PHARMA,MOA,USES AND DOSAGES

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. • 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. 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. 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. 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. 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

7. 7

8. 8

9. Anti-inflammatory Drugs
Steroidal Non-steroidal
- Cortisone
- Hydrocortisone
- Acetaminophen
- Aspirin
9

10. TYPES OF CORTICOSTEROIDS
• Natural Corticosteroids
Glucocorticoids –cortisol ,corticosterone
Mineralocorticoids –aldosterone ,deoxycorticosterone
• Synthetic corticosteroids
Prednisolone
Betamethasone
Dexamethasone
10

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. 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. ADRENAL GLAND
13

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. STRUCTURE
15

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. 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. • 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

19. 19

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

21. 21

22. 22

23. 23

24. REGULATION OF SECRETION
Regulation of glucocorticoids
24

25. Regulation of aldosterone
25

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. 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. 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. 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. 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. Phospholipids
Arachidonic acids
lipoxygenase Cycylooxygenase
Leukotriene
Prostaglandins,
Thromboxane
Prostacyclins
Phospholipase A2
Lipocortin
Corticosteroids
PAF by lipocortin
31

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. 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. •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. 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. 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. 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. 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

39. 39

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. 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. Glucocorticoids
Short acting
Intermediate acting
Long acting
Mineralocorticoids
Inhalant steroids
Topical steroids
42

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. 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. 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. 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. 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. 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. 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. 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
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. 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. THERAPUATIC USES
• Acute adrenal insufficiency
• Primary adrenocortical insufficiency
• Congenital adrenal hyperplasia
Endocrine Disorders
53

54. USES IN NONADRENAL DISORDERS
54

55. 55

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. • Other:
infection
emotional disturbances (psychosis, depression,
mania)
cataract, glaucoma
GI bleeding, perforation
• Withdrawal
Addisonian crisis
raised intracranial pressure
arthralgia/myalgia
pustular rash 57

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. 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

60. 60

61. 61

62. 62

63. 63

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. 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. ANAPHYLAXIS
66

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

68. SEPSIS/SEPTIC SHOCK
68

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
100-125mg.day-1 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. • 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. • 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. • 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. 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. 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. Thank
you
85

86. NEXT CASE PRESENTATION BY
DR ANIJA PATTNAIK
OF
CLEFT LIP AND PALATE ON
31.01.2015
86