contoversy about the use corticosteroids in pediatric

Controversy about the use of Controversy about the use of corticosteroids in pediatricscorticosteroids in pediatrics

ByByMohamed Zannoun (MD)

Associated Professor of pediatric Al-Azhar University Dameitta

112/05/03 Mohamed Zannoun

Controversy Controversy ُخالف دُب


Types of Steroids• Replacement Therapy • glucocorticoid (hydrocortisone)• mineralocorticoid (fludrocortisone)• Anti-inflammatory Therapy• Short acting: hydrocortisone• Intermediate acting: prednisolone;

methylprednisolone; triamcinolone• Long acting: dexamethasone


Routes of Administration

• Systemic : oral, transrectal, IV, IM

• Local: topical, intranasal, intraocular, intraarticular


Availability of International Guidelines on Use of Steroid

• No one-for-all guideline• Glucocorticoid Replacement Therapy : Guidelines

published by Royal College of Physicians of London, UK ; not available from Endocrine Society, USA.

• Systemic Use of Glucocorticoid: Guidelines available for EULAR (European League for Rheumatology)

• Local Use of Steroid: guidelines on individual disease, general guidelines not available


Royal College of Physicians of London Guidelines on Glucocorticoid Replacement Therapy

• Recommended Daily Dose for Glucocorticoid• Hydrocortisone (cortisol) 15-30mg• Cortisone acetate 25-37.5mg• Prednisolone 5-7.5mg• Dexamethasone 0.5mg• Recommended Daily Dose of Mineralocorticoid• Fludrocortisone 100-200mcg


Pediatric emergency


HIGH ALTITUDE CEREBRAL EDEMA HACE

• . Dexamethasone should be administered at a dose of 0.15 mg/kg per dose given orally every 6 hr. The few mild cases of HACE reported in children have recovered with dexamethasone and descent. Nelson 2016 p557


Brain Death

• Corticosteroids should generally not be used unless adrenal insufficiency is documented.

Nelson 2016 p512


Role of corticosteroids in management of hereditary angioedema

• corticosteroids have no effect. Nelson 2016 p1060.


corrosive• The use of corticosteroids or

prophylactic antibiotics is not beneficial.

Nelson 2016p464• The role of corticosteroids is

controversial. Nelson 2016 p1795


In human studies: Inconclusive so far

• NEJM. 1990: – Prospective study over an

18-year period– No benefit

• Toxicol Rev. 2005:– 1991-2004 in the English,

German, French, Spanish– No benefit


hydrocarbons and hydrocarbon-induced pneumonitis

Treatment is supportive Neither corticosteroids nor prophylactic antibiotics have shown any clear benefit. Nelson 2016 p465


Burns• Treatment is initially focused

on establishing and maintaining a patent airway through prompt and early nasotracheal or orotracheal intubation and adequate ventilation and oxygenation.

• Wheezing is common, and β-agonist aerosols or inhaled corticosteroids are useful. Nelson 2016 p574.112/05/03 Mohamed Zannoun

Generally in Pediatric emergency

• Inhaled bronchodilators, such as albuterol, augmented by oral or IV corticosteroids, remain the mainstay

of therapy:- • 1- Mild to moderate acute distress

caused by lower airway obstruction. • 2- Children with more significant

obstruction appear dyspneic, with tachypnea, retractions, and easily audible wheezing. Nelson 2016 p494


Perinatal112/05/03 Mohamed Zannoun

Antenatal corticosteroids

• A single course of antenatal corticosteroids is recommended in pregnancies 24-34 wk of gestation that are at risk for preterm delivery. Antenatal steroids decrease the risk of death, grades III and IV IVH, and PVL in the neonate.

• The prophylactic administration of low-dose indomethacin (0.1 mg/kg/day for 3 days) to VLBW preterm infants reduces the incidence of severe IVH. Nelson 2016 p836-837.


Congenital Adrenal Hyperplasia21-hydroxylase deficiency

• This suppresses secretion of steroids by the fetal adrenal, including secretion of adrenal androgens. If started by 6 wk of gestation, it ameliorates virilization of the external genitalia Nelson 2016 p2720


Congenital heart block

• Prenatal Dexamethasone thearpy , Nelson 2016 p817


Post natal corticosteroids

• Long-term adverse neurodevelopmental outcomes are also associated with high-dose postnatal corticosteroid use in VLBW infants.

• Early postnatal exposure to dexamethasone, within the 1st wk of life, is associated with metabolic derangements, poor growth, increased risk for sepsis, and an increased

risk of spontaneous bowel perforation. Nelson 2016 p838.



• Infants exposed to postnatal steroids after the 1st wk of life have an increased risk of cerebral palsy and developmental delay. The risk may be increased with prolonged steroid use (>6 wk).

• At 8 yr of age, dexamethasone-treated children are smaller, have smaller head circumferences, poorer motor skills and coordination, more difficulty with visual motor integration and lower full-scale verbal IQ and performance IQ scores. Nelson 2016 p838.112/05/03 Mohamed Zannoun


• It is recommended that postnatal corticosteroid use in VLBW infants be limited to exceptional clinical circumstances and that parents of infants in whom corticosteroids are used be informed of the potential adverse side effects, including increased risk for developmental delay, cerebral palsy, and impaired growth. Nelson 2016 p838.


Prior to extubation from mechanically ventilatted babies

• Administration of intravenous corticosteroids (dexamethasone 0.5 mg/kg every 6 hr for 4 doses prior to extubation) has been shown to minimize the incidence of postextubation airway obstruction.

• In patients in whom postextubation airway obstruction develops, the need for re-intubation may be obviated by administration of nebulized racemic epinephrine and heliox. Nelson 2016 p544.112/05/03 Mohamed Zannoun

Bronchopulmonary dysplasis BPD• Systemic corticosteroids have

been used to treat infants with RDS, to selectively treat infants who continue to require respiratory support, and to treat those in whom BPD develops. Mortality and/or BPD at 36 wk decrease with moderately early (7-14 days) administration of corticosteroids. Nelson 2016 p854.


BPD• Early (<96 hr) and delayed (>2 wk)

administration of systemic steroids as also been assessed with meta-analyses, and the results are qualitatively similar. However, there are short-term adverse effects, including hyperglycemia, hypertension, gastrointestinal bleeding, gastrointestinal perforation, hypertrophic obstructive cardiomyopathy, poor weight gain, poor growth of the head, and a trend toward a higher incidence of periventricular leukomalacia. Nelson 2016 p854.


BPD• Routine use of systemic

corticosteroids for the prevention or treatment of BPD is not recommended by the Consensus Group of the American Academy of Pediatrics and the Canadian Pediatric Society. Nelson 2016 p854.


BPD• Administration of inhaled

steroids to ventilated preterm infants during the 1st 2 wk after birth reduced the need for systemic steroids and tended to decrease rates of death and/or BPD at 36 wk without an increase in adverse effects. Nelson 2016 p854.


hypotension


hypotension

• Hypotension in some infants weighing <1,000 g does not respond to fluids or inotropic gents but may respond to therapy with intravenous hydrocortisone. Nelson 2016 p831.


Vascular Disorders112/05/03 Mohamed Zannoun

Treatment of Kawasaki Disease

• Corticosteroids have been trialed as primary therapy with the first dose of IVIG in hopes of improving coronary outcomes. A North American trial using a single pulse dose of intravenous methylprednisolone (30 mg/kg) with IVIG as primary therapy did not improve coronary outcomes. Nelson 2016 p1147.


Treatment of Kawasaki Disease• However, a trial in Japan utilizing the

Kobayashi score to identify high-risk children demonstrated improved coronary outcomes with a regimen of prednisolone (2 mg/kg) plus IVIG as primary therapy.

• Despite these promising results, administration of corticosteroids, as primary therapy to all children with KD awaits the development of a risk score that identifies high-risk children in a multiracial population. Nelson 2016 p1147.


Treatment of Kawasaki Disease• Corticosteroids in varying doses

and via different routes have also been used as secondary or “rescue” therapy when fever persists after the first IVIG. However, the lack of clear data regarding the most effective way to administer corticosteroids as rescue therapy has led to significant practice variation across centers. Nelson 2016 p1147.112/05/03 Mohamed Zannoun

Henoch-Sch ِnlein Purpura

• Treatment for mild and self-limited HSP is supportive, with an emphasis on assuring adequate hydration, nutrition, and analgesia. Steroids are most often used to treat significant gastrointestinal involvement or other life-threatening manifestations. Nelson 2016 p1218


• Prednisone (1 mg/kg/day for 1-2 wk, followed by taper) reduces abdominal and joint pain but does not alter overall prognosis nor prevent renal disease. Rapid tapering of corticosteroids may lead to a flare of HSP symptoms. Nelson 2016 p1218


ITP• Pulsed high-dose dexamethasone

therapy in children with chronic idiopathic thrombocytopenic purpura before considering splenectomy

• Dexamethasone orally or iv ??? At a dosage of 40 mg /m2 /day maximium 40 mg /day for 4 consecutive days the cycle repeated once monthly for six months

• pediatric haematol oncol. 2002 Jul-Aug 19(5):329-35


Infectious diseases 112/05/03 Mohamed Zannoun

Pharyngitis

• Systemic corticosteroids are sometimes used in children who have evidence of upper airway compromise due to mononucleosis. Although corticosteroids are used fairly commonly in adults with pharyngitis, large scale studies capable of providing safety and efficacy data are lacking in children. Corticosteroids cannot be recommended for treatment of most pediatric pharyngitis.

• Nelson 2016 p2019.


In tonsillectomy

• The Clinical Guidelines for Tonsillectomy include a recommendation for

• intravenous a single dose of intraoperative dexamethasone (0.5 mg/kg), which decreases postoperative nausea and vomiting and reduces swelling. Nelson 2016 p2026


Bronchiolitis

• Corticosteroid therapy is not indicated except in older children with an established diagnosis of asthma, because its use is associated with prolonged virus shedding and is of no proven clinical benefit. Nelson 2016 p1608


Bronchiolitis

• Corticosteroids, whether parenteral, oral, or inhaled, have been used for bronchiolitis despite conflicting and often negative studies. Corticosteroids are not recommended in previously healthy infants with RSV. Nelson 2016 p2047


Bronchiolitis

• Combined therapy with nebulized epinephrine and dexamethasone has been used with some success, but additional studies are needed to confirm its efficacy and investigate the long-term adverse effects in infants before this combination can be recommended. Nelson 2016 p2048


• Croup• The effectiveness of oral

corticosteroids in viral croup is well established. Corticosteroids decrease the edema in the laryngeal mucosa through their anti-inflammatory action. Oral steroids are beneficial, even in mild croup, as measured by reduced hospitalization, shorter duration of hospitalization, and reduced need for subsequent interventions such as epinephrine administration. Nelson 2016 p2034


Croup•Most studies that demonstrated the efficacy of oral dexamethasone used a single dose of 0.6 mg/ kg, •a dose as low as 0.15 mg/kg may be just as effective intramuscular dexamethasone and nebulized budesonide have an equivalent clinical effect; oral dosing of dexamethasone is as effective as intramuscular administration. A single dose of oral prednisolone is less effective. Nelson 2016 p2034


• croup

• There are no controlled studies examining the effectiveness of multiple doses of corticosteroids. The only adverse effect in the treatment of croup with corticosteroids is the development of Candida albicans laryngotracheitis in a patient who received dexamethasone, 1 mg/ kg/24 hr, for 8 days. Nelson 2016 p2034


Epiglottitis

• Racemic epinephrine and corticosteroids are ineffective. Nelson 2016 p2034


Meningitis• Some experts recommend

use of corticosteroids in pneumococcal meningitis early in the course of disease, but data demonstrating clear benefit in children is lacking. Nelson 2016 p1325


• Data support the use of intravenous dexamethasone, 0.15 mg/kg/ dose given every 6 hr for 2 days, in the treatment of children older than 6 wk with acute bacterial meningitis caused by H. influenzae type b. lead to reduction in sensorineural hearing loss. Data in children regarding benefits, if any, of corticosteroids in the treatment of meningitis caused by other bacteria are inconclusive. Nelson 2016 page 2943112/05/03 Mohamed Zannoun

• . Early steroid treatment of adults with bacterial meningitis, especially those with pneumococcal meningitis, results in improved outcome Corticosteroids appear to have maximum benefit if given 1-2 hr before antibiotics are initiated. They also may be effective if given concurrently with or soon after the first dose of antibiotics.

• Nelson 2016 page 2943


Pertussis Bordetella pertussis

• No randomized, blinded clinical trial of sufficient size has been performed to evaluate the usefulness of corticosteroids in the management of pertussis Nelson 2016 p1380


Salmonella typhoid fever• Although additional treatment with

dexamethasone (3 mg/kg for the initial dose, followed by 1 mg/kg every 6 hr for 48 hr) is recommended for severely ill patients with shock, stupor, or coma; corticosteroids should be administered only under strict controlled conditions and supervision, because their use may mask signs of abdominal complications. Nelson 2016 p1392


Tuberculosis

• Corticosteroids decrease mortality rates and long-term neurologic sequelae in some patients with tuberculous meningitis by reducing vasculitis, inflammation, and, ultimately, intracranial pressure. Lowering the intracranial pressure limits tissue damage and favors circulation of antituberculosis drugs through the brain and meninges.. Nelson 2016 p1459.


tuberculosis• Short courses of corticosteroids also may be

effective for children with endobronchial tuberculosis

• Several randomized clinical trials have shown that corticosteroids can help relieve symptoms and constriction associated with acute tuberculous pericardial effusion. Corticosteroids can cause dramatic improvement in symptoms in some patients with tuberculous pleural effusion and shift of the mediastinum. However, the long-term course of disease is probably unaffected. Nelson 2016 p1459.


miliary tuberculosis• in case of tuberculoma, a tumor-

like mass resulting from aggregation of caseous tubercles that usually manifests clinically as a brain tumor Corticosteroids are usually administered during the 1st few wk of treatment or in the immediate postoperative period to decrease cerebral edema

• Nelson 2016 p1452-53.112/05/03 Mohamed Zannoun

Miliary tuberculosis• Some children with severe miliary

tuberculosis have dramatic improvement with corticosteroid therapy if the inflammatory reaction is so severe that alveolocapillary block is present. There is no convincing evidence to support a specific corticosteroid preparation. The most commonly used regimen is prednisone, 1-2 mg/kg/day in 1-2 divided doses orally for 4-6 wk, followed by a taper. Nelson 2016 p1459.

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Herpes zoster

• Use of corticosteroids in the treatment of herpes zoster in children is not recommended. Nelson 2016 p1585


Infectious mononucleosis• Short courses of corticosteroids

(<2 wk) may be helpful for selected complications of infectious mononucleosis, but this use has not been evaluated critically. Some appropriate indications include incipient airway obstruction, thrombocytopenia with hemorrhaging, autoimmune hemolytic anemia, seizures, and meningitis. Nelson 2016 p1589


Infectious mononucleosis• A recommended regimen is prednisone

1 mg/kg/day (maximum: 60 mg/day) or equivalent for 7 days and tapered over another 7 days. There are no controlled data showing efficacy of corticosteroids in any of these conditions. In view of the potential and unknown hazards of immunosuppression for a virus infection with oncogenic complications, corticosteroids should not be used in uncomplicated cases of infectious mononucleosis. Nelson 2016 p1589


Sepsis and Septic shock• Corticosteroids should

not be administered for the treatment of sepsis in the absence of shock.

• Nelson 2016 p525-26


Sepsis and Septic shock• In adults if adequate fluid resuscitation

and vasopressor therapy are not able to restore hemodynamic stability In case we suggest intravenous hydrocortisone alone at a dose of 200 mg per day. Timely hydrocortisone therapy in children with fluid refractory, catecholamine resistant shock and suspected or proven absolute (classic) adrenal insufficiency. Nelson 2016 p525-26112/05/03 Mohamed Zannoun

cardiogenic shock• Currently available pediatric data

do not demonstrate an overall survival benefit in patients with cardiogenic shock treated with hydrocortisone. Determination of baseline cortisol levels prior to steroid administration may be beneficial in guiding therapy, although this idea remains controversial. Nelson 2016 p526


live vaccines

• Corticosteroids can suppress the immune system. Children receiving corticosteroids (≥2 mg/kg/day or ≥20 mg/day of prednisone or equivalent) for 14 or more days should not receive live vaccines until therapy has been discontinued for at least 1 mo. Nelson 2016 p1256


live vaccines

• Children on the same dose levels but for <2 wk may receive live viral vaccines as soon as therapy is discontinued, although some experts would wait 2 wk after therapy has been discontinued. Children receiving lower doses of corticosteroids may be vaccinated while receiving therapy. Nelson 2016 p1256


wheezing infants

• Oral steroids are generally reserved for atopic wheezing infants thought to have asthma that is refractory to other medications.

• Their use in 1st-time wheezing infants or in infants who do not need hospitalization is controversial. Nelson 2016 p2047


Bronchial Asthma

• Corticosteroids are the most potent and most effective medications used to treat both the acute (administered systemically) and chronic (administered by inhalation) manifestations of asthma. They are available in inhaled, oral, and parenteral forms Nelson 2016 p1107.


Oral vs IV• Short-course systemic corticosteroid

therapy is recommended for use in moderate to severe asthma exacerbations to hasten recovery and prevent recurrence of symptoms. Corticosteroids are effective as single doses administered in the emergency department, short courses in the clinic setting, and both oral and intravenous formulations in hospitalized

children. Nelson 2016 p1114.112/05/03 Mohamed Zannoun

Oral vs IV• Studies in children hospitalized with

acute asthma have found corticosteroids administered orally to be as effective as intravenous corticosteroids. Accordingly, oral corticosteroid therapy can often be used, although children with sustained respiratory distress who are unable to tolerate oral preparations or liquids are obvious candidates

for intravenous corticosteroid therapy. Nelson 2016 p1114


• Systemic corticosteroids are rarely indicated in the treatment of chronic AD. The dramatic clinical improvement that may occur with systemic corticosteroids is frequently associated with a severe rebound flare of AD after therapy discontinuation.. Nelson 2016 p1119.

Systemic CS in Atopic Dermatitis AD (Atopic Eczema)


• Short courses of oral corticosteroids may be appropriate for an acute exacerbation of AD while other treatment measures are being instituted in parallel. Nelson 2016 p1119.


Urticaria

• In Chronic urticaria If hives persist after maximal H1- and/or H2-receptor blockade has been achieved, a brief course of oral corticosteroids may be considered, but long-term steroid use is best avoided. Nelson 2016 p1130.


Stevens-Johnson Syndrome SJS and ToxicEpidermal Necrolysis TEN

• Adverse Reactions to Drugs• Corticosteroids are

contraindicated because they can significantly increase the risk of infection. Nelson 2016 p1147.


DIAPER DERMATITIS

• A common practice is to presumptively treat any diaper rash that has been present for longer than 3 days with topical antifungal therapy such as nystatin, clotrimazole, or miconazole. If significant inflammation is present, the addition of hydrocortisone 1% may be useful for the 1st 1-2 days, but topical corticosteroids should be used cautiously in infants because the relatively potent topical corticosteroid can lead to adverse effects. Frequent diaper changes and short periods without diapers are important adjunctive treatments. Nelson 2016 p1517


Eosinophilic Esophagitis

corticosteroids have been used successfully for nonresponders and for nonallergic (“primary”) EoE, with symptomatic and histologic remission rates reaching 90%. Nelson 2016 p1791


Eosinophilic Gastroenteritis

• A majority of patients require treatment with systemic corticosteroids, which are often effective. Nelson 2016 p1831


GIT disorders112/05/03 Mohamed Zannoun

Ulcerative colitis• Children with moderate to severe

pancolitis or colitis that is unresponsive to 5-aminosalicylate 5-ASA therapy should be treated with corticosteroids, most commonly, prednisone. The usual starting dose of prednisone is 1-2 mg/kg/24 hr (40-60 mg maximum dose). This medication can be given once daily. With severe colitis, the dose can be divided twice daily and can be given intravenously. Nelson 2016 p1824


Ulcerative colitis

Steroids are considered an effective medication for acute flares, but they are not appropriate maintenance medications because of loss of effect and side effects, Nelson 2016 p1824


Crohn disease

• Corticosteroids are utilized for acute exacerbations of pediatric Crohn disease because they effectively suppress acute inflammation, rapidly relieving symptoms (prednisone, 1-2 mg/kg/day, maximum 40-60 mg). The goal is to taper dosing as soon as the disease becomes quiescent. Nelson 2016 p1830


contoversy about the use corticosteroids in pediatric

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