Subcutaneous hydrocortisone administration for emergency use in adrenal insufficiency

Abstract

Objective: Evaluation of the pharmacokinetics and safety of s.c. hydrocortisone injection for use in adrenal emergency. Design: Single-center, open-label, sequence-randomized, crossover study in a tertiary care center. Patients and methods: Twelve patients with chronic Addison's disease. Comparison of hydrocortisone pharmacokinetics after s.c. and i.m. injection (100 mg) and after s.c. administration of sodium chloride (0.9%) respectively at three different visits. Main outcome measure: maximum serum cortisol (C max ), time to C max (t max ), and time to serum cortisol O36 mg/dl (t serum cortisol O36 mg/dl ) after s.c. administration compared with i.m. administration, safety, and patient preference. Results: Serum cortisol increased rapidly and substantially after both i.m. and s.c. injections (C max : 110G29 vs 97G28 mg/dl, PZ0.27, t max : 66G51 vs 91G34 min, PZ0.17, and t serum cortisol O 36 mg/dl : 11G5 vs 22G11 min, PZ0.004 respectively). Both i.m. and s.c. injections were well tolerated. Eleven (91.7%) patients preferred s.c. injection, whereas one patient did not have any preference. Conclusions: S.c. administration of 100 mg hydrocortisone shows excellent pharmacokinetics for emergency use with only a short delay in cortisol increase compared with i.m. injection. It has a good safety profile and is preferred by patients over i.m. injection.

EXTENSIVE EXPERTISE IN ENDOCRINOLOGY: Adrenal crisis

“…Reducing barriers to self-injection are most important in my view and the ease of s.c. injection far outweighs the short delay (11 min) in reaching concentrations above 1000 nmol/l (22 min compared with 11 min after i.m. injection) (76). This small time difference compares very favourably with current time lines from contacting health professionals until their eventual hydrocortisone injection in impending crisis (43).…”

“…Importantly, we have recently demonstrated that s.c. hydrocortisone is rapidly absorbed with only a short delay compared with i.m. injection (76). Patients clearly prefer s.c. over i.m.…”

Children with classic congenital adrenal hyperplasia experience salt loss and hypoglycemia: evaluation of adrenal crises during the first 6 years of life

“…The high number of cases without parenteral application of a glucocorticoid in spite of repeated vomiting might be reduced if -instead of i.m. injection -s.c. glucocorticoid injection or a 'hydrocortisone pen' could be established for emergency use in the future (8,32,33). As problems related to a lack of experience among health professionals are characteristic of rare diseases and not unique to CAH, they might be overcome by a generally raised awareness about these so-called 'orphan diseases' in the healthcare system (31).…”

Adrenal Crisis: Still a Deadly Event in the 21st Century

“…Subcutaneous hydrocortisone administration has been recently shown to achieve adequately high serum cortisol levels in only 11 minutes longer than intramuscular administration. 42 While absorption may be reduced in a patient with shock, if more patients are able to administer hydrocortisone at an earlier time, then this may prove to be beneficial. 43 …”