So the steroid guideline, again, came out in May of this year, both the executive summary and the full guidelines. I was the co-chair with Jalali Anand for this particular guideline. And Dr. Bach, who was here and presented earlier, was also part of our guideline task force. I'll go very quickly on the highlights of our guidelines for use of steroids in patients with sepsis and septic shock. So the difference between the 2017 guideline that we had to the most recent guidelines is that we suggest giving steroids to adult patients with septic shock. We no longer have this qualifier where you need it to be on multiple vasopressor, maybe two pressors before you start considering steroids. No, we're saying in a patient with septic shock that is not responsive to fluids and you're starting a pressor and they need to be on a pressor, you don't need to wait hours and hours until they're on a certain dose of a pressor before you give steroids. We also strongly recommend it against using very high doses of steroids, meaning hydrocortisone greater than 400 milligrams a day for less than three days. And that was based largely on analysis of both mortality, side effects, et cetera. And as I think was mentioned earlier, for short-term ICU mortality, there was really no clear signal of mortality benefit, but there seemed to be a signal at 90 days. Longer-term mortality seemed to be associated with steroid use. What was very clear was that shock reversal was definitely faster, but there was a trade-off of hyperglycemia, hypernatremia, and maybe an increase in neuromuscular weakness, and we don't have long-term studies enough to support that. But based on the shock reversal being faster and based on some of the side effects like hypernatremia, hyperglycemia, that we can safely correct, with no increase in secondary infection, GI bleeding, psychosis, from the use of steroids, we felt that we could give at least a conditional recommendation for using steroids in patients with septic shock. Hydrocortisone, 200 milligrams a day, is what's recommended, typically in divided doses. And when we produced a guideline, we had with or without fludrocortisone being added, and that recommendation for steroid use came largely from the two largest trials, the APPROACH trial and the ADRENAL trial. The ADRENAL trial was a trial that did not show a benefit with the addition of fludrocortisone, but the APPROACH trial from France showed the benefit. So we were kind of like, when we were producing this guideline, we put a caveat of an option of with or without fludrocortisone if the patient has an enteral feeding tube and you can provide an enteral medication. Duration is variable. Most commonly, steroids are used until the shock is reversed. That could be as early as three days, sometimes up to five days. But most patients kind of on steroids and on vasopressors tend to reverse their shock, usually within a 72 to 96 day, six hour period. Fortunately, since the publication of the guidelines, some cutting edge stuff came out in critical care medicine in April, which supports in this systematic review of 95,000 patients, 19 studies, adding fludrocortisone to hydrocortisone was associated with short term survival with an increased risk of hyperglycemia. Some little problems with this is that there was significant heterogeneity among the studies that they looked at, but nevertheless, the conclusion was adding the fludrocortisone to the hydrocortisone had a benefit. Similarly, in May, in the Blue Journal, again, another systematic review of the addition of fludrocortisone also supported a reduction in all cause mortality against placebo and hydrocortisone alone. So this evidence seems to be getting stronger, at least in support of adding the fludrocortisone to hydrocortisone in these patients. Turning over to ARDS, we suggested giving steroids to patients with acute respiratory distress syndrome. In the past, we said moderate to severe and we quantified the PF ratio, we quantified the timeline. We're just saying if you're gonna consider this, consider this as early, don't wait until the patient goes into moderate or severe. If they're starting like they're gonna go very quickly from mild to moderate, you can already consider, again, the use of corticosteroids in those patients. And this was the evidence. We looked at COVID studies, we looked at non-COVID studies. We found that corticosteroid use probably reduced, albeit slightly, 28-day mortality, but you can see the confidence interval did not cross one. It didn't seem to matter what type of steroid we thought maybe methylprednisolone would be preferred, but it didn't turn out that way. The trials that we evaluated varied in type of steroid, the duration of therapy, and when they were initiated. And even when we subgroup analyzed COVID-19 patients with ARDS and non-COVID ARDS, they did not demonstrate any credible subgroup effects. What was clear in all the studies so far is that steroid use reduces time on mechanical ventilation and shortens the length of stay. Probably if they're coming off the ventilator, they're getting out of the ICU, they're getting out of the hospital, so that seemed to be strongly supported. Again, these are adult guidelines, both for fever and for the steroid guidelines. They don't apply to pediatric patients because there were no RCTs done in those patients. Duration, typically patients did better when the steroids were given for a longer period of time. The panel recognized that multiple strategies are available. These are the recommendations for early ARDS. Dexamethasone can be used. Methylprednisolone can be used. The dexamethasone dosaging was based on the VILLAR study that came out just before COVID, and then we all know from the recovery trial and from trials previously by Miduri et al that methylprednisolone can be substituted as well. But no matter what steroid you use, it really, if you're using equipotent doses, there doesn't seem to be a major difference in terms of their effects on respiratory failure and discontinuation of mechanical ventilation. Finally, for CAP, I think you heard from Dr. Bach earlier, we recommended use of steroids, gave it a strong recommendation for severe community-acquired pneumonia. However, we were not able to give a recommendation for less severe bacterial pneumonia, and the criteria for severe community-acquired pneumonia was based on three groups of trials, the ATS, IDSA criteria, CAPE-COD criteria, and using the risk severity stratification. So patients on high flow, oxygen, 50% FiO2, PF less than 300 with severe community-acquired pneumonia meets that criteria for using steroids on those patients. So just not all patients on invasive mechanical ventilation. You can have patients on high flow that can meet ARDS criteria where this might be an indication for using steroids. We found that mortality was reduced only in the groups of patients that had severe, severe bacterial community-acquired pneumonia, but not so clear-cut in those with less severe community-acquired pneumonia, so we could not issue a recommendation there. We felt that the benefits outweighed the risk of hyperglycemia, and so we recommended the use of steroids. The trade-off, again, hyperglycemia, there's slight increase in secondary infection, and the dosing regimens are here. You can use any of the steroids, hydrocortisone, methylprednisolone, dexamethasone, they've all been shown, as long as you're using the same relative doses. I think we more commonly use now, based on the Cape Cod study, I think most use the hydrocortisone regimen, 200 milligrams per day. You can use it as an IV infusion or in divided doses like we do for septic shock, and usually the treatment duration is somewhere between four or eight days depending on whether the patient is clinically improving, and then we taper it. If you're using methylprednisolone, there's a longer taper schedule based on Miduri's study, so you can use any of these steroids interchangeably as well. Following the publication of the guidelines, we also, well, what about the adverse effects? Can we accumulate all of these studies and look at all the adverse effects? So we did that and published this in April 2024, where again, we showed a little bit more conclusively that steroids do indeed, whether you're using it for sepsis, community-acquired pneumonia, or ARDS, there's definitely an association with hyperglycemia and probably with hypernatremia, but likely no effect on risk of GI bleeding or secondary infection, which is always the nagging concern with using steroids, but if you're using steroids over a shorter period of time like you do for severe CAP, or even for shock reversal in patients with septic shock, you don't really have to worry so much about long-term issues, including GI bleeding and secondary infections. So here's a quick summary. Yes to steroid use, conditional recommendation in patients with septic shock. Yes, strong recommendation against using high-dose steroids. Conditional recommendation, yes, for using steroids in adult patients with ARDS regardless of severity. And yes, strong recommendation for patients, adult patients, with severe bacterial community-acquired pneumonia, and the jury's still out on using it for less severe community-acquired pneumonia. That's all I have. Thank you.

steroid use

sepsis

shock reversal

hyperglycemia

pneumonia