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Reference: Wong KH, et al. Improving Use of Oral Antihistamines in a Children’s Hospital. Pediatrics. Feb 2026;
Date: March 15, 2026
Dr. Stephanie Kubala
Guest Skeptic: Dr. Stephanie Kubala is an attending physician in the Division of Allergy and Immunology at Children’s Hospital of Philadelphia. She is double board-certified in both pediatrics and allergy and immunology.
Case: A 5-year-old girl is brought in by her parents for an itchy rash. Her symptoms started last night. The parent reports an itchy, raised red rash on her trunk and extremities. She has not had any fever. She does not have any difficulty breathing, wheezing, vomiting, or diarrhea. On your exam, you note hives on her body but no lip or tongue swelling. Her lungs are clear to auscultation. She intermittently scratches at the rash. Her parents tell you, “We gave her a dose of diphenhydramine last night, and it may have helped a little, but it seems to have worn off. Can you help?”
Background:
In a lot of emergency departments, “hives = diphenhydramine” is practically muscle memory. It’s familiar, it’s been around forever, and families often expect it because it’s what they already have at home. As with many medical interventions, we must weigh potential harms against potential benefits.
The problem is that diphenhydramine and other first-generation antihistamines like hydroxyzine come with a bunch of potential side effects, such as sedation, anticholinergic side effects, and unpredictable behavior changes in some kids. It doesn’t always last very long, which can lead to repeat dosing and frustrated families when symptoms come back a few hours later.
On the other hand, second-generation antihistamines like cetirizine target the same H1 receptor for itch and urticaria but tend to be longer-acting and better tolerated, which is why many guidelines and expert groups prefer them for routine allergic symptoms. And there’s a bigger safety angle here, too: first-generation agents show up in dosing errors and misuse/overdose cases.
The real issue isn’t whether second-generation antihistamines like cetirizine work. They do. We need to start asking why our systems still nudge clinicians toward the older first-generation antihistamines as a default.
The issue is well-suited to a quality improvement (QI) study. Before we dive into the details of the study itself, let’s talk about some basics around QI.
QI helps close the gap between best practice and day-to-day care. It starts with a clear, measurable aim (what you want to improve, by how much, by when). This is followed by a simple measurement plan: an outcome measure (the main result you’re trying to change), process measures (the steps that should drive that result), and balancing measures (what might worsen unintentionally).
Teams then map the current workflow, identify barriers, and build a key driver diagram that links the aim to the handful of system levers most likely to move the needle.
The work is tested and refined using Plan–Do–Study–Act (PDSA) cycles. [2] These are iterative rather than a single big rollout. Data is tracked over time with run/control charts to show whether changes are real and sustained.
Clinical Question: Can a bundled QI approach meaningfully reduce first generation antihistamine use and increase cetirizine use among pediatric patients receiving oral antihistamines in the ED and inpatient settings?
Reference: Wong KH, et al. Improving Use of Oral Antihistamines in a Children’s Hospital. Pediatrics. Feb 2026;
- Population: Patients 6 months to 21 years in the pediatric ED and inpatient units at a tertiary academic children’s hospital
- Excluded: Patients in NICU, PICU, or hematology-oncology units
- Intervention: There were 3 main drivers: education/awareness, cetirizine availability, and standardization through clinical pathways.
- Comparison: Pre-intervention baseline prescribing practices
- Outcome:
- Primary Outcomes: There are two primary outcomes: The proportion receiving oral FGA and the proportion receiving cetirizine
- Secondary Outcomes: PED revisits within 48 hours, median LOS, clinicians’ knowledge, frequency of clinical pathway use and monthly antihistamine cost.
- Type of Study: Quality improvement initiative
Authors’ Conclusions: “Using the Model for Improvement, we reduced FGA use and increased cetirizine use in the PED and inpatient setting.”
Quality Checklist for Ql Study (adapted from QI-MQCS):
- Do they clearly state the problem and why it mattered? Yes
- Do they explain why the intervention should improve the outcome? Yes
- Are the specific changes described in enough detail that another site could reproduce them? Unsure
- Do they describe the setting the intervention took place (type of hospital/clinic, size, population)? Yes
- Do they describe the approach to designing and introducing the program? Yes
- Is the evaluation approach explicit? Yes
- Do they describe what they are comparing against? Yes
- Are data sources clear and is the primary outcome operationally defined? Yes
- Is the timeline clear? Yes
- Do they measure whether the intervention was actually delivered/used as intended? Yes
- Do they include patient health outcomes? No
- Do they describe organizational barriers/facilitators that affect readiness? Yes
- Do they report who/what was eligible vs who/what actually participated? Yes
- Do they describe the maintenance and sustainability of their interventions over time? Yes
- Do they address whether the intervention could be replicated elsewhere? Yes
- Do they discuss limitations? Yes
- Funding of the Study. No funding for this study. No declared conflicts of interest.
Results: The study included 1235 pediatric ED patients and 737 inpatients. They undertook a total of 5 PDSA cycles, including the ED and inpatient units.
Key Results: FGA use decreased and cetirizine use increased after implementation of QI initiatives.
The use of FGA decreased from 74% to 28% in the pediatric ED and 54% to 36% in the inpatient units.
The use of cetirizine went from 31% to 75% in the pediatric ED and 54% to 74% un the inpatient units.
The changes were sustained for 8.5 months in the pediatric ED and 9 months in the inpatient units.
Secondary Outcomes
- Knowledge assessment improved (among 31 surveyed participants): Median 50% to 100%.
- Clinical pathway usage increased: Median 36 to 44 clinicians/month.
- Balancing measures: ED revisit within 48 hours and median inpatient LOS remained stable.
- Cost: Monthly median antihistamine costs increased (PED $53 to $177; inpatient $57 to $104), with discussion of unit cost drivers for cetirizine formulation.
A crucial part of any QI process is the identification of key stakeholders. This study included representation from the pediatric ED, a pediatric resident (a great inclusion given that residents rotate through so many units in the hospital), allergy and immunology, and pharmacy.
These stakeholders helped the group identify the key drivers that included education and awareness, availability of cetirizine, and standardization of preferred medication. Individuals from each group of stakeholders also acted as champions to help push the QI initiative.
Uncontrolled Before-After Design
QI studies do not necessarily need to include control groups. However, without a concurrent control group/unit, improvements can reflect background practice drift, staffing changes, guideline diffusion, seasonal case-mix shifts, or other QI initiatives rather than the intervention itself. are a classic threat in time-based comparisons.
In addition, when clinicians are aware a practice is being measured (or receive peer-to-peer feedback), behavior can shift independent of the intrinsic effectiveness of the intervention. This is well described as the Hawthorne effect and the related sentinel effect [3].
Intervention Bundle
Because they implemented multiple components (education, stocking, reminders, pathway updates, audit/feedback), the observed effect can’t be confidently attributed to any single change. This is a common challenge with complex interventions, where fidelity and mechanism can vary across units and time.
Education and Awareness
Reliance on purely educational interventions for QI will likely only have a limited effect.
For this study, the authors did a 30-minute lecture during a staff meeting and emailed the lecture materials to absent staff. They also put up flyers in work areas. This intervention in the first PDSA cycle did not result in a consistent reduction in first-generation antihistamine use. Based on feedback from a PDSA flyer, they also shortened the educational sessions for the inpatient implementation phase, recognizing that attention wanes after 15-20 minutes.
Cetirizine Availability
The group worked with the pharmacy in the hospital to ensure the cetirizine solution and tablets were available in the medication dispensing machines. They emailed the pediatric ED staff to let them know. It is important to recognize that some children may either be too young or unable to swallow tablets or pills. This seems like a basic step, but if we want people to start using something new or different, we should try to make it accessible to them.
Standardizing Preferred Antihistamines
Now that the alternative second-generation antihistamine is available, there’s another step this group took to help with adopting the change. They looked at the existing clinical pathways for anaphylaxis and penicillin allergy delabeling and changed the primary antihistamine recommendation from diphenhydramine to cetirizine. This is a nice way of making it easy for people to adopt the change. For those already accustomed to using the clinical pathway and order set, this does not really change workflow at all.
Indications for Antihistamines
The authors chose to include all patients who received antihistamines for any medical indication. When we look at the chief complaints in Supplemental Table 1, we can see that it includes some behavioral health chief complaints like agitation or aggression. We acknowledge that there are other pharmacologic and non-pharmacologic approaches to address these concerns, but the use of a first-generation antihistamine in these conditions is appropriate, given that we often seek a sedative effect. The use of a second-generation antihistamine for these indications would not be appropriate.
The authors do acknowledge this in their discussion, “we focused on the reduction of FGA use as we anticipated that the cessation of FGA use was not possible, as sedative, antiemetic, and anxiolytic effects may be desired…”
Balancing Measures
A balancing measure in QI is a metric that ensures the improvement we’re striving for doesn’t cause unintended harm elsewhere in the system. Basically, “what might get worse if this gets better?” The authors chose the proportion of ED revisits, median length of stay and cost as their balancing measures.
These are reasonable as big picture safety checks, but lack nuance. A child can have an awful experience (too sleepy to function, paradoxically hyper/agitated, trouble sleeping later, dry mouth/urinary retention, etc.) and still never come back within 48 hours. Symptom control could be suboptimal. Itching persists, hives rebound when a short-acting med wears off, or families are confused about dosing without necessarily changing LOS or triggering a revisit. There are other outcomes that can matter more to families and frontline clinicians.
The same issue applies to medication safety. Dosing errors (wrong dose, wrong interval, duplicate antihistamines at home, confusion between formulations) are common real-world failure points, but hard to capture unless you’re actively monitoring them or reviewing charts with that outcome in mind. One of the motivations to move away from first-generation antihistamines is to reduce sedation and other adverse effects. The study didn’t directly measure those patient-level effects. There was no standardized sedation scale, no agitation tracking, no patient-reported itch scores, no parent satisfaction measures, and no documentation audit for adverse drug effects.
The project shows a prescribing shift, and the lack of change in revisit/LOS is reassuring, but it can’t fully answer the question, “Did kids and families feel better, function better, and experience fewer side effects?” Show us the POOs (patient-oriented outcomes) of benefit.
Generalizability
Keep in mind that this is a single-institution study. The key drivers they identified may not apply to your site of practice. One example is that your emergency department may not have predefined pathways for anaphylaxis, or it may not have a culture of using pathways to begin with. In those circumstances, there may be other more appropriate drivers to focus on.
Comment on the Authors’ Conclusion Compared to the SGEM Conclusion: We agree with the author’s conclusion.
SGEM Bottom Line: Second-generation antihistamines are preferred over first-generation anti-histamines for the treatment of allergic conditions. QI efforts can help facilitate this change.
Case Resolution: In the ED, you confirm this is isolated urticaria and not anaphylaxis. Instead of reaching for diphenhydramine, you give an age-appropriate dose of oral cetirizine, reassess after a short period, and the child’s itching settles without her getting sedated or paradoxically agitated. You review some potential triggers or urticaria (often viral, sometimes idiopathic, occasionally exposure-related) and set expectations that hives can wax and wane for a few days. The family is discharged with a scheduled cetirizine plan for the next 24–48 hours.
Clinical Application: For most kids with uncomplicated hives, itching, or allergic rhinitis symptoms who can take oral meds, consider making a second-generation antihistamine like cetirizine your default rather than a first-generation agent like diphenhydramine or hydroxyzine, because you can usually get similar symptom relief with fewer unwanted CNS and anticholinergic effects and a longer duration of action.
From a systems standpoint, this paper is a reminder that sometimes knowing the right drug to give isn’t enough. If we want practice change to be reliable, we should take steps across the system to make implementation easier: make the preferred option easy to use on a busy shift by stocking cetirizine where clinicians pull meds, align pathways and order guidance with the preferred choice, and reinforce the message with brief, repeated education.
Keep the nuance: first-generation antihistamines aren’t “never,” but they probably shouldn’t be the reflex choice for routine allergic symptoms when the main goal is itch control rather than leveraging sedation for a specific indication.
What Do I Tell My Patient/Family?
Your child has hives, which are very common. They can come from a virus or a temporary sensitivity. Sometimes we never find a single trigger. The main treatment is an antihistamine to control the itching and rash. We’re going to use cetirizine, which works well for hives and usually causes less sleepiness and fewer side effects than older medicines like diphenhydramine. It also lasts longer, so you don’t have to keep re-dosing as often. The rash may come and go for a couple of days, but if your child is breathing comfortably and acting well, that’s expected.
Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.
References:
- Jones B, Vaux E, Olsson-Brown A. How to get started in quality improvement. BMJ. 2019 Jan 17;364:k5408. doi: 10.1136/bmj.k5437. PMID: 30655245; PMCID: PMC6335598.
- Taylor MJ, McNicholas C, Nicolay C, Darzi A, Bell D, Reed JE. Systematic review of the application of the plan-do-study-act method to improve quality in healthcare. BMJ Qual Saf. 2014 Apr;23(4):290-8. doi: 10.1136/bmjqs-2013-001862. Epub 2013 Sep 11. PMID: 24025320; PMCID: PMC3963536.
- Boudreaux ED, Bock B, O’Hea E. When an event sparks behavior change: an introduction to the sentinel event method of dynamic model building and its application to emergency medicine. Acad Emerg Med. 2012 Mar;19(3):329-35. doi: 10.1111/j.1553-2712.2012.01291.x. PMID: 22435866; PMCID: PMC3664550.
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