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outcomes research

Taking a Bite Out of Rabies

Enhancing Rabies Postexposure Prophylaxis Treatment in Emergency Departments Improves Patient Outcomes

Infection with rabies virus in humans is almost universally fatal. Transmitted through the bites of infected animals, rabies prevention through postexposure prophylaxis (PEP) is critical to saving patient lives. Unfortunately, rabies PEP is quite expensive and requires multiple follow-up visits to the doctor. For these reasons, compliance isn’t 100%. In addition, because rabies is rare, in the US PEP is usually only available in emergency departments (ED) and in limited quantity. And not everyone is trained properly in its administration. That, combined with less than full compliance, results in reduced efficacy for rabies PEP. Rabies PEP consists of wound cleansing, and administration of human rabies immune globulin (HRIG) and the rabies vaccine. HRIG provides immediate virus-neutralizing antibodies while the body’s immune system develops immunity from the rabies vaccine series. It’s critical that ED staff are proficient in appropriate HRIG patient selection for, and delivery of, rabies PEP. If rabies PEP is not given correctly, human rabies infection can occur. Intramuscular administration of HRIG results in low systemic antibody levels that may not be protective, so it’s important it be administered directly in and around wounds, if possible. However, administration of HRIG and rabies vaccine into the same muscle group can reduce efficacy of the vaccine. In addition, administration of HRIG into the buttock can cause sciatic nerve injury. This means those providing PEP to patients must effectively balance the limitations, risks and requirements of PEP administration. A pharmacist-led research team at Houston Methodist including Clinical pharmacy fellow Farrah Yuan PharmD, identified opportunities to improve delivery of HRIG in the ED then developed and implemented a rabies PEP enhancement bundle to test whether it could drive improved adherence to six quality indicators for HRIG patient selection and delivery that are based on CDC guideline recommendations and prescribing information: (1) patient selection based on history of rabies prophylaxis, (2) dosing within 10% of 20 IU/kg, (3) timing within seven 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. Their results were published in June with Yuan as first author.
Farrah Yuan, PharmD Clinical Pharmacy Fellow Houston Methodist
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.”
The rabies PEP enhancement bundle included electronic health record (EHR) enhancements, and education for ED staff and patients in 15 EDs across a healthcare system. More specifically, it included a rabies PEP order set with clinical decision support for clinicians and administration instructions for nurses, structured fields for HRIG administration documentation, and a rabies PEP discharge order set to facilitate discharge planning. To facilitate appropriate patient selection, the order set provided guidance on animals that transmit rabies. Retail pharmacies and outpatient clinics that stock and can administer rabies vaccine were identified and 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. The study included 324 patients; 254 patients were in preimplementation group and 70 in the postimplementation group. Most patients were bitten by animals and presented to community hospital EDs. Five patients had a history of rabies prophylaxis, and eight patients were immunocompromised. Patient characteristics were similar between study groups except for an increase in bat exposure (63 of 254 preimplementation patients to 37 of 70 postimplementation patients; P < .001) and decrease in presence of wounds (213 of 254 preimplementation patients to 44 of 70 postimplementation patients; P < .001). Exposure to high-risk animals increased from 32% preimplementation to 63% postimplementation, which were predominately bats but 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. No instances of sciatic nerve injury or compartment syndrome were observed. The rabies PEP bundle was associated with significant improvements in adherence to HRIG quality indicators based on CDC guidelines and prescribing information. The bundle was associated with improvements in all three quality indicators related to HRIG administration previously identified as opportunities for improvement: infiltration into wounds, administration distant from rabies vaccine site, and administration that avoids the buttock. Because education only reached 36% of ED staff and the educational flyers were given to patients at ED discharge, the rabies PEP order set likely contributed the most to improving adherence to HRIG quality indicators. The rabies PEP order set presented bundles of orders for five clinical pathways, prompted clinicians to specify a target HRIG infiltration volume for patients with wounds, and provided nurses with critical medication administration instructions. Yuan explained, “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.” As noted by the authors, the study did have some limitations. For example, the bundle was simultaneously implemented at all EDs, so there was no contemporary control group. In addition, the COVID-19 pandemic changed patterns of seeking ED care and ED workflow at many EDs, and this may have affected eight of 12 months during the postimplementation period. This study did not follow-up on patients after the rabies PEP, but no human rabies infection cases were reported in Texas during the historical control period or postimplementation period. In this published study, implementation of a rabies PEP bundle in EDs was associated with significantly improved HRIG patient selection and delivery. While ED staff education and patient discharge education, were included in the bundle, the observed improvement was likely driven by clinical decision support from the rabies PEP ED order set. Future research is needed to evaluate implementation of this clinical decision support in other health-care systems.
Fangzheng Yuan, PharmD; Tomona Iso, PharmD; Elsie Rizk, PharmD; R. Benjamin Saldana, DO; Anh Thu Tran, PharmD; Ngoc-anh A. Nguyen, MD; Prasanth R. Boyareddigari, MD; Daniela Espino, PharmD; Joshua T. Swan, PharmD, MPH
Heather Lander, PhD
September 2022
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