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Corticosteroids the often used but least understood drug


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Corticosteroids the often used but least understood drug

  1. 1. CORTICOSTEROIDS The most coveted drug used but least understood . Dr Avijit K Prusty,2nd year PG student Dept. of Anaesthesiology SCB medical college, Guided By-.Assoc Prof Dr Mahendra kumar Nayak 1
  2. 2. • The term “CORTICOSTEROIDS” derived from 2 words • CORTEX=secreted from adrenal cotex • STEROIDS=have a common steroid nucleus • These drugs are most commonly used as anti- inflammatory drugs and hence before going into topic proper we should have knowledge about • 1. inflammation 2.stages 3.mediators 4.inflammatory cascade 2
  3. 3. Inflammation: • it is a biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. • Inflammation may ends with either : Complete healing of tissues Permanent destruction of tissues 3
  4. 4. Signs of Acute inflammation • Celsus 4 cardinal signs Redness: Due to vasodilatation by effects mediated by histamine, bradykinin and prostaglandin. Hotness: Due to increased blood flow. 4
  5. 5. Signs of Acute inflammation • Swelling: due to increased vascular permeability by the released mediators and increased exudate in the inflammed area • Pain: due to irritation of nerve ending by inflammation and the pressure of the swelling on the nerve ending and also from chemical mediators like substance P and bradykinin. 5
  6. 6. The Inflammatory Cascade Inflammation (redness, edema, warmth, pain, tissue destruction) Inflammatory mediators Leukocyte & endothelial cell activation Tissue injury Adaptive immune system Innate immune system Perceived threat Infection NSAIDS, acetaminophen Antihistamines 6
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  9. 9. Anti-inflammatory Drugs Steroidal Non-steroidal - Cortisone - Hydrocortisone - Acetaminophen - Aspirin 9
  10. 10. TYPES OF CORTICOSTEROIDS • Natural Corticosteroids Glucocorticoids –cortisol ,corticosterone Mineralocorticoids –aldosterone ,deoxycorticosterone • Synthetic corticosteroids Prednisolone Betamethasone Dexamethasone 10
  11. 11. Coming to Natural corticosteroids,we will now discuss under following headings- • Site of synthesis • Prototype and physiological effects • Structure –similarites and dissimilarites in gluco/mineralo • Biosynthesis • Basal secretion and variation • Reguln of secretion 11
  12. 12. INTRODUCTION • The adrenal gland produces various classes of hormones each of which aid in dealing with the stress faced by people almost daily. • At least two of these groups – Glucocorticoids and Mineralocorticoids are necessary for life. • Corticosteriods refer to natural gluco- and Mineralo-corticoids and their synthetic analogues. 12
  13. 13. ADRENAL GLAND 13
  14. 14. Adrenal cortex • The adrenal cortex is a factory of steroid hormones • 10-30 different steroids are synthesized from this tissue but two classes are are of importance Steroid Class Prototype Physiological effect Mineralocorticoid Aldosterone(z.glomerulosa) Na,K and H2O homeostasis Glucocorticoid Cortisol Corticosterone(z.fasiculata) Glucose and many other homeostasis Adrenal cortex also produces sex steroids-Androgens,Dehydropiandrosterone(DHEA) 14
  15. 15. STRUCTURE 15
  16. 16. SIMILARITIES A double bond between carbons 4 & 5 in Ring A. A ketone (=0) on carbon 3 in Ring A. Carbons 18, 19, 20, and 21 are present. Carbons 18 and 19 are methyl groups. Carbon 20 has a ketone group attached (=0) and carbon 21 has a hydroxyl group attached (-OH). 16
  17. 17. CONTD.. • Glucocorticoids, in addition, have: • 1. A functional oxy group at Carbon 11. Either a ketone or a hydroxyl; actually, those with 11-ketone (cortisone the naturally occurring one) are converted to 11-OH before becoming biologically active. 17
  18. 18. • Mineralocorticoids, on the other hand: • 1. Do not have a functional oxy group at Carbon 11. • a. Deoxycorticosterone has no 11-oxy group. • b. The 11-oxy group on aldosterone is interfered with by the -CHO group at Carbon position 18 (hemiacetal formation). 18
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  20. 20. Basal secretions Group Hormone Daily secretions Glucocorticoids • Cortisol • Corticosterone 10– 30 mg 2 – 5 mg Mineralocorticoids • Aldosterone • 11- deoxycorticosterone 5 – 150 mcg Trace Sex Hormones •Androgen •Progestogen •Oestrogen • DHEA • Progesterone • Oestradiol 15 – 30 mg 0.4 – 0.8 mg Trace From Essential of Pharmacotherapeutics, ed. FSK Barar. P.351 20
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  24. 24. REGULATION OF SECRETION Regulation of glucocorticoids 24
  25. 25. Regulation of aldosterone 25
  26. 26. Glucocorticoids Regulate Transcription GR, glucocorticoid receptor; HSP, heat shock protein; IP, immunophilin;GRE, glucocorticoid receptor Cortisol GR HSPHSP IP Cortisol GR Cortisol GR Cortisol GRE NUCLEUS mRN A Proteins mRN A ­ transcription (eg, lipocortin) or ¯transcription (IL-1, IL-2, TNF- a, IF-g)GR Cortisol 26
  27. 27. Glucocorticoids - MOA • Not stored: – rate of synthesis = rate of release • Synthesize rhythmically and controlled by irregular pulses of ACTH, influenced by light and major pulses occur early in the morning and after meals • Glucocorticoids act via their receptors located in nucleus (GR) • GRs are widely distributed and located almost in all cells of the body • They are made up of almost 800 amino acids 27
  28. 28. Glucocorticoids - MOA • GR receptors are located in the cytoplasm • One GR receptor has a DNA binding domain and a ligand binding domain along with stabilizing proteins (HSP 90 and HSP 70) • This receptor is incapable of activating transcription • Binding of free steroid molecule to GR forms an unstable compound • Therefore HSP and other proteins get dissociated • The S+GR complex enters the nucleus and binds to Glucocorticoids response element (GRE) on gene and regulate transcription by RNA polymerase II and others • The resulting mRNA is transported to cytoplasm for production of protein and bring about final response 28
  29. 29. The Mighty Corticosteroids Inflammation (redness, edema, warmth, pain, tissue destruction) Inflammatory mediators Leukocyte & endothelial cell activation Tissue injury Adaptive immune system Innate immune system Perceived threat Infection Corticosteroids Corticosteroids Corticosteroids Corticosteroids 29
  30. 30. Corticosteroids Inhibit Eicosanoid Production Phospholipase A2 Arachidonic acid Prostaglandins & thromboxanesLipoxygenase products (leukotrienes) Cyclooxygenase (COX)Lipoxygenase Corticosteroids inhibit induction of COX-2 expression Corticosteroids Lipocortin 30
  31. 31. Phospholipids Arachidonic acids lipoxygenase Cycylooxygenase Leukotriene Prostaglandins, Thromboxane Prostacyclins Phospholipase A2 Lipocortin Corticosteroids PAF by lipocortin 31
  32. 32. Glucocorticoids Are Powerful Immuno- suppressants Corticosteroids affect nearly every facet of immune function, although less inhibition of humoral arm than cell-mediated arm; they also induce apoptosis in rapidly-dividing leukocytes 32
  33. 33. 3.Antiinflammatory and immunosupressive action • Multiple mechanisms are involved - Decrease movement of neutrophils from blood vessels and decreased activity of neutrophils & macrophages by altering the gene transcription . - In macrophages and monocytes – Arachidonic acid and metabolites(↓Prostaglandins and ↓interleukins) are inhibited by inducing Lipocortins that inhibit phospholipaseA2 33
  34. 34. •Cytokines are inhibited – Decreased activity of T-helper cells and proliferation of T-cells – Decrease proliferation of fibroblasts. – Inhibition of chronic inflammation – Repair is also delayed. • In endothelial cells-Endothelial leucocyte adhesion molecule (ELAM) inhibited. • Release of histamine from basophils is inhibited • In lymphocytes: cytokines-interleukins, TNF alpha are inhibited. 34
  35. 35. Glucocorticoids – anti-inflammatory and immunosuppressive effects • Suppress inflammatory response to all noxious stimuli: Pathogens, chemical,physical and immune mediated stimuli, hypersensitivity • However,Underlying cause of disease is not corrected • Reduction in cardinal signs of inflammation • Anti-inflammatory effects are non—specific and covers all components of inflammation: – Effects on concentration, distribution and functions of peripheral leukocytes – increased neutrophils & their activity – In macrophages: reduction of arachidonic acid metabolites (mediators) like PG, LT and PAF synthesis that results from activation of phospholipase A2 Basis of exogenous use of most clinical uses 35
  36. 36. Glucorticoids - Multiple Mechanisms • Recruitment of WBC & monocyte - macrophage into affected area & elaboration of chemotactic substances • Lipocortin: decreased production of PG, LT and PAF • Negative regulation of COX 2: inducible PG production • Negative regulation of genes in cytokines of macrophages, endothelial cells and lymphocytes: • production of IL (1, 2, 3, 6), TNFα, GM-CSF etc. – fibroblast proliferation and T-lymphocyte function – interference with chemotaxis 36
  37. 37. 7.CIRCULATION • BP regulation & cardiovascular function - Sensitizes arterioles to action of noradrenaline • Decreased capillary permeability • Maintains normal renal function 8.CNS Direct: Euphoria – in pharmacological doses Addison's disease – apathy, depression and psychosis High doses – induce seizure Indirect: -maintain glucose, circulation and electrolyte balance 37
  38. 38. 9.Lymphoid and blood cells • Minor effects on Haemoglobin and RBCs • Protect against haemolysis of RBC. • Decrease the number of circulating lymphocytes,eosinophils, monocytes and basophils. • Increase circulating polymorphnuclear leukocytes. • GCs are effective in lymphoid malignancies-- activate programmed cell death (apoptosis)(T CELLS>B CELLS). 38
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  40. 40. PHARMACOKINETICS • Absorption: all are rapidly & completely absorbed (Except DOCA) • Transport: • Transcortin 75%(levels increased in pregnancy) • Albumin 5% • Free form 20% • Metabolism: • by liver enzymes, conjugation & excretion by urine • partly excreted as 17-ketosteroids.(test=Zimmerman reaction) • t1/2 of cortisol =1.5 hours 40
  41. 41. PREPARATIONS •An ideal GC should have no mineralocorticoid activity. • Structural changes to the basic cortisol molecule has resulted in a number of compounds with – minimal mineralocorticoid activity. – Greater potency – Longer duration of action 41
  42. 42. Glucocorticoids Short acting Intermediate acting Long acting Mineralocorticoids Inhalant steroids Topical steroids 42
  43. 43. Short Acting Preparations (t1/2 < 12 h) Drug Anti-inflam. Salt retaining Preapartions & dose Cortisol 1 1.0 • 5 mg tablet • 100 mg/vial (i.m., i.v) • Topical; enema Cortisone 0.8 0.8 • 5 mg tablet • 25 mg/vial (i.m) Intermediate Acting Preparations (t1/2 = 12 -36 h) Prednisone 4 0.8 - Prednisolone 5 0.3 • 5, 10 mg tablet • 20 mg/vial (i.m, intrarti) Methyl prednisolone 5 0 • 0.5, 1.0 gm inj. for i.m. or slow i.v. Triamcinolone 5 0 • 4 mg Tab., • 10, 40 mg/ml for i.m. & intrarticular inj.43
  44. 44. Drug Anti- inflam. Salt retaining Preapartions & dose Long Acting Preparations (t1/2 > 36 h) Dexamethasone 25 0 0.5 mg tab. 4mg/ml inj (i.m., i.v.) Betamethasone 25 0 0.5, 1 mg tab. 4mg/ml inj (i.m., i.v.) Paramethasone 10 0 2- 20 mg/day (oral) 44
  45. 45. Inhalant Steroids: Bronchial Asthma Beclomethasone dipropionate 50,100,200 mcg/md inhaler 100, 200, 400 mcg Rotacaps Fluticasone propionate 25, 50 mcg/md inhaler 25,50,125/md MDI 50, 100, 250 mcg Rotacaps Budesonide 100,200 mcg/md inhaler 0.25, 0.5 mg/ml respules 45
  46. 46. Drug Topical preparation Potency Beclomethasone dipropionate 0.025 % cream Potent Betamethasone benzoate & B. valerate 0.025 % cream, ointment 0.12 % cream, ointment Potent Clobetasol propionate 0.05 % cream Potent Halcinonide 0.1 cream Potent Triamcinolone actonide 0.1 % ointment Potent Fluocinolone actonide 0.025% ointment Moderate Mometasone 0.1 % cream, ointment Moderate Fluticasone 0.05 % cream Moderate Hydrocortisone acetate 2.5 % ointment Moderate Hydrocortisone acetate 0.1 – 1.0% ointment Mild Topical steroids 46
  47. 47. The relative equivalency of different steroids has generally been defined on the basis of pituitary ACTH suppressive effect in the morning after single dose of oral steroids. 47
  48. 48. Pharmacological Actions • For most clinical purposes, synthetic glucocorticoids are used because they have a higher affinity for the receptor, are less activated and have little or no salt-retaining properties. • Hydrocortisone used for: orally for replacement therapy, i.v. for shock and asthma, topically for eczema (ointment) and enemas (ulcerative colitis). • Prednisolone the most widely used drug given orally in inflammation and allergic diseases. 48
  49. 49. Pharmacological Actions • Betamethasone and dexamethasone: very potent, w/o salt-retaining properties; thus, very useful for high-dose therapies (e.g., cerebral edemas). • Beclometasone, diproprionate, budesonide: pass membranes poorly; more active when applied topically (severe eczema for local anti- inflammatory effects) than orally; used in asthma, (aerosol). • Triamcinolone: used for severe asthma and for local joint inflammation (intra-articular inj.). 49
  50. 50. DOSE • Steroid dose is commonly characterised into: -Low dose (e.g. <10mg/day of prednisone) -Medium dose (e.g. 10-20 mg/day of prednisone) -High dose (e.g. >20mg/day of prednisone. ) • Treatment for less than one month is considered short term treatment. • Treatment continuing for more than 3 months is regarded as long term, and results in the majority of undesirable side effects. • Corticosteroids for a few days or weeks are relatively safe. 50
  51. 51. 51 Dosage & schedule • Low dosage for replacement therapy Addison’s disease, anteriorhypopituitarism , post subtotal bilateral adrenalectomy cortisone12.5~25 mg/d, or hydrocortisone 10~20 mg/d. • Universal dosage for long term therapy inflammations, rheumatoid arthritis, lymphoma, lymphoblastic leukemia Started with prednisone 10~20 mg, 3/d; gradually decreased to the maintenance dose after obtained the initial effect. • High dosage for implosive therapy Serious infections: hydrocortisone i.v.d. 200-300 mg, ≥1 g/d. Shocks: hydrocortisone v.d. 1 g, 4-6 g/d.
  52. 52. STEROID WITHDRWAL • Do not suddenly stop systemic steroids. • No tapering is necessary if the course of steroids has been for less than one week. • After taking a dose of 30 mg or more per day for 3-4 weeks, reduce the dose by7- 10 mg(25-30%) or less per day, taking days to weeks to stop altogether. • A much slower reduction in dose may be required if the medication has been taken for several months or longer. • HPA AXIS MAY TAKE MORE THAN 2YRS FOR RECOVERY 52
  53. 53. THERAPUATIC USES • Acute adrenal insufficiency • Primary adrenocortical insufficiency • Congenital adrenal hyperplasia Endocrine Disorders 53
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  56. 56. UNWANTED EFFECTS • Metabolic: – growth suppression – diabetes mellitus – muscle wasting – osteoporosis – fat redistribution – skin atrophy – hirsutism – acne – hypertension – hypokalemia – menstrual irregularities – adrenal suppression 56
  57. 57. • Other: infection emotional disturbances (psychosis, depression, mania) cataract, glaucoma GI bleeding, perforation • Withdrawal Addisonian crisis raised intracranial pressure arthralgia/myalgia pustular rash 57
  58. 58. STEROID THERAPY-PERIOPERATIVE PERIOD • Steroids are a widely used group of drugs in anaesthesia practice, sometimes with definite indication and sometimes without indication. • There is an increasing application of steroid therapy during perioperative period . Some of the current indications are:- 1. Perioperative replacement therapy. 2. Anti-inflammatory uses --hyper-reactive airway 3. Post operative nausea and vomiting (PONV) 4. Analgesia adjunct 5. Day care surgery 6. Anaphylaxis 7. Septic shock 8. Other indications like – cerebral oedema, spinal cord injury, various surgical causes. 58
  59. 59. Steroids in replacement therapy • Steroid administration is necessary in perioperative period in patients treated for hypoadrenocorticism or in a patient with separation of pituitary adrenal axis owing to present or previous steroid intake. • The increase in circulating cortisone levels in response to surgical trauma is one of the important components of stress response of our body. • In perioperative setting this response is essential to avoid haemodynamic instability, metabolic,electrolyte, and fluid imbalances • Certainly more suppression may be expected in the setting of higher and longer duration of steroid therapy. 59
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  64. 64. Steroids in hyper-reactive airway • Their action is mainly anti-inflammatory action leading to decreased mucosal oedema and prevention of release of broncho-constricting substances. • They have a permissive role for bronchodilator medication (inhaled glucocorticoids- beclomethasone,triamcinolone) • The most commonly encountered hyper-reactive states in anaesthetic practice are-- -patients with history of asthma, recent upper respiratory tract infection, difficult airway, multiple intubation attempts,aspiration, foreign body bronchus, airway surgeries and COPD. 64
  65. 65. 4. Ipratropium Bromide 250 mcg by nebulizer with Salbutamol 5. Inj. Hydrocortisone 10mg/kg IV 6. Inj. Aminophylline 5 mg/kg bolus slowly followed by 0.8-1.2 mg/kg/hr slow infusion 7. Inj. Magnesium sulphate 40mg/kg in 50 ml 5% dextrose as slow infusion over 30 minutes(?) ---- NO RESPONSE?---- ABG—X-ray chest---Serum electrolytes Managing Acute Exacerbations BA 65
  66. 66. ANAPHYLAXIS 66
  67. 67. Steroids and anaphylactic/ allergic reaction. • Steroids cannot be the mainstay of therapy in anaphylaxis because of the delayed onset of action,so they are used as adjunct after initial treatment with epinephrine • Glucocorticoids can supplement to primary therapy to suppress manifestations of allergic diseases • In very severe diseases intravenous methylprednisolone 125mg every 6 hours, or Hydrocortisone 200-300mg iv orequivalent can be used. 67
  69. 69. Steroids and sepsis/septic shock • Patients having severe sepsis or in septic shock were found to have occult or unrecognized adrenal insufficiency. • sepsis with adrenal insufficiency, steroid supplementation was associated with significantly higher rate of success in the withdrawal of vasopressor therapy. • Some studies have suggested steroid therapy in sepsis is not only associated with no clinical improvement, but may be harmful. • Usually steroids are administered in this setting to meet the steroid requirement of body, for fighting the ongoing stressful condition. • The commonly used steroid is hydrocortisone OR IV Methyl Prednisolone in dose of 30mg/kg over a period of 30 min followed by 5.4mg/kg /hr for 24 hrs. 69
  70. 70. Cerebral oedema • Steroids reduce or prevent of cerebral oedema by- (1) stabilization of cerebral endothelium, leading to a decrease in plasma filtration; (2) increase in lysosomal activity of cerebral capillaries; (3) inhibition of release of potentially toxic substances such as free radicals, fatty acids, and prostaglandins; (4) electrolyte shifts favouring transcapillary efflux of fluid; (5) increase in local and global cerebral glucose use, leading to improved neuronal function. 70
  71. 71. CEREBRAL EDEMA • The usual but empirical initial dose in brain tumor patients is an intravenous bolus of 10-50 mg of dexamethasone, followed by a maintenance dose of 4-6 mg given by the intravenous (IV) route every 6 hours (16 mg/day) (Szabo & Winkler, 1995). • Corticosteroids can produce an improvement in neurologic symptoms and reduction in cerebral edema within the first 8 to 48 hours, with 12 to 24 hours being the usual time frame. 71
  72. 72. Steroids in PONV • It is thought to be due to decrease in production of inflammatory mediators which are known to act on the CTZ area as well as improve the blood-brain barrier function. • It is also known to act synergistically with 5HT3receptors antagonists. • Optimum dose was found to be 10mgof dexamethasone, and same dose was found to be highly effective when given immediately before induction rather than at the end of anaesthesia • . In meta-analysis of randomized trials ,Hirayama et al found that dexamethasone was more effective than either droperidol or metoclopramide in the prevention of PONV induced by morphine after surgery 72
  73. 73. Steroids and analgesia • Various routes of administration of steroids include parenteral, local infiltration at operated site as an adjuvant in nerve blocks and central- neuraxial blockade. The mode of analgesic effect is ill defined, it may be due to their anti- inflammatory action resulting in decrease of production of various inflammatory mediators that play a major role in amplifying and maintenance of pain perception. • They have also been seen to increase the endorphin levels and mood elevation 73
  74. 74. Steroids and day care surgery • Steroids decrease the incidence of PONV , postoperative pain, establish early oral intake, produce euphoric effect by decreasing level of prostaglandins , and elevating those of endorphins. • Aasboe et al used betamethasone12 mg intramuscularly, 30minutes prior to ambulatory hemorrhoidectomy or hallux valgus correction and they found significantly less postoperative pain, less PONV, and better patient satisfaction 74
  75. 75. Spinal cord injury • Treatment should begin within 8 hrs of injury. • A suggested protocol for traumatic cord injury within 3 hrs of injury includes the use of high dose methyl prednisolone with an intravenous bolus of 30mg/kgover 15 min followed by a 45 min pause and then a continuos IV infusion @5.4mg/kg/hr infusion for 23 hours. • For Pts within 3-8 hrs of injury,adminster 30 mg/kg IV bolus over 15 min period followed by a 45 min pause and then a continuos IV infusion @5.4mg/kg/hr infusion for 47hours 75
  76. 76. Steroids in surgery • Anti-inflammatory action of steroids have beneficial role to play in surgery. • Shimada et al in their retrospective study of patients undergoing resection of esophagealcarcinoma,reported that those patients who received methylprednisolone 250mg prior and two days following surgery had low morbidity rates from anastomotic leakage and liver dysfunction . • The inflammatory mediators,body temperature and heart rate were significantly low in steroid group,the author suggested that improvement may be because of suppression of local edema leading to improved microcirculation at operative site and reduction in tissue injury due to inflammation mediated substances 76
  77. 77. ROLE OF STERIODS IN THE ICU? • “Critical Illness Related Corticosteroid Insufficiency” Inadequate corticosteroid activity for the severity of the illness • Thought to be comprised of both a relative lack of cortisol, as well as tissue resistance to its effects Possibly due to decreased expression of active form of GC receptor • Overall incidence of adrenal insufficiency is estimated to be 20% for all-comers, and as high as 60% for pts with septic shock and burns due to their exaggerated pro-inflammatory response 77
  78. 78. Diagnosis • Diagnosis of adrenal insufficiency has traditionally relied upon use of total serum cortisol measurement, usually checking baseline levels and repeating measurements after stimulation testing with high dose (250mcg) of cosyntropin (synthetic ACTH). 78
  79. 79. International Task Force Recommendations • Concerning diagnosis and management of corticosteroid insufficiency in critically ill patient Recommendations were classified as strong (grade 1) or weak (grade 2) Quality of evidence for the recommendation also provided A = high quality evidence B = moderate quality C = low quality 79
  80. 80. • 1. Dysfunction of the HPA axis in critical illness is best described by the term critical illness related corticosteroid insufficiency (CIRCI) • 2. The terms absolute or relative adrenal insufficiency are best avoided in the context of critical illness • 3. At this time, adrenal insufficiency in critical illness is best diagnosed by cortisol of <9mcg/dL (after 250 mcg cosyntropin), or a random cortisol of < 10mcg/dL (2B) • 4. The use of free cortisol measurements cannot be recommended for routine use at this time. Although the free cortisol assay has advantages…(it) is not readily available. Furthermore, the normal range of free cortisol in critically ill pts is currently unclear (2B) 80
  81. 81. • 5. The ACTH stimulation test should not be used to identify those patients with septic shock or ARDS who receive glucocorticoids (2B) • 6. Hydrocortisone should be considered in the management strategy of patients with septic shock, particularly those who have responded poorly to fluid resuscitation and vasopressor agents (2B) • 7. Moderate dose glucocortidoids should be considered in the management strategy of patients with early severe ARDS (PaO2 / FiO2 <200) and before day 14 in patients with unresolving ARDS (2B) • 8. In patients with septic shock, intravenous hydrocortisone should be given in a dose of 200mg/day in four divided doses or as a continuous infusion at 10mg/hr (240mg/day). The optimal initial dosing regimen in patients with early severe ARDS is 1mg/kg/day of methylprednisolone as a continuous infusion. (1B) 81
  82. 82. • 9. The optimal duration of glucocorticoid treatment…is unclear. However, based on published studies and pathophysiological data, patients with septic shock should be treated for 7 or more days before tapering…patients with early ARDS for 14 or more days before tapering. (2B) • 10. Glucocorticoid treatment should be tapered slowly and not stopped abruptly (2B) • 11. Treatment with oral fludrocortisone is considered optional (2B) • 12. Dexamethasone is not recommended for the treatment of septic shock or ARDS (1B) 82
  83. 83. SUMMARY • DO NOT Say no to steroids as STEROIDS are life saving drugs. • But in following conditions where we have to be extremely cautious: - Peptic ulcer, Hypertension,Diabetes mellitus, Viral and fungal infections, Tuberculosis, Osteoporosis Epilepsy and psychosis, CHF and renal failure. • Efforts should be made to reduce steroids induced side effects. • Choosing a Steroid Benefit/risk ratio is a major consideration Drugs with primary glucocorticoid activity are used .Minimal dose to achieve the desired effects is chosen 83
  84. 84. References  Miller’s Anesthesia  Stoelting Anesthesia & Co-Existing Disease  K.D Tripathy,Medical pharmacology.  W,F Ganong, Medical physiology  Robbin’s Pathological Basis of Disease  Internet Sources 84
  85. 85. Thank you 85