These are the ‘Roids you are looking for – Steroids in the ED

In the acute care setting, steroids have various usages and indications, but their usage can often be nuanced. From adrenal crises to septic shock, severe community-acquired pneumonia, and even acute pharyngitis, steroids play a pivotal role in managing a variety of conditions encountered in the Emergency Department (ED). However, their use is far from straightforward—balancing indications, dosing, and potential adverse effects is a critical challenge. In this post, we delve into the science and practice of steroids in the emergency department, equipping you with the knowledge to wield these powerful agents effectively and safely, because these are indeed the ‘roids you’re looking for.

We’re going to discuss the use of steroids in 4 primary indications:

1. Adrenal insufficiency
2. Septic Shock
3. Pharyngitis
4. Community acquired pneumonia

Physiology overview

• HPA Axis Overview: The hypothalamus releases CRH, signaling the pituitary to produce ACTH, which stimulates the adrenal glands to release glucocorticoids and mineralocorticoids. Exogenous steroids vary in their affinities for these receptors.
• Circadian Rhythm: Cortisol levels naturally peak during the day and are lowest at night.
• Cortisol Production: Baseline production is ~20 mg/day under non-stressed conditions, but this can rise to 150–200 mg/day during high stress.
• Systemic Effects of Cortisol: (Can maybe ignore this portion if its getting too wordy)
  • CNS: Regulates the sleep-wake cycle, memory, and appetite.
  • CVS: Potentiates vasoactive agents to support blood pressure.
  • Kidneys: Promotes sodium resorption and potassium excretion (mineralocorticoid effect).
  • Immune: Exerts anti-inflammatory and immunosuppressive actions.
  • Bone: Involved in remodeling; high levels are linked to osteoporosis.
  • Metabolism: Increases insulin resistance, diabetes risk, abdominal obesity, and muscle wasting.
• Purpose of Exogenous Steroids: Used for anti-inflammatory effects and/or to supplement a depleted endogenous system.

Dosing Equivalencies

• Formulations Overview: The table highlights commonly used steroids, their duration of effect, dosing equivalencies, and their relative downstream effects.
• Example Insight: 50 mg prednisone ≈ 40 mg methylprednisolone. In asthma or COPD exacerbations, a common pitfall is using 125 mg methylprednisolone is equivalent to 155 mg oral prednisone—much higher than necessary.
• Dosing Practices: Historical patterns often involve excessive doses, unsupported by evidence for improved outcomes. Rethink dosing based on evolving data. When in doubt, MD Calc has a great calculator that is easy to use.

Adverse Effects of Steroid use:

Long-term Use – i.e. steroid use >30 days at a time are not durations we are prescribing from the ED

Short-term use:

• Limited Evidence: Few high-quality studies address the short-term effects of steroids, especially for single doses in the ED.
• Common Side Effects: While commonly discussed, the risk of these effects from a single dose remains unclear. Here are some we should counsel our patients on:
  • Insomnia – can try timing administration to morning if applicable
  • Hunger – sometimes desirable too
  • Hyperglycemia – Insulin-dependent diabetics should be made aware especially
  • Risk of precipitated psychosis/delirium – elderly patients, prev hx of psychosis. Incidence of this is very unclear

Here is an example of a retrospective cohort study and self controlled case series that looked at some adverse effects associated with short term steroid use:

Study Objective: Evaluated the frequency of short-term oral corticosteroid prescriptions (<30 days) and associated adverse events (sepsis, VTE, fractures).

Population: 1.5 million adults (aged 18-64) with private insurance from 2012 to 2014; 21.1% received at least one short-term steroid prescription.

Common Indications: Prescriptions were frequently given for upper respiratory tract infections, spinal conditions, and allergies, across various medical specialties.

Adverse Events: Within 30 days of starting corticosteroids

• Sepsis: 5.3x increased risk
• Venous thromboembolism (VTE): 3.33x increased risk
• Fracture: 1.87x increased risk

Low Dose Risks: Increased risks persisted even at low doses (<20 mg/day prednisone equivalent).

Conclusion: Short-term corticosteroid use, prescribed to 1 in 5 adults in a three-year period, is associated with notable risks, highlighting the need for careful consideration.

Limitations:

• Unclear indication for giving steroids.
• Very high prescription rate, not sure this reflects our Canadian ED population.
• Only reported on these 3 adverse effects, would have been nice to see others

Indication 1: Adrenal Insufficiency

Definition: A condition where the adrenal glands do not produce adequate amounts of steroid hormone.

Classes of AI and Key Features:

1. Primary AI (PAI)

• • Caused by direct adrenal damage or removal.
  • Characterized by inappropriately high ACTH due to the absence of negative feedback.
  • Symptoms may include hyponatremia, and in ~1/3 of cases, hyperkalemia.
    

2. Secondary

• Result of disrupted pituitary signalling (e.g., pituitary resection or damage).

3. Tertiary

• Commonly results from prolonged exogenous steroid use, leading to suppression of CRH and ACTH production via negative feedback.
• 1% of the Western population have had >3 months of long-term glucocorticoids, increasing the risk for TAI.
• Definitions of long-term use vary:
  • >5 mg prednisolone daily for >21 days.
  • 40 mg prednisone daily for >1 week, or repeated short courses of high-dose steroids.
  • Patients with multiple recent high-dose steroid courses (e.g., for poorly controlled asthma) are particularly at risk.

Clinical Considerations

• Symptoms are often vague and challenging to evaluate, including fatigue, weakness, and nonspecific complaints.
• Use patient history, medication review, and a high index of suspicion to for AI for patient presenting with vague symptoms
• Hyponatremia is common across all classes, while hyperkalemia is not consistently present in PAI.
• Recognize they are at risk for adrenal crisis (below)

Sick Day Rules

Adrenal Crisis Risk: Patients with adrenal insufficiency (AI), particularly tertiary AI (TAI), face a dose-dependent increase in all-cause mortality, partly due to under recognition of adrenal crises during illness. While most patients understand sick-day rules, healthcare providers play a critical role in identifying and managing those at risk to prevent future deterioration. 

• Option 1 – double their steroid dose during illness if tolerating oral intake
• Option 2 – if unable to tolerate PO, they require an IV stress dose in the ED until tolerating PO
  • Hydrocortisone 100 mg IV to start

Adrenal Crisis

• Adrenal crisis is an acute deterioration with hypotension in patients with adrenal insufficiency, resolving rapidly with IV steroid administration.
• Lifetime incidence includes
  • ~50% of primary adrenal insufficiency (PAI) patients
  • ~33% of secondary (SAI) or tertiary (TAI) cases, though likely underestimated due to missed diagnoses.

• Challenges in recognition
  • Symptoms like weakness, back pain, and confusion, along with lab findings (hyponatremia, hypoglycemia, and rarely hyperkalemia), are non-specific, making diagnosis difficult.
  • Think of it for the hypotensive or septic patient without obvious etiology
• Key Clinical Considerations
  • Any sick patient on “home dose” steroids should be presumed adrenally insufficient. Patients with multiple short steroid courses may also have relative insufficiency, particularly if hypotensive.
• Management
  • Treat shock and precipitating factors as you would normally
  • In suspected cases, administering a stress dose of IV steroids can rapidly reverse the shock state.
  • Recommend: Hydrocortisone 100 mg IV STAT

Adrenal Insufficiency Key Points:

• Adrenal insufficiency (AI) is common and often under-recognized. Exogenous steroid use is the most common etiology of tertiary AI.
• Proper sick-day management is key to prevent adrenal crisis
  • Doubling the steroid dose during illness (if tolerating PO),
  • IV Stress dose in ED if not tolerating PO
• In distributive shock with suspected adrenal crisis, standard shock management applies, supplemented with steroid administration.
  • Hydrocortisone 100 mg IV

Indication 2 – Steroid Use in Septic Shock

Background: There have been fluctuating recommendations on the benefits of steroids in septic shock over the past few years.

• 4 major RCTs on the subject: Annane et. al (2002), CORTICUS Sprung et. al (2008), APROCCHSS Annane et. al (2018), ADRENAL Venkatesh et. al (2018)
• Study interventions:
  • Predominantly hydrocortisone 200 mg/day (divided doses) ± fludrocortisone,
• Mortality Benefits:
  • Two French studies demonstrated a mortality benefit Hydrocortisone + fludrocortisone
    • Note the additional mineralocorticoid effect of fludrocortisone over hydrocortisone alone is debated.
  • These studies had a higher baseline mortality compared to ADRENAL, potentially enhancing effect size detection.
• Secondary Benefits:
  • All showed a faster time to shock reversal.
  • ADRENAL:
    • 3700 patients with septic shock, admitted to the ICU on mechanical ventilation and requiring ≥4 hours of vasopressors/inotropes, hydrocortisone infusion (200mg/d) compared to placebo
      • Faster time to shock reversal,
      • More ventilator free days
      • fewer blood transfusions required
    • Key Caveat:
      • Lack of mortality benefit in other studies may be due to delays in randomization, as late interventions in critically ill patients are less likely to improve outcomes.

2024 Focused Update: Guidelines on Use of Corticosteroids in Sepsis, Acute Respiratory Distress Syndrome, and Community-Acquired Pneumonia:

Focused Update Overview: A total of 46 randomized controlled trials (RCTs) compared corticosteroids to placebo or standard care in sepsis or septic shock.

• Evidence Findings:
  • Corticosteroid use may reduce hospital/long-term mortality (60 days to 1 year) with a relative risk (RR) of 0.94 (95% CI, 0.89–1.00, low certainty).
  • Corticosteroid use probably reduces ICU/short-term mortality (14–30 days) with a relative risk (RR) of 0.93 (95% CI, 0.88–0.98, moderate certainty)
• Key differences in 2024 update:
  • Broader Criteria for Use:
    • The 2024 panel recommends corticosteroids for septic shock requiring vasopressors, regardless of dose, compared to the 2017 guideline, which limited use to patients not responsive to fluids and moderate-to-high-dose vasopressors.

• High-Dose/Short-Duration Regimens:
  • The panel advises against high-dose, short-duration corticosteroids (>400 mg/day hydrocortisone equivalent for <3 days) due to associated adverse effects.
• Sepsis Without Shock: No specific recommendation was made for corticosteroid use
• Dosing and Regimens:
  • Most studies used IV hydrocortisone 200–300 mg/day (divided doses or continuous infusion) for 5–7 days, with or without a taper.
  • Some studies added fludrocortisone, though its additional benefit remains unclear.

Septic Shock (Indication 2) Key Points

• Steroid use in septic shock is constantly evolving, the current consensus would suggest the following:
  • The SCCM 2024 focused update suggests we should add a stress dose of steroid for pressor-dependent septic shock – REGARDLESS OF DOSE
  • We know timely steroid administration is key
  • Recommend Hydrocortisone 100 mg IV, and ICU can reassess upon admission

Indication 3 – Steroids in Pharyngitis

This 2017 SR summarizes the role of steroids in pharyngitis well.

Study Overview: A systematic review of 10 trials (1,500 patients) evaluated steroid use, primarily dexamethasone, for acute sore throat in emergency or primary care settings, including viral and bacterial pharyngitis.

Key Findings:

• Moderate to high-certainty evidence supports that 1–2 doses of steroids:
• Decrease pain scores at 24 hours.
• Improve pain resolution at 24 and 48 hours.
• Accelerate time to pain relief (~5 hours earlier) and complete relief (~11 hours sooner).

Adverse Effects: No meaningful differences in adverse effects were observed between groups.

Dosing Note: Most studies used 8–10 mg dexamethasone, aligning with its duration of effect.

Clinical Perspective: This represents a moderate patient-centered outcome. For patients, starting to feel better 5 hours sooner might be worthwhile. Using a shared decision-making model, steroids can be an option for patients who have maximized other symptomatic treatments at home. With minimal adverse effects reported and potential benefits, many patients may opt for a dose of steroids.

Indication 4 – Steroids in Severe Community Acquired Pneumonia (CAP)

 Background: The evidence on the role of steroids in severe pneumonia is quite robust and with the recent publication of the CAPE-COD trial (below) I think we have a very clear answer of steroid’s role in Severe CAP.

Study Design:

• Type: Multicenter, double-blind, randomized controlled trial with 795 adults with severe community-acquired pneumonia (CAP) admitted to the ICU.
• Intervention: Continuous intravenous hydrocortisone at 200 mg/day for 4–7 days, followed by a taper for 4–7 days. Compared to placebo with matching saline infusion.

Key Outcomes:

• Mortality: 6.2% in the hydrocortisone group vs. 11.8% in the placebo group (p = 0.006).
• Intubation Rates: Reduced to 18% with hydrocortisone vs. 29.5% with placebo.
• Non-Invasive Ventilation Rates: Lower in the hydrocortisone group (6.8%) compared to placebo (10.9%).
• Vasopressor Use: 15.3% with hydrocortisone vs. 25% with placebo, indicating a vasopressor-sparing effect.
• Safety Profile: Comparable between groups, with no significant differences in adverse events.

The confusion in the ED may be who qualifies as a severe pneumonia:

Defining severe pneumonia in the CAPE-COD study was simplified into practical categories:

• Intubated with pneumonia: This is clearly severe and straightforward to identify.
• High-Flow Nasal Cannula (HFNC): Requires intervention, and is a definitive marker of severe pneumonia.
• Non-Rebreather (NRB): Likely severe but not always straightforward to measure PaO2/FiO2 ratios; clinical trajectory is key.
• PSI Score: Indicates severity in highly comorbid patients, even if they don’t meet traditional ICU thresholds.

Challenges in Applying PSI Scores

While the PSI score can guide severity classification, it may not always align with our clinical setting. The study’s limited ICU inclusion may reflect an infusion protocol dependency. However, many step-down and AMA units often function at ICU-level care. Thus, ICU admission isn’t a strict requirement for additional interventions.

Practical Approach

For day-to-day practice, consider the following:

• Treat HFNC and above as definitive markers of severe pneumonia.
• With NRB, evaluate their clinical trajectory and consider using the PSI score for additional context.
• Recognize that severe pneumonia management doesn’t always necessitate ICU admission
• In high-volume EDs with delays to assessment by general internal medicine teams, there is a role for ED consideration of initiating steroids

SCCM 2024 update has STRONG recommendations in line with CAPE-COD’s findings.

• Mortality Benefit: “Probable” reduction in mortality (moderate certainty).
• Mechanical Ventilation: Reduction in the need for invasive mechanical ventilation (moderate certainty).
• ICU Stay: Decreased ICU length of stay (low certainty).
• Hospital Stay: Reduced overall hospital stay (low certainty).

Steroids in Severe CAP (Indication 4) Key Points

Steroid use in Severe CAP has strong consensus evidence that we in the ED need to consider in our management 

• Common ED Presentation: Severe community-acquired pneumonia (CAP) is frequently encountered in emergency settings.
• Positive Outcomes: Steroids offer patient-centered benefits, such as reduced mortality, decreased need for mechanical ventilation, and shorter hospital stays.
• Timeliness Matters: Early administration of steroids is crucial to maximizing their effectiveness. Especially in high-volume EDs, early ED-based consideration for steroids can significantly improve outcomes.
• Severity of pneumonia matters: Consider pneumonia requiring admission to AMA/Step-down-level care as severe, warranting steroid use.
• Consider HFNC/Intubation and above as definitive markers, use NRB in context of clinical trajectory or PSI scores, and recognize that ICU admission isn’t always necessary for steroid initiation.
• Class Effect: Use the steroid of your choice, as the benefits likely apply across the class. When in doubt – Hydrocortisone 100 mg IV is a great starting point

Summary – Steroids in the ED

• Dosing: Important to consider duration of effect, relative anti-inflammatory and mineralocorticoid activity when selecting your steroid. See Table above.
• Side Effects: While evidence on short-term steroid effects from single ED doses is limited, patients should be counseled on potential side effects such as insomnia (manageable with morning dosing), hunger (potentially beneficial), hyperglycemia (notably in insulin-dependent diabetics), and rare risks like psychosis or delirium, particularly in the elderly or those with a history of psychosis.
• Adrenal Insufficiency: Often underrecognized and commonly caused by exogenous steroids, requires proper sick-day management with doubled oral doses during illness or IV hydrocortisone (100 mg) in the ED for those unable to tolerate PO, with steroids also supplementing standard shock management in suspected adrenal crisis.
• Septic Shock: The SCCM 2024 update recommends adding a stress dose of hydrocortisone (100 mg IV) for pressor-dependent septic shock, regardless of dose of pressor or duration of pressor dependence, emphasizing the importance of timely administration with reassessment by the ICU upon admission.
• Severe community-acquired pneumonia: This is a common ED presentation, warrants timely steroid administration to improve outcomes like reduced mortality and shorter hospital stays, with HFNC, intubation, or step-down-level care as markers of severity, and hydrocortisone 100 mg IV as a reliable starting option if in doubt.
• Pharyngitis: A systematic review of 10 trials (1,500 patients presenting to primary care and ED settings) demonstrated that 1–2 doses of dexamethasone (8–10 mg) effectively reduce pain scores and accelerate symptom resolution (~5 hours earlier for onset, ~11 hours for complete relief) in acute sore throat with minimal adverse effects, making it a viable option for patients seeking faster relief after exhausting other treatments.