Acute Respiratory Distress Syndrome in Two Rhesus Macaques (Macaca mulatta)

Acute respiratory distress syndrome (ARDS) is an important and potentially life-threatening complication in humans that arises subsequent to a variety of primary insults including noxious fume inhalation, infection, and trauma. Here we describe the first two cases of ARDS reported in association with postoperative complications in rhesus macaques. In agreement with the multifactorial nature of the human syndrome, ARDS in one monkey was attributed to sepsis, whereas in the other it was ascribed to neurogenic trauma. Despite the different etiologies, both monkeys demonstrated clinical features of ARDS, including progressive dyspnea and pulmonary edema, and syndrome-defining histopathologic criteria including edema with intraalveolar neutrophils, fibrinohemorrhagic effusions with crescentic membranes, and interstitial vascular degeneration. Recognition and aggressive treatment of ARDS at an early stage may improve survival rates in dyspneic nonhuman primates with underlying extrapulmonary diseases.Abbreviation: ARDS, acute respiratory distress syndromeAcute respiratory distress syndrome (ARDS) is a leading cause of morbidity and mortality in humans, with approximately 200,000 diagnoses annually.¹³ This syndrome can be initiated by either indirect or direct pulmonary injury. Indirect causes include sepsis, severe trauma such as long bone fractures, blood transfusion, acute pancreatitis, drug overdose, and shock. Direct injury includes viral, bacterial, and fungal pneumonias, near drowning, toxin or gas inhalation, gastric aspiration, fat and amniotic-fluid inhalation, pulmonary contusion, alveolar hemorrhage, reperfusion injury, and unilateral lung reimplantation.²⁶Acute respiratory distress syndrome is characterized by 2 phases. The initial phase, known as the ‘exudative phase,’ occurs within 24 to 48 h of the initial insult. Grossly, this phase is characterized by dusky reddish-blue lungs with frothy, often blood-tinged, fluid in the airways.¹⁰ On histopathology there is diffuse protein-rich pulmonary edema admixed with variable numbers of neutrophils, alveolar hemorrhage, and atelectasis.²⁶ Alveolar edema exhibits organization with fibrin and hyaline membrane formation. The disease progresses to the ‘fibrinoproliferative phase’ approximately 48 h after the insult.¹⁰ At autopsy, lungs may be firm and fail to collapse fully after incisure of the diaphragm. Vessels may be occluded by fibrin thrombi and exhibit intramural fibrinoid necrosis. Pulmonary hypertension may result in thickening of the tunica muscularis, luminal constriction and compensatory capillary proliferation, and neovascularization. Parenchymal changes include interstitial fibrosis and type II pneumocyte hypertrophy.¹⁰ In the fibrinoproliferative phase, hypoxemia may result from arteriovenous shunting or impaired ventilation and perfusion.⁷ Therefore, patients that survive the initial insult remain at risk for catastrophic pulmonary insufficiency due to alveolar fibrosis.¹⁰The pathogenesis of ARDS is complex and incompletely understood. Early in the disease course, inflammatory mediators are released from activated neutrophils and macrophages.^7,26 Cytokines and elastases increase capillary permeability and damage vessel walls, with extravasation of leukocytes, fluid accumulation in interstitial and alveolar spaces, and emphysematous change.^7,26 Reactive endothelial cells, neutrophils, and macrophages produce large quantities of tissue factor, an important initiator of the extrinsic clotting cascade.⁷ Decreased concentrations of anticoagulant proteins C and S and increased concentrations of antifibrinolytic proteins and plasminogen activator inhibitor 1 further promote coagulation.^9,11 This scenario results in increased formation and deposition of fibrin into the microvasculature causing an obstruction of blood flow.⁷ In addition, inflammatory mediators reduce and neutralize surfactant production, contributing to atelectasis.²⁶ Physiologically, ARDS is characterized by severe hypoxemia (partial arterial pressure of oxygen [PaO₂]/fractional concentration of oxygen in inspired air [F_IO₂] < 200).² Treatment is supportive and can be unrewarding. Prognosis depends on the age of the patient, severity of the disease at onset, and the presence of comorbidities such as shock and renal or hepatic failure.²⁶Nonhuman primates are used frequently for neurologic research because of their trainability and close similarity to human anatomy and neurophysiology. Unfortunately, the invasive instrumentation and procedures required for some experiments have the potential to incite localized or multisystem disease. Here we describe the development of ARDS in 2 rhesus macaques that developed complications after experimental craniotomy. The submitted protocols were compliant with the United States Public Health Service Policy on Humane Care and Use of Laboratory Animals and approved by the Massachusetts Institute of Technology Committee on Animal Care. As true for humans, ARDS in these monkeys was attributed to extrapulmonary diseases, including meningitis-associated septicemia and neurogenic injury. Our findings suggest that ARDS is an underdiagnosed condition in laboratory nonhuman primates.     

胰岛素在急性呼吸窘迫综合症中的临床应用

目的:观察胰岛素在急性呼吸窘迫综合症中的抗炎作用,并探讨其机制.方法:将78名急性呼吸窘迫综合症的患者随机分成胰岛素治疗组(A组)和对照组(B组),对A组患者给予呼吸机辅助等常规治疗的同时持续性静脉输注胰岛素.使其血糖维持在4.0～8.0mmol/L;对B组患者常规使用呼吸机辅助及抗生素治疗,分别于入院当时(0 h)、入院后24 h、48 h、72 h留取外周静脉血标本,用放射免疫法测定血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-4(IL-4)浓度.结果:A组和B组TNF-α、IL-6浓度逐渐下降,IL-4浓度逐渐上升;与对照组比较有统计学意义.结论:胰岛素可降低促炎细胞因子浓度,同时升高抗炎细胞因子浓度,从而恢复细胞因子稳态.     

急性呼吸窘迫综合征及护理进展

急性呼吸窘迫综合征 (ａｃｕｔｅｒｅｓｐｉｒａｔｏｒｙｄｉｓｔｒｅｓｓｓｙｎｄｒｏｍｅ ,ＡＲＤＳ)是指由各种非心源性肺内因素导致急性进行性缺氧性呼吸衰竭 ,是全身炎症反应综合征 (ＳＩＲＳ)在肺部的严重表现。ＡＲＤＳ是各种危重病人较常见的并发症 ,其病死率高达 40 %～70 % [1] 。近年在ＡＲＤＳ病人的护理、治疗等方面取得了一些进展 ,现综述如下。1　ＡＲＤＳ概念的转变1.1　ＡＲＤＳ概念的提出　Ａｓｈｂａｕｇｈ等[2 ] 于 1967年首次提出 ,称其为ａｃｕｔｅｒｅｓｐｉｒａｔｏｒｙｄｉｓｔｒｅｓｓｉｎａｄｕｌｔｓ ,4ａ后他…     

Intravenous Chlorhexidine Gluconate Causing Acute Respiratory Distress Syndrome

Case Report: A 67-year-old man undergoing a colectomy for colon cancer was unintentionally administered 0.8 mg of chlorhexidine gluconate intravenously and subsequently developed acute respiratory distress syndrome. The operation was discontinued immediately. Respiratory failure progressed despite three cycles of plasma exchange beginning on day 1. Extracorporeal membrane oxygenation for 72 h beginning on day 3 was associated with dramatic improvement. The patient showed complete recovery of intellectual function and subsequently underwent a colectomy with lymph node dissection for colon cancer. Conclusion: For acute respiratory distress syndrome secondary to chlorhexidine gluconate intoxication, consideration should be given to the treatment of initial respiratory distress and subsequent pneumonia. The benefit of extracorporeal membrane oxygenation and plasma exchange may merit further investigation.     

急性呼吸窘迫综合征24例临床分析

目的：探讨急性呼吸窘迫综合征(ARDS)的临床治疗。方法：回顾性分析24例ARDS的临床治疗。结果：24例ARDS采用呼吸末正压机械通气(PEEP)治疗，有效率为70．83％，其中6例加用连续性静脉-静脉血液滤过(CVVH)治疗，疗效更佳；7例死于多器官功能不全综合征(MODS)，死亡率为29．17％。结论：机械通气治疗ARDS时动态监测动脉血气指标和呼吸指数(RI)，选择适宜的PEEP值，在综合治疗基础上加用CVVH，疗效更好。     

Decision support tool for differential diagnosis of Acute Respiratory Distress Syndrome (ARDS) vs Cardiogenic Pulmonary Edema (CPE): a prospective validation and meta-analysis

Introduction

We recently presented a prediction score providing decision support with the often-challenging early differential diagnosis of acute lung injury (ALI) vs cardiogenic pulmonary edema (CPE). To facilitate clinical adoption, our objective was to prospectively validate its performance in an independent cohort.

Methods

Over 9 months, adult patients consecutively admitted to any intensive care unit of a tertiary-care center developing acute pulmonary edema were identified in real-time using validated electronic surveillance. For eligible patients, predictors were abstracted from medical records within 48 hours of the alert. Post-hoc expert review blinded to the prediction score established gold standard diagnosis.

Results

Of 1,516 patients identified by electronic surveillance, data were abstracted for 249 patients (93% within 48 hours of disease onset), of which expert review (kappa 0.93) classified 72 as ALI, 73 as CPE and excluded 104 as “other”. With an area under the curve (AUC) of 0.81 (95% confidence interval =0.73 to 0.88) the prediction score showed similar discrimination as in prior cohorts (development AUC = 0.81, P = 0.91; retrospective validation AUC = 0.80, P = 0.92). Hosmer-Lemeshow test was significant (P = 0.01), but across eight previously defined score ranges probabilities of ALI vs CPE were the same as in the development cohort (P = 0.60). Results were the same when comparing acute respiratory distress syndrome (ARDS, Berlin definition) vs CPE.

Conclusion

The clinical prediction score reliably differentiates ARDS/ALI vs CPE. Pooled results provide precise estimates of the score’s performance which can be used to screen patient populations or to assess the probability of ALI/ARDS vs CPE in specific patients. The score may thus facilitate early inclusion into research studies and expedite prompt treatment.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0659-x) contains supplementary material, which is available to authorized users.     

右美托咪定在急性呼吸窘迫综合征机械通气患者中的应用

目的探析急性呼吸窘迫综合征机械通气病人应用右美托咪定镇静镇痛作用的临床观察。方法选择我院2014年4月~2015年4月急性呼吸窘迫呼吸综合征机械通气病人90例,根据随机数字表法分为研究组和对照组各45例,研究组进行右美托咪定麻醉诱导及维持,对照组进行咪达唑仑麻醉诱导及维持,比较两组镇静前、镇静半小时后的呼吸频率(RR)、舒张压(DBP)、收缩压(SBP)、心率(HR)等各项指标变化;比较两组的机械通气时间、唤醒时间、VAS评分等指标。结果研究组镇静半小时后的呼吸频率(RR)、舒张压(DBP)、收缩压(SBP)、心率(HR)等各项指标显著优于对照组,差异有统计学意义(P0.05);研究组的机械通气时间、唤醒时间、VAS评分等各项指标显著优于对照组,差异有统计学意义(P0.05)。结论急性呼吸窘迫病人进行右美托咪定镇静麻醉,生命体征平稳,术后苏醒迅速,效果确切,值得临床推广。     

肺表面活性物质及呼气末正压联合治疗急性呼吸窘迫综合征的护理

目的 探讨运用肺表面活性物质(PS)及呼气末正压(PEEP)联合治疗急性呼吸窘迫综合征(ARDS)的护理措施.方法 对13例ARDS用小潮气量(6-8mL/kg),PEEP(15-20cmH2O)机械通气,经纤维支气管镜给予PS治疗.结果 13例中有9例血气分析指标得到改善,PaO2>75mmHg,氧合指数>200mmHg,病情好转,生命体征趋于稳定;4例血气分析指标无改善,最后死于多器官功能衰竭.结论 ARDS患者应用PS及PEEP联合治疗应注意用药前后呼吸道的护理,选用小潮气量高PEEP通气.密切注意生命体征变化及循环系统的监护.     

加用纳洛酮救治急性呼吸窘迫综合征的疗效分析

目的研究综合治疗同时加用纳洛酮（Ｎａｌｏｘｏｅｎ,ＮＬＸ）救治急性呼吸窘迫综合征（ＡＤＲＳ）的疗效。方法将我院同期ＡＤＲＳ患者随机分为综合治疗组（对照组,３１例）,ＮＬＸ治疗组（３３例）,于治疗前、治疗后４小时、１２小时、２４小时分别检测动脉血氧分压（ＰａＯ２）、动脉血氧合指数（ＰａＯ２／ＦｉＯ２）水平。结果ＮＬＸ治疗组及对照组治疗后２４小时,ＰａＯ２值分别为１１．８６±０．６４ｋＰａ,９．１４±０．２６ｋＰａ;ＰａＯ２／ＦｉＯ２值分别为３６．６±１．４ｋＰａ,２２．４±１．７ｋＰａ。两组病死率分别为１８．２％,４５．１％,差异均有显著性（Ｐ＜０．０５）。结论加用ＮＬＸ救治ＡＲＤＳ可快速纠正严重低氧血症,改善肺气体交换功能,明显降低病死率,是临床救治ＡＲＤＳ时一种安全、有效的方法     

Review: Artifical ventilation with positive end-expiratory pressure (PEEP)

CPPV (continuous positive pressure ventilation) is obviously superior to IPPV (intermittent positive pressure ventilation) for the treatment of patients with acute respiratory insufficiency (ARI) and results within a few minutes in a considerable increase in the oxygen transport.The principle is to add a positive end-expiratory plateau (PEEP) to IPPV, with a subsequent increase in FRC (functional residual capacity) resulting in re-opening in first and foremost,the declive alveolae, which can then once again take part in the gas exchange and possibly re-commence the disrupted surfactant production. In this manner the ventilation/perfusion ratio in the diseased lungs is normalized and the intrapulmonary shunting of venous blood will decrease. At the same time the dead space ventilation fraction (V_D/V_T) normalizes and the compliance of the lungs (C_L) increases.The PEEP value, which results in a maximum oxygen transport, and the lowest dead space fraction, also appears to result in the greatest total static compliance (CT) and the greatest increase in mixed venous oxygen tension ; this value can be termed optimal PEEP.The greater the FRC is, with an airway pressure = atmospheric pressure, the lower the PEEP value required in order to obtain maximum oxygen transport.If the optimal PEEP value is exceeded the oxygen transport will fall because of a falling (cardiac output) due to a reduction in venous return. CT and will fall and V_D/V_T will increase. Increasing hyperinflation of the alveolae will result in a rising danger of alveolar rupture.The critical use of CPPV treatment means that the lungs may be safeguarded against high oxygen percents.The mortality of newborn infants with RDS (respiratory distress syndrome) has fallen considerably after the general introduction of CPPV and CPAP (continuous positive airway pressures). The same appears to be the case with adults suffering from ARI (acute respiratory insufficiency).Abbreviations and explanations (A-a)DO₂ Alveolo - arterial - O₂ - difference - ARI Acute respiratory insufficiency - CaO₂ Arterial O₂-content - O₂-extraction ratio - O₂-uptake, consumption - CC Closing capacity - CV Closing volume - CPAP Continuous positive airway pressure - CPPV (IPPV + PEEP) Continuous positive pressure ventilation - C_L Lung compliance - C_T Total static compliance - Mixed venous O₂-content (O₂-reserve) - ETP End Tidal point - ERV Expiratory reserve volume - FRC Functional residual capacity - IC Inspiratory capacity - IPPV Intermittent positive pressure ventilation - IRV Inspiratory reserve volume     

大黄对急性呼吸窘迫综合征患者的治疗价值

60例ARDS患者分为大黄治疗组 ( 4 0例 )和对照组 ( 2 0例 ,未用大黄治疗组 )。分析比较两组患者第 1、3、7天氧合指数的变化、机械通气时间、应急性溃疡的发生率以及病死率。结果两组患者第 1天氧合指数均下降 ,组间无显著性差异 (P >0 .0 5)。大黄治疗组患者氧合指数第 3天开始上升 ,7天后明显改善 (P <0 .0 5)。两组患者机械通气时间分别为大黄治疗组 1 0± 3.0天、非大黄治疗组 2 8± 9.0天 (P <0 .0 1 ) ;应急性溃疡的发生率大黄治疗组为 1 0 .0 %、非大黄治疗组为 35.0 % (P <0 .0 5) ;病死率分别为大黄治疗组为 2 5.0 %、非大黄治疗组为 4 5.0 % (P <0 .0 5)。大黄可以明显改善ARDS患者的氧合指数 ,缩短机械通气时间 ,降低应急性溃疡的发生率和病死率 ,可作为救治ARDS的有效措施之一     

全身炎症反应综合征患者低蛋白血症在急性呼吸窘迫综合征中的意义

目的:分析血浆蛋白水平的不同与危重症患者ARDS的发生、病死率的关系.方法:测定符合SIRS标准245例患者血清蛋白水平,按血清蛋白水平分为低蛋白组(50g/L)、临界组(50～60g/L)、正常组(＞60g/L),观察各组体重变化、ARDS发生率、病死率.结果:低蛋白组(50g/L)、临界组(50～60g/L)、正常组(＞60g/L)患者ARDS发生率分别为45%、41%、21%,P=0.01;病死率分别为45%、47%、14%,P=0.03;体重变化分别为+4.5kg、+3.6kg、-2.8kg,P=0.004,结论:低蛋白血症是ARDS发生、死亡、液体潴留、体重增加的重要危险因素.     

Submersion and Early-Onset Acute Respiratory Distress Syndrome: A Case Report

Abstract

Drowning is a common cause of accidental death, particularly in younger people, and acute respiratory failure is common in these patients. This case report describes a healthy 18-year-old man who suffered a cardiorespiratory arrest due to submersion while swimming in a freshwater lake. First-responder cardiopulmonary resuscitation and defibrillation using an automated external defibrillator resulted in a return of spontaneous circulation. The patient was evacuated to a tertiary care center by a rotor-wing air medical crew. The crew experienced difficulties in oxygenating and ventilating the patient because of early-onset acute respiratory distress syndrome (ARDS). This case report describes the pathophysiology and prehospital management of a patient with suspected early-onset ARDS secondary to drowning. This case report is unique because it describes the oxygenation and ventilation difficulties encountered in managing this patient in the transport setting, and possible strategies to deal with these difficulties. Finally, this case report highlights the prehospital bypass decision-making process for patients requiring specialized medical care.