1. 1/9/2016 1 Steroids and Anesthetic Considerations Sass Elisha, CRNA, Ed.D sass.m.elisha@kp.org

2. 1/9/20162 WORLDS FAVORITE PHARMACOLOGIST

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4. 4 REGULATION OF THE HPA AXIS Stimulation Inhibition  Corticotropin-releasing hormone  Decreased cortisol  Transition from sleep to awake Physiologic Stress  Hypoglycemia  Trauma/Sepsis  Alpha and Beta-agonists Adrenocorticotropic hormone (ACTH) Increased cortisol General anesthesia Etomidate

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6. 6 HPA Axis Suppression Patients who have received supraphysiologic doses of steroids for a period of ___________should be considered to have some degree of HPA axis impairment during acute stress. HPA axis dysfunction is dependent on the _____ and ______of steroid therapy. Who should receive steroids preoperatively?

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11. Drug Potency NA Retain Duration Cortisol (Hydrocortisone) 118-12h Prednisone40.818-36h Dexamethasone25036-54h

12. 1/9/201612 Various Steroids and Equipotent Dosages Hydrocortisone 100 mg Prednisone 25 mg Methylprednisolone 20mg Dexamethasone 3.75 mg Your patient is at risk for acute adrenal crises. There is no hydrocortisone in the hospital. What do you do? Dexamethasone 8 mg is: A. a lot of steroid, B. a little bit of steroid

13. 1/9/201613 Mechanism of Action of Steroid Hormones  Acute response occurs in seconds to minutes and rapidly increases cortisol production by increasing the supply of cholesterol substrate. Chronic response occurs over hours to days and reflects genetic changes that increases steroidogenic enzymes.

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17. 1/9/201617 Cortisol Secretion Cortisol secretion=Highest in the morning (20ug/dl) Lowest around midnight (5ug/dl) Normal daily output of cortisol=_________ Maximum daily output of cortisol= ______ Why don’t patients develop adrenal insufficiency after 8 mg of Decadron?

18. 1/9/201618 Absorption of Exogenous Steroids Steroids are given by IV, IM, PO, IA, epidural routes. Absorption occurs by; inhalation, mucosal and skin applications. Do patients taking steroids via inhalation or skin routes need preoperative steroids? Epidural steroids?

19. 1/9/201619 Transport to Tissues Cortisol is 90% bound to cortisol- binding globulin (CBG) and albumin in the blood Only 10% of cortisol is actively available to exert actions via intracellular receptors

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21. 1/9/201621 Metabolism and Excretion In the liver, cortisol undergoes phase 1 oxidation reduction reaction to form dihydrocortisol and tetrahydrocortisol. The above metabolites are conjugated to water soluble substances and excreted by the kidneys.

22. Signs and Symptoms Associated with Acute Adrenal Crises Neurologic Hemodynamic Metabolic-Hypog _ _ _ _ _ _ _ Hypov _ _ _ _ _ _ Hypon _ _ _ _ _ _ _ Hyperk_ _ _ _ _ _ Metabolic _ _ _ _ _ _ _ _ 1/9/201622

23. 1/9/201623 Electrolyte Abnormality Associated with Acute Adrenal Crises Acute Adrenal Crises H M

24. 1/9/201624 Treatment of Acute Adrenal Crises Hydrocortisone 100 mg IV Hydrocortisone 200 mg IV infusion over 24 hours Fluid replacement Glucose replacement and monitoring Arterial line placement Vasopressor and inotropic support as needed

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26. Minor Surgical Stress (inguinal hernia) 25 mg hydrocortisone or equivalent Moderate Surgical Stress (cholecystectomy, hysterectomy, colon resection) 50-75 mg/d of hydrocortisone or equivalent for 1-2 d, then resume preoperative dosage Major Surgical Stress (AAA repair, cardiac bypass) 100-150 mg/d of hydrocortisone or equivalent for 2-3 days then resume preoperative dosage

27. 1/9/201627 Etomidate-Inhibition of Cortisol

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30. Concerns about Etomidate and Acute Adrenal Crises Higher mortality after Etomidate administration in patients with septicemia despite dosage Alternative drug choices for induction in critically ill patients? 1/9/201630

31. 1/9/201631 MOC-Etomidate Soft analogue of Etomidate Rapid metabolism No adrenocortical suppression

32. 1/9/201632 Physiologic Effects of Cortisol/Synthetic Steroids Redistribution of blood flow to CNS Increased cardiac output Increased respiratory rate Increased gluconeogenesis Decreased inflammatory and immune response Enhanced analgesia

33. 1/9/201633 Steroids and Drug Interactions Digoxin (inc toxicity, cardiomyopathy) Barbiturates/phenytoin (dec steroid effects) Diuretics (hypokalemia) NSAIDS (stomach ulcers) Oral anticoagulants (enhanced or decreased efficacy) Antidiabetics (decreased effectiveness)

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36. 1/9/201636 Got STEROIDS for PONV? Decadron most efficacious if given prior to induction of anesthesia Decadron most effective with 8 mg dose 1. Onset 1 h 2. Peak 8-10 h 3. Duration 72 h Should I give 100 mg hydrocortisone for potential adrenal insufficiency and 8mg decadron for PONV?

37. 1/9/201637 Steroids and Septic Shock Sepsis=iNOS Increased nitric oxide=vasodilator Cytokines decrease #’s/affinity of glucocorticoid receptors for cortisol Surviving sepsis campaign (SSC), 2013 200 mg hydrocortisone if ↓BP after volume resuscitation and max vasopressors

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39. 1/9/201639 Steroids to Reduce Postoperative Pain De Oliveira, 2011 Decadron 0.1 mg/kg is effective in reducing postoperative pain and decreasing opioid consumption after ambulatory gynecologic surgery.

40. 1/9/201640 Steroids and Interscalene Nerve Blocks Cummings KC, 2011 Grp A-Ropivicane/Bupivicaine 0.5% Grp B-Medication above w Decadron 8 mg Decadron increased time of analgesia from 11-15 h to 23 h with Decadron postop

41. 1/9/201641 Steroids and Diabetes Physiologic stress response Steroids increase gluconeogenesis Decadron 10 mg IV significantly increases blood sugar 180 minutes post injection in healthy volunteers Effects greatest in insulin dependent diabetics Should we give steroids for PONV to patients with diabetes?

42. 1/9/201642 References Boonen E., Reduced cortisol metabolism during critical illness., 2013. NEJM, 1477-1488. Chan MC., Mitchell, AL., Shorr, AF. 2012. Etomidate is associated with mortality and adrenal insufficiency in sepsis: A meta-analysis. Crit Care Med, 40(11), 2945-2952. Cotton B. A., 2008. Increased risk of adrenal insufficiency following etomidate exposure in critically injured patients, Arch Surg. 143(1), 62-67. Cummings KC., 2011. Effect of dexamethasone on the duration of interscalene nerve blocks with ropivicaine or bupivicaine,107(3),446-453. De Oliveira GS., 2011. Dose ranging study of the effect of preoperative dexamethasone on postoperative quality of recovery and opioid consumption after gynecologic surgery, BJA, 3, 362-371. Elisha S, Gabot M, Giron S. 2011. Steroids. In Pharmacology for Nurse Anesthesiology, Ouelette R, Joyce J, eds. 303-311. Fujii Y, Itakura M. 2010. Reduction of postoperative nausea, vomiting, and analgesic requirement with dexamethasone for patients undergoing laparoscopic cholecystectomy. Surgical Endoscopy, 24, 692-696.

43. 1/9/201643 More References Grover V. K., 2007. Steroid therapy-Current indications in practice, Indian Journal of Anesthesia. 51(5), 389-393. Jakobsson J., 2010.Preoperative single dose intravenous dexamethasone during ambulatory surgery. Curr Opin Anesthes. 23, 682-686. Khan Shariq., 2013. Wound complications and dexamethosone, Anesth & Analg. 116(5), 965-967. Legrand M., Plaud, B. 2013. Etomidate and general anesthesia: The butterfly effect? Anes & Analg, 117(6) 1267-1268. Marik PE, Varon J. 2008. Requirement of postoperative stress doses of corticosteroids. Arch Surg. 143(12), 1222-1226. Vinclair M., 2007. Duration of adrenal inhibition following a single bolus dose of etomidate in critically ill patients, Intensive Care Med. 37-43. Wakim J., 2006. Anesthetic implications for patients receiving exogenous corticosteroids. AANA Journal, 74(2), 133-139. Wang Y., 2009. Effects of different glucocorticoids on blood sugar during surgery under general anesthesia. Zhonghua, 89(27),1913-15. Wang J.J., 2000. The effect of timing of dexamethasone administration on its efficacy as a prophylactic antiemetic for postoperative nausea and vomiting. Anes & Analg, 91, 139-139.