Implementation of Clinical Decision Support on Emergency Department Delivery of Human Rabies Immune Globulin

Key Points

Question

Is implementation of a rabies postexposure prophylaxis bundle, consisting of electronic health record enhancements, staff education, and patient education, associated with improved human rabies immune globulin (HRIG) patient selection and delivery in the emergency department?

Findings

In this quality improvement study that included 324 patients, the primary outcome of full adherence to 6 HRIG quality indicators increased from 37% preimplementation to 61% postimplementation.

Meaning

These results suggest that a rabies postexposure prophylaxis bundle was associated with a statistically significant improvement in HRIG patient selection and delivery in emergency departments across a health system.

This quality improvement study examines improvements in the administration of rabies vaccinations in a US hospital system following the implementation of a patient selection and vaccine administration education program.

Abstract

Importance

Fatal human rabies infections can be prevented through appropriate rabies postexposure prophylaxis (PEP). Errors in patient selection and administration of human rabies immune globulin in the emergency department (ED) setting were identified in a previous study of rabies PEP administration.

Objective

To test the a priori hypothesis that implementation of a rabies PEP bundle in the ED would improve full adherence to 6 human rabies immune globulin quality indicators compared with preimplementation controls.

Design, Setting, and Participants

This quality improvement study was conducted in 15 EDs in a US multihospital health system. Patients who received human rabies immune globulin or rabies vaccine in the ED from January 2015 to June 2018 were included in the preimplementation control group and from December 2019 to November 2020 were included in the postimplementation intervention group. Data were analyzed in January 2021.

Exposure

The PEP bundle was implemented in December 2019 and consisted of electronic health record enhancements, including clinical decision support, ED staff education, and patient education.

Main Outcomes and Measures

Full adherence to 6 human rabies immune globulin quality indicators: patient selection, dose, timing, infiltration into wounds, administration distant from rabies vaccine site, and administration that avoids the buttock.

Results

The study included 324 patients; 254 patients were in preimplementation group (mean [SD] age, 39 [21] years; 135 [53%] women) and 70 in the postimplementation group (mean [SD] age, 38 [19] years; 33 [47%] women). Most patients presented to EDs embedded in a community hospital (231 patients [71%]). Full adherence increased from 37% in the preimplementation group to 61% postimplementation (absolute increase, 24%; 95% CI, 11% to 37%; P < .001). Adherence improved for quality indicators for infiltration into wounds (137 of 254 patients [54%] to 50 of 70 patients [71%]; P = .009), administration distant from rabies vaccine site (180 of 254 [71%] to 58 of 70 [83%]; P = .04), and administration that avoids the buttock (168 of 254 [66%] to 58 of 70 [83%]; P = .007). No instances of sciatic nerve injury or compartment syndrome were observed.

Conclusions and Relevance

In this quality improvement study, implementation of a rabies PEP bundle was associated with improved patient selection and delivery of human rabies immune globulin in EDs across a multihospital health system. Although the bundle included ED staff education and patient discharge education, the observed improvement was likely driven by clinical decision support from the rabies PEP ED order set. Future research should evaluate implementation of this clinical decision support at other health systems.

Introduction

Human rabies infection is almost always fatal if clinical symptoms develop following exposure to a rabid animal. Fortunately, infection can be prevented through appropriate rabies postexposure prophylaxis (PEP) that consists of wound cleansing, administration of human rabies immune globulin (HRIG), and administration of rabies vaccine.^1,2 An estimated 30 000 to 60 000 patients initiate rabies PEP each year in the US.³ A single administration of HRIG provides an immediate supply of virus-neutralizing antibodies while the body is developing active immunity from the rabies vaccine series. Since rabies is a rare disease and HRIG is a high-cost medication, HRIG is rarely stocked in non–emergency department (ED) facilities in the US. Therefore, patients are commonly referred to the ED for evaluation and initiation of rabies PEP, including HRIG; thus, ED staff should be proficient in appropriate HRIG patient selection and delivery.⁴

Human rabies infection can occur if rabies PEP is not given appropriately.^1,5,6,7 Because intramuscular administration of HRIG results in low systemic antibody levels that may not confer protection, infiltration of HRIG into and around wounds, if anatomically feasible, is critical to provide effective passive immunity.^{2,5,7,8,9,10,11} Administration of HRIG and rabies vaccine into the same muscle group may attenuate the effect of the vaccine.^12,13 Administration of HRIG into the buttock can cause sciatic nerve injury.^{14,15,16,17,18,19,20} Therefore, we previously identified 3 opportunities to improve delivery of HRIG in the ED: (1) increase the proportion of patients who receive HRIG infiltration of wounds, (2) avoid administration of HRIG and rabies vaccine into the same muscle group, and (3) avoid HRIG administration into the buttock area.²¹

A pharmacist-led research team developed and implemented a rabies PEP bundle consisting of electronic health record (EHR) enhancements, ED staff education, and patient education in 15 EDs across a health system. The objective of this quality improvement study was to test the hypothesis that implementation of a rabies PEP bundle in the ED would improve full adherence to 6 HRIG quality indicators compared with preimplementation controls.

Methods

Study Design and Setting

This pre-post quality improvement study was conducted in 15 EDs of a multihospital health system, which includes 1 academic medical center, 6 community hospitals, and 8 freestanding emergency care centers staffed by board-certified physicians, in Houston, Texas. During the study period, HRIG 150 IU/mL and 300 IU/mL (Grifols Therapeutics), rabies human diploid cell culture vaccine (Sanofi Pasteur), and rabies chick embryo cell–derived vaccine (GlaxoSmithKline) were used. The study was approved by the Houston Methodist health system’s institutional review board, and a waiver of informed consent was granted for this minimal risk study. The study was registered at ClinicalTrials.gov (identifier NCT04213950) prior to bundle implementation. This study adhered to revised Standards for Quality Improvement Reporting Excellence (SQUIRE 2.0) reporting guidelines.

Selection of Participants

Patients who received rabies PEP (defined as ≥1 dose of HRIG or rabies vaccine) at any ED in the health system were included. Patients treated from January 2015 to June 2018 were included in the preimplementation group and were identified using reports extracted from the EHR. The bundle was implemented in December 2019. Using a protocol that was specified a priori, the first 4 patients treated after bundle implementation were used for quality assurance of the bundle and were not included in the study analysis. Following this quality assurance period, patients treated from December 2019 to November 2020 were included in the postimplementation group and were identified using real-time alerts (VigiLanz) of rabies PEP medication orders. These alerts were validated by medical record review of the EHR and monthly extract reports from the EHR. This real-time identification of postimplementation patients facilitated monthly reports of bundle performance to the study team. The main outcomes were analyzed in January 2021.

Interventions

A quality improvement team of ED clinicians and clinical investigators developed the rabies PEP bundle using historical data on rabies PEP delivery from our health system, guidance from the state department of health, and national guidelines from the US Centers for Disease Control and Prevention (CDC).^1,21,22 The rabies PEP bundle included EHR enhancements, ED staff education, and patient education (eFigure 1 in the Supplement). An additional component of the rabies PEP bundle was changing the health system’s preferred formulary product from HRIG 150 IU/mL to HRIG 300 IU/mL with a goal of increasing the proportion of the HRIG dose that is infiltrated into wounds because a smaller volume is required (eAppendix in the Supplement).

The EHR enhancements included a rabies PEP order set with clinical decision support for clinicians (ie, physicians and advanced practice clinicians) and administration instructions for nurses, structured fields for HRIG administration documentation, and a rabies PEP discharge order set to facilitate discharge planning (Figure 1). Hospital formulary committee approval was obtained to restrict rabies PEP medications to the new rabies PEP order set, which required clinicians to interact with the new clinical decision support during order entry. To assist with patient selection, the order set presented guidance on animals that carry rabies based on Texas State Department of Health guidance and the telephone number for Zoonosis Control Unit consultation for patient-specific decisions.²² The order set provided preconfigured orders for wound management, rabies vaccine, HRIG, and tetanus vaccine. Although the EHR medication administration record only provides 1 documentation site per medication order, HRIG is commonly administered at multiple sites. Therefore, the EHR enhancement provided nurses with additional structured fields to document multiple HRIG administration sites and administration volumes, as necessary. The quality improvement team identified retail pharmacies and outpatient clinics that stock and can administer rabies vaccine. A discharge order set was built to dynamically display nearby referral locations to facilitate discharge planning, provide preconfigured discharge prescriptions for rabies vaccine, and print patient educational materials. The educational campaign to ED staff consisted of live education sessions that reached 36% of ED staff, emails, and tip sheets (eMethods in the Supplement).

Figure 1. Rabies Postexposure Prophylaxis (PEP) Electronic Health Record Enhancements.

ED indicates emergency department; HRIG, human rabies immune globulin; IM, intramuscular.

Measurements

Two investigators (F.Y. and T.I.) independently abstracted study data and outcomes from the EHR using standardized procedures and data collection forms built in Microsoft Access 2013. Discrepancies between investigators were arbitrated through study team discussion. Documentation of compartment syndrome within 7 days and sciatic nerve injury within 21 days of HRIG administration was collected for both preimplementation and postimplementation groups. After implementation, investigators adjudicated all adverse events documented within 21 days of HRIG administration.

Outcomes

The primary outcome was full adherence to all 6 quality indicators for HRIG patient selection and delivery that were based on CDC guideline recommendations and prescribing information.^1,17 The 6 quality indicators were (1) patient selection based on history of rabies prophylaxis, (2) dosing within 10% of 20 IU/kg, (3) timing within 7 days of the first dose of rabies vaccine, (4) infiltration into wounds if anatomically feasible, (5) administration distant from rabies vaccine site, and (6) administration that avoids the buttock unless wounds are in the buttock. Each quality indicator was assigned a score of 1 for adherence or 0 for nonadherence. The primary outcome was a total score of 6. The primary outcome was assessed once per patient during the index ED visit, defined as the first ED visit where a patient met inclusion criteria.

Secondary outcomes were adherence to each quality indicator individually, incidence of compartment syndrome within 7 days of HRIG administration, and incidence of sciatic nerve injury within 21 days of HRIG administration. Other adverse events in the postimplementation group that were possibly or definitely related to HRIG were reported.

Exploratory Subgroup Analyses

We conducted 3 a priori and 3 post hoc subgroup analyses. For a priori subgroup analysis 1, the proportion of patients with clear documentation of HRIG administration sites was evaluated among those who received HRIG. For subgroup analysis 2, the proportion with HRIG infiltration was evaluated among patients with clear documentation of HRIG administration sites and wounds for which infiltration was anatomically feasible. For subgroup analysis 3, percentage of HRIG infiltrated into wounds and the proportion receiving the full dose of HRIG as wound infiltration were evaluated among patients with clear documentation of HRIG infiltration volume.

For post hoc analysis 1, full adherence was analyzed among patients with active wounds (readily visible and unhealed) and treated using the new EHR implemented in 2016. For post hoc analysis 2, full adherence was stratified by ED location (academic medical center vs 14 other locations) because all study team members practiced at the academic medical center. For post hoc analysis 3, full adherence in the postimplementation group was stratified by appropriate use of the rabies PEP order set. Appropriate use was defined as ordering rabies PEP (vaccine or HRIG) through the order set and choosing the clinical pathway that matched that patient’s wound status and history of rabies prophylaxis.

Statistical Analysis

A sample size of 254 preimplementation patients and 70 postimplementation patients was determined a priori to have 80% power to detect an absolute increase of 20% in the primary outcome from 37% to 57% using a 2-sided α = .05. Pearson χ² test was used to evaluate the primary analysis, adherence to individual quality indicators, subgroup analyses 1 through 3, and post hoc analysis 1. Multivariable logistic regression was used for a sensitivity analysis and for subgroup analysis 2. Multivariable linear regression was used for subgroup analysis 3. Fisher exact test was used for post hoc analysis 3. Patient demographics and characteristics were analyzed using an unpaired t test for continuous variables and a Pearson χ² test or Fisher exact test for categorical variables. All analyses were conducted using Stata version 16.0 (StataCorp).

Results

Characteristics of Study Subjects

The study included 324 patients; 254 patients were in preimplementation group (mean [SD] age, 39 [21] years; 135 [53%] women) and 70 in the postimplementation group (mean [SD] age, 38 [19] years; 33 [47%] women) (Figure 2 and Table). Most patients were bitten by animals (245 of 324 [76%]) and presented to community hospital EDs (231 of 324 [71%]). Five patients (1%) had a history of rabies prophylaxis, and 8 patients (2%) were immunocompromised. Patient characteristics were similar between study groups except for an increase in bat exposure (63 of 254 preimplementation patients [25%] to 37 of 70 postimplementation patients [53%]; P < .001) and decrease in presence of wounds (213 of 254 preimplementation patients [84%] to 44 of 70 postimplementation patients [63%]; P < .001). Exposure to high-risk animals increased from 32% preimplementation to 63% postimplementation (risk difference, 31%; 95% CI, 18%-44%; P < .001), which were predominately bats and also included coyotes, foxes, raccoons, and skunks. Of 224 preimplementation patients who received HRIG, 222 (99%) received HRIG 150 IU/mL and 2 (1%) received HRIG 300 IU/mL. Of 60 postimplementation patients who received HRIG, 59 (98%) received HRIG 300 IU/mL and 1 (2%) received both HRIG 300 IU/mL and 150 IU/mL.

Figure 2. Patient Inclusion Flowchart.

HRIG indicates human rabies immune globulin; PEP, postexposure prophylaxis.

^aPatients who received HRIG or rabies vaccine.

^bPatients did not receive HRIG in our health system.

Table. Patient Demographics and Characteristics.

Demographics and characteristics	Patients, No. (%)		P value
	Preimplementation group (n = 254)	Postimplementation group (n = 70)
Age, mean (SD), y	39 (21)	38 (19)	.62
Sex
Women	135 (53)	33 (47)	.37
Men	119 (47)	37 (53)
Dosing weight, mean (SD), kga	73 (26)	71 (28)	.51
Immunocompromised statusb	7 (3)	1 (1)	>.99
History of rabies prophylaxisc	2 (1)	3 (4)	.07
ED setting
Community hospital	183 (72)	48 (69)	.30
Academic medical center	54 (21)	20 (29)	.30
Freestanding ED	17 (7)	2 (3)	.30
Hospital admission	16 (6)	2 (3)	.38
Animal type
Bat	63 (25)	37 (53)	<.001
Dogd	121 (48)	17 (24)
Cate	36 (14)	8 (11)
Raccoons	16 (6)	7 (10)
Otherf	18 (7)	1 (1)
Animal exposure type
Bite	193 (76)	40 (57)	.005
Close encounter	25 (10)	19 (27)
Direct contact	16 (6)	7 (10)
Bite and scratch	10 (4)	2 (3)
Scratch	6 (2)	2 (3)
Lick	4 (2)	0
Wound location
Head/face/neck	14 (6)	2 (3)	.02
Torso/buttock	4 (2)	1 (1)
Arm/hand	109 (43)	20 (29)
Leg/foot	63 (25)	15 (21)
Multiple locations	20 (8)	5 (7)
Wound location was not documented	3 (1)	1 (1)
No wound	41 (16)	26 (37)
Days from animal exposure to rabies PEPg
Same day	140 (55)	31 (44)	.15
1 d After exposure	46 (18)	21 (30)
2 d After exposure	15 (6)	5 (7)
3 d After exposure	19 (7)	3 (4)
≥4 d After exposure	27 (11)	10 (14)
Date of exposure was not documented	7 (3)	0

Abbreviations: ED, emergency department; PEP, postexposure prophylaxis.

^a Weight was missing for 4 preimplementation patients.

^b Patients on immunosuppressive agents or had active immunosuppressive disorders.

^c Patients had history of rabies vaccines and/or human rabies immune globulin (HRIG) administration prior to the animal exposure for the index ED visit.

^d The domestication status of the dogs was stray (58 patients preimplementation and 9 postimplementation), domestic (35 preimplementation and 7 postimplementation), or unknown (28 preimplementation and 1 postimplementation).

^e The domestication status of the cats was stray (29 patients preimplementation and 8 postimplementation), domestic (3 preimplementation), or unknown (4 preimplementation).

^f Other animal types include rodent (3 patients), squirrel (3 patients), monkey (3 patients), direct contact with a domestic dog that was exposed to a suspected/confirmed rabid bat (3 patients), calf (2 patients), otter (1 patient), health care worker exposure to blood of a patient who was initiating rabies PEP (1 patient), coyote (1 patient), and skunk (1 patient) in the preimplementation group and rodent (1 patient) in the postimplementation group.

^g Rabies PEP was defined as rabies HRIG or vaccine.

Adherence to 6 Quality Indicators

Full adherence increased from 37% (95 of 254 patients) in the preimplementation group to 61% (43 of 70 patients) in the postimplementation group, for an absolute increase of 24% (95% CI, 11%-37%; P < .001) and an odds ratio (OR) of 2.67 (95% CI, 1.55-4.59; P < .001) (Figure 3). This association remained statistically significant (adjusted OR [aOR], 2.32; 95% CI, 1.32-4.07; P = .003) in a sensitivity analysis that adjusted for animal type (bat vs other) and animal exposure (bite vs other).

Figure 3. Full Adherence to Human Rabies Immune Globulin (HRIG) Quality Indicators Following Implementation of Rabies Postexposure Prophylaxis (PEP) Bundle.

Circles represent the proportion of patients with full adherence for each year, and whiskers represent 95% CIs. The horizontal dotted line at 37% represents the proportion with full adherence during the entire preimplementation period. Data in 2018 only includes January 2018 through June 2018. One postimplementation patient was treated in December 2019 following bundle implementation and is displayed under 2020. EHR indicates electronic health record.

For secondary outcomes, the rabies PEP bundle was associated with an absolute increased adherence of 17% (95% CI, 5% to 30%) for infiltration into wounds, 12% (95% CI, 2%-22%) for administration distant from rabies vaccine site, and 17% (95% CI, 6%-27%) for administration that avoids the buttock, which were identified as focus areas during development of the rabies PEP bundle (Figure 4; eTable 1 in the Supplement). A high baseline adherence of 91% to patient selection, 89% to dosing, and 91% to timing was observed preimplementation, and implementation of the rabies PEP bundle was not associated with a change in adherence to these quality indicators.

Figure 4. Adherence to Individual Human Rabies Immune Globulin (HRIG) Quality Indicators Following Implementation of Postexposure Prophylaxis (PEP) Bundle.

Absolute differences in adherence were significant for infiltration into wounds (17%; 95% CI, 5%-30%; P = .009), administration distant from wound site (12%; 95% CI, 2%-22%; P = .04), and administration avoids the buttock (17%; 95% CI, 6%-27%; P = .007).

A total of 29 patients (23 preimplementation and 6 postimplementation) were not adherent to the patient selection indicator and were therefore not adherent to the 5 other quality indicators (eTable 2 in the Supplement). The HRIG dose was inappropriate for 8 patients (4 preimplementation and 4 postimplementation). Insufficient HRIG inventory in the ED led to 2 of 4 (50%) dosing errors postimplementation. Among 21 patients (18 preimplementation and 3 postimplementation) who received both HRIG and rabies vaccines in the same muscle groups, the medications were injected in the deltoid muscle (10 preimplementation and 3 postimplementation), gluteus muscle (6 preimplementation), and thigh muscle (2 postimplementation).

No instances of sciatic nerve injury or compartment syndrome were observed. Fourteen adverse events from 3 postimplementation patients were possibly related to HRIG 300 IU/mL (eTable 3 in the Supplement).

A Priori Subgroup Analyses

In subgroup analysis 1, the proportion with clear administration site documentation did not change from 198 of 224 patients (88%) in the preimplementation group to 57 of 60 (95%) in the postimplementation group (absolute difference, 7%; 95% CI, 0% to 14%; P = .16). In subgroup analysis 2, HRIG infiltration of anatomically feasible wounds did not change from 97 of 172 patients (56%) preimplementation to 22 of 35 (63%) postimplementation (absolute difference, 6%; 95% CI, –11% to 24%; P = .48), even after adjusting for wound location (leg and foot vs other) and animal type (aOR, 1.26; 95% CI, 0.58 to 2.73; P = .56). In subgroup analysis 3, infiltration of the entire HRIG dose increased from 34 of 142 patients (24%) preimplementation to 13 of 30 (43%) postimplementation (absolute difference, 19%; 95% CI, 0% to 38%; P = .03). The mean (SD) infiltration volume did not change from 2.9 (4.1) mL preimplementation to 2.2 (2.5) mL postimplementation (absolute difference, –0.7; 95% CI, –2.2 to 0.8; P = .39). The mean (SD) percentage of HRIG infiltrated into wounds was unchanged from 31% (42%) preimplementation and 47% (48%) postimplementation (unadjusted coefficient, 15%; 95% CI, –2% to 32%; P = .08), even after adjusting for wound location and animal type (adjusted coefficient, 15%; 95% CI, –1% to 32%; P = .06).

Post Hoc Analyses

For post hoc analysis 1 (eFigure 2 in the Supplement), full adherence increased from 42 of 111 patients (38%) preimplementation to 22 of 39 (56%) postimplementation (absolute increase, 19%; 95% CI, 1% to 37%; P = .04). For post hoc analysis 2, the relative risk for full adherence was 2.0 (95% CI, 1.3 to 3.2) at the academic medical center and 1.5 (95% CI, 1.1 to 2.0) at other EDs with a nonsignificant Mantel-Haenszel test for homogeneity (P = .34). For post hoc analysis 3, full adherence was attained for 39 of 60 patients (65%) with appropriate use of order set and 4 of 10 (40%) otherwise (absolute increase, 25%; 95% CI, –8% to 58%; P = .17). The ED clinician specified a target infiltration volume for 21 of 29 HRIG orders (72%) generated using the wound present clinical pathway. Nurses correspondingly administered the prescribed volume (9 patients), a smaller volume (4 patients), a larger volume (4 patients), or an undocumented volume (4 patients).

Discussion

The rabies PEP bundle was associated with significant improvements in adherence to HRIG quality indicators that were based on CDC guidelines and prescribing information.^1,17 The bundle was associated with improvements in all 3 quality indicators related to HRIG administration that we previously identified as opportunities for improvement: infiltration into wounds, administration distant from rabies vaccine site, and administration that avoids the buttock. The rabies PEP order set likely had the largest contribution for improving adherence to HRIG quality indicators since education only reached 36% of ED staff and the educational flyers were given to patients at ED discharge. The rabies PEP order set presented bundles of orders for 5 clinical pathways, prompted clinicians to specify a target HRIG infiltration volume for patients with wounds, and provided nurses with critical medication administration instructions. These clinical decision support features were designed to help address previously identified knowledge gaps related to suboptimal HRIG wound infiltration, administration of HRIG near rabies vaccine, and unnecessary administration of HRIG into the buttock.^{4,21,23,24,25} The low adherence to quality indicators observed preimplementation is not unique to our center, as a 2021 study from Germany²⁶ reported deviations from guideline recommendations regarding HRIG selection and wound infiltration in 51% of patients.

Infiltration of wounds with HRIG is critical to prevent the spread of the rabies virus from wounds to the central nervous system.^5,6,7,8,9,27 The proportion of patients who received infiltration of the full dose of HRIG significantly increased from 24% to 43% in subgroup analysis 3. This has meaningful implications, as recent international guidelines recommend HRIG infiltration only without supplemental intramuscular injection.² Although the mean infiltration volume provided did not increase after implementation, the proportion of patients who received infiltration of the full dose of HRIG increased, and this increase is likely because of the use of concentrated HRIG 300 IU/mL postimplementation compared with HRIG 150 IU/mL preimplementation.

Since limited guidance exists on HRIG infiltration volume targets based on wound size and location, our rabies PEP bundle provided guidance on HRIG infiltration volume targets by wound location based on internal data and published literature.^8,9,27,28 Researchers in India are developing recommendations for HRIG infiltration volume based on wound site, size, and severity.^29,30 Further research is needed to provide a consensus on HRIG infiltration volume targets based on wound location, size, and depth and to optimize clinician-nurse collaboration regarding patient-specific HRIG infiltration volume targets.

In the US, more than 90% of animal rabies cases occur in wildlife.³¹ Although rabies PEP is commonly started following exposure to a dog or cat, rabies PEP is unnecessary following low-risk exposure to dogs or cats that are vaccinated or available for observation.^24,32,33 The Texas Department of State Health Services designates bats, coyotes, foxes, raccoons, and skunks as having a high risk of carrying rabies.³⁴ The rabies PEP ED order set emphasized risk assessment based on animal type, encouraged clinicians to consult the Texas Department of State Health Services for complex cases, and encouraged working with animal control agencies to capture and observe animals before starting rabies PEP. The order set generated a nursing order to contact animal control and provided phone numbers for local animal control agencies. Exposures to high-risk animals increased from preimplementation to postimplementation, which suggests improvements in risk assessment and patient selection for rabies PEP and may warrant further investigation.

Despite EHR enhancements with preconfigured HRIG dosing and vial size rounding logic, we observed errors of low doses (14.0 to 17.9 IU/kg) in 4 postimplementation patients. Clinicians and pharmacists modified the orders that were generated by the order set. Two dosing errors occurred when the currently available inventory of 4500 IU of HRIG in a single ED was insufficient to provide 2 concurrently treated patients with obesity with 20 IU/kg doses. Maintaining a minimum inventory of 5100 IU of HRIG would be sufficient to prevent these types of dosing errors. Dosing HRIG for patients with obesity is a known challenge that can lead to high injection volumes, dosing errors, and exhaustion of HRIG inventory on-hand.²⁵ Although the CDC and manufacturer’s labeling recommend actual body weight, some institutions may use lean body weight for patients with obesity to limit HRIG doses for this patient group.²⁵

Limitations

This study had several limitations. The bundle was simultaneously implemented at all EDs, and therefore a contemporary control group was not available. An 18-month transition period (June 2018 to December 2019) occurred between the preimplementation group and implementation to provide time to analyze preimplementation data, secure research funding, and develop EHR enhancements. The COVID-19 pandemic changed patterns of seeking ED care and ED workflow at many EDs,^35,36,37 and this may have affected 8 of 12 months during the postimplementation period. Although the study did not conduct follow-up monitoring, no human rabies infection cases were reported in Texas during the historical control period or postimplementation period.³⁸ Some study data were collected from unstructured EHR fields; to address this limitation, 2 independent reviewers abstracted data using standardized processes. However, the study did not analyze interrater reliability between reviewers. The EHR documentation that investigators used to determine if a wound could be feasibly infiltrated with HRIG was not standardized between the old EHR and the new EHR implemented in 2016. Small (eg, bat bites) or healing wounds were classified as anatomically feasible for HRIG infiltration; however, there is a lack of consensus among clinicians on infiltrating these small or healing wounds. Therefore, post hoc analysis 1 was conducted among patients with active wounds who were treated using the new EHR, and the bundle remained associated with improved adherence. Future research is needed to evaluate the impact of ED discharge order sets on postdischarge care and completion of the rabies vaccine series

Conclusions

In this quality improvement study, implementation of a rabies PEP bundle was associated with significantly improved HRIG patient selection and delivery in the ED. Although the bundle included ED staff education and patient discharge education, the observed improvement was likely driven by clinical decision support from the rabies PEP ED order set. Future research should evaluate implementation of this clinical decision support at other health systems.

Supplement.

eTable 1. Adherence to HRIG Quality Indicators

eTable 2. Quality Indicator Subcategories

eTable 3. Adverse Events That Were Possibly Related to HRIG 300 IU/mL Administration Among 70 Postimplementation Patients

eFigure 1. Rabies PEP Bundle

eFigure 2. Patient Inclusion Flowchart for Post-hoc Analysis 1

eMethods.

eAppendix. Investigator Initiated Clinical Study Protocol