Acute Respiratory Distress Syndrome

Signs, Symptoms, Predisposition, and Diagnosis of ARDS

Predisposing Factors and Mortality in ARDS

The earliest signs of ARDS are tachypnea and progressive hypoxemia (often refractory to O2) in a predisposed patient. Within 24 hours the CXR should display bilateral infiltrates. Hallmarks are 1) Predisposing condition 2) PAO2/FIO2 < 200 3) Bilateral infiltrates 4) wedge < 18 mm Hg. Wedge is only an estimate of capillary pressure, to correct it Pcap = PCWP + 0.4(PPulm.Art. – PCWP). In fact, PCWP should probably be abandoned, because in an ARDS lung a PCWP of 15 can represent a pulmonary capillary hydrostatic pressure of up to 30 mm Hg (2x estimate). Acute lung injury is like ARDS but has a PAO2/FIO2 < 300, i.e., it is not quite as severe.

Condition ARDS Incidence ARDS Mortality Non-ARDS Mortality Sepsis Syndrome 41% 69% 50% Multiple Transfusions 36% 70% 35% Gastric Aspiration 22% 48% 21% Pulmonary Contusion 22% 49% 12% Multiple Fractures 11% 49% 9% Drug Overdose 9% 35% 4%

Data from Am Rev Respir Crit Care Med 151: 293, 1995

Others include head injury, inhalation injury, shock, DIC< pancreatitis, TRALI

Diseases Which Mimic ARDS

Importantly, ARDS can be imitated by left heart failure, pneumonia, or PE

Condition Fever Bilateral Infiltrates Pleural Effusion Wedge Pressure Lung Lavage Protein ARDS Yes Yes Unlikely Normal High Left Heart Failure Possible Yes Yes High Low Pneumonia Yes Possible Possible Normal High Pulmonary Embolus Yes Unlikely Possible Normal High
To further aid in distinguishing ARDS from other etiologies, calculate plasma oncotic pressure as COP = 2.1 (ProtTotal) + 0.16 (ProtTotal2) + 0.009 (ProtTotal 3) and compare to Pcap. If Pcap more than 4 mm Hg above COP, hydrostatic pulmonary edema is likely. If Pcap more than 4 mm Hg less than COP, hydrostatic pulmonary edema is unlikely. Also, if Protedema/Protserum < 0.5, hydrostatic edema is likely, whereas if > 0.7 it is probably inflammatory (ARDS vs. pneumonia). Lastly, a BAL with proteinlavage/proteinserum > 0.7 is likely inflammatory, whereas < 0.5 is probably edema. [Clin Chest Med 6: 459, 1985]

Treatment/Management of ARDS

Low Tidal Volumes and ARDS

Patients with ARDS (PaO2/FiO2 < 300, bilateral pulmonary infiltrates on a CXR, no clinical evidence of left atrial hypertension or if measured a wedge < 18 mm Hg, excluding all patients with elevated ICP, neuromuscular, sickle cell, or severe chronic respiratory disease, obesity > 1 kg/cm height, or burns > 30% of BSA) given AC ventilation at either 12 ml/kg (average plateau pressure 33 cm H2O) or 6 ml/kg, subsequently reduced stepwise by 1 ml/kg of PBW if necessary to maintain Pplateau at a level of no more than 30 cm of water, if Pplateau dropped below 25 cm of water, tidal volume was increased in steps of 1 ml/kg of PBW until the Pplateau was at least 25 cm of water or the TV was 6 ml/kg of PBW. (average plateau pressure 25 cm H2O). Results showed improvements in death before discharge (39.8  31.0%, p = 0.007), % of patients breathing without the vent at 28 days (55.0  65.7%, p < 0.001), number of ventilator-free days (10  12, p 0.007), and days free of non-pulmonary organ failure (12  15,p = 0.006, see [NEJM 342: 1301, 2000])

Prone Positioning and ARDS

According to Miller, ‘Prone positioning is fraught with difficulty and can result in accidental extubation, dislodgement of the line or chest tube, and patient injury, but it can lead to higher functional residual capacity, better drainage of secretions, and improved oxygenation. Gattinoni and colleagues performed a multicenter, prospective randomized trial in patients with ARDS to compare supine positioning with prone positioning for 6 or more hours per day for 10 days. Three hundred four patients were enrolled. Oxygenation was improved in the prone group, but again, mortality did not differ between the two groups. Although there may be specific patients who can benefit from this technique, routine use of prone positioning is not supported by the data.

The follow up Prone-Supine II Study Group (multicenter, unblinded, randomized controlled trial of 342 adults with ARDS) showed higher complications and no difference in mortality in the prone group [Taccone P et al. JAMA 302: 1977, 2009]

Advantages of Prone Positioning (from Miller p. 2857-8)

  • Higher FRC
  • Better drainage of secretions
  • Improved oxygenation

Miller, RD et al. Miller’s Anesthesia, 7th ed, Churchill Livingstone: p 2857-8. 2009
Taccone P et al. Prone positioning in patients with moderate and severe acute respiratory distress syndrome: a randomized controlled trial. JAMA 302: 1977, 2009

Steroids and ARDS

There are three major trials studying steroids in ARDS.

JAMA 8: 280, 1998

In the first, a randomized, double-blind, placebo-controlled trial of 24 patients with severe ARDS who had failed to improve by the seventh day of respiratory failure, given either methylprednisolone (2 mg/kg/day for 32 days) or placebo. Four patients whose LIS failed to improve by at least 1 point after 10 days of treatment were blindly crossed over to the alternative treatment. The methylprednisolone group showed reduced LIS (P<0.001), improved ratio of PaO2 to FIO2 (P<.001); decreased MODS score (P<.001), increased successful extubation (7 vs 0; P=.05), and improved mortality (0% vs 62%, P=.002) hospital-associated mortality (P=.03). The rate of infections was similar in both groups [JAMA 8: 280, 1998].

NEJM 20: 354, 2006

In the second randomized double blind study, 180 patients with >= 7 days of ARDS were given methylpredinosolone (2 mg/kg loading dose and then 2 mg/kg/day tapering after 14 days) vs. placebo. At 60 and 180 days mortality was equal. Subgroup analysis showed 60 and 180 day mortality was worse in steroid-treated patients who were enrolled after 14 or more days. Methylprednisolone did increase the number of ventilator-free and shock-free days during the first 28 days and did not increase the rate of infectious complications but was associated with a higher rate of neuromuscular weakness [NEJM 20: 354, 2006].

Chest 131: 954, 2007

In the last, a randomized, double-blind, placebo-controlled multicenter trial of 91 patients with severe early ARDS (<= 72 h, 66% with sepsis) randomized to methylprednisolone (1 mg/kg/d for up to 28 days) vs placebo. By in intention-to-treat analysis, twice the proportion of treated patients achieving a 1-point reduction in LIS (69.8% vs 35.7%; p = 0.002) and breathing without assistance (53.9% vs 25.0%; p = 0.01). Treated patients by day 7 had lower LIS and multiple organ dysfunction syndrome scores. Treatment was associated with a reduction in the duration of mechanical ventilation (p = 0.002), ICU stay (p = 0.007), and ICU mortality (20.6% vs 42.9%; p = 0.03). Treated patients had a lower rate of infections (p = 0.0002), and infection surveillance identified 56% of nosocomial infections in patients without fever. [Chest 131: 954, 2007]

Late Effects of steroids: Chest 105S: 127S, 1994

Appears that steroids may be useless in the first 7 days [NEJM 317: 1565, 1987; Chest 92: 1032, 1987] but effective after day 7, the fibroproliferative phase. [Chest 105S: 127S, 1994]

Another Study: Chest 128: 129S, 2005

Methylprednisolone (MP) loading 1 mg/kg IV followed by tapering dose of steroids over 28 days (1 mg/kg/day for 2 weeks, 0.5 mg/kg/day for 1 week, 0.25 mg/kg/day for days 22-25, and 0.125 mg/kg/day for days 26-28). Patients failing to improve lung injury score (LIS) by day 7-9 received open label MP (2mg/kg/day) treatment as previously reported [JAMA 1998; 280: 159]. 79 patients eligible for analysis (55 treated and 24 control) on study day 7. By day 7 almost twice the proportion of treated patients achieving a1-point reduction in LIS (69.8% vs. 37.5%; p = 0.002) and about 50% more treated patients breathing without assistance (53.9% vs. 25.0%; p = 0.01). Treated patients had significantly lower LIS and MODS score. Treatment was associated with a reduction in the duration of MV, ICU stay, and ICU mortality. The treatment group developed more frequently hyperglycemia (52.5% vs. 28.6%; p = 0.06), and polyneuropathy (2 vs. 0). Among treated patients, infection surveillance identified most nosocomial infections (65%) in the absence of fever. [Chest 128: 129S, 2005]


549 patients with ARDS were randomized to receive mechanical ventilation with either lower or higher PEEP levels (8.3±3.2 cm vs. 13.2±3.5). There were no differences in death rates before hospital discharge, number of days breathing off the vent, ICU days, or barotrauma [NEJM 351: 327, 2004]. Also note that PEEP is only effective when it does not adversely effect cardiac output, which is not always the case.

Oxygen, carbon dioxide, cardiac output, and ARDS

Hyperoxia may be bad (free radicals) so increase respiration by increasing PEEP and inspiratory time rather than FIO2 (which you want < 0.60). Check the following parameters: if VO2 < 100 mL/min/m2, venous lactate > 4 mM, or gastric pH < 7.32, oxygenation is likely insufficient. Note that in non-neurosurgical patients, permissive hypercapnia may be an acceptable consequence of low tidal volumes – in fact, data suggest that pCO2 of 60-70 mm Hg and pH levels of 7.2 – 7.25 are safe in most non-neurosurgical patients [Crit Care Med 22: 1568, 1994], with some individual reports suggesting that levels of 375 and 6.6 are acceptable as long as oxygenation is adequate. [Chest 102: 1742, 1992] Cardiac output (CI should be > 3) is essential in these patients, especially on PEEP. First look at filling pressures and give volume if needed. If not, consider intervening with dobutamine if necessary [J Intensive Care Med 2: 190, 1987]. Do not give dopamine as it constricts pulmonary veins, and avoid vasodilators as a means to increase CO as they exacerbate gas exchange abnormalities.

Note: only 40% of deaths in ARDS are due to respiratory failure – the majority are due to multiple organ failure. [NEJM 353: 1685, 2005]

Muscle Relaxation in ARDS

While neuromuscular blockade is often avoided in the ICU setting for fear of inducting critical illness myopathy, a recent randomized controlled trial comparing cisatracurium-based paralysis to no paralysis in patients with severe ARDS showed a significant decrease in overall mortality rates with no increase in myopathy [2) of less than 150, with a positive end-expiratory pressure of 5 cm or more of water and a tidal volume of 6 to 8 ml per kilogram of predicted body weight. The primary outcome was the proportion of patients who died either before hospital discharge or within 90 days after study enrollment (i.e., the 90-day in-hospital mortality rate), adjusted for predefined covariates and baseline differences between groups with the use of a Cox model. RESULTS: The hazard ratio for death at 90 days in the cisatracurium group, as compared with the placebo group, was 0.68 (95% confidence interval [CI], 0.48 to 0.98; P=0.04), after adjustment for both the baseline PaO2:FIO2 and plateau pressure and the Simplified Acute Physiology II score. The crude 90-day mortality was 31.6% (95% CI, 25.2 to 38.8) in the cisatracurium group and 40.7% (95% CI, 33.5 to 48.4) in the placebo group (P=0.08). Mortality at 28 days was 23.7% (95% CI, 18.1 to 30.5) with cisatracurium and 33.3% (95% CI, 26.5 to 40.9) with placebo (P=0.05). The rate of ICU-acquired paresis did not differ significantly between the two groups. CONCLUSIONS: In patients with severe ARDS, early administration of a neuromuscular blocking agent improved the adjusted 90-day survival and increased the time off the ventilator without increasing muscle weakness. (Funded by Assistance Publique-Hôpitaux de Marseille and the Programme Hospitalier de Recherche Clinique Régional 2004-26 of the French Ministry of Health; number, NCT00299650.)” style=”color:green”>Papazian L et al. N Engl J Med 363: 1107, 2010]

Intraoperative Mechanical Ventilation and ARDS

Most of the data on low tidal volumes is based on critically ill patients in the ICU. However, a study from Mayo Clinic suggested that large tidal volumes on initiation of mechanical ventilation (including post-operative patients) are related (positive correlation) to the risk of post-operative ALI [Gajic O, et al. Crit Care Med 32: 1817, 2004]. This hypothesis is further supported by Lellouche et al.’s retrospective analysis of tidal volumes on presentation to the ICU following cardiac surgery, which showed that tidal volumes > 10 cc/kg were a risk factor for prolonged ICU stay and organ failure [Lellouche et al. Anesthesiology 116: 1072, 2012]

Neurosurgical Considerations in ARDS

  • The incidence of ALI/ARDS in head-injury patients is 20-50% [Neurosurgery 40: 707, 1997; J Trauma 55: 106, 2003]
  • Retrospective study of 188 brain injury (study to assess ICP vs CBP goals) patients showed that those treated by CBF goals had a 5x increase in ARDS incidence compared to those treated with ICP goals. Epinephrine and above average dopamine doses caused 5 and 10x increase, respectively [J Neurosurg 95: 560, 2001]
  • The ARDS net trial excluded head injury patients (because of potential increases in PaCO2).

Note, however, that the mean PaCO2 in ARDS and ALVEOLI (ARDS II) trials was 40 and 41 mm Hg, respectively.

  • Techniques for lowering PaCO2 while still using low tidal volumes (i.e., in difficult cases)
  1. Minimize deadspace in the ventilator circuit
  2. Verify that patient-ventilator synchrony is adequate
  3. Check the ETT and circuit for obstruction
  4. Minimize compliance (ex. drain pleural effusions and ascites)
  • Further considerations:
    • If ARDS does not truly exist (i.e., prophylactic 6 cc/kg), let the tidal volume rise
    • If ARDS does exist but ICP is normal, consider letting the PaCO2 rise gently (45-55)
    • If ARDS and elevated ICP coexist, sacrifice the lungs for the brain