📘 Rethinking the Stress Dose🤔: Evidence-Based Perioperative Steroid Management in 2025

2025年10月31日

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Contents

♦️Introduction

Picture this familiar moment: your patient on 15 mg of prednisone daily for rheumatoid arthritis is heading to major surgery. The question you need to answer—right now—is simple but high-stakes: do they need extra steroids, and if so, which dose and for how long?🤔

For years, many of us reached reflexively for high “stress doses,” influenced by 1950s case reports linking perioperative deaths to adrenal collapse. Today’s evidence tells a more nuanced story. Blanket supplementation can cause real harm—hyperglycemia, poor wound healing, and higher infection risk—without proven benefit in many scenarios.

Because roughly 1% of the population takes long-term glucocorticoids (GCs), you will see these patients often. Your job is to strike the balance: prevent life-threatening adrenal crisis (AC) while avoiding iatrogenic complications from unnecessary dosing.

This guide is built for busy clinicians, anesthesia residents, and the perioperative team. You’ll review HPA axis essentials, apply a practical risk-based dosing protocol, and know exactly what to do when AC is on the table.

♦️ Understanding the HPA Axis and Types of Adrenal Insufficiency

Effective care for steroid-dependent patients starts with the physiology you’re supporting.

🔷 The HPA Axis: Your Body’s Stress Manager

Think of the Hypothalamic-Pituitary-Adrenal (HPA) axis as your built-in stress control system.

Stressor activation (e.g., surgery, infection): The hypothalamus releases corticotropin-releasing hormone (CRH).
Pituitary cascade: CRH prompts the anterior pituitary to secrete adrenocorticotropic hormone (ACTH).
Adrenal activation: ACTH travels to the adrenal cortex and triggers cortisol synthesis and release.

Why does this matter clinically? Cortisol helps maintain vascular tone (by increasing catecholamine sensitivity), mobilizes glucose for metabolic demands, and tempers inflammation.
Healthy adults secrete about 10–20 mg of cortisol daily, but output can rise to 75–150 mg during major surgical stress.

🔷 The Three Types of Adrenal Insufficiency (AI)

When the body can’t make enough cortisol, adrenal insufficiency develops—and the type guides management.

1️⃣ Primary AI (Addison’s Disease)

The adrenal glands fail (often autoimmune). The pituitary ramps up ACTH, but the adrenals can’t respond.

🏥 Clinical Pearl:
These patients lack both glucocorticoid (cortisol) and mineralocorticoid (aldosterone). They need dual chronic replacement (e.g., hydrocortisone plus fludrocortisone) to maintain hemodynamics and electrolytes.

During acute perioperative care, high-dose hydrocortisone (≥100 mg/day) provides enough mineralocorticoid effect; you typically resume/add fludrocortisone when returning to maintenance therapy.

2️⃣ Secondary AI:

Pituitary disease (tumor, radiation, etc.) leads to low ACTH, adrenal atrophy, and reduced cortisol. Mineralocorticoid function usually remains intact.

3️⃣ Tertiary AI (Glucocorticoid-Induced AI):

The most common perioperative issue. Chronic exogenous steroids suppress hypothalamic and pituitary drive through negative feedback. With CRH/ACTH turned down, the HPA axis idles and atrophies. If you stop exogenous steroids or a big stressor hits without dose adjustment, the axis can’t respond—acute AI follows.

🎓 Exam Focus☝️:

How do you check HPA recovery after stopping steroids? The gold standard is the ACTH (cosyntropin) stimulation test—give 250 µg IV, measure cortisol at 30 and 60 minutes.
A peak <500 nmol/L (18 µg/dL) suggests AI. A pragmatic screen (per 2023 ESE/ES Guideline) is an 8–9 AM cortisol at least 24 hours after the last GC dose:
- >10 µg/dL (300 nmol/L): HPA axis likely intact
- <5 µg/dL (140 nmol/L): AI very likely

♦️ Who Actually Needs Perioperative Steroid Cover?

Here’s the key clinical decision: not everyone needs supplementation. Use risk stratification instead of a one-size-fits-all approach.

⚠️ High-Risk Patients (Supplementation Required)

Provide supplementation if the chance of HPA suppression is high:

All patients with Primary or Secondary AI
Patients with confirmed Tertiary AI
Patients with Cushingoid features (moon facies, truncal obesity, skin atrophy)
High-dose therapy: Prednisone ≥20 mg/day for >3 weeks
Moderate-dose therapy: Some guidelines (Woodcock 2020) use ≥5 mg/day for ≥1 month.
💡 When unsure between 5–20 mg/day, covering is safer.
Recent cessation: Stopped long-term GCs within the past 3–6 months

📌 Remember: Route matters. High-dose inhaled, frequent intra-articular, and potent topical steroids can suppress the HPA axis. Always ask about all steroid formulations.

🔷 The Paradigm Shift: The “At-Risk” Patient

Have a patient on 10 mg prednisone daily for years with no prior crisis? Historically, many received 300 mg hydrocortisone “just in case.”
Newer evidence suggests that’s often unnecessary. Systematic reviews (Chen Cardenas 2022, Chilkoti 2019) show that for at-risk patients without confirmed AI, continuing the baseline dose (oral or IV equivalent) is usually enough for minor-to-moderate procedures—spare the supraphysiologic dosing and its risks.

🌐 International Comparison

Different groups set different thresholds:

UK (Woodcock 2020): ≥5 mg prednisone/day for ≥4 weeks
Europe (ESE/ES 2023): ≥5 mg/day for ≥1 month
US practice (varied): Often ≥10–20 mg/day

These gaps reflect limited RCT data. Bottom line: individualize care rather than cling to a single cut-off.

🔷 Low-Risk Patients (No Supplementation Required)

Extra “stress doses” are generally unnecessary for:

Any GC dose taken for <3 weeks
Low-dose therapy (prednisone <5 mg/day)
Alternate-day therapy
- Even with alternate-day administration, if the dosage corresponds to a supraphysiologic glucocorticoid level and the therapy has been continued for a prolonged period (more than 3–4 weeks), suppression of the hypothalamic–pituitary–adrenal (HPA) axis cannot be completely ruled out, and stress-dose supplementation may need to be considered.

♦️ A Practical Protocol: Dosing by Surgical Stress

When supplementation is needed, match the dose to surgical stress.

💊 Drug of Choice: Hydrocortisone

Hydrocortisone (HC) is your go-to. It’s bioidentical to cortisol and provides both glucocorticoid and mineralocorticoid effects—ideal for hemodynamic support.

⚠️ Dexamethasone Considerations:
Great for anti-inflammation and PONV prophylaxis, but it lacks meaningful mineralocorticoid activity. That means it’s not suitable as the sole replacement in Primary AI (Addison’s). You can use it in Secondary/Tertiary AI, but hydrocortisone’s shorter half-life makes titration and tapering easier.

📝 Tiered Dosing Regimen

This consensus approach draws on Woodcock 2020 and ESE/ES 2023.

😊 Minor Stress

Examples: Endoscopy, cataract surgery, minor dermatologic procedures
Action: Give the usual morning dose. Extra steroids typically not needed. An optional HC 25–50 mg IV at induction is reasonable.

🙁 Moderate Stress

Examples: Laparoscopic cholecystectomy, joint arthroplasty, uncomplicated hysterectomy
Action: Usual morning dose plus HC 50–75 mg/day (e.g., 25 mg IV q8h) for 24–48 hours.

😣 Major Stress

Examples: Major open abdominal or thoracic surgery, cardiac surgery, major trauma
Action: Full replacement.
Regimen: HC 100 mg IV at induction, then 200 mg over 24 hours—either continuous infusion (~8.3 mg/hr) or HC 50 mg IV q6h.

⤵️ Tapering and Discontinuation

Surgical stress peaks within 48–72 hours. If recovery is smooth (afebrile, stable hemodynamics, no complications), reduce quickly. After major surgery, you can often halve the dose daily (e.g., 200 mg Day 1 → 100 mg Day 2 → 50 mg Day 3) until you reach baseline.
Once oral intake resumes, switch to double the usual oral dose for 24–48 hours, then taper back to baseline.

♦️ How to Recognize and Manage Adrenal Crisis

Adrenal crisis (AC) is a true emergency. Fast recognition and treatment save lives.

🔷 Assessment: The Non-Specific Signs of AC

AC can masquerade as common postoperative problems:

Nausea and vomiting
Abdominal pain
Lethargy, confusion, or profound weakness
Fever
Hypoglycemia

The red flag is refractory hypotension—low blood pressure despite adequate fluids and vasopressors.

Labs may show:

Hyponatremia
Hyperkalemia

…but these can be absent early on.

⚠️ Differential Diagnosis:
AC overlaps with septic shock, hypovolemia, and acute abdomen. What sets it apart is persistent hypotension despite appropriate resuscitation—especially in someone with AI risk factors.

🔷 The Golden Rule: Treat First, Diagnose Later

Suspect AC? Treat immediately. A single 100 mg hydrocortisone dose has minimal downside; delayed therapy can be fatal.

If it won’t slow treatment, draw STAT cortisol, ACTH, and electrolytes first. But never postpone steroids to get labs.

💉 Emergency Adrenal Crisis Protocol (Adults)

Based on Society for Endocrinology (2020):

STAT: Hydrocortisone 100 mg right away
Prefer IV if you have access
IM is acceptable if IV is delayed
FLUIDS: Rapidly rehydrate with 1 liter 0.9% Normal Saline (or balanced crystalloid) in the first hour
MAINTAIN: Hydrocortisone 200 mg/24 h
Continuous infusion (8.3 mg/hr), or
HC 50 mg IV q6h
SUPPORT: Correct hypoglycemia with dextrose; monitor/fix electrolytes
INVESTIGATE: After stabilization, look for the trigger (infection, surgical stress, hemorrhage)

♦️ The Harms of Overdosing: Why “Less is More”

The move away from routine high “stress doses” reflects both harm data (Chen Cardenas 2022) and clearer physiology.

Mid-20th-century practice leaned on anecdotes rather than trials. We now know even during severe illness or major surgery, endogenous cortisol production rarely tops 150 mg/day (Chilkoti 2019). Pushing to 300–500 mg/day doesn’t add hemodynamic benefit—and it does add risk:

Hyperglycemia needing insulin
Delayed wound healing
Higher surgical site and nosocomial infection rates
Fluid retention and electrolyte issues

By tailoring supplementation to surgical stress (50–75 mg/day for moderate; 100–200 mg/day for major), you support physiology while minimizing complications.

♦️ Clinical Challenges and Guideline Gaps

Still feels messy? You’re not alone.

Low-Quality Evidence: Many recommendations rely on physiology and expert consensus, not large RCTs.
Guideline Discrepancies: Thresholds vary (5 mg vs. 10 mg vs. 20 mg prednisone).
Poor Compliance: A 2025 UK audit (PREdS) found only 9% of at-risk patients received guideline-compliant perioperative supplementation.

🌐 International Comparison:
These implementation challenges aren’t unique to the UK. Comparable audit data from Japan are limited, underscoring the need for better adherence tracking across systems.

🏥 Clinical Pearl:
Without big RCTs, play it safe and structured. Clearly separate low risk (no cover) and high risk (full cover). For the gray zone (e.g., 10 mg prednisone/day), HC 50–75 mg/day is a reasonable, defensible middle path that balances AC prevention with avoiding overdosing.

📖 Frequently Asked Questions (FAQs)😊

☝️Q1: Which patients absolutely require perioperative steroid supplementation?

Patients with Primary, Secondary, or confirmed Tertiary AI. Also those with Cushingoid features, taking ≥20 mg/day prednisone for ≥3 weeks, or who recently stopped long-term steroids. A conservative approach using ≥5 mg/day for ≥1 month is also widely used.

☝️Q2: What is the immediate treatment for suspected adrenal crisis?

Don’t wait for labs. Give Hydrocortisone 100 mg IV (or IM) and start 1 L of 0.9% Normal Saline rapidly. Continue with HC 200 mg/24 h (continuous infusion or 50 mg q6h).

☝️Q3: How does supplementation dose vary by surgical type?

Match dose to stress:

Minor: Usual oral dose ± HC 25–50 mg IV once
Moderate: Usual oral dose + HC 50–75 mg/day for 1–2 days
Major: HC 100–200 mg/day for 2–3 days, then taper

☝️Q4: Which long-term steroid users are considered low-risk and don’t need supplementation?

Those on <5 mg prednisone/day or any dose for <3 weeks typically don’t need extra coverage.

☝️Q5: Is continuing baseline dose sufficient for some at-risk patients?

Yes. For many “at-risk” patients without confirmed AI (e.g., 10–15 mg/day chronically), simply continuing the baseline dose (or IV equivalent) is often enough for minor-to-moderate surgery and helps avoid over-supplementation.

☝️Q6: How long should supplemental steroids continue postoperatively?

Stress peaks at 48–72 hours. If recovery is uncomplicated, start tapering after Day 2–3. Aim to return to baseline within one week after surgery.

📝 Summary and Take Home Messages

Perioperative steroid care has evolved from automatic high doses to thoughtful, risk-stratified plans. Your aim is twofold: prevent adrenal crisis and avoid over-supplementation.

🔑 Key Points

Suspect Adrenal Crisis? Administer Hydrocortisone 100 mg IV/IM immediately with 1 L saline before diagnostic confirmation
Chronic Users (No Confirmed AI): Continuing the usual baseline dose (or IV equivalent) is often adequate and avoids overdosing harm
Tiered Dosing (Hydrocortisone):
Minor Stress: 25–50 mg once
Moderate Stress: 50–75 mg/day
Major Stress: 100–200 mg/day
Tapering: Highest stress period is 48–72 hours. Taper to baseline within one week if recovery is uncomplicated
Dexamethasone: Lacks mineralocorticoid activity. NOT appropriate as primary replacement for Primary AI (Addison’s)
HPA Axis Recovery: Morning serum cortisol >10 µg/dL (300 nmol/L) generally indicates a stress-ready axis

🎓 For Exam Candidates:

Know the three AI types and mechanisms
Memorize the AC protocol: HC 100 mg IV + 1 L NS STAT, then HC 200 mg/24 h
Remember the HPA recovery marker: AM cortisol >10 µg/dL (300 nmol/L)
Understand why dexamethasone is not primary replacement in Primary AI

🏥 For Clinical Practice:

Risk-stratify every patient and ask about all steroid routes
Match dose to stress—not everyone needs 200 mg/day
Use clinical judgment: refractory hypotension post-op? Give HC 100 mg IV while you investigate
Adopt the new paradigm: for many chronic users without confirmed AI, continuing the baseline dose is evidence-based and safer than routine high “stress” dosing

📚 References & Further reading

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