Because there is no proven specific treatment for ARDS, therapy primarily involves supportive measures to maintain life while the lung injury resolves. Such measures include identifying and treating predisposing conditions, mechanical ventilatory support with oxygen, nutritional support, nonpulmonary organ support, and hemodynamic monitoring as necessary. Attention to detail is necessary to avoid nosocomial infection and iatrogenic complications.
Fluid Management and Hemodynamic Support
One of the hallmark pathological changes in ARDS is increased endothelial and epithelial permeability, resulting in extravasation of fluid and plasma elements, including albumin, in the interstitium and alveolar space. This leads to hypoxemia, atelectasis, decreased lung compliance, and increased pulmonary artery pressures.62 Fluid management is one of the most important measures shown to impact ARDS. On the basis of the known pathophysiologic mechanisms, current management is in favor of limiting the forces that favor fluid filtration from the capillaries or augmenting those factors implicated in fluid reabsorption can limit fluid accumulation in the lung.
One of the most important trials in the treatment of ARDS has been the fluid and catheter treatment (FACT) trial.63 This study randomized 1000 patients to liberal versus conservative fluid management, based on targeted central venous pressure or PCWP. There was no significant 60-day mortality difference between the groups but patients in the conservative strategy group had significantly more days alive and free of mechanical ventilation and ICU. Importantly, there was no increase in organ failures in these patients at 7 and 28 days. However, a recent analysis using a validated telephone-based neuropsychological test battery suggests that conservative fluid management may be a risk factor for the development cognitive impairment in long term64—this observation requires further investigation.
As ARDS is a common complication in patients with severe sepsis or septic shock, proper fluid management is essential for optimal outcomes. The correct assessment, however, of fluid status in ICU patients is still a challenge. An important tool in estimating lung fluid balance is extravascular lung water (EVLW), calculated using the single thermodilution method.65 Traditionally, EVLW has been indexed to actual body weight (mL/kg); however, a recent observational cohort study of patients with ARDS has shown that baseline EVLW when indexed to predicted body weight is a better prognostic indicator of mortality, after adjusting for severity of illness and other important factors, than EVLW indexed to actual body weight.66 Indexes of pulmonary permeability obtained derived from thermodilution methods such as the global end-diastolic volume index and pulmonary vascular permeability index, have also shown utility in differentiating ARDS from hydrostatic pulmonary edema.67
With respect to colloids, there is no evidence that their use for acute resuscitation improves outcome. A study in hypoproteinemic patients suggests that gas exchange can be improved in late ALI by using colloid in concert with diuretics to mobilize interstitial fluid and promote diuresis.66 A 2006 randomized clinical study (RCT) study suggested that critically ill patients with profound hypoproteinemia have fewer organ failures (by SOFA score) when given colloid therapy.67 Short-term improvement in physiology is not, however, accompanied by an improved outcome in these investigations. The very large Australian SAFE study revealed no difference in mortality and other significant clinical endpoints for patients resuscitated with albumin, as compared to those resuscitated with normal saline.68 However, the patient population in this study was heterogeneous. Further large randomized studies of albumin use only in ARDS patients are needed.
Most patients with ARDS require endotracheal intubation for mechanical ventilation. This technique reduces shunt physiology and administers high concentrations of oxygen. Emergent intubation is associated with significantly higher morbidity and mortality. Accordingly, early elective intubation should be considered in all patients with deteriorating gas exchange or mental status. The use of noninvasive positive pressure mask ventilation should be used very cautiously, if at all, for hypoxemic respiratory failure as several studies have shown a higher mortality and increased risk of intubation related complications.69,70
Respiratory support with a mechanical ventilator is a cornerstone in the supportive management of patients with or at risk for ARDS. The goals of mechanical ventilation in ARDS are to maintain oxygenation while avoiding oxygen toxicity. Typically, this involves maintaining oxygen saturation in the range of 85–90%, and decreasing Fio2 to less than 65% in the first 24–48 hours. It has long been recognized that the ventilator settings can contribute to VILI by worsening lung injury, and causing barotrauma (mediastinal emphysema, pneumothorax, etc). This recognition supported many early experimental studies in animals showing that high-tidal volume (VT) ventilation caused injury morphologically similar to ARDS in humans, and even multiorgan system failure in otherwise healthy animals, which was associated with release of inflammatory cells and proinflammatory cytokines.71,72 Early RCTs examining low VT strategies were inconclusive with limited sample size and lack of statistical power. The hallmark clinical study by the ARDS Network (ARDSNet) was the first to conclusively show the benefit of low VT ventilation compared to traditional strategies.73 In this trial, volume-controlled, continuous mandatory ventilation was used and VT was set based on ideal body weight (IBW). In the group treated with traditional VT, the target VT was 12 mL/kg IBW. In the group treated with lower VT, the target VT was 6 mL/kg IBW if the plateau pressure (Pplat) did not exceed 30 cm H2O and 4 mL/kg if Pplat was greater than or equal to 30 cm H2O. For patients with severe dyspnea, the VT could be increased to 8 mL/kg IBW. The trial was stopped after the enrollment of 861 patients because mortality was significantly lower in the group treated with lower VT than in the group treated with traditional VT (31% vs 39.8%). Importantly, plasma IL-6 plasma levels and the number of organ-failure-free days were lower among the low VT group.
Whereas previous studies employing low VT allowed permissive hypercapnia and acidosis to achieve the protective ventilation goals of low VT and inspiratory airway pressure, the ARDSNet study allowed increases in respiratory rate as the VT was decreased and administration of bicarbonate to correct acidosis. This may explain the positive outcome in this study compared to earlier studies that had failed to demonstrate a benefit. The ARDSNet trial was also criticized for relying on strict ventilator protocols for the higher-tidal-volume group.
With the results of the ARDSNet trial and two subsequent concordant meta-analyses,74,75 current standard of care now includes lower-tidal-volume ventilatory strategy (“ARDSNet lung-protective strategy”) and the use of incremental Fio2-PEEP combinations to achieve oxygenation goals.
Controlled hypoventilation (relative to CO2 production) with increased Paco2 is referred to as permissive hypercapnia. The widespread acceptance of the ARDSNet lung protective strategies, has led to a shift in clinical paradigms regarding hypercapnic acidosis (HCA)—from intolerance to acceptance. In fact, not only is it accepted that permissive HCA is well tolerated, there is emerging data regarding the benefits of permissive hypercapnia in experimental models of lung injury.
HCA has multiple physiologic effects on different organs, particularly the pulmonary, cardiovascular and cerebrovascular systems. Because CO2 diffuses freely across cell membranes, an increase in extracellular Pco2 will result in intracellular acidosis. Cytosolic pH is normally tightly regulated between 6.9 and 7.2.76 Gradual increases in Paco2 are usually well tolerated, provided renal compensation is adequate (see Chapter 59) and severe acidosis (pH <7.1) usually does not occur. Three mechanisms are responsible for this regulation: (1) physiochemical buffering, mainly due to proteins and phosphates; (2) reduced intracellular generation of protons; and (3) changes in transmembrane ion exchange. Physiochemical buffering is immediate, while the other mechanisms require 1–3 hours. These regulatory mechanisms are remarkably powerful and efficient. As a result, normoxic HCA has only limited potential for resulting in intracellular acidosis, and is generally well tolerated.
Moderate HCA enhances tissue perfusion and oxygenation, through multiple mechanisms. In both normal and diseased lungs, there is evidence that HCA reduces ventilation–perfusion heterogeneity, likely through increasing compliance and directing ventilation to underventilated lung regions with higher alveolar Pco2.77,78,79 The overall hemodynamic response to acute HCA in human experiments is increased cardiac output, heart rate, and stroke volume, with decreased systemic vascular resistance. Although HCA can result in reversible impairment of myocardial contractility due to intracellular acidosis, which interferes with myofilament responsiveness to activator calcium,80 the net increase in cardiac output, appears to be mediated through increased sympathoadrenal activity.81 For each 10 mm Hg increase in Paco2, cardiac index rises by 10–15%.82
HCA has multiple effects on the central nervous system. CO2 is an important regulator of cerebrovascular tone. It has long been recognized that hypercarbia increases cerebral blood flow and intracranial pressure secondary to diminished vascular tone and enlargement of cerebral blood volume.83 Indeed, traditional management of traumatic brain injury (TBI) historically included hypocapnia to reduce cerebral blood volume and intracranial pressure. Accumulating evidence, however, has shown that sustained hypocapnia reduces cerebral O2 supply, and increases brain ischemia, vasospasm risk, and seizures.84 In fact, recent studies have shown that prehospital hypocapnia worsens outcomes after severe TBI.85,86
The direct contribution of HCA to the protective effects observed with lung protective ventilator strategies remains an area of debate. A secondary analysis of ARDSNet data, using multivariate logistic regression and controlling for comorbidities and severity of lung injury, showed that HCA on day 1 was associated with reduced mortality in patients ventilated with 12 mL/kg but not in patients ventilated with 6 mL/kg.87 Recent studies have introduced the concept of therapeutic hypercapnia, whereby deliberately elevated Paco2 can lessen lung and systemic organ injury. Substantial evidence demonstrates that moderate HCA directly reduces VILI through several mechanisms including prevention of stretch-induced lung inflammation.88,89 HCA has been shown to directly attenuate indices of ALI in in-vivo and ex-vivo models of primary and secondary ischemia-reperfusion lung injury.90,91 These effects appear to be mediated in part through inhibition of the NF-κB.92 In contrast to the observed beneficial effects of HCA described above, there is data to suggest that HCA can be deleterious in prolonged, untreated pneumonia, through reduction of neutrophil- and macrophage-mediated bacterial killing.93 Also, HCA appears to impair pulmonary epithelial wound healing by diminishing cellular migration through inhibition of NF-κB.94 Despite these concerns, the potential for therapeutic HCA in attenuating lung injury is promising.
A major area of controversy in regards to HCA is the role of buffering with sodium bicarbonate infusion, a common practice in many ICUs. While bicarbonate may correct arterial pH, it may actually worsen intracellular acidosis because the CO2 produced from reaction of metabolic acids with bicarbonate diffuses readily across cell membranes.95 Accumulating evidence also suggests that the protective effects of HCA are attenuated by pH buffering,95,96,97 suggesting that these benefits are a function of pH, rather than elevated CO2.
There has been a lack of human trials to establish guidelines for the use of buffering during therapeutic hypercapnia. In most institutions, sodium bicarbonate would not be administered unless the pH was less than 7.2. With increased experience, however, many centers reserve bicarbonate infusion for pH less than 7.0. An alternative is to use, trishydroxymethyl aminomethane (THAM), which does not increase CO2 production but is not specifically labeled for this use.98 Sedation is mandatory with permissive hypercapnia in mechanically ventilated patients in order to control respiratory drive and prevent discomfort. Even with heavy sedation, however, respiratory drive may be insufficiently suppressed, resulting in patient–ventilator dyssynchrony. Neuromuscular blockade is often necessary in these patients.
Positive End-Expiratory Pressure
PEEP is one of several methods of increasing mean airway pressure and improving oxygenation. It improves oxygenation by enhancing lung volume, and increasing functional residual capacity (FRC) through recruitment of collapsed alveoli. Lung compliance may also be improved. The use of PEEP in patients with ARDS has two primary goals: adequate tissue oxygen delivery and the reduction of Fio2 to nontoxic (generally below 0.6) levels. Increasing PEEP above a certain level, however, may have significant adverse effects. By raising intrathoracic pressure, PEEP may significantly reduce venous return and cardiac output.70 This may result in decreased tissue oxygen delivery despite improvement in arterial oxygen saturation. This effect is accentuated in the hypovolemic patient, and can usually be reversed with intravascular volume expansion. Cardiac depression is rarely seen with PEEP levels less than or equal to 10 cm H2O. If PEEP greater than 10 cm H2O is required, assessment of intravascular volume status and cardiac function is warranted.
PEEP may also result in alveolar overdistention with compression and obliteration of surrounding pulmonary capillaries. This alveolar overdistention may actually worsen oxygenation by increasing the shunt fraction. Moreover, dead space ventilation may be increased, resulting in a higher minute ventilation requirement. Finally, PEEP may cause a maldistribution of tidal volumes and pressures, creating overdistension of normally aerated lung regions. This hyperinflated form of lung injury may result in barotrauma referred to as “volutrauma.”
The optimal approach to PEEP for ARDS remains a matter of debate. In the ARDSNet study, patients ventilated with lower VT required higher levels of PEEP (9.4 vs 8.6 cm water) to maintain oxygen saturation at 85% or morel leading some to speculate that the improved survival rates were due to higher levels of PEEP. However, three subsequent RCTs, including the ARDSNet trial of higher versus lower PEEP levels in patients with ARDS, have failed to demonstrate additional benefit of higher PEEP in patient outcomes.99,100,101 It is likely, however, that these trials enrolled patients who had both a lower and a greater potential for alveolar recruitment. Gattinoni et al found that in patients with ARDS, the percentage of potentially recruitable lung differs widely.102 With the use of higher levels of PEEP, there can be an associated increase in Pplat in patients who have regions of lung that are nonrecruitable with a higher risk of overdistention. Patients with recruitable lungs have proportionally less increase in Pplat when higher levels of PEEP are used, and may benefit from PEEP with less risk of overdistention.103
In the individual patient, the application of PEEP needs to be balanced between providing a sufficient inspiratory plateau pressure (peak alveolar pressure) to maintain adequate oxygenation and at the same time avoiding derecruitment of the alveoli during exhalation. Today, many centers have adopted the algorithm-driven approach adopted by the ARDSNet investigators where PEEP was individually titrated with combinations of PEEP and Fio2 selected for a target level of arterial oxygenation. The advantage of a ratio approach is that it can be done without measurement of pulmonary compliance curves or invasive hemodynamic monitoring. One disadvantage is that it is not necessarily applicable to an individual patient with individual physiology. Despite this criticism, this approach has been used in all of the trials conducted by ARDSNet and carries validity.
The pressure–volume curve has also been used to select optimal PEEP. In this approach, static PV curves are used to select a PEEP level above the lower inflection point to prevent alveolar end-expiratory collapse. Although this approach is intriguing, static pressure–volume curves can be difficult to obtain as well as to implement. Measurement of the PV also requires sedation and often paralysis as patient effort may confound measurements of inflection points. Further evidence is needed before the PV curve can used routinely to determine optimal PEEP. Other methods for selecting PEEP include use of the stress index tress (the shape of the pressure–time curve during constant flow volume controlled ventilation), use of esophageal pressure monitoring to maintain positive transpulmonary pressure, and use of imaging techniques such as CT, electrical impedance tomography, and ultrasound to evaluate PEEP settings.103
A recruitment maneuver is a transient increase in transpulmonary pressure to promote reopening of collapsed alveoli. The use of recruitment maneuvers in ARDS for the symptomatic treatment of hypoxemia is still a matter of debate. Complications in secondary to recruitment maneuvers such as desaturation or hypotension are common, but serious complications, such as a new air leak through an existing chest tube, are infrequent.104 A systematic review and meta-analysis105 including 10 RCTs reported a decrease in hospital mortality with the use of recruitment maneuvers; however, there is concern about the risk of bias in the included studies and the use of concomitant therapeutic strategies. Some groups advocate use of recruitment maneuvers as rescue therapy in patients with ARDS who have life-threatening hypoxemia.
Prone positioning has been used for more than 30 years in patients with acute hypoxemic respiratory failure and ARDS. Initially, prone positioning in ARDS patients was found to be an efficient technique to improve oxygenation as a rescue treatment in case of life-threatening hypoxemia; however, it is now evident that prone positioning is able to prevent VILI. Therefore, prone positioning is a strategy that covers the two major goals of ventilator support in ARDS patients, maintaining safe oxygenation, and preventing VILI.
Since the initial description by Bryan106 of the beneficial effects of the prone position on arterial oxygenation more than 30 years ago, it is remarkable that it took 20 years for the first RCT to be performed. The trial, reported by Gattinoni et al,107 consisted of 152 patients randomized to a prone group and 152 patients to a supine group and showed no differences in mortality rates were noted between the two groups after a 10-day period (21.1% vs 25%), but the study was underpowered to detect a statistical difference. Several follow-up RCTs after this trial also failed to strongly show an improvement in survival with prone positioning.107,108,109,110 However, several meta-analyses111,112 have since shown that survival in severely hypoxemic ARDS patients is significantly improved with prone positioning as compared with supine positioning. A recently published RCT by the Proning Severe ARDS Patients (PROSEVA) study investigators113 assigned 466 patients with severe ARDS to undergo prone-positioning sessions of at least 16 hours or to be left in the supine position. The 28-day mortality was 16.0% in the prone group and 32.8% in the supine group (p <0.001). Furthermore, unadjusted 90-day mortality was 23.6% in the prone group versus 41.0% in the supine group (p <0.001), with a hazard ratio of 0.44 (95% CI, 0.29–0.67). Importantly, there was no significant difference in the incidence of complications between the groups, except for the incidence of cardiac arrests, which was higher in the supine group.
There mechanisms by which prone positioning improves survival in patients with severe ARDS are multifactorial.114 Pappert et al used the multiple inert gas elimination technique and showed that the improvement in oxygenation was the result of decreased intrapulmonary shunt fraction.115 Albert and coworkers have investigated the mechanism of prone ventilation in a canine oleic acid model of ARDS. The prone position consistently reduced shunt fraction compared with the supine position. The improvement in gas exchange was independent of changes in cardiac output or FRC between the two positions. Subsequently, pulmonary blood flow was shown to be distributed preferentially to dorsal lung regions in the supine and prone positions.116 In supine animals, pleural pressure increases from nondependent to dependent regions. This may lead to dependent atelectasis in the highly perfused dorsal lung regions, resulting in intrapulmonary shunt and hypoxemia. In the prone position, the pleural pressure gradient is less, and the dorsal (now nondependent) regions are exposed to a lower pleural pressure. This results in opening of previously atelectatic alveoli. Intrapulmonary shunting is reduced because perfusion of the dorsal lung regions is maintained.117 Using chest CT, Gattinoni et al showed that in the supine position, gasless lung was found predominantly in the dorsal regions.87 With prone positioning, densities redistributed to the ventral areas and dorsal regions were well aerated. Thus, prone positioning results in recruitment of previously atelectatic dorsal lung regions.
In addition to improvement in oxygenation, there is increasing evidence regarding the effects of prone position on respiratory mechanics and lung volume. In adult humans with ARDS, chest wall elastance, which contributes to set the end expiratory lung volume (EELV), has consistently been found to be higher in the prone than in the supine position.114 Pelosi et al found that sighs superimposed on the prone position further increased EELV and oxygenation only in the prone position, suggesting that the prone position either extends the potential for recruitment.118 Lung CT scan studies have also shown that the prone position promotes lung recruitment as compared to the supine position regardless of whether PEEP was low or high in the supine position.102
As vascular dysfunction is a major independent factor associated with ARDS mortality, the beneficial effects of prone positioning on hemodynamics have been shown to be important. These effects include the reduction of the transpulmonary gradient (the difference of mean pulmonary arterial pressure relative to pulmonary artery occlusion pressure).119 Also, the increase in pulmonary arterial occlusion pressure induced by prone positioning is thought to result in pulmonary vascular recruitment thus decreasing dead space, another factor independently related to ARDS mortality.119 There is also evidence that prone positioning unloads the right ventricle in severe ARDS,120 which may play a role in patient outcome.
Another important benefit of prone positioning appears to be prevention of VILI. Broccard et al showed that prone positioning attenuates and redistributes ventilator-induced lung injury in dogs.121 Papazian et al also found lower concentrations of proinflammatory cytokines in BAL fluid in ARDS patients after 12 hours the in prone position compared to supine position in similar settings.122
The technical aspects of prone positioning require a coordinated team effort. Prone positioning must be performed with care to avoid inadvertent extubation or loss of intravenous lines or chest tubes. Transient hemodynamic instability and desaturation also may occur during repositioning. Cardiopulmonary resuscitation is difficult, if not impossible, in the prone position. Placement of multifunction electrode pads, which allow defibrillation, cardioversion, and pacing, has been recommended to facilitate cardiopulmonary resuscitation in the prone position. Other areas of concern that accompany prone positioning include facial and eyelid edema, peripheral nerve injury, tongue injuries, and skin necrosis. Multiply injured patients may present unique problems due to the presence of incisions, drainage tubes, extremity fractures, cervical spine, or facial fractures, and the like.
High Frequency Ventilation
Recognition of the impact of mechanical ventilation on VILI naturally led to an interest in the use of high frequency oscillatory ventilation (HFOV); after all, this might be considered the ultimate in “low tidal volume ventilation.” High frequency ventilation techniques such as HFOV use very small tidal volumes (1–5 mL/kg) delivered at rates of 60–3600 cycles/min. Although peak airway pressures are reduced compared with conventional modes, mean airway pressures, barotrauma, and hemodynamic compromise appear unchanged. The recently published OSCILLATE (OSCillation in ARDS Treated Early)123 showed that HFOV did not reduce, and may increase, in-hospital mortality. HFOV was also associated with higher mean airway pressures, greater use of sedatives, neuromuscular blockers, and vasoactive drugs. The OSCAR (high-frequency oscillation in ARDS)124 trial also showed that HFOV failed to reduce 30-day mortality in patients undergoing mechanical ventilation for ARDS. The disappointing results of these two major trials have casted doubt on the benefits of HFOV in ARDS. A number of potential mechanisms to explain the results have been proposed include, including the negative effects of increased sedation in patients treated with HFOV—this was also associated with the administration of an additional liter of fluid over the first 72 hours to maintain hemodynamic stability in the OSCILLATE trial. Also, the increased mean airway pressure in these patients may increase pulmonary vascular resistance and right ventricular afterload due to passive compression of alveolar vessels. Others have also argued the inclusion of patients receiving mechanical ventilation for up to 1 week and the high prevalence of direct lung injury in the OSCILLTE trial may have contributed to the lack of benefit.125 Finally, as it has been reported that a profound heterogeneity exists in the extent of alveolar recruitment in response to increases in airway pressure,102 patients lacking “recruitable lung,” may suffer increased mean airway pressures and worsening alveolar strain and increased right ventricular afterload.126
In light of the available evidence and until further trials address the above issues, HFOV should likely be reserved for a subset patients with refractory hypoxemia. When using HFOV, monitoring lung recruitment and right ventricular function to ensure achievement of appropriate physiological goals is crucial.
Extracorporeal Life Support
Extracorporeal life support (ECLS), also called extracorporeal membrane oxygenation (ECMO), has been in clinical use since 1972. The most common type of ECLS used in ARDS patients is “venovenous” ECLS, where blood is both withdrawn from and returned to the venous system. Most centers have shifted to the use of a single (dual lumen) large (~31 F) cannula placed under fluoroscopic guidance as the preferred approach for adults requiring VV-ECLS.127 Blood is withdrawn into an extracorporeal circuit by a mechanical pump before entering an oxygenator. A membrane within the oxygenator provides a blood–gas interface for diffusion of gases. The oxygenated extracorporeal blood can be warmed or cooled as needed and then returned to the body.
The results of two early RCTS in patients with ARDS (published in 1979128 and 1994129) did not show a survival benefit with ECLS, including extracorporeal carbon dioxide removal (a related technique). The old ECLS circuits were difficult to manage and potentially hazardous, with a relatively high complication rate. Recently, technological advancements in circuitry including introduction of dual lumen percutaneous catheters, better pumps and oxygenators, has been instrumental in improvement in patient outcomes and wider adaptation of this therapy. Recent observational studies have suggested a benefit in severe cases of ARDS, with survival rates ranging from 47% to 66%.130,131,132 Widespread interest in use of ECLS intensified with the H1N1 influenza epidemic in 2008–2009 that resulted in thousands of cases of severe respiratory failure, often with concomitant septic shock generated. The use of ECLS in these critically ill patients was associated with an impressive 70% survival rate.133,134,135
The conventional ventilator support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR)136 trial has been the only controlled clinical trial using modern ECMO technology. In this trial, 180 were allocated to either continued conventional management or referral to a specialized center with a standardized management protocol that included consideration for treatment with ECLS—75% of those allocated patients eventually received ECLS. Of the patients randomized to ECLS, 63% survived to 6 months without disability compared to 47% of those assigned to conventional management. However, this study was not a randomized trial of ECLS compared with standard lung-protective ventilation. In fact, only 70% of patients in the conventional management group received lung-protective ventilation. Despite these limitations, this trial provides support for transferring patients with severe ARDS to a tertiary care center that is capable of advanced ventilator management techniques and not necessarily the ability to carry out ECMO.
There is still uncertainty regarding which patients with ARDS are the best candidates for this treatment and what the optimal timing for initiation of therapy. In general, indications for ECLS in patients with ARDS include one or more of the following: severe hypoxemia, uncompensated hypercapnia, and the presence of excessively high end-inspiratory plateau pressures (Table 57-7).137 According to the Extracorporeal Life Support Organization (ELSO) guidelines,138 the use of ECMO should be considered when the ratio of Pao2 to Fio2 is less than 150, and ECMO is indicated when the ratio is less than 80. A Paco2 greater than 80 mm Hg or an end-inspiratory plateau pressure greater than 30 cm of water is also considered an indication for ECMO in patients with ARDS.
TABLE 57-7Indications and Contraindications for ECMO in Severe Cases of ARDS ||Download (.pdf) TABLE 57-7 Indications and Contraindications for ECMO in Severe Cases of ARDS
In hypoxic respiratory failure due to any cause (primary or secondary) ECLS should be considered when the risk of mortality is 50% or greater, and is indicated when the risk of mortality is 80% or greater.
50% mortality risk is associated with a Pao2/Fio2 <150 on Fio2 >90% and/or Murray score 2–3.
80% mortality risk is associated with a Pao2/Fio2 <100 on Fio2>90% and/or Murray score 3–4 despite optimal care for 6 h or more.
CO2 retention on mechanical ventilation despite high Pplat (>30 cm H2O)
Severe air leak syndromes
Need for intubation in a patient on lung transplant list
Immediate cardiac or respiratory collapse (pulmonary embolus, blocked airway, unresponsive to optimal care)
Contraindications: There are no absolute contraindications to ECLS, as each patient is considered individually with respect to risks and benefits. There are conditions, however, that are associated with a poor outcome despite ECLS, and can be considered relative contraindications.
Mechanical ventilation at high settings (Fio2 >.9, P-plat >30) for 7 days or more
Major pharmacologic immunosuppression (absolute neutrophil count <400/mm3)
Central nervous system hemorrhage that is recent or expanding
Nonrecoverable comorbidity such as major CNS damage or terminal malignancy
Age: no specific age contraindication but consider increasing risk with increasing age
The most appropriate strategy for weaning patients with ARDS from ECMO is a matter of debate. Typically, weaning from ECMO starts when improvement is noted in oxygenation, chest radiography findings, or lung compliance. At that time, the flow rate of sweep gas is decreased to compensate for increase in lung ventilation. Lung-resting ventilation is then transitioned to standard lung-protective settings or pressure-support ventilation. When ECLS support is less than 30% of total, native lung function may be adequate and a trial off is indicated.139
The usual duration of ECLS in patients with ARDS is 7–10 days; however, survival rates of 50–70% with native lung recovery are increasingly reported in cases of prolonged duration ECLS (>14 days).131,140 With advances in component technology and the techniques used to perform ECLS, serious complications have been reduced significantly. In the CESAR trial, only one serious adverse event related to ECLS was reported (a death related to vessel perforation during cannulation). In the largest single institutional review, the most common complication was nonintracranial bleeding, usually associated with cannula insertion sites (39% of the patients). The second most common complication was renal failure, defined as the need for dialysis or hemofiltration (31%). The least common complications were pump malfunction (2%), air entry into the circuit (8%), and intracranial bleeding or infarction (8%).141