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000000000000 Corticosteroids Overview • LITFL • CCC

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000000000000 Corticosteroids Overview • LITFL • CCC

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  1. 31.12.2021 20:51 Cort?costero?ds Overv?ew • LITFL • CCC Corticosteroids Overview Chris Nickson Nov 3, 2020 ● HOME CCC PHYSIOLOGY hormones two types: glucocorticoids (cortisol) and mineralocorticoids (aldosterone) both cholesterol based GLUCLOCORTICOIDS cortisol produced from zona fasiculata in adrenal cortex produced in response to stress: hypoglycaemia, fear, pain, exercise, infection there is circadian variation in cortisol release controlled via hypothalamic-pituitary-adrenal axis stress -> release of CRH from hypothalamus -> release of ACTH from anterior pituitary -> cortisol released from adrenal cortex normal secretion of cortisol = 15-30mg/day -> 5-7mg of prednisone or 20-30mg of hydrocortisone Effects CNS – behavioural changes METABOLIC – increased plasma glucose (decreased gluconeogenesis, insulin antagonism, increased in protein catabolism, increased FFA oxidation), potentiate action of GH, catecholamines, glucagons, T3/T4 GASTROINTESTINAL – increased acid and pepsin secretion, decreased prostaglandin synthesis, increased rate of peptic ulceration. HAEMATOLOGICAL – increased RBC, PLTs, neutrophils, decreased lymphocytes and eosinophils CARDIOVASCULAR – increased reactivity of peripheral blood vessels to catecholamines MUSCULO-SKELETAL – increased bone break down -> OP, muscle wasting MINERALOCORTICOIDS aldosterone produced in the zona glomerulosa daily output: 100-150mcg/day secreted in response to; Na+ deficiency -> elevated angiotensin II, elevated plasma K+ Effects RENAL – 1. acts on collecting ducts -> increases production of the Na+/K+ ATPase in the basement membrane, increased Na+ and K+ channels in the apical membrane -> increase in Na+ reabsorption and K+ secretion -> ECF volume expansion. https://l?tfl.com/cort?costero?ds-overv?ew/ 1/8

  2. 31.12.2021 20:51 Cort?costero?ds Overv?ew • LITFL • CCC 2. increases excretion of H+ and NH4+ 3. increases Cl- reabsorption OTHER – increased Na+ reabsorption in sweat, salivary and distal colon glands. ADRENAL INSUFFICIENCY (AI) Types: primary, secondary and tertiary + acute/chronic Primary = Addison’s destruction of > 90% of adrenal glands rare causes: autoimmune destruction, haemorrhage, tumour (breast and melanoma), infection (Tb, HIV, meningococcaemia, purpura fulminans) or inflammatory process loss of mineralocorticoid and glucocorticoid activity Secondary insufficient production of ACTH rare mineralocorticoid function intact causes: destruction or dysfunction of the pituitary Tertiary/Iatrogenic/Relative suppression of HPA axis over time most common cause: administration of exogenous glucocorticoids mechanism: chronic ACTH suppression -> adrenal atrophy Adrenal Crisis concurrent illness, surgery, failure to take medications GI: abdominal pain, vomiting and diarrhoea CVS: dehydration, hypotension, refractory shock, poor response to inotropes/pressors fever confusion Chronic adrenal insufficiency GENERAL: weight loss, arthralgia, myalgia CNS: fatigue, anorexia, mood change CVS: postural hypotension, syncope, salt craving SKIN: pigmentation, vitiligo ELECTROLYTES: hypoglycaemia, hyponatraemia, hyperkalaemia, increased urea Diagnosis plasma cortisol level < 80mmol/L short synacthen test: 250mcg (normal response = cortisol > 525mmol/L) Management fluid resuscitation reversal of electrolyte abnormalities https://l?tfl.com/cort?costero?ds-overv?ew/ 2/8

  3. 31.12.2021 20:51 Cort?costero?ds Overv?ew • LITFL • CCC high dose hydrocortisone (100mg IV Q6 hrly) PERIOPERATIVE STEROID THERAPY glucocorticoids introduced into clinical practice in 1949 soon after there were two deaths from withheld steroids in perioperative period -> “stress doses” in the perioperative period. for many years we overcooked these patients with large doses of steroids new guidelines: those on 5mg or less of prednisone OD -> don’t need supplementation minor operation -> normal dose + 25mg hydrocortisone in OT moderate operation -> normal dose + 25mg hydrocortisone Q6hourly for 24 hours high risk operation -> normal dose + 25mg hydrocortisone Q6 hours for 48-72 hours Conversion Prednisone 1mg = Hydrocortisone 4mg = Dexamethasone 0.15mg = Triamcinolone 0.8mg = Methylprednisolone 0.8mg = Betamethasone 0.15mg = SEVERE SEPSIS + SEPTIC SHOCK basis: that patients with severe sepsis has relative adrenal insufficiency difficult to diagnose because of the questionable validity of using plasma cortisol and the synacthen test. benefit shown in meningitis see Corticosteroids in Refractory Shock ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS) mortality = 40-60% pathophysiology: excessive inflammation and vascular permeability with extravasation of plasma and leukocyte infiltration (fibroproliferative stage) -> steroids thought to reduce the extent of these processes Meduri study (JAMA) = cross over trial -> reduction in lung injury score -> improved mortality Meduri study -> reduction in length of ICU stay -> reduction in duration of IPPV Steinberg KP, Hudson LD, Goodman RB, et al: National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network: “Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome.” N Engl J Med 2006; 354:1671-1684. n = 180 MRCT methylprednisolone for 14 days with taper VS placebo -> reduced shock symptoms -> reduced ventilator days -> improved pulmonary compliance -> increased mortality in patient who had had steroids > 14 days https://l?tfl.com/cort?costero?ds-overv?ew/ 3/8

  4. 31.12.2021 20:51 Cort?costero?ds Overv?ew • LITFL • CCC -> increased neuromuscular weakness -> NO improvement in survival – outcomes in trials have varied -> two recent systematic reviews have reached opposite conclusions! Agarwal R, Nath A, Aggarwal AN, Gupta D. “Do glucocorticoids decrease mortality in acute respiratory distress syndrome? A meta- analysis.” Respirology 2007;12:585-90. urrent evidence does not support the efficacy of steroids in ARDS Meduri G, Marik P, Chrousos G, Pastores S, Arlt W, Beishuizen A, et al. Steroid treatment in ARDS: a critical appraisal of the ARDS network trial and the recent literature. Intensive Care Med 2007 prolonged glucocorticoid treatment substantially and significantly improves meaningful patient-centered outcome variable and has a distinct survival benefit What about steroids for ARDS prophylaxis? increase in ARDS and subsequent mortality (weak trend) Summary exact place of steroids in ARDS is unknown further investigation required MENINGITIS van de Beek D, de Gans J, McIntyre P, et al: Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev 2007; 1 de Gans J, van de Beek D: European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators: Dexamethasone in adults with bacterial meningitis. N Engl J Med 2002; 347:1549-1556 systematic reviews dexamethasone with first antibiotics in community acquired bacterial meningitis -> reduces mortality -> reduces severe hearing loss -> reduces neurological sequelae TRAUMATIC BRAIN INJURY Roberts I, Yates D, Sandercock P, et al: CRASH trial collaborators: Effect of intravenous corticosteroids on death within 14 days in 10,008 adults with clinically significant head injury (MRC CRASH trial): Randomised placebo-controlled trial. Lancet 2004; 364:1321- 1328. Edwards P, Arango M, Balica L, et al: CRASH trial collaborators: Final results of MRC CRASH, a randomised placebo-controlled trial of intravenous corticosteroid in adults with head injury-outcomes at 6 months. Lancet 2005; 365:1957-1959. 48 hours of IV steroids vs placebo -> increased mortality within 14 days -> increases mortality @ 6 months -> increased risk of severe disability ACUTE SPINAL CORD INJURY https://l?tfl.com/cort?costero?ds-overv?ew/ 4/8

  5. 31.12.2021 20:51 Cort?costero?ds Overv?ew • LITFL • CCC Bracken MB, Shepard MJ, Collins WF, et al: A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study. N Engl J Med 1990; 322:1405-1411. high dose methylprednisolone within 8 hours in injury -> supported use Miller SM: Methylprednisolone in acute spinal cord injury: A tarnished standard. J Neurosurg Anesthesiol 2008; 20:140-142. George ER, Scholten PJ, Buechler CM: Failure of methylprednisolone to improve the outcome of spinal cord injury. Am Surg 1995; 61:659-663. Pointillart V, Petitjean ME, Wiart L: Pharmacotherapy of spinal cord injury during the acute phase. Spinal Cord 2000; 38:71-76. criticisms of NASCIS: study design flawed, statistical analysis flawed, conflicting evidence Bracken MB: Steroids for acute spinal cord injury. Cochrane Database Syst Rev 2002.CD001046 supports use of methylprednisolone, but written by the lead investigator of NASCIS Tsutsumi S, Ueta T, Shiba K, et al: Effects of the Second National Acute Spinal Cord Injury Study of high-dose methylprednisolone therapy on acute cervical spinal cord injury results in spinal injuries center. Spine 2006; 31:2992-2996. NASCCIS II supports use of methylprednisolone Leypold BG, Flanders AE, Schwartz ED, et al: The impact of methylprednisolone on lesion severity following spinal cord injury. Spine 2007; 32:373-378. patients who had methylprednisolone had significantly less intramedullary haemorrhage than those who were no treated. Eck JC, Nachtigall D, Humphreys SC, et al: Questionnaire survey of spine surgeons on the use of methylprednisolone for acute spinal cord injury. Spine 2006; 31:E250-253. n = 305 spine surgeons -> 90% would initiate methylprednisolone especially within the 8 hour window -> reasons given: institutional protocol, medicolegal reasons -> only 24% used steroids because of a belief in improved outcomes! Summary controversial issue methylprednisolone may have role in neurological protection in early spinal cord injury a well designed RCT’s is required SUMMARY OF PROVEN ROLES FOR STEROIDS Airway croup decreased post-extubation stridor in those at risk Breathing anaphylaxis asthma https://l?tfl.com/cort?costero?ds-overv?ew/ 5/8

  6. 31.12.2021 20:51 Cort?costero?ds Overv?ew • LITFL • CCC COPD PJP pneumonia Nervous bacterial meningitis myasthenic crises myxoedema coma decreases cerebral oedema associated with brain tumour Endocrine Addison’s hypercalcaemia myxoedema coma hypothalamic-pituitary-adrenal insufficiency previous steroid use Other purpura fulminans vasculitidies (e.g. GCA) organ transplantation various malignancy (lymphoma) anti-emetic palliative care ACCEPTED BUT CONTROVERSIAL USES OF STEROIDS – severe sepsis with resistant shock – spinal injury – early ARDS CONTRAINDICATIONS TO USE OF STEROIDS – Cushing disease – traumatic brain injury – late ARDS (after 2 weeks) Critical Care Compendium …more CCC Chris Nickson Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an https://l?tfl.com/cort?costero?ds-overv?ew/ 6/8

  7. 31.12.2021 20:51 Cort?costero?ds Overv?ew • LITFL • CCC internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives. After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education. He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference. His one great achievement is being the father of two amazing children. On Twitter, he is @precordialthump. | INTENSIVE | RAGE | Resuscitology | SMACC Related Adrenal insufficiency Corticosteroid Therapy for Shock Metabolic Alkalosis Leave a Reply Enter your comment here... Enter your comment here... This site uses Akismet to reduce spam. Learn how your comment data is processed. Subscribe to LITFL via Email Subscribe #FOAMed Medical Education Resources by LITFL is licensed under a Creative Commons https://l?tfl.com/cort?costero?ds-overv?ew/ 7/8

  8. 31.12.2021 20:51 Cort?costero?ds Overv?ew • LITFL • CCC Attribution-NonCommercial-ShareAlike 4.0 International License. Based on a work at https://litfl.com About • Authors • Blog • Contact Cookies • Disclaimer• Privacy Blog Stats 94,740,226 visitors   LITFL posts by EMAIL or RSS   FFFF by EMAIL or RSS 8.999 TL 2.199 TL 9.199 TL 6.799 TL 8.749 TL 219 TL https://l?tfl.com/cort?costero?ds-overv?ew/ 8/8

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