Steroid Stewardship.

Steroid stewardship is the systematic effort to prescribe and monitor glucocorticoids in a rational manner, while balancing benefit and potential risk, in patients who require this therapy. Steroid stewardship includes pre-prescription screening, rational prescription, medical care during corticosteroid use, and appropriate monitoring after corticosteroid use has been discontinued. The current usage of this class of drugs has highlighted the need to focus on this collective responsibility, and ensure effective prescription, while minimizing adverse events. Copyright:

INTRODUCTION

The term antibiotic stewardship has been in use for many years now. The Centers for Disease Control and Prevention defines antibiotic stewardship as “the effort to measure and improve how antibiotics are prescribed by clinicians and used by patients”.[1] This concept has been extrapolated by experts to call for insulin stewardship and steroid stewardship (cdc.gov/antibiotic-use).[234]

Steroid stewardship is gaining traction with regards to acute exacerbations of chronic obstructive pulmonary disease and asthma management.[34] Steroids, however, are used in a wide variety of indications, by various medical specialties. This makes it imperative to address disease specific steroid stewardship in a broader context, rather than limiting it to respiratory medicine alone. The current Coronavirus disease 2019 (COVID-19) pandemic, with its myriad challenges, makes this topic even more relevant today.

In this brief communication, we define and describe steroid stewardship, create a pedagogic structure to facilitate ease of understanding, share endocrine and infectious disease viewpoints, and invite suggestions to help make this a global, pan-specialty movement.

DEFINITION

Steroid stewardship is the systematic effort to prescribe and monitor glucocorticoids in a rational manner, while balancing benefit and potential risk, in patients who require this therapy. Steroid stewardship includes pre-prescription screening, rational prescription, medical care during corticosteroid use, and appropriate monitoring after corticosteroid use has been discontinued. We use the term “steroid” as a synonym for glucocorticoid or glucocorticosteroid throughout the manuscript.

Steroid stewardship is a collective responsibility: the prescribing physician, other specialists who monitor the patient, the clinical pharmacologist, pharmacist, clinical nurse, and hospital administrator all need to work in cohesive collaboration to ensure effective steroid stewardship. The wide spectrum of corticosteroid usage, across specialties from pediatrics to obstetrics, from nephrology to neurology, and from rheumatology to endocrinology, suggests that this rubric has global relevance. It is the frequent use of corticosteroids in COVID-19,[5] in pulmonology and infectious disease setups, which has spurred the need to focus on steroid stewardship.

COMPONENTS

Steroid stewardship has the following components

Pre-prescription

Clarity of indication for use

Patient counseling and education

Medical and endocrine screening

During usage

Type of steroid

Dosage and mode of administration

Duration of therapy and expected dose changes

Monitoring for potential adverse effects

Sick day rules/troubleshooting

Tapering and weaning off from steroids

Post-usage

Medical and endocrine monitoring

Mitigation of long-term adverse effects

Each of these components is important, irrespective of the clinical situation in which corticosteroids are being used. For ease of understanding, we classify steroid use as indoor and outdoor, and as short term (less than three weeks) and long term (more than three weeks). We do not focus on specific indications of corticosteroid use, though we do differentiate between steroid replacement for adrenal insufficiency, and steroid supplementation for its anti-inflammatory response.

PRE-PRESCRIPTION STEROID STEWARDSHIP

The responsible physician should have clarity of thought, and certainty regarding indication and aim of steroid prescription. This should be explained to the patient in easy-to-understand language. The mnemonic BLACK provides a checklist for steroid counseling: Benefits, Limitations, possible Adverse events, Cost, and Knowledge/skills required to use steroid.[6] The mnemonic 4C: contraindications, concerns, caveats, and checkpoints[6] remind the treating physician to rule out contraindications, remember the caveats related to steroid use, and observe the checkpoints (or monitoring rules) during steroid use. The 5D rubric – dosage for initiation delivery, duration of treatment, dose titration/holiday, sick day management, and documentation is another tool which helps appropriate patient counseling and care.

The indication for steroid prescription: replacement in adrenal insufficiency, anti-inflammatory effect, or hemodynamic stability, should be cleared mentioned, along with expected duration and dosage of treatment. Pre-prescription diligence should include screening for medical metabolic and endocrine conditions which may be unmasked or worsened by steroid use. These include obesity, dysglycemia, osteoporosis, sarcopenia, worsening of diabetes, or new onset diabetes and mood disorders, among others. Appropriate plans should be delineated for monitoring and management of potential adverse events during steroid usage.

We once again reinforce the need for detailed documentation of plan of action, to ensure seamless management in case of change of health care provider or health care system.

STEWARDSHIP DURING STEROID ADMINISTRATION

Prescribing instructions should be clearly mentioned. In indoor settings, orders should be updated daily. For outdoor patients, it may help to write the duration of therapy, and tapering schedule, if relevant, when any steroid is prescribed.

The prescribing physician should be aware of the relative potency of various steroids [Table 1]. A background knowledge of the mineralocorticoid effects of various steroids is also needed as it helps in decision-making in agent selection is some cases, for example, those having poor cardiovascular reserve may be unable to tolerate the volume overload that results from sodium retention.

Table 1

Relative potency of various steroids

Steroid	Anti-inflammatory effect	HPA Axis suppression	Salt retention
Cortisol	1	1	1
Prednisolone	3	4	0.75
Methylprednisolone	6.2	4	0.75
Dexamethasone	26	17	0
Fludrocortisone	12	12	125
Triamcinolone	5	4	0

Table adapted from William’s textbook of Endocrinology 14th ed.. ition. (HPA- Hypothalamo Pituitary Adrenal axis)[7]

Multiple topical steroid preparations are available, including ocular drops, ear drops, lotions, and creams. These are used by experts in the concerned specialties, and merit a separate debate on steroid stewardship [Table 2]. Non-judicious topical administration can lead to local and systemic side effects [Image 1]. Topical steroids should be used with caution in children and elderly as they have larger surface area to body weight ratio with poor skin barrier function in the children and skin fragility in elderly.[8]

Table 2

Different forms of steroid formulation available for topical, mucosal, and inhalational use

Formulation type	Clinical usage	Benefits	concerns
Skin
Ointment	Infiltrated, thick lichenified skin lesions	Occlusive property provides skin hydration	Systemic absorption
Cream	Various dermatoses	Ease of application	Systemic absorption
Lotion	Various dermatoses	Ease of application	Systemic absorption
Gel	Used in various types of skin diseases	Ease of application	Systemic absorption
Mucosa
Eye	Used in inflammatory conditions of eye	Direct delivery	Glaucoma
Inhaled steroids	Used in asthma and COPD	Target organ delivery, lesser systemic side effects	Oropharyngeal candidiasis

Image 1

35-year-old female on topical steroids, development of striae on one side in axilla at the site of application

It does not make clinical and logical sense to prescribe two systemic steroids, whether oral or injectable, together. Contemporary guidelines should be followed while deciding doses, and unnecessarily high doses should be avoided. Metabolic and endocrine monitoring must be performed as per the clinical situation [Table 3]. In the short term, hemodynamic status, glycemic health and mood, are of paramount importance. In the longer term, musculoskeletal health becomes equally important.

Table 3

Baseline assessment and long-term monitoring of patients planned for long-term systemic corticosteroid therapy

Baseline clinical examination

Weight

Height

BMI

Blood Pressure

Acanthosis nigricans/skin tags

Pedal edema

Baseline Investigations

Glucose (FPG, A1C, 2-h OGTT)

Lipid Profile

DEXA BMD

Follow up monitoring

Clinical examination - weight gain, BP monitoring.

Growth monitoring in children

Glucose (FPG, A1C, 2-h OGTT)

Lipid Profile

Bone Health

Assessment of risk of fragility fractures.

DEXA BMD

X-ray spine

change in height (Vertebral fracture) back pain, limping (Avascular Necrosis of Hip).

FRAX scoring and risk assessment for vertebral fracture risk.

Timely administration of the bisphosphonates other measures to maintain good bone health needs to be ensured.

Ophthalmological assessment for cataract and glaucoma

Appropriate management of steroid-induced complications must be instituted in a timely manner, to prevent complications.

For persons on long-term steroid replacement for adrenal or pituitary insufficiency, sick day rules must be clarified.[8] Emergency administration of steroids, and increase in their dosage, must be done in case of sickness. The patient, close care givers, and health care team must be aware of these rules.

TAPERING OF STEROIDS

The negative feedback control of the hypothalamic–pituitary–adrenal (HPA) axis by corticosteroids suppresses the function of the HPA axis in a dose and duration dependent manner. Consequently, the sudden cessation of steroid therapy can cause unmasking of adrenal failure. This suppression may be seen with use of the progestogen, medroxyprogesterone acetate, which has glucocorticoid agonist activity. If the duration of therapy is less than three weeks, suppression of the HPA axis unlikely, and sudden cessation of steroids can be done with no ill effect. Longer duration therapy must be tapered gradually, and time given to the HPA axis to recover. [Table 4]

Table 4

Steroid Tapering and withdrawal

Steroid Dose	Duration <3 weeks	Duration >3 weeks
>7.5 mg Prednisolone	Can stop without tapering	Reduce every 3-4 days to reach a dose of 5 mg per day, thereafter reduce 1 mg every 2-4 weeks. Or Convert 5 mg pred to 20 mg HC, then↓2.5 mg/wk to 10 mg/day. After 2-3 months on HC 10 mg/day, go for stimulation testing and look for response. Pass→Withdraw Fail→Continue
5-7.5 mg Prednisolone	Can stop without tapering
<5 mg Prednisolone	Can stop without tapering

Table adapted from William’s textbook of Endocrinology 14th Edition.[7]

POST-STEROID STEWARDSHIP

The responsibility of the steroid stewardship continues even after the course has ceased. Steroid usage may be associated with multiple adverse events, and pharmacovigilance is required to minimize their impact on health and metabolism. The nature and intensity of pharmacovigilance depends upon the premorbid health status, dose and duration of steroid intake, natural history of disease, and complications encountered.

The law of therapeutic parsimony applies to steroid usage.[9] Long-term complications of steroid use can be mitigated by using the minimum required dose of steroids, for the shortest duration necessary.

Supplementation with calcium and vitamin D, lifestyle measures to prevent weight gain, and early detection and management of possible metabolic, musculoskeletal or mood disorders may be helpful.

One must keep a watch for development or worsening of dysglycemia, dyslipidemia, weight, hypertension, osteoporosis, and mood disorders during and after steroid use. It is also necessary to screen for second and opportunistic infections, including skin and soft tissue infection.

Person with steroid-induced hyperglycemia should be monitored for dysglycemia at regular intervals, even after the initial episode of high glucose has resolved.

SUMMARY

Steroid stewardship is a concept which adds value to glucocorticoid usage. By increasing safety and tolerability, it improves the benefit risk ratio of the steroid prescription. Each healthcare team should have a written steroid stewardship document, relevant for its clinical environment. This must contain a prescription checklist, preferred names, doses and route of administration of steroids, protocols for dose titration and tapering, and instructions for post-prescription follow-up. Such stewardship documents will ensure rational and effective use of these life-saving drugs.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.