Acute Respiratory Distress Syndrome Treatment & Management
- Author: Eloise M Harman, MD; Chief Editor: Michael R Pinsky, MD, CM, FCCP, FCCM more...
Approach Considerations
No drug has proved beneficial in the prevention or management of acute respiratory distress syndrome (ARDS). Early administration of corticosteroids to septic patients does not prevent the development of ARDS. A study by Martin-Loeches et al concluded that the early use of corticosteroids was also ineffective in patients with the pandemic H1N1 influenza A infection, resulting in an increased risk of superinfections.[23] This finding was also echoed in a study by Brun-Buisson et al, who found no evidence of benefit associated with corticosteroids in patients with ARDS secondary to influenza pneumonia but did find that early corticosteroid therapy may be harmful.[24]
Numerous pharmacologic therapies, including the use of inhaled synthetic surfactant, intravenous (IV) antibody to endotoxin, ketoconazole, and ibuprofen, have been tried and are not effective.[25]
A study that examined the use and outcomes associated with rescue therapies in patients with ALI determined that these therapies offered no survival benefit.[26] The study also determined that rescue therapies are most often used in younger patients with more severe oxygenation deficits.
A randomized, clinical trial determined that simvastatin, a hydroxymethylglutaryl-coenzyme A reductase inhibitor, improved oxygenation and respiratory mechanics in patients with ALI.[27] Further studies are needed, but treatment with simvastatin appears safe and may be associated with improved organ dysfunction in patients with ALI.
Small sepsis trials suggest a potential role for antibody to tumor necrosis factor (TNF) and recombinant interleukin (IL)-1 receptor antagonist. Inhaled nitric oxide (NO), a potent pulmonary vasodilator, seemed promising in early trials, but in larger controlled trials, it did not change mortality rates in adults with ARDS.[28, 29] A systematic review, meta-analysis, and trial sequential analysis of 14 randomized controlled trials, including 1303 patients, found that inhaled nitric oxide did not reduce mortality and results in only a transient improvement in oxygenation.[30]
Although no specific therapy exists for ARDS, treatment of the underlying condition is essential, along with supportive care, noninvasive ventilation or mechanical ventilation using low tidal volumes, and conservative fluid management. Because infection is often the underlying cause of ARDS, early administration of appropriate antibiotic therapy broad enough to cover suspected pathogens is essential, along with careful assessment of the patient to determine potential infection sources. In some instances, removal of intravascular lines, drainage of infected fluid collections, or surgical debridement or resection of an infected site (eg, the ischemic bowel) may be necessary because sepsis-associated ARDS does not resolve without such management.
Other important interventions in sepsis have included early goal-directed therapy, use of drotrecogin alfa (Xigris) in selected patients with severe sepsis (APACHE score ≥25) and no contraindications, prevention of bleeding complications by means of prophylaxis for deep venous thrombosis (DVT) and stress ulcers, early mobilization, turning and skin care, removal of catheters and tubes as soon as possible, and elevation of the head of the bed and other strategies to prevent ventilator-associated pneumonia, including facilitation of weaning from mechanical ventilation by daily interruption of sedation coordinated with daily spontaneous breathing trials.
Drotrecogin alfa was withdrawn from the worldwide market October 25, 2011. In the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS)-SHOCK clinical trial, drotrecogin alfa failed to demonstrate a statistically significant reduction in 28-day all-cause mortality in patients with severe sepsis and septic shock. Trial results observed a 28-day all-cause mortality rate of 26.4% in patients treated with activated drotrecogin alfa compared with 24.2% in the placebo group of the study.
The use of stress-dose steroids in patients with septic shock did not change survival in a recently reported controlled trial,[31] although an earlier trial showed a survival benefit.
With the development of the National Institutes of Health (NIH)–sponsored ARDS Clinical Trials Network, several large well-controlled trials of ARDS therapies have been completed. Thus far, the only treatment found to improve survival in ARDS is a mechanical ventilation strategy using low tidal volumes (6 mL/kg based upon ideal body weight).
The main concerns are missing a potentially treatable underlying cause or complication of ARDS. In these critically ill patients, pay careful attention to early recognition of potential complications in the intensive care unit (ICU), including pneumothorax, IV line infections, skin breakdown, inadequate nutrition, arterial occlusion at the site of intra-arterial monitoring devices, DVT and pulmonary embolism (PE), retroperitoneal hemorrhage, gastrointestinal (GI) hemorrhage, erroneous placement of lines and tubes, and the development of muscle weakness.
In situations where the patient requires the use of paralyzing agents to allow certain modes of mechanical ventilation, take meticulous care to ensure that an adequate alarm system is in place to alert staff to mechanical ventilator disconnection or malfunction. In addition, adequate sedation is important in most patients on ventilators and is essential when paralytic agents are in use.
As in all situations in which patients are critically ill, family and friends are under stress and likely have many questions and concerns. Keep them informed and allow them to be at the bedside as much as possible. Caretakers should assume that even though sedated, the patient may be capable of hearing and understanding all conversations in the room and may experience pain. Keeping this in mind, all conversation at the bedside should be appropriate and all procedures should be performed with local anesthesia and pain medication.
Fluid Management
Distinguishing between initial fluid resuscitation, as used for early goal-directed therapy of septic shock, and maintenance fluid therapy is important. Early aggressive resuscitation for associated circulatory shock and its associated remote organ injury are central aspects of initial management. However, several small trials have demonstrated improved outcome for ARDS in patients treated with diuretics or dialysis to promote a negative fluid balance in the first few days. Thus, distinction between primary ARDS due to aspiration, pneumonia, or inhalational injury, which usually can be treated with fluid restriction, from secondary ARDS due to remote infection or inflammation that requires initial fluid and potential vasoactive drug therapy is central in directing initial treatments to stabilize the patient.
An ARDS Clinical Trials Network study of a fluid-conservative strategy versus a fluid-liberal strategy in the management of patients with ARDS or acute lung injury (ALI) found no statistically significant difference in 60-day mortality between the 2 groups 72 hours after presentation with ARDS.[32] However, patients treated with the fluid-conservative strategy had an improved oxygenation index and lung injury score and an increase in ventilator-free days, without an increase in nonpulmonary organ failures.
It is worth noting that the fluid-conservative group actually had an even rather than a negative fluid balance over the first 7 days, which raises the possibility that the benefit may have been underestimated. Patients whose fluids were managed conservatively did not have an increased need for vasopressors or dialysis.
Maintaining a low-normal intravascular volume may be facilitated by hemodynamic monitoring with a central venous or pulmonary artery (Swan-Ganz) catheter, aimed at achieving a central venous pressure (CVP) or pulmonary capillary wedge pressure (PCWP) at the lower end of normal. The ARDS clinical trials network of pulmonary artery catheter versus CVP to guide fluid management in ARDS showed no difference in mortality or ventilator-free days, regardless of whether fluid status was monitored by pulmonary artery catheter or CVP.
Closely monitor urine output and administer diuretics to facilitate a negative fluid balance. In oliguric patients, hemodialysis with ultrafiltration or continuous veno-venous hemofiltration/dialysis (CVVHD) may be required.
A study by Lakhal et al determined that respiratory pulse pressure variation fails to predict fluid responsiveness in patients with ARDS.[33] Careful fluid challenges may be a safer alternative.
Noninvasive Ventilation
Because intubation and mechanical ventilation may be associated with an increased incidence of complications, such as barotrauma and nosocomial pneumonia, noninvasive positive-pressure ventilation (NIPPV) may be beneficial in patients with acute lung injury (ALI). This is usually given by full facemask. Sometimes continuous positive airway pressure (CPAP) ventilation alone may be sufficient to improve oxygenation.
Noninvasive ventilation has been studied best in patients with hypercapnic respiratory failure caused by chronic obstructive pulmonary disease (COPD) or neuromuscular weakness; however, in small series of patients with ARDS/ALI, the use of this technique may have allowed some patients to avoid intubation. This may be an especially useful approach in immunocompromised or neutropenic patients.
Patients who have a diminished level of consciousness, vomiting, upper GI bleeding, or other conditions that increase aspiration risk are not candidates for NIPPV. Other relative contraindications include hemodynamic instability, agitation, and inability to obtain good mask fit.
Mechanical Ventilation
The goals of mechanical ventilation in ARDS are to maintain oxygenation while avoiding oxygen toxicity and the complications of mechanical ventilation. Generally, this involves maintaining oxygen saturation in the range of 85-90%, with the aim of reducing the fraction of inspired oxygen (FIO2) to less than 65% within the first 24-48 hours. Achieving this aim almost always necessitates the use of moderate-to-high levels of positive end-expiratory pressure (PEEP).
Experimenal studies have shown that mechanical ventilation may promote a type of acute lung injury termed ventilator-associated lung injury. A protective ventilation strategy using low tidal volumes and limited plateau pressures improves survival when compared with conventional tidal volumes and pressures.
In an ARDS Network study, patients with ALI and ARDS were randomized to mechanical ventilation either at a tidal volume of 12 mL/kg of predicted body weight and an inspiratory pressure of 50 cm water or less or at a tidal volume of 6 mL/kg and an inspiratory pressure of 30 cm water or less; the study was stopped early after interim analysis of 861 patients demonstrated that subjects in the low-tidal-volume group had a significantly lower mortality rate (31% versus 39.8%).[34]
Whereas previous studies employing low tidal volumes allowed patients to be hypercapnic (permissive hypercapnia) and acidotic to achieve the protective ventilation goals of low tidal volume and low inspiratory airway pressure, the ARDS Network study allowed increases in respiratory rate and administration of bicarbonate to correct acidosis. This may account for the positive outcome in this study as compared with earlier studies that had failed to demonstrate a benefit.
Thus, mechanical ventilation with a tidal volume of 6 mL/kg predicted body weight is recommended, with adjustment of the tidal volume to as low as 4 mL/kg if needed to limit the inspiratory plateau pressure to 30 cm water or less. Increase the ventilator rate and administer bicarbonate as needed to maintain the pH at a near normal level (7.3).
In the ARDS Network study, patients ventilated with lower tidal volumes required higher levels of PEEP (9.4 vs 8.6 cm water) to maintain oxygen saturation at 85% or more. Some authors have speculated that the higher levels of PEEP may also have contributed to the improved survival rates. However, a subsequent ARDS Network trial of higher versus lower PEEP levels in patients with ARDS showed no benefit from higher PEEP levels in terms of either survival or duration of mechanical ventilation.[35]
Patients with severe ARDS receiving mechanical ventilation responded more favorably to early administration of a neuromuscular blocking agent (ie, cisatracurium) than to placebo. Compared with the placebo group, the cisatracurium group showed improvement in 90-day survival and increased time off the ventilator. No significant difference in ICU-acquired paresis was observed.[36]
Managing physicians should not use paralytics in all cases; rather, they should use them only in those where length of ventilation is expected to exceed a few hours. Patients should not remain ventilated for longer than it takes for the paralytics to have their effect. The duration of paralysis will depend upon the condition.[36]
A study by Jaber et al examined diaphragmatic weakness during mechanical ventilation along with the relationship between mechanical ventilation duration and diaphragmatic injury or atrophy.[37] The study determined that longer periods of mechanical ventilation were associated with significantly greater ultrastructural fiber injury, increased ubiquitinated proteins, higher expression of p65 nuclear factor-kB, greater levels of calcium-activated proteases, and decreased cross-sectional area of muscle fibers in the diaphragm. The conclusion was that weakness, injury, and atrophy can occur rapidly in the diaphragms of patients on mechanical ventilation and are significantly correlated with the duration of ventilator support.
Go to Barotrauma and Mechanical Ventilation for complete information on this topic.
Positive end-expiratory pressure and continuous positive airway pressure
ARDS is characterized by severe hypoxemia. When oxygenation cannot be maintained despite high inspired oxygen concentrations, the use of CPAP or PEEP usually promotes improved oxygenation, allowing the FIO2 to be tapered.
With PEEP, positive pressure is maintained throughout expiration, but when the patient inhales spontaneously, airway pressure decreases to below zero to trigger airflow. With CPAP, a low-resistance demand valve is used to allow positive pressure to be maintained continuously. Positive-pressure ventilation increases intrathoracic pressure and thus may decrease cardiac output and blood pressure. Because mean airway pressure is greater with CPAP than PEEP, CPAP may have a more profound effect on blood pressure.
In general, patients tolerate CPAP well, and CPAP is usually used rather than PEEP. The use of appropriate levels of CPAP is thought to improve the outcome in ARDS. By maintaining the alveoli in an expanded state throughout the respiratory cycle, CPAP may decrease shear forces that promote ventilator-associated lung injury.
The best method for finding the optimal level of CPAP in patients with ARDS is controversial. Some favor the use of just enough CPAP to allow reduction of the FIO2 below 65%.
Another approach, favored by Amato et al, is the so-called open lung approach, in which the appropriate level is determined by the construction of a static pressure volume curve.[38] This is an S-shaped curve, and the optimal level of PEEP is just above the lower inflection point. Using this approach, the average PEEP level required is 15.
However, as noted above, an ARDS Network study of higher versus lower PEEP levels in ARDS patients did not find higher PEEP levels advantageous.[35] In this study, PEEP level was determined by how much inspired oxygen was required to achieve a goal oxygen saturation of 88-95% or a target partial pressure of oxygen (PO2) of 55-80 mm Hg. The PEEP level averaged 8 in the lower PEEP group and 13 in the higher PEEP group. No difference was shown in duration of mechanical ventilation or survival to hospital discharge.
A 2010 review by Briel et al found that treatment with higher of PEEP demonstrated no advantage over treatment with lower levels in patients with ALI or ARDS; however, among patients with ARDS, higher levels were associated with improved survival.[39]
A study by Bellani et al found that in patients with ALI managed with relatively high PEEP, metabolic activity of aerated regions was associated with plateau pressure and regional tidal volume that was normalized by end-expiratory lung gas volume; no association was found between cyclic recruitment/derecruitment and increased metabolic activity.[40]
Pressure-controlled ventilation and high-frequency ventilation
If high inspiratory airway pressures are required to deliver even low tidal volumes, pressure-controlled ventilation (PCV) may be initiated. In this mode of mechanical ventilation, the physician sets the level of pressure above CPAP (delta P) and the inspiratory time (I-time) or inspiratory/expiratory (I:E) ratio. The resultant tidal volume depends on lung compliance and increases as ARDS improves. PCV may also result in improved oxygenation in some patients not doing well on volume-controlled ventilation (VCV).
If oxygenation is a problem, longer I-times, such that inspiration is longer than expiration (inverse I:E ratio ventilation) may be beneficial; ratios as high as 7:1 have been used. PCV, using lower peak pressures, may also be beneficial in patients with bronchopleural fistulae, facilitating closure of the fistula.
Evidence indicates that PCV may be beneficial in ARDS, even without the special circumstances noted. In a multicenter controlled trial comparing VCV with PCV in ARDS patients, Esteban found that PCV resulted in fewer organ system failures and lower mortality rates than VCV, despite use of the same tidal volumes and peak inspiratory pressures.[41] A larger trial is needed before a definite recommendation is made.
High-frequency ventilation (jet or oscillatory) is a ventilator mode that uses low tidal volumes and high respiratory rates. Given that distention of alveoli is known to one of the mechanisms promoting ventilator-associated lung injury, high-frequency ventilation would be expected to be beneficial in ARDS. Results of clinical trials comparing this approach with conventional ventilation in adults have generally demonstrated early improvement in oxygenation but no improvement in survival.
The largest randomized controlled trial, in which 148 adults with ARDS were randomized to conventional ventilation or high-frequency oscillatory ventilation (HFOV), found that the HFOV group had early improvement in oxygenation that did not persist beyond 24 hours.[42] The 30-day mortality in the HFOV group was 37%, compared with 52% in the conventional ventilation group, but this difference was not statistically significant. HFOV may be the most useful for patients with bronchopleural fistulae.
Partial liquid ventilation has also been tried in ARDS. A randomized controlled trial that compared it with conventional mechanical ventilation determined that partial liquid ventilation resulted in increased morbidity (pneumothoraces, hypotension, and hypoxemic episodes), and a trend toward higher mortality.[43]
Prone positioning
Some 60-75% of patients with ARDS have significantly improved oxygenation when turned from the supine to the prone position. The improvement in oxygenation is rapid and often substantial enough to allow reductions in FIO2 or level of CPAP. The prone position is safe, with appropriate precautions to secure all tubes and lines, and does not require special equipment. The improvement in oxygenation may persist after the patient is returned to the supine position and may occur on repeat trials in patients who did not respond initially.
Possible mechanisms for the improvement noted are recruitment of dependent lung zones, increased functional residual capacity (FRC), improved diaphragmatic excursion, increased cardiac output, and improved ventilation-perfusion matching.
Despite improved oxygenation with the prone position, randomized controlled trials of the prone position in ARDS have not demonstrated improved survival. In an Italian study, the survival rate to discharge from the ICU and the survival rate at 6 months were unchanged compared with patients who underwent care in the supine position, despite a significant improvement in oxygenation.[44] This study was criticized because patients were kept in the prone position for an average of only 7 hours per day.
However, a subsequent French study, in which patients were in the prone position for at least 8 hours per day, did not document a benefit from the prone position in terms of 28-day or 90-day mortality, duration of mechanical ventilation, or development of ventilator-associated pneumonia (VAP).[45]
Tracheostomy
In patients requiring prolonged mechanical ventilation, tracheostomy allows the establishment of a more stable airway, which may allow for mobilization of the patient and, in some instances, may facilitate weaning from mechanical ventilation. Tracheostomy, may be performed in the operating room or percutanseously at the bedside. Timing of the procedure should be individualized, but it is generally performed after about 2 weeks of mechanical ventilation.
Extracorporeal Membrane Oxygenation
A large multicenter trial in the 1970s demonstrated that extracorporeal membrane oxygenation (ECMO) did not improve the mortality rate in ARDS patients. A later trial using extracorporeal carbon dioxide removal along with inverse ratio ventilation also did not improve survival in ARDS.[46] However, ECMO is still used as a rescue therapy in selected cases. During the H1N1 epidemic in 2009, ECMO appeared to improve survival in patients with H1N1-associated ARDS who could not be oxygenated with conventional mechanical ventilation.[47]
Nutritional Support
Institution of nutritional support after 48-72 hours of mechanical ventilation usually is recommended. Enteral nutrition via a feeding tube is preferable to IV hyperalimentation unless it is contraindicated because of an acute abdomen, ileus, GI bleeding, or other conditions.
A low-carbohydrate high-fat enteral formula including anti-inflammatory and vasodilating components (eicosapentaenoic acid and linoleic acid) along with antioxidants has been demonstrated in some studies to improve outcome in ARDS.[48, 49] In a prospective, randomized study of ARDS patients in Brazil given an enteral formula containing antioxidants, eicosapentaenoic acid, and gamma-linoleic acid compared with a standard isocaloric formula, Pontes-Arruda demonstrated improved survival and oxygenation with the specialized diet.[49]
The ARDSNet recently completed a trial of feeding in ARDS (the EDEN-OMEGA study), in which patients were randomized to supplements containing omega-3 fatty acid and antioxidants versus placebo. This study was terminated early for futility, but the full results have not yet been published.[50]
Activity Restriction
Patients with ARDS are on bed rest. Frequent position changes should be started immediately, as should passive—and, if possible, active—range-of-motion activities of all muscle groups. Elevation of the head of the bed to a 45° angle is recommended to diminish the development of VAP.
Transfer Considerations
Once the acute phase of ARDS resolves, patients may require a prolonged period to be weaned from mechanical ventilation and to regain muscle strength lost after prolonged inactivity. This may necessitate transfer to a rehabilitation facility once the acute phase of the illness is resolved.
Transfer of the ARDS patient to a tertiary care facility may be indicated in some situations, provided that safe transport can be arranged. Transfer may be indicated if the FIO2 cannot be lowered to less than 0.65 within 48 hours.
Other patients who may potentially benefit from transfer include those who have experienced pneumothorax and have persistent air leaks, patients who cannot be weaned from mechanical ventilation, patients who have upper airway obstruction after prolonged intubation, or those with a progressive course in which an underlying cause cannot be identified.
If ARDS develops in a patient who previously has undergone organ or bone marrow transplantation, transfer to an experienced transplant center is essential for appropriate management.
Prevention
Although multiple risk factors for ARDS are known, no successful preventive measures have been identified. Careful fluid management in high-risk patients may be helpful. Because aspiration pneumonitis is a risk factor for ARDS, taking appropriate measures to prevent aspiration (eg, elevating the head of the bed and evaluating swallowing mechanics before feeding high-risk patients) may also prevent some ARDS cases.
In patients without ARDS on mechanical ventilation, the use of high tidal volumes appears to be a risk factor for the development of ARDS, and, therefore, the use of lower tidal volumes in all patients on mechanical ventilation may prevent some cases on ARDS.[51]
Consultations
Treatment of patients with ARDS requires special expertise with mechanical ventilation and management of critical illness. Accordingly, it is appropriate to consult a physician specializing in pulmonary medicine or critical care.
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