Executive Summary: International Clinical Practice Guidelines for Pediatric Ventilator Liberation, A Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Document.

Rationale: Pediatric-specific ventilator liberation guidelines are lacking despite the many studies exploring elements of extubation readiness testing. The lack of clinical practice guidelines has led to significant and unnecessary variation in methods used to assess pediatric patients' readiness for extubation. Methods: Twenty-six international experts comprised a multiprofessional panel to establish pediatrics-specific ventilator liberation clinical practice guidelines, focusing on acutely hospitalized children receiving invasive mechanical ventilation for more than 24 hours. Eleven key questions were identified and first prioritized using the Modified Convergence of Opinion on Recommendations and Evidence. A systematic review was conducted for questions that did not meet an a priori threshold of ⩾80% agreement, with Grading of Recommendations, Assessment, Development, and Evaluation methodologies applied to develop the guidelines. The panel evaluated the evidence and drafted and voted on the recommendations. Measurements and Main Results: Three questions related to systematic screening using an extubation readiness testing bundle and a spontaneous breathing trial as part of the bundle met Modified Convergence of Opinion on Recommendations criteria of ⩾80% agreement. For the remaining eight questions, five systematic reviews yielded 12 recommendations related to the methods and duration of spontaneous breathing trials, measures of respiratory muscle strength, assessment of risk of postextubation upper airway obstruction and its prevention, use of postextubation noninvasive respiratory support, and sedation. Most recommendations were conditional and based on low to very low certainty of evidence. Conclusions: This clinical practice guideline provides a conceptual framework with evidence-based recommendations for best practices related to pediatric ventilator liberation.

Inhaled magnesium versus inhaled salbutamol in rescue treatment for moderate and severe asthma exacerbations in pediatric patients.

OBJECTIVE: To compare the effectiveness of inhaled Magnesium Sulfate associated with Salbutamol versus Inhaled Salbutamol alone in patients with moderate and severe asthma exacerbations. METHOD: Clinical, prospective and randomized study with patients between 3 and 14 years of age divided into two groups: one to receive inhaled salbutamol associated with magnesium sulfate (GSM), the other to receive inhaled salbutamol alone (GS). The sample consisted of 40 patients, 20 patients in each group. Severity was classified using the modified Wood-Downes score, with values between 4 and 7 classified as moderate and 8 or more classified as severe. RESULTS: Post-inhalation scores decreased both in patients who received salbutamol and magnesium and in those who received salbutamol alone, with no statistically significant difference between the groups. CONCLUSIONS: Despite the benefits when administered intravenously, inhalation of the drug alone or in combination did not reduce the severity of the exacerbation.

Association of Extubation Failure Rates With High-Flow Nasal Cannula, Continuous Positive Airway Pressure, and Bilevel Positive Airway Pressure vs Conventional Oxygen Therapy in Infants and Young Children: A Systematic Review and Network Meta-Analysis.

Importance: Extubation failure (EF) has been associated with worse outcomes in critically ill children. The relative efficacy of different modes of noninvasive respiratory support (NRS) to prevent EF is unknown. Objective: To study the reported relative efficacy of different modes of NRS (high-flow nasal cannula [HFNC], continuous positive airway pressure [CPAP], and bilevel positive airway pressure [BiPAP]) compared to conventional oxygen therapy (COT). Data Sources: MEDLINE, Embase, and CINAHL Complete through May 2022. Study Selection: Randomized clinical trials that enrolled critically ill children receiving invasive mechanical ventilation for more than 24 hours and compared the efficacy of different modes of postextubation NRS. Data Extraction and Synthesis: Random-effects models were fit using a bayesian network meta-analysis framework. Between-group comparisons were estimated using odds ratios (ORs) or mean differences with 95% credible intervals (CrIs). Treatment rankings were assessed by rank probabilities and the surface under the cumulative rank curve (SUCRA). Main Outcomes and Measures: The primary outcome was EF (reintubation within 48 to 72 hours). Secondary outcomes were treatment failure (TF, reintubation plus NRS escalation or crossover to another NRS mode), pediatric intensive care unit (PICU) mortality, PICU and hospital length of stay, abdominal distension, and nasal injury. Results: A total of 11 615 citations were screened, and 9 randomized clinical trials with a total of 1421 participants were included. Both CPAP and HFNC were found to be more effective than COT in reducing EF and TF (CPAP: OR for EF, 0.43; 95% CrI, 0.17-1.0 and OR for TF 0.27, 95% CrI 0.11-0.57 and HFNC: OR for EF, 0.64; 95% CrI, 0.24-1.0 and OR for TF, 0.34; 95% CrI, 0.16- 0.65). CPAP had the highest likelihood of being the best intervention for both EF (SUCRA, 0.83) and TF (SUCRA, 0.91). Although not statistically significant, BiPAP was likely to be better than COT for preventing both EF and TF. Compared to COT, CPAP and BiPAP were reported as showing a modest increase (approximately 3%) in nasal injury and abdominal distension. Conclusions and Relevance: The studies included in this systematic review and network meta-analysis found that compared with COT, EF and TF rates were lower with modest increases in abdominal distension and nasal injury. Of the modes evaluated, CPAP was associated with the lowest rates of EF and TF.

Operational Definitions Related to Pediatric Ventilator Liberation.

BACKGROUND: Common, operational definitions are crucial to assess interventions and outcomes related to pediatric mechanical ventilation. These definitions can reduce unnecessary variability among research and quality improvement efforts, to ensure findings are generalizable, and can be pooled to establish best practices. RESEARCH QUESTION: Can we establish operational definitions for key elements related to pediatric ventilator liberation using a combination of detailed literature review and consensus-based approaches? STUDY DESIGN AND METHODS: A panel of 26 international experts in pediatric ventilator liberation, two methodologists, and two librarians conducted systematic reviews on eight topic areas related to pediatric ventilator liberation. Through a series of virtual meetings, we established draft definitions that were voted upon using an anonymous web-based process. Definitions were revised by incorporating extracted data gathered during the systematic review and discussed in another consensus meeting. A second round of voting was conducted to confirm the final definitions. RESULTS: In eight topic areas identified by the experts, 16 preliminary definitions were established. Based on initial discussion and the first round of voting, modifications were suggested for 11 of the 16 definitions. There was significant variability in how these items were defined in the literature reviewed. The final round of voting achieved ≥ 80% agreement for all 16 definitions in the following areas: what constitutes respiratory support (invasive mechanical ventilation and noninvasive respiratory support), liberation and failed attempts to liberate from invasive mechanical ventilation, liberation from respiratory support, duration of noninvasive respiratory support, total duration of invasive mechanical ventilation, spontaneous breathing trials, extubation readiness testing, 28 ventilator-free days, and planned vs rescue use of post-extubation noninvasive respiratory support. INTERPRETATION: We propose that these consensus-based definitions for elements of pediatric ventilator liberation, informed by evidence, be used for future quality improvement initiatives and research studies to improve generalizability and facilitate comparison.

Use of Dexamethasone to Prevent Extubation Failure in Pediatric Intensive Care Unit: A Randomized Controlled Clinical Trial.

Extubation failure is a common event in intensive care units. Corticosteroids are effective in preventing failure in adults, but no consensus has been reached on this matter in pediatrics. We assessed the efficacy of intravenous dexamethasone in mechanically ventilated children and adolescents for more than 48 hours, with at least one risk factor for failure. Extubations were scheduled 24 hours in advance when possible, and patients were randomly assigned into two groups: one group received a loading dose followed by up to four doses of dexamethasone, and the other group received no corticosteroids. Need for reintubation and length of stay in the pediatric intensive care unit were similar in both groups, and frequency of reintubation was 12.9%.

Antibiotic treatment schemes for very severe community-acquired pneumonia in children: a randomized clinical study.

OBJECTIVE: To compare clinical response to initial empiric treatment with oxacillin plus ceftriaxone and amoxicillin plus clavulanic acid in hospitalized children diagnosed with very severe community-acquired pneumonia (CAP). METHODS: A prospective randomized clinical study was conducted among children 2 months to 5 years old with a diagnosis of very severe CAP in the pediatric ward of São Paulo State University Hospital in Botucatu, São Paulo, Brazil, from April 2007 to May 2008. Patients were randomly divided into two groups by type of treatment: an oxacillin/ceftriaxone group (OCG, n = 48) and an amoxicillin/clavulanic acid group (ACG, n = 56). Analyzed outcomes were: time to clinical improvement (fever and tachypnea), time on oxygen therapy, length of stay in hospital, need to widen antimicrobial spectrum, and complications (including pleural effusion). RESULTS: The two groups did not differ statistically for age, sex, symptom duration before admission, or previous antibiotic treatment. Time to improve tachypnea was less among ACG patients than OCG patients (4.8 ± 2.2 versus 5.8 ± 2.4 days respectively; P = 0.028), as was length of hospital stay (11.0 ± 6.2 versus 14.4 ± 4.5 days respectively; P = 0.002). There were no statistically significant differences between the two groups for fever improvement time, time on oxygen therapy, need to widen antimicrobial spectrum, or frequency of pleural effusion. CONCLUSIONS: Both treatment plans are effective in treating very severe CAP in 2-month-to 5-year-old hospitalized children. The only analyzed outcome that favored amoxicillin/clavulanic acid treatment was time required to improve tachypnea. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT01166932.

Diagnosis and treatment of streptococcal toxic shock syndrome in the pediatric intensive care unit: a case report. / Diagnóstico e tratamento da síndrome do choque tóxico estreptocócico em unidade de terapia intensiva pediátrica: relato de caso.

Among the infections caused by Streptococcus ß hemolyticus from the Lancefield serogroup A, toxic shock syndrome is perhaps the most severe, and its mortality rate is high. Its clinical similarity to other forms of shock, especially septic shock, can often confuse the evaluator and interfere with the selection of the most appropriate therapy. This report aims to inform readers of the need to add this syndrome as a differential diagnosis in cases of shock, especially those with no well-defined clinical manifestations. For this purpose, we present the case of an infant with common flu-like symptoms who progressed rapidly with a rash, a reduced level of consciousness and clinical and laboratory signs of shock that required intensive support. In addition to cultures indicating the etiological agent, the appearance of exanthema and necrotizing fasciitis led to the diagnosis. However, less than 50% of cases present classic clinical signs of this entity. Penicillins combined with aminoglycosides are still the therapy of choice and are supported by a high level of evidence. Despite the severity of this patient's presentation, the progression was satisfactory.

Dentre as infecções causadas por Streptococcus ß hemolyticus do grupo A de Lancefield, talvez a síndrome do choque tóxico seja a mais grave, com alto índice de mortalidade. A semelhança clínica com outras formas de choque, principalmente séptico, pode, muitas vezes, confundir o avaliador e interferir na escolha da terapêutica mais adequada. Esse relato tem o objetivo de auxiliar seus leitores quanto à necessidade de adicionar tal síndrome como diagnóstico diferencial, frente a quadros de choque, principalmente aqueles que não apresentam manifestações clínicas bem definidas. Para isso, apresentamos o quadro de um lactente com sintomas gripais comuns, que evoluiu rapidamente com exantema, rebaixamento do nível de consciência, sinais clínicos e laboratoriais de choque, com necessidade de suporte intensivo. Além de culturas indicando o agente etiológico, o aparecimento de exantema e fasciíte necrosante levou ao diagnóstico, mas, em menos de 50% dos casos temos sinais clínicos clássicos dessa entidade. As penicilinas em terapia combinada com aminoglicosídeos ainda são a terapia de escolha e possuem alto nível de evidência. Apesar da gravidade a evolução foi satisfatória.

Inflammatory lung injury in rabbits: effects of high-frequency oscillatory ventilation in the prone position.

OBJECTIVE: To compare the effects that prone and supine positioning during high-frequency oscillatory ventilation (HFOV) have on oxygenation and lung inflammation, histological injury, and oxidative stress in a rabbit model of acute lung injury (ALI). METHODS: Thirty male Norfolk white rabbits were induced to ALI by tracheal saline lavage (30 mL/kg, 38°C). The injury was induced during conventional mechanical ventilation, and ALI was considered confirmed when a PaO2/FiO2 ratio < 100 mmHg was reached. Rabbits were randomly divided into two groups: HFOV in the supine position (SP group, n = 15); and HFOV with prone positioning (PP group, n = 15). For HFOV, the mean airway pressure was initially set at 16 cmH2O. At 30, 60, and 90 min after the start of the HFOV protocol, the mean airway pressure was reduced to 14, 12, and 10 cmH2O, respectively. At 120 min, the animals were returned to or remained in the supine position for an extra 30 min. We evaluated oxygenation indices and histological lung injury scores, as well as TNF-α levels in BAL fluid and lung tissue. RESULTS: After ALI induction, all of the animals showed significant hypoxemia, decreased respiratory system compliance, decreased oxygenation, and increased mean airway pressure in comparison with the baseline values. There were no statistically significant differences between the two groups, at any of the time points evaluated, in terms of the PaO2 or oxygenation index. However, TNF-α levels in BAL fluid were significantly lower in the PP group than in the SP group, as were histological lung injury scores. CONCLUSIONS: Prone positioning appears to attenuate inflammatory and histological lung injury during HFOV in rabbits with ALI.

Inhaled magnesium versus inhaled salbutamol in rescue treatment for moderate and severe asthma exacerbations in pediatric patients

Abstract Objective To compare the effectiveness of inhaled Magnesium Sulfate associated with Salbutamol versus Inhaled Salbutamol alone in patients with moderate and severe asthma exacerbations. Method Clinical, prospective and randomized study with patients between 3 and 14 years of age divided into two groups: one to receive inhaled salbutamol associated with magnesium sulfate (GSM), the other to receive inhaled salbutamol alone (GS). The sample consisted of 40 patients, 20 patients in each group. Severity was classified using the modified Wood-Downes score, with values between 4 and 7 classified as moderate and 8 or more classified as severe. Results Post-inhalation scores decreased both in patients who received salbutamol and magnesium and in those who received salbutamol alone, with no statistically significant difference between the groups. Conclusions Despite the benefits when administered intravenously, inhalation of the drug alone or in combination did not reduce the severity of the exacerbation.

Electrocardiogram as Part of the Evaluation of Children and Adolescents Before Starting Physical Exercise

Abstract Background: Children and adolescents should be encouraged to participate in sports; however, physicians should screen for cardiac abnormalities that can lead to sudden death. The European Society of Cardiology, the Brazilian Society of Cardiology and the Brazilian Society of Sports Medicine indicate performing an electrocardiogram (ECG) in evaluating athletes, while the American Heart Association indicates complementary exams only when there is a personal or family history of cardiovascular diseases or changes in clinical examination. Objectives: To evaluate the need for an ECG in evaluating children and adolescents before starting physical activities. Methods: We recruited 983 children and adolescents who practiced physical activities for anthropometric assessment, clinical examination and conventional ECG at rest. Variables were analysed using the Goodman test with a significance level of 5%. Results: Participants had a higher incidence of overweight, obesity and severe obesity compared to standard World Health Organization (WHO) values. The most common finding in clinical examination was heart murmur (18.5% of participants). Electrocardiographic changes were found in 3.3% of participants, including paroxysmal supraventricular tachycardia and pre-excitation syndrome, which may be responsible for sudden death, even in asymptomatic individuals with no personal or family history of heart disease and no abnormality on clinical examination. Conclusions: ECG revealed arrhythmias that were not detected by clinical examination and may precede sudden death in individuals subjected to physical exertion, indicating its role in the assessment of children and adolescents before starting regular physical exercise.

Echocardiographic abnormalities in children with obstructive breathing disorders during sleep.

OBJECTIVES: To assess cardiac morphology and function by means of echocardiograms of children with obstructed breathing while asleep. METHODS: The study enrolled 40 children of both sexes, aged from 3 to 11 years; 30 of them had obstructed breathing during sleep (group I) and 10 children were healthy controls (group II). The two groups were similar in terms of sex, age, weight and height. The 40 children underwent echocardiogram, viewing all four chambers during systole and diastole, paying special attention to the right ventricle (RV). These data were compared by means of Student's t test (p < 0.05). RESULTS: In group I, increased diameter and area of the right ventricle were observed during both systole and diastole. There was less variation in RV area between systole and diastole. Reduced left ventricle (LV) diastolic diameter was also observed, together with reduced ejection fraction and reduced contraction. CONCLUSIONS: The morphological and functional cardiac abnormalities observed in the RV and LV suggest that, in children, obstructed breathing during sleep can lead to cardiovascular repercussions. These abnormalities may expose these children to increased anesthetic and surgical risks.

Comparison between conventional protective mechanical ventilation and high-frequency oscillatory ventilation associated with the prone position. / Comparação entre ventilação mecânica convencional protetora e ventilação oscilatória de alta frequência associada à posição prona.

OBJECTIVE: To compare the effects of high-frequency oscillatory ventilation and conventional protective mechanical ventilation associated with the prone position on oxygenation, histology and pulmonary oxidative damage in an experimental model of acute lung injury. METHODS: Forty-five rabbits with tracheostomy and vascular access were underwent mechanical ventilation. Acute lung injury was induced by tracheal infusion of warm saline. Three experimental groups were formed: healthy animals + conventional protective mechanical ventilation, supine position (Control Group; n = 15); animals with acute lung injury + conventional protective mechanical ventilation, prone position (CMVG; n = 15); and animals with acute lung injury + high-frequency oscillatory ventilation, prone position (HFOG; n = 15). Ten minutes after the beginning of the specific ventilation of each group, arterial gasometry was collected, with this timepoint being called time zero, after which the animal was placed in prone position and remained in this position for 4 hours. Oxidative stress was evaluated by the total antioxidant performance assay. Pulmonary tissue injury was determined by histopathological score. The level of significance was 5%. RESULTS: Both groups with acute lung injury showed worsening of oxygenation after induction of injury compared with the Control Group. After 4 hours, there was a significant improvement in oxygenation in the HFOG group compared with CMVG. Analysis of total antioxidant performance in plasma showed greater protection in HFOG. HFOG had a lower histopathological lesion score in lung tissue than CMVG. CONCLUSION: High-frequency oscillatory ventilation, associated with prone position, improves oxygenation and attenuates oxidative damage and histopathological lung injury compared with conventional protective mechanical ventilation.

OBJETIVO: Comparar os efeitos da ventilação oscilatória de alta frequência e da ventilação mecânica convencional protetora associadas à posição prona quanto à oxigenação, à histologia e ao dano oxidativo pulmonar em modelo experimental de lesão pulmonar aguda. MÉTODOS: Foram instrumentados com traqueostomia, acessos vasculares e ventilados mecanicamente 45 coelhos. A lesão pulmonar aguda foi induzida por infusão traqueal de salina aquecida. Foram formados três grupos experimentais: animais sadios + ventilação mecânica convencional protetora, em posição supina (Grupo Controle; n = 15); animais com lesão pulmonar aguda + ventilação mecânica convencional protetora, posição prona (GVMC; n = 15); animais com lesão pulmonar aguda + ventilação oscilatória de alta frequência, posição prona (GVAF; n = 15). Após 10 minutos do início da ventilação específica de cada grupo, foi coletada gasometria arterial, sendo este momento denominado tempo zero, após o qual o animal foi colocado em posição prona, permanecendo assim por 4 horas. O estresse oxidativo foi avaliado pelo método de capacidade antioxidante total. A lesão tecidual pulmonar foi determinada por escore histopatológico. O nível de significância adotado foi de 5%. RESULTADOS: Ambos os grupos com lesão pulmonar aguda apresentaram piora da oxigenação após a indução da lesão comparados ao Grupo Controle. Após 4 horas, houve melhora significante da oxigenação no grupo GVAF comparado ao GVMC. A análise da capacidade antioxidante total no plasma mostrou maior proteção no GVAF. O GVAF apresentou menor escore de lesão histopatológica no tecido pulmonar que o GVMC. CONCLUSÃO: A ventilação oscilatória de alta frequência, associada à posição prona, melhora a oxigenação, e atenua o dano oxidativo e a lesão pulmonar histopatológica, comparada com ventilação mecânica convencional protetora.

Diagnóstico e tratamento da síndrome do choque tóxico estreptocócico em unidade de terapia intensiva pediátrica: relato de caso / Diagnosis and treatment of streptococcal toxic shock syndrome in the pediatric intensive care unit: a case report

RESUMO Dentre as infecções causadas por Streptococcus β hemolyticus do grupo A de Lancefield, talvez a síndrome do choque tóxico seja a mais grave, com alto índice de mortalidade. A semelhança clínica com outras formas de choque, principalmente séptico, pode, muitas vezes, confundir o avaliador e interferir na escolha da terapêutica mais adequada. Esse relato tem o objetivo de auxiliar seus leitores quanto à necessidade de adicionar tal síndrome como diagnóstico diferencial, frente a quadros de choque, principalmente aqueles que não apresentam manifestações clínicas bem definidas. Para isso, apresentamos o quadro de um lactente com sintomas gripais comuns, que evoluiu rapidamente com exantema, rebaixamento do nível de consciência, sinais clínicos e laboratoriais de choque, com necessidade de suporte intensivo. Além de culturas indicando o agente etiológico, o aparecimento de exantema e fasciíte necrosante levou ao diagnóstico, mas, em menos de 50% dos casos temos sinais clínicos clássicos dessa entidade. As penicilinas em terapia combinada com aminoglicosídeos ainda são a terapia de escolha e possuem alto nível de evidência. Apesar da gravidade a evolução foi satisfatória.

ABSTRACT Among the infections caused by Streptococcus β hemolyticus from the Lancefield serogroup A, toxic shock syndrome is perhaps the most severe, and its mortality rate is high. Its clinical similarity to other forms of shock, especially septic shock, can often confuse the evaluator and interfere with the selection of the most appropriate therapy. This report aims to inform readers of the need to add this syndrome as a differential diagnosis in cases of shock, especially those with no well-defined clinical manifestations. For this purpose, we present the case of an infant with common flu-like symptoms who progressed rapidly with a rash, a reduced level of consciousness and clinical and laboratory signs of shock that required intensive support. In addition to cultures indicating the etiological agent, the appearance of exanthema and necrotizing fasciitis led to the diagnosis. However, less than 50% of cases present classic clinical signs of this entity. Penicillins combined with aminoglycosides are still the therapy of choice and are supported by a high level of evidence. Despite the severity of this patient's presentation, the progression was satisfactory.

Inflammatory lung injury in rabbits: effects of high-frequency oscillatory ventilation in the prone position / Lesão inflamatória pulmonar em coelhos: efeitos da ventilação oscilatória de alta frequência em posição prona

ABSTRACT Objective: To compare the effects that prone and supine positioning during high-frequency oscillatory ventilation (HFOV) have on oxygenation and lung inflammation, histological injury, and oxidative stress in a rabbit model of acute lung injury (ALI). Methods: Thirty male Norfolk white rabbits were induced to ALI by tracheal saline lavage (30 mL/kg, 38°C). The injury was induced during conventional mechanical ventilation, and ALI was considered confirmed when a PaO2/FiO2 ratio < 100 mmHg was reached. Rabbits were randomly divided into two groups: HFOV in the supine position (SP group, n = 15); and HFOV with prone positioning (PP group, n = 15). For HFOV, the mean airway pressure was initially set at 16 cmH2O. At 30, 60, and 90 min after the start of the HFOV protocol, the mean airway pressure was reduced to 14, 12, and 10 cmH2O, respectively. At 120 min, the animals were returned to or remained in the supine position for an extra 30 min. We evaluated oxygenation indices and histological lung injury scores, as well as TNF-α levels in BAL fluid and lung tissue. Results: After ALI induction, all of the animals showed significant hypoxemia, decreased respiratory system compliance, decreased oxygenation, and increased mean airway pressure in comparison with the baseline values. There were no statistically significant differences between the two groups, at any of the time points evaluated, in terms of the PaO2 or oxygenation index. However, TNF-α levels in BAL fluid were significantly lower in the PP group than in the SP group, as were histological lung injury scores. Conclusions: Prone positioning appears to attenuate inflammatory and histological lung injury during HFOV in rabbits with ALI.

RESUMO Objetivo: Comparar os efeitos das posições prona e supina durante ventilação oscilatória de alta frequência (VOAF) sobre oxigenação e inflamação pulmonar, lesão histológica e estresse oxidativo em um modelo de lesão pulmonar aguda (LPA) em coelhos. Métodos: Trinta coelhos Norfolk machos brancos foram submetidos à LPA por meio de lavagem traqueal com salina (30 ml/kg, 38°C). A lesão foi induzida durante a ventilação mecânica convencional, e a LPA foi considerada confirmada na presença de relação PaO2/FiO2 < 100 mmHg. Os coelhos foram aleatoriamente divididos em dois grupos: VOAF em posição supina (grupo PS, n = 15); e VOAF em posição prona (grupo PP, n = 15). Para a VOAF, a pressão média das vias aéreas foi inicialmente estabelecida em 16 cmH2O. No 30º, 60º e 90º min após o início do protocolo de VOAF, a pressão média das vias aéreas foi reduzida para 14, 12 e 10 cmH2O, respectivamente. No 120º min, os animais foram recolocados ou permaneceram na posição supina por mais 30 min. Foram avaliados os índices de oxigenação e escores histológicos de lesão pulmonar, bem como os níveis de TNF-α em lavado broncoalveolar e tecido pulmonar. Resultados: Após a indução da LPA, todos os animais apresentaram hipoxemia significativa, diminuição da complacência do sistema respiratório, diminuição da oxigenação e aumento da pressão média das vias aéreas em comparação aos valores basais. Não houve diferenças estatisticamente significativas entre os dois grupos, em nenhum dos momentos avaliados, quanto a PaO2 e índice de oxigenação. Entretanto, os níveis de TNF-α no lavado broncoalveolar foram significativamente menores no grupo PP que no grupo PS, assim como os escores histológicos de lesão pulmonar. Conclusões: A posição prona parece atenuar a lesão pulmonar inflamatória e histológica durante a VOAF em coelhos com LPA.

Interactive effects of mechanical ventilation, inhaled nitric oxide and oxidative stress in acute lung injury.

To compare conventional mechanical ventilation (CMV) and high-frequency oscillatory ventilation (HFOV), with/without inhaled nitric oxide (iNO), for oxygenation, inflammation, antioxidant/oxidative stress status, and DNA damage in a model of acute lung injury (ALI). Lung injury was induced by tracheal infusion of warm saline. Rabbits were ventilated at [Formula: see text] 1.0 and randomly assigned to one of five groups. Overall antioxidant defense/oxidative stress was assessed by total antioxidant performance assay, and DNA damage by comet assay. Ventilatory and hemodynamic parameters were recorded every 30min for 4h. ALI groups showed worse oxygenation than controls after lung injury. After 4h of mechanical ventilation, HFOV groups presented significant improvements in oxygenation. HFOV with and without iNO, and CMV with iNO showed significantly increased antioxidant defense and reduced DNA damage than CMV without iNO. Inhaled nitric oxide did not beneficially affect HFOV in relation to antioxidant defense/oxidative stress and pulmonary DNA damage. Overall, lung injury was reduced using HFOV or CMV with iNO.

Interleukin-12 in children with sepsis and septic shock. / Interleucina-12 em crianças com sepse e choque séptico.

OBJECTIVE: To examine the behavior of interleukin-12 and verify whether it can be used to differentiate septic conditions in children. METHODS: Septic children aged between 28 days and 14 years, prospectively enrolled from 01/2004 to 12/2005, were divided into sepsis (SG; n=47) and septic shock (SSG; n=43) groups. Interleukin-12 levels were measured at admission (T0) and 12 hours later (T12). Disease severity was assessed by the PRISM score. RESULTS: Interleukin-12 levels did not differentiate children with sepsis from those with septic shock at admission [SSG: 0.24 (0-226.4)=SG: 1.23 (0-511.6); p=0.135)] and T12 [SG: 6.11 (0-230.5)=SSG: 1.32 (0-61.0); p=0.1239)]. Comparing time points, no significant difference was observed in the SG [SG, T0: 1.23 (0-511.6)=T12: 6.11 (0-230.5); p=0.075]. In SSG however, interleukin-12 increased from T0 to T12 (SSG, T0: 0.24 (0-226.4)0.05). There was no correlation between onterleukin-12 levels at admission and the PRISM score for either group. CONCLUSION: Interleukin-12 levels cannot differentiate between septic conditions and are not related to disease severity at admission. In septic shock patients, interleukin-12 increases with time.

Biomarkers for oxidative stress in acute lung injury induced in rabbits submitted to different strategies of mechanical ventilation.

Oxidative damage has been said to play an important role in pulmonary injury, which is associated with the development and progression of acute respiratory distress syndrome (ARDS). We aimed to identify biomarkers to determine the oxidative stress in an animal model of acute lung injury (ALI) using two different strategies of mechanical ventilation. Rabbits were ventilated using either conventional mechanical ventilation (CMV) or high-frequency oscillatory ventilation (HFOV). Lung injury was induced by tracheal saline infusion (30 ml/kg, 38°C). In addition, five healthy rabbits were studied for oxidative stress. Isolated lymphocytes from peripheral blood and lung tissue samples were analyzed by alkaline single cell gel electrophoresis (comet assay) to determine DNA damage. Total antioxidant performance (TAP) assay was applied to measure overall antioxidant performance in plasma and lung tissue. HFOV rabbits had similar results to healthy animals, showing significantly higher antioxidant performance and lower DNA damage compared with CMV in lung tissue and plasma. Total antioxidant performance showed a significant positive correlation (r = 0.58; P = 0.0006) in plasma and lung tissue. In addition, comet assay presented a significant positive correlation (r = 0.66; P = 0.007) between cells recovered from target tissue and peripheral blood. Moreover, antioxidant performance was significantly and negatively correlated with DNA damage (r = -0.50; P = 0.002) in lung tissue. This study indicates that both TAP and comet assay identify increased oxidative stress in CMV rabbits compared with HFOV. Antioxidant performance analyzed by TAP and oxidative DNA damage by comet assay, both in plasma, reflects oxidative stress in the target tissue, which warrants further studies in humans.

Comparação entre ventilação mecânica convencional protetora e ventilação oscilatória de alta frequência associada à posição prona / Comparison between conventional protective mechanical ventilation and high-frequency oscillatory ventilation associated with the prone position

RESUMO Objetivo: Comparar os efeitos da ventilação oscilatória de alta frequência e da ventilação mecânica convencional protetora associadas à posição prona quanto à oxigenação, à histologia e ao dano oxidativo pulmonar em modelo experimental de lesão pulmonar aguda. Métodos: Foram instrumentados com traqueostomia, acessos vasculares e ventilados mecanicamente 45 coelhos. A lesão pulmonar aguda foi induzida por infusão traqueal de salina aquecida. Foram formados três grupos experimentais: animais sadios + ventilação mecânica convencional protetora, em posição supina (Grupo Controle; n = 15); animais com lesão pulmonar aguda + ventilação mecânica convencional protetora, posição prona (GVMC; n = 15); animais com lesão pulmonar aguda + ventilação oscilatória de alta frequência, posição prona (GVAF; n = 15). Após 10 minutos do início da ventilação específica de cada grupo, foi coletada gasometria arterial, sendo este momento denominado tempo zero, após o qual o animal foi colocado em posição prona, permanecendo assim por 4 horas. O estresse oxidativo foi avaliado pelo método de capacidade antioxidante total. A lesão tecidual pulmonar foi determinada por escore histopatológico. O nível de significância adotado foi de 5%. Resultados: Ambos os grupos com lesão pulmonar aguda apresentaram piora da oxigenação após a indução da lesão comparados ao Grupo Controle. Após 4 horas, houve melhora significante da oxigenação no grupo GVAF comparado ao GVMC. A análise da capacidade antioxidante total no plasma mostrou maior proteção no GVAF. O GVAF apresentou menor escore de lesão histopatológica no tecido pulmonar que o GVMC. Conclusão: A ventilação oscilatória de alta frequência, associada à posição prona, melhora a oxigenação, e atenua o dano oxidativo e a lesão pulmonar histopatológica, comparada com ventilação mecânica convencional protetora.

ABSTRACT Objective: To compare the effects of high-frequency oscillatory ventilation and conventional protective mechanical ventilation associated with the prone position on oxygenation, histology and pulmonary oxidative damage in an experimental model of acute lung injury. Methods: Forty-five rabbits with tracheostomy and vascular access were underwent mechanical ventilation. Acute lung injury was induced by tracheal infusion of warm saline. Three experimental groups were formed: healthy animals + conventional protective mechanical ventilation, supine position (Control Group; n = 15); animals with acute lung injury + conventional protective mechanical ventilation, prone position (CMVG; n = 15); and animals with acute lung injury + high-frequency oscillatory ventilation, prone position (HFOG; n = 15). Ten minutes after the beginning of the specific ventilation of each group, arterial gasometry was collected, with this timepoint being called time zero, after which the animal was placed in prone position and remained in this position for 4 hours. Oxidative stress was evaluated by the total antioxidant performance assay. Pulmonary tissue injury was determined by histopathological score. The level of significance was 5%. Results: Both groups with acute lung injury showed worsening of oxygenation after induction of injury compared with the Control Group. After 4 hours, there was a significant improvement in oxygenation in the HFOG group compared with CMVG. Analysis of total antioxidant performance in plasma showed greater protection in HFOG. HFOG had a lower histopathological lesion score in lung tissue than CMVG. Conclusion: High-frequency oscillatory ventilation, associated with prone position, improves oxygenation and attenuates oxidative damage and histopathological lung injury compared with conventional protective mechanical ventilation.

High-frequency oscillatory ventilation associated with inhaled nitric oxide compared to pressure-controlled assist/control ventilation and inhaled nitric oxide in children: Randomized, non-blinded, crossover study.

PURPOSE: To compare the acute oxygenation effects of high-frequency oscillatory ventilation (HFOV) plus inhaled nitric oxide (iNO) with pressure-controlled assist/control ventilation (PCACV) plus iNO in acute hypoxemic respiratory failure (AHRF) children. METHODS: Children with AHRF, aged between 1 month and 14 years under PCACV with PEEP ≥ 10 cmH(2) O were randomly assigned to PCACV (PCVG, n = 14) or HFOV (HFVG, n = 14) in a crossover design. Oxygenation indexes and hemodynamic variables were recorded at enrollment (Tind), 1 hr after PCACV start (T0) and then every 4 hr (T4h, etc.). RESULTS: PO(2)/FiO(2) significantly increased after 4 hr compared to enrollment in both groups [(PCVG-Tind: 111.95 ± 37 < T4h: 143.88 ± 47.5 mmHg, P < 0.05; HFVG-Tind: 123.76 ± 33 < T4h: 194.61 ± 62.42 mmHg, P < 0.05)] without any statistical differences between groups. At T8h, PO(2)/FiO(2) was greater for HFVG compared with PCVG (HFVG: 227.9 ± 80.7 > PCVG: 171.21 ± 52.9 mmHg, P < 0.05). FiO(2) could be significantly reduced after 4 hr for HFVG (HFVG-T4h: 0.53 ± 0.09 < Tind: 0.64 ± 0.2; P < 0.05) but only after 8 hr for PCVG. Comparing groups at T8h, it was observed that FiO(2) decrease was greater for HFVG (HFVG: 0.47 ± 0.06 < PCVG: 0.58 ± 0.1; P < 0.05). CONCLUSION: Both ventilatory techniques with iNO improve oxygenation. HFOV causes earlier FiO(2) reduction and increased PO(2)/FiO(2) ratio compared to PCACV at 8 hr. However, at the end of the protocol, there was no significant difference and no clinical improvement derived from the application of both ventilatory strategies with iNO. It is not possible to say what would have happened if a different conventional ventilatory mode and a fully protective ventilatory strategy had been used, given the fact that our study is non-blind, and that a limited number of patients were included in each group.

High-frequency oscillatory ventilation attenuates oxidative lung injury in a rabbit model of acute lung injury.

Mechanical ventilation (MV) can induce lung oxidative stress, which plays an important role in pulmonary injury. This study compared protective conventional mechanical ventilation (CMV) and high-frequency oscillatory ventilation (HFOV) for oxygenation, oxidative stress, inflammatory and histopathological lung injury in a rabbit model of acute lung injury (ALI). Rabbits (n = 30) were ventilated at FiO(2) 1.0. Lung injury was induced by tracheal saline infusion (30 mL/kg, 38°C). Animals were randomly assigned to: (a) sham control (CG: tidal volume [V(T)] 6 mL/kg, positive end expiratory pressure [PEEP] 5 cmH(2)O, respiratory rate [RR] 40 ipm); (b) ALI + CMV (CMVG: V(T) 6 mL/kg, PEEP 10 cmH(2)O, RR 40 ipm); or (c) ALI + HFOV (HFG: mean airway pressure [Paw] 14 cmH(2)O, RR 10 Hz) groups. Lung oxidative stress was assessed by total antioxidant performance assay, inflammatory response by the number of polymorphonuclear leukocytes/bronchoalveolar lavage fluid/lung and pulmonary histological damage was quantified by a score. Ventilatory and hemodynamic parameters were recorded every 30 min. Both ALI groups showed worse oxygenation after lung injury induction. After four hours of ventilation, HFG showed better oxygenation (partial pressure of oxygen [PaO(2)] - CG: 465.9 ± 30.5 = HFG: 399.1 ± 98.2 > CMVG: 232.7 ± 104 mmHg, P < 0.05) and inflammatory responses (CMVG: 4.27 ± 1.50 > HFG: 0.33 ± 0.20 = CG: 0.16 ± 0.15; polymorphonuclear cells/bronchoalveolar lavage fluid/lung, P < 0.05), less histopathological injury score (CMVG: 5 [1-16] > HFG: 1 [0-5] > CG: 0 [0-3]; P < 0.05), and lower lung oxidative stress than CMVG (CG: 59.4 ± 4.52 = HFG: 69.0 ± 4.99 > CMVG: 47.6 ± 2.58% protection/g protein, P < 0.05). This study showed that HFOV had an important protective role in ALI. It improved oxygenation, reduced inflammatory process and histopathological damage, and attenuated oxidative lung injury compared with protective CMV under these experimental conditions considering the study limitations.