Sara Moassesfar
April 8, 2015
Protocol, assignment 1
Hi all, I changed my topic to be more suitable in regards to evidence ready for translation, thank you for your feedback:
1. What evidence are you proposing to translate into practice?
I propose the development of a protocol for use by the pediatric oncology team for the gradual weaning of glucocorticoids (steroids) in oncological patients who have been on steroids (i.e. prednisone) for longer than 10 days, and then retesting their hypothalamic-pituitary-adrenal axis with an ACTH stimulation test, in order to prevent undiagnosed and untreated adrenal insufficiency in these patients.
A. Justify that this evidence is “ready for translation.”
There is an abundance of evidence in the literature from the past 40 years that adrenal suppression can occur when a patient is on high-dose steroids for more than 10-14 days (i.e. our usual doses of prednisone given in conjunction with chemotherapy for oncological conditions such as tumors or leukemia). This adrenal suppression means there is less or no signaling from the hypothalamus to the pituitary gland, and then from the pituitary gland to the adrenal gland, to stimulate the adrenal gland to produce cortisol. This results in low serum levels of cortisol, which can be dangerous to the patient. Cortisol is a critical hormone that is necessary to maintain normal blood pressure, normal blood sugars and a normal sense of energy. Those with deficiencies in cortisol are at risk for severe drops in blood pressure, blood sugars and even coma/death, particularly at times of stress, such as with a severe illness. As a result, pediatric endocrinologists have long been advising steroid replacement for those with cortisol deficiency, usually with hydrocortisone. The need for steroid replacement is more obvious in patients with adrenal gland diseases that clearly don’t have functioning glands. However, when pediatric patients are placed on high-dose steroids for 10 days or longer for treatment of another condition, such as cancer, sometimes their providers don’t consider that the hypothalamic-pituitary-adrenal (HPA) axis could be suppressed by this and do not provide a gradual weaning of the steroid so to reawaken the HPA axis. Nor do they retest the axis with an ACTH stimulation test after topping the steroid, to ensure the axis is intact and the adrenal gland is capable of secreting normal levels of cortisol. This puts patients at severe risk, particularly those who are already ill with cancer or other serious illnesses (1-5).
As endocrinologist, when we are consulted for pediatric oncology patients who have received high-dose steroids for prolonged periods of time, we make such recommendations and monitor. However, we have noticed that we are often not consulted on such a patient and the oncology team may discontinue the steroid without these considerations, which again, can be detrimental to the patient. Thus, I am interested in putting a protocol into place to translate the abundant evidence in the literature into actual practice and ensure every oncological patient in who receives a prolonged course of steroids (>10 days) in conjunction with their chemotherapy, eventually undergoes a standardized weaning of the steroid and formal retesting of the HPA axis. My endocrinology team believes this would be the best standard of care
B. Identify a single, key behavior change target for your translational activity.
I would like to increase awareness amongst pediatric oncologists of the dangers of abrupt discontinuation of a prolonged steroid course (that is >10 days) and have them follow guidelines for gradual tapering of the steroids and retesting of the HPA axis to ensure its normalization, before the discontinuation of the steroids.
2. Conduct a “gap analysis” of your target behavior. Look to diverse sources for “best guess” estimates if specific measures are not available.
A. What is the quality (performance) gap?
Currently, in practice, we often see that pediatric oncologists discontinue steroids abruptly after a prolonged course without consulting endocrinology, and without gradually tapering the dose and retesting the HPA axis with an ACTH stimulation test. When we look at their protocols for the doses of prednisone given with chemotherapy, we see there are no guidelines for how to eventually taper off the medication and perform follow up lab evaluation. Each oncologist seems to have different practices in this regards and there is no standardization.
B. What is the outcome gap?
With this protocol, we hope to close this gap and put a standard process in place, to be followed by each pediatric oncologist. Our goal is this will lead to gradual tapering of the medication with each and every patient in this situation, and retesting with an ACTH stimulation test when appropriate.
3. Is there evidence that changing performance will improve health (clinical outcomes)?
There is a lot of evidence from previous cohort studies and reviews that shows that adrenal insufficiency can happen from an abrupt discontinuation after a prolonged course of steroids and that some of these patients can become ill with severely low blood pressure and hypoglycemia, often requiring rehospitalization (1-5). Changing our approach to these patients will prevent these detrimental consequences and will improve health outcomes.
References
- Maartje S Gordijn, Reinoud JBJ Gemke, Elvira C van Dalen, Joost Rotteveel, Gertjan JL Kaspers. Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia. Cochrane Library. Published Online May 16, 2012.
- Stefan R. Bornstein. Predisposing Factors for Adrenal Insufficiency. N Engl J Med 2009; 360:22.
- R Schlaghecke, E Kornely, et al. The effect of long-term glucocorticoid therapy on pituitary–adrenal responses to exogenous corticotropin-releasing hormone. New England Journal of Medicine. January 23, 1992; 326:4.
- James C. Melby. Drug Spotlight Program: Systemic Corticosteroid Therapy: Pharmacology and Endocrinologic Considerations. Ann Intern Med.1974; 81(4):505-512.
- Briana C. Patterson, Karen Wasilewski-Masker, A. Blythe Ryerson, Ann Mertens, Lillian Meacham. Endocrine Health Problems Detected in 519 Patients Evaluated in a Pediatric Cancer Survivor Program. The Journal of Clinical Endocrinology & Metabolism. Volume: 97 Issue: 3. Published online Dec 21, 2011.