Corticosteroid

Report
Topic review
Glucocorticoids
R2Parichat Nilyam
R2Sasiya Siriratwarangkul
Supervised by Dr.Kittipong Sujirattanawimol
Glucocorticoids + Mineralocorticoids + Sex hormone
Glucocorticoids
Corticosteroid
= Cortex + Steroid
Adrenal gland
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.
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
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”
buffalo hump
• 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
• 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
• Bone and Calcium Metabolism
- Inhibit osteoblast function
- Excess glucocorticoid causes osteopenia
and osteoporosis
Effect of Anaesthesia and Surgery
• Plasma cortisol levels typically increase from 210 folds
• Maximum ACTH and cortisol levels are reached
in the early postoperative period
• Cortisol return to normal within 24 hrs
postoperatively
• May remain elevated as long as 72 hrs
Anesthetic drugs VS HPA response
– Etomidate
– Large doses of opioid
– Volatile anesthetics
glucocorticoid
AntiNa-retaining duration
inflammatory potency
potency
Cortisol
1
Prednisolone 4
Methyl-P
5
Dexa
-methasone
25
Equivalent
dose
1
<12 hr
0.8
0.5
12-36 hr 5
4
0
>36 hr
20
0.75
Adverse Drug Effects of
Steroid Supplementation
• Risks with Short-Term (Perioperative)
Supplementation
aggravation of hypertension
fluid retention
delayed wound healing
hypokalemia
increased susceptibility to infection
decreased glucose tolerance
• 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
Application of Steroids in
anesthesia
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/m2/day
or about 10 mg/day
• In severe surgical stress: 75-150 mg/day
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
• 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
• 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.
• 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
• Patient currently taking steroids
<10 mg/d
Assume normal
HPA response
Additional steroid cover not required
>10 mg/d
Minor Sx
25mg of hydrocortisone at induction
Moderate Sx
Usual periop. steroid
+25mg of hydrocortisone at induction
+100 mg/d for 24 hr
Major Sx
Usual 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.
• Patient stopped taking steroid
Stopped < 3 mo
Treat as if on steroids
Stopped > 3 mo
No 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.
• 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
• 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
• 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
• 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
• 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
• 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
Thank you

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