EXECUTIVE SPONSOR(S): Bradley Monash, MD
ABSTRACT: Diphenhydramine is a first-generation antihistamine that is frequently used for a broad range of indications such as pruritis, allergy, nausea, vomiting and insomnia. Its useis linked with various side effects including sedation, delirium, and cognitive dysfunction. It is also one of the most abused medications in the United States;with its presence detected in approximately 15% of deaths from overdose.
Most use of parental diphenhydramine in the hospitalized patient is unnecessary and prolonged. For most indications, there are other safer, more effective medications. Preliminary data from UCSF Health shows a longer length of stay (~21 days) for those receiving ongoing IV diphenhydramine than the average hospitalized adult patient. In focus groups asking providersat UCSF about management of complex patients, a source of distress for providers has been the often-contentious negotiations around weaning off IV diphenhydramine on the path to safe discharge.
Reduction of the use of IV diphenhydramine at UCSF Health can be achieved through agreement across stakeholders to develop a system wide standard. Work on this topic has stalled in the past because of the breadth of applications for the medicine. Now with increased on the ground acknowledgement of IV diphenhydramine as an issue (despite very little published data) there is widespread interest in addressing the problem in the health system. Our first step is to standardize IV diphenhydramine ordering and recommendations around alternatives. Next, we will work to enhance EHR ordering guidelines and potentially develop “hard stops” especially for ongoing IV diphenhydramine use. Finally, we plan to create education and support around the shift in practice, especially in supporting patients for whom this change in practice may affect most.
TEAM:
- Omid Shah, MD (Hospital Medicine Faculty)
- Ethel Wu, MD (Hospital Medicine Faculty)
- CandyTsourounis, PharmD (Professor, Department of Clinical Pharmacy)
- Elise Wozniak, PharmD (Department of Pharmaceutical Services)
- Nader Najafi, MD (Hospital Medicine, Data Core Director)
- Keerthana Radhakrishnan (Data Core Analyst)
- Sarah Apgar, MD (Hospital Medicine Faculty, Code CARE Medical Director)
PROBLEM:
Diphenhydramine was approved by FDA in the 1940s and has long been used by patients and providers alike as a go-to medication for a broad range of indications. It is a first generation H1-antihistamine that has effects throughout the body including the respiratory, gastrointestinal and central nervous systems. It is used to treat mild to severe allergic reactions, migraines, nausea and vomiting, pruritis and insomnia amongst other complaints. Second generation antihistamines do not cross the blood brain barrier and so do not have sedating and other CNS effects that are commonly seen with diphenhydramine.Its anticholinergic properties add to the list of side effects that second generation antihistamines do not have.
In CDC data from 2019-2020, antihistamines were found in 15% of deaths due to overdose, almost all diphenhydramine, 3.6% of those deaths were due to antihistamines alone. Most were found to co-involve opioids. Abuse of antihistamines has been reported in medical literature since the 1970s and 1990s, little has been further published on the subject since. It is theorized that diphenhydramine hasadditional direct and indirect effects on neurotransmitters which can then have euphoric and anxiolytic effects.
For most indications, there are other safer, more effective medications than diphenhydramine. Most use of parental diphenhydramine in the hospitalized patient is unnecessary and prolonged. Preliminary data from UCSF Health shows a longer length of stay (~21 days) for those receiving ongoing IV diphenhydramine than the average hospitalized adult patient. Ongoing use is defined in this data set as more than 8 administrations of IV diphenhydramine per encounter via standing orders or ongoing PRN orders (all one-time IV diphenhydramine orders were excluded). Over fiscal year 2023-2024, this subset of patients represented nearly 3000 patient days at UCSF Health. Discussions around its administration and preparation for discharge has become a point of distress for patients and providers. In focus groups asking providers at UCSF about management of complex patients, a repeated topic to address has been around use of IV diphenhydramine.
TARGET:
Our goal is to decrease overall use of parental diphenhydramine for adult patients hospitalized at UCSF medical center. Specifically, we would like to see an overall decrease in its administration in at least 20% of patients who receive ongoing IV diphenhydramine over the course of one year. While there are subcategories of patients who frequently get this medication, from an equity lens we are choosing not to focus on a specific diagnosis. We will partner with multiple stakeholders to develop a comprehensive policy and plan to roll out this change that will provide support to both patients and providers.
GAPS:
Systems gaps: it is easy to order IV diphenhydramine, there is no stewardship around use of this medication,there is no guidance, no alternative given
Education: Because diphenhydramine has been an available over the counter medication since the 1940s there is familiarity and comfort in using this medicine amongst providers and patients. Outside of education around its avoidance in older patients, there is lack of knowledge around its additional harms.
Patient preferences: There is likely a degree of ongoing use driven by patient experience, prior use and preference.
Current State:
In 2023-24, UCSF Health had 137 encounters of patients who were ordered and administered ongoing IV diphenhydramine during their hospital stay. Eighty-six patients made up these 137 encounters.
The average length of stay for these encounters was 21.3 days, and equaled 2917 total patient days.
INTERVENTION:
Stakeholder engagement: We aim to put together a multidisciplinary working group to develop standardization around the use of IV diphenhydramine and recommendations for alternative options. Alignment on how to limit IV diphenhydramine and policy around its use will need to be determined amongst many stakeholders across our institution. We have already engaged representatives from the emergency department, pharmacy, code CARE and chronic pain. We plan to reach out to many more stakeholders.
EHR modification: Based on the policy agreed upon, we will design a new APeX orderset that likely put some limit to access of IV diphenhydramine as well as develop guidelines for use and provide alternative medications for different indications.
Education: We plan to develop educational materials, talking points, and patient facing materials around use of diphenhydramine. Among side the stakeholder engagement, we will also explore ways to provide educational sessions for specific and targeted provider groups. With engagement of the Code CARE team, we will develop strategies to inform and prepare patients of upcoming changes.
PROPOSED EHR MODIFICATIONS: Please see above the above section.
RETURN ON INVESTMENT (ROI):
In work done at our institution, when a concerted effort was made to reduce IV opioids in specific patients with targeted care plans by the Chronic Pain team, the Code CARE team, and Hospital Medicine, LOS and readmissions were drastically reduced.
In a retrospective study, looking specifically at the sickle cell patient population, patients on oral diphenhydramine had an average length of stay of ~10 days compared to the patients receiving IV diphenhydramine ~29 and 30 days.
Taking UCSF Health, 2023-2024, patient data, if we candecrease LOS by 25-50% in 20% ofpatient encounters, we anticipate a direct cost savings of $242,600 - $485,200.
137 patient encounters (86 unique patients) | 20% patient encounters | 27 patient encounters | |
Average LOS | 21.3 days | 25-50% reduction in LOS | 5.3 to 10.6 days |
Estimated room & board per day | $1688 | ||
Estimated cost savings | $242,600-485,200 | ||
SUSTAINABILITY: These interventions will be sustained by Hospital Medicine leadership, specifically service directors, who will continue to support faculty and faculty education. They will continue engagement with specific key stakeholder groups such as Code CARE to determine ongoing patient and nursing needs.
BUDGET:
- Omid Shah – project lead – 25K
- Ethel Wu – project team – 10k
- Data analytics, campaign and educational material, IT support– 15k
Comments
For those patients who
For those patients who struggle with substance use disorders, the mixed messages about the use of IV Benadryl can cause emotional distress and challenges building trust with their care team. We have all had patients leave against medical advice when IV Benadryl is provided and then withheld due to concerns about potential abuse, which compromises patient safety. I would welcome clear guardrails about appropriate and inappropriate uses of IV Benadryl and alternatives so that we can set standards as an institution about how we can use this medication with a high abuse potential more appropriately.
As a physician working with
As a physician working with this patient population, I have often wished for an effort to help us decrease length of stay through evidence-based management of IV benadryl. A systems-based approach is necessary to achieve this.