Give an ICU scenario where a 62‑year‑old man with hypertension and poorly controlled type 2 diabetes, admitted for community‑acquired pneumonia progressing to septic shock, receives hydrocortisone 200 mg per day and develops severe hyperglycemia, opportunistic fungal infection, and secondary adrenal insufficiency after abrupt discontinuation.

ICU Scenario: Hydrocortisone Complications in Septic Shock

Clinical Presentation

A 62-year-old man with hypertension and poorly controlled type 2 diabetes admitted for community-acquired pneumonia progressing to septic shock receives hydrocortisone 200 mg per day and develops severe hyperglycemia, opportunistic fungal infection, and secondary adrenal insufficiency after abrupt discontinuation—illustrating multiple preventable complications of corticosteroid therapy in critical illness.

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Initial Clinical Course

Day 1-3: Appropriate Indication but High-Risk Patient

• The patient presents with community-acquired pneumonia progressing to septic shock requiring norepinephrine at 0.4 μg/kg/min despite adequate fluid resuscitation 1
• Hydrocortisone 200 mg/day is initiated per Surviving Sepsis Campaign guidelines for vasopressor-dependent septic shock 1, 2
• Critical oversight: The patient's poorly controlled diabetes (likely HbA1c >8%) places him at extremely high risk for steroid-induced hyperglycemia 1
• The hydrocortisone is administered as bolus doses (50 mg IV every 6 hours) rather than continuous infusion, which significantly increases blood glucose peaks 1

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Complication #1: Severe Hyperglycemia (Days 2-7)

Mechanism and Manifestation

• Repetitive bolus dosing causes severe inter-individual blood glucose peaks that are not detectable with continuous infusion 1
• Hydrocortisone trials consistently demonstrate significant increases in hyperglycemia (RR 1.72,95% CI 1.38-2.14) 1, 3
• Blood glucose levels spike to 350-450 mg/dL within 2-4 hours of each hydrocortisone bolus 1
• The patient's pre-existing poorly controlled diabetes amplifies this effect 3

Clinical Consequences

• Persistent hyperglycemia (>250 mg/dL for 72+ hours) impairs neutrophil function and increases infection risk 3, 4
• Inadequate insulin titration fails to achieve tight glycemic control 3
• Osmotic diuresis from hyperglycemia worsens intravascular volume depletion 1

Prevention Strategy Missed

• The Surviving Sepsis Campaign explicitly recommends continuous infusion over repetitive bolus injections to avoid glucose peaks (grade 2D) 1
• Intensive insulin therapy with hourly glucose monitoring should have been initiated immediately 3

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Complication #2: Opportunistic Fungal Infection (Days 5-10)

Development of Invasive Candidiasis

• On day 5, the patient develops fever (38.5°C) despite broad-spectrum antibiotics 5, 4
• Blood cultures grow Candida albicans on day 7 5
• Corticosteroids exacerbate systemic fungal infections and should not be used in their presence unless needed to control drug reactions 5
• The FDA label explicitly warns that corticosteroids may mask signs of current infection, delaying recognition 5

Pathophysiology

• Corticosteroids at 200 mg/day hydrocortisone cause dose-dependent immunosuppression 5, 4
• Persistent hyperglycemia (>250 mg/dL) creates an optimal environment for fungal growth 3, 4
• The combination of corticosteroid-induced immunosuppression and hyperglycemia dramatically increases fungal infection risk 5, 4
• Corticosteroids blunt the febrile response, masking the infection until it becomes severe 5

Clinical Impact

• Invasive candidiasis in septic shock carries 40-60% mortality 4
• The patient requires escalation to micafungin and removal of central venous catheter 5
• ICU length of stay is prolonged by 12-15 days 4

Prevention Missed

• The FDA label recommends that patients on corticosteroids are more susceptible to infections and require heightened surveillance 5
• Prophylactic antifungal therapy should have been considered given multiple risk factors (diabetes, corticosteroids, broad-spectrum antibiotics, central line) 5

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Complication #3: Secondary Adrenal Insufficiency from Abrupt Discontinuation (Day 8)

The Critical Error

• On day 8, vasopressors are successfully weaned off 1
• The ICU team abruptly stops hydrocortisone without tapering 1, 2
• Within 18-24 hours, the patient develops recurrent hypotension (BP 75/45 mmHg), tachycardia, and requires reinitiation of norepinephrine 1, 2

Mechanism of Hemodynamic Collapse

• One crossover study demonstrated hemodynamic and immunologic rebound effects after abrupt cessation of corticosteroids 1
• Exogenous corticosteroids suppress the hypothalamic-pituitary-adrenal axis within 5-7 days of continuous therapy 2, 6
• Abrupt withdrawal causes acute relative adrenal insufficiency with reconstituted inflammatory response 2
• The patient's endogenous cortisol production remains suppressed for days to weeks after stopping exogenous steroids 2, 6

Guideline Violation

• The Surviving Sepsis Campaign explicitly suggests tapering steroids when vasopressors are no longer required rather than stopping abruptly (grade 2D) 1, 2
• The SCCM/ESICM 2017 guideline recommends tapering gradually over 6-14 days to avoid rebound inflammation 2
• Full-dose hydrocortisone should be maintained for at least 3-5 days before initiating taper 2

Clinical Consequences

• The patient requires reinitiation of vasopressors and hydrocortisone 1, 2
• An additional 5 days of ICU care is needed 2
• Risk of recurrent septic shock and multi-organ dysfunction increases 2, 4

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Complication #4: ICU-Acquired Weakness (Days 10-21)

Neuromuscular Manifestation

• By day 14, the patient demonstrates profound proximal muscle weakness (Medical Research Council score <48/60) 1
• Unable to lift arms against gravity or perform straight leg raise 1
• Corticosteroids may increase the risk of neuromuscular weakness (low quality evidence from seven RCTs) 1

Pathophysiology

• Toxic effects on nerve and muscle cells from prolonged corticosteroid exposure 1
• Hyperglycemia from corticosteroid use contributes to neuropathy 1
• The combination of corticosteroids, neuromuscular blocking agents (if used), and critical illness creates synergistic toxicity 1

Long-Term Impact

• Weakness compromises the patient's ability to function independently and delays recovery 1
• Prolonged mechanical ventilation (additional 7-10 days) due to inability to protect airway 1
• Requires transfer to long-term acute care facility for rehabilitation 1
• Quality of life at 6 months is significantly impaired 1

Underrecognition Problem

• RCTs that relied on investigator identification probably underestimated the risk of neuromuscular weakness 1
• Only two of seven RCTs prospectively evaluated weakness one month after enrollment 1

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Additional Metabolic Complications

Hypernatremia (Days 4-9)

• Serum sodium rises to 152 mEq/L by day 6 1, 3
• Corticosteroids probably increase the risk of hypernatremia 1
• Requires free water replacement and contributes to altered mental status 1, 3

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What Should Have Been Done: Evidence-Based Prevention

Optimal Hydrocortisone Administration

1. Use continuous infusion (10 mg/hour = 240 mg/24 hours) instead of bolus dosing to minimize glucose peaks 1
2. Initiate intensive insulin protocol immediately with hourly glucose monitoring targeting 140-180 mg/dL 3
3. Monitor serum sodium daily for hypernatremia 1, 3

Infection Surveillance

1. Heightened surveillance for opportunistic infections given immunosuppression from corticosteroids 5
2. Consider prophylactic antifungal therapy in high-risk patients (diabetes, central line, broad-spectrum antibiotics) 5
3. Recognize that corticosteroids mask fever and other infection signs 5

Proper Discontinuation Protocol

1. Maintain full-dose hydrocortisone for at least 3-5 days after vasopressor discontinuation 2
2. Taper gradually over 6-14 days (e.g., 200 mg/day × 3 days → 100 mg/day × 3 days → 50 mg/day × 3 days → 25 mg/day × 2 days → stop) 2
3. Monitor closely for hemodynamic deterioration during and after taper 1, 2
4. If shock recurs, immediately reinitiate full-dose corticosteroids 1, 2

Neuromuscular Monitoring

1. Perform daily awakening trials and assess muscle strength 1
2. Early mobilization and physical therapy to mitigate weakness 1
3. Avoid neuromuscular blocking agents if possible 1

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Key Clinical Pitfalls Illustrated

Pitfall #1: Bolus Dosing in Diabetic Patients

• Never use repetitive bolus hydrocortisone in patients with diabetes—the glucose peaks are severe and unpredictable 1

Pitfall #2: Inadequate Infection Surveillance

• Corticosteroids mask infection signs—maintain high index of suspicion and low threshold for cultures 5

Pitfall #3: Abrupt Discontinuation

• Never stop corticosteroids abruptly after ≥5-7 days of therapy—always taper over 6-14 days 1, 2

Pitfall #4: Ignoring Baseline Risk Factors

• Patients with poorly controlled diabetes are at extreme risk for all corticosteroid complications—consider whether the mortality benefit (2% absolute reduction) outweighs the harm in this specific patient 1, 3

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Outcome of This Case

• Total ICU stay: 28 days (expected 10-14 days without complications) 1, 4
• Developed invasive candidiasis requiring 21 days of antifungal therapy 5, 4
• Severe ICU-acquired weakness requiring transfer to long-term acute care facility 1
• Unable to return to independent living at 6 months 1
• All complications were preventable with adherence to guideline recommendations 1, 2