Steroids and ARDS

            Acute Respiratory Distress Syndrome is frequently encountered in the ICU setting and often carries a high mortality rate.  One proposed therapy for this condition is prolonged use of methylprednisolone.  A randomized controlled study by Meduri et al published in 1998 tested one such protocol and found success.  The protocol in this paper started at day 7 of ventilation and involved a Lung injury Score (LIS) of >2.5.  The LIS is calculated by considering 4 factors: the level of positive-end-expiratory pressure of the ventilator, the ratio of arterial pressure of oxygen to the fraction of inspired oxygen, the static lung compliance, and the degree of infiltration on chest radiograph.  The protocol for steroid administration was the following:

• Loading dose of 2mg/kg
• 2mg/kg /day for treatment days 1-14
• 1mg/kg/day for treatment days 15-21
• 0.5mg/kg/day for treatment days 22-28
• 0.25mg/kg day for treatment days 29-30
• 0.125mg/kg day for treatment days 31-32

If patient was extubated before day 14, then treatment progressed immediately to the treatment-day-15 dosage and continued.  A control group given placebo was also established.  The members of the control group were evaluated at treatment day 10, and if they had not improved in LIS, they were started on an unblended dose of methylprednisolone.

With this protocol, Meduri found all members of the treatment group improved their LIS by treatment day 10, compared to only a few members of the control group.  The methylprednisolone group was found to have a statistically significant survival benefit over the control group.  Of the 4 control group member who were crossed over, 2 died.  This brings up an important issue of when to initiate treatment. 

Two other studies tested the timing of methylprednisolone treatment: “Efficacy and Safety of Cortiosteroids for Persistent Acute Respiratory Distress Syndrome” in 2006 and “Methylprednisolone Infusion in Early Severe ARDS” in 2007.  Both studies were randomized controlled trials.  The former study was a looked at patients 7-28 days after the onset of ARDS and used a similar dosing schedule as the 1998 Meduri study.  There was also an established control group that received placebo.  Patients were followed until death, 48 hours of breathing without a ventilator, or 180 days, whichever came first.  This study found no difference in mortality at day 60 or 180.  They did find an increase in ventilator free days in the steroid group.  Another significant finding was that mortality actually increased in the steroid group if they started treatment 14 days or more after diagnosis of ARDS.  Conveniently, the latter study was published the following year studying early treatment of ARDS with steroids.

“Methylprednisolone Infusion in Early Severe ARDS” used a similar dosing schedule as the original Meduri paper, but started with a loading dose of 1mg/kg and continued with 1mg/kg/day for 14 days, then 0.5mg/kg/day for 7 days, then tapering for another 7 days.  This study also compared the steroid group to a control group who received placebo and had a cutoff for crossing over control patients to the steroid group.  Unlike the other studies, this one did not measure success by decreased mortality.  The measure of success was 1-point reduction in LIS or successful extubation by day 7.  The findings of this study showed a decreased mortality, decreased LIS, and decreased inflammatory factors. 

When considering these three studies, there are some drawbacks.  These are all small studies, with the largest having only 180 participants.  In addition, many of the control patients were crossed over to receive steroids.  This means that there never was a true control group for statistical analysis.  However, the cross over groups did teach us the limits of corticosteroids and the downside to treating late. 

Corticosteroid treatment in ARDS is still a heavily debated concept.  Studies contradict each other in regards to mortality benefits.  As a practitioner considering corticosteroids for a patient suffering from ARDS, it would be best to try the treatment earlier in the course of the disease.  Treating with steroids 14 days after the diagnosis will do more harm to the patient then good.  In the search for new ways to treat patients, practitioners must above all else ensure to do no harm.

 

submitted by: Jeremy Strohmayer, M4