Comparison between noninvasive mechanical ventilation and standard oxygen therapy in children up to 3 years old with respiratory failure after extubation: a pilot prospective randomized clinical study.

OBJECTIVES: The effectiveness of noninvasive positive-pressure ventilation in preventing reintubation due to respiratory failure in children remains uncertain. A pilot study was designed to evaluate the frequency of extubation failure, develop a randomization approach, and analyze the feasibility of a powered randomized trial to compare noninvasive positive-pressure ventilation and standard oxygen therapy post extubation for preventing reintubation within 48 hours in children with respiratory failure. DESIGN: Prospective pilot study. SETTING: PICU at a university-affiliated hospital. PATIENTS: Children aged between 28 days and 3 years undergoing invasive mechanical ventilation for greater than or equal to 48 hours with respiratory failure after programmed extubation. INTERVENTIONS: Patients were prospectively enrolled and randomly assigned into noninvasive positive-pressure ventilation group and inhaled oxygen group after programmed extubation from May 2012 to May 2013. MEASUREMENTS AND MAIN RESULTS: Length of stay in PICU and hospital, oxygenation index, blood gas before and after tracheal extubation, failure and reason for tracheal extubation, complications, mechanical ventilation variables before tracheal extubation, arterial blood gas, and respiratory and heart rates before and 1 hour after tracheal extubation were analyzed. One hundred eight patients were included (noninvasive positive-pressure ventilation group, n = 55 and inhaled oxygen group, n = 53), with 66 exclusions. Groups did not significantly differ for gender, age, disease severity, Pediatric Risk of Mortality at admission, tracheal intubation, and mechanical ventilation indications. There was no statistically significant difference in reintubation rate (noninvasive positive-pressure ventilation group, 9.1%; inhaled oxygen group, 11.3%; p > 0.05) and length of stay (days) in PICU (noninvasive positive-pressure ventilation group, 3 [1-16]; inhaled oxygen group, 2 [1-25]; p > 0.05) or hospital (noninvasive positive-pressure ventilation group, 19 [7-141]; inhaled oxygen group, 17 [8-80]). CONCLUSIONS: The study indicates that a larger randomized trial comparing noninvasive positive-pressure ventilation and standard oxygen therapy in children with respiratory failure is feasible, providing a basis for a future trial in this setting. No differences were seen between groups. The number of excluded patients was high.

Effects of inhaled nitric oxide on oxidative stress and histopathological and inflammatory lung injury in a saline-lavaged rabbit model of acute lung injury.

BACKGROUND: Conventional mechanical ventilation (CMV) is fundamental in acute respiratory distress syndrome (ARDS) treatment. Inhaled nitric oxide (INO), an adjunctive therapy, has been used with ventilation in an attempt to improve oxygenation and reduce lung injury. OBJECTIVE: To analyze the early effects of low INO dose on oxygenation, oxidative stress, inflammatory, and histopathological lung injury in a rabbit model of acute lung injury (ALI). METHODS: This was a prospective, controlled, in vivo animal laboratory study. Forty rabbits were instrumented and ventilated at F(IO(2)) 1.0. ALI was induced by tracheal infusion of warm saline (30 mL/kg, 38°C) and lung oxidative stress was assessed by total antioxidant performance (TAP) assay. Animals were assigned to groups: control group (no. = 10, low tidal volume [V(T)] = 6 mL/kg, PEEP = 5 cm H(2)O), ALI without INO (no-INO group, no. = 10, low V(T) = 6 mL/kg, PEEP = 10 cm H(2)O), ALI plus INO (INO group, no. = 10, low V(T) = 6 mL/kg, PEEP = 10 cm H(2)O, INO = 5 ppm). Plateau pressure was limited to 30 cm H(2)O in all groups. Ten non-instrumented animals (healthy group) were studied for TAP assay. Ventilatory and hemodynamic parameters were recorded every 30 min for 4 hours. RESULTS: After lung injury, the instrumented groups were worse than the control group for P(aO(2)) (control group 438 ± 87 mm Hg, no-INO group 80 ± 13 mm Hg, INO group 81 ± 24 mm Hg, P < .001). The INO group showed decreased lung inflammation by leukocyte count in lung lavage fluid (no-INO group 4.8 ± 1.64, control group 0.16 ± 0.15, INO group 0.96 ± 0.35 polymorphonuclear cells × 10(6)/bronchoalveolar lavage fluid/lung, P < .001), decreased histopathological injury score (no-INO group 5 [range 1-16], INO group 2 [range 0-5], control group 0 [range 0-3], P < .001), and better lung protection against oxidative injury than the no-INO group (healthy group 68 ± 8.7, control group 66.4 ± 6.8, INO group 56.3 ± 5.1, no-INO group 45.9 ± 3.4 percent protection/g protein, P < .001). CONCLUSIONS: INO attenuates oxidative stress and histopathological and inflammatory lung injury in a saline-lavaged rabbit ALI model.

Comparison between procalcitonin and C-reactive protein for early diagnosis of children with sepsis or septic shock.

OBJECTIVE AND DESIGN: The objective of the paper is to examine the behavior of C-reactive protein (CRP) and procalcitonin (PCT) in the first 12 h of admission and verify which performs better to differentiate children with septic conditions. SUBJECTS: Septic children aged between 28 days and 14 years were divided into sepsis (SG; n = 46) and septic shock (SSG; n = 41) groups. CRP and PCT were measured at admission (T0) and 12 h later (T12 h). PCT results were classed as: 0.5 ng/ml = sepsis unlikely; >or=0.5 to <2 = sepsis possible; >or=2 to <10 = systemic inflammation; >or=10 = septic shock. RESULTS: At T0, there was a higher frequency of SSG with PCT >10 compared to SG [SSG: 30 (73.1%) > SG: 14 (30.4%); P < 0.05]. Similar results were observed at T12 h. Pediatric Risk of Mortality I score was significantly higher for SSG patients with higher PCT than SG patients. CRP levels were not statistically different for groups and time points. CONCLUSIONS: PCT was better than CRP for diagnosing sepsis and septic shock, mainly at admission, and is related to disease severity.

Comparação entre ventilação mandatória intermitente e ventilação mandatória intermitente sincronizada com pressão de suporte em crianças / Comparison between intermittent mandatory ventilation and synchronized intermittent mandatory ventilation with pressure support in children

OBJETIVO: Comparar a ventilação mandatória intermitente (IMV) com a ventilação mandatória intermitente sincronizada com pressão de suporte (SIMV+PS) quanto à duração da ventilação mecânica, desmame e tempo de internação na unidade de terapia intensiva pediátrica (UTIP). MÉTODOS: Estudo clínico randomizado que incluiu crianças entre 28 dias e 4 anos de idade, admitidas na UTIP no período correspondente entre 10/2005 e 06/2007, que receberam ventilação mecânica (VM) por mais de 48 horas. Os pacientes foram alocados, por meio de sorteio, em dois grupos: grupo IMV (GIMV; n = 35) e grupo SIMV+PS (GSIMV; n = 35). Foram excluídas crianças traqueostomizadas e com insuficiência respiratória crônica. Dados relativos à oxigenação e ventilação foram anotados na admissão e no início do desmame. RESULTADOS: Os grupos não diferiram estatisticamente quanto à idade, sexo, indicação da VM, escore PRISM, escala de Comfort, uso de sedativos e parâmetros de ventilação e oxigenação. A mediana da duração da VM foi de 5 dias para ambos os grupos (p = 0,120). Também não houve diferença estatística quanto à duração do desmame [GIMV: 1 dia (1-6) versus GSIMV: 1 dia (1-6); p = 0,262] e tempo de internação [GIMV: 8 dias (2-22) versus GSIMV: 6 dias (3-20); p = 0,113]. CONCLUSÃO: Não houve diferença estatisticamente significativa entre IMV e SIMV+PS quanto à duração da VM/desmame e tempo de internação nas crianças avaliadas. ClinicalTrials.govID: NCT00549809.

OBJECTIVE: To compare intermittent mandatory ventilation (IMV) with synchronized intermittent mandatory ventilation plus pressure support (SIMV+PS) in terms of time on mechanical ventilation, duration of weaning and length of stay in a pediatric intensive care unit (PICU). METHODS: This was a randomized clinical trial that enrolled children aged 28 days to 4 years who were admitted to a PICU between October of 2005 and June of 2007 and put on mechanical ventilation (MV) for more than 48 hours. These patients were allocated to one of two groups by drawing lots: IMV group (IMVG; n = 35) and SIMV+PS group (SIMVG; n = 35). Children were excluded if they had undergone tracheotomy or had chronic respiratory diseases. Data on oxygenation and ventilation were recorded at admission and at the start of weaning. RESULTS: There were no statistical differences between the groups in terms of age, sex, indication for MV, PRISM score, Comfort scale, use of sedatives or ventilation and oxygenation parameters. The median time on MV was 5 days for both groups (p = 0.120). There were also no statistical differences between the two groups for duration of weaning [IMVG: 1 day (1-6) vs. SIMVG: 1 day (1-6); p = 0.262] or length of hospital stay [IMVG: 8 days (2-22) vs. SIMVG: 6 days (3-20); p = 0.113]. CONCLUSION: Among the children studied here, there was no statistically significant difference between IMV and SIMV+PS in terms of time on MV, duration of weaning or time spent in the PICU. ClinicalTrials.govID: NCT00549809.

Comparison between intermittent mandatory ventilation and synchronized intermittent mandatory ventilation with pressure support in children.

OBJECTIVE: To compare intermittent mandatory ventilation (IMV) with synchronized intermittent mandatory ventilation plus pressure support (SIMV+PS) in terms of time on mechanical ventilation, duration of weaning and length of stay in a pediatric intensive care unit (PICU). METHODS: This was a randomized clinical trial that enrolled children aged 28 days to 4 years who were admitted to a PICU between October of 2005 and June of 2007 and put on mechanical ventilation (MV) for more than 48 hours. These patients were allocated to one of two groups by drawing lots: IMV group (IMVG; n = 35) and SIMV+PS group (SIMVG; n = 35). Children were excluded if they had undergone tracheotomy or had chronic respiratory diseases. Data on oxygenation and ventilation were recorded at admission and at the start of weaning. RESULTS: There were no statistical differences between the groups in terms of age, sex, indication for MV, PRISM score, Comfort scale, use of sedatives or ventilation and oxygenation parameters. The median time on MV was 5 days for both groups (p = 0.120). There were also no statistical differences between the two groups for duration of weaning [IMVG: 1 day (1-6) vs. SIMVG: 1 day (1-6); p = 0.262] or length of hospital stay [IMVG: 8 days (2-22) vs. SIMVG: 6 days (3-20); p = 0.113]. CONCLUSION: Among the children studied here, there was no statistically significant difference between IMV and SIMV+PS in terms of time on MV, duration of weaning or time spent in the PICU. ClinicalTrials.govID: NCT00549809.

Interleukin-6 and procalcitonin in children with sepsis and septic shock.

OBJECTIVES: To examine the behavior of interleukin-6 (IL-6) and procalcitonin (PCT) and verify whether they can be used to differentiate children with septic conditions. 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. IL-6 and PCT were measured at admission (T0) and 12h later (T12h). PCT results were classed as: 0.5 ng/mL=sepsis unlikely; > or =0.5 to <2=sepsis possible; > or =2 to <10=systemic inflammation; > or =10=septic shock. RESULTS: Ninety children were included. At T0, there was a higher frequency of SSG with higher PCT compared with SG [SSG: 30 (69.7%)>SG: 14 (29.8%); p<0.05]. Similar results were observed at T12h. PRISM was significantly higher for SSG patients with higher PCT than SG patients. At T0, IL-6 levels were higher in SSG [SSG: 213.10 (10.85-396.70)>SG: 63.21 (0.86-409.82); p=0.001], but not statistically different at T12h. IL-6 levels positively correlated with PRISM score in SSG patients at admission (p=0.001; r=0.86). CONCLUSION: PCT and IL-6 appear to be helpful in early assessment of pediatric sepsis, are of diagnostic value at admission, and are related to disease severity.

Procalcitonina em crianças com sepse e choque séptico / Procalcitonin in children with sepsis and septic shock

OBJETIVOS: Estudar o comportamento da procalcitonina e verificar se é capaz de diferenciar crianças com quadros sépticos. MÉTODOS: Crianças de 28 dias a 14 anos de idade, admitidas de 01/2004 a 12/2005 na unidade de tratamento intensivo pediátrica da UNESP com sepse ou choque séptico, foram incluídas prospectivamente. Dois grupos foram constituídos: grupo sepse (GS; n = 47) e grupo choque séptico (GCS; n = 43). Procalcitonina foi medida à admissão (T0) e depois de 12 h (T12h), e os resultados apresentados em classes: < 0,5 ng/mL = sepse improvável; > 0,5 a < 2 = sepse possível; > 2 a < 10 = inflamação sistêmica e > 10 = choque séptico. RESULTADOS: No T0, foi maior a freqüência de pacientes do GCS na classe mais alta de procalcitonina, comparada às crianças do GS [GCS: 30 (69,7 por cento) > GS: 14 (29,8 por cento); p < 0,05]. Para o GCS, a freqüência de pacientes que ocupou a classe mais elevada foi maior que a de pacientes em outras classes (> 10 = 69,7 por cento; > 2 a < 10 = 18,6 por cento; > 0,5 a < 2 = 11,6 por cento; < 0,5 = 0,0 por cento; p < 0,05). No T12h, o comportamento da procalcitonina foi semelhante ao T0. O escore pediatric risk of mortality (PRISM) dos pacientes do GCS na classe mais alta de procalcitonina foi mais elevado que o das crianças do GS [GCS: 35,15 (40,5-28,7) versus GS: 18,6 (21,4-10,2); p < 0,05]. CONCLUSÃO: Procalcitonina permite diferenciar sepse de choque séptico, pode auxiliar no diagnóstico de quadros sépticos em crianças e pode estar relacionada à gravidade dos pacientes.

OBJECTIVES: To study the behavior of procalcitonin and to verify whether it can be used to differentiate children with septic conditions. METHODS: Children were enrolled prospectively from among those aged 28 days to 14 years, admitted between January 2004 and December 2005 to the pediatric intensive care unit at Universidade Estadual Paulista UNESP with sepsis or septic shock. The children were classified as belonging to one of two groups: the sepsis group (SG; n = 47) and the septic shock group (SSG; n = 43). Procalcitonin was measured at admission (T0) and again 12 hours later (T12h), and the results classed as: < 0.5 ng/mL = sepsis unlikely; > 0.5 to < 2 = sepsis possible; > 2 to < 10 = systemic inflammation and > 10 = septic shock. RESULTS: At T0 there was a greater proportion of SSG patients than SG patients in the highest PCT class [SSG: 30 (69.7 percent) > SG: 14 (29.8 percent); p < 0.05]. The proportion of SSG patients in this highest PCT class was greater than in all other classes (> 10 = 69.7 percent; > 2 to < 10 = 18.6 percent; > 0.5 to < 2 = 11.6 percent; < 0.5 = 0.0 percent; p < 0.05). The behavior of procalcitonin at T12h was similar to at T0. The pediatric risk of mortality (PRISM) scores for the SSG patients in the highest procalcitonin class were more elevated than for children in the SG [SSG: 35.15 (40.5-28.7) vs. SG: 18.6 (21.4-10.2); p < 0.05]. CONCLUSIONS: Procalcitonin allows sepsis to be differentiated from septic shock, can be of aid when diagnosing septic conditions in children and may be related to severity.

Acute and sustained effects of early administration of inhaled nitric oxide to children with acute respiratory distress syndrome.

OBJECTIVE: To determine the acute and sustained effects of early inhaled nitric oxide on some oxygenation indexes and ventilator settings and to compare inhaled nitric oxide administration and conventional therapy on mortality rate, length of stay in intensive care, and duration of mechanical ventilation in children with acute respiratory distress syndrome. DESIGN: Observational study. SETTING: Pediatric intensive care unit at a university-affiliated hospital. PATIENTS: Children with acute respiratory distress syndrome, aged between 1 month and 12 yrs. INTERVENTIONS: Two groups were studied: an inhaled nitric oxide group (iNOG, n = 18) composed of patients prospectively enrolled from November 2000 to November 2002, and a conventional therapy group (CTG, n = 21) consisting of historical control patients admitted from August 1998 to August 2000. MEASUREMENTS AND MAIN RESULTS: Therapy with inhaled nitric oxide was introduced as early as 1.5 hrs after acute respiratory distress syndrome diagnosis with acute improvements in Pao(2)/Fio(2) ratio (83.7%) and oxygenation index (46.7%). Study groups were of similar ages, gender, primary diagnoses, pediatric risk of mortality score, and mean airway pressure. Pao(2)/Fio(2) ratio was lower (CTG, 116.9 +/- 34.5; iNOG, 62.5 +/- 12.8, p <.0001) and oxygenation index higher (CTG, 15.2 [range, 7.2-32.2]; iNOG, 24.3 [range, 16.3-70.4], p <.0001) in the iNOG. Prolonged treatment was associated with improved oxygenation, so that Fio(2) and peak inspiratory pressure could be quickly and significantly reduced. Mortality rate for inhaled nitric oxide-patients was lower (CTG, ten of 21, 47.6%; iNOG, three of 18, 16.6%, p <.001). There was no difference in intensive care stay (CTG, 10 days [range, 2-49]; iNOG, 12 [range, 6-26], p >.05) or duration of mechanical ventilation (TCG, 9 days [range, 2-47]; iNOG, 10 [range, 4-25], p >.05). CONCLUSIONS: Early treatment with inhaled nitric oxide causes acute and sustained improvement in oxygenation, with earlier reduction of ventilator settings, which might contribute to reduce the mortality rate in children with acute respiratory distress syndrome. Length of stay in intensive care and duration of mechanical ventilation are not changed. Prospective trials of inhaled nitric oxide early in the setting of acute lung injury in children are needed.

Early administration of inhaled nitric oxide to pediatric acute respiratory distress syndrome patients and its effects on oxygenation and ventilator settings: prospective preliminary report of ten patients

Aim: To establish a protocol for the early introduction of inhaled nitric oxide (iNO) therapy in pediatric acute respiratory distress syndrome (ARDS) patients and to assess its acute and sustained effects on oxygenation and ventilator settings. Patients and methods: Ten children with ARDS aged 1 to 132 months (median, 11 months) with arterial saturation of oxygen menor 88 por cento while receiving a fraction of inspired oxygen (FIO2)3 0.6 and a positive end-expiratory pressure of 3 10cm H2O were included. The acute response to iNO was assessed in a fourhour dose-response test, and positive response was defined as an increase in the PaO2/FIO2 ratio of 10mm Hg above baseline values. Conventional therapy was not changed during the four-hour-test. In the following days, patients who had shown positive response continued to receive the lowest iNO dose. Hemodynamic, PaO2/FIO2 oxigenation index (OI), gas exchange, and methemoglobin levels were obtained when needed. Inhaled nitric oxide withdrawal followed predetermined rules. Results: At the end of the four-hour test, all the children showed significant improvement in the PaO2/FIO2 ratio (63,6 por cento) and the OI (44,9 por cento) from the baseline values. Prolonged treatment was associated with improvement in oxygenation, so that FIO2 and peak inspiratory pressure could be quickl and significantly reduced. No toxicity from methemoglobin or nitrogen dioxide was seen during the study. Conclusions: 1 - The iNO causes acute and sustained improvement in oxygenation without adverse effects; 2 - There is an early reduction in ventilator settings during iNO treatment;3) iNO administration to pediatric patients is safe. Key words: inhaled nitric oxide, acute respiratory distress syndrome, arterial oxygenation, mechanical ventilation