Comparison of central venous minus arterial carbon dioxide pressure to arterial minus central venous oxygen content ratio and lactate levels as predictors of mortality in critically ill patients: a systematic review and meta-analysis. / Comparação da proporção entre pressão venosa central menos arterial de dióxido de carbono e conteúdo de oxigênio arterial menos venoso central e níveis de lactato como preditores de mortalidade em pacientes críticos: uma revisão sistemática e metanálise.

OBJECTIVE: The central venousarterial carbon dioxide pressure to arterial-central venous oxygen content ratio (Pcv-aCO2/Ca-cvO2) is frequently used as a surrogate for tissue oxygenation. We aimed to identify and synthesize literature and quality of evidence supporting Pcv-aCO2/Ca-cvO2 as a predictor of mortality in critically ill patients compared with lactate. METHODS: We searched several databases for studies measuring Pcv-aCO2/Ca-cvO2 in critically ill patients. Independent investigators performed the article screening and data extraction. A random-effects metaanalysis was performed. Pooled standardized mean differences (SMD) were used to compare the prognostic ability of Pcv-aCO2/Ca-cvO2 and lactate. RESULTS: We initially retrieved 172 studies; 17 were included for qualitative description, and 10 were included for quantitative synthesis. The mean Pcv-aCO2/Ca-cvO2 was higher in nonsurvivors than in survivors (pooled SMD = 0.75; 95%CI 0.34 - 1.17; I2 = 83%), as was the case with lactate levels (pooled SMD = 0.94; 95%CI 0.34 - 1.54; I2 = 92%). Both tests were statistically significant predictors of mortality, albeit with overlapping 95%CIs between them. CONCLUSION: Moderate-quality evidence showed little or no difference in the ability of Pcv-aCO2/Ca-cvO2, compared with lactate, to predict mortality. Nevertheless, our conclusions are limited by the considerable heterogeneity among the studies.PROSPERO registration: CRD42019130387.

OBJETIVO: A proporção entre pressão venosa central menos arterial de dióxido de carbono e conteúdo de oxigênio arterial menos venoso central (Pcv-aCO2/Ca-cvO2) é frequentemente usada como substituta para a oxigenação tecidual. O objetivo deste estudo foi identificar e sintetizar a literatura e a qualidade das evidências que suportam a Pcv-aCO2/Ca-cvO2 como um preditor de mortalidade em comparação com o lactato em pacientes críticos. MÉTODOS: Pesquisamos vários bancos de dados procurando estudos que tivessem medido a Pcv-aCO2/Ca-cvO2 em pacientes críticos. Pesquisadores independentes realizaram a triagem dos artigos e a extração de dados. Uma metanálise de efeitos aleatórios foi realizada. Diferenças médias padronizadas agrupadas foram usadas para comparar a capacidade prognóstica da Pcv-aCO2/Ca-cvO2 e do lactato. RESULTADOS: Inicialmente, obtivemos 172 estudos; 17 foram incluídos para descrição qualitativa, e dez foram incluídos para síntese quantitativa. A média de Pcv-aCO2/Ca-cvO2 foi maior nos não sobreviventes do que nos sobreviventes (diferença média padronizada agrupada de 0,75; IC95% 0,34 - 1,17; I2 = 83%), assim como os níveis de lactato (diferença média padronizada agrupada = 0,94; IC95% 0,34 - 1,54; I2 = 92%). Ambos os testes foram preditores estatisticamente significativos de mortalidade, embora com sobreposição de IC95% entre eles. CONCLUSÃO: Evidências de qualidade moderada mostraram pouca ou nenhuma diferença na capacidade da Pcv-aCO2/Ca-cvO2, em comparação com o lactato, em predizer mortalidade. No entanto, nossas conclusões são limitadas pela considerável heterogeneidade entre os estudos.Registro no PROSPERO: CRD42019130387.

Comparação da proporção entre pressão venosa central menos arterial de dióxido de carbono e conteúdo de oxigênio arterial menos venoso central e níveis de lactato como preditores de mortalidade em pacientes críticos: uma revisão sistemática e metanálise / Comparison of central venous minus arterial carbon dioxide pressure to arterial minus central venous oxygen content ratio and lactate levels as predictors of mortality in critically ill patients: a systematic review and meta-analysis

RESUMO Objetivo: A proporção entre pressão venosa central menos arterial de dióxido de carbono e conteúdo de oxigênio arterial menos venoso central (Pcv-aCO2/Ca-cvO2) é frequentemente usada como substituta para a oxigenação tecidual. O objetivo deste estudo foi identificar e sintetizar a literatura e a qualidade das evidências que suportam a Pcv-aCO2/Ca-cvO2 como um preditor de mortalidade em comparação com o lactato em pacientes críticos. Métodos: Pesquisamos vários bancos de dados procurando estudos que tivessem medido a Pcv-aCO2/Ca-cvO2 em pacientes críticos. Pesquisadores independentes realizaram a triagem dos artigos e a extração de dados. Uma metanálise de efeitos aleatórios foi realizada. Diferenças médias padronizadas agrupadas foram usadas para comparar a capacidade prognóstica da Pcv-aCO2/Ca-cvO2 e do lactato. Resultados: Inicialmente, obtivemos 172 estudos; 17 foram incluídos para descrição qualitativa, e dez foram incluídos para síntese quantitativa. A média de Pcv-aCO2/Ca-cvO2 foi maior nos não sobreviventes do que nos sobreviventes (diferença média padronizada agrupada de 0,75; IC95% 0,34 - 1,17; I2 = 83%), assim como os níveis de lactato (diferença média padronizada agrupada = 0,94; IC95% 0,34 - 1,54; I2 = 92%). Ambos os testes foram preditores estatisticamente significativos de mortalidade, embora com sobreposição de IC95% entre eles. Conclusão: Evidências de qualidade moderada mostraram pouca ou nenhuma diferença na capacidade da Pcv-aCO2/Ca-cvO2, em comparação com o lactato, em predizer mortalidade. No entanto, nossas conclusões são limitadas pela considerável heterogeneidade entre os estudos. Registro no PROSPERO:CRD42019130387

ABSTRACT Objective: The central venousarterial carbon dioxide pressure to arterial-central venous oxygen content ratio (Pcv-aCO2/Ca-cvO2) is frequently used as a surrogate for tissue oxygenation. We aimed to identify and synthesize literature and quality of evidence supporting Pcv-aCO2/Ca-cvO2 as a predictor of mortality in critically ill patients compared with lactate. Methods: We searched several databases for studies measuring Pcv-aCO2/Ca-cvO2 in critically ill patients. Independent investigators performed the article screening and data extraction. A random-effects metaanalysis was performed. Pooled standardized mean differences (SMD) were used to compare the prognostic ability of Pcv-aCO2/Ca-cvO2 and lactate. Results: We initially retrieved 172 studies; 17 were included for qualitative description, and 10 were included for quantitative synthesis. The mean Pcv-aCO2/Ca-cvO2 was higher in nonsurvivors than in survivors (pooled SMD = 0.75; 95%CI 0.34 - 1.17; I2 = 83%), as was the case with lactate levels (pooled SMD = 0.94; 95%CI 0.34 - 1.54; I2 = 92%). Both tests were statistically significant predictors of mortality, albeit with overlapping 95%CIs between them. Conclusion: Moderate-quality evidence showed little or no difference in the ability of Pcv-aCO2/Ca-cvO2, compared with lactate, to predict mortality. Nevertheless, our conclusions are limited by the considerable heterogeneity among the studies. PROSPERO registration:CRD42019130387

Clinical and epidemiological features of tuberculosis isolated from critically ill patients.

Human tuberculosis is still a major world health concern. In Uruguay, contrary to the world trend, an increase in cases has been observed since 2006. Although the incidence of MDR-resistant strains is low and no cases of XDR-TB were registered, an increase in the number of patients with severe tuberculosis requiring critical care admission was observed. As a first aim, we performed the analysis of the genetic structure of strains isolated from patients with severe tuberculosis admitted to an intensive care unit. We compared these results with those corresponding to the general population observing a statistically significant increase in the Haarlem genotypes among ICU patients (53.3% vs 34.7%; p<0.05). In addition, we investigated the association of clinical outcomes with the genotype observing a major incidence of hepatic dysfunctions among patients infected with the Haarlem strain (p<0.05). The cohort presented is one of the largest studied series of critically ill patients with tuberculosis.

Plano de análise estatística para o estudo do tratamento precoce baseado em metas com utilização de uma visão fisiológica holística - estudo ANDROMEDA-SHOCK: um estudo randomizado e controlado / Statistical analysis plan for early goal-directed therapy using a physiological holistic view - the ANDROMEDA-SHOCK: a randomized controlled trial

RESUMO Fundamentação: O estudo ANDROMEDA-SHOCK é um estudo internacional, multicêntrico, randomizado e controlado comparando ressuscitação guiada pela perfusão periférica com ressuscitação guiada pelo lactato em pacientes com choque séptico, com a finalidade de testar a hipótese de que a ressuscitação guiada pela perfusão periférica associa-se a menor morbidade e mortalidade. Objetivo: Relatar o plano de análise estatística para o estudo ANDROMEDA-SHOCK. Métodos: Descrevemos o delineamento do estudo, os objetivos primário e secundários, pacientes, métodos de randomização, intervenções, desfechos e tamanho da amostra. Descrevemos nossos planos de análise estatística para os desfechos primários, secundários e terciários. Também descrevemos as análises de subgrupos e sensibilidade. Finalmente, fornecemos detalhes para a apresentação dos resultados, inclusive modelos de tabelas para apresentar as características basais, a evolução das variáveis de hemodinâmica e perfusão, e os efeitos dos tratamentos nos desfechos. Conclusão: Segundo as melhores práticas de pesquisa, relatamos nosso plano de análise estatística e plano de gestão de dados antes do fechamento da base de dados e do início da análise dos dados. Nossa expectativa é que este procedimento previna a ocorrência de vieses na análise e incremente a utilidade dos resultados relatados.

ABSTRACT Background: ANDROMEDA-SHOCK is an international, multicenter, randomized controlled trial comparing peripheral perfusion-targeted resuscitation to lactate-targeted resuscitation in patients with septic shock in order to test the hypothesis that resuscitation targeting peripheral perfusion will be associated with lower morbidity and mortality. Objective: To report the statistical analysis plan for the ANDROMEDA-SHOCK trial. Methods: We describe the trial design, primary and secondary objectives, patients, methods of randomization, interventions, outcomes, and sample size. We describe our planned statistical analysis for the primary, secondary and tertiary outcomes. We also describe the subgroup and sensitivity analyses. Finally, we provide details for presenting our results, including mock tables showing baseline characteristics, the evolution of hemodynamic and perfusion variables, and the effects of treatments on outcomes. Conclusion: According to the best trial practice, we report our statistical analysis plan and data management plan prior to locking the database and initiating the analyses. We anticipate that this procedure will prevent analysis bias and enhance the utility of the reported results.

Statistical analysis plan for early goal-directed therapy using a physiological holistic view - the ANDROMEDA-SHOCK: a randomized controlled trial. / Plano de análise estatística para o estudo do tratamento precoce baseado em metas com utilização de uma visão fisiológica holística - estudo ANDROMEDA-SHOCK: um estudo randomizado e controlado.

BACKGROUND: ANDROMEDA-SHOCK is an international, multicenter, randomized controlled trial comparing peripheral perfusion-targeted resuscitation to lactate-targeted resuscitation in patients with septic shock in order to test the hypothesis that resuscitation targeting peripheral perfusion will be associated with lower morbidity and mortality. OBJECTIVE: To report the statistical analysis plan for the ANDROMEDA-SHOCK trial. METHODS: We describe the trial design, primary and secondary objectives, patients, methods of randomization, interventions, outcomes, and sample size. We describe our planned statistical analysis for the primary, secondary and tertiary outcomes. We also describe the subgroup and sensitivity analyses. Finally, we provide details for presenting our results, including mock tables showing baseline characteristics, the evolution of hemodynamic and perfusion variables, and the effects of treatments on outcomes. CONCLUSION: According to the best trial practice, we report our statistical analysis plan and data management plan prior to locking the database and initiating the analyses. We anticipate that this procedure will prevent analysis bias and enhance the utility of the reported results.

FUNDAMENTAÇÃO: O estudo ANDROMEDA-SHOCK é um estudo internacional, multicêntrico, randomizado e controlado comparando ressuscitação guiada pela perfusão periférica com ressuscitação guiada pelo lactato em pacientes com choque séptico, com a finalidade de testar a hipótese de que a ressuscitação guiada pela perfusão periférica associa-se a menor morbidade e mortalidade. OBJETIVO: Relatar o plano de análise estatística para o estudo ANDROMEDA-SHOCK. MÉTODOS: Descrevemos o delineamento do estudo, os objetivos primário e secundários, pacientes, métodos de randomização, intervenções, desfechos e tamanho da amostra. Descrevemos nossos planos de análise estatística para os desfechos primários, secundários e terciários. Também descrevemos as análises de subgrupos e sensibilidade. Finalmente, fornecemos detalhes para a apresentação dos resultados, inclusive modelos de tabelas para apresentar as características basais, a evolução das variáveis de hemodinâmica e perfusão, e os efeitos dos tratamentos nos desfechos. CONCLUSÃO: Segundo as melhores práticas de pesquisa, relatamos nosso plano de análise estatística e plano de gestão de dados antes do fechamento da base de dados e do início da análise dos dados. Nossa expectativa é que este procedimento previna a ocorrência de vieses na análise e incremente a utilidade dos resultados relatados.

Effects of early hemodynamic resuscitation on left ventricular performance and microcirculatory function during endotoxic shock.

BACKGROUND: Microcirculation and macrohemodynamics are severely compromised during septic shock. However, the relationship between these two compartments needs to be further investigated. We hypothesized that early resuscitation restores left ventricular (LV) performance and microcirculatory function but fails to prevent metabolic disorders. We studied the effects of an early resuscitation protocol (ERP) on LV pressure/volume loops-derived parameters, sublingual microcirculation, and metabolic alterations during endotoxic shock. METHODS: Twenty-five pigs were randomized into three groups: LPS group: Escherichia coli lipopolysaccharide (LPS); ERP group: LPS + ERP based on volume expansion, dobutamine, and noradrenaline infusion; Sham group. LV pressure/volume-derived parameters, systemic hemodynamics, sublingual microcirculation, and metabolic profile were assessed at baseline and after completing the resuscitation protocol. RESULTS: LPS significantly decreased LV end-diastolic volume, myocardial contractility, stroke work, and cardiac index (CI). Early resuscitation preserved preload, and myocardial contractility, increased CI and heart rate (p < .05). LPS severely diminished sublingual microvascular flow index (MFI), perfused vascular density (PVD), and the proportion of perfused vessels (PPV), while increased the heterogeneity flow index (HFI) (p < .05). Despite MFI was relatively preserved, MVD, PVD, and HFI were significantly impaired after resuscitation (p < .05). The macro- and microcirculatory changes were associated with increased lactic acidosis and mixed venous O2 saturation when compared to baseline values (p < .05). The scatter plot between mean arterial pressure (MAP) and MFI showed a biphasic relationship, suggesting that the values were within the limits of microvascular autoregulation when MAP was above 71 ± 6 mm Hg (R (2) = 0.63). CONCLUSIONS: Early hemodynamic resuscitation was effective to restore macrohemodynamia and myocardial contractility. Despite MAP and MFI were relatively preserved, the persistent microvascular dysfunction could explain metabolic disorders. The relationship between micro- and systemic hemodynamia and their impact on cellular function and metabolism needs to be further studied during endotoxic shock.

Interrater Reliability and Diagnostic Performance of Subjective Evaluation of Sublingual Microcirculation Images by Physicians and Nurses: A Multicenter Observational Study.

INTRODUCTION: This was a cross-sectional multicenter study to investigate the ability of physicians and nurses from three different countries to subjectively evaluate sublingual microcirculation images and thereby discriminate normal from abnormal sublingual microcirculation based on flow and density abnormalities. METHODS: Forty-five physicians and 61 nurses (mean age, 36 ± 10 years; 44 males) from three different centers in The Netherlands (n = 61), Uruguay (n = 12), and Japan (n = 33) were asked to subjectively evaluate a sample of 15 microcirculation videos randomly selected from an experimental model of endotoxic shock in pigs. All videos were first analyzed offline using the A.V.A. software by an independent, experienced investigator and were categorized as good, bad, or very bad microcirculation based on the microvascular flow index, perfused capillary density, and proportion of perfused capillaries. Then, the videos were randomly assigned to the examiners, who were instructed to subjectively categorize each image as good, bad, or very bad. An interrater analysis was performed, and sensitivity and specificity tests were calculated to evaluate the proportion of A.V.A. score abnormalities that the examiners correctly identified. RESULTS: The κ statistics indicated moderate agreement in the evaluation of microcirculation abnormalities using three categories, i.e., good, bad, or very bad (κ = 0.48), and substantial agreement using two categories, i.e., normal (good) and abnormal (bad or very bad) (κ = 0.66). There was no significant difference between the κ three and κ two statistics. We found that the examiner's subjective evaluations had good diagnostic performance and were highly sensitive (84%; 95% confidence interval, 81%-86%) and specific (87%; 95% confidence interval, 84%-90%) for sublingual microcirculatory abnormalities as assessed using the A.V.A. software. CONCLUSIONS: The subjective evaluations of sublingual microcirculation by physicians and nurses agreed well with a conventional offline analysis and were highly sensitive and specific for sublingual microcirculatory abnormalities.

Desarrollo y validación de un cuestionario específico de evaluación de la satisfacción del paciente diabético con glucómetros / Development and validation of a specific questionnaire to evaluate diabetic patient satisfaction with the use of glucometers

OBJETIVO: Desarrollar un cuestionario específico de evaluación de la satisfacción del paciente diabético con el uso del glucómetro y evaluar sus propiedades psicométricas (factibilidad, fiabilidad y validez). MATERIAL Y MÉTODOS: 1) Tras una revisión bibliográfica se construyó un banco de 53 ítems inicial. Un panel de 6 expertos y 50 pacientes concluyeron una versión del cuestionario de 25 ítems (dimensiones: satisfacción, molestias, valor añadido y aspecto). 2) Para la validación del instrumento se diseñó un estudio epidemiológico, multicéntrico y transversal de 2 meses de duración en el que participaron 283 pacientes mayores de edad con diabetes mellitus (DM) (tipo 1 y tipo 2) que usaban un glucómetro portátil. Se recogieron las respuestas al cuestionario SATIGLU, junto con variables complementarias en visita única. Para evaluar la fiabilidad Test-Retest, 51 pacientes han respondido al cuestionario tras 15 días de la primera visita. RESULTADOS: El cuestionario demuestra tener alta consistencia interna (α de Cronbach de 0,88). Además muestra correlación positiva y estadísticamente significativa con los cuestionarios de medida de la satisfacción del paciente con el tratamiento en general (SAT-Q) y con el tratamiento para la DM (DTSQs(c)). Se observaron diferencias estadísticamente significativas en la puntuación total del cuestionario en función del tipo de DM a favor de los DMT1 (z = 6,69; p = 0,000), y en hemoglobina glucosilada a favor de los pacientes con HbA1c < 7 (z = -3,13; p = 0,002). CONCLUSIONES: El cuestionario SATIGLU muestra unas adecuadas propiedades psicométricas como instrumento de evaluación de la satisfacción de los pacientes diabéticos con el uso del glucómetro

OBJECTIVE: The aim of the study was to develop a specific questionnaire to assess patient satisfaction with the use of glucometers, and to evaluate their psychometric properties (feasibility, reliability and validity). MATERIAL AND METHODS: (I) An initial 53 item bank was constructed from a systematic review of literature. A panel composed of 6 experts and 50 patients concluded a 25 item version of the questionnaire (dimensions: Satisfaction, inconveniences, added value and appearance). (II) In order to evaluate the psychometric properties, an epidemiological multi-centred, crosssectional and 2 month long study was designed, for which 283 patients 18 years or older who were suffering from DM (type 1 and 2) and using a portable glucometer were recruited. Responses to the questionnaire that was the purpose of the study were gathered, together with complementary variables in a single visit. To evaluate test-retest reliability, 51 patients responded again 15 days after initial visit. RESULTS: There was high internal consistency (Cronbach alpha = 0.88). Moreover, it showed a positive and statistically significant correlation with patient overall satisfaction (SAT-Q), and with patient treatment-satisfaction (DTSQs(c)) questionnaires. Statistically significant differences were found in SATIGLU total score depending on the type of DM, in favour of type 1 DM patients (z = 6.69; P = 0.000), and glycated haemoglobin favouring patients who observe a good control of their disease, HbA1c < 7 (z = -3.13; P = 0.002). CONCLUSION: The SATIGLU Questionnaire showed adequate psychometric properties as an evaluation tool of patient satisfaction with the use of glucometers

[Salbutamol improves diaphragm force generation in experimental sepsis]. / El salbutamol mejora la fuerza diafragmática en la sepsis experimental.

OBJECTIVE: In a high percentage of cases, severe sepsis is accompanied by acute respiratory failure, in which weakness of the respiratory muscles plays an important role. Weakened respiratory muscles that are subjected to an increased mechanical load may develop muscle fatigue, with exacerbation of the respiratory failure. Because beta2-adrenergic drugs increase muscle contraction force, they may play a role in preventing and managing respiratory failure in septic patients. Our aim was to study the effects of salbutamol on diaphragm function in an animal model of peritoneal sepsis. MATERIAL AND METHODS: The study included 3 groups of animals: a) a control group (n=7), in which the animals underwent a median laparotomy without visceral manipulation; b) a septic group (n=10), in which peritoneal sepsis was induced by cecal ligation and puncture (CLP); and c) a salbutamol group (n=7), in which peritoneal sepsis (CLP) was treated with salbutamol. Hemodynamic parameters and blood gases were measured in vivo. Diaphragm function was evaluated in vitro. RESULTS: Salbutamol increased aortic blood flow and heart rate while it reduced mean arterial pressure in the animals with peritoneal sepsis (P< .05). Sepsis produced a significant drop in diaphragmatic force both before and after the application of a muscle-fatigue protocol. Treatment with salbutamol improved muscle contraction force before and after application of the protocol (P< .05). CONCLUSIONS: The use of beta2-adrenergic drugs such as salbutamol improves diaphragm function in experimental sepsis. The mechanisms that produce this improvement require further study.

El salbutamol mejora la fuerza diafragmática en la sepsis experimental / Salbutamol improves diaphragm force generation in experimental sepsis

Objetivo: La sepsis grave se acompaña en un alto porcentaje de casos de insuficiencia respiratoria aguda, donde la debilidad de los músculos respiratorios desempeña un papel importante. Los músculos respiratorios debilitados y sometidos a una carga mecánica aumentada pueden evolucionar a fatiga muscular con agravamiento de la insuficiencia respiratoria. Los fármacos adrenérgicos β2, al mejorar la fuerza de contracción muscular, podrían ser de utilidad en la prevención y el manejo de la insuficiencia respiratoria de pacientes con sepsis. El objetivo de este trabajo ha sido estudiar los efectos del salbutamol en la función diafragmática en un modelo animal de sepsis peritoneal. Material y métodos: Se estudiaron 3 grupos de animales: a) grupo control (n = 7), al que se realizó laparotomía mediana sin abordaje visceral; b) grupo sepsis (n = 10), al que se indujo sepsis peritoneal por ligadura y punción cecal (LPC), y c) grupo salbutamol (n = 7), en el que la sepsis peritoneal se trató con salbutamol (LPC + salbutamol). Los parámetros hemodinámicos y los gases sanguíneos se midieron in vivo. La función diafragmática se evaluó in vitro. Resultados: El salbutamol aumentó el flujo aórtico y la frecuencia cardíaca a la vez que disminuyó la presión arterial media en la sepsis peritoneal (p < 0,05). La sepsis determinó una caída significativa de la fuerza diafragmática tanto antes como después de un protocolo de fatiga muscular. El tratamiento con salbutamol mejoró la fuerza de contracción muscular en ambos casos (p < 0,05). Conclusiones: El uso de agentes adrenérgicos β2 como el salbutamol mejora la función diafragmática durante la sepsis experimental. Los mecanismos de esta mejoría deben estudiarse en mayor profundidad

Objective: In a high percentage of cases, severe sepsis is accompanied by acute respiratory failure, in which weakness of the respiratory muscles plays an important role. Weakened respiratory muscles that are subjected to an increased mechanical load may develop muscle fatigue, with exacerbation of the respiratory failure. Because β2-adrenergic drugs increase muscle contraction force, they may play a role in preventing and managing respiratory failure in septic patients. Our aim was to study the effects of salbutamol on diaphragm function in an animal model of peritoneal sepsis. Material and methods: The study included 3 groups of animals: a) a control group (n=7), in which the animals underwent a median laparotomy without visceral manipulation; b) a septic group (n=10), in which peritoneal sepsis was induced by cecal ligation and puncture (CLP); and c) a salbutamol group (n=7), in which peritoneal sepsis (CLP) was treated with salbutamol. Hemodynamic parameters and blood gases were measured in vivo. Diaphragm function was evaluated in vitro. Results: Salbutamol increased aortic blood flow and heart rate while it reduced mean arterial pressure in the animals with peritoneal sepsis (P<.05). Sepsis produced a significant drop in diaphragmatic force both before and after the application of a muscle-fatigue protocol. Treatment with salbutamol improved muscle contraction force before and after application of the protocol (P<.05). Conclusions: The use of β2-adrenergic drugs such as salbutamol improves diaphragm function in experimental sepsis. The mechanisms that produce this improvement require further study

The role of bundles in sepsis care.

The understanding of the pathogenesis of sepsis has substantially changed in past years and continues to improve. New therapeutic options are being developed and incorporated into clinical practice. There are different specific interventions and therapies that benefit patients' outcome. As demonstrated by the early goal-directed therapy strategy, the success of the resuscitation treatment is strongly time dependent. The recognition of severe sepsis should be accompanied without delay by very well defined therapeutic measures. In 2002 the Surviving Sepsis Campaign was introduced with the overall goal of increasing clinicians' awareness and improving outcome in severe sepsis and septic shock.