Severe CAP: The 'Roid Debate Rages On
A 72 year old man presents to the ED with Shortness of breath, productive cough and fever of 102.1 F.
Physical Exam: Decreased breath sounds on the left with positive egophony in the left lower lung field. No wheezing or evidence of bronchospasm.
Vitals: Tachypnic and febrile, otherwise stable.
Significant Labs: WBC 20, PCT 2.1 and mild AKI.
You order a lactate, a set of blood cultures and start ceftriaxone/azithro for CAP and....
You decide to order 40mg of PO prednisone daily.
Steroids in CAP - maybe you agree, or maybe you don't. In the literature, steroids as an adjunct therapy in pneumonia dates back as far as 1956 - and they've been controversial ever since.
Cortisol is an endogenous steroid hormone- a hydrophobic molecule derived from cholesterol. These don't need to bind to a receptor outside of the cell and are able to go past membrane to bind to receptor inside cell. Due to this they have widespread systemic effects
It is released in response to activty by HPA axis in acute stress (infection or bear)
Cortisol secreting hormone released by hypothalamus, which goes to pituitary gland; ACTH is produced which goes to adrenal cortex and secretes cortisol
Three important roles:
Primes body for improved performace (incr HR, bronchodilation)
Mobilizes nutrient resources to sustain that performance
Calms down inflammation and supresses immune system
So what is rationale for exogenous steroids in CAP?
Local bacterial infections produce local inflammatory effects which become systemic (SIRS)
High burdens of inflammatory cytokines are BAD - high PNA severity index scores, higher risk of antimicrobial treatment failure, ARDS, ARF; higher mortality
CIRCI: Critical illness related corticosteroid insufficiency
A phenomenon described by SCCM/ESICM. When someone is critically ill there is dysregulation of HPA axis, decreased cortisol production and tissue resistance to cortisol
So by supressing the immune system, reducing the expression and secretion of pro-inflammatory cytokines and reducing leukocyte trafficking we SHOULD be able to calm inflammatory storm and benefit mortality
There are thousands of articles to sift through, but we are going to briefly touch on three studies relevant to the discussion.
1) 2015 - Corticosteroid Therapy for Patients Hospitalized With Community-Acquired Pneumonia: A Systematic Review and Meta-analysis
Six studies and just over 400 patients with pneumonia, both ICU & acute care patients
Primary outcome: mortality
Time to resolution of symptoms/clinical stability, pneumonia recurrence, mechanical ventilation/pressosr support, for ICU patients ICU discharge time
Findings: corticosteroids didn't reduce mortality among patients with PNA but it did find improvement in almost all secondary outcomes (but not in pediatric patients with RSV)
Evidence quality: LOW (small, single studies, poor blinding, small number of participants)
No formal recommendations made.
2) 2015 - Corticosteroids for Pneumonia
A SRMA study of 13 trials and ~2000 patients that specifically looked at steroids for hospitalized patients with CAP
Primary outcome: all cause mortality
Need for mechanical ventilation, development of ARDS, hospital LOS
When it was published, started to frame the conversation about WHICH patients would benefit from steroids
Findings: corticosteroid therapy was associated with a ~5% absolute reduction in need for mechanical ventilation and development of ARDS; reduced hospital LOS ~1 day
Benefit in mortality varied on degree of CAP - severe (defined by CURB65, APACHE II and ATS definitions at time) had ~3% absolute reduction
Most common adverse effect: hyperglycemia (but authors of included RCTs often excluded patient sat risk for adverse events related to steroids such as GIB, immunosuppression)
3) 2017 Cochrane Review - Is treatment with corticosteroids beneficial and safe for people with pneumonia?
17 RCTs and just over 2200 patients
Primary outcome: all cause mortality
Among all patients all cause mortality was decreased in corticosteroid therapy - driven primarily by cohort of patients with severe CAP (NNT 18, relative risk of death 0.58)
Improvement in secondary morbidity outcomes in severe and non severe CAP
Evidence quality: moderate for mortality reduction and high for reduction in early clinical failure
Most common adverse effect: hyperglycemia
Mean age of patients in this study was 69.8
Lack of data prevented authors from performing subgroup analysis
Concern that patients at high risk of adverse reactions may have not been enrolled
In all but 3 studies, classification of severe CAP was done at trial level, not patient level - may have reduced external validity
High risk of publication/reporting bias - possibly exacerbated in setting of SRMA
Dose and schedule of steroids varied
so what's our takeaway?
Should we give steroids?
What dose to use?
How do you treat steroid induced leukocytosis?
Final nail in the coffin?
ESCAPe trial (extended steroid in CAP) - longer duration
Trial by Hassan et. al looking at IV steroids given according to a variety of pneumonia severity scoring systems - trying to evaluate which is best/which patients benefit most
Updated ATS/IDSA Guidelines this summer
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