: five-day sheep survival studies.

OBJECTIVE: Since hyperthermia selectively kills lung cancer cells, we developed a venovenous perfusion-induced systemic hyperthermia system for advanced lung cancer therapy. Our objective was to test the safety and accuracy of our venovenous perfusion-induced systemic hyperthermia system in 5-day sheep survival studies, following Good Laboratory Practice standards. METHODS: Our venovenous perfusion-induced systemic hyperthermia system, which included a double-lumen cannula (Avalon Elite, Rancho Dominguez, Calif), a centrifugal pump (Bio-Pump 560; Medtronic Inc, Minneapolis, Minn), a heat exchanger (BIOtherm; Medtronic Perfusion Systems, Brooklyn Park, Minn), and a heater/cooler (modified Blanketrol IIIl Cincinnati Subzero, Cincinnati, Ohio), was tested in healthy adult sheep (n=5). The perfusion circuit was primed with prewarmed Plasma-Lyte A (Baxter Healthcare Corp, Deerfield, Ill) and de-aired. Calibrated temperature probes were placed in the right and left sides of the nasopharynx, bladder, and blood in/out tubing in the animal. The double-lumen cannula was inserted through the jugular vein into the superior vena cava, with the tip in the inferior vena cava. RESULTS: Therapeutic core temperature (42°C-42.5°C), calculated from the right and left sides of the nasopharynx and bladder temperatures, was achieved in all sheep. Heating time was 21±5 minutes. Therapeutic core temperature was maintained for 120 minutes followed by a cooling phase (35±6 minutes) to reach baseline temperature. All sheep recovered from anesthesia with spontaneous breathing within 4 hours. Arterial, pulmonary, and central venous pressures were stable. Transient increases in heart rate, cardiac output, and blood glucose occurred during hyperthermia but returned to normal range after venovenous perfusion-induced systemic hyperthermia termination. Electrolytes, complete blood counts, and metabolism enzymes were within normal to near normal range throughout the study. No significant venovenous perfusion-induced systemic hyperthermia-related hemolysis was observed. Neurologic assessment showed normal brain function all 5 days. CONCLUSIONS: Our venovenous perfusion-induced systemic hyperthermia system safely delivered the hyperthermia dose with no significant hyperthermia-related complications.

Practical guidelines: lung transplantation in patients with cystic fibrosis.

There are no European recommendations on issues specifically related to lung transplantation (LTX) in cystic fibrosis (CF). The main goal of this paper is to provide CF care team members with clinically relevant CF-specific information on all aspects of LTX, highlighting areas of consensus and controversy throughout Europe. Bilateral lung transplantation has been shown to be an important therapeutic option for end-stage CF pulmonary disease. Transplant function and patient survival after transplantation are better than in most other indications for this procedure. Attention though has to be paid to pretransplant morbidity, time for referral, evaluation, indication, and contraindication in children and in adults. This review makes extensive use of specific evidence in the field of lung transplantation in CF patients and addresses all issues of practical importance. The requirements of pre-, peri-, and postoperative management are discussed in detail including bridging to transplant and postoperative complications, immune suppression, chronic allograft dysfunction, infection, and malignancies being the most important. Among the contributors to this guiding information are 19 members of the ECORN-CF project and other experts. The document is endorsed by the European Cystic Fibrosis Society and sponsored by the Christiane Herzog Foundation.

Experience of Treatments of Amanita phalloides-Induced Fulminant Liver Failure with Molecular Adsorbent Recirculating System and Therapeutic Plasma Exchange.

Ingestion of the mushroom containing Amanita phalloides can induce fulminant liver failure and death. There are no specific antidotes. Blood purifications, such as molecular adsorbent recirculating system (MARS) and therapeutic plasma exchange (TPE), are potential therapies. However, the extent to which these technologies avert the deleterious effects of amatoxins remains controversial; the optimal intensity, duration, and initiation criteria have not been determined yet. This study aimed to retrospectively observe the effects of MARS and TPE on nine patients with A. phalloides-induced fulminant liver failure. The survival rate for the nine patients was 66.7%. Both TPE and MARS might remove toxins and improve liver functions. However, a single session of TPE produced immediately greater improvements in alanine aminotransferase (-60% vs. -16.3%), aspartate aminotransferase (-47.6% vs. -15.4%), and total bilirubin (-37.3% vs. -17.1%) (compared with the values of pretreatment, all p < 0.05) than MARS compared with MARS. Early intervention may be more effective than delayed therapy. Additionally, the presence of severe liver failure and renal failure indicated worse outcome. Although these findings are promising, additional case-controlled, randomized studies are required to confirm our results.

Hemorragia masiva después de anticoagulación con bivalirudina en 2 casos de pacientes con trasplante cardiaco / Massive haemorrhage after bivalirudin anticoagulation in two heart transplant patients

La trombopenia inducida por heparina es una complicación autoinmunitaria frecuente. Se trata de un estado protrombótico debido a la formación de anticuerpos contra los complejos heparina/factor plaquetario 4. Ante esta situación es necesario el empleo de fármacos alternativos a la heparina para la anticoagulación durante la circulación extracorpórea. Se exponen 2 casos de trasplante cardiaco en los que se empleó bivalirudina como anticoagulante durante la circulación extracorpórea. En ambos pacientes se observó la aparición de complicaciones hemorrágicas severas. Es necesario mejorar el diagnóstico de la trombopenia inducida por heparina y desarrollar protocolos de empleo de nuevos fármacos alternativos a la heparina. Por ello revisamos los protocolos de actuación y las alternativas terapéuticas a la heparina(AU)

Heparin-induced thrombopenia is a common autoimmune complication. It is a prothrombotic state due to the formation of antibodies against heparin/platelet factor 4 complexes. In this situation drugs other than heparin must be used for anticoagulation during extracorporeal circulation (bypass) surgery. Two cases of heart transplantation are presented in whom bivalirudin was used as an anticoagulant during the cardiopulmonary bypass. Severe bleeding complications were observed in both patients. The diagnosis of heparin-induced thrombopenia needs to be improved, as well as the development of protocols for using new drugs other than heparin. For this reason, we have reviewed current protocols and alternative therapies to heparin(AU)