Diaphragmatic Ultrasound Predictors of High-Flow Nasal Cannula Therapeutic Failure in Critically Ill Patients With SARS-CoV-2 Pneumonia.

OBJECTIVES: High flow nasal cannula (HFNC) is frequently used in patients with acute respiratory failure, but there is limited evidence regarding predictors of therapeutic failure. The objective of this study was to assess diaphragmatic ultrasound criteria as predictors of failure to HFNC, defined as the need for orotracheal intubation or death. METHODS: Prospective cohort study including adult patients consecutively admitted to the critical care unit, from July 24 to October 20, 2020, with respiratory failure secondary to SARS-CoV-2 pneumonia who required HFNC. After 12 hours of HFNC initiation we measured ROX index (ratio of SpO2 /FiO2 to respiratory rate), excursion and diaphragmatic contraction speed (diaphragmatic excursion/inspiratory time) by ultrasound, both in supine and prone position. RESULTS: In total, 41 patients were analyzed, 25 succeeded and 16 failed HFNC therapy. At 12 hours, patients who succeeded HFNC therapy presented higher ROX index in supine position (9.8 [9.1-15.6] versus 5.4 [3.9-6.8], P < .01), and higher PaO2 /FiO2 ratio (186 [135-236] versus 117 [103-162] mmHg, P = .03). To predict therapeutic failure, the supine diaphragmatic contraction speed presented sensitivity of 89% and a specificity of 57%, while the ROX index presented a sensitivity of 92.8% and a specificity of 75%. CONCLUSIONS: Diaphragmatic contraction speed by ultrasound emerges as a diagnostic complement to clinical tools to predict HFNC success. Future studies should confirm these results.

IL-6 -572C>G and CARD8 304T>A Genetic Polymorphisms are Associated with the Absolute Neutrophil Count in Patients with Hematological Malignancies Under Chemotherapy: An Application of Multilevel Models to a Preliminary Pharmacogenetic Study.

PURPOSE: Neutropenia is a common event in patients undergoing cytotoxic chemotherapy for the treatment of a hematological malignancy. Some polymorphisms, as IL-6 -572C>G (rs1800796), IL-1ß -31 G>A (rs1143627), and CARD8 304T>A (rs2043211), in genes related to the inflammatory process, could affect the level of absolute neutrophil count (ANC) after chemotherapy. Since an efficient inflammatory process enhances neutrophil survival, we hypothesize that these polymorphisms are associated with ANC. PATIENTS AND METHODS: We carried out a prospective cohort study in two hospitals in Santiago, Chile. The patients included were adults diagnosed with acute myeloblastic leukemia, acute lymphoblastic leukemia, or non-Hodgkin's lymphoma, undergoing cytotoxic chemotherapy. We use a multilevel linear regression model to test our hypothesis. The best model was selected using the Akaike's information criterion (AIC). RESULTS: We analyzed 1726 hemograms and ANCs from 172 hospitalizations from 32 patients. The results show that CC and CG genotypes of IL-6 -572 C>G polymorphism are associated with higher ANCs compared with the GG genotype (Ln (ANC) ~ 0.81 IC95% 0.02-1.55). Similarly, TT and AT genotypes of CARD8 304T>A polymorphism were related to higher ANCs compared with AA (Ln (ANC) ~ 0.95 IC95% 0.02-1.82). IL-1ß genetic polymorphism had no statistically significant association with ANC. CONCLUSION: IL-6 rs1800796 -572C>G and CARD8 rs2043211 304T>A polymorphisms are associated with the absolute neutrophil count in patients undergoing cytotoxic chemotherapy for treatment of hematological malignancies. Our findings might be useful to improve the safety of chemotherapy through predictive ANC models.

[The challenge in colistin dosing: Updating available recommendations]. / El desafio en la dosificación de colistin: actualización de las recomendaciones disponibles.

Polymyxins have been available since the 1960s, however, because of their adverse effects, their use has been reserved for the treatment of infections caused by multiresistant bacteria. The increase in the clinical experience acquired in recent years and the published medical literature have raised doubts about the information provided by the product, indicating the need to update dosage recommendations, pharmacokinetics and pharmacokinetic/pharmacodynamic information (PK/PD). In addition, differences in concentration and dose between the different products of colistin may lead to errors of indication/administration and pose a risk to patients. In 2013, the European Medicines Agency (EMA) commissioned the Committee for Medicinal Products for Human Use (CHPM) to review available data and to make updated recommendations on the use of colistin. This procedure yielded a first report in 2014. This review highlights critical safety and efficacy aspects, reviews the recent pharmacokinetic and stability advances, the available pharmaceutical forms in Chile, providing the schemes currently recommended by health care agencies and experts in the field.

El desafio en la dosificación de colistin: actualización de las recomendaciones disponibles / The challenge in colistin dosing: updating available recommendations

Resumen Las polimixinas están disponibles desde la década de los 60; sin embargo, debido a sus efectos adversos su uso ha sido reservado para el tratamiento de infecciones provocadas por bacterias multi-resistentes. El aumento en la experiencia clínica adquirida en los últimos años y la literatura médica publicada han planteado dudas respecto de la información entregada del producto, poniendo en manifiesto la necesidad de actualizar las recomendaciones posológicas, su farmacocinética y la información farmacocinética/farmacodinámica. Además, las diferencias en cuanto a concentración y dosis entre los distintos productos del colistín pueden dar lugar a errores de indicación/administración y suponer un riesgo para los pacientes. El año 2013, la Agencia Europea de Medicamento (EMA) encargó al Comité de Productos Medicinales para uso Humano (CHPM) la revisión de los datos disponibles y que formulara recomendaciones actualizadas del uso de colistín. Dicho procedimiento arrojó un primer informe en 2014. Esta revisión destaca los aspectos críticos de seguridad y eficacia, revisa los recientes avances farmacocinéticos y de estabilidad, las formas farmacéuticas disponibles en Chile, proporcionando los esquemas actualmente recomendados por agencias sanitarias y expertos en el tema para distintos escenarios clínicos.

Polymyxins have been available since the 1960s, however, because of their adverse effects, their use has been reserved for the treatment of infections caused by multiresistant bacteria. The increase in the clinical experience acquired in recent years and the published medical literature have raised doubts about the information provided by the product, indicating the need to update dosage recommendations, pharmacokinetics and pharmacokinetic/pharmacodynamic information (PK/PD). In addition, differences in concentration and dose between the different products of colistin may lead to errors of indication/administration and pose a risk to patients. In 2013, the European Medicines Agency (EMA) commissioned the Committee for Medicinal Products for Human Use (CHPM) to review available data and to make updated recommendations on the use of colistin. This procedure yielded a first report in 2014. This review highlights critical safety and efficacy aspects, reviews the recent pharmacokinetic and stability advances, the available pharmaceutical forms in Chile, providing the schemes currently recommended by health care agencies and experts in the field.