scholarly journals Does lumbar drainage reduce postoperative cerebrospinal fluid leak after endoscopic endonasal skull base surgery? A prospective, randomized controlled trial

2019 ◽  
Vol 131 (4) ◽  
pp. 1172-1178 ◽  
Author(s):  
Nathan T. Zwagerman ◽  
Eric W. Wang ◽  
Samuel S. Shin ◽  
Yue-Fang Chang ◽  
Juan C. Fernandez-Miranda ◽  
...  
Keyword(s):  
Skull Base ◽  
Skull Base Surgery ◽  
Controlled Trial ◽  
Csf Leak ◽  
Inclusion Criteria ◽  
Endoscopic Endonasal ◽  
Randomized Controlled ◽  
Lumbar Drain ◽  
Prospective Randomized Controlled Trial ◽  
Csf Leaks

OBJECTIVEBased on a null hypothesis that the use of short-term lumbar drainage (LD) after endoscopic endonasal surgery (EES) for intradural pathology does not prevent postoperative CSF leaks, a trial was conducted to assess the effect of postoperative LD on postoperative CSF leak following standard reconstruction.METHODSA prospective, randomized controlled trial of lumbar drain placement after endoscopic endonasal skull base surgery was performed from February 2011 to March 2015. All patients had 3-month follow-up data. Surgeons were blinded to which patients would or would not receive the drain until after closure was completed. An a priori power analysis calculation assuming 80% of power, 5% postoperative CSF leak rate in the no-LD group, and 16% in the LD group determined a planned sample size of 186 patients. A routine data and safety check was performed with every 50 patients being recruited to ensure the efficacy of randomization and safety. These interim tests were run by a statistician who was not blinded to the arms they were evaluating. This study accrued 230 consecutive adult patients with skull base pathology who were eligible for endoscopic endonasal resection. Inclusion criteria (high-flow leak) were dural defect greater than 1 cm2 (mandatory), extensive arachnoid dissection, and/or dissection into a ventricle or cistern. Sixty patients were excluded because they did not meet the inclusion criteria. One hundred seventy patients were randomized to either receive or not receive a lumbar drain.RESULTSOne hundred seventy patients were randomized, with a mean age of 51.6 years (range 19–86 years) and 38% were male. The mean BMI for the entire cohort was 28.1 kg/m2. The experimental cohort with postoperative LD had an 8.2% rate of CSF leak compared to a 21.2% rate in the control group (odds ratio 3.0, 95% confidence interval 1.2–7.6, p = 0.017). In 106 patients in whom defect size was measured intraoperatively, a larger defect was associated with postoperative CSF leak (6.2 vs 2.9 cm2, p = 0.03). No significant difference was identified in BMI between those with (mean 28.4 ± 4.3 kg/m2) and without (mean 28.1 ± 5.6 kg/m2) postoperative CSF leak (p = 0.79). Furthermore, when patients were grouped based on BMI < 25, 25–29.9, and > 30 kg/m2, no difference was noted in the rates of CSF fistula (p = 0.97).CONCLUSIONSAmong patients undergoing intradural EES judged to be at high risk for CSF leak as defined by the study’s inclusion criteria, perioperative LD used in the context of vascularized nasoseptal flap closure significantly reduced the rate of postoperative CSF leaks.Clinical trial registration no.: NCT03163134 (clinicaltrials.gov).

Pneumocephalus patterns following endonasal endoscopic skull base surgery as predictors of postoperative CSF leaks

2014 ◽  
Vol 121 (4) ◽  
pp. 961-975 ◽  
Author(s):  
Matei A. Banu ◽  
Oszkar Szentirmai ◽  
Lino Mascarenhas ◽  
Al Amin Salek ◽  
Vijay K. Anand ◽  
...  
Keyword(s):  
Learning Curve ◽  
Skull Base ◽  
Skull Base Surgery ◽  
Postoperative Management ◽  
Csf Leak ◽  
Histopathological Diagnosis ◽  
Endoscopic Endonasal ◽  
Postoperative Imaging ◽  
Interhemispheric Fissure ◽  
Csf Leaks

Object Postoperative pneumocephalus is a common occurrence after endoscopic endonasal skull base surgery (ESBS). The risk of cerebrospinal fluid (CSF) leaks can be high and the presence of postoperative pneumocephalus associated with serosanguineous nasal drainage may raise suspicion for a CSF leak. The authors hypothesized that specific patterns of pneumocephalus on postoperative imaging could be predictive of CSF leaks. Identification of these patterns could guide the postoperative management of patients undergoing ESBS. Methods The authors queried a prospectively acquired database of 526 consecutive ESBS cases at a single center between December 1, 2003, and May 31, 2012, and identified 258 patients with an intraoperative CSF leak documented using intrathecal fluorescein. Postoperative CT and MRI scans obtained within 1–10 days were examined and pneumocephalus was graded based on location and amount. A discrete 0–4 scale was used to classify pneumocephalus patterns based on size and morphology. Pneumocephalus was correlated with the surgical approach, histopathological diagnosis, and presence of a postoperative CSF leak. Results The mean follow-up duration was 56.7 months. Of the 258 patients, 102 (39.5%) demonstrated pneumocephalus on postoperative imaging. The most frequent location of pneumocephalus was frontal (73 [71.5%] of 102), intraventricular (34 [33.3%]), and convexity (22 [21.6%]). Patients with craniopharyngioma (27 [87%] of 31) and meningioma (23 [68%] of 34) had the highest incidence of postoperative pneumocephalus compared with patients with pituitary adenomas (29 [20.6%] of 141) (p < 0.0001). The incidence of pneumocephalus was higher with transcribriform and transethmoidal approaches (8 of [73%] 11) than with a transsellar approach (9 of [7%] 131). There were 15 (5.8%) of 258 cases of postoperative CSF leak, of which 10 (66.7%) had pneumocephalus, compared with 92 (38%) of 243 patients without a postoperative CSF leak (OR 3.3, p = 0.027). Pneumocephalus located in the convexity, interhemispheric fissure, sellar region, parasellar region, and perimesencephalic region was significantly correlated with a postoperative CSF leak (OR 4.9, p = 0.006) and was therefore termed “suspicious” pneumocephalus. In contrast, frontal or intraventricular pneumocephalus was not correlated with postoperative CSF leak (not significant) and was defined as “benign” pneumocephalus. The amount of convexity pneumocephalus (p = 0.002), interhemispheric pneumocephalus (p = 0.005), and parasellar pneumocephalus (p = 0.007) (determined using a scale score of 0–4) was also significantly related to postoperative CSF leaks. Using a series of permutation-based multivariate analyses, the authors established that a model containing the learning curve, the transclival/transcavernous approach, and the presence of “suspicious” pneumocephalus provides the best overall prediction for postoperative CSF leaks. Conclusions Postoperative pneumocephalus is much more common following extended approaches than following transsellar surgery. Merely the presence of pneumocephalus, particularly in the frontal or intraventricular locations, is not necessarily associated with a postoperative CSF leak. A “suspicious” pattern of air, namely pneumocephalus in the convexity, interhemispheric fissure, sella, parasellar, or perimesencephalic locations, is significantly associated with a postoperative CSF leak. The presence and the score of “suspicious” pneumocephalus on postoperative imaging, in conjunction with the learning curve and the type of endoscopic approach, provide the best predictive model for postoperative CSF leaks.

Sensitivity and specificity of intrathecal fluorescein and white light excitation for detecting intraoperative cerebrospinal fluid leak in endoscopic skull base surgery: a prospective study

2016 ◽  
Vol 124 (3) ◽  
pp. 621-626 ◽  
Author(s):  
Shaan M. Raza ◽  
Matei A. Banu ◽  
Angela Donaldson ◽  
Kunal S. Patel ◽  
Vijay K. Anand ◽  
...  
Keyword(s):  
Skull Base ◽  
Sensitivity And Specificity ◽  
Skull Base Surgery ◽  
False Negative ◽  
Cerebrospinal Fluid Leak ◽  
Csf Leak ◽  
Endoscopic Endonasal ◽  
Predictive Values ◽  
Endoscopic Skull Base Surgery ◽  
Csf Leaks

OBJECT The intraoperative detection of CSF leaks during endonasal endoscopic skull base surgery is critical to preventing postoperative CSF leaks. Intrathecal fluorescein (ITF) has been used at varying doses to aid in the detection of intraoperative CSF leaks. However, the sensitivity and specificity of ITF at certain dosages is unknown. METHODS A prospective database of all endoscopic endonasal procedures was reviewed. All patients received 25 mg ITF diluted in 10 ml CSF and were pretreated with dexamethasone and Benadryl. Immediately after surgery, the operating surgeon prospectively noted if there was an intraoperative CSF leak and fluorescein was identified. The sensitivity, specificity, and positive and negative predictive power of ITF for detecting intraoperative CSF leak were calculated. Factors correlating with postoperative CSF leak were determined. RESULTS Of 419 patients, 35.8% of patients did not show a CSF leak. Fluorescein-tinted CSF (true positive) was noted in 59.7% of patients and 0 false positives were encountered. CSF without fluorescein staining (false negative) was noted in 4.5% of patients. The sensitivity and specificity of ITF were 92.9% and 100%, respectively. The negative and positive predictive values were 88.8% and 100%, respectively. Postoperative CSF leaks only occurred in true positives at a rate of 2.8%. CONCLUSIONS ITF is extremely specific and very sensitive for detecting intraoperative CSF leaks. Although false negatives can occur, these patients do not appear to be at risk for postoperative CSF leak. The use of ITF may help surgeons prevent postoperative CSF leaks by intraoperatively detecting and confirming a watertight repair.

From research to clinical practice: long-term impact of randomized clinical trial examining the effect of lumbar drains on cerebrospinal fluid leak rates following endonasal skull base surgery.

2021 ◽  
Author(s):  
Philippe Lavigne ◽  
paul gardner ◽  
Eric W Wang ◽  
Carl H. Snyderman
Keyword(s):  
Cerebrospinal Fluid ◽  
Skull Base ◽  
Controlled Trial ◽  
Posterior Cranial Fossa ◽  
Csf Leak ◽  
Endoscopic Endonasal ◽  
Increased Risk ◽  
Cranial Fossa ◽  
Csf Diversion ◽  
Csf Leaks

Intraoperative cerebrospinal fluid (CSF) leaks are associated with increased risk of post-operative CSF leaks despite multilayered reconstruction with vascularized tissue. A recent randomized controlled trial (RCT) examining the use of peri-operative lumbar drains (LD) in high-risk skull base defects identified a significant reduction in post-operative CSF leak incidence (21.2% vs. 8.2%; p=0.017). This study was conducted to assess the efficacy of the selective use of CSF diversion, for patients with intraoperative CSF leaks involving endoscopic endonasal approaches (EEA) to the skull base. Method: Consecutive endoscopic endonasal surgeries of the skull base from a pre-RCT cohort and post-RCT cohort were compared. The following case characteristics between the two cohorts were examined: patient age, body mass index (BMI), rate of revision surgery, tumor histology, use of CSF diversion, and vascularized reconstruction. The primary measured outcome was post-operative CSF leak. Results: The pre-RCT cohort included 76 patients and the post-RCT cohort, 77 patients, with dural defects in either the anterior or posterior cranial fossa (pituitary and parasellar/suprasellar surgeries excluded). There was a significant reduction in the incidence of post-operative CSF leak in the post-RCT cohort (27.6% vs. 12.9%; p=0.04). On subgroup analysis, there was a trend toward improvement in CSF leak rate of the anterior cranial fossa (19.2% vs 10.5%; p=0.27) whereas CSF leak rates of the posterior cranial fossa were significantly reduced compared to the pre-RCT cohort (41.4% vs 12.8%; p=0.02). Conclusion This study demonstrates that the integration of selective CSF diversion into the reconstructive algorithm improved post-operative CSF leak rates.

Detection of Cerebrospinal Fluid Leaks Using the Endoscopic Fluorescein Test in the Post-Operative Period Following Pituitary and Ventral Skull Base Surgery

2021 ◽  
Author(s):  
Peter A. Benedict ◽  
Joseph R. Connors ◽  
Micah R. Timen ◽  
Nupur Bhatt ◽  
Richard Lebowitz ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Skull Base ◽  
Postoperative Period ◽  
Skull Base Surgery ◽  
Tertiary Care ◽  
Csf Leak ◽  
Csf Rhinorrhea ◽  
Predictive Values ◽  
Ventral Skull Base ◽  
Csf Leaks

Objective: Diagnosis of cerebrospinal fluid (CSF) leaks is sometimes challenging in the postoperative period following pituitary and ventral skull base surgery. Intrathecal fluorescein (ITF) may be useful in this setting. Design: Retrospective chart review Setting: Tertiary care center Methods and Participants: All patients who underwent pituitary and ventral skull base surgery performed by a single rhinologist between January 2017–March 2020 were included. There were 103 patients identified. Eighteen patients received 20 ITF injections due to clinical suspicion for CSF leak during the postoperative period without florid CSF rhinorrhea on clinical exam. Computed tomography scans with new or increasing intracranial air and intra-operative findings were used to confirm CSF leaks. Clinical courses were reviewed for at least 6 months after initial concern for leak as the final determinate of CSF leak. Main Outcome Measures: Specificity and safety of ITF Results: Eleven (61%) ITF patients were female and 7 (39%) were male. Average patient age was 52.50±11.89. There were 6 patients with confirmed postoperative CSF leaks, 3 of whom had evaluations with ITF. ITF use resulted in 2 true positives, 1 false negative, 17 true negatives and 0 false positives. ITF sensitivity was 67%, specificity was 100%, and positive and negative predictive values were 100% and 94.4%, respectively. There were no adverse effects from ITF use. Conclusions: Existing modalities for detecting postoperative CSF leaks suffer from suboptimal sensitivity and specificity, delayed result reporting, or limited availability. Intrathecal fluorescein represents a specific and safe test with potential utility in the postoperative setting.

Outcomes In Pediatric Endoscopic Skull Base Surgery: A Systematic Review

2021 ◽  
Author(s):  
Erin Mamuyac Lopez ◽  
Zainab Farzal ◽  
Kelly Marie Dean ◽  
Craig Miller ◽  
Justin Cates Morse ◽  
...  
Keyword(s):  
Systematic Review ◽  
Skull Base ◽  
Pediatric Patients ◽  
Skull Base Surgery ◽  
Tertiary Care ◽  
Case Series ◽  
Csf Leak ◽  
Inclusion Criteria ◽  
Endoscopic Skull Base Surgery ◽  
Tertiary Care Medical Center

Objectives: The frequency of endoscopic skull base surgery in pediatric patients is increasing. This study’s aim is to systematically review the literature for endoscopic skull base surgery outcomes in children/adolescents ages 0-18 years. Design: A systematic review of the literature was performed in PubMed and SCOPUS databases querying studies from 2000-2020 using PRISMA guidelines. Final inclusion criteria included: case series with 10+ patients with pediatric patients age ≤18 years, endoscopic or endoscopic-assisted skull base surgery, and outcomes reported. Setting: Tertiary care medical center Participants: Children/adolescents ages 0-18 years who underwent endoscopic skull base surgery Main Outcome Measures: Patient demographics, pathology, reconstructive technique, intra-operative findings, intra-operative and post-operative surgical complications. Results: Systematic literature search yielded 287 publications. Of these, 12 studies discussing a total of 399 patients age 0-18 years met inclusion criteria for final analysis. 7 of 12 studies discussed a single pathology. The most common pathology was a skull base defect causing CSF leak. The majority of skull base repairs were made with free tissue grafts. The most common post-operative complication was CSF leak (n=40). Twelve cases of meningitis occurred post-operatively with two of these episodes resulting in death. Conclusions: Endoscopic skull base surgery has been performed recently in the pediatric population in a variety of disease states. Inconsistent individual-level data and reporting standards are present in existing studies posing challenges for comparative analysis. Standardized reporting will aid future reviews and meta-analysis for rare skull base pathology.

scholarly journals Endoscopic Endonasal Reconstruction of High-Flow Cerebrospinal Fluid Leak with Fascia Lata “Button” Graft and Nasoseptal Flap: Surgical Technique and Case Series

2019 ◽  
Vol 81 (06) ◽  
pp. 645-650
Author(s):  
Roshni V. Khatiwala ◽  
Karthik S. Shastri ◽  
Maria Peris-Celda ◽  
Tyler Kenning ◽  
Carlos D. Pinheiro-Neto
Keyword(s):  
Cerebrospinal Fluid ◽  
Skull Base ◽  
Fascia Lata ◽  
High Flow ◽  
Csf Leak ◽  
Nasoseptal Flap ◽  
Endoscopic Endonasal ◽  
Skull Base Reconstruction ◽  
Csf Diversion ◽  
Csf Leaks

Abstract Background The endoscopic endonasal approach (EEA) has become increasingly used for resection of skull base tumors in the sellar and suprasellar regions. A nasoseptal flap (NSF) is routinely used for anterior skull base reconstruction; however, there are numerous additional allografts and autografts being used in conjunction with the NSF. The role of perioperative cerebrospinal fluid (CSF) diversion is also unclear. Objective This study was aimed to analyze success of high-flow CSF leak repair during EEA procedures without use of CSF diversion through lumbar drainage. Methods A retrospective chart review of patients who had intraoperative high-flow CSF leak during EEA procedures at our institution between January 2013 and December 2017 was performed. CSF leaks were repaired with use of a fascia lata button graft and nasoseptal flap, without use of perioperative lumbar drains. Results A total of 38 patients were identified (10 male, 28 female). Patient BMIs ranged from 19.7 to 49 kg/m2 (median = 31 kg/m2), with 18 patients meeting criteria for obesity (BMI > 30 kg/m2) and 12 patients overweight (25 kg/m2 < BMI < 29.9 kg/m2). There was no incidence of postoperative CSF leak. Conclusion In our experience, the nasoseptal flap used in conjunction with the fascia lata button graft is a safe, effective and robust combination for cranial base reconstruction with high-flow intraoperative CSF leaks, without need for lumbar drains.

scholarly journals Effects of nasal lavage with and without mupirocin after endoscopic endonasal skull base surgery: a randomised, controlled study

2019 ◽  
Vol 133 (12) ◽  
pp. 1059-1063
Author(s):  
B H K Ng ◽  
I P Tang ◽  
P Narayanan ◽  
R Raman ◽  
R L Carrau
Keyword(s):  
Skull Base ◽  
Skull Base Surgery ◽  
Controlled Trial ◽  
Nasal Lavage ◽  
Nasal Endoscopy ◽  
Controlled Study ◽  
Endoscopic Endonasal ◽  
Randomised Controlled Study ◽  
Skull Base Lesions ◽  
Randomised Controlled

AbstractBackgroundNasal lavage with mupirocin has the potential to reduce sinonasal morbidity in endoscopic endonasal approaches for skull base surgery.ObjectiveTo evaluate the effects of nasal lavage with and without mupirocin after endoscopic endonasal skull base surgery.MethodsA pilot randomised, controlled trial was conducted on 20 adult patients who had undergone endoscopic endonasal approaches for skull base lesions. These patients were randomly assigned to cohorts using nasal lavages with mupirocin or without mupirocin. Patients were assessed in the out-patient clinic, one week and one month after surgery, using the 22-item Sino-Nasal Outcome Test questionnaire and nasal endoscopy.ResultsPatients in the mupirocin nasal lavage group had lower nasal endoscopy scores post-operatively, and a statistically significant larger difference in nasal endoscopy scores at one month compared to one week. The mupirocin nasal lavage group also showed better Sino-Nasal Outcome Test scores at one month compared to the group without mupirocin.ConclusionNasal lavage with mupirocin seems to yield better outcomes regarding patients’ symptoms and endoscopic findings.

Predictors and incidence of orthostatic headache associated with lumbar drain placement following endoscopic endonasal skull base surgery

2017 ◽  
Vol 159 (8) ◽  
pp. 1379-1385 ◽  
Author(s):  
Buqing Liang ◽  
Sathwik R. Shetty ◽  
Sacit Bulent Omay ◽  
Joao Paulo Almeida ◽  
Shilei Ni ◽  
...  
Keyword(s):  
Skull Base ◽  
Skull Base Surgery ◽  
Orthostatic Headache ◽  
Endoscopic Endonasal ◽  
Lumbar Drain ◽  
Drain Placement

Is a Single-Dose, Single-Agent Perioperative Antibiotic Protocol Adequate for Endoscopic Endonasal Skull Base Surgery? A 10-Year Review of 422 Cases

2020 ◽  
Author(s):  
Mark A. Hughes ◽  
Nick Phillips ◽  
Atul Tyagi ◽  
Asim Sheikh ◽  
Kavita Sethi ◽  
...  
Keyword(s):  
Single Dose ◽  
Skull Base ◽  
Skull Base Surgery ◽  
Single Agent ◽  
Prophylactic Antibiotic ◽  
Antibiotic Use ◽  
Anterior Skull Base ◽  
Csf Leak ◽  
Endoscopic Endonasal ◽  
Postoperative Meningitis

Abstract Objectives Postoperative meningitis is a rare but potentially fatal complication of endoscopic endonasal skull base surgery. Prophylactic antibiotic use varies considerably worldwide. We sought to analyze the safety of a single-agent, single-dose protocol. Design, Setting, and Participants A retrospective review of 422 procedures performed during 404 admission episodes from 2009 to 2019, encompassing sella, parasella, and other anterior skull base pathologies. Main Outcome Measures Primary outcome measure was development of meningitis within 30 days of surgery. Additional information collected: underlying pathological diagnosis, intraoperative cerebrospinal fluid (CSF) leak, postoperative CSF leak, and primary or revision surgery. Results Of 404 admission episodes for endoscopic anterior skull base surgery, 12 cases developed meningitis. Seven had positive CSF cultures and all 12 recovered. For pathology centered on the sella (including pituitary adenoma), the rate of meningitis was 1.1% (3/283). For pathologies demanding an extended approach (including meningioma and craniopharyngioma), the rate of meningitis was 14.5% (9/62). Postoperative CSF leak requiring surgical repair increased the relative risk by 37-fold. There were no cases of meningitis following repair of long-standing CSF fistula or encephalocoele (0/26) and no cases following surgery for sinonasal tumors with skull base involvement (0/33). Conclusion For sella-centered pathologies, a single dose of intravenous co-amoxiclav (or teicoplanin) is associated with rates of meningitis comparable to those reported in the literature. Postoperative meningitis was significantly higher for extended, intradural transphenoidal approaches, especially when postoperative CSF leak occurred. Fastidious efforts to prevent postoperative CSF leak are crucial to minimizing risk of meningitis.

Safety and Efficacy of TachoSil (Absorbable Fibrin Sealant Patch) Compared With Current Practice for the Prevention of Cerebrospinal Fluid Leaks in Patients Undergoing Skull Base Surgery: A Randomized Controlled Trial

Neurosurgery ◽  
2017 ◽  
Vol 80 (6) ◽  
pp. 847-853 ◽  
Author(s):  
Bernard George ◽  
Christian Matula ◽  
Lars Kihlström ◽  
Enrique Ferrer ◽  
Vilhelm Tetens
Keyword(s):  
Cerebrospinal Fluid ◽  
Skull Base ◽  
Dura Mater ◽  
Primary Endpoint ◽  
Current Practice ◽  
Skull Base Surgery ◽  
Csf Leak ◽  
Similar Frequency ◽  
Csf Leakage ◽  
Csf Leaks

Abstract BACKGROUND: Cerebrospinal fluid (CSF) leakage associated with incomplete sealing of the dura mater is a major complication of intradural procedures. OBJECTIVE: To compare the efficacy and safety of adjunctive TachoSil (Takeda Pharma A/S, Roskilde, Denmark) with current practice for the prevention of postoperative CSF leaks in patients undergoing elective skull base surgery involving dura mater closure. METHODS: Patients were intraoperatively randomized to TachoSil or current practice immediately before primary dura closure by suturing ± duraplasty. Choice of adjunctive treatment in the current practice group was at the surgeon's discretion. Primary efficacy endpoint was occurrence of clinically evident verified postoperative CSF leak or clinically evident pseudomeningocele within 7 weeks after surgery or treatment failure (third application of trial treatment or use of other treatment). RESULTS: A total of 726 patients were randomized to TachoSil (n = 361) or current practice (n = 365). More current practice patients had sutures plus duraplasty for primary dura closure compared with TachoSil (49.6% vs 35.7%) and fewer had sutures only (45.5% vs 63.2%). The primary endpoint of estimated leak rate favored TachoSil with events in 25 (6.9%) patients vs 30 (8.2%) current practice patients; however, this was not statistically significant (odds ratio: 0.82; 95% confidence interval: 0.47, 1.43; P = .485). Both treatments were well tolerated with similar frequency of adverse events. CONCLUSION: Very low rates of postoperative CSF leaks can be achieved in patients undergoing skull base surgery of various indications. Although the study did not meet its primary endpoint, TachoSil appears to be safe and effective for the prevention of CSF leaks and associated complications.

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