急性呼吸窘迫综合征机械通气策略的新进展

急性呼吸窘迫综合征（ARDS）机械通气的目标是保证足够的氧合和最小的呼吸机相关肺损伤。无创机械通气应慎用于ARDS。小潮气量通气的肺保护性通气策略能降低ARDS死亡率,以驱动压为导向设置潮气量更合理。建议根据静态压力-容积曲线采用低位转折点法来确定理想的呼气末正压（PEEP）,不支持常规使用高水平PEEP。俯卧位通气、高频振荡通气和体外膜氧合技术可用于拯救重症ARDS。机械通气中保持ARDS患者自主呼吸很重要,可采用双相气道正压通气、压力支持通气和神经电活动辅助通气等辅助通气模式。不推荐补充外源性肺泡表面活性物质、吸入一氧化氮或支气管扩张剂、气道压力释放通气和部分液体通气。     

Pediatric acute lung injury

Among ventilated children, the incidence of acute lung injury (ALI) was 9%; of that latter group 80% developed the acute respiratory distress syndrome (ARDS). The population-based prevalence of pediatric ARDS was 5.5 cases/100.000 inhabitants. Underlying diseases in children were septic shock (34%), respiratory syncytial virus infections (16%), bacterial pneumonia (15%), near-drowning 9%, and others. Mortality ranged from18% to 27% for ALI (including ALI-non ARDS and ARDS) and from 29% to 50% for ARDS. Mortality was only 3%–11% in children with ALI-non ARDS. As risk factors, oxygenation indices and multi-organ failure have been identified. New insights into the pathophysiology (for example the interplay between intraalveolar coagulation/fibrinolysis and inflammation and the genetic polymorphism for the angiotensin-converting enzyme) offer new therapeutic options. Lung protective mechanical ventilation with optimal lung recruitment is the mainstay of supportive therapy. New therapeutic modalities refer to corticosteroid and surfactant treatment. Well-designed follow up studies are needed.     

新生儿急性肺损伤的诊断与治疗策略

急性肺损伤(ALI)和急性呼吸窘迫综合征(ARDS)是新生儿临床的常见危重症,随着对ALI/ARDS实验与临床研究的不断深入,人们对新生儿ALI/ARDS的认识明显提高,文章提出了新生儿ALI/ARDS诊断依据与治疗策略,在控制原发疾病基础上,应用肺保护性通气策略、加强液体管理、降低肺动脉压力和给予抗炎治疗等,对提高新生儿ALI/ARDS抢救成功率具有重要意义.     

Acute respiratory failure in children

Recent studies in the treatment of acute respiratory failure in children have been targeted at reducing ventilator-induced lung injury, providing treatment adjuncts to mechanical ventilation, and assessing innovative therapies directed at immunomodulation. Ventilator-associated lung injury has been demonstrated in animal models during the delivery of moderate-to-large tidal volumes and has also been described in adult populations. Subsequently, a significant survival benefit of a low tidal volume, high positive end expiratory pressure strategy on the ventilatory was found in adults. Investigation of the effects of inhaled nitric oxide in acute respiratory failure patients continues to show transient improvements in oxygenation, but no evidence of improved outcomes. The use of intratracheal surfactant within 24 hours of intubation in pediatric respiratory failure may be beneficial in reducing the days of mechanical ventilation. Neutrophil oxidative damage has been demonstrated, but therapies directed at decreasing neutrophil adherence have failed to demonstrate improvements. Enteral anti-inflammatory and antioxidant therapy may be promising, because these modalities have been shown to improve a number of surrogate outcomes in patients with respiratory failure. The use of corticosteroids in the late stages of lung injury has also recently been shown to have promise.     

儿童急性呼吸窘迫综合征的治疗进展

Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome that lacks definitive treatment. The cornerstone of management is sound intensive care treatment and early anticipatory ventilation support. A mechanical ventilation strategy aiming at optimal alveolar recruitment, judicious use of positive end-respiratory pressure (PEEP) and low tidal volumes (VT) remains the mainstay for managing this lung disease. Several treatments have been proposed in rescue settings, but confirmation is needed from large controlled clinical trials before they be recommended for routine care. Non-invasive ventilation (NIV) is suggested with a cautious approach and a strict selection of candidates for treatment. Mild and moderate cases can be efficiently treated by NIV, but this is contra-indicated with severe ARDS. The extra-corporeal carbon dioxide removal (ECCO₂R), used as an integrated tool with conventional ventilation, is playing a new role in adjusting respiratory acidosis and CO₂. The proposed benefits of ECCO₂R over extra-corporeal membrane oxygenation (ECMO) consist in a reduction of artificial surface contact, avoidance of pump-related side effects and technical complications, as well as lower costs. The advantages and disadvantages of inhaled nitric oxide (iNO) are better recognized today and iNO is not recommended for ARDS and acute lung injury (ALI) in children and adults because iNO results in a transient improvement in oxygenation but does not reduce mortality, and may be harmful. Several trials have found no clinical benefit from various surfactant supplementation methods in adult patients with ARDS. However, studies which are still controversial have shown that surfactant supplementation can improve oxygenation and decrease mortality in pediatric and adolescent patients in specific conditions and, when applied in different modes and doses, also in neonatal respiratory distress syndrome (RDS) of preemies. Management of ARDS remains supportive, aimed at improving gas exchange and preventing complications. Progress in the treatment of ARDS must be addressed toward the new paradigm of the disease pathobiology to be applied to the disease definition and to predict the treatment outcome, also with the perspective to develop predictive and personalized medicine that highlights new and challenging opportunities in terms of benefit for patient''s safety and doctor''s responsibility, with further medico-legal implication.     

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.     

Acute lung injury and acute respiratory distress syndrome

Acute lung injury and acute respiratory distress syndrome are an important challenge for pediatric intensive care units. These disorders are characterized by a significant inflammatory response to a local (pulmonary) or remote (systemic) insult resulting in injury to alveolar epithelial and endothelial barriers of the lung, acute inflammation and protein rich pulmonary edema. The reported rates in children vary from 8.5 to 16 cases /1000 pediatric intensive care unit (PICU) admissions. The pathological features of ARDS are described as passing through three overlapping phases-an inflammatory or exudative phase (0–7 days), a proliferative phase (7–21 days) and lastly a fibrotic phase (from day 10). The treatment of ARDS rests on good supportive care and control of initiating cause. The goal of ventilating patients with ALI/ARDS should be to maintain adequate gas exchange with minimal ventilator induced lung injury. This can be achieved by use of optimum PEEP, low tidal volume and appropriate FiO². High frequency ventilation can improve oxygenation but does affect the outcomes. Prone positioning is a useful strategy to improve oxygenation. Pharmacological strategies have not made any significant impact on the outcomes. Preliminary data suggests some role for use of corticosteroids in non-resolving ARDS. The mortality rates have declined over the last decade chiefly due to the advances in supporting critically ill patients.     

Surfactant for pediatric acute lung injury

This article reviews exogenous surfactant therapy and its use in mitigating acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) in infants, children, and adults. Biophysical and animal research documenting surfactant dysfunction in ALI/ARDS is described, and the scientific rationale for treatment with exogenous surfactant is discussed. Major emphasis is placed on reviewing clinical studies of surfactant therapy in pediatric and adult patients who have ALI/ARDS. Particular advantages from surfactant therapy in direct pulmonary forms of these syndromes are described. Also discussed are additional factors affecting the efficacy of exogenous surfactants in ALI/ARDS.     

肺泡表面活性物质对新生儿急性肺损伤氧合功能的影响

目的 研究肺泡表面活性物质（pulmonary surfactant,PS）对新生儿急性肺损伤、急性呼吸窘迫综合征氧合功能的影响.方法 纳入符合急性肺损伤、急性呼吸窘迫综合征诊断标准的新生儿98例,分为PS治疗组30例及常规治疗组68例,PS治疗组经气管插管注入PS 70 ～ 100 mg/kg,其余治疗同常规治疗组.结果 两组新生儿的性别、胎龄、出生体重、肺损伤程度差异无统计学意义;PS治疗组在急性肺损伤、急性呼吸窘迫综合征治疗后6h、12h、24 h、48 h的PaO3/FiO2、呼吸机有效指数均高于常规治疗组,而氧合指数、呼吸指数均低于常规治疗组,差异有统计学意义（P＜0.05）;PS治疗组在急性肺损伤、急性呼吸窘迫综合征治疗后机械通气时间[（66±13）h、（82 ±26）h]和用氧时间[（86±13）h、（103±25）h）]均较常规治疗组[（80 ±18）h、（101 ±36）h和（104±16）h、（125 ±29） h]缩短,差异有统计学意义（P＜0.05）.结论 应用PS治疗新生儿急性肺损伤、急性呼吸窘迫综合征可改善肺顺应性及氧合功能,缩短机械通气及氧疗时间,有利于改善预后.     

Acute lung injury in pediatric intensive care in Australia and New Zealand: a prospective, multicenter, observational study.

OBJECTIVE: Acute lung injury (ALI) is poorly defined in children. The objective of this prospective study was to clarify the incidence, demographics, management strategies, outcome, and mortality predictors of ALI in children in Australia and New Zealand. DESIGN: Multicenter prospective study during a 12-month period. SETTING: Intensive care unit. PATIENTS: All children admitted to intensive care and requiring mechanical ventilation were screened daily for development of ALI based on American-European Consensus Conference guidelines. Identified patients were followed for 28 days or until death or discharge. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 117 cases of ALI during the study period, giving a population incidence of 2.95/100,000 <16 yrs. ALI accounted for 2.2% of pediatric intensive care unit admissions. Mortality was 35% for ALI, and this accounted for 30% of all pediatric intensive care unit deaths during the study period. Significant preadmission risk factors for mortality were chronic disease, older age, and immunosuppression. Predictors of mortality during admission were ventilatory requirements (peak inspiratory pressures, mean airway pressure, positive end-expiratory pressure) and indexes of respiratory severity on day 1 (Pao2/Fio2 ratio and oxygenation index). Higher maximum and median tidal volumes were associated with reduced mortality, even when corrected for severity of lung disease. Development of single and multiple organ failure was significantly associated with mortality. CONCLUSIONS: ALI in children is uncommon but has a high mortality rate. Risk factors for mortality are easily identified. Ventilatory variables and indexes of lung severity were significantly associated with mortality.     

A critical appraisal of a randomized controlled trial: Willson et al: Effect of exogenous surfactant (calfactant) in pediatric acute lung injury (JAMA 2005, 293: 470-476).

OBJECTIVE: To evaluate the use of exogenous surfactant in pediatric acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in decreasing the duration of respiratory failure. DESIGN: A critical appraisal of a randomized controlled trial. FINDINGS: This was a multiple-center, randomized, double-blinded, placebo-controlled trial evaluating the effect of calfactant via endotracheal tube in pediatric ALI/ARDS. The primary outcome was duration of respiratory failure measured by ventilator-free days at 28 days. Secondary outcomes included hospital course, adverse events, and failure of conventional mechanical ventilation (use of high-frequency oscillatory ventilation, inhaled nitric oxide, or extracorporeal membrane oxygenation). One hundred and fifty-two patients were enrolled and randomized with strict inclusion and exclusion criteria. Aside from the experimental interventions, the treatment and placebo groups were similar at baseline. Ventilator management guidelines were defined a priori. No significant difference in ventilator-free days was found, although the treatment group had a greater improvement in oxygenation. Mortality rate was significantly greater in the placebo group (relative risk, 1.9; 95% confidence interval, 1.1-3.2). However, when controlled for immunocompromised status, the statistical significance is lost. Subgroup analysis of infants showed a greater effect on mortality (relative risk, 3.3; 95% confidence interval, 1.1-10.5) and a significant difference in ventilator-free days (15.2 days vs. 7.0 days, p = .01) for the placebo group. No other differences in measured outcomes were seen. The treatment group had an increased rate of hypotension and transient hypoxia but not of airleaks or nosocomial pneumonias. CONCLUSIONS: This is a well-designed study with an appropriate intention-to-treat analysis, but it is underpowered, making it difficult to identify which patients with pediatric ALI/ARDS might benefit from calfactant. Given the uncertainty of the benefits, calfactant cannot be routinely recommended in pediatric ALI/ARDS.     

Ventilatory strategies and adjunctive therapy in ARDS

Acute respiratory distress syndrome, a diagnosis based on physiologic and radiological criteria, occurs commonly in critical care setting. A major challenge in evaluating therapies that may improve survival in ARDS is that it is not a single disease entity but, rather, numerous different diseases that result in endothelial injury, where the most obvious manifestation is within the lung resulting in pulmonary oedema. It has been shown that poor ventilatory technique that is injurious to the lungs can propagate systemic inflammatory response and adversely affect the mortality. The current data suggest that high tidal volumes with high plateau pressures are deleterious and a strategy of ventilation with lower tidal volumes and lower plateau pressure is associated with lower mortality. There may be a role for recruitment manoeuvres as well. Other forms of respiratory support still require further research. The present understanding of optimal ventilatory management and other adjunctive therapies are reviewed.     

不同机械通气方式联合肺表面活性物质对新生儿急性肺损伤/急性呼吸窘迫综合征疗效比较

目的 比较高频振荡通气+肺表面活性物质 （HFOV+PS）、常频机械通气+肺表面活性物质 （CMV+PS）、常频机械通气 （CMV）3种治疗方式对新生儿急性肺损伤/急性呼吸窘迫综合征 （ALI/ARDS）的临床疗效。方法 纳入ALI/ARDS新生儿136例 （ALI73例,ARDS63例）,其中HFOV+PS组45例,CMV+PS组53例,CMV组38例,前两组应用肺表面活性物质气管内滴入 （70~100mg/kg）。分别检测机械通气0h、12h、24h、48h、72h的PaO2、PaCO2、PaO2/FiO2、氧合指数 （OI）、呼吸指数 （RI）。结果 机械通气12h、24h、48h时HFOV+PS组的PaO2高于CMV+PS组和CMV组,PaCO2低于CMV+PS组和CMV组 （P < 0.05）;在机械通气12h、24h、48h、72h时HFOV+PS组PaO2/FiO2高于CMV+PS组和CMV组,OI、RI低于CMV+PS组和CMV组 （P < 0.05）;HFOV+PS组机械通气时间、用氧时间均低于CMV+PS组和CMV组 （P < 0.05）;3组气漏、颅内出血发生率及治愈率比较差异无统计学意义。结论 与单纯CMV以及CMV联合PS治疗相比,HFOV联合PS更可改善ALI/ARDS新生儿的肺功能,缩短通气时间及用氧时间,且不增加并发症的发生。     

体外膜肺氧合在儿童急性呼吸窘迫综合征中的应用

急性呼吸窘迫综合征（ARDS）患儿常需要呼吸机支持治疗,目前推荐实施肺保护性通气策略。体外膜肺氧合（ECMO）能通过体外循环改善患者氧合和去除二氧化碳,从而部分或完全替代心肺功能,在ARDS应用时具有减少呼吸机相关性肺损伤、改善低氧血症等优势。近年来该技术在儿童ARDS应用的报道逐渐增多。该文就ECMO在儿童ARDS中的应用进行综述。     

Management of Acute Lung Injury/ARDS

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are disorders of pulmonary inflammation characterized by hypoxemia and respiratory failure. Children have varying incidence of ALI/ARDS from 2.2 to 16 per 100,000 pediatric population associated with high morbidity, mortality, and financial burden. The diagnostic criteria include: acute onset, severe arterial hypoxemia resistant to oxygen therapy alone (PaO₂/FIO₂ ratio ≤200 for ARDS and ≤300 for ALI), diffuse pulmonary inflammation (bilateral infiltrates on chest radiograph) and No evidence of left atrial hypertension. Management includes ventilatory therapy including lower tidal volume, relatively high PEEP and supportive care. Guidelines for diagnosis, ventilator management, rescue therapies and supportive care are being discussed in the protocol.     

急性肺损伤患儿肺复张策略联合小潮气量通气治疗15例

目的 观察采用肺复张策略(RM)联合小潮气量机械通气治疗儿童急性肺损伤(ALI)的临床有效性及可耐受性,探索在ALI患儿中建立合理的机械通气模式.方法 前瞻性观察我院儿科重症监护室(PICU)收治的15例ALI患儿,诊断标准参照1994年欧美联席会议所制定,给予小潮气量联合RM的通气方式.实施RM时采用持续肺膨胀(SI)法,每8小时进行1次,共5 d.于入组的第1天,第3天,第5天记录当天第1次RM后的血气指标、呼吸机参数及血流动力学指标,入组1周内复查胸片,随访患儿的上机时间及预后..结果 第1、3、5天复张前的PaO2/FiO2(P/F)比值分别为243.8 mm Hg(1 mm Hg=0.133 kPa)、281.8 mm Hg及309.9 mm Hg,复张后1 h的P/F比值相应为300.5 mm Hg、333.4 mm Hg及363.7 mm Hg,较复张前有显著上升(P＜0.01);入组第1、3、5天复张前的呼吸动态顺应性(Cdyn)分别为0.762 ml/(cm H2O·kg)(1 cm H2O=0.098 kPa)、0.835ml/(cm H2O·kg)及0.928 ml/(cm H2O·kg),整体也呈逐渐递增表现(P＜0.05);复张后患儿的心率及血压有轻度波动,但均能于复张后15 min恢复至复张前水平,前后差异无统计学意义;采用RM后患儿胸片表现的好转率为93.3%,平均机械通气时间为(10.15±4.3)d,死亡率为13.3%.结论 RM联合小潮气量机械通气可以改善ALI患儿的氧合功能并提高其肺顺应性,患儿的耐受性良好,具有临床可行性.     

Acute lung injury: pathophysiology, assessment and current therapy

Acute respiratory distress syndrome (ARDS) is a clinically defined entity describing the severity of diffuse alveolar injury caused by direct or indirect injury to the lung. Pathophysiology, clinical course and outcome of ARDS depend on the underlying cause, the severity of the disease and co-morbidities. Pulmonary function tests show restrictive lung disease, which is characterised by a reduction in lung compliance and functional residual capacity, resulting in marked ventilation-perfusion inequality. Current ventilator strategies aim to minimise ventilator-induced lung injury by targeting mechanical ventilation between the lower and upper inflection point of the pressure volume curve. This includes recruitment manoeuvres and the use of high PEEP to open the atelectatic lung and the use of permissive hypercapnia and the limitation of peak inspiratory pressure below 35 cm H2O to avoid overinflation. The clinical benefit of newer modes of ventilatory support such as inverse ratio ventilation, high frequency oscillatory ventilation, surfactant replacement, prone positioning and inhaled nitric oxide has yet to be determined in children.     

儿童急性呼吸窘迫综合征肺复张及呼气末正压滴定方法

应用小潮气量及限制气道压力进行机械通气的策略在急性呼吸窘迫综合征中的应用已经得到公认。肺复张及呼气末正压（PEEP）滴定能提高氧合并进行肺保护,但是肺复张及PEEP设定方法一直存在争议,该文就呼吸窘迫综合征患儿的肺复张策略及PEEP滴定进行综述。     

Partial liquid ventilation and nitric oxide in experimental acute lung injury

OBJECTIVE: To investigate the effects of inhaled nitric oxide (iNO) and partial liquid ventilation (PLV) on oxygenation and pulmonary haemodynamics in acute lung injury (ALI), and to assess their effects on lung function, systemic haemodynamics and lung injury. METHODS: Using saline lung lavage, ALI was induced in 18 piglets. A control group was ventilated with conventional mechanical ventilation (CMV) for 2 h. An iNO-first group received iNO for the first hour and then iNO with PLV. A PLV-first group received PLV for the first hour and then PLV with iNO. Variables were measured at baseline, 5 min postlavage, and at 1 h and 2 h postlavage. RESULTS: During the first hour, both treatment groups showed improvement in oxygenation index (OI). At 2 h, the dif-ferences in OI were statistically significant (P = 0.037), with a mean +/- SD of 23.8 +/- 20.7 in the control group, 4.4 +/- 0.9 in the PLV-first group and 6.5 +/- 3.1 in the iNO-first group. The OI was similar in both treatment groups (P = 0.178). At 2 h, the pulmonary artery pressure (PAP) was significantly different (P = 0.04) between groups, with a mean +/- SD PAP of 36.3 +/- 7.2 mmHg in the control group, 27.4 +/- 4.0 mmHg in the PLV-first group and 30.0 +/- 4.1 mmHg in the iNO-first group. The PAP was similar in both treatment groups (P = 0.319). CONCLUSION: In ALI, oxygenation and pulmonary hypertension are improved with PLV and iNO given together, regardless of the order in which they are commenced.     

Partial liquid ventilation with low-dose perfluorochemical and high-frequency oscillation improves oxygenation and lung compliance in a rabbit model of surfactant depletion

BACKGROUND: Partial liquid ventilation (PLV) with perfluorochemical (PFC) has been advocated as a new therapy for acute respiratory distress syndrome in both clinical and animal studies, meconium aspiration syndrome, and RDS. PFC is referred to as liquid PEEP because it gets distributed to the most gravity-dependent regions of the lung due to its density. High-frequency oscillation (HFO) has been shown to prevent both acute and chronic lung injury in the management of very low birth weight infants with RDS, with gentle ventilation approach. Specifically, HFO with aggressive and adequate lung volume recruitment has been shown to reduce the incidence of chronic lung disease in very low birth weight infants. We hypothesized that PLV along with HFO might be effective in ARDS in an adult rabbit model. OBJECTIVES: To examine the efficiency of low-dose PLV with with HFO on pulmonary gas exchange and lung compliance in a surfactant-depleted rabbit model. METHODS: After induction of severe lung injury by repeated saline lung lavage, 19 adult white Japanese rabbits were randomized into two groups that received PLV with HFO (n=9) or HFO gas ventilation (n=10). Physiological and blood gas data were compared between the two groups by analysis of variance. RESULTS: The HFO-PLV group showed improved total lung compliance with maintenance of significantly lower mean airway pressure as compared with the HFO-GAS group so as to keep SpO2>90%. CONCLUSIONS: The addition of a low dose of PFC with HFO was effective in achieving adequate oxygenation, with a reduction in further lung injury in neonates.