RESUMEN
BACKGROUND: Rezafungin (RZF) is a novel echinocandin exhibiting distinctive pharmacokinetics/pharmacodynamics. STRIVE was a phase 2, double-blind, randomized trial designed to compare the safety and efficacy of RZF once weekly (QWk) to caspofungin (CAS) once daily for treatment of candidemia and/or invasive candidiasis (IC). METHODS: Adults with systemic signs and mycological confirmation of candidemia and/or IC were randomized to RZF 400 mg QWk (400 mg), RZF 400 mg on week 1 then 200 mg QWk (400/200 mg), or CAS 70 mg as a loading dose followed by 50 mg daily for ≤4 weeks. Efficacy assessments included overall cure (resolution of signs of candidemia/IC + mycological eradication) at day 14 (primary endpoint), investigator-assessed clinical response at day 14, and 30-day all-cause mortality (ACM) (secondary endpoints), and time to negative blood culture. Safety was evaluated by adverse events and ACM through follow-up. RESULTS: Of 207 patients enrolled, 183 were in the microbiological intent-to-treat population (~21% IC). Overall cure rates were 60.5% (46/76) for RZF 400 mg, 76.1% (35/46) for RZF 400/200 mg, and 67.2% (41/61) for CAS; investigator-assessed clinical cure rates were 69.7% (53/76), 80.4% (37/46), and 70.5% (43/61), respectively. In total, 30-day ACM was 15.8% for RZF 400 mg, 4.4% for RZF 400/200 mg, and 13.1% for CAS. Candidemia was cleared in 19.5 and 22.8 hours in RZF and CAS patients, respectively. No concerning safety trends were observed; ACM through follow-up was 15.2% (21/138) for RZF and 18.8% (13/69) for CAS. CONCLUSIONS: RZF was safe and efficacious in the treatment of candidemia and/or IC. CLINICAL TRIALS REGISTRATION: NCT02734862.
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Candidemia , Candidiasis Invasiva , Caspofungina , Equinocandinas , Adulto , Antifúngicos/efectos adversos , Candidemia/tratamiento farmacológico , Candidiasis Invasiva/tratamiento farmacológico , Caspofungina/efectos adversos , Método Doble Ciego , Equinocandinas/efectos adversos , Humanos , Resultado del TratamientoRESUMEN
BACKGROUND: Pseudomonas aeruginosa infections are a serious threat in intensive care units (ICUs). The aim of this confirmatory, randomized, multicenter, placebo-controlled, double-blind, phase 2/3 study was to assess the efficacy, immunogenicity, and safety of IC43 recombinant Pseudomonas aeruginosa vaccine in non-surgical ICU patients. METHODS: Eight hundred patients aged 18 to 80 years admitted to the ICU with expected need for mechanical ventilation for ≥ 48 h were randomized 1:1 to either IC43 100 µg or saline placebo, given in two vaccinations 7 days apart. The primary efficacy endpoint was all-cause mortality in patients 28 days after the first vaccination. Immunogenicity and safety were also evaluated. FINDINGS: All-cause mortality rates at day 28 were 29.2% vs 27.7% in the IC43 and placebo groups, respectively (P = .67). Overall survival (Kaplan-Meier survival estimates, P = .46) and proportion of patients with ≥ one confirmed P. aeruginosa invasive infection or respiratory tract infection also did not differ significantly between both groups. The geometric mean fold increase in OprF/I titers was 1.5 after the first vaccination, 20 at day 28, after the second vaccination, and 2.9 at day 180. Significantly more patients in the placebo group (96.5%) had ≥ one adverse event (AE) versus the IC43 100 µg group (93.1%) (P = .04). The most frequently reported severe AEs in the IC43 and placebo groups were respiratory failure (6.9% vs 5.7%, respectively), septic shock (4.1% vs 6.5%), cardiac arrest (4.3% vs 5.7%), multiorgan failure (4.6% vs 5.5%), and sepsis (4.6% vs 4.2%). No related serious AEs were reported in the IC43 group. INTERPRETATION: The IC43 100 µg vaccine was well tolerated in this large population of medically ill, mechanically ventilated patients. The vaccine achieved high immunogenicity but provided no clinical benefit over placebo in terms of overall mortality. TRIAL REGISTRATION: https://clinicaltrials.gov (NCT01563263). Registration was sent to ClinicalTrials.gov on March 14, 2012, but posted by ClinicalTrials.gov on March 26, 2012. The first subject was included in the trial on March 22, 2012.
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Inmunogenicidad Vacunal/inmunología , Pseudomonas aeruginosa/efectos de los fármacos , Resultado del Tratamiento , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Femenino , Humanos , Unidades de Cuidados Intensivos/organización & administración , Unidades de Cuidados Intensivos/estadística & datos numéricos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Infecciones por Pseudomonas/fisiopatología , Infecciones por Pseudomonas/prevención & control , Pseudomonas aeruginosa/patogenicidad , Respiración Artificial/efectos adversos , Respiración Artificial/métodosRESUMEN
Following publication of the original article [1], we have been notified that the approved number by the Ethical Committee was given incorrectly. In the section "Methods" stated that: The Central Ethical Committee of the University Hospital approved the study protocol (B.U.N. 143201318818), this number is incorrect and should be expressed as follows: B.U.N. 143201318819."
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Microaspiration of bacteriologically contaminated oropharyngeal secretions alongside the cuff of an endotracheal tube (ETT) is a key mechanism for development of ventilator-associated pneumonia. We have constructed a prototype double-cuffed ETT equipped with a supplemental port in-between the cuffs through which continuous positive airway pressure (CPAP) is delivered. Pressure in the intercuff space propels secretions upwards and produces 100% tracheal sealing in an in vitro model. We conducted a 24 h study to investigate the sealing effect of this ETT in 12 critically ill mechanically ventilated patients. Methylene blue, instilled through a bronchoscope on top of the proximal cuff, was used as leakage tracer. Fiberoptic visualisation of the trachea was performed 1 h and 24 h thereafter. Leakage was confirmed if blue dye was detected on the tracheal mucosa beyond the tip of the ETT. In no patient, dye passed by the cuffs during the study period. Presence of the ETT did not interfere with ventilator settings, patient mobilization, physiotherapy, and technical acts. Overall, pressures in the intercuff space remained between 10 and 15 cmH2O. Excessive pressure swings were swiftly corrected by the CPAP system. A double-cuffed ETT, offering "pressurized sealing" of the trachea, safely and effectively prevented leakage during 24 h mechanical ventilation.
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Enfermedad Crítica , Respiración Artificial , Diseño de Equipo , Humanos , Intubación Intratraqueal/efectos adversos , Proyectos Piloto , Respiración Artificial/efectos adversosRESUMEN
PURPOSE OF REVIEW: To review recent literature on the management of patients with severe acute pancreatitis (SAP) admitted to an ICU. RECENT FINDINGS: SAP is a devastating disease associated with a high morbidity and mortality. Recent evidence advocates adequate risk assessment and severity prediction (including intra-abdominal pressure monitoring), tailored fluid administration favoring balanced crystalloids, withholding prophylactic antibiotic therapy, and early detection and treatment of extra-pancreatic and fungal infections. Urgent (within 24-48âh after diagnosis) endoscopic retrograde cholangiopancreatography is indicated when persistent biliary obstruction or cholangitis are present. Corticosteroid therapy (mainly dexamethasone) can reduce the need for surgical interventions, length of hospital stay, and mortality. Peritoneal lavage may significantly lower morbidity and mortality. Hemofiltration may offer substantial benefit but more studies are needed to prove its efficacy. Enteral feeding using a polymeric formula and provided early through a nasogastric tube is recommended but has no survival benefit compared with parenteral nutrition. Probiotics could be beneficial, however no clear recommendations can be made. SUMMARY: Management of SAP is multimodal with emphasis on monitoring, adequate fluid resuscitation, avoiding prophylactic use of antibiotics, cause-directed procedures or treatment, and organ support. There is a role for early enteral nutrition including probiotics.
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Enfermedad Crítica , Nutrición Enteral , Pancreatitis , Enfermedad Aguda , Humanos , Pancreatitis/terapia , Nutrición ParenteralRESUMEN
BACKGROUND: The objective of this study was to assess the cumulative incidence of invasive candidiasis (IC) in intensive care units (ICUs) in Europe. METHODS: A multinational, multicenter, retrospective study was conducted in 23 ICUs in 9 European countries, representing the first phase of the candidemia/intra-abdominal candidiasis in European ICU project (EUCANDICU). RESULTS: During the study period, 570 episodes of ICU-acquired IC were observed, with a cumulative incidence of 7.07 episodes per 1000 ICU admissions, with important between-center variability. Separated, non-mutually exclusive cumulative incidences of candidemia and IAC were 5.52 and 1.84 episodes per 1000 ICU admissions, respectively. Crude 30-day mortality was 42%. Age (odds ratio [OR] 1.04 per year, 95% CI 1.02-1.06, p < 0.001), severe hepatic failure (OR 3.25, 95% 1.31-8.08, p 0.011), SOFA score at the onset of IC (OR 1.11 per point, 95% CI 1.04-1.17, p 0.001), and septic shock (OR 2.12, 95% CI 1.24-3.63, p 0.006) were associated with increased 30-day mortality in a secondary, exploratory analysis. CONCLUSIONS: The cumulative incidence of IC in 23 European ICUs was 7.07 episodes per 1000 ICU admissions. Future in-depth analyses will allow explaining part of the observed between-center variability, with the ultimate aim of helping to improve local infection control and antifungal stewardship projects and interventions.
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Candidiasis Invasiva/complicaciones , Anciano , Candidiasis Invasiva/epidemiología , Infección Hospitalaria/epidemiología , Europa (Continente)/epidemiología , Femenino , Humanos , Incidencia , Unidades de Cuidados Intensivos/organización & administración , Unidades de Cuidados Intensivos/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud/métodos , Evaluación de Resultado en la Atención de Salud/normas , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: An optimal nutritional approach sustained by convenient monitoring of metabolic status and reliable assessment of energy expenditure (EE) may improve the outcome of critically ill patients on extracorporeal membrane oxygenation (ECMO). We previously demonstrated the feasibility of indirect calorimetry (IC)-the standard of care technique to determine caloric targets-in patients undergoing ECMO. This study aims to compare measured with calculated EE during ECMO treatment. We additionally provide median EE values for use in settings where IC is not available. METHODS: IC was performed in seven stable ECMO patients. Gas exchange was analyzed at the ventilator, and ECMO side and values were introduced in a modified Weir formula to calculate resting EE. Results were compared with EE calculated with the Harris-Benedict equation and with the 25 kcal/kg/day ESPEN recommendation. RESULTS: Total median oxygen consumption rate was 196 (Q1-Q3 158-331) mL/min, and total median carbon dioxide production was 150 (Q1-Q3 104-203) mL/min. Clinically relevant differences between calculated and measured EE were observed in all patients. The median EE was 1334 (Q1-Q3 1134-2119) kcal/24 hours or 18 (Q1-Q3 15-27) kcal/kg/day. CONCLUSION: Compared with measured EE, calculation of EE both over- and underestimated caloric needs during ECMO treatment. Despite a median EE of 21 kcal/kg/day, large variability in metabolic rate was found and demands further investigation.
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Metabolismo Energético , Oxigenación por Membrana Extracorpórea , Anciano , Calorimetría Indirecta , Dióxido de Carbono/metabolismo , Enfermedad Crítica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Consumo de Oxígeno , Proyectos Piloto , Estudios Prospectivos , Intercambio Gaseoso Pulmonar , DescansoRESUMEN
BACKGROUND: Carbon dioxide (CO2) accumulation is a challenging issue in critically ill patients. CO2 can be eliminated by renal replacement therapy but studies are scarce and clinical relevance is unknown. We prospectively studied CO2 and O2 behavior at different sample points of continuous veno-venous hemofiltration (CVVH) and build a model to calculate CO2 removal bedside. METHODS: In 10 patients receiving standard CVVH under citrate anticoagulation, blood gas analysis was performed at different sample points within the CVVH circuit. Citrate was then replaced by NaCl 0.9% and sampling was repeated. Total CO2 (tCO2), CO2 flow (VÌCO2) and O2 flow (VÌO2) were compared between different sample points. The effect of citrate on transmembrane tCO2 was evaluated. Wilcoxon matched-pairs signed rank test was performed to evaluate significance of difference between 2 data sets. Friedman test was used when more data sets were compared. RESULTS: VÌCO2 in the effluent (26.0 ml/min) correlated significantly with transmembrane VÌCO2 (24.2 ml/min). This represents 14% of the average expired VÌCO2 in ventilated patients. Only 1.3 ml/min CO2 was removed in the de-aeration chamber, suggesting that CO2 was almost entirely cleared across the membrane filter. tCO2 values in effluent, before, and after the filter were not statistically different. Transmembrane tCO2 under citrate or NaCl 0.9% predilution also did not differ significantly. No changes in VÌO2 were observed throughout the CVVH circuit. Based on recorded data, formulas were constructed that allow bedside evaluation of CVVH-attributable CO2 removal. CONCLUSION: A relevant amount of CO2 is removed by CVVH and can be quantified by one simple blood gas analysis within the circuit. Future studies should assess the clinical impact of this observation. TRIAL REGISTRATION: The trial was registered at https://clinicaltrials.gov with trial registration number NCT03314363 on October 192,017.
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Dióxido de Carbono/sangre , Terapia de Reemplazo Renal Continuo/métodos , Oxígeno/sangre , Anciano , Anciano de 80 o más Años , Análisis de los Gases de la Sangre/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios ProspectivosRESUMEN
PURPOSE OF REVIEW: This review aims to summarize the most recent advances on different membranes and cartridges used for extracorporeal blood purification in critically ill patients with sepsis or septic shock. RECENT FINDINGS: Despite positive signals from experimental, cases and small clinical studies, blood purification showed no distinct morbidity and mortality benefit in large clinical trials. SUMMARY: None of the discussed specific membranes or cartridges can currently be recommended as sole adjunctive treatment in sepsis and septic shock. Any available technique should be timely initiated and adapted to the patient's status. Sickest patients seem to benefit more from blood purification. Patient selection is thus of crucial importance and may be optimized by focusing on disease severity and degree of organ failure. Measurement of endotoxin activity and plasma procalcitonin levels can support the selection process but ideal cutoff values need to be defined. Well-designed prospective randomized clinical trials assessing or comparing the various available membranes and cartridges are eagerly awaited.
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Cuidados Críticos , Hemofiltración , Selección de Paciente , Sepsis/terapia , Choque Séptico/terapia , Cuidados Críticos/métodos , Enfermedad Crítica , Hemofiltración/instrumentación , Hemofiltración/métodos , Humanos , Membranas Artificiales , Sepsis/sangre , Choque Séptico/sangreRESUMEN
Renal replacement therapy (RRT) is a key component in the management of severe acute kidney injury (AKI) in critically ill patients. Many cohort studies, meta-analyses, and two recent large randomized prospective trials which evaluated the relationship between the timing of RRT initiation and patient outcome remain inconclusive due to substantial differences in study design, patient population, AKI definition, and RRT indication. A cause-specific diagnosis of AKI based on current staging criteria plus a sensitive biomarker (panel) that allows creating a homogeneous study population is definitely needed to assess the impact of early versus late initiation of RRT on patient outcome.
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Lesión Renal Aguda/terapia , Terapia de Reemplazo Renal/normas , Factores de Tiempo , Resultado del Tratamiento , Enfermedad Crítica/rehabilitación , Enfermedad Crítica/terapia , Humanos , Unidades de Cuidados Intensivos/organización & administración , Terapia de Reemplazo Renal/métodosRESUMEN
BACKGROUND: Vasopressin is widely used for vasopressor support in septic shock patients, but experimental evidence suggests that selective V1A agonists are superior. The initial pharmacodynamic effects, pharmacokinetics, and safety of selepressin, a novel V1A-selective vasopressin analogue, was examined in a phase IIa trial in septic shock patients. METHODS: This was a randomized, double-blind, placebo-controlled multicenter trial in 53 patients in early septic shock (aged ≥18 years, fluid resuscitation, requiring vasopressor support) who received selepressin 1.25 ng/kg/minute (n = 10), 2.5 ng/kg/minute (n = 19), 3.75 ng/kg/minute (n = 2), or placebo (n = 21) until shock resolution or a maximum of 7 days. If mean arterial pressure (MAP) ≥65 mmHg was not maintained, open-label norepinephrine was added. Co-primary endpoints were maintenance of MAP >60 mmHg without norepinephrine, norepinephrine dose, and proportion of patients maintaining MAP >60 mmHg with or without norepinephrine over 7 days. Secondary endpoints included cumulative fluid balance, organ dysfunction, pharmacokinetics, and safety. RESULTS: A higher proportion of the patients receiving 2.5 ng/kg/minute selepressin maintained MAP >60 mmHg without norepinephrine (about 50% and 70% at 12 and 24 h, respectively) vs. 1.25 ng/kg/minute selepressin and placebo (p < 0.01). The 7-day cumulative doses of norepinephrine were 761, 659, and 249 µg/kg (placebo 1.25 ng/kg/minute and 2.5 ng/kg/minute, respectively; 2.5 ng/kg/minute vs. placebo; p < 0.01). Norepinephrine infusion was weaned more rapidly in selepressin 2.5 ng/kg/minute vs. placebo (0.04 vs. 0.18 µg/kg/minute at 24 h, p < 0.001), successfully maintaining target MAP and reducing norepinephrine dose vs. placebo (first 24 h, p < 0.001). Cumulative net fluid balance was lower from day 5 onward in the selepressin 2.5 ng/kg/minute group vs. placebo (p < 0.05). The selepressin 2.5 ng/kg/minute group had a greater proportion of days alive and free of ventilation vs. placebo (p < 0.02). Selepressin (2.5 ng/kg/minute) was well tolerated, with a similar frequency of treatment-emergent adverse events for selepressin 2.5 ng/kg/minute and placebo. Two patients were infused at 3.75 ng/kg/minute, one of whom had the study drug infusion discontinued for possible safety reasons, with subsequent discontinuation of this dose group. CONCLUSIONS: In septic shock patients, selepressin 2.5 ng/kg/minute was able to rapidly replace norepinephrine while maintaining adequate MAP, and it may improve fluid balance and shorten the time of mechanical ventilation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01000649 . Registered on September 30, 2009.
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Receptores de Vasopresinas/agonistas , Choque Séptico/tratamiento farmacológico , Vasopresinas/farmacocinética , Adolescente , Adulto , Anciano , Bélgica , Niño , Dinamarca , Método Doble Ciego , Femenino , Humanos , Hipotensión/tratamiento farmacológico , Hipotensión/etiología , Hipotensión/fisiopatología , Masculino , Persona de Mediana Edad , Norepinefrina/farmacocinética , Norepinefrina/uso terapéutico , Placebos , Choque Séptico/complicaciones , Choque Séptico/fisiopatología , Estados Unidos , Vasoconstrictores/farmacocinética , Vasoconstrictores/uso terapéutico , Vasopresinas/uso terapéuticoRESUMEN
BACKGROUND: Currently, no vaccine against Pseudomonas is available. IC43 is a new, recombinant, protein (OprF/I)-based vaccine against the opportunistic pathogen, Pseudomonas aeruginosa, a major cause of serious hospital-acquired infections. IC43 has proven immunogenicity and tolerability in healthy volunteers, patients with burns, and patients with chronic lung diseases. In order to assess the immunogenicity and safety of IC43 in patients who are most at risk of acquiring Pseudomonas infections, it was evaluated in mechanically ventilated ICU patients. METHODS: We conducted a randomized, placebo-controlled, partially blinded study in mechanically ventilated ICU patients. The immunogenicity of IC43 at day 14 was determined as the primary endpoint, and safety, efficacy against P. aeruginosa infections, and all-cause mortality were evaluated as secondary endpoints. Vaccinations (100 µg or 200 µg IC43 with adjuvant, or 100 µg IC43 without adjuvant, or placebo) were given twice in a 7-day interval and patients were followed up for 90 days. RESULTS: Higher OprF/I IgG antibody titers were seen at day 14 for all IC43 groups versus placebo (P < 0.0001). Seroconversion (≥4-fold increase in OprF/I IgG titer from days 0 to 14) was highest with 100 µg IC43 without adjuvant (80.6%). There were no significant differences in P. aeruginosa infection rates, with a low rate of invasive infections (pneumonia or bacteremia) in the IC43 groups (11.2-14.0%). Serious adverse events (SAEs) considered possibly related to therapy were reported by 2 patients (1.9%) in the group of 100 µg IC43 with adjuvant. Both SAEs resolved and no deaths were related to study treatment. Local tolerability symptoms were mild and rare (<5% of patients), a low rate of treatment-related treatment-emergent adverse events (3.1-10.6%) was observed in the IC43 groups. CONCLUSION: This phase II study has shown that IC43 vaccination of ventilated ICU patients produced a significant immunogenic effect. P. aeruginosa infection rates did not differ significantly between groups. In the absence of any difference in immune response following administration of 100 µg IC43 without adjuvant compared with 200 µg IC43 with adjuvant, the 100 µg dose without adjuvant was considered for further testing of its possible benefit of improved outcomes. There were no safety or mortality concerns. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00876252 . Registered on 3 April 2009.
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Infecciones por Pseudomonas/prevención & control , Vacunas contra la Infección por Pseudomonas/farmacología , Adulto , Anciano , Método Doble Ciego , Femenino , Humanos , Unidades de Cuidados Intensivos/organización & administración , Masculino , Persona de Mediana Edad , Placebos , Infecciones por Pseudomonas/tratamiento farmacológico , Vacunas contra la Infección por Pseudomonas/uso terapéutico , Pseudomonas aeruginosa/patogenicidad , Respiración Artificial/métodos , Sepsis/prevención & controlRESUMEN
Statins essentially are cholesterol-lowering drugs that are extensively prescribed for primary and secondary prevention of cardiovascular disease. Compelling evidence suggests that the beneficial effects of statins may not only be due to controlling cholesterol levels but also due to a pleiotropic cholesterol-independent anti-inflammatory, antioxidant, endothelial-protective and plaque-stabilizing activity. Along this line, statins may also exert acute and long-term effects on renal function. We present a narrative literature review that summarizes arguments in favour or against the preventive and/or therapeutic use of statins in kidney-related diseases or complications. We also highlight the ongoing controversy regarding statin therapy in chronic and end-stage kidney disease.
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Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Enfermedades Renales/tratamiento farmacológico , Enfermedades Cardiovasculares/tratamiento farmacológico , Humanos , Riñón/efectos de los fármacosRESUMEN
BACKGROUND: No currently used tracheal tube offers full protection against aspiration of oropharyngeal secretions into the lower airways. OBJECTIVE: We developed a tracheal tube equipped with two polyvinylchloride (PVC) cuffs with a supplementary port opening between the cuffs through which a continuous positive pressure of 5âcmH2O is provided [double-cuffed PVC (PVCdc)]. We compared this PVCdc with four different cuff types (cylindrical PVC, conical PVC, cylindrical polyurethane and conical polyurethane). DESIGN: A comparison study using an in-vitro benchtop model of an artificial rigid trachea. INTERVENTIONS: Tracheal tubes were placed in the artificial trachea. Both cuffs were kept inflated at 25âcmH2O. Total 3âml dyed water was placed above the cuff and leakage recorded under static and dynamic [5âcmH2O positive end-expiratory pressure (PEEP) alone or positive pressure ventilation plus 5âcmH2O PEEP] conditions. At the end of the dynamic experiments, PEEP was zeroed (PEEP alone) or the tracheal tubes were disconnected from the ventilator (positive pressure ventilation plus PEEP). RESULTS: In the static model, leakage flows [medians (range)] were 9.8 (6.2 to 20) for the cylindrical PVC, 1.3 (0.2 to 3.8) for the conical PVC, 0.03 (0.007 to 0.1) for the cylindrical polyurethane, 0.04 (0.003 to 0.2) for the conical polyurethane and 0.0 (0.0 to 0.0) mlâmin for the PVCdc cuff (Pâ<â0.001, PVCdc vs. all other cuffs). In the dynamic setting, no leakage was detected for up to 60âmin with any of the cuffs studied. Loss of PEEP or tracheal tube disconnection resulted in dye inflow alongside all cuffs except for the PVCdc (Pâ<â0.001, PVCdc vs. all other cuffs). CONCLUSION: A 'pressure seal' incorporated in a double-cuffed tracheal tube prevented fluid passage into the lower airways. Clinically, this may translate into absence of inflow of bacteriologically contaminated secretions into the lungs and thus a lower incidence of ventilator-associated infection.
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Diseño de Equipo/instrumentación , Intubación Intratraqueal/instrumentación , Ensayo de Materiales/instrumentación , Modelos Biológicos , Cloruro de Polivinilo , Diseño de Equipo/métodos , Diseño de Equipo/normas , Intubación Intratraqueal/métodos , Intubación Intratraqueal/normas , Ensayo de Materiales/normas , Cloruro de Polivinilo/normas , Respiración con Presión Positiva/instrumentación , Respiración con Presión Positiva/métodos , Respiración con Presión Positiva/normasRESUMEN
Sepsis-induced acute kidney injury (SAKI) is traditionally viewed as a process driven by a reduced blood flow and prone to benefit from vasopressive support. In ovine hyperdynamic septic shock, Lankadeva et al. report a significant and flow-independent intrarenal perfusion and oxygenation "mismatch" jeopardizing the renal medulla that was aggravated by norepinephrine. Medullary and urinary oxygenation changed in parallel, suggesting that urinary oxygenation may act as a biomarker to predict SAKI.
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Circulación Renal/efectos de los fármacos , Choque Séptico , Lesión Renal Aguda , Animales , Humanos , Norepinefrina , Sepsis , OvinosRESUMEN
To lower the risk of incorrectly feeding critically ill patients, indirect calorimetry (IC) is proposed as the most ideal method to evaluate energy expenditure and to establish caloric goals. New IC devices are progressively introduced but validation of this new generation remains challenging and arduous.
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Calorimetría Indirecta/instrumentación , Calorimetría Indirecta/normas , Fenómenos Fisiológicos de la Nutrición/fisiología , Enfermedad Crítica/enfermería , Ingestión de Energía/fisiología , Metabolismo Energético/fisiología , HumanosRESUMEN
BACKGROUND: Citrate, the currently preferred anticoagulant for continuous veno-venous hemofiltration (CVVH), may influence acid-base equilibrium. METHODS: The effect of 2 different citrate solutions on acid-base status was assessed according to the Stewart-Figge approach in two consecutive cohorts of critically ill adult patients. The first group received Prismocitrate 10/2 (PC10/2; 10 mmol citrate/L). The next group was treated with Prismocitrate 18/0 (PC18; 18 mmol citrate/L). Both groups received bicarbonate-buffered fluids in post-dilution. RESULTS: At similar citrate flow, the metabolic acidosis present at baseline in both groups was significantly attenuated in PC18 patients but persisted in PC10/2 patients after 24 h of treatment (median pH 7,42 vs 7,28; p = 0.0001). Acidosis in the PC10/2 group was associated with a decreased strong ion difference and an increased strong ion gap (respectively 43 vs. 51 mmol/L and 17 vs. 12 mmol/L, PC10/2 vs. PC18; both p = 0.001). Chloride flow was higher in PC10/2 than in PC18 subjects (25.9 vs 14.3 mmol/L blood; p < 0.05). CONCLUSION: Correction of acidosis was blunted in patients who received 10 mmol citrate/L as regional anticoagulation during CVVH. This could be explained by differences in chloride flow between the applied citrate solutions inducing hyperchloremic acidosis.
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Acidosis/tratamiento farmacológico , Anticoagulantes/efectos adversos , Anticoagulantes/química , Cloruros/análisis , Ácido Cítrico/efectos adversos , Equilibrio Ácido-Base/efectos de los fármacos , Acidosis/sangre , Acidosis/etiología , Lesión Renal Aguda/terapia , Anciano , Anciano de 80 o más Años , Bicarbonatos/uso terapéutico , Tampones (Química) , Femenino , Hemofiltración/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
INTRODUCTION: We conducted an 8-month prospective single-center observational study in patients with acute kidney injury treated with continuous veno-venous hemofiltration (CVVH) to compare the impact of two citrate formulations on filter lifespan (FLS). METHODS: Patients received CVVH at a delivered dose of 25 ml/kg/h. Multivariable linear regression was performed to assess the influence of different variables on circuit lifespan. RESULTS: We included 59 patients, 28 received the 10/2 formulation and 31 received the 18/0 formulation. Median (interquartile range) FLS was significantly prolonged with the 18/0 solution compared with the 10/2 solution (4.10 (2.45-5.75) vs. 2.68 (0.47-4.99) days, p = 0.001). No confounding variables (difference in ionized calcium target, citrate flow or dose, platelet count, hematocrit, vascular access location) affecting filter capacity or lifespan between the 2 formulations were identified. CONCLUSIONS: Under similar conditions of CVVH and calcium targets, a Prismocitrate 18/0 formulation significantly improved FLS as compared with Prismocitrate 10/2.
Asunto(s)
Lesión Renal Aguda/terapia , Citratos/química , Soluciones para Hemodiálisis/química , Hemofiltración/instrumentación , Membranas Artificiales , Lesión Renal Aguda/patología , Anciano , Anciano de 80 o más Años , Femenino , Hematócrito , Hemorreología , Humanos , Riñones Artificiales , Modelos Lineales , Masculino , Ensayo de Materiales , Persona de Mediana Edad , Recuento de Plaquetas , Estudios ProspectivosRESUMEN
BACKGROUND: Cancer is a common disease and many patients are diagnosed with advanced stages. Due to cancer generalization, patients may become ill-nourished and even cachectic. Malignancy-related cachexia is associated with worsening physical function, reduced tolerance to anticancer therapy and increased mortality. We assessed the effect of a patient-tailored nutritional approach in newly discovered, treatment-naive cancer patients with cachexia. METHODS: In a randomized, single-blinded, controlled pilot study, patients were treated with either intensive, biometric parameter-oriented dietary counseling (nutrition therapy) compared to regular dietary counseling (control), before and during conventional cancer treatment. Twenty patients were enrolled over a one-year period, 10 receiving nutrition therapy and 10 controls. The primary endpoint was recovery of body composition after nutrition therapy. Secondary endpoints declined in morbidity and mortality with nutrition therapy. RESULTS: Average weight evolution in the control group after 3, 6 and 12 months was 0.19 ± 7.87 kg, -9.78 ± 7.00 kg and -5.8 kg, and in the nutrition therapy group 0.69 ± 2.4 kg, 0.77 ± 2.58 kg and 1.29 ± 3.76 kg. Control patients had a significantly longer average hospital stay than subjects from the nutrition therapy group (37.6 vs. 3.4 days). Eight nutrition therapy patients and 1 control patient were still alive after 2 years. CONCLUSIONS: Nutrition therapy based on patient-specific biophysical parameters helps to maintain body weight and induces a more optimal nutritional balance in cachectic cancer patients. Moreover, survival in cancer patients improved when their nutritional status, even partially, ameliorated.