Successful use of surfactant to treat severe intrapulmonary hemorrhage after iatrogenic lung injury--A case report.

OBJECTIVE: To describe the beneficial clinical effect of the use of surfactant in a patient with severe unilateral pulmonary hemorrhage after iatrogenic lung injury during corrective surgery for congenital heart defects. DESIGN: Case report. SETTING: Pediatric cardiac intensive care unit of a tertiary care hospital. PATIENT: An 11-wk-old boy. INTERVENTIONS: Intratracheal instillation of 4 mL (100 mg) of surfactant (Survanta) per kilogram of body weight to treat profound and refractory hypoxia and hypercapnia despite high-ventilation pressures, high respiratory rate, and the use of nitric oxide caused by severe pulmonary hemorrhage and atelectasis. MEASUREMENTS AND MAIN RESULTS: The aggressive ventilation variables could be reduced within the following 2 hrs after surfactant use (from Fio2 0.8, peak inspiratory pressure 36 cm, positive end-expiratory pressure 10 cm, respiratory rate 50, tidal volume 63 mL, and nitric oxide 10 ppm to Fio2 0.4, peak inspiratory pressure 28 cm, positive end-expiratory pressure 10, respiratory rate 40, tidal volume 38 mL, and nitric oxide 5 ppm). There was rapid improvement of clinical variables (inotropic support, chest radiograph) as well as oxygenation (Pao2 from 56 to 149 mm Hg), CO2 exchange (Paco2 from 85 to 39 mm Hg), and acidosis (from pH 7.13 to 7.44). CONCLUSIONS: The administration of surfactant may be a promising approach to treat severe respiratory failure caused by severe pulmonary hemorrhage.     

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.     

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   

Expanded use of surfactant replacement therapy

There are a number of respiratory diseases affecting infants in which there is surfactant dysfunction or deficiency. Surfactant is inactivated by cholesterol, free fatty acids and bilirubin in meconium aspiration syndrome, by haemoglobin and red blood cell lipids in pulmonary haemorrhage and plasma proteins are the culprit in conditions associated with increased alveolar capillary permeability. Surfactant production can be adversely affected by damage to the type 2 pneumocytes by viruses and neutrophil derived reactive oxygen metabolites. Not surprisingly, therefore, the efficacy of exogenous surfactant has been tested, usually in animal models and anecdotal series in “non respiratory distress syndrome” respiratory disorders. Improvements in oxygenation have usually been described. Relatively few randomized trials, however, have been performed, but those undertaken have demonstrated longer term benefits. In term infants with severe respiratory failure, surfactant administration significantly shortened the duration of extracorporeal membrane oygenation and, in those in the early phase of severe respiratory failure or with meconium aspiration syndrome, it significantly reduced the need for extracorporeal membrane oygenation. In meconium aspiration syndrome, a smaller number of surfactant treated patients compared to controls developed airleaks. Surfactant administration was also associated with a reduction in the duration of ventilation and intensive care unit stay in patients with meconium aspiration syndrome or bronchiolitis. Those data are very promising and should encourage studies to identify the optimum type of surfactant, dosage regimen and administration method. Conclusion Further randomized trials are required to fully assess the efficacy and cost benefit ratio of surfactant treatment in “non respiratory distress syndrome” respiratory diseases. Received: 24 January 2000 / Accepted: 6 April 2000     

Surfactant treatment for acute respiratory distress syndrome.

OBJECTIVE: To determine prospectively the efficacy of surfactant in acute respiratory distress syndrome. STUDY DESIGN: Twenty patients, 1 month to 16 years of age, diagnosed with an acute pulmonary disease with severe hypoxaemia (PaO2/FiO2 < 100) (13 with systemic or pulmonary disease and seven with cardiac disease) were treated with one to six doses of 50-200 mg/kg of porcine surfactant administered directly into the trachea. The surfactant was considered to be effective when the PaO2/FiO2 improved by > 20%. RESULTS: After initial surfactant administration the PaO2/FiO2 increased significantly in patients with systemic or pulmonary disease from 68 to 111, and the oxygenation index (OI) diminished significantly from 36.9 to 27.1. The PaO2/FiO2 and OI did not improve in children with cardiac disease. The improvement of the patients who survived was greater than that of those who died. CONCLUSIONS: Surfactant moderately improves oxygenation in some children with severe acute respiratory distress syndrome secondary to pulmonary or systemic disease.     

Neonatal acute respiratory failure

Acute respiratory failure is the most common problem seen in the preterm and term infants admitted to neonatal intensive care units. In preterm infants, the most common cause of acute respiratory failure is respiratory distress syndrome caused by surfactant deficiency. Acute respiratory failure in term and near term infants is usually a result of meconium aspiration syndrome, sepsis, pulmonary hypoplasia, and primary pulmonary hypertension of the newborn. The response to various methods of treatment may vary, depending on the severity of respiratory failure and the cause of the acute respiratory failure. We reviewed the evidence for efficacy and current utilization of newer treatment modalities, including exogenous surfactant administration, high frequency ventilation, inhaled nitric oxide therapy, antenatal steroids for the prevention of respiratory distress syndrome, and use of postnatal steroids for the prevention of chronic lung disease.     

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.     

Advances in management of meconium aspiration syndrome

Meconium Aspiration Syndrome (MAS) is a leading cause of respiratory distress in the newborn. Antenatal diagnosis of meconium stained amniotic fluid and fetal distress is important to reduce morbidity and mortality in the neonates. Amnioinfusion of saline and tracheal suctioning of meconium are preventive interventions. Babies with MAS who continue to have respiratory distress need to be put on conventional ventilators. Increasing hypoxia, hypercarbia and barotrauma warrants changing to high frequency oscillatory ventilation. Pulmonary hypertension is an important complication which should be promptly recognized. Nitric oxide therapy used with high frequency ventilation has improved the outcome of babies with severe MAS and pulmonary hypertension. Some of these babies who continue to worsen clinically need to be put on ECMO circuit. Surfactant infusion in babies with MAS has been shown to improve gas exchange, resolve pulmonary hypertension and decrease oxygenation index. Total and partial liquid ventilation with perflurocarbon improves oxygenation, increases lung expansion and increases pulmonary blood flow in model studies of animals with MAS. Surfactant infusion and liquid ventilation are newer promising modes of therapeutic interventions in babies with severe MAS.     

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。     

High-frequency oscillatory ventilation in the management of respiratory distress syndrome

Early use of high-frequency oscillatory ventilation with a high volume strategy (HFOV-HVS) has been proposed to decrease the incidence of chronic lung disease following respiratory distress syndrome (RDS) in extremely immature infants. Despite encouraging results of animal experiments, clinical trials have provided discordant results. Our own multicenter trial showed that using HFOV-HVS, compared with conventional ventilation, decreased exogenous surfactant requirements, but did not modify pulmonary outcome, and increased the risk of severe intraventricular hemorrhage. This prompted us to change our management of RDS, by switching from elective use of HFOV to an 'early rescue' approach.     

Surfactant replacement therapy

OBJECTIVE: To analyze and update information about surfactant therapy replacement in newborns with lung diseases. SOURCES: Literature review, including textbooks, meta-analyses, prospective, randomized controlled trials, retrospective assessments and case studies. Literature was reviewed based on the authors clinical and scientific experience regarding surfactant replacement therapy in neonatal lung diseases. SUMMARY OF THE FINDINGS: Surfactant replacement therapy for the neonatal respiratory distress syndrome improves respiratory function, and reduces the need for oxygen supplementation and pressure support ventilation, in addition to minimizing the air leak syndrome. However, the use of surfactant did not prevent the occurrence of other intercurrent diseases such as patent ductus arteriosus, intraventricular hemorrhage, necrotizing enterocolitis, retinopathy of prematurity, and bronchopulmonary dysplasia. The surfactant treatment decreased neonatal mortality up to 40%. The effectiveness of exogenous surfactant on other respiratory diseases with surface film dysfunction, such as meconium aspiration syndrome, pneumonia, acute respiratory distress syndrome and congenital diaphragmatic hernia has not yet been widely accepted. CONCLUSIONS: Surfactant replacement is now considered the standard treatment for newborns with respiratory distress syndrome. We hope that, in the future, new synthetic surfactant preparations will be more effective in treating other infant respiratory diseases.     

早期或晚期抢救性给予肺表面活性物质对呼吸窘迫综合征早产儿的影响

目的 观察早期或晚期抢救性给予肺表面活性物质(PS)对呼吸窘迫综合征(RDS)早产儿的影响.方法 回顾性分析99例需要机械通气的RDS患儿的临床资料.按照PS的给予时间分为早期组(出生2 h内)48例和晚期组(出生2～12 h)51例,观察2组在机械通气时间、氧疗时间、病死率以及并发症:气漏(肺间质气肿、气胸)、肺出血、支气管肺发育不良(BPD)、坏死性小肠结肠炎(NEC)、PDA、严重脑室内出血(IVH)的发生率方面的变化.结果 早期组和晚期组机械通气时间[(4.14±1.88) d vs (5.84±3.36) d]比较有统计学差异(P＜0.05).2组氧疗时间[(5.84±3.36) d vs (8.05±5.48) d]比较差异有统计学意义(P＜0.05).28 d内早产儿的病死率:早期组为6.25%、晚期组为5.88%,出生12 h内不同时间给予PS对病死率无影响(OR=1.07,95% CI 0.21～5.56,P=1.00).早期组BPD的发生率8.7%,低于晚期组16.0%,但无统计学差异(OR=0.49,95%CI 0.13～1.74,P=0.36).其他并发症如气漏、肺出血、PDA、NEC、严重IVH发生率,2组患儿之间均无明显差异(Pa＞0.05).结论 早期抢救性给予PS能显著减少RDS早产儿的机械通气时间和氧疗时间,降低BPD的发生率.     

1108例新生儿呼吸衰竭的临床流行病学特征

目的 对1 108 例新生儿呼吸衰竭病例的临床流行病学特征进行分析,为提高临床治疗水平和开展多中心临床研究提供参考。方法 采用统一调查表收集1 108 例呼吸衰竭新生儿的临床资料,对原发疾病、临床治疗方法、治疗结局、病死率等流行病学指标进行统计学分析。结果 1 108 例患儿中位胎龄为37+1 周,中位出生体重为2 600 g,入NICU 中位日龄为0.71 d(17 h),男/ 女比例为3.1:1。主要原发疾病为呼吸窘迫综合征(30.51%)、肺部感染/ 败血症(23.55%)和湿肺(13.18%)。治疗中采用经鼻持续气道正压通气(nCPAP)占48.64%,高频振荡通气占12.81%、使用肺表面活性物质占13.45%、NO 吸入治疗占8.66%,病死率达24.19%。结论 呼吸窘迫综合征为新生儿呼吸衰竭的主要原发疾病,使用肺表面活性物质、nCPAP、高频振荡通气、NO 吸入治疗已经成为新生儿呼吸衰竭的主要救治手段,但新生儿呼吸衰竭的病死率仍然较高。     

新型鼻塞持续气道正压与肺表面活性物质治疗新生儿呼吸窘迫综合征疗效观察

目的　探讨新型鼻塞持续气道正压通气 (NCPAP)与肺表面活性物质 (PS)联合应用治疗新生儿呼吸窘迫综合征 (NRDS)的疗效及临床价值。方法　对 2 3例NRDS患儿进行NCPAP通气同时给予PS治疗 ,观察治疗前后血气、X线胸片和临床效果。结果　与用药前相比 ,用药后 0 5h ,PaO2 和a/APO2 即明显升高。至 6、12、2 4和 72h ,PaO2 和a/APO2 仍高于用药前水平 ,有显著性差异 (P均 <0 0 1)。用药后 6h ,PaCO2 开始下降 ,6、12、2 4和 72h ,PaCO2 明显下降 ,有显著性差异 (P均 <0 0 1)。用药后 1h ,呼吸窘迫症状消失 9例 (39 1% ) ;明显减轻 14例 (6 0 9% )。 2 4h后 ,X胸片显示肺野透明度明显改善 2 2例 (95 7% )。 2 3例中治愈 2 2例 ,治愈率 95 7%。 1例改为机械通气。结论　NCPAP与PS联合治疗NRDS疗效显著 ,能快速有效地改善NRDS的肺换气和通气功能 ,可节省PS及减少机械通气率     

Noninvasive Mechanical Ventilation

Patients presenting to pediatric EDs with respiratory distress represent an array of diagnostic and therapeutic challenges. With the development of NIPPV, there is an effective tool in our armamentarium to provide significant respiratory support. NIPPV has demonstrated benefits in decreasing work of breathing, relieving fatigued muscles of respiration, improving oxygenation, and possibly avoiding common complications of endotracheal intubation. There are clear clinical scenarios in which NIPPV is contraindicated, such as an obtunded patient, certain postoperative patients, patients with vomiting, and patients in which mask ventilation is not tolerated. More frequently, it is the patient with pulmonary disease resulting in respiratory distress that is amenable to this therapy. It is important to obtain any history of NIPPV usage in the ED. Increasing numbers of children are on nocturnal settings for OSA and support settings for chronic respiratory insufficiency with diseases such as myopathies, cystic fibrosis, and bronchiectasis. Advancements in the knowledge of NIPPV management strategies for respiratory distress and early initiation of mask ventilation in the ED will enable the emergency physician to approach respiratory distress in a similar manner as sepsis; using goal-directed therapies to improve oxygenation, ventilation, and comfort of breathing.     

Clinical events in association with timing of intraventricular hemorrhage in preterm infants.

To ascertain whether any routine practices or clinical manipulations in a neonatal intensive care unit could induce intraventricular hemorrhage (IVH) in preterm infants, we performed ultrasonic monitoring of the germinal layer continuously for 48 hours in 33 extremely premature infants with respiratory distress. Intraventricular hemorrhage developed in 16 of these infants. In four infants the timing of the germinal layer hemorrhage was confirmed with ultrasonic monitoring. Three of the four cases were apparently associated with clinical events occurring at the moment of IVH: manual ventilation for improvement of hypercapnia associated with primary pulmonary hypertension of the newborn; correction of hyperkalemia, which was causing an arrhythmia, with administration of calcium gluconate and sodium bicarbonate; and administration of surfactant-TA to improve respiratory failure caused by pulmonary hemorrhage. In these three infants it appeared that one of the basic factors inducing IVH might be an increase in blood pressure with or without hypercapnia, causing cerebral reperfusion after ischemic damage of the germinal layer.     

Effect of preoperative stabilization on respiratory system compliance and outcome in newborn infants with congenital diaphragmatic hernia

To determine whether preoperative stabilization and delay of operative repair of congenital diaphragmatic hernia (CDH) may decrease operative risk, we performed serial pulmonary function tests on 22 newborn infants with CDH and on four infants without pulmonary hypoplasia (two with ileal atresia and two with tracheoesophageal anomalies) who served as control subjects. We used 2 passive respiratory mechanics technique to measure respiratory system compliance. All patients with CDH had respiratory distress immediately after birth, and required mechanical ventilation. Thirteen babies underwent emergency repair (six survived, seven died); nine of them received extracorporeal membrane oxygenation (ECMO) after the operation (two survived, seven died). Operative repair was delayed deliberately for 2 to 11 days in nine infants with severe hypoxemia. Six immediately received ECMO for 4 to 10 days; one died of intraventricular hemorrhage, and five survived and later underwent surgical repair. The seventh patient did not receive ECMO but appeared to have respiratory distress syndrome of infancy and improved after administration of synthetic surfactant. Improvement was seen in two additional infants who received conventional assisted ventilation during a 48-hour delay before surgery, and survived. In all, eight of nine infants who underwent preoperative stabilization survived (p less than 0.05 compared with survival after emergency surgery). Following surgical repair immediately after birth, respiratory system compliance improved only slightly during the first week of life, a time when control infants had a rapid increase in respiratory system compliance (p less than 0.001). In contrast, respiratory system compliance increased nearly twofold in the nine patients undergoing preoperative stabilization (p less than 0.02). Preoperative ECMO was associated with an increase in respiratory system compliance of more than 60% for 1 week, a significant difference from respiratory system compliance among patients undergoing emergency CDH repair (p less than 0.05). These observations provide physiologic evidence of possible benefits of preoperative stabilization before repair of CDH.     

Improved neonatal survival following multiple doses of bovine surfactant in very premature neonates at risk for respiratory distress syndrome

To determine whether multiple doses of bovine surfactant would improve neonatal mortality in very premature neonates, we conducted two multicenter controlled trials under identical protocols; the results were combined for analysis. Four hundred and thirty neonates born between 23 and 29 weeks gestation and weighing 600 to 1250 g at birth were assigned randomly at birth to receive either 100 mg of phospholipids/kg of Survanta, a modified bovine surfactant (n = 210), or a sham air placebo (n = 220) within 15 minutes of birth. Neonates who developed respiratory distress syndrome and required mechanical ventilation with at least 30% oxygen could be given up to three more doses in the first 48 hours after birth. Dosing was performed by investigators not involved in the clinical care of the neonates; nursery staff were kept blinded as to the treatment assignment. Cause of death was determined by a panel of three independent, board-certified neonatologists after blindly reviewing case report forms and autopsy reports. Fewer Survanta-treated neonates died of any cause (11.4% vs 18.8%, P = .031), died of respiratory distress syndrome (1.9% vs 15.6%, P less than .001), and either died or developed bronchopulmonary dysplasia due to respiratory distress syndrome (39.5% vs 49.1%, P = .044). The incidence of respiratory distress syndrome was also lower in Survanta-treated neonates (28.0% vs 56.9%, P less than .001), and the Survanta-treated neonates' oxygenation and ventilatory status were improved significantly at 72 hours. Survanta-treated neonates were also at lowered risk of developing pulmonary interstitial emphysema (23.3% vs 36.9%, P = .002) and other forms of pulmonary air leaks (9.6% vs 20.8%, P .002).(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

The significance of pulmonary surfactant deficiency during extracorporeal membrane oxygenation

Extracorporeal membrane oxygenation (ECMO) is gaining widespread acceptance as a therapy for newborns with severe respiratory distress. However, in some cases with pulmonary opacification or air-bronchograms on chest radiograph during ECMO, pulmonary function does not readily improve despite successful ECMO practice. We applied artificial pulmonary surfactant in two such cases. The effect was remarkable, and successful weaning from ECMO could be achieved. It appears likely that alveolar collapse due to deficient pulmonary surfactant is one cause of abnormal pulmonary shadows on chest radiographs and delayed resolution of pulmonary function during ECMO.