Multi-Incident Analysis Identifies Opportunities to Improve Treatment and Prevention of Adrenal Crisis
Adrenal crisis is a potentially fatal yet preventable event for patients with adrenal insufficiency. This multi-incident analysis shares opportunities to improve the timely and effective use of corticosteroids for maintenance doses, stress doses, and emergency treatment in this patient population.
INTRODUCTION
Adrenal crisis is a life-threatening emergency that occurs when patients experiencing adrenal insufficiency do not receive adequate and timely corticosteroid replacement (e.g., hydrocortisone).1 This bulletin highlights findings from an analysis of medication incident reports associated with the prevention or treatment of adrenal crisis. Opportunities are shared to improve timely and effective use of corticosteroids in this patient population.
BACKGROUND
Patients with adrenal insufficiency have impaired adrenal gland function and cannot produce sufficient cortisol.1,2 Figure 1 outlines the different types of adrenal insufficiency. Cortisol is a hormone that regulates blood pressure, electrolyte balance, and the body’s response to stress.1,3
FIGURE 1. Types of adrenal insufficiency. CRH = corticotropin-releasing hormone; ACTH = adrenocorticotropic hormone
To prevent adrenal crisis, these patients require corticosteroid treatment, typically with oral hydrocortisone. During periods of physiological stress, such as illness, surgery, or trauma, increased or “stress”/“sick day” doses of corticosteroids are needed to meet the body’s heightened demands.2
Patients experiencing an acute adrenal crisis (including those not yet diagnosed with adrenal insufficiency) often present with nonspecific symptoms,1,2,5 such as fatigue, nausea/vomiting, abdominal pain, diarrhea, confusion, and syncope.1 Failure to recognize the need for stress doses or immediate treatment can result in rapid deterioration (e.g., altered mental status, hypotension, hypoglycemia, shock) and, in severe cases, death.2
METHODOLOGY
Medication incidents associated with adrenal crisis, submitted in the 5-year period between March 2020 and February 2025, were extracted from ISMP Canada’s Consumer Reporting program, Individual Practitioner Reporting database, and the National Incident Data Repository for Community Pharmacies (NIDR), as well as the Canadian Institute for Health Information (CIHI) National System for Incident Reporting (NSIR).* Key search terms included “hydrocortisone” and “adrenal”. Reports were excluded if they described indications unrelated to adrenal insufficiency or adrenal crisis. The analysis was conducted according to the multi-incident analysis methodology outlined in the Canadian Incident Analysis Framework.6
QUANTITATIVE FINDINGS
Of the 979 medication incidents retrieved, 76 incidents were included for analysis.† Of these incidents, 44% were associated with harm (Figure 2 ).
FIGURE 2. Distribution of reported incidents by level of harm.
Almost half (49%) of included incidents were reported to have been discovered by patients or their caregivers, followed by nursing staff (30%) and pharmacists (12%) (Figure 3).
FIGURE 3. Distribution of reported incidents by discoverer.
QUALITATIVE ANALYSIS
Three main themes and related subthemes associated with adrenal crisis were identified in the analysis (Figure 4).
FIGURE 4. Themes and subthemes identified in the analysis.
THEME: Treatment of Acute Adrenal Crisis
In the treatment of adrenal crisis, timely recognition of signs and symptoms is crucial.
Subtheme: Delayed or omitted treatment
Delayed or omitted treatment was reported in multiple incidents. In some reports, patients shared that they did not receive treatment, even when they (or their caregiver) provided a documented emergency care plan developed by their health care team.7 Reported contributing factors included lack of emergency injectable supply, expired doses of injectable hydrocortisone, and insufficient health care provider knowledge.
Incident example: A patient experiencing an adrenal crisis was not given an emergency dose of injectable hydrocortisone by paramedics prior to transfer of care at the hospital because there was no supply and the patient’s own vials were expired. The patient was subsequently discharged from hospital with neither the appropriate treatment nor a prescription for hydrocortisone. As a result, the patient had to be admitted to hospital a second time for adrenal crisis.
RECOMMENDATIONS:
- Develop a written/electronic emergency care plan or wallet card for patients who may experience adrenal insufficiency, to be shared with health care providers in the event of an adrenal crisis. The care plan should include a description of the health condition, potential signs and symptoms of concern, and specific care needed.7,8
- Stock all ambulances with vials of hydrocortisone for intravenous/intramuscular administration in the event of adrenal crisis. This measure has already been implemented in many jurisdictions.
- Provide a prescription for oral and injectable hydrocortisone (and appropriate injection training) for patients with adrenal insufficiency discharged from hospital. The oral tablets are needed for maintenance dosing, while the injection is needed in case of another adrenal crisis.
THEME: Stress Dosing to Prevent Adrenal Crisis
Situations that may be associated with predictable physiological stressors, during which patients with adrenal insufficiency must receive elevated corticosteroid dosing, include trauma, surgical procedures, labour and delivery, and acute infections.
Subtheme: Inconsistent perioperative considerations
Inconsistencies in stress dosing protocols before and after surgical procedures were reported, with miscommunication (e.g., ambiguous or unclear orders) as a key contributing factor.
RECOMMENDATION:
- Use clear and specific instructions in all orders according to evidence-informed perioperative guidelines.9
- Instead of “resume steroids pre-op” or “continue stress-dose steroids,” specify the drug, dose, route, and frequency. For example, “Resume maintenance dose of hydrocortisone X mg by mouth Y times per day”.
Subtheme: Incomplete assessment during infections
The need for stress doses during episodes of illness was frequently reported as having been overlooked during clinical assessment of patients with adrenal insufficiency. Contributing factors included insufficient knowledge on the part of health care providers, absence of critical information in the patient’s medical records, and inadequate patient education.
Incident example: A patient with adrenal insufficiency was experiencing symptoms of a COVID-19 infection, so Paxlovid (nirmatrelvir/ritonavir) was prescribed. The pharmacist noticed a drug interaction between Paxlovid and hydrocortisone and advised the patient to temporarily reduce the dose of their hydrocortisone. However, given that the patient was experiencing an acute infection (a source of stress), the dose of hydrocortisone should have been increased, to prevent adrenal crisis.
RECOMMENDATIONS:
- Perform a medication review to determine the most appropriate therapeutic management of the patient’s clinical condition.
- Start with a Best Possible Medication History (BPMH) interview10 when assessing new patients to capture all critical patient information (e.g., allergies, medications, emergency care plans).
- Provide written information to the patient about when and how to use stress dosing.11, 12
THEME: Maintenance Dosing to Prevent Adrenal Crisis
Patients with chronic adrenal insufficiency rely on daily corticosteroids. Even brief interruptions in maintenance therapy can be detrimental.
Subtheme: Complex diagnostic procedures for adrenal insufficiency
In one study, more than 90% of patients presenting to the emergency department in adrenal crisis had undiagnosed adrenal insufficiency.5 The diagnostic process for adrenal insufficiency is complex and relies heavily on interdisciplinary coordination in hospital; in particular, the required laboratory work depends on time-sensitive drug administration and corresponding blood draws.
RECOMMENDATIONS:
- When cosyntropin (synthetic ACTH, a medication used in the diagnosis of adrenal insufficiency) is ordered, create an automated note in the electronic order to ensure the phlebotomy team is contacted before medication administration and will be available to draw blood at the appropriate times.
- Identify patients at risk for secondary adrenal insufficiency, through discussion about recent medication (e.g., corticosteroid, opioid) use and dose changes.
Subtheme: Unavailability or inaccessibility of hydrocortisone
Issues with lack of a commercially available product in pediatric strengths, dilution errors in compounding, and interruptions to the medication supply13 were reported to contribute to medication errors.
Incident example: An infant with diagnosed adrenal insufficiency was prescribed a dose of hydrocortisone that was smaller than the commercially available product. One quarter of a 10 mg tablet was tucked into the infant’s cheek pocket before they drank from a baby bottle . The quartered tablets were unequal and sharp, and the infant would repeatedly dislodge and expel the medication, resulting in missed or omitted doses.
RECOMMENDATIONS:
- Advocate for commercially available hydrocortisone in pediatric strengths or pediatric-friendly formulations (e.g., Alkindi Sprinkle granules) to be made available in Canada.
- Require documentation of pharmacy-compounded products on a standardized worksheet, including a documented independent double check by a pharmacist or registered technician of the selected product, calculations, and measured amount/volume.14,15
CONCLUSION
Adrenal crisis is a potentially fatal yet preventable event for patients with adrenal insufficiency. This multi-incident analysis has highlighted opportunities to improve the timely and effective use of corticosteroids for emergency treatment, stress doses, and maintenance doses. Preventing adrenal crisis requires clinical knowledge, coordinated care, communication, proactive planning, and shared decision-making with the patient.
The Canadian Medication Incident Reporting and Prevention System (CMIRPS) is a collaborative pan-Canadian program of Health Canada, the Canadian Institute for Health Information (CIHI), the Institute for Safe Medication Practices Canada (ISMP Canada) and Healthcare Excellence Canada (HEC). The goal of CMIRPS is to reduce and prevent harmful medication incidents in Canada.
Funding support provided by Health Canada. The views expressed herein do not necessarily represent the views of Health Canada.
The Healthcare Insurance Reciprocal of Canada (HIROC) provides support for the bulletin and is a member owned expert provider of professional and general liability coverage and risk management support.
The Institute for Safe Medication Practices Canada (ISMP Canada) is an independent national not-for-profit organization committed to the advancement of medication safety in all healthcare settings. ISMP Canada’s mandate includes analyzing medication incidents, making recommendations for the prevention of harmful medication incidents, and facilitating quality improvement initiatives.
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