The Adjuvant Efficacy of Angong Niuhuang Pill in the Treatment of Viral Encephalitis: A Meta-Analysis of Randomized Controlled Trials

Published: April 19, 2024

doi:

Chuyao Huang, Rui Wang, Jinhan Lv, Ningxiang Zheng, Zhenwen Wei, Xiaolang Wu, Qi Wang, Wei Zhao²

¹Science and Technology Innovation Center,Guangzhou University of Chinese Medicine, ²Maoming Hospital of Guangzhou University of Chinese Medicine

Summary

Here, we present a protocol to analyze the effectiveness and safety of Angong Niuhuang Pill in the treatment of viral encephalitis.

Abstract

This meta-analysis aims to evaluate the efficacy of Angong Niuhuang Pill (ANP) as an adjuvant therapy in the treatment of viral encephalitis. Seven databases (PubMed, Cochrane Library, Embase, SinoMed, CNKI, VIP and WanFang) were included for literature retrieval from inception to July 2023. Randomized controlled trials comparing ANP plus conventional therapy with conventional therapy alone were eligible. Pooled effect sizes and 95% confidence intervals (CIs) were calculated for evaluating efficacy and safety. Sensitivity analysis and publication bias assessments were performed for analyzing the inconclusiveness of findings. 13 studies involving 1045 cases were included for meta-analysis. Adjuvant treatment with ANP increased the probability of the total effective rate by 17% compared with conventional treatment (Risk ratios (RR) = 1.17, 95%CI [1.08, 1.27]). The disappearance time of clinical syndromes and signs was significantly decreased after adjuvant treatment with ANP, including the time of defervescence (weighted mean difference (WMD) = -1.59, 95%CI [-2.09, -1.09]), the time of consciousness recovery (WMD = -1.79, 95%CI [-2.06, -1.51]), the time of headache disappearance (WMD = -1.51, 95%CI [-1.93, -1.08]), the time of tic disappearance (WMD = -1.88, 95%CI [-2.39, -1.36]). The adjuvant efficacy of ANP for treating viral encephalitis (VE) appears to improve the total effective rate and shorten the disappearance time of clinical syndromes. More high-quality randomized controlled trials (RCTs) are needed to support our findings.

Introduction

Encephalitis is defined as the inflammation of the brain parenchyma with high mortality, characterized by neurological pathological signs, fever, abnormal mental status, and altered electroencephalographic (EEG) and neuroimaging¹^,². The incidence of encephalitis ranges between 7 and 15 cases per 100,000 people³^,⁴^,⁵. The cause of approximately half of encephalitis cases is unknown, and viral encephalitis (VE) accounts for about 20% to 50% of diagnosed cases⁵^,⁶. Common viruses include human enterovirus, human herpesvirus, herpes simplex virus, human immunodeficiency virus, and cytomegalovirus⁷. Patients with VE require intensive monitoring and supportive measures to maintain vital signs and alleviate cerebral inflammation⁸. Acyclovir is an empiric treatment for all cases of VE⁹. Evidence for the use of glucocorticoids, immunoglobulins, and interferon alfa are inconsistent⁸. Angong Niuhuang Pill (ANP), one of the well-known orifice-opening medicines, is widely used in mental and conscious abnormalities due to critical illness. China Medical Education Association recommended ANP as an A-level strength of recommendation and II-level quality of evidence (evidence from non-randomized studies or randomized controlled trials)¹⁰.

A systematic review (SR) is a comprehensive collection and rigorous evaluation of all clinical studies that meet the inclusion criteria. Meta-analysis is a methodology for quantitative analysis in SR. Distinguishing from the methods of basic meta-analysis, a trim and fill procedure was adopted to test the robustness of the effect size estimate to the assessment of publication bias¹¹. A small number of studies were removed until a new effect size made the plot symmetrical. Additional studies were added back to the plot based on imputed mirror-image studies. If the difference of the recalculated pooled estimate (PE) before and after the trim and fill procedure was less than 0.05, the effect size estimate of publication bias was robust. TSA 0.9.5.10 software was used to reduce the risk of false-positive results and calculate the required information size (RIS), which was beneficial to make our findings more robust. Given that no systematic review of the data on the improvement of symptoms, signs, biochemical indicators, and adverse reactions of ANP in the treatment of VE, we therefore performed this meta-analysis of the available randomized controlled trials.

Protocol

1. Protocol registration Register the systemic review. NOTE: PROSPERO (Table of Materials) was built by National Institute for Health Research for the registration of systematic review. This systemic review protocol has been registered under the number CRD42022301182. 2. Software installation EndNote software installation Purchase EndNote software and download the exe file as an insta…

Representative Results

Search results and study characteristics Systematic retrieval yielded 122 studies and manual searching added 9 relevant literatures. After removing 49 duplicates, 82 studies remained to be screened by abstract and full-text. Ultimately, 13 studies12,13,14,15,16,17,<sup class="x…

Discussion

This meta-analysis provides evidence that the adjunctive ANP can improve the total effective rate by 17% in patients with VE. Adjuvant therapy with ANP can significantly shorten the disappearance time of positive pathological signs and symptoms. Xingnaojing (XNJ) injection extracted from ANP is widely used for abnormal consciousness associated with encephalopathy. A recent meta-analysis verified the adjunctive effect of XNJ for treating VE, contributing to an increase in the number of cure cases and shortening the time o…

Disclosures

The authors have nothing to disclose.

Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 81973919), the National Natural Science Foundation of Guangdong Province (No. 2019A1515011299), and the Innovation and Strong School project of the Department of Education of Guangdong Province (No. 2016KTSCX015).

Materials

PROSPERO	National Institute for Health and Care Research	https://www.crd.york.ac.uk/PROSPERO/
STATA	StataCorp	https://www.stata.com/
TSA	Copenhagen Trial Unit, Centre for Clinical Intervention Research	https://ctu.dk/tsa/downloads/
PubMed	National Library of Medicine	https://pubmed.ncbi.nlm.nih.gov/
Cochrane Library	Cochrane Library	https://www.cochranelibrary.com/
Embase	Elsevier	https://www.embase.com/search/quick
SinoMed	SinoMed	http://www.sinomed.ac.cn/index.jsp
CNKI	China National Knowledge Infrastructure	https://www.cnki.net/
VIP	Chongqing VIP Information Co., Ltd.	http://www.cqvip.com/
WanFang database	Wanfang Data Knowledge Service Platform	https://www.wanfangdata.com.cn/index.html

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