Steroids

Corticosteroids

• The actions of corticosteroids are classified according to the potencies of their compounds to:

  • Mineralocorticoid Effect: Evokes distal renal tubular reabsorption of sodium in exchange for potassium ions.

  • Glucocorticoid Effect: Produces an anti-inflammatory effect.

    • Critical for maintaining homeostasis during severe stress.

• Mechanism of Action:

  • Glucocorticoids:

    • Produced in the zona fasciculata of the adrenal cortex.

    • Attach to cytoplasmic receptors to enhance or suppress transcription of DNA.

    • Leads to changes in protein synthesis.

    • Inhibit cytokine secretion via posttranslational effects.

  • Mineralocorticoids:

    • Produced in the zona glomerulosa of the adrenal gland.

    • Regulate water and electrolyte balance.

    • Receptors present in distal renal tubules, colon, salivary glands, and hippocampus.

Cortisol

• Cortisol is a stress hormone produced in the zona fasciculata of the adrenal cortex. It is the most potent endogenous glucocorticoid produced.

  • Controls body homeostasis, stress, and immune responses.

  • Aids in the metabolism of fats, proteins, carbohydrates.

  • Increases blood glucose levels, providing additional energy for muscles.

• Released by the adrenal gland but regulated by the pituitary gland.

• Cortisol Levels:

  • Maximal levels occur just before awakening (6-9 am).

  • Lowest levels between 11 pm to 1 am.

  • Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, increasing serum ACTH and cortisol levels.

• High Cortisol Level Symptoms:

  • High blood pressure.

  • Fatigue.

  • Erectile dysfunction.

  • reduced sex drive

  • weakened immune response

  • weight gain

  • hyperglycemia

  • insomnia

  • poor concentration/memory

• Low Cortisol Level Symptoms:

  • Sugar and salt cravings.

  • Decreased sex drive.

  • Anxiety.

  • Weight gain.

  • Insomnia

  • Irritability.

  • Bone and muscle loss.

  • Depressed mood.

  • fatigue

Exogenous Glucocorticoids

• Purpose of Administration: Have anti-inflammatory and immunosuppressive properties.

• Anti-inflammatory Properties:

  • Glucocorticoids reduce both early and late stages of inflammation.

  • Suppress initial vasodilation and infiltration of leukocytes, leading to decreased pain.

• Immunosuppressive Properties:

  • Used to treat diseases associated with an overactive immune system, such as:

    • Allergic reactions (e.g., angioneurotic edema, asthma).

    • Collagen-vascular disorders (e.g., lupus erythematosus).

    • Eye diseases (e.g., acute uveitis).

    • Gastrointestinal diseases (e.g., inflammatory bowel disease).

    • Hematologic disorders (e.g., acquired hemolytic anemia).

    • Systemic inflammation and infections.

    • Inflammatory conditions of bones and joints (e.g., arthritis).

    • Neurologic disorders (e.g., cerebral edema).

    • Organ transplants (to prevent rejection).

    • Pulmonary diseases (e.g., aspiration pneumonia).

    • Renal disorders (e.g., nephrotic syndrome).

    • Skin diseases (e.g., atopic dermatitis).

    • Thyroid diseases (e.g., malignant exophthalmos).

  • Immunosuppression occurs via three mechanisms:

  1. Direct the development of undifferentiated T helper cells.

  2. Inhibit synthesis of interleukins 1 and 2.

  3. Induce T cell apoptosis.

Exogenous Corticosteroids

• Administration Routes: Topical, oral, intravenous, intramuscular, inhaled, intranasal, rectal, and ophthalmic.

• Metabolism:

  • Metabolized by the liver.

  • Excreted by the kidneys.

• Side Effects:

  • Redistribution of fat from extremities to face and trunk.

  • Acne.

  • Insomnia.

  • Increased appetite.

  • Increased gluconeogenesis.

  • Opportunistic infections.

  • Psychosis.

  • Long-term high doses may cause iatrogenic Cushing's syndrome.

• Examples of synthetic corticosteroids:

• Short Acting:

  • Hydrocortisone.

  • Cortisone.

  • Prednisone.

  • Prednisolone.

  • Methylprednisolone.

• Intermediate Acting:

  • Triamcinolone.

  • Paramethasone.

• Long Acting:

  • Betamethasone.

  • Dexamethasone.

Dexamethasone

• Glucocorticoid steroid that is a fluorinated derivative of prednisolone.

• Common Dosages:

  • 4 mg for postoperative nausea and vomiting (PONV).

  • 4-12 mg for airway edema.

  • 10 mg for head and back surgeries.

  • **0.75 mg is equivalent to 20 mg of cortisol.

• Uses in Anesthesia:

  • Postoperative nausea and vomiting (PONV).

  • Airway edema.

  • Cerebral edema.

  • Pain management.

  • Anaphylaxis.

  • Epidural steroid injection.

  • Regional nerve blocks

Hydrocortisone (Solu-Cortef)

• Commonly used for “Stress Dose” in patients with recent steroid history.

  • Stress dosing

  • Anaphylaxis.

  • Allergic reactions.

• Dosage: 100 mg.

Methylprednisolone (Solu-Medrol)

• Glucocorticoid with minimal mineralocorticoid activity.

  • 5 times more potent than hydrocortisone.

• Uses:

  • Anti-inflammatory.

  • Respiratory support (short-term to inhibit bronchoconstriction).

  • Treat or prevent allergic reactions.

  • Spinal shock.

• Dosage:

  • Standard: 40-60 mg IV q6 hours.

  • For spinal cord injury: 30 mg/kg over 15 minutes followed by infusion of 5.4 mg/kg for 23 hours (up to 48 hours).

  • Common anesthesia dose: 125 mg (not frequently used due to hyperglycemic and immunosuppressive effects).

  • 4 mg has an anti-inflammatory effect equivalent to 20 mg of cortisol.

Prednisolone

• Often used as the sole treatment for adrenocorticoid insufficiency.

• Predominant glucocorticoid activity; minimal mineralocorticoid activity.

Triamcinolone (Kenalog)

• Corticosteroid with reduced mineralocorticoid effect compared to prednisolone.

• Commonly used for epidural steroid injections off-label.

• Side Effects:

  • May cause mild diuresis initially with sodium loss.

  • Might induce edema in patients with decreased GFR

  • Can lead to unusual side effects: skeletal muscle weakness, anorexia, and sedation.

Steroid Main Points

• 25 mg Cortisone Equivalents:

  • 20 mg Hydrocortisone

  • 4 mg Methylprednisone

  • 5 mg Prednisolone/prednisone

  • 0.75 mg Dexamethsone

• Short acting: cortisone and hydrocortisone

• intermediate acting: methylprednisone, prednisolone/prednisone

• long acting: dexamethasone

• Most to least antiinflammatory effects:

  • Aldosterone (0)

  • Cortisone (0.8)

  • Cortisol (1)

  • Prednisolone/prednisone (4)

  • Methylprednisone (5)

  • Dexamethasone (25)

Perioperative Management

• Patients receiving glucocorticoids for a limited time should continue their medication as prescribed, as the likelihood of short-term use affecting the HPA axis is minimal.

• For patients on glucocorticoids for an extended period, the perioperative management with a “stress dose” of steroids remains controversial.

  • Dosing Recommendations:

    • For Minor Surgery (e.g., inguinal hernia repair): Hydrocortisone 100 mg intravenously at induction + maintenance dose (approx. 20 mg/d).

    • For Major Surgery (e.g., chest or abdominal surgery): Hydrocortisone 100 mg at induction + 100 mg every 8 hours for 24 hours.

    • Nagelhout has the following recs:

      • Minor stress is 25 mg hydrocortisone

      • Moderate stress is 50-75 mg hydrocortisone

      • Major stress (e.g., CABG) is 100-150 mg hydrocortisone

• HPA Response Assessment:

  • Patients currently taking steroids < 10 mg/d: Assume normal HPA response.

  • Patients currently on steroids > 10 mg/d may have a compromised HPA response and need coverage.

    • Nagelhout says patients taking >20 mg/day of prednisone for >3 weeks have a suppressed HPA axis and require stress-dose steroids

  • Patients who stopped taking steroids < 3 months ago may have a compromised HPA response, while those who stopped > 3 months ago can assume normal HPA response.