Negative mesenteric effects of lung recruitment maneuvers in oleic acid lung injury are transient and short lasting

OBJECTIVE: To test the hypothesis that repeated recruitment maneuvers (RMs) have sustained negative effects on mesenteric circulation, metabolism, and oxygenation 60 mins after RMs in pigs with oleic acid lung injury. Further, we aimed to test the hypothesis that an infusion of prostacyclin (PC) at 33 ng.kg.min would attenuate such possible negative mesenteric effects. DESIGN: Randomized, experimental, controlled study. SETTING: University hospital animal laboratory. SUBJECTS: A total of 31 anesthetized, fluid-resuscitated pigs with oleic acid lung injury. INTERVENTIONS:: Animals were randomized to one of the following four groups: a control group (n = 7) that received no intervention, recruitment group (n = 8) that underwent the RM sequence, a prostacyclin group (n = 8) that received an infusion of PC, and a recruitment-prostacyclin group (n = 8) that received an infusion of PC and concomitant RM sequence. MEASUREMENTS AND MAIN RESULTS: We measured systemic and mesenteric hemodynamic variables, jejunal mucosal perfusion, mesenteric lactate flux, jejunal tissue oxygen tension, and mesenteric oxygen delivery, uptake, and extraction ratio. Five minutes after RMs, mesenteric oxygen extraction ratio and mesenteric lactate flux were more prominently increased in the recruitment group, giving evidence of worsened mesenteric conditions after RMs. These signs of worsened conditions were further supported by more decreased jejunal tissue oxygen tension and portal vein oxygen saturation in the recruitment group. PC preserved mesenteric oxygenation, as indicated by less of a decrease in portal vein oxygen saturation at the time corresponding to 5 mins after RM and less of a decrease in mesenteric oxygen delivery at the time corresponding to 15 mins after RM. PC preserved mesenteric oxygenation as indicated by less of a decrease in portal vein oxygen saturation at 5 mins after RM and an attenuated increase in mesenteric oxygen extraction ratio at 5 mins after RM. There was a trend toward worsened jejunal mucosal perfusion, although not significant. CONCLUSIONS: In an oleic acid lung injury model, three repeated RMs did not improve systemic oxygenation or lung mechanics. Negative effects on mesenteric oxygenation and metabolism were transient and short lasting. The intestinal effects of PC during RMs were minor and opposing, showing preserved oxygenation but a trend toward worsened mucosal perfusion.     

IPPV和APRV通气模式对健康和ALI犬心肺功能影响的比较

目的比较间歇正压通气（ＩＰＰＶ）和气道压力释放通气（ＡＰＲＶ）模式对健康和急性肺损伤（ＡＬＩ）犬心肺功能的影响。方法对健康和ＡＬＩ犬,分别用ＩＰＰＶ和ＡＰＲＶ模式通气,观察通气期间血流动力学、血气和呼吸生理的变化。结果对健康犬,采用相似的峰压进行通气,ＡＰＲＶ的平均气道压高于ＩＰＰＶ,除平均肺动脉压外,对血气和血流动力学影响,两者差别不显著。对ＡＬＩ犬,采用相似的平均气道压通气,ＩＰＰＶ的峰压显著高于ＡＰＲＶ,而血流动力学、血气变化相似,ＡＰＲＶ时ＰａＯ２／ＦｉＯ２比值显著优于ＩＰＰＶ时。结论ＡＰＲＶ与ＩＰＰＶ相比,能以较小的峰压达到相似的通气效果且氧合功能优于ＩＰＰＶ,更适用于ＡＬＩ者     

Airway pressure release ventilation

Airway pressure release ventilation (APRV) delivers continuous positive airway pressure (CPAP) and may support ventilation simultaneously. This investigation tested whether, after acute lung injury (ALI), APRV promotes alveolar ventilation and arterial oxygenation without increasing airway pressure (Paw) above the CPAP level and without depressing cardiac function. Ten anesthetized dogs randomly received either intermittent positive-pressure ventilation (IPPV) or APRV. APRV was delivered with a continuous-flow CPAP system. Expiration occurred when a switch in the expiratory limb opened and Paw decreased to near-ambient, which decreased lung volume. After baseline data collection, ALI was induced by infusing oleic acid iv. Two hours later, IPPV and APRV were administered randomly, and data were collected. With normal lungs, APRV and IPPV achieved similar gas exchange and hemodynamic function. During ALI, arterial oxygenation was improved, and peak Paw which did not exceed the CPAP level, was lower during APRV. Similar minute ventilations were delivered by both modes but resulted in lower PaCO2 with APRV. Thus, APRV decreased physiologic deadspace ventilation. Hemodynamic status was similar during both modes. Therefore, APRV is an improved method of oxygenation and ventilatory support for patients with ALI that will allow unrestricted spontaneous ventilation and may decrease the incidence of barotrauma.     

Evaluation of intestinal preconditioning in a porcine model using classic ischemic preconditioning or lung recruitment maneuvers

To test the hypotheses that repeated brief intestinal ischemic insults would elicit an intestinal preconditioning response to a subsequent intestinal I/R injury and that a similar response would be elicited by repeated lung recruitment maneuvers (RMs). Randomized experimental controlled animal study. University hospital animal laboratory. Eighteen anesthetized pigs. Animals were randomized to one of three groups, with six animals in each group. Control group 75-min superior mesenteric artery (SMA) occlusion followed by 60-min reperfusion. Ischemic preconditioning group, three 5-min-long SMA occlusions preceding 75-min SMA occlusion and 60-min reperfusion. Recruitment maneuver (RM) group, three 2-min-long RMs preceding 75-min SMA occlusion and 60-min reperfusion. We measured systemic and mesenteric hemodynamic parameters, jejunal mucosal perfusion, net mesenteric lactate flux, jejunal tissue oxygen tension, and mesenteric oxygenation. Every 15 min, jejunal microdialysate samples were collected and analyzed for glucose, lactate, and glycerol. Jejunal tissue samples were collected postmortem. After occlusion of SMA, regional parameters in all groups indicated abolished perfusion and gradually increasing intraluminal microdialysate lactate and glycerol levels. At reperfusion, regional parameters indicated mesenteric hyperperfusion, whereas microdialysis markers of mucosal anaerobic metabolism and cell injury decreased, although not reaching baseline. Histological examination revealed severe mucosal injury in all groups. There were no significant differences between groups in the observed parameters. No protective preconditioning response could be observed when performing repeated brief intestinal ischemic insults or repeated lung RMs before an intestinal I/R injury.     

Recombinant human activated protein C ameliorates oleic acid-induced lung injury in awake sheep

Introduction

Acute lung injury (ALI) may arise both after sepsis and non-septic inflammatory conditions and is often associated with the release of fatty acids, including oleic acid (OA). Infusion of OA has been used extensively to mimic ALI. Recent research has revealed that intravenously administered recombinant human activated protein C (rhAPC) is able to counteract ALI. Our aim was to find out whether rhAPC dampens OA-induced ALI in sheep.

Methods

Twenty-two yearling sheep underwent instrumentation. After 2 days of recovery, animals were randomly assigned to one of three groups: (a) an OA+rhAPC group (n = 8) receiving OA 0.06 mL/kg infused over the course of 30 minutes in parallel with an intravenous infusion of rhAPC 24 mg/kg per hour over the course of 2 hours, (b) an OA group (n = 8) receiving OA as above, or (c) a sham-operated group (n = 6). After 2 hours, sheep were sacrificed. Hemodynamics was assessed by catheters in the pulmonary artery and the aorta, and extravascular lung water index (EVLWI) was determined with the single transpulmonary thermodilution technique. Gas exchange was evaluated at baseline and at cessation of the experiment. Data were analyzed by analysis of variance; a P value of less than 0.05 was regarded as statistically significant.

Results

OA induced profound hypoxemia, increased right atrial and pulmonary artery pressures and EVLWI markedly, and decreased cardiac index. rhAPC counteracted the OA-induced changes in EVLWI and arterial oxygenation and reduced the OA-induced increments in right atrial and pulmonary artery pressures.

Conclusions

In ovine OA-induced lung injury, rhAPC dampens the increase in pulmonary artery pressure and counteracts the development of lung edema and the derangement of arterial oxygenation.     

Airway pressure release ventilation in acute respiratory distress syndrome

Airway pressure release ventilation (APRV) is an alternative mode of ventilation that is increasingly used in patients with acute respiratory failure, acute lung injury (ALI), and acute respiratory distress syndrome (ARDS). Animal and clinical studies have demonstrated that, compared with conventional ventilation, APRV has beneficial effects on lung recruitment, oxygenation, end-organ blood flow, pulmonary vasoconstriction, and sedation requirements. Further studies, however, are required to directly compare APRV to ARDSnet protocol ventilation, specifically in patients with ALI/ARDS, and to determine whether managing ALI/ARDS with APRV will also achieve mortality reduction.     

Heparin nebulization attenuates acute lung injury in sepsis following smoke inhalation in sheep

Pseudomonas pneumonia is a common complication of smoke inhalation injury. Airway casts formed from clotted mucous occur frequently in this condition. A recent report shows that intravenous heparin improves oxygenation and reduces lung damage in a sheep model of smoke inhalation. We hypothesized that nebulized heparin could be an effective means of reducing cast formation. Female sheep (n = 19) were surgically prepared for a study of acute lung injury (ALI). After a tracheotomy, 48 breaths of cotton smoke (<40 degrees C) were inflated into the airway. Afterwards, live Pseudomonas aeruginosa (5 x 10(11) CFU) was instilled into the lung. All sheep were mechanically ventilated with 100% O2 and were divided into four groups: a heparin-nebulized group (n = 5; animals received aerosolized heparin [10,000 I.U.] 1 h after the bacterial instillation and subsequently every 4 h thereafter), an intravenous heparin group (n = 5,300 U/kg/23 h, infusion was started 1 h after the injury), a saline-nebulization group (n = 5; animals received inhaled nebulized saline), and a sham injury group (n = 4, treated in the same fashion, but no injury). The animals were sacrificed after 24 h of mechanical ventilation, and lung samples were harvested. Sheep exposed to lung injury presented with typical hyperdynamic cardiovascular changes and a corresponding drop in PaO2. These changes were significantly attenuated in the heparin groups. Histological changes consisting of cellular infiltrates, lung edema, congestion, and cast formation were reduced by heparin. These data suggest that nebulized inhaled heparin is a beneficial therapy for sepsis-induced ALI.     

前列腺素E1对猪肺损伤的保护效应研究

目的 应用肺损伤模型全面研究前列腺素E1脂微球制剂(1ipo-PGEl)对肺损伤的保护效应.方法 应用静脉输注内毒素加大容量控制通气法制备猪肺损伤模型.将16头猪随机均分为给药组及对照组.置人肺动脉导管,监测动脉、混合静脉血气分析;测定基础值及给予内毒素后2、3、4和5 h的血液动力学及肺气体交换参数.用气道阻塞技术描记两组动物的静态压力-容积(P-V)曲线,并利用S形曲线回归公式拟合,P-V曲线以进一步确定和比较其呼吸力学参数.用酶联免疫吸附法(ELISA)检测血清肿瘤坏死因子-α(TNF-α)及白细胞介素-8(IL-8)浓度.结果 实验期间对照组平均动脉压(MAP)及心排血指数(CI)均明显下降(P 均<0.05),给药组血流动力学较稳定.除基础测定外,给药组在各监测时间点所有氧合指标[包括动脉血氧分压(PaO2、氧合指数(PaO2/FiO2)、肺-动脉血氧分压差(A-aDO2)和肺内分流率(Qs/Qt)]的改善均显著优于对照组(P均相似文献   

静脉输注高氧液对急性肺损伤的治疗作用

目的探讨静脉输注高氧液对急性肺损伤（ALI）的疗效。方法将高浓度氧气溶解在常规输液用液体内制备成高氧液，通过静脉输液的方式进行输氧。33例ALI患者入选，给予高浓度面罩吸氧2h后仍缺氧者即给予静脉输氧，于静脉输氧1、3h后进行血气分析，并与治疗前比较；对低氧血症仍未纠正并进展为急性呼吸窘迫综合征（ARDS）者，给予机械通气并继续静脉输氧治疗。结果在静脉输注高氧液1h和3h后，有25例患者动脉血氧分压（PaO2）升高明显（P〈0．01），氧合指数改善明显（P〈0．01）；对8例进展为ARDS者，及时进行机械通气并继续静脉输氧，其中5例低氧血症纠正并最终脱机。结论静脉输氧对AL1患者的低氧血症具有较好的治疗作用，并能防止AL1进展为ARDS。     

Effects of overinflation on procollagen type III expression in experimental acute lung injury

Introduction  

In acute lung injury (ALI), elevation of procollagen type III (PC III) occurs early and has an adverse impact on outcome. We examined whether different high-inflation strategies of mechanical ventilation (MV) in oleic acid (OA) ALI alter regional expression of PC III.     

Approaches to refractory hypoxemia in acute respiratory distress syndrome: current understanding, evidence, and debate

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) cause substantial morbidity and mortality despite our improved understanding of lung injury, advancements in the application of lung-protective ventilation, and strategies to prevent ventilator-induced lung injury. Severe refractory hypoxemia may develop in a subset of patients with severe ARDS. We review several approaches referred to as "rescue" therapies for severe hypoxemia, including lung-recruitment maneuvers, ventilation modes, prone positioning, inhaled vasodilator therapy, and the use of extracorporeal membrane oxygenation. Each shows evidence for improving oxygenation, though each has associated risks, and no single therapy has proven superior in the management of severe hypoxemia. Importantly, increased survival with these strategies has not been clearly established.     

Lost in translation? The pursuit of lung-protective ventilation

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) remain important causes of morbidity and mortality in the critically ill patient, with far-reaching short-term and long-term implications for individual patients and for healthcare providers. It is well accepted that mechanical ventilation can worsen lung injury, potentially worsening systemic organ function, and can thus impact on mortality in acute lung injury (ALI)/ARDS. Unfortunately, although the concept of minimizing such damage via lung-protective ventilatory strategies is widely acknowledged, effective integration of such an approach into clinical practice remains more elusive. The study by the Irish Critical Care Trials Group published in the previous edition of Critical Care describes a 10-week real-life survey of all intensive care unit admissions across Ireland, detailing for the first time the epidemiology of ALI/ARDS in this population and clinician's attempts to deliver lung-protective ventilation. The authors also report hypothesis-generating data on the implications of statin use in this population. The present commentary reviews aspects of this work, with particular attention to the implementation of low-tidal-volume/lung-protective ventilatory strategies in ALI/ARDS.     

Recruitment maneuvers and positive end-expiratory pressure/tidal ventilation titration in acute lung injury/acute respiratory distress syndrome: translating experimental results to clinical practice

Recruitment maneuvers and positive end-expiratory pressure (PEEP)/tidal ventilation titration in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) are the cornerstone of mechanical ventilatory support. The net result of these possible adjustments in ventilatory parameters is the interaction of the pressure applied in the respiratory system (airway pressure/end expiratory pressure) counterbalanced by chest wall configuration/abdominal pressure along the mechanical ventilatory support duration. Refinements in the ventilatory adjustments in ALI/ARDS are necessary for minimizing the biotrauma in this still life-threatening clinical problem.     

High-frequency oscillatory ventilation in ALI/ARDS

In the last 2 decades, our goals for mechanical ventilatory support in patients with acute respiratory distress syndrome (ARDS) or acute lung injury (ALI) have changed dramatically. Several randomized controlled trials have built on a substantial body of preclinical work to demonstrate that the way in which we employ mechanical ventilation has an impact on important patient outcomes. Avoiding ventilator-induced lung injury (VILI) is now a major focus when clinicians are considering which ventilatory strategy to employ in patients with ALI/ARDS. Physicians are searching for methods that may further limit VILI, while still achieving adequate gas exchange.     

肠系膜淋巴管结扎对失血性休克大鼠肺损伤的影响

目的观察结扎肠系膜淋巴管对不同时期重症失血性休克大鼠肺组织自由基、炎症介质的影响，探讨肠淋巴途径在休克大鼠急性肺损伤（ALI）中的作用。方法78只雄性Wistar大鼠被随机分为假手术组、休克组和结扎组。休克组与结扎组复制重症失血性休克模型。结扎组于休克复苏后行肠系膜淋巴管结扎术，于休克90min、液体复苏后0、1、3、6、12和24h各处死6只大鼠，制备肺组织匀浆，检测丙二醛（MDA）、超氧化物歧化酶（SOD）、肿瘤坏死因子-α（TNF—α）、白细胞介素-6（IL-6）以及髓过氧化物酶（MPO）活性。结果休克组大鼠输液复苏后各时间点肺组织匀浆MDA、TNF—α、IL-6以及MPO活性均有不同程度的升高，3～12h持续在较高水平，均显著高于假手术组，肺组织匀浆SOD活性显著低于假手术组（P〈0．05或P〈0．01）；结扎组输液复苏后3，6、12和24h肺组织匀浆MDA、TNF-α、IL-6以及MPO活性均显著低于休克组，SOD活性高于休克组（P〈0．05或P〈0．01）。结论肠系膜淋巴管结扎可干预重症失血性休克大鼠ALI，其机制与减少肺中性粒细胞扣押，降低TNF—α、IL-6、自由基释放与SOD消耗等因素有关。     

经鼻持续气道正压通气联合一氧化氮治疗婴幼儿急性肺损伤

目的观察经鼻持续气道正压通气(NCPAP)联合一氧化氮(NO)治疗婴幼儿急性肺损伤(ALI)的临床疗效。方法选择2009年6月~2010年2月收治的ALI患儿36例,均符合吸入NO和(或)NCPAP指征。给予患儿抗感染、控制体液、改善循环、化痰、解痉等治疗,同时采用NCPAP并给予NO 10 ppm。观察患儿转归、治疗前后血气变化等情况。结果 36例患儿中,病情好转31例,转为有创通气5例。NCPAP治疗24 h后,患儿氧合指数由治疗前的(256.9±40.3)显著升至(347.2±41.6),且患儿呼吸频率、心率均显著改善(P<0.05)。结论 NCPAP联合NO相对无创,效果良好,患儿及家属接受度高。     

Cardiorespiratory effects of spontaneous breathing in two different models of experimental lung injury: a randomized controlled trial

Introduction  

Acute lung injury (ALI) can result from various insults to the pulmonary tissue. Experimental and clinical data suggest that spontaneous breathing (SB) during pressure-controlled ventilation (PCV) in ALI results in better lung aeration and improved oxygenation. Our objective was to evaluate whether the addition of SB has different effects in two different models of ALI.     

Assisted breathing is better in acute respiratory failure

PURPOSE OF REVIEW: Mechanical ventilation is usually provided in acute lung injury to ensure alveolar ventilation and reduce the patients' work of breathing without further damaging the lungs by the treatment itself. Although partial ventilatory support modalities were initially developed for weaning from mechanical ventilation, they are increasingly used as primary modes of ventilation, even in patients in the acute phase of pulmonary dysfunction. The aim of this paper is to review the role of spontaneous breathing ventilatory modalities with respect to their physiologic or clinical evidence. RECENT FINDINGS: By allowing patients with acute lung injury to breathe spontaneously, one can expect improvement in gas exchange and in systemic blood flow, on the basis of both experimental and clinical trials. In addition, by increasing end-expiratory lung volume, as will occur when airway pressure release ventilation is used, recruitment of collapsed or consolidated lung is likely to occur, especially in juxtadiaphragmatic lung regions. Until recently, traditional approaches to mechanical ventilatory support of patients with acute lung injury have called for adaptation of the patient to the mechanical ventilator using heavy sedation and administration of neuromuscular blocking agents. Recent investigations have questioned the utility of sedation, muscle paralysis, and mechanical control of ventilation. Further, evidence exists that lowering sedation levels will decrease the duration of mechanical ventilatory support, the length of stay in the intensive care unit, and the overall costs of hospitalization. SUMMARY: On the basis of currently available data, the authors suggest the use of techniques of mechanical ventilatory support that maintain, rather than suppress, spontaneous ventilatory effort, especially in patients with severe pulmonary dysfunction.     

Autoregulation of ventilation with neurally adjusted ventilatory assist on extracorporeal lung support

Purpose  

Extracorporeal membrane oxygenation (ECMO) can support oxygenation and carbon dioxide elimination in severe lung failure. Usually it is accompanied by controlled mechanical ventilation. Neurally adjusted ventilatory assist (NAVA) is a new mode of ventilation triggered by the diaphragmatic electrical activity and controlled by the patient’s respiratory centre, which may allow a close interaction between ventilation and extracorporeal perfusion. This pilot study intended to measure the physiologic ventilatory response in patients with severe lung failure treated with ECMO and NAVA. We hypothesized that the combination of both methods could automatically provide a protective ventilation with optimized blood gases.     

不同时间给予猪肺表面活性物质对大鼠油酸型急性肺损伤疗效的影响

目的 探讨不同时间给予猪肺表面活性物质(PPS)混悬液对油酸致大鼠急性肺损伤(ALI)的治疗作用.方法 将48只SD大鼠随机分为假手术组、模型组、0.5 h PPS治疗组和2 h PPS治疗组.假手术组仅行气管和颈动脉插管手术操作,其余各组大鼠静脉注入油酸诱发ALI;0.5 h PPS治疗组和2 h PPS治疗组分别于油酸注入后0.5 h和2 h经气道均滴入100 mg/kg和150 mg/kg两个剂量的PPS,实验过程中计数大鼠呼吸频率,测定动脉血气指标;于实验4 h计算大鼠存活率后处死动物,观察肺组织病理学改变,并检测肺系数及支气管肺泡灌洗液(BALF)中总蛋白(TP)含量和血浆中肿瘤坏死因子-α(TNF-α)浓度.结果 与模型组比较,0.5 h给予PPS 100 mg/kg和150 mg/kg以及2 h给予PPS 150 mg/kg治疗都能显著降低大鼠的呼吸频率,提高动脉血氧分压(PaO2)及大鼠存活率,降低肺毛细血管通透性及肺出血、肺水肿发生率,降低血浆中TNF-α和BALF中TP含量(P均＜0.05).而2 h给予100 mg/kg PPS的治疗作用不明显.结论 早期气道内滴入≥100 mg/kg的PPS,能明显改善油酸型ALI大鼠的呼吸功能、减轻肺损伤;晚期较大剂量的PPS(150 mg/kg)才有治疗作用.