Corticosteroids: What is their place in pneumonia and sepsis?

Two experts drew on both personal experience and extant literature in the debate “Steroids for Pneumonia and Sepsis ... Do You Believe?” on Tuesday.

Daniel Dressler, MD, MSC, SFHM, of Emory University, Atlanta, and Daniel J. Brotman, MD, SFHM, director of the hospitalist program at Johns Hopkins Hospital, Baltimore, used a series of case studies to illustrate the conundrum. Despite their “pro” and “con” stances, though, both agreed in the end: First, do no harm.

There are no blanket recommendations for the use of steroids for pneumonia, because historically, studies have come to varied conclusions. However, Dr. Dressler, who advocated for the medications, said in an interview that recent publications paint a more complete picture.

“I think the newer studies in 2015 have made us more comfortable, because they look like there is more benefit” for steroids, especially among more severely ill patients, he noted. These international studies added more than 800 cases to the literature. A Spanish trial randomized 120 patients with high C-reactive protein to placebo or 0.5 mg/kg methylpred-nisolone every 12 hours for 5 days. There were fewer treatment failures in the prednisone group (13% vs. 31%), and fewer adverse clinical outcomes of intubation, shock, or death (3% vs. 14%). The number needed to treat to prevent one event was just six. (JAMA. 2015;313[7]:677-86).

In addition, a Cochrane meta-analysis analyzed 13 randomized trials, comprising more than 2,000 hospitalized patients. It found consistently lower rates of mortality, acute respiratory distress syndrome, early treatment failure, and hyperglycemia (Cochrane Database Syst Rev. 2017 Dec 13;12:CD007720).

 

“My recommendation is that inpatient clinicians should consider a brief course [5-7 days] of moderate-dose steroids (20-60 mg of prednisone equivalent) in patients admitted with CAP [community acquired pneumonia],” he said in an interview. “I personally give 40 mg prednisone for 5 days. I give even stronger consideration for severe CAP.”

Dr. Brotman countered with another set of articles from the literature, citing several studies with different conclusions. A separate meta-analysis of 12 trials appeared in the Annals of Internal Medicine (2015;163[7]:519-28). Half of the studies looked at outcomes in severe CAP, and the other half in less-severe cases. In the severe population, corticosteroids were associated with an overall decrease of about 40% in mortality, but that finding was driven largely by a single study; the others found nonsignificant decreases. The picture was less equivocal in the milder cases: Corticosteroids did not significantly reduce the risk of death.

In both groups, however, the drugs did significantly reduce the amount of hospital time. But this reduction came at a price, according to another review published in Clinical Infectious Diseases (2018 Jan 18;66[3]:346-54). Hospital stay was indeed reduced by a day, but there was no significant reduced risk of death (5.0% vs. 5.9% placebo). Similar rates of ICU admission and treatment failure, a doubling in the risk of hyperglycemia that required insulin, and a significantly higher risk of CAP-related rehospitalization (5.0% vs. 2.7%) rounded out the findings.

“Steroids may help patients feel better and have more reassuring vital signs and get out sooner, but at the expense of some toxicity, which might account for the readmissions,” Dr. Brotman said in an interview.

He then turned to the subject of sepsis. Before administering steroids for sepsis, physicians need to determine whether the powerful anti-inflammatory effect is worth the risks they carry. Adrenal failure is the biggest risk, Dr. Brotman said, citing last year’s ADRENAL study of 3,658 mechanically ventilated patients (N Engl J Med. 2018;378:797-808). They were randomized to a week of hydrocortisone 200 mg per day or placebo. The overall death rate was 28%, and steroids reduced the risk by only 5% (odds ratio, 0.95). The treatment group also had higher mean arterial pressure and lactate, a slower heart rate, and more serious diverse events, including hyperglycemia, hypernatremia, myopathy, and encephalopathy.

Initially, treated patients appeared to do better clinically, with a shorter period of ventilation, a shorter discharge from intensive care. But overall, there was no difference in ventilator-free days or hospital length of stay.“You may be improving clinical outcomes, but if you’re suppressing inflammation completely, you’re also suppressing a healthy response to an infectious process. There are some infections we need to be particularly cautious with, including tuberculosis,” Dr. Brotman added in the interview.

For his part, Dr. Dressler stated that the steroids-for-sepsis issue is “slightly murky.”

“A couple of new trials came out recently, and they lead us to reassess our thinking on this,” he said. Together, the studies comprised about 5,000 patients with septic shock – more than doubling the already studied cohort in 1 year. The reassessment came by means of a 2018 meta-analysis of all 9,000 patients. The findings actually led to new treatment guidelines, which were published in the British Medical Journal last year (2018;362:k3284).

The conclusion made a “weak recommendation” for corticosteroids in patients with sepsis. “Both steroids and no steroids are reasonable management options,” when also considering the overall clinical picture. For example, the recommendations advise against giving steroids to pregnant women, neonates, and patients with preexisting adrenal insufficiency.

However, the article noted, “Fully informed patients who value avoiding death over quality of life and function would likely choose corticosteroids.”

“I’m not sure these [studies] are changing what most people are doing,” Dr. Brotman countered in his interview. “I think the studies do help somewhat, because now we have enough numbers to suggest we can achieve a statistically significantly benefit. Septic shock is a life-threatening situation with a 40% risk of death. Now we can see that for every 50 people we treat with steroids, we can prevent 1 death. But that’s not the whole picture. Steroids won’t change the morality rate from 40% to 10%, but these studies do suggest that we can capture a small percent of people who may otherwise die.”

Dr. Dressler reported no financial disclosures. Dr. Brotman reported relationships with Bristol-Myers Squibb, Pfizer, and Portola.

Two experts drew on both personal experience and extant literature in the debate “Steroids for Pneumonia and Sepsis ... Do You Believe?” on Tuesday.

Daniel Dressler, MD, MSC, SFHM, of Emory University, Atlanta, and Daniel J. Brotman, MD, SFHM, director of the hospitalist program at Johns Hopkins Hospital, Baltimore, used a series of case studies to illustrate the conundrum. Despite their “pro” and “con” stances, though, both agreed in the end: First, do no harm.

There are no blanket recommendations for the use of steroids for pneumonia, because historically, studies have come to varied conclusions. However, Dr. Dressler, who advocated for the medications, said in an interview that recent publications paint a more complete picture.

“I think the newer studies in 2015 have made us more comfortable, because they look like there is more benefit” for steroids, especially among more severely ill patients, he noted. These international studies added more than 800 cases to the literature. A Spanish trial randomized 120 patients with high C-reactive protein to placebo or 0.5 mg/kg methylpred-nisolone every 12 hours for 5 days. There were fewer treatment failures in the prednisone group (13% vs. 31%), and fewer adverse clinical outcomes of intubation, shock, or death (3% vs. 14%). The number needed to treat to prevent one event was just six. (JAMA. 2015;313[7]:677-86).

In addition, a Cochrane meta-analysis analyzed 13 randomized trials, comprising more than 2,000 hospitalized patients. It found consistently lower rates of mortality, acute respiratory distress syndrome, early treatment failure, and hyperglycemia (Cochrane Database Syst Rev. 2017 Dec 13;12:CD007720).

 

“My recommendation is that inpatient clinicians should consider a brief course [5-7 days] of moderate-dose steroids (20-60 mg of prednisone equivalent) in patients admitted with CAP [community acquired pneumonia],” he said in an interview. “I personally give 40 mg prednisone for 5 days. I give even stronger consideration for severe CAP.”

Dr. Brotman countered with another set of articles from the literature, citing several studies with different conclusions. A separate meta-analysis of 12 trials appeared in the Annals of Internal Medicine (2015;163[7]:519-28). Half of the studies looked at outcomes in severe CAP, and the other half in less-severe cases. In the severe population, corticosteroids were associated with an overall decrease of about 40% in mortality, but that finding was driven largely by a single study; the others found nonsignificant decreases. The picture was less equivocal in the milder cases: Corticosteroids did not significantly reduce the risk of death.

In both groups, however, the drugs did significantly reduce the amount of hospital time. But this reduction came at a price, according to another review published in Clinical Infectious Diseases (2018 Jan 18;66[3]:346-54). Hospital stay was indeed reduced by a day, but there was no significant reduced risk of death (5.0% vs. 5.9% placebo). Similar rates of ICU admission and treatment failure, a doubling in the risk of hyperglycemia that required insulin, and a significantly higher risk of CAP-related rehospitalization (5.0% vs. 2.7%) rounded out the findings.

“Steroids may help patients feel better and have more reassuring vital signs and get out sooner, but at the expense of some toxicity, which might account for the readmissions,” Dr. Brotman said in an interview.

He then turned to the subject of sepsis. Before administering steroids for sepsis, physicians need to determine whether the powerful anti-inflammatory effect is worth the risks they carry. Adrenal failure is the biggest risk, Dr. Brotman said, citing last year’s ADRENAL study of 3,658 mechanically ventilated patients (N Engl J Med. 2018;378:797-808). They were randomized to a week of hydrocortisone 200 mg per day or placebo. The overall death rate was 28%, and steroids reduced the risk by only 5% (odds ratio, 0.95). The treatment group also had higher mean arterial pressure and lactate, a slower heart rate, and more serious diverse events, including hyperglycemia, hypernatremia, myopathy, and encephalopathy.

Initially, treated patients appeared to do better clinically, with a shorter period of ventilation, a shorter discharge from intensive care. But overall, there was no difference in ventilator-free days or hospital length of stay.“You may be improving clinical outcomes, but if you’re suppressing inflammation completely, you’re also suppressing a healthy response to an infectious process. There are some infections we need to be particularly cautious with, including tuberculosis,” Dr. Brotman added in the interview.

For his part, Dr. Dressler stated that the steroids-for-sepsis issue is “slightly murky.”

“A couple of new trials came out recently, and they lead us to reassess our thinking on this,” he said. Together, the studies comprised about 5,000 patients with septic shock – more than doubling the already studied cohort in 1 year. The reassessment came by means of a 2018 meta-analysis of all 9,000 patients. The findings actually led to new treatment guidelines, which were published in the British Medical Journal last year (2018;362:k3284).

The conclusion made a “weak recommendation” for corticosteroids in patients with sepsis. “Both steroids and no steroids are reasonable management options,” when also considering the overall clinical picture. For example, the recommendations advise against giving steroids to pregnant women, neonates, and patients with preexisting adrenal insufficiency.

However, the article noted, “Fully informed patients who value avoiding death over quality of life and function would likely choose corticosteroids.”

“I’m not sure these [studies] are changing what most people are doing,” Dr. Brotman countered in his interview. “I think the studies do help somewhat, because now we have enough numbers to suggest we can achieve a statistically significantly benefit. Septic shock is a life-threatening situation with a 40% risk of death. Now we can see that for every 50 people we treat with steroids, we can prevent 1 death. But that’s not the whole picture. Steroids won’t change the morality rate from 40% to 10%, but these studies do suggest that we can capture a small percent of people who may otherwise die.”

Dr. Dressler reported no financial disclosures. Dr. Brotman reported relationships with Bristol-Myers Squibb, Pfizer, and Portola.

Two experts drew on both personal experience and extant literature in the debate “Steroids for Pneumonia and Sepsis ... Do You Believe?” on Tuesday.

Daniel Dressler, MD, MSC, SFHM, of Emory University, Atlanta, and Daniel J. Brotman, MD, SFHM, director of the hospitalist program at Johns Hopkins Hospital, Baltimore, used a series of case studies to illustrate the conundrum. Despite their “pro” and “con” stances, though, both agreed in the end: First, do no harm.

There are no blanket recommendations for the use of steroids for pneumonia, because historically, studies have come to varied conclusions. However, Dr. Dressler, who advocated for the medications, said in an interview that recent publications paint a more complete picture.

“I think the newer studies in 2015 have made us more comfortable, because they look like there is more benefit” for steroids, especially among more severely ill patients, he noted. These international studies added more than 800 cases to the literature. A Spanish trial randomized 120 patients with high C-reactive protein to placebo or 0.5 mg/kg methylpred-nisolone every 12 hours for 5 days. There were fewer treatment failures in the prednisone group (13% vs. 31%), and fewer adverse clinical outcomes of intubation, shock, or death (3% vs. 14%). The number needed to treat to prevent one event was just six. (JAMA. 2015;313[7]:677-86).

In addition, a Cochrane meta-analysis analyzed 13 randomized trials, comprising more than 2,000 hospitalized patients. It found consistently lower rates of mortality, acute respiratory distress syndrome, early treatment failure, and hyperglycemia (Cochrane Database Syst Rev. 2017 Dec 13;12:CD007720).

 

“My recommendation is that inpatient clinicians should consider a brief course [5-7 days] of moderate-dose steroids (20-60 mg of prednisone equivalent) in patients admitted with CAP [community acquired pneumonia],” he said in an interview. “I personally give 40 mg prednisone for 5 days. I give even stronger consideration for severe CAP.”

Dr. Brotman countered with another set of articles from the literature, citing several studies with different conclusions. A separate meta-analysis of 12 trials appeared in the Annals of Internal Medicine (2015;163[7]:519-28). Half of the studies looked at outcomes in severe CAP, and the other half in less-severe cases. In the severe population, corticosteroids were associated with an overall decrease of about 40% in mortality, but that finding was driven largely by a single study; the others found nonsignificant decreases. The picture was less equivocal in the milder cases: Corticosteroids did not significantly reduce the risk of death.

In both groups, however, the drugs did significantly reduce the amount of hospital time. But this reduction came at a price, according to another review published in Clinical Infectious Diseases (2018 Jan 18;66[3]:346-54). Hospital stay was indeed reduced by a day, but there was no significant reduced risk of death (5.0% vs. 5.9% placebo). Similar rates of ICU admission and treatment failure, a doubling in the risk of hyperglycemia that required insulin, and a significantly higher risk of CAP-related rehospitalization (5.0% vs. 2.7%) rounded out the findings.

“Steroids may help patients feel better and have more reassuring vital signs and get out sooner, but at the expense of some toxicity, which might account for the readmissions,” Dr. Brotman said in an interview.

He then turned to the subject of sepsis. Before administering steroids for sepsis, physicians need to determine whether the powerful anti-inflammatory effect is worth the risks they carry. Adrenal failure is the biggest risk, Dr. Brotman said, citing last year’s ADRENAL study of 3,658 mechanically ventilated patients (N Engl J Med. 2018;378:797-808). They were randomized to a week of hydrocortisone 200 mg per day or placebo. The overall death rate was 28%, and steroids reduced the risk by only 5% (odds ratio, 0.95). The treatment group also had higher mean arterial pressure and lactate, a slower heart rate, and more serious diverse events, including hyperglycemia, hypernatremia, myopathy, and encephalopathy.

Initially, treated patients appeared to do better clinically, with a shorter period of ventilation, a shorter discharge from intensive care. But overall, there was no difference in ventilator-free days or hospital length of stay.“You may be improving clinical outcomes, but if you’re suppressing inflammation completely, you’re also suppressing a healthy response to an infectious process. There are some infections we need to be particularly cautious with, including tuberculosis,” Dr. Brotman added in the interview.

For his part, Dr. Dressler stated that the steroids-for-sepsis issue is “slightly murky.”

“A couple of new trials came out recently, and they lead us to reassess our thinking on this,” he said. Together, the studies comprised about 5,000 patients with septic shock – more than doubling the already studied cohort in 1 year. The reassessment came by means of a 2018 meta-analysis of all 9,000 patients. The findings actually led to new treatment guidelines, which were published in the British Medical Journal last year (2018;362:k3284).

The conclusion made a “weak recommendation” for corticosteroids in patients with sepsis. “Both steroids and no steroids are reasonable management options,” when also considering the overall clinical picture. For example, the recommendations advise against giving steroids to pregnant women, neonates, and patients with preexisting adrenal insufficiency.

However, the article noted, “Fully informed patients who value avoiding death over quality of life and function would likely choose corticosteroids.”

“I’m not sure these [studies] are changing what most people are doing,” Dr. Brotman countered in his interview. “I think the studies do help somewhat, because now we have enough numbers to suggest we can achieve a statistically significantly benefit. Septic shock is a life-threatening situation with a 40% risk of death. Now we can see that for every 50 people we treat with steroids, we can prevent 1 death. But that’s not the whole picture. Steroids won’t change the morality rate from 40% to 10%, but these studies do suggest that we can capture a small percent of people who may otherwise die.”

Dr. Dressler reported no financial disclosures. Dr. Brotman reported relationships with Bristol-Myers Squibb, Pfizer, and Portola.