Keywords
gelatin–thrombin matrix sealants - intraoperative blood loss - lumbar disc herniation
- minimally invasive microscopic discectomy - postoperative drainage volume - tubular
retractor
Introduction
Sciatica is often caused by lumbar disc herniation (LDH).[1] Patients with LDH often have a good natural history, and conservative treatment
is the initial treatment of choice.[2] Surgery is recommended when patients with intractable pain are refractory to conservative
treatment or experience progressive neuropathy.[3]
Since the first successful lumbar disc surgery was reported by Mixter and Barr[4] in 1934, various surgical techniques have been developed. With the development of
operating microscopes, microscopic discectomy was introduced by Caspar and Yasargil.[5] Conversely, the development of the tubular retractor has allowed for less invasive
and faster postoperative recovery than the traditional subperiosteal discectomy with
dissection of the multifidus muscle.[6] Furthermore, the use of a tubular retractor and an operating microscope has been
reported to be as invasive as endoscopic surgery and helps in overcoming the disadvantage
of the two-dimensional nature of endoscopic images.[7] Therefore, we use a 16-mm-diameter tubular retractor in our institution to make
microscopic discectomy less invasive.
However, the risk of postoperative bleeding is reported to be higher for minimally
invasive, small skin incisions than that of conventional surgery.[8] Gelatin–thrombin matrix sealants (GTMSs), which are absorbent localized hemostatic
agents using gelatin containing human thrombin, are excellent hemostatic agents with
strong primary and secondary hemostatic effects in addition to the tamponade effect
of the gelatin foam.[9] In the field of spine surgery, its usefulness for anterior decompression and fixation
of the cervical spine[10] and endoscopic laminectomy[11] has been reported; however, no reports on microscopic discectomy exist.
Therefore, this study aimed to investigate the usefulness and safety of the GTMS in
minimally invasive microscopic discectomy.
Materials and Methods
Patients
This study was approved by the ethics committee of our hospital. During the period
from April 2018 to December 2022, we included patients who underwent single-level
microscopic discectomy at our hospital as the subjects of this study. Exclusion criteria
comprised cases with previous surgery at the same level. LDH was diagnosed by spinal
surgery attending physicians in all patients based on clinical findings, and magnetic
resonance imaging (MRI) and computed tomography myelography results, and nerve root
blocks were performed as required. All patients experienced symptoms in the lower
extremities, and surgery was performed in patients with poor response to preoperative
medical therapy and epidural block. GTMS was employed in instances characterized by
a pronounced likelihood of hemorrhage emanating from the epidural venous plexus due
to manipulation surrounding the nerve root, instances wherein achieving hemostasis
posed a formidable challenge despite the utilization of collagen-based absorbable
local hemostatic agents, and instances involving patients who had been administered
antiplatelet or anticoagulant medications prior to undergoing surgery. Preoperative
antiplatelet and anticoagulant medications were withdrawn preoperatively and resumed
on the day after drain removal. During the period from April 2018 to December 2022,
cases where GTMS was employed intraoperatively were categorized into Group G, while
cases utilizing collagen-based absorbable local hemostatic agents were allocated to
Group C.
Surgical Procedures, Application of the Hemostatic Agent, and Postoperative Measurement
of Drainage
Surgery was performed under a microscope using a tubular retractor for discectomy.
All the patients underwent surgery under general anesthesia in the supine position.
A 20-mm skin section and fascial incision were made, and a 16-mm-diameter tubular
retractor was placed at the base of the spinous process using a dilator. The vertebral
arch at the ligamentum flavum attachment site was osteotomized using a high-speed
drill, and the ligamentum flavum was resected from the cephalad side using a Kerrison
punch. Decompression of the lateral recess was performed up to the medial margin of
the navicular vertebral arch while preserving the intervertebral joint as much as
possible. Herniated disc removal was then performed using a nerve hook and retractor
with suction while deflecting the dura mater and nerve root medially.
If used, GTMS was injected into the bleeding site ([Fig. 1A, B]), and compression was applied over it for 2 minutes using sterilized Ben Sheets
XR (Kawamoto Sangyo, Osaka-shi, Osaka, Japan) ([Fig. 1C]). The sheets were then deflected, and the GTMS and blood clot complex were flushed
with saline and removed through aspiration ([Fig. 1D]). When using collagen-based absorbable local hemostatic agents, the bleeding site
was filled in the same manner, followed by compression with the sheet for 2 minutes,
and then rinsing with saline for removal. After confirming complete hemostasis, the
surgical field was washed again with saline solution, and a closed negative pressure
drain was placed to close the wound. All patients were fitted with a soft orthosis,
and gait training was initiated the day after surgery. Postoperative drainage was
measured on the mornings of the day following surgery and second postoperative day.
The drain was removed on the second postoperative day in all patients. Almost all
patients were discharged home 1 to 2 weeks after the surgery.
Fig. 1 (A) Intraoperative photos of L4/5 right lumbar disk herniation. The surgeon is standing
on the left side. Venous bleeding continues from the foraminal area (arrow). (B, C)
gelatin–thrombin matrix sealant is applied to the bleeding site, followed by 2 minutes
of compression using Ben Sheets XR. After removing Ben Sheets XR, the thrombus complex
is washed out and removed with saline solution. (D) Hemostasis has been achieved,
and a clear field of view is obtained, revealing the intervertebral disc (intervertebral
disc: arrowhead).
Data Collection and Analyses
Two independent spine surgeons, who were not involved in the treatment of enrolled
patients, performed patient selection and data collection. For all enrolled patients
in each study group, the following factors were extracted from patient records: age,
gender, body mass index (BMI), history of hypertension, history of diabetes, history
of antiplatelet medication, history of anticoagulation, preoperative platelet count,
activated partial thromboplastin time (APTT), prothrombin time (PT), and operative
levels. The primary outcomes were operative time (minutes), intraoperative blood loss
(g), total drainage volume (g), and the occurrence of intraoperative dural tear. In
the secondary assessments, we investigated the necessity of hematoma evacuation surgery
in instances of postoperative epidural hematoma. Comparisons between groups were made
using Student's t-test and considered statistically significant when the p-value <0.05.
Results
Between April 2018 and December 2022, a total of 484 patients underwent minimally
invasive microscopic discectomy in our hospital. Among them, 35 patients with a history
of surgery at the same level were excluded, resulting in 449 patients being included
in this study. Out of the 449 patients included in the study, 316 patients were in
Group G, and 133 patients were in Group C. [Table 1] summarizes the characteristics and basic clinical information of Groups G and C.
The mean age was 50.7 ± 16.6 years in Group G and 51.5 ± 16.8 years in Group C. Regarding
sex, 218 (70.0%) of the patients in Group G and 37 (68.4%) in Group C were male. No
statistically significant differences in age or sex were observed between the two
groups (p = 0.64 and 0.91, respectively). BMI was 24.6 ± 4.2 kg/m2 for patients in Group G and 24.3 ± 3.7 kg/m2 in Group C. No significant difference was noted between the two groups (p = 0.37). No significant difference was observed between the two groups in terms of
a history of hypertension (99 [31.3%] in Group G and 31 [23.3%] in Group C) and diabetes
mellitus (40 [12.7%] in Group G and 14 [10.5%] in Group C) (p = 0.81 and 0.63, respectively). No significant difference in the use of antiplatelet
(36 [11.4%] in Group G and 10 [7.5%] in Group C) and anticoagulant (2 [0.6%] in Group
G and 0 [0%] in Group C) medications was noted between the two groups (p = 0.24 and >0.99, respectively). Preoperative platelet count(×104) was 24.1 ± 5.3 in Group G and 24.2 ± 5.1 in Group C (p = 0.83). The preoperative APTT in patients of Group G was 27.3 ± 2.1 seconds, and
in patients of Group C, it was 27.7 ± 2.5 seconds, showing a tendency for a shorter
duration in Group G (p = 0.08). Moreover, the PT of patients in Group G (9.8 ± 0.5 seconds) was significantly
shorter than that of patients in Group C (10.0 ± 0.5 seconds) (p < 0.01). No significant difference was noted between the two groups in operative
levels of LDH (p = 0.98).
Table 1
Patient characteristics and basic clinical information in Groups G and C
|
Group G (n = 316)
|
Group C (n = 133)
|
p-Value
|
|
Age (y)
|
50.7 ± 16.6
|
51.5 ± 16.8
|
0.64[a]
|
|
Gender (male/female)
|
218/98
|
91/42
|
0.91[b]
|
|
BMI
|
24.6 ± 4.2
|
24.3 ± 3.7
|
0.37[a]
|
|
History of HT
|
99
|
31
|
0.81[b]
|
|
History of DM
|
40
|
14
|
0.63[b]
|
|
Medication of antiplate drugs
|
36
|
10
|
0.24[b]
|
|
Medication of anticoagulants
|
2
|
0
|
1[b]
|
|
Preoperative platelet count (×104)
|
24.1 ± 5.3
|
24.2 ± 5.1
|
0.83[a]
|
|
Preoperative APTT (s)
|
27.3 ± 2.3
|
27.7 ± 2.5
|
0.08[a]
|
|
Preoperative PT (s)
|
9.8 ± 0.5
|
10.0 ± 0.5
|
<0.01[a]
|
|
Levels of LDH
|
|
L1/2
|
2
|
1
|
0.98[b]
|
|
L2/3
|
9
|
3
|
|
L3/4
|
36
|
14
|
|
L4/5
|
132
|
54
|
|
L5/S
|
137
|
61
|
Abbreviations: APTT, activated partial thromboplastin time; BMI, body mass index;
DM, diabetes mellitus; HT, hypertension; LDH, lumbar disc herniation; PT, prothrombin
time.
a Student's t-test.
b Fisher's exact test.
[Table 2] summarizes the primary and secondary outcomes of this study. The following pertains
to the four primary outcomes. The mean operative time was 56.3 ± 20.2 minutes for
patients in Group G and 58.2 ± 20.4 minutes for those in Group C. No significant difference
was observed between the groups (p = 0.36). The mean intraoperative blood loss was 10.0 ± 15.4 g for patients in Group
G and 11.8 ± 0.6 g for patients in Group C, and although there was no significant
difference between the two groups, there was a trend toward difference (p = 0.20). The volume of drainage before drain removal was significantly lower for
patients in Group G (35.3 ± 21.8 g) than for those in Group C (49.5 ± 34.1 g) (p < 0.01). The incidence of dural injuries amounted to two occurrences in Group G and
three occurrences in Group C, indicating an observable divergence in trends (p = 0.21). As a secondary outcome, the number of cases undergoing reoperation for postoperative
epidural hematoma was one in Group G and two in Group C, indicating an observable
trend of difference (p = 0.16).
Table 2
Four postoperative measurements
|
Group G (n = 316)
|
Group C (n = 133)
|
p-Value
|
|
Surgical time (min)
|
56.3 ± 20.2
|
58.2 ± 20.4
|
0.36[a]
|
|
Intraoperative blood loss (g)
|
10.0 ± 15.4
|
11.8 ± 8.3
|
0.20[a]
|
|
Drainage volume (g)
|
35.3 ± 21.8
|
49.5 ± 34.1
|
<0.01[a]
|
|
Dural tear
|
2
|
3
|
0.16[b]
|
|
Revision surgery for PSEH (n)
|
1
|
2
|
0.21[b]
|
Abbreviation: PSEH, postoperative spinal epidural hematoma.
a Student's t-test.
b Fisher's exact test.
Discussion
In this study, we compared the surgical time, intraoperative blood loss, drainage
volume, and number of intraoperative dural injuries between the group that used GTMS
and the group that did not use it as primary and secondary outcomes. Additionally,
we compared the number of reoperations due to postoperative epidural hematoma as the
secondary outcome. Regarding drainage volume, the GTMS group exhibited a significantly
lower amount. While no statistically significant differences were observed in other
outcomes, overall, the GTMS group demonstrated favorable results. Comparing patient
backgrounds, we found that there was a tendency for differences in APTT and a significant
difference in PT, but no differences were observed in patient backgrounds between
the groups. Therefore, this study was considered to accurately reflect the effects
of the GTMS when compared with the control group.
GTMS is believed to produce local hemostatic effects in the following two aspects:
First, the GTMS has a tamponade effect, which means that it physically reduces blood
flow by expanding the volume by ∼20% after coming into contact with the blood of the
patient. Second, blood permeating between the cross-linked gelatin particles comes
into contact with human thrombin, which converts fibrinogen to fibrin, thereby promoting
the stabilization of the clot and assisting hemostasis.[9] Because of its fluidity, GTMS is also expected to be effective in the hemostasis
of bleeding from anatomically difficult sites, such as lateral recesses and depths
of the intervertebral foramen in spinal surgery where hemostasis is difficult.[10] Intraoperative hemostatic efficacy of GTMS has been reported in several cases outside
the field of orthopaedic surgery.[12]
[13]
[14]
[15] Li et al reported an anterior cervical fusion procedure and found that the volume
of fluid drained from the drain at 24 hours postoperatively and that drained per 8 hours
were <10 mL in the GTMS group compared with those in the non-GTMS group.[10] In their report on endoscopic laminectomy, Nomura et al reported that intraoperative
blood loss was higher in the GTMS group; however, postoperative drainage was lower
in the GTMS group than in the nonuser group.[11] In this study, no significant difference in intraoperative blood loss was observed;
however, postoperative drainage was significantly lower in the GTMS group, as in the
previous study. Nomura et al pointed out that postoperative hemostasis may not have
been sufficient to withstand extubation and subsequent hypertension.[11] However, the GTMS-reinforced clots were stronger than normal clots, which may have
resulted in a difference in the postoperative drainage volume.
In this study, there was no significant difference in the average operative time between
the two groups, but the operative time in Group G was about 2 minutes shorter. However,
a previous study by Nomura et al reported that the surgical time was longer in the
group using GTMS. In the study by Nomura et al, the use of GTMS required dissolving
thrombin and mixing it with gelatin, which is thought to have prolonged surgical time.
In this study, it is believed that the effectiveness of GTMS resulted in a shortened
hemostasis procedure time and facilitated the surgical technique due to improved field
visibility. As a result, the preparation time was offset, leading to no significant
differences in the surgical duration between the groups.
Conversely, postoperative epidural hematoma of the spine can cause early postoperative
neurological deterioration. The exact frequency is unknown, as most symptoms are limited
to transient buttock pain or the lower extremities. However, an MRI study on microscopic
lumbar discectomy reported that 14.6% of patients had an epidural hematoma regardless
of the presence or absence of symptoms.[16] Hematomas can occur for a variety of reasons; however, in cases of paralysis, a
high percentage of patients are left with permanent disability if not treated promptly.
Takami et al measured the hematoma area ratio on postoperative MRI in endoscopic laminectomy
for lumbar spinal canal stenosis and reported that no difference was observed in the
hematomas even with the use of prophylactic GTMS.[17] In this study, removal of postoperative epidural hematoma was performed in both
Groups G and C; however, no statistically significant difference was noted between
the groups. As most postoperative hematomas are asymptomatic or present only with
transient mild buttock or leg pain, further studies are required to determine whether
the GTMS is effective in preventing hematomas that require removal.
GTMS has been reported to have economic effects in spinal surgery. Ramirez et al used
Premier's US Perspective Hospital Database to compare cases in which GTMS alone was
used versus GTMS plus a nonflowing hemostatic agent in spine surgery.[18]
[19] According to their study, the GTMS alone group was superior in terms of average
hospital stay, surgical time, amount of blood loss, and frequency of dural injury
and bleeding-related complications, and it was reported that hospital resource utilization
and medical costs were reduced. In this study, dural injuries was observed in two
cases in Group G and three cases in Group C, and reoperation due to epidural hematoma
was observed in one case in Group G and two cases in Group C. These results indicate
that the use of GTMS in minimally invasive microscopic discectomy may reduce perioperative
complications and reduce the use of medical resources. Japan and the United States
have different medical systems, and the number of cases in this study was small, so
it is thought that it is necessary to increase the number of cases to verify the medical
economic effects in Japan.
One of the limitations of this study is that it was a retrospective study and not
a prospective randomized trial. Although some homogeneity in patient background is
expected, temporal changes in the study population and variations in surgeon skill
level may potentially influence the results. Furthermore, although there was a significant
difference in the volume of postoperative drainage, there was no significant difference
in the use of GTMS in reducing intraoperative dural damage or postoperative epidural
hematoma removal. Therefore, we were unable to determine the clinical usefulness of
this study. Third, the impact of GTMS on postoperative clinical symptoms is unknown,
and clinical outcome evaluations such as Japanese Orthopaedic Association score were
not performed.
Conclusion
The use of GTMS significantly reduced postoperative drainage volume in minimally invasive
microscopic discectomy. Additionally, there was a trend toward a reduction in intraoperative
dural injuries and postoperative epidural hematoma removal procedures. This has the
potential to be advantageous in terms of health care economics.
