Multicenter randomized controlled trial of the effects of inhaled nitric oxide therapy on gas exchange in children with acute hypoxemic respiratory failure

OBJECTIVES AND BACKGROUND: To determine whether inhaled nitric oxide (iNO) therapy can attenuate the progression of lung disease in acute hypoxemic respiratory failure, we performed a multicenter, randomized, masked, controlled study of the effects of prolonged iNO therapy on oxygenation. We hypothesized that iNO therapy would improve oxygenation in an acute manner, slow the rate of decline in gas exchange, and decrease the number of patients who meet pre-established oxygenation failure criteria. STUDY DESIGN: A total of 108 children (median age 2.5 years) with severe acute hypoxemic respiratory failure from 7 centers were enrolled. After consent was obtained, patients were randomized to treatment with iNO (10 ppm) or mechanical ventilation alone for at least 72 hours. Patients with an oxygenation index >/=40 for 3 hours or >/=25 for 6 hours were considered treatment failures and exited the study. RESULTS: Patient age, primary diagnosis, pediatric risk of mortality score, mode of ventilation, and median oxygenation index (35 +/- 22 vs 30 +/- 15; iNO vs control; mean +/- SEM) were not different between groups at study entry. Comparisons of oxygenation indexes during the first 12 hours demonstrated an acute improvement in oxygenation in the iNO group at 4 hours (-10.2 vs -2.7, mean values; P <.014) and at 12 hours (-9.2 vs -2.8; P <.007). At 12 hours 36% of the control group met failure criteria in contrast with 16% in the iNO group (P <.05). During prolonged therapy the failure rate was reduced in the iNO group in patients whose entry oxygenation index was >/=25 (P <.04) and in immunocompromised patients (P <.03). CONCLUSIONS: We conclude that iNO causes an acute improvement in oxygenation in children with severe AHRF. Two subgroups (immunocompromised and an entry oxygen index >/=25) appear to have a more sustained improvement in oxygenation, and we speculate that these subgroups may benefit from prolonged therapy.     

Noninvasive ventilation with positive airway pressure in paediatric intensive care

AIM: The aim of the present study is to retrospectively evaluate the effectiveness of noninvasive pressure ventilation in the 24-bed Pediatric Intensive Care Unit (PICU) of the G. Gaslini Institute during a 24-month period. METHODS: A retrospective analysis of the characteristics (pH, CO2, SpO2, respiratory rate, oxygen requirement) of patients treated with noninvasive mechanical ventilation for different acute pathologies has been performed. RESULTS: Twenty patients (mean age 7.4+/-0.28 years) with acute respiratory failure due to different pathologies were treated with noninvasive mechanical ventilation. They were divided into 2 groups: the hypoxic group, suffering from pulmonary diseases, and the hypercapnic group, presenting a failure of the mechanical strength or increased dead space. Modalities of ventilation were pressure assisted/controlled or pressure support, delivered through nasal or facial masks. Fifteen out of 20 patients presented a marked improvement of oxygenation and ventilation. Mean times of treatment were 69 and 200 h in the hypoxic and hypercapnic groups, respectively. Five patients required intubation. Two patients presented reversible skin lesions over the nasal bridge. CONCLUSIONS: Noninvasive ventilation can be used in PICU. Major advantages regard immunocompromised children and patients with exacerbations from chronic respiratory diseases, whereas the exact role of noninvasive positive pressure ventilation in patients affected by acute respiratory distress syndrome is still controversial.     

Non-invasive positive pressure ventilation: current status in paediatric patients

Non-invasive positive pressure ventilation (NPPV) is a treatment for patients with respiratory dysfunction accomplished by an external interface and a positive pressure ventilator. The goals of NPPV therapy are to decrease the work of breathing and to improve respiratory gas exchange. Children with respiratory dysfunction are increasingly being treated with NPPV with the belief that it is a safe and effective alternative to invasive mechanical ventilation. Reports in support of NPPV are most promising in older children with chronic respiratory failure associated with restrictive pulmonary disorders and neuromuscular weakness. In children with advanced cystic fibrosis and nocturnal hypoxaemia, NPPV appears to be superior to treatment with supplemental oxygen alone in preventing hypoventilation. The role of NPPV in children with acute hypoxaemic respiratory failure is less well defined. Although early reports are encouraging, the question remains unanswered whether early application of NPPV as opposed to standard treatment reduces the likelihood or only delays the need for invasive mechanical ventilation. As young infants may not trigger the inspiratory pressure support feature of bi-level ventilators, application of NPPV with current devices is problematic in patients of this age. The horizon is promising for NPPV in the paediatric population and will likely include novel interfaces and responsive positive pressure devices better suited to the unique mechanical properties of the developing respiratory system.     

High-frequency oscillatory ventilation in pediatric patients with acute respiratory failure.

OBJECTIVE: To evaluate the effectiveness of high-frequency oscillatory ventilation (HFOV) in pediatric patients with acute respiratory failure, failing conventional ventilation. DESIGN: A prospective, clinical study. SETTING: Tertiary care pediatric intensive care unit. PATIENTS: Twenty pediatric patients (ages 12 days to 5 yrs) with acute respiratory failure (pneumonia, 14; sepsis with acute respiratory distress syndrome, 3; pulmonary edema as a complication of upper airway obstruction, 2; salicylate intoxication with acute respiratory distress syndrome, 1), failing conventional ventilation (median alveolar-arterial oxygen difference [P(A-a)O2] 578 [489-624] torr, median oxygenation index 26 [21-32]. INTERVENTIONS: HFOV was instituted after a median length of conventional ventilation of 15.5 (3.3-43.5) hrs. MEASUREMENTS AND MAIN RESULTS: Ventilator settings, arterial blood gases, oxygenation index, and P(A-a)O2 were recorded before HFOV (0 hrs) and at predetermined intervals during HFOV and compared using the one-way Friedman rank-sum procedure and a two-tailed Wilcoxon matched-pairs test. Initiation of HFOV caused a significant decrease in FiO2 at 1 hr that continued to 24 hrs (p 相似文献   

Recognition of the child at risk of cardiopulmonary arrest

Early treatment is a major factor to improve the outcome of children at risk of cardiopulmonary arrest. That's why it is essential to recognize as soon as possible clinical signs that indicate a respiratory and/or circulatory dysfunction. Immediate systematic assessment and re-assessment of oxygenation, ventilation and organ perfusion status is one of the keys in the prevention of cardiorespiratory arrest in children. Health care staff must assure that a child with signs of acute respiratory and/or circulatory dysfunction is under constant surveillance by a person with ability to interpret signs, identify problems and to initiate emergency treatment, if needed. Respiratory assessment must include respiratory rate, signs of mechanical respiratory failure (nasal flaring, respiratory noises, paradoxical breathing, prolonged expiration) as well as skin-mucous colour. Cardiocirculatory failure assessment includes heart rate, blood pressure, peripheral perfusion (capillary refill time and temperature gradient), level of consciousness and urinary output. In a child with impending signs of cardio-respiratory failure, the priority is to warrant adequate ventilation and oxygenation. If, despite this treatment, there is no improvement in perfusion, treatment of circulatory failure with fluids and vasoactive drugs is necessary.     

Applied respiratory physiology

Respiratory failure, hypoxia with or without hypercarbia, is common in infants and children. Knowledge of the underlying abnormal physiology facilitates diagnosis and therapy. Isolated hypoxia can result from ventilation perfusion mismatch, intra- and extrapulmonary shunting and impaired diffusion. Intra- and extrapulmonary shunting can be distinguished from the other conditions by a poor response to supplementary oxygen. Hypercarbia indicates an inadequate minute ventilation which can result from upper or lower airway obstruction, reduced respiratory system compliance or conditions adversely affecting the respiratory pump.     

新生儿无创高频振荡通气的研究进展

在新生儿重症监护室,无创通气是治疗轻中度呼吸衰竭重要的呼吸管理技术,正确合理的应用可以有效避免有创呼吸机的使用及相应并发症的发生。近年研究发现,无创高频振荡通气(nHFOV)结合了经鼻持续气道正压通气(nCPAP)和高频通气(HFV)的优点,可以迅速改善氧合、有效清除二氧化碳,较好地改善呼吸衰竭,被认为是一类新型有效的无创通气模式。国际上对新生儿nHFOV技术的合理使用及有效性、安全性等进行了许多研究,取得了许多重要的经验和结果,该文就新生儿nHFOV的临床研究进展进行综述。     

小潮气量肺保护通气策略在急性低氧性呼吸衰竭中的应用

目的探讨小潮气量(VT)和传统VT机械通气在急性低氧性呼吸衰竭(AHRF)治疗中的安全性的差异,评估小VT通气策略的疗效。方法将133例AHRF患儿分为传统VT通气组32例和小VT通气组101例,根据VT调整呼气末正压(PEEP),监测肺动态顺应性(Cdyn)、呼吸功(WOB)、呼吸道阻力(Raw)、呼吸道闭合压(P0.1)、肺泡气-动脉血氧分压差[p(A-a)(O2)]、氧合指数(OI)、血气分析等指标变化,观察患儿氧合改善情况、机械通气并发症发生、撤机情况以及患儿转归情况。结果 1.小VT组与传统VT组,Cdyn、Raw在上机1 d、3 d,WOB在上机3 d、5 d,P0.1在上机5 d、7 d比较差异均有统计学意义(Pa<0.05)。小VT通气24 h氧合改善较传统VT通气明显,pa(O2)、p(A-a)(O2)、OI比较差异均有统计学意义(Pa<0.05)。2.小VT组呼吸机相关性肺损伤发生率明显低于传统VT组,差异有统计学意义(P<0.05)。3.危重患儿病死率比较无明显差异。结论 Cdyn、Raw、WOB、P0.1等呼吸力学指标有助于判断机械通气过程中患儿肺部病变情况,及时调整呼吸机参数并判断撤机时机。在降低呼吸机相关性肺损伤的发生方面,小VT通气优于传统VT通气。小VT通气在降低AHRF患儿病死率方面,并不优于传统VT通气。     

Techniques and complementary techniques. Complementary treatments: nitric oxide, prone positioning and surfactant

The management of hypoxic respiratory failure is based on oxygen delivery and ventilatory support with lung-protective ventilation strategies. Better understanding of acute lung injury have led to new therapeutic approaches that can modify the outcome of these patients. These adjunctive oxygenation strategies include inhaled nitric oxide and surfactant delivery, and the use of prone positioning. Nitric oxide is a selective pulmonary vasodilator that when inhaled, improves oxygenation in clinical situations such as persistent pulmonary hypertension of the newborn, pulmonary hypertension associated with congenital heart disease, and acute respiratory distress syndrome (ARDS). When applied early in ARDS, prone positioning improves distribution of ventilation and reduces the intrapulmonary shunt. The surfactant has dramatically decreased mortality caused by hyaline membrane disease in premature newborns, although the results have been less successful in ARDS. Greater experience is required to determine whether the combination of these treatments will improve the prognosis of these patients.     

Recurrent pneumomediastinum and pneumothorax in Langerhans cell histiocytosis

Pneumothorax is an unusual complication of pulmonary Langerhans cell histiocytosis. We report three children who developed recurrent intrathoracic air leaks. In one case, bilateral pneumothoraces may have been precipated by intermittent positive pressure ventilation during general anaesthesia. Chemical pleurodesis was unsuccessful in preventing recurrence of pneumothoraces in two children. The use of extracorporeal membrane oxygenation as an alternative to intermittent positive pressure ventilation in children with respiratory failure from Langerhans cell histiocytosis is discussed. Med. Pediatr. Oncol. 29:139–142, 1997. © 1997 Wiley-Liss, Inc.     

Rescue high frequency oscillation in neonates with acute respiratory failure

The aim was to study the efficacy of rescue High Frequency Oscillatory Ventilation (HFOV) in improving the oxygenation and ventilation in neonates with acute respiratory failure after failing Conventional Mechanical Ventilation (CMV). Primary outcome was short term oxygenation, lung recruitment, and ventilation and secondary outcome studied was survival. 675 babies were ventilated and 97 of them received HFOV. HFOV significantly improved oxygenation index, alveolararterial oxygen gradient, pH, PCO₂, PO₂ and caused better lung recruitment within 2 hours. Fifty seven babies (58.77%) survived and the mortality was more in <28 weeks, babies with pulmonary hemorrhage, sepsis and CDH.     

Approaches in the management of acute respiratory failure in children

PURPOSE OF REVIEW: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are conditions that are associated with significant morbidity and mortality in children. There have been no advances in preventing ARDS, but this review highlights strategies directed at minimizing ventilator-induced lung injury and other new adjunctive therapies in the care of these patients. RECENT FINDINGS: High-frequency oscillatory ventilation, airway pressure release ventilation, and partial liquid ventilation are potential protective ventilatory modes for children with ALI or ARDS. Recruitment maneuvers, prone positioning, and kinetic therapy are all reported to improve oxygenation by opening the lung while positive end-expiratory pressure maintains functional residual capacity. Inhaled nitric oxide and surfactant are used to reduce inspired oxygen concentration and facilitate gas exchange, but their efficacy in ARDS continues to be investigated. Also, early investigations suggest that a specialized enteral formula can be a useful adjunctive therapy by reducing lung inflammation and improving oxygenation. When mechanical ventilation and adjunctive therapies fail, extracorporeal life support continues to be used as a rescue therapy. SUMMARY: It is likely that a combination of these therapies will maximize treatment and clinical outcomes in the future, but the only way that will be proven is through large controlled clinical trials in pediatric patients.     

体外膜肺氧合技术在新生儿呼吸衰竭中的应用

体外膜肺氧合（extracorporeal membran eoxygenation,ECMO）技术是一种能在较长时间内对心肺功能进行支持的体外生命支持技术。随着一氧化氮吸入、肺表面活性物质及高频通气等治疗手段的出现,需要ECMO支持的呼吸衰竭新生儿越来越少。但临床上仍有部分难治性呼吸衰竭新生儿对以上治疗无效或反应不良,仍需要ECMO支持。本文对国外ECMO技术在新生儿呼吸衰竭的应用情况进行介绍,并与国内的情况进行对比分析,希望有助于下一步我国新生儿ECMO技术的开展。     

体外膜肺氧合支持下转运心肺功能衰竭患儿三例

目的：介绍体外膜肺氧合支持下转运3例心肺功能衰竭儿科患者的经验。方法回顾分析2016年2月至4月陆军总医院附属八一儿童医院ECMO辅助下转运完全性大动脉转位(室间隔完整)合并心功能衰竭新生儿1例(病例1)、重症肺炎合并急性呼吸窘迫综合征1例(病例2)、肾病综合征并发卡氏肺孢子虫肺炎继发急性呼吸窘迫综合征1例(病例3)临床资料。结果病例1在ECMO 辅助下转运时间8 h,ECMO辅助43 h,入院第2天行大动脉调转术,术后延迟关胸,入院后7 d撤离呼吸机,15 d转出监护室;病例2在ECMO辅助下转运时间14 h,入院后第3天撤离ECMO,ECMO辅助45 h,入院后第8天撤离呼吸机,10 d转出监护室;病例3在ECMO辅助下转运时间15 h,ECMO辅助时间32 d,ICU停留时间31 d,最终死于多脏器功能衰竭(肺、肾、消化道、心脏)。结论成熟儿科团队,在ECMO辅助下,转运心肺功能衰竭重症患儿是可行和安全的。     

儿童经鼻高流量氧疗呼吸支持早期失败的高危因素分析

目的 探讨急性呼吸功能不全患儿经鼻高流量氧疗（HFNC）早期失败的高危因素。方法 回顾性分析2018年1~6月入住儿童重症监护室的123例行HFNC呼吸支持的急性呼吸功能不全患儿的临床资料。将住院期间无需升级呼吸支持方式，且成功撤离HFNC的患儿归为HFNC成功组（69例）；其余患儿在住院期间需升级呼吸支持方式（54例），其中使用HFNC 48 h内升级呼吸支持方式的患儿归为HFNC早期失败组（46例）。采用多因素logistic回归分析评估分析HFNC早期失败的危险因素。结果 HFNC早期失败组罹患休克、脓毒症、颅内高压综合征或多器官功能障碍综合征的比例显著高于HFNC成功组（P < 0.05）。早期失败组实施呼吸支持前的格拉斯哥昏迷评分、pH值、氧合指数均显著低于HFNC成功组（P < 0.05），而小儿死亡风险评分（PRISM评分）、PaCO₂/PaO₂比值显著高于HFNC成功组（P < 0.05）。多因素logistic回归分析显示，PRISM评分 > 4.5分和PaCO₂/PaO₂比值 > 0.64是HFNC早期失败的独立危险因素（OR分别为5.535、9.089，P < 0.05）。结论 PRISM评分 > 4.5分或PaCO₂/PaO₂比值 > 0.64的急性呼吸功能不全患儿行HFNC早期失败的风险较高。     

Approach to a Child with Breathing Difficulty

Breathing difficulty and respiratory distress is the most common cause of admission to the Pediatric Emergency. Respiratory distress presents as altered breathing pattern, forced breathing efforts or obstructed breathing, and chest indrawing; respiratory failure is defined as paCO₂ >50 mmHg (inadequate ventilation) and/or a paO₂ < 60mmHg (inadequate oxygenation). Rapid assessment is aimed to ascertain adequacy of airway patency, breathing, and circulation. Immediate care is directed at (a) restoration of airway patency- by positioning (head tilt –chin lift), cleaning the oropharynx, and/or insertion of oropharyngeal airway; (b) supporting breathing- with high flow oxygen and assisted ventilation (with bag and mask or endotracheal intubation and ventilation), and (c) restoration of circulation- using fluid boluses and inotropes, if necessary. Immediate specific management may require endotracheal intubation/tracheostomy for upper airway obstruction; needle thoracotomy and drainage of pneumothorax; and first dose of antibiotic for febrile children. Thereafter meticulous history, focused physical examination, and specific laboratory/radiological investigations are undertaken to identify the underlying cause. At the end of this, one should be able to categorize the child to one of the following: (a) upper airway obstruction, (b) pneumonia (syndrome of cough, fever and breathing difficulty), (c) lower airway obstruction, (d) slow or irregular breathing without pulmonary signs, and (e) respiratory distress with cardiac findings, to initiate specific treatment. Further respiratory support by Continuous Positive Airways Pressure (CPAP) and mechanical ventilation may be required in some cases. All children with respiratory distress must be monitored for early detection of worsening/complications, assessment of response to therapy and rapid documentation of clinical state.     

小潮气量机械通气在小儿呼吸衰竭中的应用

目的探讨小潮气量机械通气的临床治疗及肺保护效果。方法选取48例呼吸衰竭患儿,原发疾病涉及严重感染、外伤和重大手术等。除综合治疗外,均采用小潮气量机械通气,观察上机前后的血气分析、呼吸机参数、机械通气相关并发症等指标。结果与大潮气量机械通气相比,小潮气量肺保护通气的呼吸性酸中毒纠正率与之无明显差异,而后者呼吸机相关性肺损伤(VILI)的发生率较前者有明显下降。结论小潮气量机械通气适用于儿童呼吸衰竭的治疗,有助于防止发生肺气肿、纵隔气肿或皮下气肿。     

One- to three-year outcome for 14 neonatal survivors of extracorporeal membrane oxygenation

Extracorporeal membrane oxygenation, using venoarterial or venovenous perfusion, is a safe and effective procedure in the term of near-term infant with life-threatening respiratory failure. Without extracorporeal membrane oxygenation, due to the severity of their disease, these children are at high risk for neurologic damage, chronic lung disease, and death. Because survival is not expected without extracorporeal membrane oxygenation therapy, there is no corresponding control group to which these survivors may be compared. In this report, we reviewed the outcome at 1 to 3 years in the first 14 survivors of extracorporeal membrane oxygenation treated at our institution. Seven of 14 neonatal extracorporeal membrane oxygenation survivors (50%) were normal or near normal at between 1 and 3 years of age. Ten (71%) had normal mental ability. We conclude that in neonates with high mortality risk from respiratory failure, near-normal growth and development can be expected in the majority who survive with extracorporeal membrane oxygenation treatment.     

Continuous positive airway pressure with modified helmet for treatment of hypoxemic acute respiratory failure in infants and a preschool population: a feasibility study.

OBJECTIVE: To analyze the feasibility of using continuous positive airway pressure (CPAP) delivered via a modified helmet to treat children with hypoxemic acute respiratory failure. DESIGN: A single-center, prospective, clinical study. SETTING: Pediatric intensive care unit in a university hospital. PATIENTS: Fifteen consecutive children (from 1 month to 5 yrs of age) with hypoxemic acute respiratory failure (defined as Pao2/Fio2 <300). INTERVENTIONS: CPAP was delivered via a modified helmet (CaStar, Starmed, Italy) of reduced size, fastened by a device we call a "baby-body." The feasibility of CPAP with the helmet was the primary end point. The improvement of gas exchange was the secondary one. MEASUREMENTS AND MAIN RESULTS: Ten of 15 children had multiple organ failure. Nine of 15 children were 相似文献   

Surfactant treatment of an infant with acute idiopathic pulmonary hemorrhage.

OBJECTIVE: To describe the successful use of surfactant for treatment of respiratory distress refractory to conventional mechanical ventilation in a 4-wk-old with pulmonary hemorrhage. DESIGN: Case report. SETTING: Tertiary care center pediatric intensive care unit. PATIENT: Four-week-old infant. MAIN RESULT: Clinical improvement of respiratory distress as evidenced by 50% reduction in oxygenation index and subsequent extubation. CONCLUSION: Pulmonary hemorrhage is a rare but potentially fatal condition in children. Previously described therapeutic approaches include high-frequency oscillation ventilation and extracorporeal membrane oxygenation. Infants with pulmonary hemorrhage and respiratory distress may benefit from a trial of surfactant before escalating care.