Introduction
Acute respiratory distress syndrome (ARDS) is a common phenomenon encountered by anesthesiologists in the operating room and intensive care unit (ICU) setting. It is also a feared complication of aspiration of gastric contents. ARDS is a syndrome of pathologic changes, caused by a variety of toxic and infectious agents that evolve over time from endothelial injury and alveolar consolidation to fibroblast proliferation and collagen deposition. In 1994, the American–European Consensus Conference on ARDS (AECC) defined ARDS to include bilateral infiltrates on a chest radiograph consistent with pulmonary edema; PaO 2 /FiO 2 ratio of less than 200 mm Hg (PaO 2 /FiO 2 ratio less than 300 mm Hg defines acute lung injury [ALI]); and a pulmonary artery occlusion pressure less than or equal to 18 mm Hg, or no evidence of left atrial hypertension. Many mediators have been implicated in its pathophysiology, including complement, cytokines, oxygen radicals, arachidonic acid products, nitric oxide, and proteases. Multiple insults incite the syndrome. Direct causes are those that directly injure the lungs such as aspiration, pneumonia, pulmonary contusion, thermal inhalation, amniotic fluid embolism, and particle inhalation. Indirect causes injure the lungs via mediator release and include pancreatitis, sepsis, and bacteremia. The presence of multiple insults increases the risk of ARDS.
The true incidence and mortality rates of ARDS remain somewhat unclear because many studies completed before the AECC did not use a standard definition. A study at Harborview Medical Center in Seattle, Washington reported an incidence of ARDS of 12.6/100,000 per year and an incidence of 18.9/100,000 per year for ALI. Recent work at the Mayo Clinic demonstrated that the incidence decreased over an 8-year period (2001-2008) from 82.4 to 38.9 per 100,000 person years, despite a higher severity of acute illness, a greater number of comorbidities, and an increased prevalence of major predisposing conditions for ARDS. Factors cited included heightened awareness of the adverse effects of high-tidal volume ventilation, implementation of transfusion protocols, and the addition of 24-hour ICU physician coverage. The hospital mortality rate has been reported to be between 40% and 60% in most studies but has decreased over the past three decades. An older age, higher Acute Physiology and Chronic Health Evaluation (APACHE) score, transfusion of blood cells, and the use of steroids before the development of ARDS predict a higher mortality rate.
Options/Therapies
Therapeutic interventions have been either directed at a specific phase of the syndrome or are more general and supportive in nature. Most deaths associated with ARDS are due to sepsis, rarely from the inability to provide adequate ventilatory support. Here we will discuss the evidence supporting or dismissing certain ventilatory strategies including low lung volumes, positioning, and oxygenation; antiinflammatory therapies such as corticosteroid administration; hemodynamic management; and other supportive techniques.
Evidence for Lower Tidal Volume Ventilation in Acute Respiratory Distress Syndrome
Traditional ventilatory strategy in ARDS included the use of tidal volumes in the 10- to 15-mL/kg range in an effort to normalize PaCO 2 and pH. This mode of ventilation has been implicated as contributing to additional lung injury and multisystem organ failure. The repetitive opening and closing of recruitable alveoli with traditional ventilation may alter endothelial permeability, increase edema, and release inflammatory mediators that may contribute to extrapulmonary organ failure and a worsened outcome.
Amato and colleagues randomly assigned 53 patients between December 1990 and July 1995 with ARDS to either a conventional or protective mechanical ventilation strategy. The mortality rate at 28 days was 38% in the protective strategy group and 71% in the conventional mechanical ventilation group. Amato and colleagues also found a lower incidence of barotrauma in the protective ventilation group. The rate of survival to hospital discharge was not different between the groups. The National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Clinical Trials Network (ARDSNet) studied patients at 10 university centers between 1996 and 1999. A total of 861 patients were enrolled and equally randomly assigned to either traditional (initial tidal volume 12 mL/kg ideal body weight [IBW]) or low tidal volume ventilation (6 mL/kg tidal volume). The mortality rate at 28 days was reduced from 40% to 30%, the death rate before hospital discharge was reduced, ventilator-free days were higher, and the number of days without failure of nonpulmonary organs or systems was increased. Interleukin-6 levels were lower, possibly indicating less lung inflammation. Kallet and colleagues applied the ARDSNet protocol to 292 patients with ALI or ARDS and found an overall mortality rate of 32% when compared with historical control subjects (51%). Work by Determan and colleagues demonstrated that the implementation of lower tidal volume in patients without ARDS results in lower release of inflammatory mediators and a lower incidence of ALI.
The benefits of a lower tidal volume strategy in patients with ALI extend beyond improved survival rates and reduction in multisystem organ failure. Cooke and colleagues suggest cost effectiveness and a savings of $22,566 per life saved, despite an early investment of $9482 to assure adherence.
Permissive hypercapnia is the elevation of PaCO 2 to levels above normal in the setting of tidal volume limitation. It is a consequence of ventilation management strategies that permit lower minute volumes in an attempt to reduce ventilator-induced lung injury and generally appears well-tolerated. Additional work is needed to determine whether permissive hypercapnia is detrimental or perhaps even beneficial.
The ARDSNet compared high levels of positive end expiratory pressure (PEEP) to lower levels in patients with early ARDS while maintaining a plateau pressure less than 30 mm Hg in both groups. The hypothesis of the study was that higher levels of PEEP would improve oxygenation and decrease ventilator-induced lung injury. No benefit was noted in terms of overall mortality, ventilator-free days, ICU-free days, or organ-failure free days. Meade and colleagues studied higher levels of PEEP and found a trend toward a lower mortality rate with higher levels of PEEP, but this did not reach statistical significance. The conclusion further supported the finding that ventilation with lower tidal volumes and inspiratory pressures improved outcomes and that increasing PEEP levels further added little benefit.
Overall, current evidence supports ventilation strategies that include lower tidal volumes (approximately 6 mL/kg IBW), lower plateau airway pressures (less than 30 cm H 2 O), higher levels of PEEP to maintain alveolar recruitment, even at the expense of elevated PaCO 2 levels, and decreased pH. Increasing PEEP beyond the recommended levels does not appear to improve outcome ( Table 28-1 ).
| Parameter | Study (Year) | Type | Results | Outcomes |
|---|---|---|---|---|
| Extracorporeal membrane oxygenation (ECMO) | Zapol (1979) | Randomized | ECMO can support respiratory gas exchange | No difference in survival |
| High-frequency jet ventilation (HFJV) | Carlon (1983) | Randomized | Oxygenation, ventilation maintained at lower peak pressure and tidal volume with HFJV | No difference in survival of intensive care unit (ICU) stay |
| ECMO | Morris (1994) | Randomized | Survival similar in both groups | Extracorporeal support not recommended in acute respiratory distress syndrome (ARDS) |
| High-frequency oscillatory ventilation (HFOV) | Fort (1997) | Prospective, clinical | Improvement in PaO 2 /FiO 2 ratio; no change in cardiac output, O 2 delivery | HFOV is safe and effective; additional studies needed |
| Protective ventilation versus conventional ventilation | Amato (1998) | Randomized | 28-day mortality 38% (protective) versus 71% (conventional); less barotrauma | No difference in survival to discharge |
| Inhaled nitric oxide (iNO) | Dellinger (1998) | Randomized, double-blind, placebo-controlled | Improvement in oxygenation after 4 hr and at 4 days | No improvement in mortality rate |
| iNO | Michael (1998) | Randomized | PaO 2 /FiO 2 improved at 1 hr, 12 hr, 24 hr | Benefits do not persist; no survival benefit |
| iNO | Troncy (1998) | Randomized | Oxygenation improved in first 24 hr | No benefit after 24 hr; similar mortality |
| Lower tidal volume versus traditional tidal volume | ARDS Network (2000) | Randomized | 28-day mortality 30%; higher ventilator free days, lower interleukin-6; death before hospital discharge reduced | Mortality reduced, but long-term benefits need to be studied |
| Continuous positive airway pressure (CPAP) | Declaux (2000) | Randomized, concealed, unblinded | Subjective response to CPAP greater than standard O 2 | No difference in intubation rate, mortality, ICU stay |
| Prone position | Gattinoni (2001) | Randomized | Increased PaO 2 /FiO 2 ; similar complication rate | No improvement in survival |
| Recruitment maneuvers | Oczenski (2004) | Randomized | Recruitment maneuvers improved PaO 2 /FiO 2 ratio | Benefits of recruitment did not persist beyond 30 min |
| High versus lower positive end expiratory pressure (PEEP) | Brower (2004) | Randomized | PaO 2 /FiO 2 was higher in the “high PEEP” group | No significant difference in mortality rate, ventilator-free days, or organ failure–free days |
| Lower tidal volume ventilation | Kallet (2005) | Retrospective, uncontrolled | Mortality rate lower in ARDS patients subject to ARDSNet protocol (32% versus 51%) | Adoption of ARDSNet protocol for acute lung injury/ARDS reduced mortality compared with historical controls |
| Lung recruitment | Gattinoni (2007) | Observational study | Percentage of recruitable lung varied among patients. On average, 24% of the lung could not be recruited. Patients with a lower respirator-system compliance, higher PaCO 2 , and lower PaO 2 :FiO 2 at the beginning demonstrated more recruitability | This observational trial did not address outcome |
| iNO | Angus (2006) | Randomized | Hospital costs, length of stay, were similar in the iNO group | No difference in survival at 1 yr |
| iNO | Adhikari (2007) | Meta-analysis | iNO may increase oxygenation until up to 4 days | No overall mortality benefit with iNO |
| Higher PEEP levels | Meade (2008) | Randomized controlled trial | Lower incidence of hypoxemia; lower use of rescue therapies | No difference in overall mortality |
| ECMO | Peek (2009) | Multicenter randomized controlled | Higher survival rate to 6 mo in ECMO patients (63% versus 47%), higher quality of life, less disability | Improved survival rate with ECMO at specialized centers |
Evidence for Additional Respiratory Strategies in Acute Respiratory Distress Syndrome
Multiple strategies have been suggested as adjuvants to traditional ventilation, including prone positioning, inhaled nitric oxide, extracorporeal membrane oxygenation (ECMO), recruitment maneuvers, and noninvasive positive pressure ventilation (NIPPV).
Prone and vertical positioning often improves oxygenation. The improvement with prone positioning is believed to be due to a more uniform distribution of tidal volume and an improvement in ventilation–perfusion matching. The issue is whether a temporary improvement in oxygenation from prone positioning improves overall outcome. Gattinoni and colleagues randomly assigned 304 patients with acute respiratory failure to either intermittent prone positioning or continual supine positioning. The PaO 2 measured each morning was higher in the prone position patients, but no survival benefit was observed at 10 days, at ICU discharge, or after 6 months’ follow-up. Although their study indicated that prone positioning can be done safely, the authors cautioned that routine use of the prone position in patients with acute respiratory failure was not justified. Prone positioning risks include facial edema, accidental extubation, and displacement of catheters.
Vertical positioning involves raising the head 45 degrees and lowering the legs by 45 degrees. The PaO 2 level increases significantly in a high number of patients and is likely due to a time-dependent increase in lung volume, suggestive of alveolar recruitment.
Inhaled nitric oxide (iNO) has been suggested as an adjunctive therapy for ARDS because of its ability to improve the intrapulmonary right-to-left shunting characteristic of ARDS and decrease pulmonary artery pressure. Multiple trials of iNO have been performed in patients with ARDS; most show a transient improvement in PaO 2 level without any outcome benefit.
ECMO accompanied by a limited ventilation strategy has been reported as a possible therapeutic modality in severe ARDS. Zapol and colleagues randomly assigned 90 patients to either conventional ventilation or partial venoarterial bypass. They reported no survival benefit but did document that ECMO could support respiratory gas exchange in patients with severe respiratory failure. An uncontrolled trial by Gattinoni and colleagues reported improved survival rates in those patients receiving ECMO. A subsequent randomized trial performed by Morris and colleagues, however, failed to show any benefit. Peek et al performed an efficacy and economic assessment of ECMO versus conventional ventilation. Patients with severe respiratory failure treated with ECMO at a specialized center had a higher survival rate and quality of life compared with conventional but generally low tidal-volume ventilation (4 to 8 mL/kg body weight). ECMO is complicated, labor intensive, not widely available, and of questionable benefit. Its routine use cannot be justified in ARDS, but highly select patients able to be treated at centers skilled in ECMO might be candidates. The results of a large randomized clinical trial may finally resolve this issue.
NIPPV has many benefits compared with traditional intubation for the management of respiratory insufficiency. Benefits include a lower incidence of nosocomial pneumonia, lower intubation rates, less sinusitis, and easier communication with the patient. It is also an alternative for patients who refuse intubation. Disadvantages include increased nursing time, poor airway protection, inability to deliver high levels of PEEP, and difficulty with implementation in the combative or delirious patient. Declaux and colleagues randomly assigned 123 patients (102 with ALI and 21 with cardiac disease) with acute hypoxemic respiratory failure to either continuous positive airway pressure (CPAP) or standard oxygen therapy. They found that subjective responses to treatment were greater with CPAP, but there was no reduction in intubation rate, ICU length of stay, or hospital mortality. Antonelli and colleagues studied NIPPV in patients with ARDS and found that early implementation may avoid intubation in up to 54% of the patients. The trial was more likely to fail and patients were more likely to require intubation if they had a higher Simplified Acute Physiology Score (SAPS) and could not improve their PaO 2 /FiO 2 ratio within an hour. Because ARDS is rarely a short-term problem and rarely a single organ abnormality, it is difficult to recommend NIPPV as a first step in all patients with ARDS, but it may be a viable option in select patients or when intubation is not desirable.
High-frequency oscillatory ventilation (HFOV) has been suggested as a possible management strategy in ARDS. The advantages of HFOV are lower tidal volumes and higher mean airway pressure for a given peak pressure, minimizing the risk of overdistention and maintaining end-expiratory lung volume and alveolar recruitment. HFOV has been reported to improve the clinical outcome in premature infants with respiratory distress syndrome compared with conventional ventilation. In adult patients, Carlon and colleagues randomly assigned 309 patients to either volume-cycled ventilation (VCV) or high-frequency jet ventilation (HFJV). They found that VCV provided a slightly improved PaO 2 level at equivalent PEEP, but with HFJV, oxygenation and ventilation were maintained with lower peak inspiratory pressures and smaller tidal volumes. There was no improvement in the overall survival rate or ICU length of stay. Fort and colleagues performed a prospective clinical study in 1997 on 17 patients with ARDS. They reported that 13 of 17 had an improvement in their PaO 2 /FiO 2 ratio, without decrements in blood pressure, cardiac output, or oxygen delivery. A large randomized controlled trial is needed to assess the benefits of HFOV.
Lung collapse is a major contributing factor to the hypoxemia of ALI and ARDS. The repeated cyclic opening and closing of individual alveoli contribute to ventilator-associated lung injury. Recruitment maneuvers involve the application of high levels of PEEP and have been demonstrated in early lung injury and ARDS to reverse hypoxemia. The ability to recruit alveoli has been demonstrated in ARDS caused by both primary pulmonary and secondary pulmonary causes. The percentage of lung tissue that can be “recruited” varies among individual patients but may sometimes actually be greater in those with more severe lung injury. Unfortunately these maneuvers generally do not result in a sustained improvement in oxygenation. Complications associated with recruitment may include barotrauma and hemodynamic compromise. No study has yet effectively demonstrated long-term benefits attributed to a particular recruitment strategy ( Table 28-2 ).
| Parameter | Study (Year) | Type | Results | Outcomes |
|---|---|---|---|---|
| Prostaglandin E 1 (PGE 1 ) | Bone (1989) | Randomized, double blind | PGE 1 increased heart rate, stroke volume, and cardiac output | PGE 1 did not increase survival rate |
| Corticosteroids | Meduri (1991) | Prospective clinical | Improvement in lung injury score and in PaO 2 /FiO 2 | Larger randomized controlled trial needed |
| Corticosteroids | Meduri (1994) | Prospective clinical | Improved lung injury score, decreased positive end expiratory pressure, improved chest radiograph score | Larger randomized controlled trial needed |
| Aerosolized surfactant | Anzueto (1996) | Randomized, placebo-controlled | No improvement: oxygenation, duration of mechanical ventilation, or survival | Aerosolized surfactant not beneficial in acute respiratory distress syndrome (ARDS) |
| Corticosteroids | Meduri (1998) | Randomized, double-blind, placebo-controlled | Lung injury score improved, PaO 2 /FiO 2 improved, Multiple Organ Dysfunction score improved; mortality: 12% versus 62% (control) | Survival rate improved with methylprednisolone; ARDSNet performing larger trial |
| Ketoconazole | ARDS Network (2000) | Randomized, placebo-controlled | No differences in organ failure–free days, adverse events, or pulmonary function | Ketoconazole did not reduce mortality rate or improve outcome |
| Lisophylline | ARDS Network (2002) | Randomized, double-blind, placebo-controlled | No difference in organ failure, ventilator-free days, or infections | Lisophylline did not improve mortality rate |
| Corticosteroids | ARDS Network (2006) | Randomized | Mortality: 28.6% in placebo group, 29.2% in treated group; higher number of ventilator and shock free days in treated group | No improvement in overall mortality; possibly higher mortality in patients who had steroids started later |
| Corticosteroids | Meduri (2007) | Randomized, controlled | Mortality reduced in treated patients (20.6% versus 42.9%); duration of mechanical ventilation and infections reduced | Mortality reduced |
Evidence for Pharmacologic Strategies in Acute Respiratory Distress Syndrome
The pharmacologic interventions that have been tested in ARDS generally are directed at blocking the inflammatory mediators released after the inciting event has occurred. Interventions have included cytokine blockers, monoclonal antibodies against endotoxins or interleukins, antioxidants, activated protein C, nonsteroidal antiinflammatory drugs, and prostanoids.
Although many of these interventions have shown benefit in initial trials and some animal studies, few benefits have been realized in human trials. Studies of prostaglandin E 1, procysteine, lisophylline, and ketoconazole have not shown a survival benefit.
Reduced surfactant production and function leads to increased surface tension, alveolar collapse, and decreased parenchyma compliance. Airway pressures needed to open these alveoli are exceedingly high. Anzueto and colleagues studied the efficacy of artificial aerosolized surfactant in ARDS patients. They found no improvement in oxygenation, ventilation, or mortality. Work continues on improved techniques of surfactant administration; however, it is unclear whether its pulmonary effects would be sufficient to alter clinical outcome (see Table 28-2 ).
Evidence for Hemodynamic Manipulation
The goals of hemodynamic management in ARDS are still an area of controversy. The ARDSNet has addressed the benefits of pulmonary versus central venous catheters and “conservative” versus “liberal” fluid management strategies in its Fluid and Catheter Treatment Trial (FACTT).
The Pulmonary Artery Catheter Consensus Conference in 1997 noted that there was inadequate evidence from existing clinical trials and case series to definitively determine benefit or harm from pulmonary artery catheter (PAC) use in patients with respiratory failure. The benefits of PACs were evaluated in 100 patients with ALI through the ARDSNet. Compared with patients managed with a central venous catheter no difference in lung or renal function, incidence of hypotension, ventilator settings, dialysis rate, or use of vasopressors was noted. The survival rate was not improved at 60 days. The incidence of complications related to catheterization was higher in the PAC group, particularly with regard to ventricular and atrial arrhythmias. The routine use of a PAC for management of patients with ARDS to improve organ function and survival rates cannot be recommended.
It is clear that increased permeability is responsible for the accumulation of alveolar fluid in ARDS. This accumulation occurs at lower pulmonary capillary wedge pressures than normal. It has been argued that diuresis and fluid restriction may benefit the ARDS patient by limiting or preventing edema. Mitchell and colleagues studied patients with ARDS who had pulmonary artery catheters in place. Those with lower extravascular lung water had shorter periods of mechanical ventilation and shorter ICU stays, but the mortality rate was not different. It is unclear, however, whether overly aggressive fluid restriction may worsen extrapulmonary organ failure. The FACTT trial compared liberal versus conservative fluid management strategies. Patients randomly assigned to the conservative arm of the clinical trial received nearly 7 L less fluid in the first 7 days of the study. Benefits were noted in oxygenation, lung injury score, and ventilator-free days without an increase in organ failure or need for dialysis. No difference was noted in the 60-day mortality rate. Accordingly, current evidence suggests that clinicians observe a more conservative management strategy for patients with ARDS ( Table 28-3 ).
Related posts:
Is a Preoperative Screening Clinic Cost-Effective?
Which Patient Should Have a Preoperative Cardiac Evaluation (Stress Test)?
What Is the Optimal Airway Management in Patients Undergoing Gastrointestinal Endoscopy?
Does the Choice of Fluid Matter in Major Surgery?
Are There Special Techniques in Obese Patients?
Is Propofol Safe If Given by Nonanesthesia Providers?
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
