Department of Paediatric Neurosurgery, Alder Hey Children's NHS Foundation Trust, Liverpool, UK.
Department of Neurosurgery, The Walton Centre NHS Foundation Trust, Liverpool, UK.
Health Technol Assess. 2020 Mar;24(17):1-114. doi: 10.3310/hta24170.
Insertion of a ventriculoperitoneal shunt to treat hydrocephalus is one of the most common neurosurgical procedures worldwide. Shunt infection affects up to 15% of patients, resulting in long hospital stays, multiple surgeries and reduced cognition and quality of life.
The aim of this trial was to determine whether or not antibiotic-impregnated ventriculoperitoneal shunts (hereafter referred to as antibiotic shunts) (e.g. impregnated with rifampicin and clindamycin) or silver-impregnated ventriculoperitoneal shunts (hereafter referred to as silver shunts) reduce infection compared with standard ventriculoperitoneal shunts (hereafter referred to as standard shunts).
This was a three-arm, superiority, multicentre, parallel-group randomised controlled trial. Patients and a central primary outcome review panel, but not surgeons or operating staff, were blinded to the type of ventriculoperitoneal shunt inserted.
The trial was set in 21 neurosurgical wards across the UK and the Republic of Ireland.
Participants were patients with hydrocephalus of any aetiology who were undergoing insertion of their first ventriculoperitoneal shunt.
Participants were allocated 1 : 1 : 1 by pressure-sealed envelope to receive a standard non-impregnated, silver-impregnated or antibiotic-impregnated ventriculoperitoneal shunt at the time of insertion. Ventriculoperitoneal shunts are medical devices, and were used in accordance with the manufacturer's instructions for their intended purpose.
The primary outcome was time to ventriculoperitoneal shunt failure due to infection. Secondary outcomes were time to failure for any cause, reason for failure (infection, mechanical), types of ventriculoperitoneal shunt infection, rate of infection after first clean (non-infected) revision and health economics. Outcomes were analysed by intention to treat.
Between 26 June 2013 and 9 October 2017, 1605 patients from neonate to 91 years of age were randomised to the trial: = 36 to the standard shunt, = 538 to the antibiotic shunt and = 531 to the silver shunt. Patients who did not receive a ventriculoperitoneal shunt ( = 4) or who had an infection at the time of insertion ( = 7) were not assessed for the primary outcome. Infection occurred in 6.0% ( = 32/533) of those who received the standard shunt, in 2.2% ( = 12/535) of those who received the antibiotic shunt and in 5.9% ( = 31/526) of those who received the silver shunt. Compared with the standard shunt, antibiotic shunts were associated with a lower rate of infection (cause-specific hazard ratio 0.38, 97.5% confidence interval 0.18 to 0.80) and a decreased probability of infection (subdistribution hazard ratio 0.38, 97.5% confidence interval 0.18 to 0.80). Silver shunts were not associated with a lower rate of infection than standard shunts (cause-specific hazard ratio 0.99, 97.5% confidence interval 0.56 to 1.74). The ventriculoperitoneal shunt failure rate attributable to any cause was 25.0% overall and did not differ between arms. Antibiotic shunts save £135,753 per infection avoided. There were no serious adverse events.
It was not possible to blind treating neurosurgeons to the ventriculoperitoneal shunt type. The return rate for patient-reported outcomes was low. Limitations to the economic evaluation included failure to obtain Hospital Episode Statistics data from NHS Digital, as per protocol. Reliance on patient-level information and costing systems data mitigated these limitations.
Antibiotic shunts have a reduced infection rate compared with standard shunts, whereas silver shunts do not. Antibiotic shunts are cost-saving.
A sample collection has been established that will enable the study of surrogate markers of ventriculoperitoneal shunt infection in cerebrospinal fluid or blood using molecular techniques. A post hoc analysis to study factors related to shunt failure will be performed as part of a future study. An impact analysis to assess change in practice is planned.
Current Controlled Trials ISRCTN49474281.
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 24, No. 17. See the NIHR Journals Library website for further project information.
将脑室腹腔分流管插入以治疗脑积水是全球最常见的神经外科手术之一。分流感染的发生率高达 15%，导致住院时间延长、多次手术以及认知和生活质量下降。
本试验旨在确定抗生素浸渍脑室腹腔分流管（以下简称抗生素分流管）（例如与利福平、克林霉素浸渍）或银浸渍脑室腹腔分流管（以下简称银分流管）是否比标准脑室腹腔分流管（以下简称标准分流管）降低感染率。
这是一项三臂、优效性、多中心、平行组随机对照试验。患者和一个中央主要结局审查小组（但不是外科医生或手术人员）对插入的脑室腹腔分流管的类型进行了盲法。
该试验在英国和爱尔兰共和国的 21 个神经外科病房进行。
参与者为任何病因导致的脑积水且首次接受脑室腹腔分流管插入的患者。
参与者通过密封信封以 1:1:1 的比例随机分配至标准非浸渍、银浸渍或抗生素浸渍的脑室腹腔分流管，在插入时使用。脑室腹腔分流管是医疗器械，根据制造商的说明用于预期用途。
主要结局是因感染导致脑室腹腔分流管失效的时间。次要结局是任何原因导致的失效时间、失效原因（感染、机械性）、脑室腹腔分流管感染类型、首次清洁（未感染）修正后的感染发生率以及卫生经济学。结果按意向治疗进行分析。
2013 年 6 月 26 日至 2017 年 10 月 9 日，年龄从新生儿到 91 岁的 1605 名患者参与了该试验：36 名接受标准分流管，538 名接受抗生素分流管，531 名接受银分流管。未接受脑室腹腔分流管的患者（4 名）或在插入时已感染的患者（7 名）未评估主要结局。在接受标准分流管的患者中，感染发生率为 6.0%（32/533），在接受抗生素分流管的患者中为 2.2%（12/535），在接受银分流管的患者中为 5.9%（31/526）。与标准分流管相比，抗生素分流管感染率较低（特定病因的危险比 0.38，97.5%置信区间 0.18 至 0.80），感染概率降低（亚分布危险比 0.38，97.5%置信区间 0.18 至 0.80）。银分流管与标准分流管相比，感染率无差异（特定病因的危险比 0.99，97.5%置信区间 0.56 至 1.74）。总的脑室腹腔分流管失效率归因于任何原因的发生率为 25.0%，各臂之间无差异。抗生素分流管可节省每例感染避免的费用 135753 英镑。没有发生严重不良事件。
无法对接受脑室腹腔分流管的神经外科医生进行分流管类型的盲法。患者报告结局的回复率较低。经济评估的局限性包括未能按照方案从 NHS Digital 获得医院事件统计数据。依赖于患者水平信息和成本核算系统数据减轻了这些局限性。
与标准分流管相比，抗生素分流管感染率降低，而银分流管则不然。抗生素分流管具有成本效益。
已建立了一个样本采集，将使用分子技术在脑脊液或血液中研究脑室腹腔分流感染的替代标志物。作为未来研究的一部分，将进行事后分析以研究与分流失败相关的因素。计划进行影响分析以评估实践的变化。
当前对照试验 ISRCTN49474281。
本项目由英国国家卫生研究所（NIHR）卫生技术评估计划资助，将在 ; 第 24 卷，第 17 期 中全文发表。有关该项目的更多信息，请访问 NIHR 期刊库网站。
