Clinical and echocardiographic characteristics of patients who developed adverse events following Benzathine penicillin G injection for secondary prophylaxis of rheumatic heart disease: a cross-sectional study from three university hospitals in Ethiopia

Abraha Hailu Weldegerima, Dejuma Yadeta, Marta Yemane, Gabriele Wehr, Christian Leuner, Samuel Berhane, Abadi Leul, Tadesse Dukessa, Abraham Haileamlak

Abstract

Background: Intramuscular (IM) Benzathine penicillin G administration (BPG) is essential to prevent the progression of acute rheumatic fever (RF) to rheumatic heart disease (RHD). Fatal adverse events during BPG administration have been reported. This study aimed to characterise the clinical features and outcomes of RHD patients who developed adverse events with BPG administration for RHD prophylaxis in Ethiopia.
Methods: Charts of Patients who received BPG for secondary prophylaxis of RHD and had fatal adverse events were reviewed. An online survey was also used to collect data on adverse events during BPG injection. The study was done in Ethiopia at Ayder, Tikur Anbessa, and Jimma University Hospital from January 1, 2017, to May 30, 2023. Data were collected using a structured questionnaire. Demographic, clinical, and echocardiographic features were documented and analysed.
Results: All five chart review cases were female. Four of them had fatal adverse events. Four of them were aged > 18 years. All had clinical evidence of heart failure (HF) and echocardiographically advanced RHD, including severe tricuspid regurgitation (TR) and moderate to severe pulmonary hypertension (PHTN). Case 1 was 24 years old with severe mitral stenosis (MS). Case 2 was 19 years old with severe mitral regurgitation (MR). Case 3 was 14 years old with moderate to severe aortic regurgitation (AR) and moderate to severe MR. Case 4 was 43 years old with severe MS and moderate MR. Case 5 was 16 years old with moderate-severe MS, severe MR and atrial fibrillation. Four had received BPG before the event with no previous adverse reaction. None of our cases met the Level 1 Brighton criteria consistent with anaphylaxis. There were four deaths, three skin rashes, and one anaphylactic shock reported from the six RHD cases from the online survey.
Conclusion: We hypothesise that the coexistence of severe valve lesions with concomitant advanced HF may be an essential risk factor in BPG injection-related deaths rather than the presence of severe valve lesions alone. Heart failure and a failure of the compensatory mechanisms in BPG injection-related adverse circulatory reactions in advanced RHD with HF could be one of the major causes of these deaths. According to the literature, we recommend that patients with advanced RHD receive special attention regarding secondary BPG prophylaxis. For the introduction of less painful BPGinjection, like the subcutaneous technique, further research is needed.