1. Topic review Glucocorticoids R2Parichat Nilyam R2Sasiya Siriratwarangkul Supervised by Dr.Kittipong Sujirattanawimol

3. Glucocorticoids + Mineralocorticoids + Sex hormone Corticosteroid= Cortex + Steroid Glucocorticoids

4. Adrenal gland

7. Introduction Cortisol is the predominant corticosteroid secreted from the adrenal cortex in humans Secreted according to a diurnal pattern under the influence of ACTH from the pituitary gland under the influence of CRH from the hypothalamus Review article: Corticosteroid Insufficiency in Acutely Ill Patients N Engl J Med 2003;348:727-34.

8. Regulation of Cortisol Secretion 3 major mechanisms 1. Negative feedback mechanism 2. Diurnal variation 3. Stress physical psychological physiological Review Article : Applications of Steroid in Clinical Practice International Scholarly Research Network ISRN Anesthesiology Volume 2012

13. Glucocorticoids: Physiological Effect Metabolism - Regulator of carbohydrate, protein, lipid, and nucleic acid metabolism - Stimulate gluconeogenesis - Promote mobilization and oxidation of fatty acids - Excess cortisol causes “buffalo hump”

14. buffalo hump

15. Blood Pressure Control - Increase vascular smooth muscle sensitivity to pressor agents - Reduce nitric oxide-mediated endothelial dilatation - Increase filtration fraction and glomerular hypertension - Synthesis of angiotensinogen and atrial natriuretic peptide - Decrease prostaglandin synthesis

16. cardiovascular system - influence on myocardial responsiveness, arteriolar tone, and capillary permeability - Hypocorticism increased capillary permeability inadequate vasomotor response decrease in cardiac output and cardiac size - Hypercorticism leads to chronic arterial hypertension

17. Blood Pressure Control - increases vascular smooth muscle sensitivity to pressor agents - reduces nitric oxide-mediated endothelial dilatation

18. Anti-Inflammatory Effects - Stabilize lysozyme membranes - Decrease the release of inflammation - Decrease capillary permeability - Interfere with complement pathway activation - Interfere with formation of inflammatory mediators

19. Bone and Calcium Metabolism - Inhibit osteoblast function - Excess glucocorticoid causes osteopenia and osteoporosis

20. CNS and Mood - depression - euphoria - psychosis - apathy - lethargy

21. Developmental Changes - maturing of number of systems in 3 rd trimester - pulmonary surfactant - enzyme in the liver - phenylethanolamine N-methyltransferase

22. Eye -raise intraocular pressure Gut - Chronic steroid used increases the risk of peptic ulcer - Pancreatitis with fat necrosis

23. Endocrine Effects - suppress thyroid axis - inhibit GRH pulsatility

24. Effect of Anaesthesia and Surgery Plasma cortisol levels typically increase from 2- 10 folds Maximum ACTH and cortisol levels are reached in the early postoperative period

25. Cortisol return to normal within 24 hrs postoperatively May remain elevated as long as 72 hrs

26. Anesthetic drugs VS HPA response – Etomidate – Large doses of opioid – Volatile anesthetics

28. glucocorticoidAnti- inflammatory potency Na-retaining potency durationEquivalent dose Cortisol11<12 hr20 Prednisolone Methyl-P 4545 0.8 0.5 12-36 hr5454 Dexa -methasone 250>36 hr0.75

29. Adverse Drug Effects of Steroid Supplementation

30. Risks with Short-Term (Perioperative) Supplementation aggravation of hypertension fluid retention delayed wound healing hypokalemia increased susceptibility to infection decreased glucose tolerance

31. Risks with Long-Term Supplementation HPA axis suppression hypokalemia metabolic alkalosis edema weight gain hyperglycemia osteoporosis peptic ulcer & GI bleeding buffalo hump proximal skeletal muscle myopathy

32. Application of Steroids in anesthesia

33. Perioperative steroid replacement therapy Normal circulating Cortisol level: -highest at 6-8 a.m. : 6-23 mcg/dL -lowest at midnight : 2.9-13 mcg/dL Mean cortisol production rate is 5.7 mg/m 2 /day or about 10 mg/day In severe surgical stress: 75-150 mg/day

34. Adrenal insufficiency Primary adrenal insufficiency: impairment of the adrenal glands – glucocorticoid,mineralocorticoid and sex hormone are lost Secondary adrenal insufficiency : secondary to hypothalamic-pituitary disease or suppression of the HPA axis – Sheehan’s syndrome, long continued exogenous steroid

35. Recovery time of normal HPA axis varies from 2 days to 12 months after discontinuation of steroid therapy Ability to respond to stress returns by 2 months after discontinuation of steroid therapy Review Article:Applications of Steroid in Clinical Practice Safiya Shaikh, International Scholarly Research Network ISRN Anesthesiology,Volume 2012, Article ID 985495

36. Degree of HPA suppression is related to choice of steroid preparation, duration and dose of steroid therapy A. S. Krasner, “Glucocorticoid-induced adrenal insufficiency,” Journal of the American Medical Association, vol. 282, no. 7, pp.671-676,1999.

37. Glucocorticoid potency correlates with risk for adrenal insufficiency The equivalence of 15 mg/day of prednisolone for more than 3 weeks should be suspected of having HPA suppression A. S. Krasner, “Glucocorticoid-induced adrenal insufficiency,” Journal of the American Medical Association, vol. 282, no. 7, pp.671-676,1999

39. Patient currently taking steroids <10 mg/dAssume normal HPA response Additional steroid cover not required >10 mg/dMinor Sx25mg of hydrocortisone at induction Moderate SxUsual periop. steroid +25mg of hydrocortisone at induction +100 mg/d for 24 hr Major SxUsual periop. steroid +25mg of hydrocortisone at induction + 100 mg/d for 48-72hr Perioperative glucocorticoid coverage: a reassessment 42 years after emergence of a problem M. Salem Annals of Surgery, vol. 219, no. 4, pp. 416–425, 1994.

40. Patient stopped taking steroid Stopped < 3 moTreat as if on steroids Stopped > 3 moNo periop. steroid necessary Perioperative glucocorticoid coverage: a reassessment 42 years after emergence of a problem M. Salem Annals of Surgery, vol. 219, no. 4, pp. 416–425, 1994.

44. Retrospective, prospective and randomised studies all methodologically flawed Continuation of the basal glucocorticosteroids is sufficient to stress Perioperative glucocorticosteroid supplementation is not supported by evidence Dylan W. de Lange : European Journal of Internal Medicine 19 (2008) 461–467

45. Current and rather defensive strategy of perioperative supraphysiological glucocorticosteroid supplementation is not embedded in medical evidence High doses of glucocorticosteroids have disadvantages that should not be ignored Perioperative glucocorticosteroid supplementation is not supported by evidence Dylan W. de Lange : European Journal of Internal Medicine 19 (2008) 461–467

47. Patients receiving therapeutic doses of corticosteroids undergo a surgical procedure do not routinely require stress doses of corticosteroids so long as they continue to receive their usual daily dose of corticosteroid Requirement of Perioperative Stress Doses of Corticosteroids A Systematic Review of the Literature Paul E. Marik, MD; Joseph Varon, MD Arch Surg. 2008;143(12):1222-1226

48. Patients receiving physiologic replacement doses of corticosteroids owing to primary adrenal insufficiency require supplemental doses of corticosteroids in the perioperative period Adrenal function testing is not required in these patients Requirement of Perioperative Stress Doses of Corticosteroids A Systematic Review of the Literature Paul E. Marik, MD; Joseph Varon, MD Arch Surg. 2008;143(12):1222-1226

50. There is currently inadequate evidence to support the use of supplemental perioperative steroids in patients with adrenal insufficiency Administration of the patient’s daily maintenance dose of corticosteroid may be sufficient and supplemental doses are not required Supplemental perioperative steroids for surgical patients with adrenal insufficiency (Review) prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2012, Issue 12

51. There is a need for high quality RCTs in various surgical settings to assess the requirement for supplemental perioperative steroids when patients with adrenal insufficiency undergo surgery Supplemental perioperative steroids for surgical patients with adrenal insufficiency (Review) prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2012, Issue 12

52. Thank you

53. Postoperative nausea and vomiting Dexamethasone inhibit the synthesis of prostaglandin and various other inflammatory mediators acting on chemoreceptor trigger zone

54. may and cause emesis

55. Post Intubation Laryngeal Oedema commonly given after multiple attempts at intubation Dexamethasone 0.1-0.2 mg/kg iv its efficacy has not been confirmed Dexamethasone 0.6 mg/kg orally is effective treatment for children with mild croup

56. Post Extubation Stridor typically occurs in people who have been intubated for several days administered at least 12 hrs prior to extubation for patients who have been intubated for more than 3 days or who are at increased risk of reintubation

57. multiple doses of steroids reduce the risk for edema and reintubation, whereas a single dose only shows a non significant trend toward effectiveness steroids were most useful when administered in high risk patients, as determined by a cuff- leak test, and when the steroids were administered at least 4 hrs before extubation. Benefits were less clear if patients were not selected according to risk

58. Epidural Steroid Injection (ESI) treat back pain (mainly due to nerve root irritation) in patients with a wide variety of spine pathologies including radiculopathy, spinal stenosis, diskspace narrowing, annular tears, spondylosis, spondylolisthesis,vertebral fractures, and postlaminectomy syndrome effective alternative to surgical treatment and is best for patients with lumbar disc disease who have not improved after 4 weeks of conservative medical therapy

59. Steroids in Traumatic Spinal Cord Injury remains controversial for cord injuries because improvement is minimal and difficult to document high dose methyl prednisolone with an IV bolus of 30 mg/Kg followed by 5.4 mg/kg/hr infusion for 23 hrs Clinicians should consider AI in patients with spinal cord injury receiving glucocorticoids

60. Sepsis and Steroid severe sepsis or in septic shock were found to have occult or unrecognized adrenal insufficiency incidence may be as high as 28% in seriously ill patients significantly higher rate of success in withdrawal of vasopressor therapy may result from suppression of overexuberant and dysregulated immune responses, suppression of inflammatory responses through a variety of mechanisms, and upregulation of adrenoreceptor function

61. Nosocomial infection, reactivation of latent infection, hyperglycaemia, bone metabolism, and psychosis as well as intensive care associated paresis must also be considered The current evidence does not support the use of hydrocortisone doses above 200 mg/day

62. Steroids and There Applications as Analgesic Adjuncts mediated by anti-inflammatory and immune suppressive effect decreased production of various inflammatory mediators that play a major role in amplifying and maintenance of pain perception Dexamethasone microspheres have been found to prolong the block duration in animal and human studies, and adding methylprednisolone to local anesthetic increases the duration of axillary brachial block

63. glucocorticoids act on the prostaglandin system differently than NSAIDs and have other antiinflammatory effects, there may be better analgesia when glucocorticoids are added to NSAIDs

64. Adverse Drug Effects of Steroid Supplementation

65. Risks with Short-Term (Perioperative) Supplementation aggravation of hypertension fluid retention stress ulcers & GI bleeding psychiatric disturbances delayed and abnormal wound healing hypokalemia osteoporosis increased susceptibility to infection decreased glucose tolerance

66. Risks with Long-Term Supplementation HPA axis suppression hypokalemia metabolic alkalosis oedema weight gain hyperglycemia redistribution of body fat buffalo hump proximal skeletal muscle myopathy