External ventricular drainage following purulent meningitis with hydrocephalus in pediatric patients

doi:10.21203/rs.3.rs-4945793/v1

Background

External ventricular drain (EVD) placement is standard of care in the management of purulent meningitis with hydrocephalus (PMH). However, there are no guidelines for EVD placement and management after PMH. Optimal EVD insertion location, techniques to reduce the risk of EVD-associated infection and methods of EVD removal are critical, yet incompletely answered management variables.

Methods

The indwelling time of conventional external ventricular drainage is relatively short, 7–10 days. Long-term external drainage devices may lead to retrograde infection. This study has modified the C-EVD procedure. Clinical outcomes, cerebrospinal fluid (CSF) test results, complications, and outcomes were compared between the modified external ventricular drainage (M-EVD) (n = 21) group and C-EVD (n = 25) group.

Results

The two groups were similar regarding age, sex, weight and other general conditions (P > 0.05). There were significant differences in the values of white blood cells (WBC), glucose(GLU) and protein(PR) in cerebrospinal fluid (CSF) between the two groups when the drainage tube was removed, which was statistically significant. The median days of removing the drainage tube in the C-EVD group and the M-EVD group were 9 days and 19 days, respectively. The median days of CSF returning to normal were 19 days and 13 days (P < 0.05). A total of 13 children in the M-EVD group underwent V-P shunt surgery, while 17 children in the C-EVD group were treated with V-P shunt surgery (P = 0.665).

Conclusion

M-EVD has more obvious advantages compared to C-EVD. The modified significantly prolonged the catheterization time, which can more effectively treat PMH in pediatric patients.

Modified

Conventional

External Ventricular Drainage

Purulent Meningitis

Hydrocephalus

Pediatric

Purulent meningitis (PM) is an important cause of child morbidity and mortality(1). Hydrocephalus is a life-threatening complication of purulent meningitis, with a incidence rate of 9% -35%(2–4). PM can aggravate the symptoms of hydrocephalus and make the condition more complicated. PM can also cause pathological changes in the structure of brain tissue, with irreversible effects on the nervous system(5). A large amount of CSF causes the ventricle to expand and results in a significant increase in ventricular pressure, which gradually aggravates the compression of brain tissue. This results in brain dysfunction, with high incidences of disability and mortality(6–8). Effectively reducing intracranial pressure and actively controlling infection can improve the prognosis. Therefore, for patients with purulent meningitis with hydrocephalus (PMH), it is crucial to choose the appropriate treatment(6).

At present, V-P shunt surgery is the main surgical method for treating hydrocephalus in children(9). However, PM is a contraindication for V-P shunt, which may lead to obstruction of the shunt tube, surgical failure and even spread of infection(7). In order to temporarily alleviate the damage of hydrocephalus to brain tissue and effectively control intracranial infection, external ventricular drainage is a common treatment(6, 10).

The C-EVD can effectively improve the symptoms of hydrocephalus. However, the indwelling time of drainage tube is relatively short, 7–10 days(11, 12). PMH can hardly be effectively controlled in the short term, but long-term external drainage devices may lead to retrograde infection and even multiple infections, which may aggravate the condition(6). So PMH has become a difficult point in clinical work. In order to prolong the indwelling time of drainage tube, this study has modified the C-EVD procedure. By analyzing the preoperative and postoperative data of M-EVD and C-EVD, the safety and effectiveness of the two surgical methods were analyzed and compared.

We reviewed 46 consecutive pediatric patients who underwent the C-EVD or M-EVD for PMH treatment at Children's Hospital of Hebei Province from January 2018 to December 2023. The institutional review board approved the study, and all parents of the young child patients provided informed consent for study inclusion.

Inclusion criteria: (1) Patient age range from 1 to 3 years old. (2) Purulent meningitis. (3) Hydrocephalus (bilateral lateral ventricular dilatation) confirmed on cephalic CT or MRI. (4) Elevated CSF white blood cell count (WBC) and protein concentration (PR), and decreased CSF glucose concentration (GLU). (5) Treatment with M-EVD or C-EVD. (6) Parental provision of written informed consent for the operation and postoperative follow-up.

Exclusion criteria: (1) Patient age older than 3 years. (2) Hydrocephalus caused by ventricular hemorrhage. (3) Open craniocerebral injury. (4) Iatrogenic intracranial infection. (5) Genetic metabolic diseases. (6) Intracranial space-occupying lesions. (7) treatment refusal or death. (8) Glasgow Coma Scale of 3 points (circulatory or respiratory circulatory failure). (9) No informed consent provided by the legal representative of the pediatric patient.

Fifty-six patients with PMH treated in the Department of Neurosurgery between January 2018 to December 2023 were screened for study eligibility. After ten ineligible patients with PMH were excluded, the total study cohort comprised 46 eligible patients with PMH who received M-EVD or C-EVD. There were 21 patients in the M-EVD group (14 males and 7 females, the median age 23.7 months) and 25 in the C-EVD group (14 males and 11 females, the median age 19.1 months). All included patients completed follow-up.

Clinical Evaluation

The general conditions of all children pre- and post-operative were recorded in detail, including gender, age, temperature and weight. Whether there are symptoms of intracranial hypertension: headache, vomiting, "sunset sign". Meningeal irritation sign. The degree of ventricular dilatation was judged by head CT or MRI. Compare the amount of WBC, GLU,PR in CSF before and after surgery and during extubation in both groups of children. Record in detail the time for CSF to return to normal. The number of cases with complete removal of shunt tubes and V-P shunt surgery. Complications and prognosis.

The Neurosurgery Branch of the Chinese Medical Association proposed the criteria for the cure of intracranial infection in 2017: 1. The temperature remains normal within 1-2 weeks without any other infection foci in the body. 2. The values of WBC < 10 * 10 6/L, Glu: 2.5-4.4 mmol/L, PR: 0.2-0.4 g/L in the results of two consecutive CSF tests. 3. The CSF culture results are negative. When the CSF reaches the above criteria, it cannot be used as a standard for removing the drainage tube in the M-EVD group. After the CSF returns to normal, gradually reduce the drainage volume of CSF through a three-way valve until the drainage tube is closed. If the child does not have symptoms of intracranial hypertension, the results of head CT and MRI suggest no significant expansion of the ventricles, and the drainage tube can be removed. If there are symptoms of intracranial hypertension after stopping drainage, VP shunt surgery should be performed on the contralateral ventricle.

The time for removing the drainage tube in the EVD group was 7-10 days. Because prolonged indwelling of the drainage tube may increase the risk of retrograde intracranial infection.

Operation Procedures

Modified External Ventricular Drainage

After anesthesia, the patient is placed in a supine position with the head tilted to the left. Disinfect and lay sterile surgical sheet. The puncture point of the ventricle was 6 cm above the occipital tubercle and 3 cm to the right of the midline. An approximately 4-cm-long curved incision was made in the right occipital. A small hole (about 0.4-cm diameter) was drilled in the skull using a skull micro-dynamic system, and the dura mater was coagulated with bipolar electrocoagulation. An approximately 0.5-cm-long incision was made along the outer edge of the 10th rib. A subcutaneous tunnel was then created between the head and chest incisions using a rod. The shunt tube was led out through the tunnel. The ventricular end of the shunt tube was placed in the right ventricle perpendicular to an imaginary line connecting the bilateral external auditory canals. Then, 4 ml of CSF was extracted and sent to the laboratory for analysis. After the drainage tube was connected to the valve, the valve was pressed to check that there was CSF flowing out at the distal end of the drainage tube. The length of the external drainage tube at the chest wall was about 35 cm. The end of the drainage tube was connected to a closed drainage device. The surgical incision was sutured closed in layers. (Fig 1)

Conventional External Ventricular Drainage

The puncture point of the ventricle was 2.5 cm to the right of the midline and 1cm in front of the coronal suture. Place the drainage tube, observe the smooth flow of CSF, and then connect it to the external drainage bag. (Fig 2)

Postoperative Care

Postoperative, cephalic CT was performed to determine the position of the drainage tube in the ventricle and check for bleeding in the ventricle. The drainage volume of CSF was generally limited to 100ml. However, if the patient’s condition was poor, the amount of CSF drainage was appropriately increased. Cefotaxime sulbactam sodium was used for empirical antibacterial therapy. After the etiological results were confirmed, sensitive antibiotics were used for intrathecal antibacterial therapy. The CSF was re-examined every 3 days after surgery until the results of two consecutive CSF tests were normal. After the intracranial infection was controlled, the CSF drainage began to be restricted. The mental state of the patient was closely observed, and cephalic MRI or CT was intermittently repeated to judge the degree of hydrocephalus.

Statistical Analysis

SPSS 26.0 (IBM, Armonk, New York, USA) software was used to statistically analyze the preoperative and postoperative data of patients. Data collected at the last visit were used for comparisons with the preoperative baseline parameters. The measurement data that conformed to the normal distribution were expressed as mean ± standard deviation. Using quartiles and non-parametric methods to calculate data that do not conform to a normal distribution. The paired measurement data t-test was used for the comparison of pre- and post-operative scores, and P<0.05 was considered statistically significant.

All the patients completed follow-up, with no serious complications or deaths. There were no significant differences in gender, age, weight, temperature, and other general conditions between the two groups of children on admission (P>0.05). (Table 1)

Cerebrospinal Fluid

There were significant pre- versus postoperative differences in the WBC, GLU and PR of the CSF in both groups (P<0.05). The median days of CSF returning to normal were 19 days and 13 days, respectively. (P=0.000). When the head drainage tube was removed, the CSF results in the M-EVD group were normal. However, in the C-EVD group, the CSF results were still abnormal, but it showed significant improvement compared to pre-operative results. There was a significant difference in the CSF results between the two groups when the head drainage tube was removed, which was statistically significant. (Table 1, Table 2)

External Ventricular Drainage

In the M-EVD group, twelve patients developed symptoms of intracranial hypertension after the drainage tube was closed, and the imaging results indicated ventricular dilatation. V-P shunt surgery was performed, with a good surgical prognosis. Nine patients had no symptoms of intracranial hypertension after the drainage tube was closed, and had no ventricular dilatation found on cephalic MRI. No patient reported discomfort after the M-EVD device was removed.

After removing the drainage tube, mannitol (kg*3-5ml) was continued to be used for dehydration and reduction of intracranial pressure, and gradually decreased until discontinuation. After the CSF results returned to normal, 17 children still had symptoms of intracranial hypertension. V-P shunt was performed, and the recovery was better. Eight children did not experience symptoms of intracranial hypertension after discontinuing mannitol.

Complications

M-EVD

One patient still had not had the drainage removed at 2 months after surgery, as the CSF collected from the drainage tube showed abnormal results. Three CSF cultures all grew Streptococcus pneumoniae. However, the patient had no signs of meningeal irritation and had a normal temperature. Therefore, we consider that the S. pneumoniae had colonized the drainage tube. We performed lumbar puncture to extract CSF and obtained normal CSF test results and grew no bacteria on CSF culture. Subsequently, the patient underwent V-P shunt surgery and was in a very stable condition postoperatively.

Three patients showed redness and exudation at the chest wall incision that improved after dressing changes and anti-infection treatment.

C-EVD

A patient who underwent V-P shunt surgery experienced multiple headaches after discharge. The imaging results after reexamination showed ventricle dilation. Upon checking the pressure of the shunt valve, it was found that the pressure had changed from the time of discharge. The cause of the pressure change was unknown. After adjusting the pressure of the shunt valve, the headache symptoms improved.

At present, the treatment of PMH in children is relatively complex, which has brought great economic and psychological pressure to the families(4). Peng et al. believe that the mortality rate of pediatric patients with PM is very high if they do not receive treatment(13). During the process of infection with PM, inflammatory exudates can attach to the surface of the subarachnoid space or ependyma, resulting in meningeal obstruction(5, 14). This leads to a decrease in the ability of CSF circulation or arachnoid granules to absorb CSF, which breaks the balance between the production and absorption of CSF, thus forming hydrocephalus(14). For children with PMH, V-P shunt operation is feasible only when the intracranial infection is well controlled. So how to effectively control infection and reduce intracranial pressure has become a difficult topic for clinicians. The setting of C-EVD is one of the most frequent procedures in the PMH(4). However, this procedure has some disadvantages(10, 15). In this study, the operation method of C-EVD has been modified and achieved good results.

The puncture point of C-EVD is relatively close to the ventricle. If the drainage tube is left in place for a long time, bacteria may retrogradely invade the ventricle through the drainage tube, aggravating intracranial infection and even causing multiple infections. Therefore, the duration of C-EVD placement is usually 7–10 days(6, 10, 16). Konovalov(10) et al. analyzed 122 patients with C-EVD and concluded that the complication risks of this procedure may grow from 5–39%. The longer the drainage tube is left in place, the higher the risk of infection. In this study, the longest duration of drainage tube placement is 10 days. When removing the drainage tube, the CSF had not returned to normal, but it had significantly improved before treatment. After removing the drainage tube, sensitive antibiotics are still needed for anti-infection therapy.

In contrast, the drainage tube in M-EVD is located at the lateral edge of the 10th rib, which is relatively far from the ventricle and thus greatly decreases the risk of retrograde intracranial infection. Even if infection occurs at the exit of the drainage tube, the probability of retrograde intracranial infection is relatively low due to the distance from the ventricle. In the present study, one patient in the M-EVD group had the drainage tube retained for 61 days due to the presence of colonizing bacteria in the drainage tube. The experience we learned from this is that patients with such conditions should undergo lumbar puncture to obtain CSF for testing. However, from another perspective, this also proves the effectiveness and feasibility of M-EVD, as there was no retrograde infection or multiple infections during the 2-month catheterization process. This result also surprised us. However, only one case cannot fully prove that all M-EVDs can be left in place for several months. Under the premise of effective infection control, the drainage tube should be removed as soon as possible to avoid complications. However, compared with C-EVD, M-EVD may allow the prolongation of the drainage time and seems to have better safety and effectiveness.

Patients with PMH have a large amount of exudates and inflammatory factors in CSF(1). Preoperative WBC, PR and GLU in CSF are significantly abnormal. And the disease progresses rapidly, threatening the patient's life. Conservative treatment (intravenous antibiotic therapy for intracranial infection, mannitol to reduce intracranial pressure) has a slow effect and a long cycle, which may cause irreversible neurological damage to children(17). Because many antimicrobial drugs are difficult to penetrate the blood-brain barrier, drugs cannot reach effective therapeutic concentrations in CSF and brain tissue, resulting in slow therapeutic effects(18). For pediatric patients, the use of high doses, long-term treatment, multi-drug combination, and even possible complications such as liver and kidney dysfunction and antibiotic diarrhea may occur(19).

Compared with conservative treatment, external drainage surgery has certain advantages(4, 20). Both C-EVD and M-EVD can release a large amount of pathogenic bacteria and exudates from the CSF through external drainage, thereby accelerating the circulation of CSF and reducing the concentration of bacteria(6). After surgery, we can know the type of bacteria and drug sensitivity results through pathogen detection. Antibacterial treatment can be carried out by intrathecal injection of the most sensitive antibiotic. The intrathecal antibiotic can cross the blood-brain barrier, allowing the drug to quickly enter the ventricles and subarachnoid space, rapidly spread on the brain surface, and achieve effective drug concentration in the infection area(21–23). Therefore, it can effectively control infection, alleviate symptoms, and improve the prognosis of children.

Is it feasible to perform intrathecal antibiotic injection through lumbar puncture? Performing daily lumbar puncture increases the pain of patients, especially in pediatric patients, as the pain leads to poor cooperation and even increases the risk of central nervous system infection. Most importantly, intrathecal administration of drugs after lumbar puncture cannot achieve uniform distribution of drugs in brain tissues. Relevant research reports that after injecting antibiotics into infants, it takes at least 6 hours for the lumbar CSF to reach the highest concentration, and the time for the drug to reach the highest concentration in the cisternal CSF is 14 hours(22). Moreover, the distribution of drugs in CSF is uneven. However, after intraventricular intrathecal administration, the highest concentration can be reached within 2 hours, and antibacterial drugs can be rapidly distributed throughout the entire CSF space(22, 24, 25). However, patients with obvious surgical contraindications cannot undergo surgical treatment. Lumbar puncture can also serve as a therapeutic method(26).

Are there any complications associated with intrathecal antibiotic injection? Nau(22) believes that intrathecal antibiotic injection may cause adverse reactions. For example, vancomycin may cause temporary hearing loss, polymyxin may cause meningitis reactions and epilepsy, and a high concentration of meropenem may induce seizures(23, 27). In the present study, nine patients in the M-EVD group and seven patients in the C-EVD group experienced headache during intrathecal injection of medication, but the headache symptoms disappeared after the injection was completed. As the infection was gradually controlled, the headache symptoms during the injection process gradually decreased.

Both methods reduce intracranial pressure and relieve symptoms of hydrocephalus. Intrathecal antibacterial medications can quickly reach appropriate drug concentrations and treat intracranial infections. The main advantage of M-EVD is that it prolongs the retention time of the drainage tube and reduces the risks of drainage tube displacement and detachment, CSF leakage, and retrograde intracranial infection.

Author contributions

Yaning Sun and Xiao Jing conceived the idea for the study; Pengyuan Luo and Yanke Yue designed the study. Jiangshun Fang and Shengjuan Wang collected the relevant data and followed up the patients. Zhiguo Chen prepared the figures and tables. Jimei Luan, Zhenghai Cheng and Zhiguo Yang performed the statistical analyses. All the authors interpreted the data and contributed to preparation of the manuscript. Yaning Sun wrote the manuscript. Yi Qu reviewed and approved the final version. All authors read and approved the final manuscript.

Funding

This study was not supported by any funding organization.

Availability of data and materials

All the data will be available upon motivated request to the corresponding author of the present paper.

Ethics approval and consent to participate

The study protocol was in accordance with the Helsinki Declaration and was approved by the institutional review board of Hebei Children's Hospital and all patients provided the written informed consent.

Hebei Medical Science Research Project Plan, approval number: 20220735.

Consent for publication

Written informed consent was obtained from each patient to authorize the publication of their data.

Competing interests

The authors declare that they have no competing interests.

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Table 1 Comparison of measurement data between M-EVD and C-EVD

Variabe		M-EVD	C-EVD	P
Age（Months）		23.7(18.25,34.85)	19.1(14.55,33.3)	0.247
Gender	Male	14(66.67%)	14(56.00%)	0.460
Gender	Female	7(33.33%)	11(44.00%)	0.460
Admission Temperature		38.85±0.46	38.91±0.51	0.639
Weight（Kg）		12.94±2.35	11.87±1.76	0.085
Serum Protein		41.53(38.38,46.41)	47.1(39.55,50.1)	0.265
Albumin		63.88(54.82,69.46)	61(59.8,71.95)	0.093
Clinical Symptoms
Intracranial Hypertension	Positive	17(80.95%)	18(72.00%)	0.478
Intracranial Hypertension	Negative	4(19.05%)	7(28.00%)	0.478
Meningeal Irritation	Positive	15(71.43%)	18(72.00%)	0.966
Meningeal Irritation	Negative	6(28.57%)	7(28.00%)	0.966
Infection Control Time (Day)		13(12,14)	19(18,22.5)	0.000
Removal of Drainage Tube Time（Day）		19(13,23)	9(7,10)	0.000
V-P shunt（Cases）	Operation	13(61.90%)	17(68.00%)	0.665
V-P shunt（Cases）	Non	8(38.10%)	8(32.00%)	0.665

Albumin: 60-80g/L. Serum Protein：35-55g/L.

"Age, serum albumin, albumin, infection control and removal of drainage tube time" are quantitative variables that do not follow a normal distribution, and non-parametric tests are used.

"Admission temperature and weight " are quantitative variables that follow a normal distribution, and independent sample t-tests are used.

The data of "gender, symptoms of intracranial hypertension, meningeal irritation and V-P shunt cases" were classified variables, and chi-square test was used.

Table 2 Cerebrospinal fluid indicators when removing the drainage tube

	M-EVD (n=21)	C-EVD (n=25)	P
WBC	5.10±2.07	48.28±21.88	0.000
GLU	3.13±0.51	1.98±0.49	0.000
PR	0.39(0.29,0.49)	1.1(0.5,1.4)	0.000

WBC：0-10* 10^6/L, GLU：2.5-4.4mmol/L, PR：0.2-0.4 g/L.

No competing interests reported.

External ventricular drainage following purulent meningitis with hydrocephalus in pediatric patients

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Abstract

Background

Methods

Results

Conclusion

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Introduction

Matericals and Methods

Results

Discussion

Conclusion

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Additional Declarations

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