Safety and Efficacy of Ventricular Irrigation for Ventriculitis

Ventriculitis is a severe infectious disease of the central nervous system with diverse etiologies. Ventriculitis is associated not only with community-acquired diseases but also, more importantly, with invasive clinical procedures, including craniotomy, external ventricular drainage (EVD), lumbar cistern drainage, V-P shunt, and deep brain stimulation, among others. Depending on the diagnostic criteria, the incidence of post-neurosurgery ventriculitis ranges from approximately 5% to 20%, with risk factors including age, prolonged placement of EVD, and intracranial hemorrhage. Besides, the pathogens leading to ventricular infection are also diverse, with the main pathogens including coagulase-negative Staphylococci, Staphylococcus aureus, Propionibacterium acnes, and Gram-negative bacilli.

The treatment for ventriculitis is challenging, with poor prognosis. Under currently widely adopted treatment strategies, the mortality rate of ventriculitis is generally reported to be higher than 30%, with the highest reaching over 75%. Even among survivors, over 60% suffer from a variety of neurological sequelae, including cognitive impairment, gait disturbances, paralysis, behavioral disorders, and epilepsy. This imposes significant burden on families and society. Therefore, how to further improve prognosis of ventriculitis, and reduce the mortality and disability rates, remains to be addressed.

Currently, treatments for ventriculitis recommended by guidelines primarily focus on the selection and administration of antibiotics, while the effects of surgical interventions have not been fully elucidated. As an infectious disease, surgical procedures such as irrigation and drainage have the potential to play a role in reducing infection and improving prognosis for ventriculitis.

In recent years, several studies have explored the use of ventricular irrigation in ventriculitis, indicating that ventricular irrigation techniques (including endoscopic ventricular irrigation and dual catheter irrigation techniques) via replacing saline and draining purulent cerebrospinal fluid (CSF), may accelerate the control of ventricular infection, mitigate damage to the central nervous system caused by infections, improve the prognosis of ventriculitis, and reduce complications such as hydrocephalus. However, current studies are still relatively scarce, and mostly case reports and retrospective studies. A prospective controlled study that included 33 patients with ventriculitis divided participants into groups receiving ventricular irrigation treatment and conventional treatment. The study results showed that compared to conventional treatment, ventricular irrigation resulted in higher mRS prognosis scores, shorter hospital stays, and the study also showed a trend towards reduced mortality in irrigation group. However, this study was limited by a small sample size, limited study endpoints and not strictly randomized. Currently, high-quality evidence is still lacking for the application of ventricular irrigation in ventriculitis.

Based on these considerations, this multicenter randomized controlled trial aims to explore the safety and effectiveness of ventricular irrigation compared to conventional treatment for ventriculitis, analyze the effectiveness of ventricular irrigation across different pathogen subgroups, and investigate independent risk factors for different prognostic states in patients with ventriculitis.

• Ventricular irrigation (Procedure): Catheter ventricular irrigation can be employed by various forms. Lavage is performed with with each time at least 200ml of saline. Aside from lavage sessions, the lavage is paused, but continuous CSF drainage remains open.

Primary outcomes

• Clinical cure rate [4 weeks after enrollment]: Clinical cure rate at 4 weeks after enrollment and randomization

Secondary outcomes

• GOSE [up 6 months after enrollment and randomization]: Extended Glasgow Outcome Scale at discharge and within 6 months after diagnosis of ventriculitis
• Microbial clearance rate [4 weeks after enrollment]: Microbial clearance rate at 4 weeks after enrollment and randomization
• CSF test results [At 8th day after enrollment, and within 1 week before discharge]: Results of CSF test at 8th day after enrollment, and within 1 week before discharge, including CSF glucose, CSF protein, CSF WBC count and organism(s) identification by a culture or non-culture based microbiologic testing method
• Cranial CT or MRI indicating [At 8th day after enrollment, and within 1 week before discharge]: Cranial CT or MRI indicating at 8th day after enrollment, and within 1 week before discharge
• Length of ICU stay and hospital stay [up to 6 months after enrollment and randomization]: Length of ICU stay and hospital stay
• Complications [up to 6 months after enrollment and randomization]: Blood from puncture canal and intracranial during hospitalization

Sex: All, ages: 18 Years to 65 Years

Inclusion Criteria:

* Age 18-65 years old;
* CSF is purulent (it appears cloudy or yellow) and white blood cell count over 1000×10\^6/L.
* Fever (>38.0°C)
* Meet at least one of the following: 1. Patient has organism(s) identified from CSF by a culture or non-culture based microbiologic testing method; 2. Cranial CT or MRI indicating intraventricular floccule or pus.
* With consent form

Exclusion Criteria:

* With GCS score of 3
* With unstable vital signs such as no spontaneous breathing and blood pressure maintenance drugs
* With severe propensity for bleeding (Such as coagulation dysfunction, active bleeding, etc.), and unable to tolerate the surgical procedures or operations related to ventricular irrigation treatment.
* Pregnant or lactating women

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• Jiyao Jiang, Dr, Principal investigator, Renji Hospital, School of Medicine, Shanghai Jiaotong University
• Junfeng Feng, Dr, Study director, Renji Hospital, School of Medicine, Shanghai Jiaotong University
• Qinghua Wang, Dr, Study director, Southern Medical University, China
• Xiaofeng Yang, Dr, Study director, First Affiliated Hospital of Zhejiang University
• Yuhai Wang, Dr, Study director, 904th Hospital of the Joint Logistics Support Force of the PLA
• Xianjian Huang, Dr, Study director, Shenzhen Second People's Hospital
• Xuefei Shao, Dr, Study director, First Affiliated Hospital of Wannan Medical College
• Lijun Hou, Dr, Study director, The Second Affiliated Hospital of Naval Medical University
• Chunlong Zhong, Dr, Study director, Shanghai East Hospital
• Liang Gao, Dr, Study director, Shanghai Donglei Brain Hospital
• Rongcai Jiang, Dr, Study director, Xuanwu Hospital, Beijing
• Liansheng Long, Dr, Study director, South Taihu Hospital Affiliated to Huzhou College
• Feng Gao, Dr, Study director, he affiliated people's hospital of ningbo university
• Chunhua Hang, Dr, Study director, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Jing Ji, Dr, Study director, The First Affiliated Hospital with Nanjing Medical University
• Xiaoou Sun, Dr, Study director, The First Affiliated Hospital of Soochow University
• Aijun Peng, Dr, Study director, Yangzhou University
• Jinlong Shi, Dr, Study director, Affiliated Hospital of Nantong University
• Binghui Qiu, Dr, Study director, Nanfang Hospital, Southern Medical University
• Dan Jin, Dr, Study director, Zhongshan Hospital Of Traditional Chinese Medicine
• Yongxin Wang, Dr, Study director, First Affiliated Hospital of Xinjiang Medical University
• Chaohua Yang, Dr, Study director, West China Hospital
• Qibing Huang, Dr, Study director, Qilu Hospital of Shandong University
• Yan Qu, Dr, Study director, The Second Affiliated Hospital of Air Force Military Medical University
• Yan Zhang, Dr, Study director, Second Affiliated Hospital of Nanchang University
• Qiuhua Jiang, Dr, Study director, Ganzhou City People's Hospital
• Yijun Bao, Dr, Study director, The Fourth Affiliated Hospital of China Medical University
• Hongsheng Liang, Dr, Study director, First Affiliated Hospital of Harbin Medical University
• Wenhua Fang, Dr, Study director, First Affiliated Hospital of Fujian Medical University
• Guang Feng, Dr, Study director, Henan Provincial People's Hospital
• Kai Shu, Dr, Study director, Tongji Hospital
• Jinfang Liu, Dr, Study director, Xiangya Hospital of Central South University
• Weiping Zhao, Dr, Study director, Inner Mongolia People's Hospital
• Yongming Zhang, Dr, Study director, The Second People's Hospital of Anhui Province
• Xiangpin Wei, Dr, Study director, The First Affiliated Hospital of University of Science and Technology of China
• Xianzhen Chen, Dr, Study director, Shanghai 10th People's Hospital