Where are we with recruitment maneuvers in patients with acute lung injury and acute respiratory distress syndrome?

Reduction of tidal volume to limit plateau pressure currently is recommended for the ventilatory management of acute respiratory distress syndrome. However, sufficient evidence now exists to support the fact that excessive reduction in tidal volume may result in harmful alveolar derecruitment depending on the level at which positive end-expiratory pressure is set. The use of recruitment maneuvers has been proposed as an adjunctive lung-protective strategy to reverse low tidal volume-related derecruitment. Many questions remain regarding the basic physiologic principles of recruitment, and, therefore, the optimal way to perform recruitment maneuvers remains unknown. Moreover, apart from physiologic studies suggesting a potential benefit of recruitment maneuver in terms of recruitment and gas exchange, no data are yet available that demonstrate the ability of such a maneuver to improve outcome. In this article, we discuss the physiologic rules governing recruitment and derecruitment and review articles that provide new insights in the field of recruitment maneuver.     

Nebulization with γ-tocopherol ameliorates acute lung injury after burn and smoke inhalation in the ovine model

We hypothesize that the nebulization of γ-tocopherol (g-T) in the airway of our ovine model of acute respiratory distress syndrome will effectively improve pulmonary function following burn and smoke inhalation after 96 h. Adult ewes (n = 14) were subjected to 40% total body surface area burn and were insufflated with 48 breaths of cotton smoke under deep anesthesia, in a double-blind comparative study. A customized aerosolization device continuously delivered g-T in ethanol with each breath from 3 to 48 h after the injury (g-T group, n = 6), whereas the control group (n = 5) was nebulized with only ethanol. Animals were weaned from the ventilator when possible. All animals were killed after 96 h, with the exception of one untreated animal that was killed after 64 h. Lung g-T concentration significantly increased after g-T nebulization compared with the control group (38.5 ± 16.8 vs. 0.39 ± 0.46 nmol/g, P < 0.01). The PaO(2)/FIO(2) ratio was significantly higher after treatment with g-T compared with the control group (310 ± 152 vs. 150 ± 27.0, P < 0.05). The following clinical parameters were improved with g-T treatment: pulmonary shunt fraction, peak and pause pressures, lung bloodless wet-to-dry weight ratios (2.9 ± 0.87 vs. 4.6 ± 1.4, P < 0.05), and bronchiolar obstruction (2.0% ± 1.1% vs. 4.6% ± 1.7%, P < 0.05). Nebulization of g-T, carried by ethanol, improved pulmonary oxygenation and markedly reduced the time necessary for assisted ventilation in burn- and smoke-injured sheep. Delivery of g-T into the lungs may be a safe, novel, and efficient approach for management of acute lung injury patients who have sustained oxidative damage to the airway.     

Recombinant human activated protein C in acute lung injury: what is the role of bronchial circulation?

Impairment of the protein C pathway plays a central role in the pathogenesis of sepsis. Treatment with recombinant human activated protein C (rhAPC) has been reported to increase survival from severe sepsis. Protein C levels also decrease markedly in acute lung injury, of both septic and nonseptic origin. Low levels of protein C in acute lung injury are associated with poor clinical outcome. The present article discusses the beneficial effects of rhAPC in oleic acid-induced lung injury as well as the controversies between different animal models and the timing of drug administration. The unique bronchial circulation in ovine models seems to be responsible for the beneficial effects of rhAPC when given simultaneously to the injury.     

β2 adrenergic agonists in acute lung injury? The heart of the matter

Despite extensive research into its pathophysiology, acute lung injury/acute respiratory distress syndrome (ALI/ARDS) remains a devastating syndrome with mortality approaching 40%. Pharmacologic therapies that reduce the severity of lung injury in vivo and in vitro have not yet been translated to effective clinical treatment options, and innovative therapies are needed. Recently, the use of β₂ adrenergic agonists as potential therapy has gained considerable interest due to their ability to increase the resolution of pulmonary edema. However, the results of clinical trials of β agonist therapy for ALI/ARDS have been conflicting in terms of benefit. In the previous issue of Critical Care, Briot and colleagues present evidence that may help clarify the inconsistent results. The authors demonstrate that, in oleic acid lung injury in dogs, the inotropic effect of β agonists may recruit damaged pulmonary capillaries, leading to increased lung endothelial permeability.     

Active transforming growth factor-β1 activates the procollagen I promoter in patients with acute lung injury

Objective Fibroproliferation markers like procollagen I predict mortality in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). We sought to determine whether bronchoalveolar lavage fluid (BALF) from patients with lung injury contained mediators that would activate procollagen I promoter and if this activation predicted important clinical outcomes.Design Prospective controlled study of ALI/ARDS.Setting Intensive care units and laboratory of a university hospital.Patients and participants Acute lung injury/ARDS, cardiogenic edema (negative controls) and pulmonary fibrosis (positive controls) patients.Interventions Bronchoalveolar lavage fluid was collected within 48 h of intubation from ALI/ARDS patients. BALF was also collected from patients with pulmonary fibrosis and cardiogenic pulmonary edema. Human lung fibroblasts were transfected with a procollagen I promoter-luciferase construct and incubated with BALF; procollagen I promoter activity was then measured. BALF active TGF-1 levels were measured by ELISA.Results Twenty-nine ARDS patients, nine negative and six positive controls were enrolled. BALF from ARDS patients induced 41% greater procollagen I promoter activation than that from negative controls (p<0.05) and a TGF-1 blocking antibody significantly reduced this activation in ARDS patients. There was a trend toward higher TGF-1 levels in the ARDS group compared to negative controls (–1.056 log₁₀±0.1415 vs –1.505 log₁₀±0.1425) (p<0.09). Procollagen I promoter activation was not associated with mortality; however, lower TGF-1 levels were associated with more ventilator-free and ICU-free days.Conclusions Bronchoalveolar lavage fluid from ALI/ARDS patients activates procollagen I promoter, which is due partly to TGF-1. Activated TGF-1 may impact ARDS outcome independent of its effect on procollagen I activation.Electronic Supplementary Material Supplementary material is available in the online version of this article at     

Assessment of PEEP-induced reopening of collapsed lung regions in acute lung injury: are one or three CT sections representative of the entire lung?

OBJECTIVES: To study whether PEEP-induced reopening of collapsed lung regions--defined as the decrease in nonaerated lung volume measured on a single or three computerized tomographic (CT) sections--is representative of the decrease in overall nonaerated lung volume. DESIGN: Review of 39 CT scans obtained in consecutive patients with Acute Lung Injury. Settings: Fourteen-bed surgical intensive care unit of a University Hospital. MEASUREMENTS AND RESULTS: PEEP-induced decrease in nonaerated lung volume was measured in 39 patients with ALI on a single juxtadiaphragmatic CT section, on three CT sections--apical, hilar, and juxtadiaphragmatic--and on contiguous apex-to-diaphragm CT sections. The percentage of decrease in nonaerated lung volume following PEEP, was compared between one, three and all CT sections using a linear regression analysis and Bland and Altman's method. The decrease in nonaerated lung volume measured on a single and three CT sections was significantly correlated with the decrease in nonaerated lung volume measured on all CT sections: R=0.83, P<0.0001 for one CT section and R=0.92, P<0.0001 for three CT sections. However, measurements performed on a single CT section were poorly representative of the overall lung: bias -6%, limits of agreement ranging between -37% and +25%. Measurements performed on three CT sections overestimated by 11% the overall decrease in nonaerated lung volume: bias -11%, limits of agreement ranging between -29% and +7%. CONCLUSIONS: PEEP-induced reopening of collapsed lung regions measured on a single or three CT sections sensibly differs from the reopening of collapsed lung regions measured on the overall lung. The inhomogeneous distribution of PEEP-induced reopening of collapsed lung regions along the cephalocaudal axis probably explains these discrepancies.     

Fluid management in patients with acute kidney injury – A post-hoc analysis of the FINNAKI study

PurposeWhether positive fluid balance among patients with acute kidney injury (AKI) stems from decreased urine output, overzealous fluid administration, or both is poorly characterized.Materials and methodsThis was a post hoc analysis of the prospective multicenter observational Finnish Acute Kidney Injury study including 824 AKI and 1162 non-AKI critically ill patients.ResultsWe matched 616 AKI (diagnosed during the three first intensive care unit (ICU) days) and non-AKI patients using propensity score. During the three first ICU days, AKI patients received median [IQR] of 11.4 L [8.0–15.2]L fluids and non-AKI patients 10.2 L [7.5–13.7]L, p < 0.001 while the fluid output among AKI patients was 4.7 L [3.0–7.2]L and among non-AKI patients 5.8 L [4.1–8.0]L, p < 0.001. In AKI patients, the median [IQR] cumulative fluid balance was 2.5 L [−0.2–6.0]L compared to 0.9 L [−1.4–3.6]L among non-AKI patients, p < 0.001. Among the 824 AKI patients, smaller volumes of fluid input with a multivariable OR of 0.90 (0.88–0.93) and better fluid output (multivariable OR 1.12 (1.07–1.18)) associated with enhanced change of resolution of AKI.ConclusionsAKI patients received more fluids albeit having lower fluid output compared to matched critically ill non-AKI patients. Smaller volumes of fluid input and higher fluid output were associated with better AKI recovery.     

What is the optimal duration of ventilation in the prone position in acute lung injury and acute respiratory distress syndrome?

OBJECTIVE: To evaluate the effects of prone ventilation on respiratory parameters and extravascular lung water (EVLW) in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in order to characterise the optimal duration of ventilation in the prone position. DESIGN: Prospective, observational study. SETTING: Nine-bed general intensive care unit. PATIENTS: Eleven patients with refractory hypoxaemia due to ALI/ARDS were prospectively investigated during 12 consecutive episodes of prone ventilation. INTERVENTIONS: Ventilation in the prone position for 18 h. MEASUREMENTS AND MAIN RESULTS: Measurements were obtained supine and after 1, 2, 6, 12 and 18 h in the prone position and 1 h after returning supine. There was a progressive improvement in PaO(2)/fraction of inspired oxygen (FIO(2)) ratio which reached significance after 12 h [121 (81-151) to 258 (187-329) torr; p<0.05]. EVLW index increased transiently at 1 h [14.2 (7.6-20.8) to 15.1 (9.0-20.2); p=0.05] and thereafter declined progressively and was significantly decreased at 18 h [12.1 (7.2-17.0); p=0.043]. The shunt fraction showed an early fall [0.41 (0.40-0.42) to 0.31 (0.30-0.32) at 1 h; p<0.001] preceding a subsequent progressive fall [0.22 (0.21-0.23) at 18 h; p<0.001]. CONCLUSIONS: Over the 18 h period studied there was progressive improvement in gas exchange, pulmonary shunt and EVLW. Although it is not possible to exclude that improvement over this period was unrelated to prone positioning, these findings suggests that ventilation in the prone position for more prolonged periods may be required for optimal improvement and warrants further study.     

Extracranial complications in patients with acute brain injury: a post-hoc analysis of the SOAP study

Objective To assess the incidence and severity of nonneurological organ dysfunction and its effect on outcome in acute neurological patients in an international cohort observational study. Design and setting Analysis of database from the observational Sepsis Occurrence in Acutely Ill Patients (SOAP) study in 198 intensive care units (ICUs) in 24 European countries. Patients All adult patients admitted to the participating ICUs between 1 and 15 May 2002. Of the 3,147 patients in the SOAP database 373 (12%) were admitted with a neurological diagnosis, including 154 (41%) with traumatic brain injury and 186 (50%) with cerebrovascular accident. Measurements and results Patients were followed until death, hospital discharge, or for 60 days. Neurological patients were younger and had a higher incidence of trauma and fewer comorbidities than nonneurological patients. Neurological patients developed ICU-acquired sepsis and respiratory failure more frequently than the other patients. ICU and hospital mortality rates were higher and ICU length of stay longer in neurological than in nonneurological patients. Multivariate logistic analysis showed that, in addition to the Glasgow Coma Score (GCS) and the presence of nontraumatic brain injury, cardiovascular failure, hepatic failure, and ALI/ARDS were the only factors independently associated with a higher risk of death in the ICU in patients with a neurological diagnosis. Conclusions Although neurological patients were younger and had fewer comorbidities, they developed ICU-acquired sepsis and respiratory failure more frequently than other patients. Efforts should be oriented to reduce cardiovascular, hepatic, and respiratory complications.