Abstract
Study Design:
Retrospective cohort study.
Objectives:
To investigate the effectiveness and safety of a gelatin–thrombin matrix sealant (GTMS) during microendoscopic laminectomy (MEL) for lumbar spinal canal stenosis (LSCS).
Methods:
This study included 158 LSCS cases on hemostasis-affecting medication who underwent MEL by a single surgeon between September 2016 and August 2020. Patients were divided into 2 groups depending on whether GTMS was used (37 cases, Group A) or not (121 cases, Group B). Perioperative data related to bleeding or postoperative spinal epidural hematoma (PSEH) was investigated. Clinical outcomes were evaluated using the Japanese Orthopedic Association (JOA) score for low back pain.
Results:
The mean intraoperative blood loss per level was greater in Group A (26.0 ± 20.3 g) than in Group B (13.6 ± 9.0 g), whereas the postoperative drainage volume was smaller in Group A (79.1 ± 42.5 g) than in Group B (97.3 ± 55.6 g). No revision surgeries for PSEH were required in Group A, while 2 (1.7%) revisions were required in Group B (P = .957). The median JOA score improved significantly from the preoperative period to 1-year postoperatively in both Group A and B (total score, 16.0-23.5 and 17.0-25.0 points, respectively).
Conclusions:
The use of GTMS during MEL for LSCS may be associated with a reduction in postoperative drainage volume. The revision rate for PSEH was not affected significantly by the use of GTMS. Clinical outcomes (represented by the JOA score) were significantly improved after the surgery, regardless of GTMS use during MEL.
Keywords
Introduction
Microendoscopic laminectomy (MEL), which allows bilateral decompression via a unilateral approach, 1 has gained interest as a minimally invasive surgery for lumbar spinal canal stenosis (LSCS) and has demonstrated good clinical results. 2 The safety of microendoscopic spinal surgery was established in a nationwide survey conducted in 2018 by the Committee on Spinal Endoscopic Surgical Skill Qualification of the Japanese Orthopaedic Association (JOA). 3 The most common complication of MEL noted in this survey was dural injury (3.4%), followed by hematoma (0.57%) and infection (0.12%). The restricted working space in MEL, however, theoretically poses disadvantages, compared with conventional open surgery, once postoperative spinal epidural hematoma (PSEH) has formed. 4 Although most PSEHs are reportedly asymptomatic or accompanied by mild symptoms, 5 they are regarded as a poor prognostic factor for microendoscopic surgery. 6
The incidence of PSEH in spinal surgery is low (0.1%-0.2%).3,7-10 However, the incidence of PSEH in microendoscopic decompression surgery is relatively high (33%-67.6%), as observed in magnetic resonance imaging (MRI) studies.5,6 Nakagawa and Yoshida reported that 51.4% of the cross-sectional area of the spinal canal was occupied by PSEH in patients who had experienced transient neurological deterioration after MEL. 6 Other complications associated with MEL, such as dural injury, cauda injury, and facet fracture, were markedly reduced in this study by improvements in the procedure or the surgeons’ technique. 7
Use of a human gelatin–thrombin matrix sealant (GTMS) is indicated in surgical procedures as an adjunct to hemostasis when bleeding-control measures are ineffective. 11 GTMS is a biocompatible hemostatic matrix composed of bovine gelatin matrix and human-derived thrombin. GTMS is used in several surgical fields, 5 including spinal surgery. 12 However, the literature on the effectiveness or efficacy of GTMS in microendoscopic spine surgery is sparse and conflicting. In a recent MRI study, Kim et al. found GTMS to be effective in biportal endoscopic spine surgery: the incidence of PSEH was decreased by half, and high-grade PSEH was prevented when GTMS was used. 13 The authors also demonstrated greater improvement in clinical outcomes postoperatively, such as visual analog scale (VAS) scores of leg pain with the use of GTMS. However, in another recent randomized controlled trial (RCT) by Takami et al., the prophylactic application of GTMS during MEL did not substantially affect the extent of PSEH, as assessed both by direct measurement of drainage and postoperative surveillance MRI. 14
In our clinical practice, with the increasing average age of patients undergoing microendoscopic spinal surgery, 15 the preoperative use of antiplatelet drugs, anticoagulants, and vasodilating drugs is more frequent. Where possible, these medications are discontinued before surgery, and drains are routinely left in place after MEL in order to prevent PSEH. There are limited reports in the literature demonstrating the effectiveness of GTMS on hemostasis during MEL in patients with a history of using drugs affecting hemostasis.
The purpose of the present study was to investigate the effectiveness and safety of using GTMS in MEL, particularly in patients taking medications that affect hemostasis, with a focus on blood loss and the need for revision surgery due to PSEH.
Methods
This retrospective cohort study included patients with LSCS who underwent MEL, performed by the same surgeon (KN), between September 2016 and August 2020, at a single institute. All patients had been diagnosed with LSCS based on clinical findings, MRI, computed tomography, and additional examinations, including radicular block and electromyography, as needed. All patients had complained of leg symptoms, for which at least 3 months of conservative treatment had proven ineffective. To improve the homogeneity of the data, only patients who were taking medication affecting hemostatic ability, including antiplatelet drugs, anticoagulants, and vasodilating drugs, continuously preoperatively were included. These medications were ceased prior to surgery (depending on the non-dosing period) and were resumed after drain removal. Cases with complications other than PSEH, such as dural injury, were excluded. The included patients were divided into 2 groups depending on whether GTMS was used during surgery. Patients for whom GTMS was applied were assigned to Group A; those for whom GTMS was not applied were assigned to Group B. We obtained patients’ written informed consent for the study as well as for the surgery. The study was approved by the ethics committee of the hospital (#20 001).
The surgical procedure employed was MEL via the paramedian approach, as described by Nomura and Yoshida. 1 The patient, under general anesthesia, was placed in a prone position on a laminectomy frame. The METRx® microendoscopy system (Medtronic Sofamor Danek, Memphis, TN, USA) or the SYNCHA® microendoscopy system (KiSCO Co. Ltd., Kobe, Hyogo, Japan) was used for the surgery. These systems differed in terms of the structure of the rigid endoscope and the tubular retractor grasper, but the surgical procedures were identical. A 16 mm skin incision and a fasciotomy were made for every surgical level. The muscles were sequentially dilated, and a tubular retractor (16 mm diameter) was placed. After muscle removal, the base of the spinous process was resected with a high-speed drill to secure sufficient working space, and the tip of the tubular retractor was advanced to the midline of the lamina. The lamina was resected as far as the attachment of the ligament flavum to the lamina. Then, the ligament flavum was detached from the bone. The ligament was split from the midline, like “French doors,” using a ball-tipped probe, and resected. The lateral recess was enlarged while keeping the facet joint intact. The decompression endpoint was the outer edges of the bilateral nerve roots. When hemostasis with a bipolar coagulator was insufficient, bone wax (LUKENS® Bone Wax; Tokyo MI Co, Inc., Chuo-ku, Tokyo, Japan) was used for the osseous tissue and an absorbable microfibrillar collagen hemostat sheet (Integran® Sheet; Koken Co. Ltd., Bunkyo-ku, Tokyo, Japan) was used for soft tissues. When bleeding control was insufficient even after implementation of these conventional hemostatic procedures, use of GTMS (Floseal®; Baxter International, Inc., Deerfield, IL, USA) was considered.
The GTMS was injected at the bleeding sites, most of which were adjacent to the nerve root. Two minutes after injection, the complex of GTMS and blood clots was flushed and removed. This procedure was repeated until adequate hemostasis was achieved. Usually, 5 mL of GTMS was sufficient. After lavage, a closed low-pressure drainage catheter (3.5 mm diameter; Argyle® Multi-channel Drainage Catheter S; Cardinal Health Inc., Dublin, OH, USA) was placed at every surgical level, and up to 2 drainage catheters were connected to a 300-mL vacuum reservoir (Argyle® Multi-channel Pump Flap Type; Cardinal Health Inc., Dublin, OH, USA). The incision was closed in layers using 2-0 Vycryl Plus® (Ethicon Inc., Somervill, NJ, USA) and Steri-Strips® (3 M Health Care, St. Paul, MN, USA). Ambulation without a brace was allowed 5 hours after the surgery. When the drainage reservoir was full, the fluid content was removed. The fluid collected in the reservoir(s) was weighed with an electronic scale (KD-192; Tanita Co. Ltd., Itabashi-ku, Tokyo, Japan). Drains were removed 2 days after surgery. Most patients were discharged from the hospital at 6 to 8 days post-surgery.
For all enrolled patients in each study group, the following factors were abstracted from the patient records: age, gender, preoperative platelet count, preoperative activated partial thromboplastin time (APTT), preoperative prothrombin time (PT), systolic and diastolic blood pressure at administration, systolic and diastolic blood pressure at return from the operative room, history of medication affecting hemostatic ability, history of hypertension care, number of decompressed levels, and levels of stenosis. Surgical time per intervertebral level (total surgical time divided by the number of decompressed intervertebral levels), blood loss per intervertebral level (total intraoperative blood loss divided by the number of decompressed intervertebral levels), and drainage volume per intervertebral level (obtained analogously) were compared between groups by the unpaired t-test. The need for revision surgery for PSEH was compared between groups by the chi-square test. For patients who attended follow-up examinations for at least 1 year, the JOA score for low back pain (LBP), 16 graded on a 29-point scale (Table 1), was measured preoperatively and at 1-year postoperatively and compared between Groups A and B. The JOA score for LBP (total score and scores for subjective symptoms: LBP, leg pain and/or tingling, and gait) was compared using the Wilcoxon signed-rank test for intragroup comparisons and the Mann-Whitney U test for intergroup comparisons. Probability values of <0.05 were considered statistically significant.
Japanese Orthopedic Association Score for Low Back Pain (29-Point Scale) (From the Report by Inoue et al 16 ).
Results
Overall, 461 patients with LSCS underwent MEL, performed by the same surgeon, during the study period, of whom 158 patients met the inclusion criteria. Thirty-seven patients were assigned to Group A and 121 patients to Group B. Of these 158 patients, 101 (24 in Group A and 77 in Group B) had been followed up for at least 1 year at the time of data collection. Data from these patients was used to compare JOA scores for LBP.
Baseline Characteristics
The mean age was 73.9 ± 8.6 years in Group A and 72.9 ± 7.5 years in Group B. There were 20 (54.1%) men and 17 (46.9%) women in Group A and 68 (56.2%) men and 53 (43.8%) women in Group B. No significant differences in baseline demographics, including preoperative platelet count, APTT, PT, or blood pressure, were identified between patients in Groups A and B (Table 2). A history of medication affecting hemostatic ability or hypertensive care did not statistically differ between Groups A and B. The mean number of decompressed levels was 1.9 ± 0.8 in Group A and 2.0 ± 0.9 in Group B. Procedural criteria did not differ significantly between patients in Groups A and B (Table 3).
Baseline characteristics.
Abbreviations: APTT, activated partial thromboplastin time; PT, prothrombin time; SBP, systolic blood pressure; DPB, diastolic blood pressure; OR, operative room.
* Unpaired t-test, mean ± SD, ** Chi-square test.
Group A: GTMS used; Group B: GTMS not used.
Disease and Procedural Characteristics.
Antiplatelet drugs: Aspirin, Aspirin and dialuminate, Ticlopidine hydrochloride, Clopidogrel bisulfate, Cilostazol, Icosapent ethyl, Omega-3-acid ethyl esters, Ticagrelor, Beraprost sodium, Sarpogrelate hydrochloride, Dipyridamole.
Anticoagulants: Warfarin potassium, Rivaroxaban, Edoxaban, Apixaban.
Vasodilating drug: Limaprost alfadex.
* Chi-square test, ** Unpaired t-test.
Group A: GTMS used; Group B: GTMS not used.
Procedural Outcomes and Complications
The mean surgical time per level in Group A was significantly longer than that in Group B (61.4 ± 18.1 minutes vs. 55.5 ± 18.0 minutes; P = .041). The mean intraoperative blood loss per level in Group A was 26.0 ± 20.3 g, which was significantly greater than that observed in Group B (13.6 ± 9.0 g; P < .001). In contrast, the mean drainage volume per level in Group A (79.1 ± 42.5 g) was significantly smaller than that in Group B (97.3 ± 55.6 g; P = .034). None of the patients in Group A required revision surgery for PSEH, whereas 2 (1.7%) required revision surgery in Group B (P = .957, Table 4). These patients, who had progressive leg palsy and severe leg pain accompanied by PSEH occupying 50% to 75% of the cross-sectional area of the spinal canal on MRI after the first surgery, recovered without neurological deterioration shortly after the second surgery.
Surgical Results Per Decompressed Level and Revision Surgery for PSEH.
Abbreviation: PSEH, postoperative spinal epidural hematoma.
* Unpaired t-test, Mean ± SD; **Chi-square test.
Group A: GTMS used; Group B: GTMS not used.
Clinical Outcomes
The median JOA score for LBP (total score) in Group A improved significantly from 16.0 (range, 8-21) preoperatively to 23.5 (range, 14-28, P < .001) at 1 year postoperatively. The median JOA score in Group B also improved significantly from 17.0 (range, 8-25 points) preoperatively to 25.0 (range, 12-29 points; P < .001) at 1 year postoperatively. The median scores for LBP, leg pain and/or tingling, and gait were all improved significantly in the both groups at 1 year postoperatively. Intergroup comparisons revealed no significant differences in these scores preoperatively or 1 year postoperatively (Table 5).
Clinical Outcomes Represented by JOA Score for LBP.
Abbreviations: JOA, Japanese Orthopedic Association; LBP, low back pain; LP/T, leg pain and/or tingling; Preop., preoperatively; Postop., postoperatively.
* Wilcoxon signed-rank test; **Mann-Whitney U test.
Group A: GTMS used; Group B: GTMS not used.
Discussion
The present study is unique in the following 2 aspects: it demonstrated the effectiveness of GTMS use during MEL for LSCS on drainage volume through comparison of 158 cases operated on by a single surgeon at a single institution and only those with preoperative continuous use of medication affecting hemostatic ability were included. This study demonstrated that cases with therapeutic GTMS application required longer surgical time and bled more intraoperatively. These results are consistent with the finding that it was more difficult to manage intraoperative bleeding during MEL in Group A. In contrast, postoperative drainage volume was smaller in Group A. This leaves the question about why there was a difference in the postoperative drainage volume between the groups if the GTMS was flushed out and removed during surgery. Assuming that most of the drainage fluid resulted from postoperative bleeding, we considered that this difference was due to the hemostatic state at the end of the surgery. The surgeon, who had experience of over 3,000 microendoscopic spinal surgeries, confirmed the hemostasis prior to closure, irrespective of whether GTMS was used. It is possible that this hemostatic state, in some cases, might have been unable to endure high blood pressure that was created during extubation and thereafter. Although it was difficult to control intraoperative bleeding in Group A, hemostasis per se might have been sufficiently reinforced by the application of GTMS to resist a subsequent blood pressure increase.
Gelatin-thrombin matrix sealant (Floseal®, formerly Fusion Matrix Hemostatic Sealant®, by Fusion Medical Technologies, Inc.) was first approved in Canada in 1997. It was approved in the European Union in 1998 and by the US Food and Drug Administration in the United States in 1999. It is a biocompatible hemostatic matrix composed of bovine gelatin matrix and human-derived thrombin. GTMS exerts its hemostatic effects through multiple mechanisms. The gelatin matrix material, which swells when it comes into contact with blood, ensures hemostasis through a tamponade effect and provides a stable platform for fibrin clot formation, triggered by the presence of thrombin. 17 GTMS is used for surgeries in several surgical fields, 11 including spinal surgery. 12 However, there have been few reports demonstrating the effectiveness of GTMS on blood loss when used for microendoscopic spinal surgery.
The present study demonstrated that postoperative drainage volume was smaller in MEL cases with intraoperative therapeutic GTMS application. Kudo et al. 18 reported that they performed MELs according to Nomura and Yoshida’s procedure 1 on 48 patients with LSCS. For half of the patients, they used GTMS during surgery. They then analyzed the effectiveness of GTMS on blood loss by comparing the 2 groups. They reported a significant difference only in postoperative blood loss, as assessed from drainage content, not in terms of intraoperative blood loss per level or in the rate of anticoagulant use, as in our study. The small sample size, recognized by those authors as a limitation, may be responsible for the differences observed between their results and our findings. Recently, Takami et al. reported that the prophylactic application of GTMS during MEL, using essentially the same surgical procedures as ours, did not substantially contribute to any change in postoperative epidural hematoma, which was assessed both by direct measurement of drainage and by postoperative surveillance MRI. 14 In the RCT, patients with a bleeding predisposition, using anticoagulant/antiplatelet medication, were excluded and GTMS for prophylactic use was applied after sufficient hemostasis was achieved at the final stage of surgery. However, in current daily clinical practice, many patients have a history of using medication affecting hemostatic ability, and GTMS is applied to control ongoing bleeding, as in the eligible cases in this study. An important clinical implication of the above RCT was that routine use of GTMS after minimally invasive decompression in microendoscopic surgery was not advised. Furthermore, the present study added the clinical implication that the therapeutic use of GTMS during MEL reduces postoperative drainage volume, which may reflect the reduced postoperative blood loss.
Nomura and Yoshida reported that intraoperative blood loss per level stabilizes after a novice surgeon’s first 30 MELs. 7 Complications associated with MEL, other than PSEH, such as dural tears, have been markedly reduced by improving the procedure itself as well as the surgeons’ technique.1,7 PSEH, which can cause compression of the dural sac and lead to neurological deterioration, is regarded as a poor prognostic factor in spinal decompression surgery. 6 A significant discrepancy, however, was also reported between imaging findings and actual PSEH symptoms, with most of the patients being asymptomatic or experiencing only mild symptoms that subsided spontaneously. 5 In the present study, only 2 cases in the GTMS non-use group required revision surgeries for PSEH, but the rate was not significantly different between the 2 groups; the revision rate was 1.3% (2/158) overall. Kim et al. reported that revision surgery for PSEH was performed in 1.0% (2/206) of LSCS cases overall who were treated with biportal endoscopic spine surgery; this rate was not significant, irrespective of whether GTMS was used. 13 Using an MRI study, they reported that the incidence of PSEH in the GTMS-used group (13.5%) was decreased by half compared to that in the non-used group (26.5%). On the other hand, Takami et al. reported that the area of hematoma measured by MRI 3 to 5 days after surgery was not significantly different, irrespective of whether GTMS was used prophylactically. 14 Therefore, intraoperative GTMS use, whether used therapeutically or prophylactically, may not necessarily reduce PSEH formation or the rate of revision surgery.
The present study demonstrated a smaller drainage volume (reduced by 18.2 g on average) in the GTMS-used group by 2 days after surgery. A tubular retractor (16 mm diameter) was inserted into the body. Assuming that the depth was 6 to 8 cm, the calculated free space dorsal to the decompressed dura was approximately 20 cm3, at most. Hence the difference of 18.2 g in the mean drainage volume did not seem minor, although the revision rate for PSEH did not differ regardless of use of GTMS. We explored the method of preventing PSEH requiring revision surgery. The present study may not adequately prove that a smaller drainage volume could decrease PSEH. The relationship between the postoperative drainage volume and PSEH under therapeutic GTMS use for MEL requires detailed investigation with a sufficient sample size in future, which appears to be 720 cases according to calculations under the same conditions.
Clinical outcomes represented by the JOA score for LBP (total score) were significantly improved at 1 year after surgery in this study, irrespective of whether GTMS was used. JOA scores for subjective symptoms assessed on a 3-point scale for LBP, leg pain and/or tingling, and gait had significantly improved 1 year postoperatively in both groups, and the intergroup comparison revealed no significant differences in scores between Groups A and B. In this retrospective study, the JOA score was the only method of assessing clinical outcomes. To elucidate the effectiveness of GTMS on clinical outcomes, it is necessary to implement the VAS and other scoring systems, such as the Oswestry Disability Index, in addition to the JOA score for further survey. At least from the viewpoint of the JOA score, it appears that GTMS use does not place patients at an increased risk of adverse clinical outcomes at 1 year postoperatively.
Our study is not without any limitations. First, it was retrospective in nature. Second, during the surgery, the surgeon determined the indication for GTMS. Depending on the magnitude of bleeding, hemostatic management before use of GTMS varied. Third, although absorbable microfibrillar collagen hemostat sheets were removed immediately before GTMS use, the interaction between these was not considered. Fourth, patients with follow-up of less than 1 year were also included, as our main goal was to investigate perioperative data related to bleeding. Although clinical outcomes represented by the JOA score for LBP were compared only in patients with follow-up of at least 1 year, a longer follow-up period may be useful. Further randomized controlled trials evaluating the efficacy of GTMS in comparison with other hemostatic adjuncts would be beneficial to elucidate the role of GTMS in minimally invasive surgery. However, such studies may be impractical to perform in treatments covered by public health insurance.
Conclusions
The use of GTMS during MEL for LSCS reduced postoperative drainage volume, which may be related to a reduction in postoperative blood loss. Clinical outcomes represented by the JOA score for LBP (total score and scores for subjective symptoms) had significantly improved 1 year postoperatively, irrespective of whether or not GTMS was used, and the scores did not significantly differ between patients in the 2 groups. GTMS may reduce postoperative blood loss but does not affect the incidence of PSEH.
Footnotes
Authors’ Note
We obtained patients’ written informed consent for the study as well as for the surgery. The study was approved by the Ethics Committee of Sumiya Orthopaedic Hospital (#20001).
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
