Is a longer time interval between recombinant human deoxyribonuclease (dornase alfa) and chest physiotherapy better?: A multi‐center,randomized crossover trial

BACKGROUND: Although the benefits of recombinant human deoxyribonuclease (dornase alfa) in patients with cystic fibrosis (CF) are established, its optimal timing in relation to physiotherapy is unknown. As its enzymatic effect lasts for 6-11 hr, dornase alfa may be more efficacious if the time interval between inhalation and chest physiotherapy is increased. The aim of this study was to investigate if a longer time interval between dornase alfa nebulization and chest physiotherapy improves clinical outcomes of subjects with CF. METHODS: A single-blind randomized cross-over trial was conducted on subjects with CF from outpatients of four hospitals. Subjects were in stable health and studied over 6 weeks (utilizing 14-day blocks of morning or evening dornase alfa administration with 14 days washout). Usual regimens for physiotherapy and exercise were unaltered. Thus changing the times altered the dwell time of dornase alfa prior to physiotherapy. Long interval was defined as dwell time of >6 hr and short as < or =6 hr. Outcomes were measured at pre and post each regimen. RESULTS: Twenty subjects aged 7-40 years completed the study. At end of long interval regimen, (median interval = 11.1 hr), FEF(25-75%) and CF-specific quality of life significantly improved compared to baseline values and to short interval regimen (median interval = 0.25 hr) outcomes. FVC, FEV(1), sputum weights, and adherence were similar in both regimens. CONCLUSIONS: A longer time interval between dornase alfa and physiotherapy is more efficacious than short interval. Administration timing of dornase alfa based on patient choice to incorporate longer interval time is likely to be the best regimen for patients previously established on dornase alfa nebulization.     

A case-controlled study with dornase alfa to evaluate impact on disease progression over a 4-year period

BACKGROUND: Chronic endobronchial sepsis and profuse airway secretions dominate pulmonary disease in cystic fibrosis. Recombinant human DNase I (dornase alfa) reduces the viscoelasticity of airway secretions and hence may improve clearance of airway secretions. OBJECTIVES: To evaluate the long-term influence of dornase alfa on disease progression by performing a case-controlled study with dornase alfa over a period of 4 years. METHODS: A cohort of patients with cystic fibrosis who have been treated with dornase alfa were matched with a control group of patients with cystic fibrosis who had not received treatment with dornase alfa. The patients were matched by pulmonary function, age, and then sex. All available measurements of forced expiratory volume in one second (FEV1), height, weight and sputum bacteriology were collected for periods when the patients were free from respiratory exacerbations. RESULTS: Thirty-eight patients were matched. Slopes of median changes in FEV1 were -2.19 (-3.32, -1.06) in the control group and -0.75 (-1.87, 0.36) in the dornase alfa-treated group (p = 0.076). There were more infective exacerbations per patient year in the control group [3.13 (1.25-4.25)] in comparison to the dornase alfa group [1.25 (0.63-3.0), p = 0.035] over the 4-year treatment period. Antibiotic requirements were also greater with a median 43.75 (17.5-60.0) days of intravenous antibiotic use per patient year in the control group and 16.25 (8.5-44.0) days in the dornase alfa group (p = 0.034). CONCLUSIONS: The trends suggest that dornase alfa may have some influence on disease progression but in view of the limitations of the current study the need for further long-term studies in larger cohorts of patients is emphasised.     

Risk factors and outcome of ventilator associated tracheitis (VAT) in pediatric trauma patients

We sought to investigate the risk factors and outcome of Ventilator Associated Tracheitis (VAT) according to the Center for Disease Control (CDC) definition in pediatric trauma patients who were ventilated for ≥48 hr. In a retrospective cohort study, medical records of all pediatric trauma patients admitted to our Pediatric Intensive Care Unit (PICU) between April 2002 and April 2007 were reviewed. Medical records were reviewed for patients' demographics, Trauma Injury Severity Score (TISS), Glasgow Coma Scale (GCS), type of trauma, and other potential risk factors prior to the development of VAT (such as hyperglycemia, rate of re‐intubation and tracheotomy, presence of chest tubes and central lines, urinary tract infection, seizures, need for cardiopulmonary resuscitation, use of total parental nutrition, transfusion, use of H₂ blockers, steroids, and pressors/inotropes). Medical records were also reviewed for days of mechanical ventilation, PICU length of stay, and PICU mortality. During the study period, 217 trauma patients were admitted to the PICU, 113 patients met our inclusion criteria and 21.2% (24/113) developed VAT. On average patients with VAT (in comparison to patients without VAT), had a higher TISS score on admission [38.6 ± 16.9 vs. 24.2 ± 10.6; respectively (P < 0.01)], longer days of ventilation and PICU length of stay [11.5 ± 6.2 vs. 3.7 ± 2.3 days (P < 0.001) and 16.4 ± 8.3 vs. 5.4 ± 2.8 days (P < 0.001), respectively]. There was no difference in mortality between the two groups. In a logistic regression model adjusting for possible confounders, the TISS score (adjusted OR 7.53; CI: 2.01–28.14; P = 0.03 and use of pressors/inotropes (adjusted OR 4.64; CI: 1.28–16.86; P = 0.01) were the only independent risk factors associated with VAT. We conclude that the severity of illness and use of pressors/inotropes are associated with VAT in pediatric trauma patients. We also conclude that VAT is associated with an increase in days of mechanical ventilation and PICU length of stay in pediatric trauma patients. Pediatr Pulmonol. 2013; 48:176–181. © 2012 Wiley Periodicals, Inc.     

Demographics,Clinical Course,and Outcomes of Children with Status Asthmaticus Treated in a Pediatric Intensive Care Unit: 8-Year Review

Objective. This study was done to understand the demographics, clinical course, and outcomes of children with status asthmaticus treated in a tertiary care pediatric intensive care unit (PICU). Methods. The medical charts of all patients above 5 years of age admitted to the PICU at Nationwide Children’s Hospital, Columbus, OH, USA, with status asthmaticus from 2000 to 2007 were reviewed retrospectively. Data from 222 encounters by 183 children were analyzed. Results. The mean age at admission in years was 11 ± 3.8. The median PICU stay was 1 day (range, 1–12 days) and median hospital stay was 3 days. The ventilated group (n = 17) stayed a median of 2 days longer in the PICU and hospital. Nearly half of the children (n = 91; 50%) did not receive daily controller asthma medications. Adherence to asthma medications was reported in 125 patient charts of whom 43 (34%) were compliant. Exposure to smoking was reported in 167 of whom 70 (42%) were exposed. Among patients receiving metered dose inhaler (MDI), only 39 (18%) were using it with a spacer. Among 105 patient charts asthma severity data were available, of them 21 (20%) were labeled as mild intermittent, 29 (28%) were mild persistent, 26 (25%) were moderate persistent, and 29 (28%) were severe persistent. Compared to children with only one PICU admission during the study period (n = 161), children who had multiple PICU admissions (n = 22) experienced more prior emergency department visits and hospitalizations for asthma symptoms. There were no fatalities. Conclusion. Asthmatics with any disease severity are at risk for life-threatening asthma exacerbations requiring PICU stay, especially those who are not adherent with their daily medications.     

Systemic antibiotics fail to clear multidrug-resistant Klebsiella from a pediatric ICU

STUDY OBJECTIVEs: To determine the magnitude of infection rate and antimicrobial resistance in a pediatric ICU (PICU), and to evaluate the efficacy of using broad-spectrum antibiotics. DESIGN: A 3-month, prospective, observational cohort audit. SETTING: A 12-bed tertiary, referral PICU. PATIENTS OR PARTICIPANTS: All children admitted to the PICU for > 72 h. INTERVENTIONS: Surveillance cultures of throat and rectum on admission and once weekly thereafter. MEASUREMENTS AND RESULTS: Of the 150 admissions during the 3-month period, a total of 52 patients (24 girls and 28 boys) requiring mechanical ventilation for a minimum of 3 days were enrolled in the audit. The median age and interquartile range (IQR) was 17 months (IQR, 5.8 to 63); length of stay, 6.5 days (IQR, 4 to 13); ventilation days, 5 (IQR, 3 to 11); pediatric risk of mortality score, 14 (IQR, 9 to 19); and risk of mortality, 0.03 (IQR, 0.014 to 0.087). Fifteen patients (29%) developed 21 infections, mainly lower-airway infections and septicemias. Of the 52 children, 7 children carried multidrug-resistant bacteria and 3 patients progressed to develop four infections with those resistant bacteria. Of the seven carriers, six patients carried gentamicin-resistant Klebsiella. Methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae and gentamicin-resistant Pseudomonas aeruginosa each were carried by one child. Six of those nine resistant isolates were present in the admission flora. Despite the potent combination of piperacillin/tazobactam and amikacin, three children acquired the multidrug-resistant Klebsiella while in the PICU and became nosocomial carriers. CONCLUSIONS: Only surveillance cultures allow the distinction between import of multidrug-resistance and resistant bacteria acquired while in PICU. In this study, two thirds of the resistant isolates were imported. The introduction of newer potent systemic antibiotic combinations failed to control the endemic reservoir of multidrug-resistant Klebsiella and suggests that such policies have little impact.     

Clinical epidemiology and predictors of outcome in children hospitalised with influenza A(H1N1)pdm09 in 2009: a prospective national study

Background

There are few large-scale, prospective studies of influenza A(H1N1)pdm09 in children that identify predictors of adverse outcomes.

Objectives

We aimed to examine clinical epidemiology and predictors for adverse outcomes in children hospitalised with influenza A(H1N1)pdm09 in Australia.

Methods

Active hospital surveillance in six tertiary paediatric referral centres (June–September, 2009). All children aged <15 years admitted with laboratory-confirmed influenza A(H1N1)pdm09 were studied.

Results

Of 601 children admitted with laboratory-confirmed influenza, 506 (84·2%) had influenza A(H1N1)pdm09. Half (51·0%) of children with influenza A(H1N1)pdm09 were previously healthy. Hospital stay was longer in children with pre-existing condition (mean 6·9 versus 4·9 days; P = 0·02) as was paediatric intensive care unit (PICU) stay (7·0 versus 2·3 days; P = 0·005). Rapid diagnosis decreased both antibiotic use and length of hospital and PICU stay. Fifty (9·9%) children were admitted to a PICU, 30 (5·9%) required mechanical ventilation and 5 (0·9%) died. Laboratory-proven bacterial co-infection and chronic lung disease were significant independent predictors of PICU admission (OR 6·89, 95% CI 3·15–15·06 and OR 3·58, 95% CI 1·41–9·07, respectively) and requirement for ventilation (OR 5·61, 95% CI 2·2–14·28 and OR 5·18, 95% CI 1·8–14·86, respectively). Chronic neurological disease was a predictor of admission to PICU (OR 2·30, 95% CI 1·14–4·61).

Conclusions

During the 2009 pandemic, influenza was a major cause of hospitalisation in tertiary paediatric hospitals. Co-infection and underlying chronic disease increased risk of PICU admission and/or ventilation. Half the children admitted were previously healthy, supporting a role for universal influenza vaccination in children.     

Short-term Outcome of Infants Presenting to Pediatric Intensive Care Unit with New Cardiac Diagnoses

Aims. To outline the etiology, clinical course, short-term survival to discharge and neurological outcome of infants (<1 yr) with new cardiac diagnoses presenting to a pediatric intensive care (PICU) unit with acute cardiac compromise. Methods. Retrospective search of a computerized database and medical case notes for all acute cardiac admissions to PICU from June 2001 to 2006. Pre-existing hospital-based patients with new cardiac diagnoses were excluded. Results. Seventy patients were identified, 38 (54%) of whom were male. There were six main subgroups: obstructive left heart lesions (n= 20), transposition of the great arteries (TGA) (n= 9), total anomalous pulmonary venous drainage (TAPVD) (n= 7), dilated cardiomyopathy (n= 11), arrhythmia (n= 12), and others (n= 11). Fifty-nine patients (84%) were external referrals to our center. The median age at presentation was 13.5 days (0–272) with median duration of symptoms of 1 day (0–21). The median base deficit at presentation was −7.6 mEq/L (−43 to +4.2). Fifty-three patients (76%) required respiratory support with a median duration of ventilation of 4 days (1–49). Fifty-six patients (80%) required inotropic support. The median PICU stay was 7 days (1–64) with a median total hospital stay of 16 days (1–71). Six patients (9%) died prior to discharge. Of the survivors 7 (11%) had seizure activity or evolving clinical neurological abnormalities. Conclusions. Cardiovascular compromise due to previously unrecognized congenital or acquired heart disease is associated with clinically significant morbidity and mortality. Longer term follow-up is required to evaluate the initial effect of poor cardiac output and hypoxia on long-term neurodevelopmental outcome.     

Effect of smaller droplet size of dornase alfa on lung function in mild cystic fibrosis

Aerosolized recombinant human DNase (dornase alfa) reduces mucus viscoelasticity in vitro and improves pulmonary function in patients with cystic fibrosis (CF). We postulated that if dornase alfa could be delivered more peripherally to small airways in the lung in the form of smaller aerosol droplets in patients with early airway obstruction, the increase in pulmonary function from baseline might be improved. CF patients (n = 749) with mild lung disease (baseline forced vital capacity <*geq>70% predicted) were randomly assigned to receive dornase alfa 2.5 mg daily for 2 weeks by one of two nebulizer systems: 1) the Medic-Aid Durable SideStream nebulizer powered by the MobilAire Compressor (SS/MA) producing a droplet size with a mass median aerodynamic diameter (MMAD) of 2.1 μm; or 2) the Hudson T Up-draft nebulizer with a DeVilbiss Pulmo-Aide compressor (HT/PA) with an MMAD of 4.9 μm. Spirometry was performed at baseline and following 14 days of treatment. Dornase alfa delivered by both nebulizer systems produced small but statistically significant improvements in pulmonary function compared with baseline. There was a trend (P = 0.06) toward greater improvement in forced expiratory flow in 1 s in the SS/MA group (4.3%) compared with the HT/PA group (2.5%). These results indicate that the short-term spirometric response to dornase alfa is influenced in part by the physical characteristics of the aerosol in patients with mild lung disease. We speculate that this may be true for other therapeutic aerosols, and it appears that localization of disease in the lung plays a role in the response to inhaled agents. Pediatr. Pulmonol. 1998; 25:83–87. © 1998 Wiley-Liss, Inc.     

Efficacy of IV theophylline in children with severe status asthmaticus

STUDY OBJECTIVE: To determine whether adding IV theophylline to an aggressive regimen of inhaled and IV beta-agonists, inhaled ipratropium, and IV methylprednisolone would enhance the recovery of children with severe status asthmaticus admitted to the pediatric ICU (PICU). DESIGN: A prospective, randomized, controlled trial. Asthma scoring was performed by investigators not involved in treatment decisions and blinded to group assignment. SETTING: The PICU of an urban, university-affiliated, tertiary-care children's hospital. PATIENTS: Children with a diagnosis of status asthmaticus who were admitted to the PICU for < or = 2 h and who were in severe distress, as indicated by a modified Wood-Downes clinical asthma score (CAS) of > or = 5. INTERVENTIONS: All subjects initially received continuous albuterol nebulizations; intermittent, inhaled ipratropium; and IV methylprednisolone. The theophylline group was also administered infusions of IV theophylline to achieve serum concentrations of 12 to 17 microg/mL. A CAS was tabulated twice daily. MEASUREMENTS AND RESULTS: Forty-seven children (median age, 8.3 years; range, 13 months to 17 years) completed the study. Twenty-three children received theophylline. The baseline CASs of both groups were similar and included three subjects receiving mechanical ventilation in each group. All subjects receiving mechanical ventilation and theophylline were intubated before drug infusion. Among the 41 subjects who were not receiving mechanical ventilation, those receiving theophylline achieved a CAS of < or = 3 sooner than control subjects (18.6 +/- 2.7 h vs 31.1 +/- 4.5 h; p < 0.05). Theophylline had no effect on the length of PICU stay or the total incidence of side effects. Subjects receiving theophylline had more emesis (p < 0.05), and control patients had more tremor (p < 0.05). CONCLUSIONS: Theophylline safely hastened the recovery of children in severe status asthmaticus who were also receiving albuterol, ipratropium, and methylprednisolone. The role of theophylline in the management of asthmatic children in impending respiratory failure should be reexamined.     

无创正压通气治疗心脏术后急性呼吸衰竭的疗效和安全性研究

目的:探讨无创正压通气(NPPV)治疗心脏术后急性呼吸衰竭的疗效和安全性。方法:选择2011年9月至2012年10月,心脏外科术后发生急性呼吸衰竭适合进行NPPV的患者,随机分为无创通气组及常规治疗组。记录生命体征、血气分析测值,比较两组患者的再插管率、气管切开率、呼吸机相关性肺炎(VAP)发生率、病死率、入组后机械通气时间、住重症监护室(ICU)时间和术后住院时间。结果:研究期间,共有急性呼吸衰竭患者113例,符合纳入标准77例,男性48例,女性29例,平均年龄(61.7±11.0)岁,其中冠状动脉搭桥术38例,瓣膜手术20例,瓣膜手术+冠状动脉搭桥术9例,大血管手术7例,其他手术3例。无创通气组(n=39),常规治疗组(n=38)。无创通气组再插管率为12.8%,气管切开率10.2%,VAP发生率0,住院病死率12.8%,均明显低于常规治疗组(分别为84.2%、31.6%、18.4%和26.3%)(P<0.05或P<0.01)。无创通气组入组后机械通气时间和住ICU时间中位数分别为28.0(10.5,43.0)h和4.0(2.0,5.0)d,显著低于常规治疗组的69.5(3.8,248.0)h和5.0(4.0,9.0)d,(P<0.05或P<0.01),两组术后住院时间相近[分别为13.0(10.5,20.0)d和17.0(11.0,28.3)d,P>0.05]。NPPV治疗后2～4h,pH、PaCO2和PaO2均显著改善,心率和呼吸频率减慢(P<0.05或P<0.01),与同时间点常规治疗组水平相近。结论:NPPV选择性用于心脏术后急性呼吸衰竭,可显著降低再插管率,改善患者预后,疗效明显优于常规治疗组。需多中心大样本随机对照研究,以明确NPPV在心脏术后患者中应用的适应证和影响疗效因素。     

Sputum processing for evaluation of inflammatory mediators

Neutrophil-dominated inflammation is prominent in the cystic fibrosis (CF) and chronic bronchitis (CB) airways. We assessed the degree of airway inflammation by measuring the sputum concentrations of interleukin (IL)-8, myeloperoxidase (MPO), and deoxyribonucleic acid (DNA). We determined the relationship among the concentrations of these mediators and investigated methodological problems that may be responsible for reported variability in measurements. Sputa obtained from 31 patients were solubilized with phosphate-buffered saline, dithiothreitol (DTT) (0.1% or 1%), or dornase alfa (0.2 mg/mL). The sputum concentration of IL-8 and MPO was measured by enzyme-linked immunosorbent assay (ELISA), and DNA was measured using microfluorimetry. There was a significant relationship among sputum IL-8, MPO, and DNA. For MPO (means +/- SD), CF was 1,392 +/- 771 vs. CB at 75 +/- 65 mcg/mL; P < 0.0001. For IL-8: CF was 239 +/- 154 vs. CB at 121 +/- 108 ng/mL; P = 0.0002. For DNA, CF was 1.707 +/- 1.25 vs. CB at 0.184 +/- 0.272 mg/mL; P < 0.0001. The MPO concentration in CF sputum was approximately double after in vitro treatment with dornase alfa (P < 0.0001). There is a greater concentration of IL-8, MPO, and DNA in CF than in CB sputa. There is a significant relationship among these inflammatory markers in sputum. DNA polymers bind myeloperoxidase in the sputum, and we speculate that treatment with dornase alfa may remove a source of MPO inhibition.     

The increased cost of complications in children with status asthmaticus

Status asthmaticus is one of the most common causes of admission to a pediatric intensive care unit (PICU). There is little published data, however, examining the complications associated with the treatment of status asthmaticus in children in the PICU. Our hypothesis was that children experiencing a complication would have an increased duration of hospitalization for status asthmaticus. We performed a retrospective review of the complication profile and hospital course of all children admitted to a PICU with status asthmaticus over a 9 years period. Twenty-two (8%) of the 293 children admitted to the ICU with status asthmaticus experienced one or more complications during their treatment. The most common complications were aspiration pneumonia, ventilator-associated pneumonia, pneumomediastinum, pneumothorax, and rhabdomyolysis. Intubated children were significantly more likely than non-intubated children to experience a complication (RR 15.3; 95% CI 6.7-35). Fifteen (42%) of the 36 intubated children experienced a complication. Intubated children experiencing a complication had significantly longer duration of mechanical ventilation (163 +/- 169 hr vs. 66 +/- 65 hr, P = 0.03), ICU length of stay (237 +/- 180 hr vs. 124 +/- 86 hr, P = 0.02) and hospital charges (US dollars 117,184 +/- 111,191 vs. US dollars 38,788 +/- 27,784; P = 0.001) than intubated children not experiencing a complication. In this review, complications were associated with increased morbidity and duration of hospitalization in children with status asthmaticus, particularly in those intubated as part of their therapy. This suggests that intubation and mechanical ventilation itself may increase the risk of developing a complication in this population.     

How long does it take to initiate a child on long-term invasive ventilation? Results from a Canadian pediatric home ventilation program

OBJECTIVE:To assess the length of stay required to initiate long-term invasive ventilation at the authors’ institution, which would inform future interventional strategies to streamline the in-hospital stay for these families.METHODS:A retrospective chart review of children initiated on invasive long-term ventilation via tracheostomy at the authors’ acute care centre between January 2005 and December 2013 was performed.RESULTS:Thirty-five children were initiated on long-term invasive ventilation via tracheostomy at the acute care hospital; 19 (54%) were male. The median age at time of admission was 0.52 years (interquartile range [IQR] 0.06 to 9.58 years). Musculoskeletal disease (n=11 [31%]) was the most common reason for tracheostomy insertion. Two children died during the hospital admission. Fifteen children were discharged home directly from the acute care hospital and 18 were moved to the rehabilitation hospital. Six are current inpatients of the rehabilitation centre and were never discharged home. Combining the length of stay at the acute care and rehabilitation hospitals for the entire cohort, the median length of stay was 162.0 days (IQR 98.0 to 275.0 days) and 97.0 days (IQR 69.0 to 210.0 days), respectively, from the time of tracheostomy insertion.CONCLUSIONS:The median length of stay from the initiation of invasive long-term ventilation to discharge home from the rehabilitation hospital was somewhat long compared with other ventilation programs worldwide. Additionally, approximately 20% of the cohort never transitioned home. There is a timely need to benchmark across the country and internationally, to identify and implement strategies for cohesive, coordinated care for these children to decrease overall length of stay.     

Mucoactive agents for adults with acute lung conditions: A systematic review

Background and objectives

Inhaled mucoactive agents are used to enhance airway clearance, however efficacy and safety are unclear in adults with acute respiratory conditions.

Outcomes of Ventilated COPD Patients with Nosocomial Tracheobronchitis: A Case-Control Study

Abstract. Background: The aim of this study was to determine the impact of nosocomial tracheobronchitis (NTB) related to new bacteria on the outcome in patients with chronic obstructive pulmonary disease (COPD). Patients and Methods: A prospective observational case-control study was conducted in medical COPD patients requiring intubation and mechanical ventilation for more than 48 hours. Patients with nosocomial pneumonia were excluded. Six matching criteria were used, including the duration of mechanical ventilation before NTB occurrence. Results: 81 matched case-control pairs were studied. Although the mortality rate was similar (40% vs 34%; p = 0.48), median duration of mechanical ventilation (20 vs 12 days; p = 0.015) and intensive care unit (ICU) stay (25 vs 18 days; p = 0.022) were higher in cases than in controls. NTB was independently associated with a longer than median period of mechanical ventilation among case and control patients (OR = 4.7 [95%CI = 2–10.9]; p < 0.001). In cases with appropriate antibiotic treatment compared with those who did not receive antibiotics, a shorter median duration of mechanical ventilation (12 vs 23 days; p = 0.006) and ICU stay (16 vs 29 days; p = 0.029) were observed. Conclusion: NTB is associated with an increased duration of mechanical ventilation and ICU stays. Further studies are required to determine whether antibiotics could improve the outcome of patients with NTB.     

The use of surfactant in children with acute respiratory distress syndrome: efficacy in terms of oxygenation, ventilation and mortality

PURPOSE: The aim of this prospectively designed study was to investigate the efficacy of surfactant (S) for acute respiratory distress syndrome (ARDS) in children. MATERIALS AND METHODS: Children with ARDS were included in this study. Surfactant (Survanta, Abbott, USA) was given intratracheally at a dose of 150 mg/kg every 12 h for a total of two doses. During the study period none of the patients received permissive hypercapnia, high frequency ventilation, nitric oxide or ECMO. Peak inspiratory pressure (PIP), positive end expiratory pressure (PEEP), ventilation rate, mean airway pressure, tidal volume (TV), Murray index, PaO2/FiO2, ventilation index (VI), oxygen index (OI) and arterial oxygen tension difference (A-aDO2) were measured before and 48 h after surfactant treatment. Duration of mechanical ventilation therapy, duration in paediatric intensive care unit (PICU) and mortality rate were recorded. RESULTS: Among the 36 children who met the inclusion criteria, 12 were treated with surfactant. The mean age was 72.5+/-56.2 months; 47% of children were male. Infants were ventilated by pressure-controlled ventilators whereas for older children volume-controlled ventilators were used. Sepsis (42%) was the main predisposing factor followed by pneumonia (25%) and malignancy (17%). The baseline characteristics including age, predisposing factors, gender, PIP, PEEP, A-aDO2, PaO2/FiO2, OI, TV, VI and Murray index were similar in the surfactant and non-surfactant (NS) group (p>0.05). There were significant improvements in PIP, PEEP, A-aDO2, PaO2/FiO2, OI, TV, VI and Murray index in the surfactant group after surfactant treatment compared with NS group (p<0.05). Duration of PICU stay and ventilator treatment was longer in NS group (14+/-3.7, 1.8+/-3.2 days vs. 9.2+/-3.1, 8.6+/-1.9 days), (p<0.05). Mortality rate was 42% in surfactant compared with 63% in the NS group, (p>0.05). Children in the surfactant group lived significantly longer (p<0.05). CONCLUSIONS: Modified natural surfactant is an effective treatment option in children with ARDS for improving gas exchange, decreasing the use of ventilatory support and increasing survival time.     

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??Abstract??Objective To assess the liberal SBT safety screen criteria on weaning in intensive care unit.Methods A total of 82 patients to undergo mechanical ventilationwere randomly assigned to group A (by the liberal SBT safety screen criteria??n=42) and group B (by the traditional SBT safety screen criteria??n=80).After patients passed safety screening??SBT was performed.If SBT was completed??the procedures and results were notified to attending doctors.The decision of discontinuing mechanical ventilation or extubation was made by attending doctors.Finally??we compared the ventilator-free days??mechanical ventilation time??duration of ICU stay??28-day mortality??the rates of self-extubation and reintubation.Results Patients screened by the liberal SBT safety screen criteria spent more days breathing without assistance (25 d vs 21 d??P=0.000)??and the mechanical ventilation time (3 d vs 7.5 d??P=0.000)??time of ICU stay (11 d vs 17 d??P=0.001) and the 28-day mortality rate (14.3% vs 35.0%??P=0.029) were all decreased during the 28-day study period as compared with those by the traditional SBT safety screen criteria.The rates of self-extubation (2.4% vs 7.5%??P=0.574) and reintubation (9.5% vs 7.5%??P=1.000) were not significantly different between the two groups.Conclusion The liberal SBT safety screen criterion is superior to the traditional one??so it can be used as a routine screening standard in clinic.     

Thymosin beta4 sequesters actin in cystic fibrosis sputum and decreases sputum cohesivity in vitro

BACKGROUND: Filamentous actin (F-actin) forms polymers that contribute to the abnormal biophysical properties of sputum. Thymosin beta4 (Tbeta4) is the major monomeric actin-sequestering peptide in cells and can depolymerize F-actin. Tbeta4 could potentially decrease sputum viscoelasticity and adhesivity and improve sputum clearance. METHODS: Sputum was collected during pulmonary function testing from 17 subjects during a cystic fibrosis (CF) center visit. Sputum rheology, cough and ciliary transportability, and interfacial tension were measured before and after the addition of dornase alfa at 30 microg/mL; Tbeta4 at 0.3, 3, 30, and 150 microg/mL; and Tbeta4 with dornase alfa at 1.5 microg/mL each. Sputum was separately incubated with Tbeta4 at 30 microg/mL for 0, 10, 20, or 60 min. RESULTS: There was a direct relationship between actin filament length and sputum cohesivity. There was a dose-dependent threshold decrease in cohesivity with Tbeta4 and a time-dependent decrease in cohesivity over 60 min at 30 microg/mL. With the combination of dornase alfa and Tbeta4 at 1.5 microg/mL each, there was a 70% decrease in G*s and a 65% decrease in G' at 1 rad/s (p = 0.013). There was a 44% increase in cough transportability of sputum in vitro (p = 0.037) and a 71% increase in mucociliary transportability of sputum in vitro (p = 0.013) relative to control with the combination of dornase alfa and Tbeta4, but no significant change with dornase alfa or Tbeta4 alone at any concentration. CONCLUSIONS: Actin polymer filament length is correlated with sputum cohesivity. Tbeta4 depolymerizes CF sputum actin in both a dose-dependent and a time-dependent manner. An apparent synergy of Tbeta4 on actin and dornase on DNA may be explained by the combined effect of actin depolymerization and DNA filament severing or by virtue of actin depolymerization increasing the effectiveness of dornase alfa.     

Transfusion of blood components and postoperative infection in patients undergoing cardiac surgery

OBJECTIVE: To investigate the influence of blood derivatives on the acquisition of severe postoperative infection (SPI) in patients undergoing heart surgery. SETTING: The postoperative ICUs of a tertiary-level university hospital. DESIGN: A cohort study. METHODS: During a 4-year period, 738 patients, classified as patients with SPIs and patients without SPIs (non-SPI patients), were included in the study. We studied the influence of 36 variables on the development of SPI in general and individually for pneumonia, mediastinitis, and/or septicemia. The influence of the blood derivatives on infections was assessed for RBC concentrates, RBC and plasma, and RBC and platelets. RESULTS: Seventy patients (9.4%) were classified as having SPIs, and 668 (90.6%) were classified as not having SPIs. After multivariate analysis, the variables associated with SPI (incidence, 9.4%) were reintubation, sternal dehiscence, mechanical ventilation (MV) for > or = 48 h, reintervention, neurologic dysfunction, transfusion of > or = 4 U RBCs, and systemic arterial hypotension. The variables associated with nosocomial pneumonia (incidence, 5.9%) were reintubation, MV for > or = 48 h, neurologic dysfunction, transfusion of > or = 4 U blood components, and arterial hypotension. The variables associated with mediastinitis (incidence, 2.3%) were reintervention and sternal dehiscence, and those associated with sepsis (incidence, 1.6%) were reintubation, time of bypass > or = 110 min, and MV for > or = 48 h. The mortality rate (patients with SPI, 52.8%; non-SPI patients, 8.2%; p < 0.001) and mean (+/- SD) length of stay in the ICU (patients with SPI, 15.8 +/- 12.9 days; non-SPI patients, 4.5 +/- 4.4 days; p < 0.001) were greater for the infected patients. The transfused patients also had a greater mortality rate (13.3% vs 8.9%, respectively; p < 0.001) and a longer mean stay in the ICU (6.1 +/- 7.2 days vs 3.7 +/- 2.8 days, respectively; p < 0.01) than those not transfused. CONCLUSION: The administration of blood derivatives, mainly RBCs, was associated in a dose-dependent manner with the development of SPIs, primarily nosocomial pneumonia.