CICM SAQ 2016.1 Q5

Rationale / Indications

Conventional & generally accepted indications include:

• Pneumonia complicating exacerbated COPD
• PJP infection with lung infiltrates (data from HIV population, and by extrapolation to other
  immunosuppressed groups)
• Patients who are on long term corticosteroids or otherwise have adrenal suppression
• (With less certainty) those with shock states and vasoplegia as a catecholamine sparing
  strategy

Outside of these groups, in a general population with CAP:

• The basis for use is as an adjunctive therapy in hospitalised patients to reduce inflammation and improve morbidity or mortality.
• Some patients with CAP fail to resolve, and progress to cryptogenic organising pneumonia, (COP) with case series showing response to corticosteroids (and relapse on early cessation
• Conflicting evidence in the fibro-proliferative phase of ARDS
• Now several studies randomising patients to early use in uncomplicated CAP

Potential adverse effects

• Super-added infection
• Muscle weakness / Proximal myopathy / Critical illness polyneuromyopathy
• Difficulty weaning from ventilatory support

Evidence

A 2015 Meta-analyses (Siemieniuk et al, 2015):

• 3% decrease in all-cause mortality,
• 5% decrease rate of mechanical ventilation
• Reduced hospital length of stay by 1 day.
• Critique of metanalysis
  • Trials included in metanalyses have been small o had high heterogeneity
  • Insufficient power to analyse mortality.
  • Many exclusions
    • (e.g. immunocompromised patients at risk of superinfection, pregnant women, GI bleeding within 3 months as well as patients with neuropsychiatric conditions prone to psychotic side effects of steroids)
  • small overall effect

A recent RCT (Blum et al, Lancet 2015, 392 pt per group) showed a shorter time to reach a composite endpoint of ‘clinical stability’ with Prednisolone 50mg daily for 7 days.

Another RCT (Torres et al, JAMA 2015, 60 pt per group) showed that Methylprednisolone 0.5mg/kg 12h for 5 days reduced risk of “treatment failure” compared with placebo in patients with severe CAP and high CRP levels

Practical (Translational) Issues

• No clear data on exact steroid and regimen
  • There is no definitive data on what type of steroid to give and whether to give
    continuously or in a tapering regimen and for how long.
  • In the idiopathic pneumonia group (COP) steroid tapering can be associated with
    abrupt relapse
• Pathogen dependent response to steroids
  • Pneumonia due to pathogens like the influenza virus and aspergillus may be associated with worse outcomes with steroid use, PCP better
• Studies in progress that may help
  • The ESCAPE study by the Department of Veterans affairs is assessing the role of
    steroids in CAP with either placebo, methyl prednisolone 40 mg per day or 20 mg per day for 7 days followed by tapering over 13 days on all cause 60 day mortality.

Summary statement (For example)

• Subgroups where steroids would be conventional therapy (COPD, PJP)
• Not yet accepted therapy
• Treatment effect small
• But no evidence of adverse effect and demonstrated safety
• Listed as practice changing update in Up-to-Date
• Should ideally be a conjoint decision with clinician responsible for post ICU management

Additional comments:

Candidates were lacking in knowledge relating to the evidence for steroids in severe CAP. The detail in above template was not required for a pass mark. Satisfactory answer for a pass mark was expected to include:

• Accepted indications for steroids in CAP
• Some reference to rationale for use in other groups with CAP
• Potential adverse effects
• Some reference to evidence