Aerosolized surfactant and dextran for experimental acute respiratory distress syndrome caused by acidified milk in rats

BACKGROUND: Inhibition of pulmonary surfactant by plasma-derived proteins is an important pathogenetic factor of acute respiratory distress syndrome (ARDS). Inhalation of aerosolized surfactant may be suitable for early treatment of ARDS. However, requirement of a high dose is a drawback. Because dextran reverses surfactant inhibition, we examined whether dextran improves the therapeutic effects of aerosolized surfactant in rats with experimental ARDS. METHODS: Acidified milk (pH 1.8, 1.5 ml kg(-1)) was injected into the trachea of the rats ventilated with pure oxygen using 2.45 kPa peak inspiratory pressure and 0.74 kPa positive end-expiratory pressure. When PaO2 decreased to <13 kPa, the rats were assigned to four groups: control group (n = 8), receiving no material; D-only group (n = 6), receiving aerosolized dextran for 45 min; S-only group (n = 8), receiving aerosolized modified natural surfactant (MNS) for 30 min; and S-plus-D group (n = 9), receiving aerosolized MNS for 30 min followed by aerosolized dextran for 15 min. RESULTS: In the control group and D-only groups, the mean PaO2 remained at <10 kPa for 180 min. In the S-only and S-plus-D groups, the PaO2 increased to 50 kPa (P < 0.01 vs. untreated). The PaO2 of the surfactant-only group gradually decreased to <17 kPa at 180 min, whereas the PaO2 of the S-plus-D group was maintained at >38 kPa for 180 min (P < 0.01 vs. S-only group). CONCLUSION: Inhalation of aerosolized dextran potentiates the effects of aerosolized surfactant by prolonging the therapeutic response.     

Protective ventilation of patients with acute respiratory distress syndrome

The majority of patients with acute respiratory distress syndrome(ARDS) require mechanical ventilation. This support providestime for the lungs to heal, but the adverse effects of mechanicalventilation significantly influence patient outcome. Traditionally,these were ascribed to mechanical effects, such as haemodynamiccompromise from decreased venous return or gross air leaks inducedby large transpulmonary pressures. More recently, however, theARDS Network study has established the clinical importance oflowering the tidal volume to limit overdistension of the lungwhen ventilating patients with ARDS. This study suggests thatventilator-associated lung injury (VALI) caused by overdistensionof the lung contributes to the mortality of patients with ARDS.Moreover, the results from clinical and basic research haverevealed more subtle types of VALI, including upregulation ofthe inflammatory response in the injured and overdistended lung.This not only damages the lung, but the overflow of inflammatorymediators into the systemic circulation may explain why mostpatients who die with ARDS succumb to multi-organ failure ratherthan respiratory failure. The results of these studies, thepresent understanding of the pathophysiology of VALI, and protectiveventilatory strategies are reviewed. Br J Anaesth 2004; 92: 261–70     

Aerosolized surfactant reverses respiratory failure in lung–lavaged rats

The effects of surfactant replacement by aerosol inhalation and by bolus instillation were compared in rats with respiratory failure induced by repeated lung lavage. The rats were anesthetized with pentobarbital sodium and mechanically ventilated with 100% oxygen. The Pao₂ of control rats not given surfactant (n = 9) remained below 13 kPa. A bolus instillation of a modified natural surfactant (75 mg kg^-1 b.w. in 1.5 ml–kg^-1 b.w. saline) into the airways rapidly reversed the respiratory failure; the mean Pao₂ value (n = 9) 15–180 min after instillation remained over 50 kPa ( P < 0.05 vs. controls). Inhalation of the aerosolized surfactant for 60 min through an ultrasonic nebulizer delivering 75 mg kg^-1 b.w. of the surfactant into the lungs gradually reversed the respiratory failure. The mean Pao₂ value (n = 9) 15 min after initiation of inhalation was 19.6 kPa (NS vs. controls), but after 60 min it rose to above 43 kPa ( P < 0.05 vs. controls; NS vs. bolus instillation). Treatment with surfactant either by continuous aerosol or by bolus led to significant increases of over 24% in the dynamic lung–thorax compliance. We conclude that aerosolized surfactant reverses respiratory failure induced by lung lavage, although the response is slower than after bolus instillation.     

Microvessel damage in acute respiratory distress syndrome: the answer may not be NO

Br J Anaesth 2001; 87: 272–9     

急性呼吸窘迫综合征病人肺泡表面活性物质的变化

目的　研究患急性呼吸窘迫综合征 (ARDS)时病人肺泡表面活性物质的变化。方法　应用薄层色谱法测定ARDS早期病人 ( 5例 )和晚期病人 ( 5例 )肺泡灌洗液中肺泡表面活性物质 ,并和正常对照组 ( 5例 )作比较。结果　肺泡表面活性物质的含量在对照组、早期组、晚期组分别为6 7 6± 7 2、44 0± 7 3、31 3± 6 5 μg/ml肺灌洗液 ,呈递减改变。肺泡表面活性物质主要活性成份磷脂酰胆碱、磷脂酰甘油和二磷脂酰甘油的百分比在ARDS早期升高 ,分别达 5 6 2 %± 2 8%、9 2 %±1 5 %和 2 9%± 0 7%。在ARDS晚期 ,上述三种活性成份分别降至 39 7%± 5 2 %、5 6 %± 0 7%和 2 6 %± 0 6 %。结论　ARDS病人随着病情的进展加重 ,其肺泡表面活性物质的含量和主要活性成份逐渐减少。提示若使用外源性肺泡表面活性物质防治ARDS ,不仅要在数量上补足 ,而且需要恢复活性成份的比例 ,才有可能获得理想的疗效     

Perioperative risk analysis for acute respiratory distress syndrome after elective oesophagectomy

Background: Acute respiratory distress syndrome (ARDS) is a major contributor to respiratory morbidity and mortality after oesophagectomy. Several pre‐, intra‐ and post‐operative factors are thought to predispose to its development in the post‐oesophagectomy period. The aim of this study was to determine factors predisposing to ARDS in the post‐oesophagectomy period. Methods: A total of 112 patients who underwent elective oesophagectomy for oesophageal cancer (gastro‐oesophageal adenocarcinoma and high‐grade dysplasia, 93; oesophageal squamous cell carcinoma, 16; oesophageal oat cell tumour, 1; oesophageal anaplastic carcinoma, 1; oesophageal colloid carcinoma, 1) between 1 January 2003 and 31 December 2006 formed the study group in this retrospective study. The pre‐, intra and post‐operative data for these patients (male : female = 89:23, mean age 60.8 years) were collected from an oesophagectomy database and hospital medical records. Results: The incidence of ARDS was 13%. The in‐hospital mortality among ARDS cases was 20% and 1‐year mortality was 40%. Various factors such as preoperative chronic respiratory disease (P‐value = 0.000, odds ratio = 17.76), smoking pack‐years (P‐value = 0.045, odds ratio = 1.02), abnormal preoperative forced expiratory volume in 1 s (P‐value = 0.009, odds ratio = 7.97), high percentage of oxygen in inspired air (P‐value = 0.041, odds ratio = 1.24) and use of perioperative inotropes (P‐value = 0.021, odds ratio = 4.26) were associated with ARDS. Conclusions: Preoperative physiological status as indicated by a preoperative history of chronic respiratory disease and preoperative pulmonary function influenced the post‐operative outcome in our patients. The use of perioperative inotropes suggests perioperative cardiorespiratory instability, and could also predispose to the development of ARDS in the post‐operative period.     

急性肺损伤/急性呼吸窘迫综合征液体治疗策略

背景 高通透性肺水肿是急性肺损伤/急性呼吸窘迫综合征(acute lung injury/acute respiratory distress syndrome,ALI/ARDS)的基本病理生理特征,其程度与ALI/ARDS的预后密切相关.目的 对ALI/ARDS患者合理的液体管理,有助于改善ALI/ARDS患者的肺水肿,降低该病病死率.内容 回顾了ALI/ARDS液体治疗策略探索过程中存在争议的问题(如限制性或开放性的液体治疗策略及治疗液体种类的选择),总结了该领域近年来的研究进展(如ALI/ARDS病程不同阶段的差异化治疗及液体治疗的监测指标).趋向 今后将进一步探索该病在不同的病理生理状态下特异性的液体治疗方法,寻求高效敏感的监测指标,指导液体治疗策略的选择和调整.     

Lung surfactant in respiratory distress syndrome

Severe respiratory failure is always associated with a defect in the surfactant system. Surfactant substitution in newborn infants with respiratory distress syndrome (RDS) has gained worldwide acceptance. In the present study, we have evaluated whether surfactant diagnostics are of use in choosing recipients of exogenous surfactant. In addition, we studied whether factors apparently unrelated to surfactant influence the degree of respiratory failure and surfactant responsiveness. In small preterm infants, the surfactant indices in amniotic fluid (L/S ratio and phosphatidylglycerol), within 3 days of birth, predicted the risk of RDS with a sensitivity of 90–100%, and a specificity of 50–85%. The surfactant indices, measured in BAL, predicted the risk of ARDS (which became evident 1 to 7 days later) with a sensitivity of 50–60% and a specificity of 59–65%. In small preterm infants with RDS, the amount of fluids given during the first day correlated positively with the degree of respiratory failure and negatively with the degree of surfactant responsiveness. According to an experimental study, in hydrostatic lung edema, exogenous surfactant is diluted by edema fluid and becomes sensitive to inhibitors of surfactant function. Beside dosage, quality, and time of administration, the management of patients largely dictates the responsiveness to exogenous surfactant.     

Gas exchange and lung morphology after surfactant replacement in experimental adult respiratory distress syndrome induced by repeated lung lavage

Severe respiratory insufficiency was induced in adult guinea pigs by repeated lung lavage. The animals were then ventilated for 75 min with 100% O2, insufflation pressure 28/6-8 cmH2O (2.7/0.6-0.8 kPa), frequency 30/min, and 33% inspiration time. One group of animals (I) was treated with protein-depleted porcine surfactant, prepared by a combination of sucrose-gradient centrifugation, heating to 90 degrees C, and chloroform/methanol extraction. Another group (II) received the phospholipid fraction of porcine surfactant, isolated from minced lungs by chloroform/methanol extraction and liquid-gel chromatography. Surfactant was administered in two 1-ml doses (lipid concentration 90 mg/ml) instilled via the tracheal cannula about 15 and 45 min after the lavage procedure. Non-treated, lavaged animals served as controls. After 75 min of ventilation, control values for PaO2 and PaCO2 were 13.3 +/- 6.8 and 6.8 +/- 2.3 kPa (mean +/- s.d.), respectively. The corresponding values in Group I of surfactant-treated animals were 52.9 +/- 7.7 and 4.4 +/- 1.1 kPa, in Group II 53.5 +/- 7.3 and 4.8 +/- 1.3 kPa (P less than 0.02-0.002). The two groups of surfactant-treated animals also had significantly improved alveolar air expansion in histological sections, as reflected by increased alveolar volume density (0.67 +/- 0.05 and 0.62 +/- 0.11 vs 0.45 +/- 0.08 in controls; P less than 0.002). The benefits of surfactant replacement in this experimental model were thus similar to those previously observed in animal models of neonatal surfactant deficiency as well as in babies with respiratory distress syndrome (RDS). Our data suggest that surfactant replacement might have a therapeutic effect also in clinical adult RDS.     

Acute respiratory distress syndrome due to pulmonary involvement by neoplastic plasma cells in multiple myeloma

Pulmonary involvement with multiple myeloma occurs infrequently and may be difficult to distinguish from more common primary lung tumours, metastatic disease, or other pleural and parenchymal abnormalities. A patient who developed acute respiratory distress syndrome (ARDS) was subsequently found to have multiple myeloma with involvement of lung parenchyma by neoplastic plasma cells. Only one other report of ARDS in association with multiple myeloma was found, and there are no previous reports where the appearance of ARDS antedated a diagnosis of multiple myeloma. In patients with ARDS, parenchymal involvement from multiple myeloma should be included in the differential diagnosis.     

The laryngeal mask airway for administration of surfactant in two neonates with respiratory distress syndrome

We report the successful use of the Classic laryngeal mask airway to provide brief access to the intratracheal space for the administration of surfactant in two neonates with respiratory distress syndrome.     

Prone positioning ventilation for treatment of acute lung injury and acute respiratory distress syndrome

Patients who are diagnosed with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) usually have ventilation-perfusion mismatch, severe decrease in lung capacity, and gas exchange abnormalities. Health care work-ers have implemented various strategies in an attempt to compensate for these pathological alterations. By rotating patients with ALI/ARDS between the supine and prone position, it is possible to achieve a significant improvement in PaO2/FiO2, decrease shunting and therefore improve oxy-genation without use of expensive, invasive and experimen-tal procedures.     

The effects of multiple small doses of exogenous surfactant on experimental respiratory failure induced by lung lavage in rats

Aim: To test the effect on pulmonary gas exchange and mechanics of multiple small doses of exogenous surfactant as an alternative to bolus delivery in experimental respiratory failure induced by lung lavage.
Methods: After anesthesia, tracheostomy and constant volume ventilation, respiratory failure was induced by lung lavage in 20 rats. Animals were randomly assigned to an untreated control group or two experimental groups. Equal total doses of modified porcine surfactant (200 mg ·kg^-1 body weight,) were given by tracheal instillation, either as a single bolus or in four (50 mg·kg^-1 b.w.) fractional doses at 10-min intervals. Arterial pH and blood gases, and peak inspiratory pressure (PIP) were measured.
Results: After lavage, a rapid decrease in arterial pH and PaO₂, and an increase in PaCO₂ and PIP were observed in all animals. In both surfactant-treated groups, PaO₂ increased after surfactant instillation, and remained significantly higher than controls throughout the experiment. Arterial pH was significantly higher and PaCO₂ significantly lower only in the single bolus group. In the multiple dose group, these levels were similar to those of controls.
Conclusions: In surfactant-depleted rats with respiratory failure, instillation of four fractional surfactant doses did not result in the same enhancement on gas exchange and PIP, in the following 60 min, as same total dose given by a single bolus.     

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目的 探讨重症急性胰腺炎并发成人呼吸窘迫综合征(ARDS)的有效治疗方法。方法 对1992年8月至1997年7月(第一阶段)和1997年8月至2001年8月(第二阶段)收治的重症急性胰腺炎并发ARDS病人治疗结果进行回顾性分析和总结。结果 第一阶段收治重症急性胰腺炎23例，发生ARDS者15例(65．2％)，死亡11例，病死率73．3％；第二阶段收治重症急性胰腺炎34例，发生ARDS者13例(38．2％)，死亡4例，病死率30．8％，结论 早期积极控制ARDS的发生、发展，重视腹部情况的处理，同时有效地控制感染，是降低ARDS发生率、提高治愈率的关键。     

Effectiveness of ECMO for burn-related acute respiratory distress syndrome

Introduction

Acute respiratory distress syndrome (ARDS) is a complication that affects approximately 40% of burn patients and is associated with high mortality rates. Extracorporeal membrane oxygenation (ECMO) therapy is a management option for severe refractory hypoxemic respiratory failure; however, there is little literature reporting the effectiveness of this therapy in burns. Our study objective was to review patient outcomes in burns following severe ARDS treated with ECMO.

限制补液在胸外伤继发急性肺损伤或急性呼吸窘迫综合征治疗中的应用

目的总结限制补液在胸外伤合并急性肺损伤(ALI)或急性呼吸窘迫综合征(ARDS)治疗中的应用效果。方法单纯胸外伤合并ALI或ARDS患者132例,采用限制补液技术,适当减少补液,加控制性降压技术,收缩压控制在95~110mmHg之间,早期以维持一个满足基本灌注的偏低血压作为目标血压,减少输液量和速度。通过单纯胸部外伤(排除其他部位重症损伤的干扰)的救治,总结呼吸窘迫防治特点。结果 ALL/ARDS气管插管率为17.4%(23/132),气管切开的发生率为3.8%(5/132),死亡率为2.3%(3/132)。结论 ALI时不恰当的补液过多引发肺水肿是单纯胸外伤并发ARDS主因,而不是反常呼吸所致。适当控制输液,辅以控制性降压技术能大大降低重症胸外伤死亡率。     

Acute respiratory distress syndrome

Acute respiratory distress syndrome is a clinically and radiologically defined syndrome that is commonly diagnosed and managed in intensive care. It results in hypoxaemia and often requires mechanical ventilation. This article describes the most recent diagnostic classification and outlines the pathophysiology and current management of patients suffering from this syndrome.     

Tracheostomy in a patient with severe acute respiratory syndrome

The coronavirus which causes severe acute respiratory syndrome(SARS) is a virulent and highly contagious organism. Of the1755 SARS patients in Hong Kong, over 400 were healthcare workers.Meticulous attention to infection control and teamwork are essentialto minimize cross-contamination and prevent staff from contractingthe illness. These points are especially pertinent when anaesthetizingSARS patients for high-risk procedures such as tracheostomy.We describe the management of such a case. Br J Anaesth 2004; 92: 280–2