Efficacy and safety of polyethylene glycol dural sealant system in cranial and spinal neurosurgical procedures: Meta-analysis
- Department of Medicine, Demerdash Hospital, Cairo, Egypt.
- Department of Neurosurgery, Al-Ahly Bank Hospital, Nasr City, Egypt.
- Department of Medicine, Zagazig University Hospitals, Zagazig, Egypt.
- Department of Surgery, Demerdash Hospital, Cairo, Egypt.
- Department of Medicine, Fayoum University, Fayoum, Egypt.
Department of Neurosurgery, Al-Ahly Bank Hospital, Nasr City, Egypt.
DOI:10.25259/SNI_132_2021Copyright: © 2021 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
How to cite this article: Ahmed Diab1, Hieder Al-Shami2, Ahmed Negida3, Ahmed Gadallah4, Hossam Farag3, Doaa Mahmoud Elkadi5, Mo’tasem Muhamed Gaber4, Mahmoud Ahmed Ebada3. Efficacy and safety of polyethylene glycol dural sealant system in cranial and spinal neurosurgical procedures: Meta-analysis. 26-Apr-2021;12:182
How to cite this URL: Ahmed Diab1, Hieder Al-Shami2, Ahmed Negida3, Ahmed Gadallah4, Hossam Farag3, Doaa Mahmoud Elkadi5, Mo’tasem Muhamed Gaber4, Mahmoud Ahmed Ebada3. Efficacy and safety of polyethylene glycol dural sealant system in cranial and spinal neurosurgical procedures: Meta-analysis. 26-Apr-2021;12:182. Available from: https://surgicalneurologyint.com/surgicalint-articles/10763/
Background: We aimed to assess the efficacy of polyethylene glycol (PEG) dura sealant to achieve watertight closure, prevention of cerebrospinal fluid (CSF) leak and to investigate its possible side effects.
Methods: We searched Medline (through PubMed), Scopus, and the Cochrane Library through December 2019. We included articles demonstrating cranial or spinal procedures with the use of PEG material as a dural sealant. Data on intraoperative watertight closure, CSF leak, and surgical complications were extracted and pooled in a meta-analysis model using RevMan version 5.3 and OpenMeta (Analyst).
Results: Pooling the controlled trials showed that PEG resulted in significantly more intraoperative watertight closures than standard care (risk ratio [RR] = 1.44, 95% confidence interval [CI] [1.24, 1.66]). However, the combined effect estimate did not reveal any significant difference between both groups in terms of CSF leaks, the incidence of surgical site infections, and neurological deficits (P = 0.7, 0.45, and 0.92, respectively). On the other hand, pooling both controlled and noncontrolled trials showed significance in terms of leak and neurological complications (RR = 0.0238, 95% CI [0.0102, 0.0373] and RR = 0.035, 95% CI [0.018, 0.052]). Regarding intraoperative watertight closure, the overall effect estimate showed no significant results (RR=0.994, 95% CI [0.986, 1.002]).
Conclusion: Dura seal material is an acceptable adjuvant for dural closure when the integrity of the dura is questionable. However, marketing it as a factor for the prevention of surgical site infection is not scientifically proved. We suggest that, for neurosurgeons, using the dural sealants are highly recommended for duraplasty, skull base approaches, and in keyhole approaches.
Keywords: Dura sealant, Dural closure, Hydrogel, Polyethylene glycol
Cerebrospinal fluid (CSF) leakage after neurosurgical operations is a common phenomenon at either infratentorial or supratentorial surgeries. It ranges from 10 to 25%.[
The main method of dural closure is the primary surgical closure; however, this is not enough to achieve a watertight approximation.[
At present, the techniques used to achieve a watertight dural closure include the application of interrupted sutures, dural replacement materials (duraplasty), and hemostatic agents.[
Polyethylene glycol (PEG)-based hydrogel is a new sealant used as an adjuvant to augment primary dural closure after craniotomy.[
In this meta-analysis of clinical trials, we aimed to assess the efficacy of PEG to achieve watertight closure of the dura and prevention of CSF leak and to investigate its possible side effects.
We performed all steps of this systematic review in strict accordance with the Cochrane handbook of systematic reviews and meta-analysis. We also followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement guidelines while drafting our manuscript.[
Literature search strategy
We searched Medline (through PubMed), Scopus, and the Cochrane Library through December 2019, using the following keywords: “PEG,” “Hydrogel,” “Dural Sealant,” “Dural Closure,” “Neurosurgery,” “Cranial,” and “Spinal.”
No restrictions by language, country, or publication date were employed. We also searched the bibliography of eligible studies for relevant articles.
We included both randomized controlled trials and noncontrolled studies assessing the use of PEG hydrogel for dura matter closure in cranial or spinal neurosurgical procedures.
We excluded nonhuman studies, studies from which data cannot be reliably extracted, duplicate references, case reports, and conference abstracts.
Selection of studies
We independently applied the selection criteria; eligibility screening was conducted in two steps, (a) titles and abstracts screening for matching the inclusion criteria and (b) full-text screening for eligibility to meta-analysis. Disagreements were resolved on discussion.
Outcomes of interest
We included studies reported at least one of the following outcomes: (1) intraoperative watertight closure, (2) CSF leak, and (3) surgical complications such as meningocele, surgical site infection, sepsis, subarachnoid hemorrhage, and pneumocephalus.
We independently extracted and tabulated data on the first author, publication year, study design, baseline characteristics of the study population, type of intervention including the type of prosthesis, study period, follow-up period, and relevant outcomes data. Disagreements were resolved on discussion.
Risk of bias (ROB) assessment
Two independent reviewers used the Cochrane ROB assessment tool, clearly described in Chapter 8.5 of the Cochrane handbook of systematic reviews of interventions 5.1.0. The Cochrane ROB assessment tool is designed to detect five types of bias, including selection bias (sequence generation and allocation concealment), performance bias (blinding of participants and investigators), detection bias (blinding of outcome assessors), attrition bias (incomplete outcome data), and reporting bias (selective outcome reporting).[
We included both controlled and noncontrolled studies. We used OpenMeta (Analyst) software to calculate an overall estimate and 95% confidence interval (CI) for the outcome in the experimental groups in both sets of studies. We used Review Manager software (version 5.3) to calculate the risk ratio (RR) and 95% CI for outcomes of the controlled studies.
Assessment of heterogeneity
Heterogeneity was assessed by visual inspection of the forest plots and measured by Q statistic and I2 statistic. Significant statistical heterogeneity was indicated by Q statistic P < 0.1 or by I2 more than 50%.
According to Egger’s et al., publication bias is not reliable for <10 pooled studies. Therefore, in the present study, we could not assess the existence of publication bias by Egger’s test for funnel plot asymmetry.
Literature search results
The results of searching databases yielded 255 studies. After excluding duplicates, 169 studies entered the screening phase. Twelve studies entered full-text screening, and a total of six studies were finally included in our study. Half of the included trials were controlled trials, and the other three studies were noncontrolled. [
Characteristics of the included studies’ population
The included studies were six studies. Controlled and uncontrolled studies were in a ratio of 3:3. The total number of recruited patients from randomized studies was 493 patients. The uncontrolled studies contain 181 patients. The controlled trials measured PEG efficacy against conventional method used for dural closure. The summary of the baseline characteristics of the included studies is shown in [
Assessment of study validity
We detected an overall moderate ROB for the included clinical trials. Regarding randomization and blinding of outcome assessors, three studies did not report the methodology of randomization nor blinding of outcome assessors, therefore, were categorized as unclear ROB. As for allocation concealment, blinding of patients, attrition bias, and selective reporting, all studies were put to low risk, as they provided sufficient data for supporting these domains. Except for Osbun et al.,[
Synthesis of results
We conducted two analyses for selected outcomes; one for controlled trials and another single-arm analysis for both controlled and noncontrolled studies.
Analysis of controlled trials [ Figure 3 ]
Intraoperative watertight closure
The overall RR showed that PEG resulted in significantly more intraoperative watertight closures than standard care (RR = 1.44, 95% CI [1.24, 1.66], P < 0.001). Pooled results were homogeneous (I2 = 59%, P = 0.12),
The combined effect estimate did not reveal any significant difference between both groups in terms of CSF leaks (RR = 0.87, 95% CI [0.37, 2.04], P = 0.7). Pooled results were homogenous (I2 = 0%, P = 0.5),
Surgical site infections
The net result of analysis did not favor any of the two groups regarding the incidence of surgical site infections (RR = 0.74, 95% CI [0.33, 1.63], P = 0.45). Pooled results were homogeneous (I2 = 0%, P = 0.8),
The combined RR did not show a significant difference between PEG and standard care (RR = 0.96, 95% CI [0.46, 2.03], P = 0.92). Pooled results were homogenous (I2 = 0%, P = 0.5),
Analysis for both controlled and noncontrolled trials [ Figure 4 ]
Intraoperative watertight closure
The overall effect estimate did not reveal significant results (RR = 0.994, 95% CI [0.986, 1.002]). Pooled results were homogenous (I2 = 0%, P = 0.9),
Combined effect estimates and 95% CI showed marked significance (RR = 0.0238, 95% CI [0.0102, 0.0373]). Pooled results were heterogeneous (I2 = 61%, P = 0.026),
The net results of neurological complications (pseudomeningocele, surgical site infection, and neurological deficit) from surgery revealed significant results (RR = 0.035, 95% CI [0.018, 0.052]). Pooled results were heterogeneous (I2 = 50%, P = 0.089),
Summary of main results
Analysis of controlled trials only revealed that PEG increases intraoperative watertight closures. However, it did not show any difference between PEG and standard care in terms of neurological deficits, postoperative CSF leaks, and surgical site infections.
Single-arm analysis of all trials showed no difference in terms of intraoperative watertight closures; this may be stronger evidence than controlled trials, as the strength of meta-analysis is increased by increasing the number of included studies, provided that results remain homogeneous. However, postoperative CSF leaks and surgical site infections were significant.
Significance of main results
Watertight closure is critical, and the dura seal is an excellent material to achieve zero leakage intraoperatively. However, stopping postoperative leakage cannot be guaranteed by the dura seal in controlled trials. Prevention of surgical site infection is the matter of achieving a good medium for healing and infection control rather than the application of foreign material.
Agreement and disagreement with the previous studies
Kim et al. studied the dural sealant in various procedures in neurosurgery; they found that using it was effective in the prevention of CSF fistula.[
They found that easy and effective sealing of the field was achieved by the dura seal.[
Osbun et al. conducted a randomized controlled trial used the same material in cranial surgeries in a group (n = 120) against the traditional method group (n = 117).[
In contrast, a different outcome was achieved by Green et al.[
Tew et al. conducted a large cohort study that included 17 centers to study the effectiveness of dural sealant versus traditional methods of dural closure in cranial surgeries.[
Dura seal material is an acceptable adjuvant for dural closure when the integrity of the dura is in question. However, marketing it as a factor for the prevention of surgical site infection is not scientifically proved. We suggest that, for neurosurgeons, using the dural sealants are highly recommended for duraplasty, skull base approaches, and in keyhole approaches.
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