Preoperative evaluation using external lumbar drainage for patients with posthemorrhagic hydrocephalus

Abstract Background: External lumbar drainage (ELD) remains the most common used methods with a higher sensitivity before lumboperitoneal shunt (LPS) implantation to predict the shunt outcomes in the treatment of idiopathic normal pressure hydrocephalus. However, the benefits of such supplemental test have not been tested in the treatment of post-hemorrhagic hydrocephalus (PHH). Methods and design: In the current trial, 100 eligible patients with PHH will be recruited and randomly assigned to the ELD group (study group) and non-ELD group (control group). Lumbar puncture (LP) will be performed for participants in non-ELD group. LP plus ELD will be performed for participants in ELD group, those who will then be investigated the suitability of potential LPS 4 days after ELD. Two independent and practiced assessors will collect the baseline data and evaluate each participant 4 days after ELD or LP, 1 day after LPS, at the time of discharge and 1 month after LPS. The primary outcome is the shunting outcomes 1 month after surgery. The secondary outcomes include the complications related to ELD, complications related to LPS, and Evens index at each evaluation point. Meanwhile, serious adverse events occurring at any time is recorded to determine the safety of this trial. Discussion: The results of this trial will demonstrate whether preoperative evaluation using temporary ELD for patients with PHH could attenuate the risk of LPS failure. Trial registration number ChiCTR2000034094; Pre-results.


Introduction
Since the application of shunt surgery in clinic, a great deal of attention was directly given to quest the path to attenuate the incidence of shunt failure. [1,2] To date, preoperative accurate evaluation through supplemental test has been widely accepted to correctly select the suitable patients for shunt implantation. [3,4] In this regard, external lumbar drainage (ELD) remains the most common used methods with a higher sensitivity before lumboper-

Study Protocol Clinical Trial
Medicine ® OPEN itoneal shunt (LPS) implantation to predict the shunt outcomes in the treatment of idiopathic normal pressure hydrocephalus. [5] However, the benefits of such supplemental test have not been tested in the treatment of post-hemorrhagic hydrocephalus (PHH), a common disease occurring secondary to intracranial hemorrhage. [6] 2. Methods and design

Objective
To prove whether preoperative evaluation using ELD for patients with PHH could attenuate the risk of LPS failure.

Study design
The flow chart of the selection of patients is shown in Figure 1. In the current trial, 100 eligible patients with PHH will be recruited from the Department of outpatient of Sichuan University West China Hospital since September 1, 2020, and randomly assigned to the ELD group (study group) and non-ELD group (control group). Lumbar puncture (LP) will be performed for participants in non-ELD group. LP plus ELD will be performed for participants in ELD group, those who will then be investigated the suitability of potential LPS 4 days after ELD. Two independent and practiced assessors will collect the baseline data and evaluate each participant 4 days after ELD or LP, 1 day after LPS, at the time of discharge and 1 month after LPS. The primary outcome is the shunting outcomes 1 month after surgery. The secondary outcomes include the complications related to ELD, complications related to LPS, and Evens index at each evaluation point. Meanwhile, serious adverse events occurring at any time is recorded to determine the safety of this trial.

Sample size
Previously published reports indicated that the rate of LPS failure for patients with preoperative evaluation using ELD was 15.7%, comparing with a rate of 40.9% for patients without ELD. [7] In this regard, a sample of 45 will be required in this trial with a significance level of 5% (2-sided) and a power of 80% to demonstrate a 20% difference in rate of shunt failure. Considering about the loss to follow-up, the sample size is enlarged to 50 for each group.

Randomizing and blinding
The randomization will be performed using a random number table that is generated by the statistical program SAS Version 9.4 (SAS Institute Inc, Cary, NC) and is kept secret by the statisticians who are independent of this study. This trial is open-label, but assessors and analysts are blind to allocation and the intervention clinicians will not involve in any assessment.

Intervention
Physicians, neurosurgeons, and clinicians will be trained centrally in advance and reach uniform standard.

Preoperative evaluation
Repeated evaluation will be performed using the scale, as shown in Table 1, 4 days after ELD to investigate the suitability of potential LPS and then the ELD system will be removed. Patients with scores 4 will be included in this trial and the remaining patients will be excluded. Specifically, the improvement of clinical manifestation is defined as an improvement of 1 point or more in the National Institute of Health stroke scale, Glasgow coma scale, modified Rankin scale, or according to self-assessment.

Outcomes
Two independent and practiced assessors will collect the baseline characteristics and evaluate each participant 4 days after ELD or LP, 1 day after LPS, at the time of discharge and 1 month after LPS. The evaluation schedule is shown in Table 2.
2.9.1. Primary outcome. The primary outcome is the shunting outcomes 1 month after surgery. Shunting outcomes include shunt failure and shunt success. According to previous studies, which is defined as the shunt obstruction, breakage, tubing exposure, malfunction, or infection requiring shunt revision. Shunt success is defined as the absence of shunt failure.
2.9.2. Secondary outcomes. The secondary outcomes include the complications related to ELD, complications related to LPS, and Evens index at each evaluation point.
Meanwhile, considering about the safety of this trial, serious adverse events occurring at any time is recorded.

Data collection
Two independent and practiced assessors will collect the data. All data will be recorded in the paper-based Case Record Form and Electronic Data Capture. A third reviewer is required while there are any debates on data collection.

Data and safety monitoring
Members of independent data monitoring committee, including 1 physician, 1 statistician, and 1 data analyst, are responsible for monitoring the safety and efficacy of this trial once a month.

Statistics analysis
SPSS version 19 (IBM, Armonk, NY) is used to analyze statistics and a P-value (2-sided) under .05 is considered to have statistical difference. Kolmogorov-Smirnov test is first used to determine the normality of quantitative data. Quantitative data followed normal-distribution are statistically described as arithmetic mean ± standard deviation. Other quantitative data (non-normal distribution) are statistically described as median (range). Categorical data, such as sex, shunting outcomes, and complications, are statistically descried as number (percent). To compare the 2 groups on quantitative data followed normaldistribution, independent samples t-test is used. To compare the 2 groups on the other quantitative data, Wilcoxon rank sum test is used. To compare the 2 groups on categorical data followed normal-distribution, Chi-square test is used.

Withdrawal and dropout
If at least 2 researchers judge that it is not appropriate to continuously participant in this trial, or any participants choose Table 1 Preoperative evaluation scale after ELD.
withdrawal and dropout, the reasons of withdrawal and dropout will be recorded and submitted to the supervisor for review.

Discussion
This study will be the first randomized controlled trial that analyzes the clinical outcomes of patients diagnosed as PHH with or without evaluation using temporary ELD before LPS implantation. The results of this trial will demonstrate whether preoperative evaluation using temporary ELD for patients with PHH could attenuate the risk of LPS failure and generate the discussion about the accurate evaluation of the suitability of shunt surgery through supplemental test. Additionally, the trial will provide the evidence for the association of shunt failure with the cerebrospinal fluid count and protein level. The current trial, however, still has some limitations. First, it is a single-center study. Second, medical conditions and surgeons' experiences are contributed to the postoperative outcomes. In this regard, personnel will be trained centrally in advance and reach uniform standard.