Transaminase levels in ventilated children with respiratory syncytial virus bronchiolitis

Objectives To compare disease severity as judged by duration of ventilation, inotrope use and mortality in children ventilated for respiratory syncytial virus (RSV)-positive lower respiratory tract infection (LRTI) with and without elevated transaminase levels and to determine the aetiology of elevated transaminase levels in this patient group.Design Prospective observational study.Setting Twenty-two-bed Paediatric Intensive Care Unit.Patients Forty-eight ventilated children with RSV-positive LRTI.Measurements and results Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured daily. In patients with elevated transaminase levels infection with the following viruses was investigated: hepatitis A, B and C viruses, cytomegalovirus, Epstein Barr virus, adenovirus, influenza virus, and parainfluenza viruses (types I, II, and III). Elevated transaminase levels were detected in 22 (46%) patients. The duration of mechanical ventilation (geometric mean; 95% CI) was significantly (P<0.05) longer in the group with elevated transaminase levels: 10.6 (9.4; 11.7) days versus 3.5 (2.8; 4.2) days. This difference remained significant in patients without congenital heart disease. Inotrope use was more common and all deaths occurred in the group with elevated transaminase levels (P<0.05). All patients who died and all but two patients with inotrope requirements had underlying congenital heart disease. One patient with elevated transaminase levels had a simultaneous infection with influenza A virus.Conclusions RSV disease in ventilated children was more severe if transaminase levels were elevated. Transaminase level elevation was due to hepatitis in the majority of patients. In patients with congenital heart disease we also detected myocardial involvement.     

Impact of respiratory syncytial virus infection on surgery for congenital heart disease: postoperative course and outcome.

OBJECTIVES: a) To describe the postoperative course and outcome of cardiac surgery in children with recent respiratory syncytial virus (RSV) infection; and b) to evaluate whether timing of surgery has any impact on the outcome. DESIGN: Retrospective case series. SETTING: Intensive care unit and medical and surgical wards of a teaching pediatric hospital. PATIENTS: Twenty-five children (aged 25 days to 3.5 yrs; median, 4 months) with congenital heart disease who had cardiac surgery within 6 months after RSV infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We reviewed the clinical course and outcome of all patients. The cardiac diagnoses included ventricular septal defect (n = 11), tetralogy of Fallot (n = 3), atrioventricular canal (n = 3), and others (n = 8). Thirteen patients had surgery during the same admission as RSV infection (group I), and 12 patients had surgery electively after being discharged to home after RSV infection (group II). Two patients in group I died; both of these patients had undergone total repair of tetralogy of Fallot within 2 wks after admission for RSV infection. Postoperative complications in group I patients included pulmonary hypertension (n = 5), adult respiratory distress syndrome (n = 1), tracheal stenosis (n = 1), left ventricular dysfunction (n = 1), pericardial effusion (n = 1), secondary bacterial or fungal infection (n = 7), and deep venous thrombosis (n = 1). Of all group I patients, the ones who were operated on early appeared to be at higher risk for complications, especially for postoperative pulmonary hypertension. No patient in group II died, and only two patients had minor complications (one had reactive airway disease, and the other had a transient superior vena cava syndrome after a bidirectional Glenn operation). CONCLUSIONS: Cardiac surgery performed during the symptomatic period of RSV infection is associated with a high risk of postoperative complications, especially postoperative pulmonary hypertension. These complications appeared to be more frequent and of greater severity in patients who had earlier surgery compared with those who had later surgery. More studies are needed regarding the proper timing of cardiac surgery in patients with congenital heart disease and RSV infection.     

High-frequency oscillatory ventilation in pediatric respiratory failure: a multicenter experience

OBJECTIVE: The use of high-frequency oscillatory ventilation (HFOV) has increased dramatically in the management of respiratory failure in pediatric patients. We surveyed ten pediatric centers that frequently use high-frequency oscillation to describe current clinical practice and to examine factors related to improved outcomes. DESIGN: Retrospective, observational questionnaire study. SETTING: Ten tertiary care pediatric intensive care units. PATIENTS: Two hundred ninety patients managed with HFOV between January 1997 and June 1998. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were classified according to presence or absence of preexisting lung disease, symptomatic respiratory syncytial virus infection, or presence of cyanotic heart disease or residual right-to-left intracardiac shunt. In addition, patients for whom HFOV acutely failed were analyzed separately. Those patients with preexisting lung disease were significantly smaller, had a significantly higher incidence of pulmonary infection as the triggering etiology, and had a significantly greater duration of conventional ventilation before institution of HFOV compared with patients without preexisting lung disease. Stepwise logistic regression was used to predict mortality and the occurrence of chronic lung disease in survivors. In patients without preexisting lung disease, the model predicted a 70% probability of death when the oxygenation index (OI) after 24 hrs was 28 in the immunocompromised patients and 64 in the patients without immunocompromise. In the immunocompromised patients, the model predicted a 90% probability of death when the OI after 24 hrs was 58. In survivors without preexisting lung disease, the model predicted a 70% probability of developing chronic lung disease when the OI at 24 hrs was 31 in the patients with sepsis syndrome and 50 in the patients without sepsis syndrome. In the patients with sepsis syndrome, the model predicted a 90% probability of developing chronic lung disease when the OI at 24 hrs was 45. CONCLUSIONS: Given the number of centers involved and the size of the database, we feel that our results broadly reflect current practice in the use of HFOV in pediatric patients. These results may help in deciding which patients are most likely to benefit from aggressive intervention by using extracorporeal techniques and may help identify high-risk populations appropriate for prospective study of innovative modes of supporting gas exchange (e.g., partial liquid breathing or intratracheal pulmonary ventilation).     

Palivizumab in congenital heart disease: should international guidelines be revised?

Palivizumab has reduced the incidence of respiratory syncytial virus hospitalization in infants and children with congenital heart disease by 45%. Although the mortality rate of children with congenital heart disease hospitalized with respiratory syncytial virus infection has declined from 37% to ～ 3% over the past 3 decades, palivizumab has not been shown to improve mortality. There has been considerable controversy over the cost-effectiveness of administering palivizumab according to international guidelines, including children with congenital heart disease. In particular, the number of children that need to be treated with palivizumab to prevent one respiratory syncytial virus hospitalization increases dramatically in children > 12 months of age. As a result, the authors recommend that countries re-examine their recommendations for providing palivizumab up to age 24 months in children with congenital heart disease.     

Palivizumab in congenital heart disease: should international guidelines be revised?

Palivizumab has reduced the incidence of respiratory syncytial virus hospitalization in infants and children with congenital heart disease by 45%. Although the mortality rate of children with congenital heart disease hospitalized with respiratory syncytial virus infection has declined from 37% to approximately 3% over the past 3 decades, palivizumab has not been shown to improve mortality. There has been considerable controversy over the cost-effectiveness of administering palivizumab according to international guidelines, including children with congenital heart disease. In particular, the number of children that need to be treated with palivizumab to prevent one respiratory syncytial virus hospitalization increases dramatically in children > 12 months of age. As a result, the authors recommend that countries re-examine their recommendations for providing palivizumab up to age 24 months in children with congenital heart disease.     

儿童先天性心脏病体外循环术后呼吸道合胞病毒感染临床研究

目的探讨先天性心脏病(先心病)体外循环术后呼吸道合胞病毒感染的特点、转归及治疗原则。方法回顾性分析2 423例行体外循环心脏畸形矫治术患儿临床资料,对术后发生呼吸道合胞病毒感染的11例患儿进行统计分析。结果先心病体外循环术后呼吸道合胞病毒感染发生率为0.46%,11例感染患儿中死亡6例;术后ICU停留中位时间25d,机械通气中位时间429h;二次气管插管8例,使用经鼻持续气道正压通气4例,使用高频振荡呼吸机通气7例;术后合并其他细菌感染8例,其中多重感染5例。结论先心病体外循环术后呼吸道合胞病毒感染的发生率低,但病情进展迅速、预后不良。     

Improved oxygenation after discontinuing neuromuscular blockade

Objective: To evaluate the effects of prolonged neuromuscular blockade (NMB) on oxygenation and duration of mechanical ventilation in children with respiratory failure. Design: Retrospective case control study. Setting: The pediatric intensive care unit (PICU) of a tertiary university hospital. Patients: All children (n=68) in the PICU ventilated for pulmonary parenchymal disease for 3 days or longer over a 412 year period. Interventions: None. Measurements and results: Diagnoses, pediatric risk of mortality scoring, indications for, and duration of, mechanical ventilation and neuromuscular blockade, and blood gas data with corresponding ventilator parameters were extracted from the medical records. Twenty-eight patients received NMB at the initiation of mechanical ventilation and this was continued for 72 h or longer. Cessation of NMB was associated with a significant improvement in ventilator parameters and oxygenation index. The subset of children with respiratory syncytial virus disease (RSV) receiving prolonged NMB had longer ventilator courses compared to those in whom NMB was not used, despite similar demographics, severity of illness and oxygenation impairment. Conclusions: Stopping NMB is associated with a rapid improvement in oxygenation and prolonged use of NMB in children with RSV is associated with a protracted ventilatory course. Definition: Oxygenation index (OI)^*: Mean Airway Pressure ×FiO₂×100/PaO₂ ^* Higher scores represent deterioration in oxygenation Received: 26 January 1996 Accepted: 5 August 1996     

Concurrent bacterial infection and prolonged mechanical ventilation in infants with respiratory syncytial virus lower respiratory tract disease

Objective To identify demographic, clinical, and laboratory variables predictive for a concurrent bacterial pulmonary infection in ventilated infants with respiratory syncytial virus (RSV) lower respiratory tract disease (LRTD) and investigate antimicrobial drug use.Design and setting Retrospective, observational study in a 14-bed pediatric intensive care unit.Patients 82 infants younger than 1 year of age with a virologically confirmed RSV LRTD during 1996 – 2001, of whom 65 were mechanically ventilated.Results Microbiological data were available from 38 ventilated infants, 10 of whom had a positive blood culture (n=1) or endotracheal aspirate (n=9) obtained upon admission to the pediatric intensive care unit (PICU). Infants with a positive culture had a lower mean gestational age but were otherwise demographically comparable to those with negative culture results. Infants with a positive culture were ventilated 4 days longer. Indicators for a concurrent bacterial infection were comparable between ventilated and nonventilated infants. Antimicrobial drugs were used in 95.1% of infants (100% of ventilated infants) with a mean duration of 7.8±0.3 days. The moment of initiation and duration of antimicrobial drug treatment varied considerably.Conclusions We observed in ventilated infants a low occurrence of concurrent bacterial pulmonary infection, but infants with positive cultures needed prolonged ventilatory support. Improvement in the diagnosis of a pulmonary bacterial infection is warranted to reduce the overuse of antimicrobial drugs among ventilated infants with RSV LRTD and to restrict these drugs to the proper patients.     

心脏疾病伴肺动脉高压术后患者呼吸道的护理

目的总结心脏疾病伴肺动脉高压患者术后的呼吸道护理经验。方法对32例心脏疾病伴肺高压患者在围手术期进行针对性的护理,术后合理应用呼吸机,保持有效供氧,加强肺高压监护和呼吸道护理。结果 30例患者术后肺动脉压力控制理想,治愈出院。2例死亡,死亡原因为严重低心排出量综合征和肺部感染。结论术后加强呼吸道管理,保证有效供氧,可以降低心脏疾病伴肺动脉高压术后死亡率和并发症发生率。     

Prognosis factors and outcome of community-acquired pneumonia needing mechanical ventilation

PURPOSE: To evaluate the variables associated with mortality of patients with community-acquired pneumonia who require mechanical ventilation and to determine the attributable morbidity and intensive care unit (ICU) mortality of community-acquired pneumonia. MATERIAL AND METHODS: Retrospective cohort study carried out in 361 ICUs from 20 countries including 124 patients who required mechanical ventilation on the first day of admission to the hospital due to acute respiratory failure secondary to severe community-acquired pneumonia. To assess the factors associated with outcome, a forward stepwise logistic regression analysis was performed, and to determine the attributable mortality of community-acquired pneumonia, a matched study design was used. RESULTS: We found 3 independent variables significantly associated with death in patients with community-acquired pneumonia requiring mechanical ventilation: simplified acute physiological score greater than 45 (odds ratio, 5.5 [95% confidence interval, 1.7-12.3]), shock (odds ratio, 5.7 [95% confidence interval, 1.7-10.1]), and acute renal failure (odds ratio, 3.0 [95% confidence interval, 1.1-4.0]). There was no statistically significant difference in ICU mortality among patients with or without community-acquired pneumonia (32% vs 35%; P=.59). CONCLUSIONS: Community-acquired pneumonia needing mechanical ventilation is not a disease associated with higher mortality. The main determinants of patient outcome were initial severity of illness and the development of shock and/or acute renal failure.     

Prospects of antiviral and anti-inflammatory therapy for respiratory syncytial virus infection

Respiratory syncytial virus is the leading viral cause of death in children less than 2 years of age, and is an increasing cause of morbidity and mortality in transplant patients and the elderly. Respiratory syncytial virus causes upper and lower respiratory tract infections, which can lead to severe bronchiolitis and pneumonia. High-risk groups for severe respiratory syncytial virus infection include infants with a history of premature birth with or without chronic lung disease, children with congenital heart disease, children with cystic fibrosis or chronic lung diseases, and immunosuppressed patients or patients with immunodeficiency. However, the majority of infants who have severe respiratory syncytial virus disease are born at full term and are otherwise healthy. It is unclear why children, the elderly and the immunosuppressed are at much higher risk for severe disease; however, a respiratory syncytial virus-induced immune pathologic mechanism has long been suspected. Attempts to develop a safe and effective vaccine against respiratory syncytial virus have failed. Antirespiratory syncytial virus immunotherapy, although effective prophylactically, does not provide any beneficial clinical outcome when administered therapeutically, indicating that respiratory syncytial virus-induced pathology is most likely the result of the inflammatory response to infection, rather than a direct viral cytopathic effect. Thus, a combined antiviral and anti-inflammatory therapy may represent the safest and most efficient treatment for acute respiratory syncytial virus infection. In this review, the current knowledge that has set the rationale for the development of such therapy is summarized.     

小儿心脏术后早期合并呼吸道合胞病毒感染的影响和转归

目的 总结小儿心脏术后早期(<72 h)合并呼吸道合胞病毒(Respiratory Sncytial Virus,Rsv)感染对患儿术后病程的影响及其转归并分析总结治疗经验.方法回顾分析2005年5月至2008年5月浙江大学医学院附属儿童医院SICU收治的39名先天性心脏病(先心病)心内直视术后早期合并RSV感染的患儿的术后病程和转归.并1:1随机配对抽取同期收治的同年龄、同病种、无RSV感染的先心病心内直视后的39名患儿作为对照组.采取成组配对设计资料的t检验法比较两组患儿的呼吸机辅助通气时间、住ICU时间和住院时间;采取Fisher精确检验法检验二次插管率、无创辅助通气应用率以及术后常见并发症的发生率.再根据患儿年龄、先心病病种以及是否合并肺动脉高压进行分组比较.结果 两组患儿均痊愈出院.RSV感染显著延长患儿的呼吸机辅助通气时间、住ICU时间和住院时间,并增加术后肺不张的发生率(P<0.05).对年龄<6个月的患儿RSV感染不仅显著延长呼吸机辅助通气时间、住ICU时间和住院时间(P<0.05),还增加术后低心排综合征和合并感染的发生率(P=0.05);而对>24月的患儿无显著影响.对紫绀型先心病患儿显著延长其呼吸机辅助通气时间,住ICU时间和住院时间(P<0.05);对非紫绀型先心病患儿仅显著延长住ICU时间和住院时间(P均<0.05).对合并肺动脉高压患儿RSV感染不仅显著延长呼吸机辅助通气时间,住ICU时间和住院时间,还增加术后合并感染的发生率(P均<0.05);而对无肺动脉高压患儿仅延长住院时间(P<0.05).结论小儿心脏手术后早期合并RSV感染会对术后病程产生不良影响,尤其对小婴儿,紫绀型先心及合并肺动脉高压的患儿影响更大.早期诊断,采取有效的循环、呼吸支持结合抗病毒等综合治疗取得了较满意的治疗效果.     

Prospects of antiviral and anti-inflammatory therapy for respiratory syncytial virus infection

Respiratory syncytial virus is the leading viral cause of death in children less than 2 years of age, and is an increasing cause of morbidity and mortality in transplant patients and the elderly. Respiratory syncytial virus causes upper and lower respiratory tract infections, which can lead to severe bronchiolitis and pneumonia. High-risk groups for severe respiratory syncytial virus infection include infants with a history of premature birth with or without chronic lung disease, children with congenital heart disease, children with cystic fibrosis or chronic lung diseases, and immunosuppressed patients or patients with immunodeficiency. However, the majority of infants who have severe respiratory syncytial virus disease are born at full term and are otherwise healthy. It is unclear why children, the elderly and the immunosuppressed are at much higher risk for severe disease; however, a respiratory syncytial virus-induced immune pathologic mechanism has long been suspected. Attempts to develop a safe and effective vaccine against respiratory syncytial virus have failed. Antirespiratory syncytial virus immunotherapy, although effective prophylactically, does not provide any beneficial clinical outcome when administered therapeutically, indicating that respiratory syncytial virus-induced pathology is most likely the result of the inflammatory response to infection, rather than a direct viral cytopathic effect. Thus, a combined antiviral and anti-inflammatory therapy may represent the safest and most efficient treatment for acute respiratory syncytial virus infection. In this review, the current knowledge that has set the rationale for the development of such therapy is summarized.     

新生儿期先天性心脏病术后合并重度肺动脉高压的护理

目的:探讨新生儿期先天性心脏术后合并重度肺动脉高压的护理策略。方法:2005年1月～2010年10月我科共收治155例新生儿先天性心脏病术后并发重度肺动脉高压的患儿,通过严密监护加强护理,改变患儿肺顺应性,降低肺血管阻力和肺动脉高压,提高肺血流量,改善肺通气-血流比例,提高肺动脉血氧压力,改善患儿缺氧状态,改善心功能,加强呼吸道护理,降低了肺部并发症的发生,避免了肺高压危象的发生。结果:治愈127例,死亡3例,25例因经济原因放弃治疗出院。平均住院时间22 d,平均使用呼吸机时间4 d。结论:新生儿期先天性心脏术后合并重度肺动脉高压患儿,术后护理难度大、危险高,全面、规范的护理对提高手术成功率至关重要,大大降低了手术死亡率和提高了生存质量。     

Respiratory syncytial virus triggered adult respiratory distress syndrome in infants: A report of two cases

Two infants with severe respiratory syncytial virus infection which resulted eventually in classical adult respiratory distress syndrome (ARDS) are presented. Both infants had severe apneic spells, necessitating intubation and mechanical ventilation (MV). Chest radiographs changed after a few days after institution of MV from initial bronchopneumonia like pattern to severe ARDS. Assessment of respiratory system mechanics (single breath occlusion technique) revealed severe restrictive disease in both cases. The first patient recovered with residual restrictive changes determined during a follow-up 2.5 months later, whereas the second infant died because of ARDS, pulmonary interstitial emphysema and hypoxemic hypoxia.     

A technique for the administration of ribavirin to mechanically ventilated infants with severe respiratory syncytial virus infection

Fifteen infants with respiratory syncytial virus pulmonary infection admitted to our pediatric ICU from December 1, 1985 through April 30, 1986, required mechanical ventilation. These patients were placed on an open trial of ribavirin therapy. We describe a technique for the safe delivery of aerosolized ribavirin to these infants while on the ventilator. The agent was delivered for 16 h/day for 7 days. Modifications of the ventilator circuit were needed to prevent the condensation of the drug in the ventilator tubing and to allow for the safe and effective operation of the ventilator. A common ventilator strategy was used for all patients. The highest positive inspiratory pressure generated was 42 +/- 9.5 (SD) cm H2O, the highest PEEP was 5.9 +/- 3.2 cm H2O, the duration of ventilation was 10.7 +/- 8.5 days, and exposure to fraction of inspired oxygen was greater than or equal to 0.6 for 55.3 h. Ribavirin levels were measurable in two patients, thereby demonstrating that the drug was in fact delivered and absorbed. Our preliminary results demonstrate that ribavirin can be delivered to the patients with respiratory syncytial viral infections who require mechanical ventilation; however, further studies are indicated to evaluate the efficacy and dose responsiveness, alterations in pulmonary dynamics, and safety of ribavirin in delivery to infants requiring ventilation.     

Palivizumab in the prophylaxis of respiratory syncytial virus infection

Respiratory syncytial virus infection continues to be one of the most important health problems in infancy. Active prophylaxis against this infection (i.e., vaccination) is not available. Therefore, protection of high-risk infants is possible only by passive prophylaxis with specific antibodies. Palivizumab (Synagis®) and respiratory syncytial virus intravenous immune globulin are licensed by the US Food and Drug Administration for the prevention of severe lower respiratory tract infections caused by respiratory syncytial virus in infants with bronchopulmonary dysplasia, infants with a history of premature birth (≤35 weeks gestational age) and children with hemodynamically significant congenital heart disease. Palivizumab is a humanized monoclonal antibody produced by recombinant DNA technology, directed to an epitope in the A antigenic side of the F-protein of the respiratory syncytial virus. This review discusses the characteristics of this drug in detail.     

Diagnosing heart failure in children with congenital heart disease and respiratory syncytial virus bronchiolitis

ObjectiveThe objective of this study is to examine if the B-type natriuretic peptide (BNP) can be used in diagnosing heart failure (HF) in children with congenital heart disease (CHD) who present to the emergency department (ED) with acute bronchiolitis.MethodsA prospective cohort single-group study of children with CHD and respiratory syncytial virus bronchiolitis was conducted in a pediatric ED. The reference standard for the presence of HF was the clinical and echocardiographic assessment of a pediatric cardiologist blinded to the BNP test results.ResultsEighteen cases were diagnosed, 7 (39%) had acute HF and 11 (61%) did not have acute HF. Patients with HF had a higher level of BNP compared with patients who did not have HF (783 pg/mL [interquartile range, 70-1345] vs 59 pg/mL [interquartile range, 23-90]; P < .013). A BNP level of 95 pg/mL was the optimal cutoff point, having a sensitivity of 0.71 (95% confidence interval, 0.29-0.96) and a specificity of 0.91 (95% confidence interval, 0.58-0.99).ConclusionThe results of this small study suggest that the BNP test can be useful to ascertain the presence of HF in children with CHD who present to the ED with respiratory syncytial virus bronchiolitis.     

Palivizumab in the prophylaxis of respiratory syncytial virus infection

Respiratory syncytial virus infection continues to be one of the most important health problems in infancy. Active prophylaxis against this infection (i.e., vaccination) is not available. Therefore, protection of high-risk infants is possible only by passive prophylaxis with specific antibodies. Palivizumab (Synagis) and respiratory syncytial virus intravenous immune globulin are licensed by the US Food and Drug Administration for the prevention of severe lower respiratory tract infections caused by respiratory syncytial virus in infants with bronchopulmonary dysplasia, infants with a history of premature birth (< or =35 weeks gestational age) and children with hemodynamically significant congenital heart disease. Palivizumab is a humanized monoclonal antibody produced by recombinant DNA technology, directed to an epitope in the A antigenic side of the F-protein of the respiratory syncytial virus. This review discusses the characteristics of this drug in detail.     

Management of respiratory syncytial virus with lower respiratory tract infection in infants and children

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in infants and children requiring pediatric hospitalizations. Infants with chronic lung, cardiac, or neuromuscular conditions are at increased risk for RSV infection. Early RSV is associated with subsequent diagnosis of reactive airway disease. The management of RSV with lower respiratory track infection in infants and children remains controversial. Bronchodilators may have some short-term benefit, but are not recommended as standard practice for infants and children. Antiviral therapy may be used for high-risk and severely ill patients. Corticosteroids may be effective in cases of moderate to severe RSV with lower respiratory track infection. Monoclonal antibodies have shown some promise in achieving passive immunity for those at greatest risk, including preterm infants younger than 1 year or infants younger than 2 years with chronic lung disease. Emergency management remains primarily supportive, with vigilant monitoring of oxygenation and hydration status. Interventions include supplemental oxygen therapy, ventilation, and fluid and nutrition therapy. Respiratory syncytial virus prophylaxis for high-risk patients includes intramuscular injections of palivizumab (Synagis) each month during RSV season, from November through April. Prevention strategies include washing hands, cleaning environment surfaces, and isolating infants and children with RSV in the emergency care area.