For Part I of to ARDSnet and Beyond, we delve into the basics of the deadly disease ELSO guidelines on ECMO in acute respiratory failure. Overall, the ARDSNet protocol just “tolerates” atelectasis by .. to the approach proposed in the guidelines for management of pain. The study was a multi-centered randomized controlled trial performed by a group called the ARDSNet who were funded by the National Heart, Lung and Blood.

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Severe ARDS is often associated with refractory hypoxemia, and early identification and treatment of hypoxemia is mandatory. For the management of severe ARDS ventilator settings, positioning therapy, infection control, and supportive measures are essential to improve survival. A precise definition of life-threating hypoxemia is not identified. Typical zrdsnet determinations are: For mechanical ventilation specific settings are recommended: A negative fluid balance is associated with improved lung giidelines and the use of hemofiltration might be indicated for specific indications.

A specific standard of care is required for the management of severe ARDS with refractory hypoxemia. The acute respiratory distress syndrome ARDS is characterized by life-threatening impairment of pulmonary gas exchange, resulting in hypoxemia, hypercapnia, and respiratory acidosis and requiring acute rescue measures.

Oxygen delivery to the tissues is necessary for all aerobic life, and tissue hypoxia will result in various deleterious effects including altered vascular reactivity, inflammation, cell apoptosis, and organ dysfunction or failure [ 1 ].

A recent Ardsnft review failed to identify any relevant studies evaluating hypoxemia versus normoxemia in ventilated patients with ARDS [ 5 ]. It remains to be evaluated in further studies whether selected biomarkers may help identify tissue hypoxia in the individual patient. However an individualized, organ-specific approach for monitoring of hypoxemia is currently not available. The applied volume is only distributed to aerated regions, and the larger the non-aerated regions, the greater the associated hyperinflation strain.

The driving pressure gguidelines a given V T is responsible for opening lung areas which are collapsed at end-expiration. A lower pressure will not reopen these areas and ardsjet will worsen.

This will also reduce the driving pressure required [ 910 ]. It would allow more individualized settings based on physiologic measurements and considerations [ 11 — 13 ardsneg. Since flow, driving pressure, and frequency determine the power, and the factor by which ventilation injures the lungs, it seems unlikely that the manner in which this power is delivered i. Airway pressure release ventilation ardsnnet a potential recruitment by increased airway pressure and allows spontaneous breathing, with some potential benefits decreased sedation, shorter mechanical ventilation, and improvement in cardiac performance.

High-frequency oscillatory ventilation delivers very arrsnet tidal volumes, to prevent volutrauma, at a constant relatively high mean airway pressure. Despite their theoretical benefits, the clinical evidence of both techniques remains unproven and controversial for ARDS patients [ 16 ]. Lung injury may be related to the frequency of repetitive collapse and expansion [ 17 ], i. The degree of tissue damage probably depends on the pressure amplitude and to a lesser extent on the frequency with which it is applied [ 1819 ].

However, a higher respiratory rate might prevent expiratory derecruitment by reducing expiratory time and causing intrinsic PEEP [ 20 ]. In a large animal model of VALI, higher RR was associated with less pulmonary inflammation, but increased lung edema [ 21 ]. Accordingly, a high RR might influence the amount of extrinsic PEEP, and the current status of the lungs in terms of de recruitment, regional compliance, and resistance.

Increasing inspiratory time has been suggested to improve oxygenation. The effect of a high I: The results regarding the effect of different I: E ratios are conflicting [ 2223 ].

To ARDSnet and Beyond

Using extrinsic PEEP is perhaps the more physiological approach guidelinse it maintains a controlled and constant level. Heat and moisture exchangers are widely used because of low cost, simple handling, and condensate elimination from the breathing circuit. However, they increase dead space and airway resistance, as well as work of breathing during assisted ventilation with the risk of hypercapnia [ 27 ].

In ARDS patients, heated humidifiers but not heat and moisture exchangers can safely reduce PaCO 2 without changing ventilator settings [ 28 ]. These findings question the use of heat and moisture exchangers in ARDS patients, where the primary target is to provide the optimum lung-protective ventilation.


At present, the aim of alveolar recruitment is not only to improve oxygenation but also to prevent VALI by minimizing tidal alveolar opening and collapse atelectrauma [ 31 ].

However, despite a myriad of clinical and translational studies and three large clinical trials, the effectiveness of recruitment remains controversial [ 32 — 35 ]. Hence, decisions are based on surrogates, such as arterial oxygenation, end-inspiratory plateau pressure, or driving pressure.

Electrical impedance tomography EITlung ultrasound, and the stress index have been guldelines to monitor alveolar recruitment, but are seldom used in clinical practice [ 1136 ]. Nevertheless, two major issues remain controversial: A meta-analysis of the three major clinical trials [ 37 ] evaluated the first issue and suggested that the application of LRMs and PEEP levels higher than those suggested by the ARDSNet protocol could improve both lung aeration and clinical outcome.

The second issue is a major clinical challenge in a small, but not negligible, cohort of patients. The first approach to persistent severe hypoxemia should be prone position [ 38 ] and neuromuscular blockade [ 39 ].

Another important approach, though seldom applied in clinical practice, is to optimize the transpulmonary pressure P L. Simultaneously measuring the airway opening and the esophageal pressure swings generated by positive guideelines tidal inflation allows partitioning of the mechanical properties of the lung and chest wall.

The most aggressive open lung approach has been proposed by Barbas et al. The open lung approach may dramatically improve oxygenation, while minimizing VALI. The potential for alveolar recruitment in the individual patient is unfortunately extremely variable and difficult to estimate a priori [ 42 ].

ARDSnet Ventilation Strategy

In poor recruiters, the guidelies lung approach may induce alveolar hyperinflation and hence VALI [ 31 ]. The stress index identification of injurious mechanical ventilation from the shape of the pressure—volume curve could be a valuable tool to monitor open lung approach-induced hyperinflation [ 11 ].

Another potential adverse effect of the open lung approach is the gjidelines impairment due to reduced preload or increased right ventricular afterload [ 44 ]. Prone position ventilation consists of delivering mechanical ventilation to the patient turned face-down. This method frequently and sometimes markedly improves oxygenation in patients with ARDS [ 45 ].

As a treatment, prone position ventilation results in significantly better oxygenation than mechanical ventilation applied in the supine position in ARDS patients [ 46 ]. As such prone positioning is used as an important strategy in life-threatening hypoxemia to avoid serious adverse events or death due to severe hypoxemia.

However, in a recent trial that ardsnwt significantly better survival in the prone position group compared to the supine position [ 48 ] in patients with moderate to severe ARDS, the benefit of proning was observed at any level of hypoxemia at the time of randomization and no correlation was found between the magnitude of oxygenation response of the first session and patient survival [ 49 ].

Therefore, the beneficial effect of proning is likely explained by factors other than improvement in oxygenation. Among them the prevention of VALI [ 5051 ] is likely a major contributing factor to the benefit of proning.

As such, it should be applied as first-line therapy to any patient with moderate or severe ARDS. It should be stressed that the effect of proning on VILI prevention is distinct from its effect on oxygenation. Henceforth, proning should be applied as early as possible after identification of hypoxemic ARDS to make the lung more homogeneous and to reduce the stress and strain [ 52 ] imposed on the entire lung by mechanical ventilation. In the Proseva trial, however, patients were, enrolled after a to h stabilization period which was used to confirm ARDS.

It is srdsnet that this strategy led to selecting patients with a more recruitable and more heterogeneous lung [ 53 ], which would benefit from proning. Nevertheless, the control group was not disfavored as its mortality was exactly the same as in another trial on similar patients [ 54 ]. Early guidelinss used proning for 7- to 8-h sessions [ 5556 ]. It is interesting to note that in many centers that have used prone position for many years the procedure is simple and done routinely by 3—4 caregivers.

In other centers which do not prone patients frequently the procedure is described as complex, cumbersome, and risky. It should be stressed that the procedure really gguidelines a specific implementation program in the ICU and it is likely that, as for other techniques, the volume effect does matter.


In the last meta-analyses of trials on prone versus supine position [ 5859 ], pressure sores and endotracheal tube obstruction were still significantly more frequent with proning. It should also be stressed that no trial showed harmful effects of prone position as a group. Specific contraindications to proning have been defined in the trials. The likely single absolute contraindication is an unstable spine fracture. In guidelinee early phase of ARDS, at the time of admission to an ARDS center a lung and whole body computed tomography CT may be performed especially in the combination of sepsis and ARDS—if the indication is supported by careful anamnesis, clinical history, and examination—to diagnose a focus of infection as the major cause of ARDS; b typical complications of ARDS; c concomitant guldelines requiring therapeutic interventions; and d risk factors for extracorporeal lung support.

CT is performed for detection of several causal agents of infection pulmonary infiltrates, ground glass opacities, pleural effusions, pleural empyema, lung abscess, lymphadenopathy, cerebral abscess, cerebral septic embolus, intra-abdominal abscess or infection.

Mechanical ventilation: lessons from the ARDSNet trial

Transesophageal echocardiography is useful to exclude endocarditis and pericardial guidelies and to assess right and left ventricular function. Protected specimen brush is used rarely, as it is costly and disposable. Major causes of ARDS are infections.

A specific anti-infective strategy based on culture results is more effective compared to empiric broad-spectrum treatment [ 60 ]. The cutoff for significant number of colony forming units to differentiate atdsnet colonization and infection depends on the diagnostic test: Gram-staining is still recommended, since in patients without anti-infective treatment a high negative predictive value is documented. For exclusion of atypical pneumonia, Legionella antigen assessment urine, sputum with two negative tests is recommended.

Of note careful examination may help to exclude some clinical entities that are mistaken for ARDS e.


Various diagnostic tools of BAL analysis hemogram, cytology, and flow cytometric analysis have been described as guidelinew complete diagnostic workup [ 68 ].

In immunosuppressed patients specific diagnostic and therapeutic procedures are essential. Pretreatment with anti-infectives, local resistance, and severity of illness with organ failure have to be considered for calculated use of broad-spectrum antibiotics [ 69 ].

Targeted treatment after successful detection of the responsible pathogen is more effective and lowers mortality. Moreover, de-escalation and targeted anti-infective treatment of pneumonia reduce superinfection qrdsnet resistant pathogens.

All these diagnostic measures are subject to individual patient assessments and indications. TBS tracheobronchial guidelimes obtained by noninvasive technique in intubated patients using suction catheter, BAL bronchioalveolar lavage obtained invasively by bronchoscopy. To diagnose sepsis resulting from invasive candidiasis, early BCs and laboratory examinations e.

Open lung biopsy should not be performed to demonstrate the presence of diffuse alveolar damage, but only considered if there is high clinical suspicion of contributive results for risky empirical therapy or when empirical therapy has failed [ 70 ].

Immunosuppressed patients are at high risk of invasive pulmonary aspergillosis. In these patients BAL galactomannan levels in CT-suspected areas are more sensitive and specific than in serum [ 71 ]. New diagnostic methods using lateral flow devices might enable bedside diagnoses in the future [ 72 ].

In conclusion, ARDS patients with suspected infection are candidates for advanced broad-spectrum antibiotics after obtaining BCs and fiber bronchoscopy results, and a daily reassessment of de-escalation is recommended as well as a strict infection prevention strategy including all aspects of interfering determinants of VAP [ 73 ].

The precise mechanism resulting in improved outcomes is not clear. In terms of lung mechanics, better synchrony may lead to more-uniform lung recruitment and improved compliance, gas exchange, and systemic oxygenation. With respect to lung inflammation, it is plausible that improved control of inspiratory volumes and pressures reduces volutrauma, while better control of expiratory volumes and pressures reduces atelectrauma; the result is less pulmonary and systemic inflammation [ 75 ].

The outcome benefit for rescue therapy with neuromuscular blockade is applicable only to cisatracurium besylate and not to all neuromuscular blocking agents.