Let’s talk about ARDSnet
Acute respiratory distress syndrome or ARDS is a condition that has been most frequently seen in the MICU. The classic presentation is respiratory failure with b/l lung white out requiring intubation from severe sepsis or drowning and most recently, COVID-19 Pneumonia. However, I have increasingly seen more ARDS patients in the cardiac intensive care unit. The typical ARDS patient would be someone who is hospitalized in the CICU for a few days to weeks after suffering from a devastating STEMI or cardiogenic shock, or cardiac arrest and perhaps has fevers of unknown origin or had a large aspiration event; the patient has prolonged ventilator requirements and has failed SBT or trials of extubation and has worsening lung function with severe b/l inflammation. As an intensive care unit, we should be able to manage this but our knowledge is limited as a cardiac group with less pulmonary training (I state this more so about the advance practice provider group, fellows, and nurses as our attendings are critical care trained/intensivists). So let’s talk about ARDSnet.
ARDSnet is a research network online that provides pivotal and recent studies in order to protocolize the management of ARDS. As the ARDSnet homepage states: “ARDS, or Acute Respiratory Distress Syndrome, is an inflammatory lung condition involving both lungs that may complicate severe pneumonia (including influenza), trauma, sepsis, aspiration of gastric contents, and many other conditions. Inflammation leads to injury of lung tissue and leakage of blood and plasma into the airspaces resulting in low oxygen levels in the blood.”
This inflammation eventually leads to inactivation, decreased production, and destruction of surfactant.
There are a bunch of trials and studies that have become the foundation of how we manage ARDS as we know it today.
The first study was KARMA, a randomized control trial conducted in 1996 to 1997 that was published in JAMA 2000 titled “Ketoconazole for Early Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome.” Briefly, ketoconazole has anti-inflammatory activity and a few clinical studies have suggested that it may help prevent ARDS/ALI. N=234 with end-primary end point of unassisted breathing at discharge and number of ventilator free days. There were no statistical differences between the placebo and ketoconazole group and thus the study concluded that ketoconazole was safe to use but did not reduce mortality or duration of ventilation and did not support its use in early treatment of ARDS/ALI.
Next was ARMA. Initial ventilator management of ARDS/ALI prior to the strial was to use generous TV (10–15 ml/kg)with PEEP. This trial was conducted in 1996 and was a 2x2 design comparing 6 ml/kg TV to 12 ml/kg TV on VCV and comparing lisofylline injection (anti-inflammatory agent used to prevent type 1 diabetes) to placebo. N = 861 and stopped early because mortality was lower in the group receiving TV 6 ml/kg. 31% vs 39.8% mortality with a P=0.007. This was a pivotal trial that showed the traditional high TV approach was no good and that low TV showed lower mortality and increased ventilator-free days. This was eventually published in the NEJM in 2000 titled “Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and the Acute Respiratory Distress Syndrome.” For the lisofylline injection vs placebo portion called LARMA, it was concluded that the injection had no evidence of beneficial effects on ARDS/ALI.
Now they also tested the use of steroids in ARDS/ALI (sound familiar)? “Efficacy and Safety of Corticosteroids for Persistent ARDS” was published in the NEJM in 2006. This was a RCT double-blinded 180 patients with at least seven days of methyprednisolone vs placebo. The primary endpoint was mortality at 60 days with our important secondary endpoint of ventilator-free days and organ-failure free days (given the severe inflammation of ARDS can lead to MOSF). They included those with ARDS defined by continous ventilation and PF ratio<200.Mortality in the steroid group was 29.2% and in the placebo group 28.6%. Steroid use led to increased mortality at 60 and 180 day among patients enrolled 14 days after onset of ARDS. But steroid use led to more ventilator-free days and shock-free days during the first 28 days. Less vasopressor days and better blood pressures (surviving sepsis anyone?). It seems like the steroid group did better from reading the study but didn’t change overall prognosis. However, it seems because although the steroid group got off the ventilator sooner, they also had increased rate of return to assisted breathing. They attributed this likely due to corticosteroid complications such as neuromyopathy, which led to more critical illness. Shock was also common among those who returned to the ventilator. High dose steriod group were noted with increased secondary infections but not in the moderate dose group. This is probably why they did not recommend the use of steroids for ARDS/ALI.
This begs to question if steroid treatment should last longer and patients should have a longer steroid taper. Or perhaps with the advent and increased frequency of tracheostomy nowadays we can forgo the ventilator free days with concurrent steroid treatment. Of course, this depends on the patients desire and QOL.
Pearl for me: *procollagen peptid type 3 is a specific biomarker of post ARDS fibroproliferation. Can be sent to see if patients with high levels may be candidates for corticosteroid use to resolve lung fibroproliferation.
There are a lot more studies such as the FACCT trial which tests the use of swan catheters vs regular CVL in ALI patients. Interesting because most of our patients have swans. ALI patients with swans did not have better mortality outcomes and there were more complications in that group. Good to know. The complications included PTX, arrhythmias, local clots and bleeding.
Next, ALTA (Albuterol for the treatment of ALI). Beta-2 agonist nebulizers are not recommended because it did not statistically change the number of ventilator free days and mortality was no different.
There are a bunch more studies that are included in ARDSnet II that I won’t talk about now.
But another useful tool for me is the NIH NHLBI Mechanical Ventilation protocol included below:
Thanks for reading.
Dk
