ARDS, or Acute Respiratory Distress Syndrome, is an inflammatory lung condition involving both lungs that may complicate severe pneumonia including influenza , trauma, sepsis, aspiration of gastric contents, and many other conditions. Inflammation leads to injury of lung tissue and leakage of blood and plasma into the airspaces resulting in low oxygen levels in the blood. Mechanical ventilation is required both to deliver higher concentrations of oxygen to and provide ventilation to remove carbon dioxide from the body.
Inflammation in the lung may lead to inflammation elsewhere causing shock and injury or dysfunction in the kidneys, heart, and muscles. There is no proven drug treatment for ARDS per se. Current management of ARDS begins with treatment and stabilization of the underlying disease that caused ARDS, such as early and effective antibiotics for pneumonia or sepsis.
The injured lung should be managed gently with small breaths and low pressures from the ventilator so called low tidal volume and pressure ventialtion. There are various theories why prone positioning helps , such as by reducing ARDS's injurious heterogeneous alveolar overdistension. The improved oxygen levels have never translated into improved outcomes in ARDS patients treated with prone positioning in individual multicenter randomized trials , but meta-analyses have concluded prone positioning improves survival from ARDS , especially in the most hypoxemic patients.
The patients were well matched statistically, but the control group supine, face-up were slightly sicker , with SOFA scores of The benefit was only slightly smaller at 90 days.
There was a clear mechanism of benefit, with prone-positioned patients having higher paO2:FiO2 ratios, lower plateau pressures average 2 cm H2O , and lower required PEEP.
There were no excess adverse events -- such as unplanned extubations -- in the prone-positioning group. After adjusting for the imbalance in SOFA scores, pressors and neuromuscular blockade at randomization, the benefits of prone positioning persisted.
Whether this study heralds the coming of a new standard of care, or yet another boom-bust cycle in the critical care collective consciousness see our previous love affairs with Xigris and intensive glucose therapy, ending in disillusionment , only time will tell. The question now is, who will rush to be the early adopters, and how will prone positioning disseminate and be evaluated over time?
Prone positioning is not brain surgery, but it's not a practice change you make overnight see the videos linked from the article. Someone has to teach staff how to do it, and it takes time for everyone to get familiar and comfortable with the new routines. Louis, Missouri, USA. ARDS is associated with many diagnoses, including trauma and sepsis, can lead to multiple organ failure and has high mortality. The present article is a narrative review of the literature on ARDS, including ARDS pathophysiology and therapeutic options currently being evaluated or in use in clinical practice.
The literature review covers relevant publications until January Recent developments in the therapeutic approach to ARDS include refinements of mechanical ventilatory support with emphasis on protective lung ventilation using low tidal volumes, increased PEEP with use of recruitment maneuvers to promote reopening of collapsed lung alveoli, prone position as rescue therapy for severe hypoxemia, and high frequency ventilation.
Supportive measures in the management of ARDS include attention to fluid balance, restrictive transfusion strategies, and minimization of sedatives and neuromuscular blocking agents. Inhaled bronchodilators such as inhaled nitric oxide and prostaglandins confer short term improvement without proven effect on survival, but are currently used in many centers.
Use of corticosteroids is also important, and appropriate timely use may reduce mortality. Finally, extra corporeal oxygenation methods are very useful as rescue therapy in patients with intractable hypoxemia, even though a survival benefit has not, to this date been demonstrated. Despite intense ongoing research on the pathophysiology and treatment of ARDS, mortality remains high. Many pharmacologic and supportive strategies have shown promising results, but data from large randomized clinical trials are needed to fully evaluate the true effectiveness of these therapies.
In , Laennec described a new syndrome characterized by pulmonary edema without heart failure [ 1 ]. The diagnosis of ARDS requires all these features. However, as these clinical criteria do not always correlate well with diffuse alveolar damage, which is the typical pathologic ARDS feature, ARDS remains a syndrome associated with multiple diagnoses [ 3 ], rather than a disease in itself.
Increased capillary permeability is the hallmark of ARDS. Damage of the capillary endothelium and alveolar epithelium in correlation to impaired fluid remove from the alveolar space result in accumulation of protein-rich fluid inside the alveoli, thereby producing diffuse alveolar damage, with release of pro-inflammatory cytokines, such as Tumor Necrosis Factor TNF , IL-1 and IL-6 [ 5 ].
Neutrophils are recruited to the lungs by cytokines, become activated and release toxic mediators, such as reactive oxygen species and proteases [ 6 ]. Extensive free radical production overwhelms endogenous anti-oxidants and causes oxidative cell damage [ 7 ]. Inflammation due to neutrophil activation is key in the pathogenesis of ARDS. Fundamental transcription abnormalities, involving NF-kappa B that is required for transcription of genes for many pro-inflammatory mediators, are present in the lungs of ARDS patients [ 8 ].
In addition, other factors such as endothelin-1, angiotensin-2 and phospholipase A-2 increase vascular permeability and destroy micro-vascular architecture, enhancing inflammation and lung damage. Computed Tomography studies in the s helped us understand the pathophysiologic alterations in the lungs of ARDS patients [ 10 ]. PH etiology includes parenchymal destruction and airway collapse, hypoxic pulmonary vasoconstriction, presence of other pulmonary vasoconstrictors and vascular compression [ 13 ].
The initial phase of fluid accumulation is followed by a proliferation phase characterized by resolution of pulmonary edema, proliferation of type II alveolar cells, fibroblasts and myofibroblasts, and new matrix deposition. This phase starts early within 72 h in ARDS, and lasts for more than 7 days. Factors influencing the progression to fibro-proliferation vs. However, based on existing data it is not clear whether ARDS is the manifestation of a disease, or it is a disease that causes the MOF syndrome.
Improved understanding of ARDS pathophysiology and advances in technology have introduced new treatments and improved therapeutic strategies. The following paragraphs discuss recent developments in the therapeutic approach to ARDS. Several animal studies showed that ventilation with large tidal volumes and high inspiratory pressures resulted in development of hyaline membranes and inflammatory infiltrates in the lungs, and development of respiratory failure [ 17 ].
In the late s four randomized controlled trials RCTs evaluated the potential benefit of low tidal volume ventilation in ARDS [ ].
Although all four studies had limited power, one study by Amato et al [ 21 ] demonstrated that the low tidal volume group had higher survival, higher rate of weaning from mechanical ventilation and reduced rate of barotrauma. In-hospital mortality was significantly lower and the number of days without mechanical ventilation was significantly higher in the low tidal volume group.
Although this study has been criticized for the high difference of tidal volume between groups, it demonstrated that high tidal volumes should be avoided, and underlined the importance of maintaining low plateau pressures, with 30 cm H 2 O as an acceptable cut-off.
Low tidal volume ventilation is generally well tolerated and it has not been associated with clinically important adverse outcomes, except for hypercapnic respiratory acidosis in some patients. In conclusion, hypercapnia and respiratory acidosis are expected consequences of low tidal volume ventilation.
However, there is no evidence that hypercapnia is harmful in ARDS patients, and it may in fact confer some protection against ventilator-associated lung injury. High PEEP levels may open collapsed alveoli and decrease intrapulmonary shunt. Additionally, ventilation-induced alveolar injury is reduced by decreasing alveolar over-distention, because the volume of each subsequent tidal breath is shared by more open alveoli [ 23 ].
On the other hand, high PEEP levels may decrease repetitive alveolar opening and closing during the respiratory cycle, thereby promoting lung injury [ 24 ]. Three RCTs have evaluated modest vs. Several years later, the Canadian Critical Care Trials Group performed a similar study to determine whether the combination of low tidal volume ventilation with high PEEP could improve mortality to a greater extent compared to low tidal ventilation alone [ 26 ].
Results of this study showed reduced need for other rescue therapies such as prone position or NO, but did not show any benefit in survival. However, data from the RCTs mentioned above suggest that high PEEP levels improve lungs function without any adverse effect on mortality [ 28 ]. A recruitment maneuver is a transient increase of trans-pulmonary pressure intended to promote reopening of collapsed alveoli [ 29 ].
Techniques described for recruitment maneuvers include sustained high-pressure inflation and increased PEEP, with concurrent reduction of tidal volume [ 30 ], but it is not clear if any maneuver is superior to others.
Based on currently available data, although routine recruitment maneuvers are not recommended in ARDS, such maneuvers can dramatically improve oxygenation in certain patients, and should be considered as rescue therapy in patients with life-threatening refractory hypoxia [ 33 ]. Prone positioning has been used in ARDS for over 30 years. In Piehl et al. Since then, several observational studies on ARDS have found similar results, and improvement in oxygenation can sometimes be dramatic [ 35 ].
Mechanisms proposed to explain the observed beneficial effects of prone positioning include increased chest wall elastance decreased compression of lung tissue in the dependent regions and recruitment of alveoli, more homogeneous ventilation due to decreased ventilation-perfusion inequalities and reduced ventilator induced lung injury [ 36 ]. Four RCTs have investigated the effect of prone positioning on outcome. The first trial by the Prone-Supine Study group randomized patients with a wide range of severity of acute lung injury [ 37 ].
Two subsequent RCTs attempted to correct some shortcomings of the earlier study: they only included patients with ARDS, and patients remained prone for most of the day about 20 h.
The first RCT by Mancebo et al was terminated prematurely, after only including patients, because of problems with patient recruitment [ 39 ].
A more recent multicenter RCT by Taccone et al, included patients [ 40 ], and showed significantly increased frequency of adverse events airway obstruction, hypotension, vomiting, accidental extubation in patients treated with prone position. Neither of the last two studies showed any survival benefit using the prone position in patients with severe ARDS.
In conclusion, existing data do not support routine use of the prone position in ARDS. However, because all published studies have shown improved oxygenation, prone positioning is an attractive rescue treatment for ARDS patients with severe hypoxemia, even though a survival benefit has never been demonstrated.
Compared to conventional mechanical ventilation, mean airway pressure is higher [ 41 ]. Two studies, by Hamilton and Chan, showed reduced risk for barotrauma and lung over-distention, after performing high frequency ventilation [ 42 , 43 ]. High frequency ventilation can be applied by different modes, such as high-frequency percussive ventilation, high-frequency jet ventilation and high-frequency oscillatory ventilation HFOV [ 44 ].
In the absence of studies showing superiority of one method over another, HFOV is the HFV method used more often in adult critical care [ 43 ]. However, the use of HFOV as rescue therapy in patients with refractory hypoxia remains controversial. The first RCT by Derdak et al found a trend for decreasing day mortality [ 46 ] even though relatively high tidal volume was used in the control group.
The second RCT by Bollen et al was terminated prematurely because of slow enrollment, but found an opposite trend in mortality [ 47 ]. Two meta-analyses also had conflicting results. Direct lung injury Indirect lung injury Pneumonia Severe sepsis Aspiration of gastric contents Blood transfusion Lung contusion Trauma Toxic inhalation Cardiopulmonary bypass Near-drowning Pancreatitis. Table 3 Multivariable-adjusted predisposing conditions and clinical risk factors for acute lung injury Lung Injury Prediction Study Diagnosis The diagnosis of ARDS is often clinically challenging because of nonspecific features of this condition.
Therapeutic strategies Therapeutic strategies for ARDS focus upon treating the underlying etiology and providing supportive care that reduces the progression of lung injury.
Figure 1. Mechanical ventilation Most patients with ARDS develop respiratory failure severe enough to require mechanical ventilatory support. Low tidal—volume ventilation Preclinical animal studies suggested that using low-tidal volumes to ventilate injured lungs minimized lung injury. Positive end-expiratory pressure Another strategy for reducing injury during mechanical ventilation is application of PEEP, which is used to reduce lung collapse at end expiration and improve oxygenation.
Figure 2. High-frequency ventilation High-frequency ventilation takes the concept of low tidal—volume, open-lung ventilation to an extreme, using elevated continuous airway pressure 20—40 cm H 2 O and very low tidal volumes at very high frequencies 3—7 Hz 53 to oxygenate and ventilate lungs through convective gas motion.
Nonmechanical ventilator adjunctive therapies Prone positioning Repositioning from supine to prone position alleviates lung compression from mediastinal and abdominal structures, redistributes lung edema to less perfused areas enhancing oxygenation , and potentially reduces injurious transpulmonary pressures. Inhaled pulmonary vasodilator therapy Inhaled pulmonary vasodilators eg, nitric oxide, prostacyclins are intended to induce vasodilation of the pulmonary vasculature in ventilated lung in order to improve pulmonary hypertension, ventilation—perfusion matching, and oxygenation.
Corticosteroid therapy Because inflammation is thought to be a primary driver of lung injury, there has been considerable interest in using anti-inflammatory medications to treat ARDS.
Neuromuscular blocking agents Neuromuscular blocking medications are used to induce paralysis and decrease patient—ventilator dysynchrony. Prevention Because there are few beneficial treatments, recent studies have focused on identifying ways to prevent the development of ARDS.
Future directions Clinical epidemiologists have myriad opportunities to continue to enhance our understanding of ARDS. Footnotes Disclosure The authors report no conflicts of interest in this work. References 1. Montgomery AB. Early description of ARDS. Morris MJ.
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