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Steroids
- 1. Steroids in ICU Alun Ellis
- 2. OVERVIEW PRIMARY Physiology of steroid hormones Steroid production Commonly used preparations and pharmacology FELLOWSHIP Steroid syndromes Indications for steroids in critical illness
- 7. Steroid hormones Glucocorticoids Mineralocorticoids Androgens Oestrogens Progestrogens No storage capability
- 10. Biological effects of cortisol Carbohydrate metabolism Stimulate gluconeogenesis via cell signaling Mobilise AA’s from extrahepatic tissues Reduction of glucose utilisation by cells by inhibiting action of glucose Protein metabolism Diminishes tissue stores of protein and increases liberation of AA’s Decreases protein synthesis (except liver) Fat metabolism Increases fatty acid breakdown and oxidation in the liver Water/electrolytes Enhances Na reabsorption and K excretion Increases renal blood flow and water excretion Blood Increase RBC and platelet production, reduction of circulating lymphocytes and eosinophils Cardiovascular system ‘Permissive effect’ on vascular tone Inhibit production of prostaglandins which are vasodilators Reduces permeability of capillaries GIT Increases acid and pepsin production Foetus Important in production of foetal surfactant
- 13. Potency The amount of drug required to produce the desired/measured biological effect
- 15. HYDROCORTISONE Pharmacokinetics A Rapid, 96% bioavail. D High VD, 90% protein bound to CBG M Half life 60-90 mins, CY3A4 E Glucuronidation
- 16. DEXAMETHASONE Pharmacokinetics A 70-80% bioavailability D 70-80% protein bound M Half life 190 mins E Glucuronidation
- 17. METHYLPREDNISOLON E Pharmacokinetics A 80-90% bioavail D 80% protein bound M Half-life 1.8-5 hours E Hydroxylation, 20% in bile, 10% in faeces
- 18. STEROID TRIALS IN ICU SEPTIC SHOCK ARDS ACUTE SPINAL CORD INJURY
- 19. SEPTIC SHOCK Bone 1987 Annane 2002 CORTICUS 2008 Follows the concept of relative adrenal insufficiency
- 20. Jurney 1987
- 21. Bone 1987
- 22. Annane 2002
- 23. CORTICUS 2008
- 26. ARDS MEDURI 1998 & 2007 – Early ARDS (<7 days) LaSRS 2006 – Late ARDS(>7 days)
- 27. MEDURI JAMA n=24 Q6H infusions of methylprednisolone 2mg/kg/day tapered down after two weeks If extubated jumped to day 15 RESULTS: Reduced lung injury score, reduced mortality ( 0 vs 63%) Half of placebo group crossed over to steroids Chest n=72, ARDS within 72 hours of admission 1mg/kg/day as IV infusions Switched to oral doses once extubated as daily dose RESULTS: Reduced lung injury score after 7 days, reduced days of mechanical ventilation, reduced ICU length of stay, reduced ICU mortality. No hospital LOS/mortality benefit.
- 28. LaSRS
- 31. Acute Spinal Injury NASCIS I-III trials NASCIS I (1984) – Methyl pred NASCIS II (1990) – Methylpred and naloxone NASCIS III (1997) – Methylpred and tirilazad
- 33. WHAT TO TAKE HOME Use steroids early in ARDS Don’t use in ARDS after 14 days Steroids may not affect overall mortality but may reverse shock earlier Don’t do short synacthen test and a normal cortisol is not necessarily reassuring Current recommendations are against using methylprednisolone for acute spinal injury THANK YOU
Editor's Notes
- IN response to neural stimulation, releasing or inhibiting hormones produced in hypothalamus travel down hypophyseal circulation and stimulate release of hormones from anterior pituitary4
- Trials looking at steroids in shock since 1950’s
- Little data on safety of methylpred or on glucose control.
- Major criticism if the study is long duration of recruitment where there are significant improvements in the management of patients with ARDS e.g. lung protection, sedation breaks etc
- I – high vs low dose methyl pred 100mg vs 100mg QID for 10 days) high dose did not improve neurological outcome, more wound infections. F/U 6 weeks, 6 months and 1 yr II – methylpred 30mg/kg then infusion for 23 hours or naloxone infusion or placebo…. Neurological outcome measures criticised (numerical scale) More common wound infection and GI bleeding III – tirilizad – aminosteroid that inhibits lipid peroxidation (used with mixed success with ischaemic stroke). Randomised to receive 20-40mg/kg methylpred or tirilizad. Overall results iproved motor function and QoL, but higher incidence of sepsi
- Consensus guidelines (2013) from American Association of Neurosurgeons and Congress of Neurosurgeons reported significant reporting bias in earlier studies and missing data regarding harmful effects Additional studies looking into harmful effects trend towards higher wouond infection, hyperglycaemia and episodes of sepsis