RESUMO

OBJECTIVE: To determine whether adalimumab administration before mechanical ventilation reduces ventilator-induced lung injury (VILI). METHODS: Eighteen rats randomized into 3 groups underwent mechanical ventilation for 3 hours with a fraction of inspired oxygen = 0.40% including a low tidal volume group (n = 6), where tidal volume = 8mL/kg and positive end-expiratory pressure = 5cmH2O; a high tidal volume group (n = 6), where tidal volume = 35mL/kg and positive end-expiratory pressure = 0; and a pretreated + high tidal volume group (n = 6) where adalimumab (100ug/kg) was administered intraperitoneally 24 hours before mechanical ventilation + tidal volume = 35mL/kg and positive end-expiratory pressure = 0. ANOVA was used to compare histological damage (ATS 2010 Lung Injury Scoring System), pulmonary edema, lung compliance, arterial partial pressure of oxygen, and mean arterial pressure among the groups. RESULTS: After 3 hours of ventilation, the mean histological lung injury score was higher in the high tidal volume group than in the low tidal volume group (0.030 versus 0.0051, respectively, p = 0.003). The high tidal volume group showed diminished lung compliance at 3 hours (p = 0.04) and hypoxemia (p = 0,018 versus control). Pretreated HVt group had an improved histological score, mainly due to a significant reduction in leukocyte infiltration (p = 0.003). CONCLUSION: Histological examination after 3 hours of injurious ventilation revealed ventilator-induced lung injury in the absence of measurable changes in lung mechanics or oxygenation; administering adalimumab before mechanical ventilation reduced lung edema and histological damage.

Assuntos

RESUMO

RESUMO Objetivo: Determinar se a administração de adalimumabe previamente à ventilação mecânica reduz a lesão pulmonar induzida por ventilação mecânica. Métodos: Randomizaram-se 18 ratos em três grupos submetidos à ventilação mecânica por 3 horas com uma fração inspirada de oxigênio de 0,40%. Os três grupos foram assim caracterizados: um grupo com baixo volume corrente (n = 6), no qual se utilizaram volume corrente de 8mL/kg e pressão expiratória final positiva de 5cmH2O; um grupo com alto volume corrente (n = 6), no qual se utilizaram volume corrente de 35mL/kg e pressão expiratória final positiva de zero; e um grupo pré-tratado com alto volume corrente (n = 6), no qual se administraram adalimumabe (100µg/kg) por via intraperitoneal 24 horas antes do início da ventilação mecânica, volume corrente de 35mL/kg e pressão expiratória final positiva de zero. Realizou-se ANOVA para comparação de dano histológico (com utilização de escores segundo o ATS 2010 Lung Injury Scoring System), edema pulmonar, complacência pulmonar, pressão parcial de oxigênio arterial e pressão arterial média entre os grupos. Resultados: Após 3 horas de ventilação, o escore médio de lesão histológica pulmonar foi mais elevado no grupo com alto volume corrente do que no grupo com baixo volume corrente (0,030 versus 0,0051; p = 0,003). O grupo com alto volume corrente demonstrou complacência pulmonar diminuída após 3 horas (p = 0,04) e hipoxemia (p = 0,018 versus controle). O grupo alto volume corrente tratado previamente teve melhora do escore histológico, principalmente devido à redução significante da infiltração leucocitária (p = 0,003). Conclusão: O exame histológico após 3 horas de ventilação lesiva revelou lesão pulmonar induzida por ventilação mecânica na ausência de modificações mensuráveis na mecânica pulmonar e na oxigenação; a administração de adalimumabe antes da ventilação mecânica diminuiu o edema pulmonar e o dano histológico.

ABSTRACT Objective: To determine whether adalimumab administration before mechanical ventilation reduces ventilator-induced lung injury (VILI). Methods: Eighteen rats randomized into 3 groups underwent mechanical ventilation for 3 hours with a fraction of inspired oxygen = 0.40% including a low tidal volume group (n = 6), where tidal volume = 8mL/kg and positive end-expiratory pressure = 5cmH2O; a high tidal volume group (n = 6), where tidal volume = 35mL/kg and positive end-expiratory pressure = 0; and a pretreated + high tidal volume group (n = 6) where adalimumab (100ug/kg) was administered intraperitoneally 24 hours before mechanical ventilation + tidal volume = 35mL/kg and positive end-expiratory pressure = 0. ANOVA was used to compare histological damage (ATS 2010 Lung Injury Scoring System), pulmonary edema, lung compliance, arterial partial pressure of oxygen, and mean arterial pressure among the groups. Results: After 3 hours of ventilation, the mean histological lung injury score was higher in the high tidal volume group than in the low tidal volume group (0.030 versus 0.0051, respectively, p = 0.003). The high tidal volume group showed diminished lung compliance at 3 hours (p = 0.04) and hypoxemia (p = 0,018 versus control). Pretreated HVt group had an improved histological score, mainly due to a significant reduction in leukocyte infiltration (p = 0.003). Conclusion: Histological examination after 3 hours of injurious ventilation revealed ventilator-induced lung injury in the absence of measurable changes in lung mechanics or oxygenation; administering adalimumab before mechanical ventilation reduced lung edema and histological damage.

Assuntos

Assuntos

RESUMO

PURPOSE: We evaluated the effect of antibiotics administered via the respiratory tract to prevent the ventilator-associated pneumonia (VAP) in mechanically ventilated (MV) patients. METHODS: We searched relevant articles for trials that evaluated the impact of prophylactic antibiotics administered through the respiratory tract on the occurrence of VAP. The end-point was the occurrence of VAP in MV patients. RESULTS: We included 6 comparative trials involving 1158 patients (632 received prophylactic antibiotic). Our meta-analysis revealed that prophylactic antibiotics administered through the respiratory tract reduced the occurrence of VAP when compared to placebo or no treatment (OR 0.53; 95% CI 0.34-0.84). This effect was seen when the antibiotics were given by nebulization (OR 0.46; 95% CI 0.22-0.97), but not when they were administered by intratracheal instillation (OR 0.57; 95% CI 0.28-1.15). We did not find a significant difference between the compared groups in the intensive care unit (ICU) mortality (OR 0.89; 95% CI 0.64-1.25). Antibiotic prophylaxis did not impact occurrence of VAP due to multidrug resistant (MDR) pathogens (OR 0.67; 95% CI 0.17-2.62). CONCLUSIONS: Prophylactic antibiotics administered through the respiratory tract by nebulization reduce the occurrence of VAP, without a significant effect on either the ICU mortality or occurrence of VAP due to MDR pathogens.

Assuntos

RESUMO

Acute respiratory distress syndrome is a challenging entity for the intensivist. The pathological hallmark of the acute phase is diffuse alveolar damage, which is present in approximately half of living patients with acute respiratory distress syndrome. It is clear that respiratory support for acute respiratory distress syndrome has gradually been improving over recent decades. However, it is also evident that these procedures are beneficial, as they reduce lung injury and keep the patient alive. This could be interpreted as a time-gaining strategy until the trigger or causal or risk factor improves, the inflammatory storm decreases and the lung heals. However, all except two pharmacological treatments (neuromuscular blockers and steroids) were unable to improve the acute respiratory distress syndrome outcome. The hypothesis that pharmacological negative results may be explained by the histological heterogeneity of acute respiratory distress syndrome has been supported by the recent demonstration that acute respiratory distress syndrome with diffuse alveolar damage constitutes a specific clinical-pathological entity. Given that diffuse alveolar damage is a pathological diagnosis and that open lung biopsy (the most common technique to obtain lung tissue) has several side effects, it is necessary to develop surrogate biomarkers for diffuse alveolar damage. The aim of this narrative review is to address the following three topics related to acute respiratory distress syndrome: (a) the relationship between acute respiratory distress syndrome and diffuse alveolar damage, (b) how diffuse alveolar damage could be surrogated in the clinical setting and

A síndrome do desconforto respiratório agudo é um desafio para o intensivista. A característica principal desta doença aguda é o dano alveolar difuso, presente em cerca de metade dos pacientes com a síndrome. É claro que o suporte respiratório à síndrome do desconforto respiratório agudo tem melhorado gradualmente nas últimas décadas. É também evidente que todos estes procedimentos são benéficos, já que reduzem a lesão pulmonar e mantêm o paciente vivo. Isto deve ser interpretado como uma estratégia de ganho de tempo, até que o fator desencadeante ou de risco causal melhore, assim como a tempestade inflamatória diminua e o pulmão se cure. Por outro lado, todos - exceto dois tratamentos farmacológicos (bloqueadores neuromusculares e esteroides) - são incapazes de melhorar o desfecho da síndrome do desconforto respiratório agudo. A hipótese de que os resultados farmacológicos negativos podem ser explicados pela heterogeneidade histológica da síndrome do desconforto respiratório agudo tem sido apoiada pelas recentes demonstrações de que a síndrome com dano alveolar difuso tem característica clínico-patológica específica. O dano alveolar difuso é um diagnóstico patológico, e a biópsia pulmonar a céu aberto (a técnica mais comum para obtenção de tecido pulmonar) tem efeitos colaterais graves, sendo necessário que se desenvolvam biomarcadores substitutos para o dano alveolar difuso. O objetivo desta revisão é discutir três tópicos relacionados à síndrome do desconforto respiratório agudo: o relacionamento entre a síndrome do desconforto respiratório agudo e o dano alveolar difuso; como o dano alveolar difuso pode ser representado no quadro clínico; e como o enriquecimento pode melhorar os resultados de estudos clínicos farmacológicos realizados com pacientes com a síndrome e com dano alveolar difuso.

Assuntos

RESUMO

RESUMO A síndrome do desconforto respiratório agudo é um desafio para o intensivista. A característica principal desta doença aguda é o dano alveolar difuso, presente em cerca de metade dos pacientes com a síndrome. É claro que o suporte respiratório à síndrome do desconforto respiratório agudo tem melhorado gradualmente nas últimas décadas. É também evidente que todos estes procedimentos são benéficos, já que reduzem a lesão pulmonar e mantêm o paciente vivo. Isto deve ser interpretado como uma estratégia de ganho de tempo, até que o fator desencadeante ou de risco causal melhore, assim como a tempestade inflamatória diminua e o pulmão se cure. Por outro lado, todos - exceto dois tratamentos farmacológicos (bloqueadores neuromusculares e esteroides) - são incapazes de melhorar o desfecho da síndrome do desconforto respiratório agudo. A hipótese de que os resultados farmacológicos negativos podem ser explicados pela heterogeneidade histológica da síndrome do desconforto respiratório agudo tem sido apoiada pelas recentes demonstrações de que a síndrome com dano alveolar difuso tem característica clínico-patológica específica. O dano alveolar difuso é um diagnóstico patológico, e a biópsia pulmonar a céu aberto (a técnica mais comum para obtenção de tecido pulmonar) tem efeitos colaterais graves, sendo necessário que se desenvolvam biomarcadores substitutos para o dano alveolar difuso. O objetivo desta revisão é discutir três tópicos relacionados à síndrome do desconforto respiratório agudo: o relacionamento entre a síndrome do desconforto respiratório agudo e o dano alveolar difuso; como o dano alveolar difuso pode ser representado no quadro clínico; e como o enriquecimento pode melhorar os resultados de estudos clínicos farmacológicos realizados com pacientes com a síndrome e com dano alveolar difuso.

ABSTRACT Acute respiratory distress syndrome is a challenging entity for the intensivist. The pathological hallmark of the acute phase is diffuse alveolar damage, which is present in approximately half of living patients with acute respiratory distress syndrome. It is clear that respiratory support for acute respiratory distress syndrome has gradually been improving over recent decades. However, it is also evident that these procedures are beneficial, as they reduce lung injury and keep the patient alive. This could be interpreted as a time-gaining strategy until the trigger or causal or risk factor improves, the inflammatory storm decreases and the lung heals. However, all except two pharmacological treatments (neuromuscular blockers and steroids) were unable to improve the acute respiratory distress syndrome outcome. The hypothesis that pharmacological negative results may be explained by the histological heterogeneity of acute respiratory distress syndrome has been supported by the recent demonstration that acute respiratory distress syndrome with diffuse alveolar damage constitutes a specific clinical-pathological entity. Given that diffuse alveolar damage is a pathological diagnosis and that open lung biopsy (the most common technique to obtain lung tissue) has several side effects, it is necessary to develop surrogate biomarkers for diffuse alveolar damage. The aim of this narrative review is to address the following three topics related to acute respiratory distress syndrome: (a) the relationship between acute respiratory distress syndrome and diffuse alveolar damage, (b) how diffuse alveolar damage could be surrogated in the clinical setting and (c) how enrichment in diffuse alveolar damage may improve the results of pharmacological clinical trials tried out on patients with acute respiratory distress syndrome.

Assuntos

RESUMO

OBJECTIVE: To demonstrate that among patients with acute respiratory distress syndrome (ARDS), the presence of diffuse alveolar damage (DAD) at histological examination, as compared to its absence, defines a specific subphenotype. METHODS: We studied 149 patients who died in our ICU with the clinical diagnosis of ARDS according to the Berlin Definition (BD) and who had autopsy examination. We compared the change over time of different clinical variables in patients with (n = 49) and without (n = 100) DAD. A predictive model for the presence of DAD was developed and validated in an independent cohort of 57 patients with ARDS and postmortem examination (21 of them with DAD). RESULTS: Patients with DAD, as compared to patients without DAD, had a lower PaO2/FiO2 ratio and dynamic respiratory system compliance, and a higher SOFA score and INR, and were more likely to die of hypoxemia and less likely to die of shock. In multivariate analysis, variables associated with DAD [odds ratio, 95% confidence interval (CI)] were PaO2/FiO2 ratio [0.988 (0.981-0.995)], dynamic respiratory system compliance [0.937 (0.892-0.984)] and age [0.972 (0.946-0.999)]. Areas under the ROC curve (95 % CI) for the classification of DAD using the regression model or the BD were, respectively, 0.74 (0.65-0.82) and 0.64 (0.55-0.72) (p = 0.03). In the validation cohort, the areas under the ROC curve for the diagnosis of DAD were 0.73 (0.56-0.90) and 0.67 (0.54-0.81) for the regression model and the BD, respectively. CONCLUSIONS: The presence of DAD appears to define a specific subphenotype in patients with ARDS. Targeting patients with DAD within the population of patients with the clinical diagnosis of ARDS might be appropriate to find effective therapies for this condition.

Assuntos

RESUMO

La tuberculosis es una patología cuya incidencia mundial se ha incrementado sensiblemente en los últimos años.El cuadro clínico de sepsis severa y shock séptico puede serdesencadenado por cualquier microorganismo. Sin embargo, algunos de ellos, como el complejo micobacterium tuberculosum, solo excepcionalmente lo provocan, por lo cual su diagnóstico constituye un verdadero desafío para el equipo sanitario. Se presenta un caso clínico de una mujer de 23 años de edad,inmunocompetente, que cursando una gestación de 28 semanas ingresó a la unidad de terapia intensiva por un cuadro de insuficiencia respiratoria. Se realizo diagnóstico de shock séptico respiratorio bacteriémico debido a complejo Micobacterium tuberculosum y se confirmó la transmisión materno-fetaldel microorganismo. La enferma falleció a las 48 horas de la admisión con hipoxemia extrema y shock refractario. (AU)

Tuberculosis is a pathology that has evidenced a significant global increase in the last years. Severe sepsis and septic shock may be caused by anymicro-organism. However, some of them, such as the Micobacterium tuberculosum complex, only result inthese clinical symptoms exceptionally, and thus diagnosis constitutes a challenge for the health team. The study presents the case of a 23 year old immunocompetent female patient who was admitted into the Intensive Care Unit at 28 week of gestation due to a respiratory failure. The patient was diagnosed with bacteremia and septic shock caused by Micobacterium tuberculosis and mother-to-child transmission was confirmed. The patient died 48 hours after admission withhypoxemia and refractory shock. (AU)

A tuberculose é uma patologia cuja incidência mundial vem aumentando nos últimos anos. El quadro clínico de sepse severa e choque séptico pode ser desencadeado por qualquer microorganismo. No entanto alguns deles, como o Complexo Micobacteriumtuberculosum, excepcionalmente o provocam e por isso fazer seu diagnóstico é um verdadeiro desafiopara a equipe de saúde. Apresenta-se o caso clínico de uma mujer de 23 anosde idade, imunocompetente na 28ª semana de gravidez ingressou à Unidade de Terapia Intensiva por um quadro de insuficiência respiratória. Realizou-se diagnóstico de choque séptico respiratório bacteriêmico devidoao Complexo Micobacterium tuberculosis e a transmissäo materno-fetal do microorganismo foi confirmada. A paciente faleceu 48 horas depois do ingresso com hipoxemia extrema e choque refratário. (AU)

Assuntos

RESUMO

La tuberculosis es una patología cuya incidencia mundial se ha incrementado sensiblemente en los últimos años.El cuadro clínico de sepsis severa y shock séptico puede serdesencadenado por cualquier microorganismo. Sin embargo, algunos de ellos, como el complejo micobacterium tuberculosum, solo excepcionalmente lo provocan, por lo cual su diagnóstico constituye un verdadero desafío para el equipo sanitario. Se presenta un caso clínico de una mujer de 23 años de edad,inmunocompetente, que cursando una gestación de 28 semanas ingresó a la unidad de terapia intensiva por un cuadro de insuficiencia respiratoria. Se realizo diagnóstico de shock séptico respiratorio bacteriémico debido a complejo Micobacterium tuberculosum y se confirmó la transmisión materno-fetaldel microorganismo. La enferma falleció a las 48 horas de la admisión con hipoxemia extrema y shock refractario.

Tuberculosis is a pathology that has evidenced a significant global increase in the last years. Severe sepsis and septic shock may be caused by anymicro-organism. However, some of them, such as the Micobacterium tuberculosum complex, only result inthese clinical symptoms exceptionally, and thus diagnosis constitutes a challenge for the health team. The study presents the case of a 23 year old immunocompetent female patient who was admitted into the Intensive Care Unit at 28 week of gestation due to a respiratory failure. The patient was diagnosed with bacteremia and septic shock caused by Micobacterium tuberculosis and mother-to-child transmission was confirmed. The patient died 48 hours after admission withhypoxemia and refractory shock.

A tuberculose é uma patologia cuja incidência mundial vem aumentando nos últimos anos. El quadro clínico de sepse severa e choque séptico pode ser desencadeado por qualquer microorganismo. No entanto alguns deles, como o Complexo Micobacteriumtuberculosum, excepcionalmente o provocam e por isso fazer seu diagnóstico é um verdadeiro desafiopara a equipe de saúde. Apresenta-se o caso clínico de uma mujer de 23 anosde idade, imunocompetente na 28ª semana de gravidez ingressou à Unidade de Terapia Intensiva por um quadro de insuficiência respiratória. Realizou-se diagnóstico de choque séptico respiratório bacteriêmico devidoao Complexo Micobacterium tuberculosis e a transmissão materno-fetal do microorganismo foi confirmada. A paciente faleceu 48 horas depois do ingresso com hipoxemia extrema e choque refratário.

Assuntos

RESUMO

OBJECTIVE: Analyze the clinical usefulness of lactate clearance (CL6) immediately after admission to the intensive care unit (ICU) in the first 6 hours. SETTING: Surgical-ICU. Centro de Asistencia del Síndicato Médico of Uruguay. DESIGN: Prospective, analytic and observational study performed between December 1, 2004 and March 31, 2006 in patients over 18 years whose arterial lactate level is higher than 2 mEq/l on admission to the ICU. Lactate clearance (CL6) was defined as the quotient between admissions (L0) minus the six hour lactate level (L6) divided by the admission lactate level. Sensitivity, specificity, positive and negative prognostic value for different CL6 cutoff were analyzed. The optimal CL6 was considered as the cutoff with the highest sum of sensitivity plus specificity. RESULTS: One hundred and eight patients were included; 64 patients died (mortality intra-ICU 59.3%). ICU mortality related variables, identified by Cox regression analysis, were CL6 (HR=0.458; CI 95%, 0.239-0.876), L0 (HR=1.16; CI 95%, 1.033-1.303) and SAPSII (HR=1.019; CI 95%, 1.006-1.034). A CL6 equal to or lower than 0.4 was considered as optimal cutoff with a positive prognostic value of 74% and negative prognostic value of 61%. It was also associated with lower survival adjusted by the SAPSII value and L0. CONCLUSIONS: In critically ill surgical patients, whose CL6 on admission was over 2 mEq/l, lactate clearance in the first six hours could be useful to predict the ICU outcome.

Assuntos