Using flowable gelatin in anterior cervical spine surgery in real-world practice: a retrospective cohort study

This was a retrospective study including patients who underwent ACSS for cervical degenerative disease at a single institution from January 2014 to December 2016. The research proposal of this study was reviewed and approved by the research ethics board in the study institution.

The hospital (ward II and III, Department of Orthopedics) identified 425 patients in 2014 and 930 patients in 2015 and 2016, who had the diagnosis of cervical spondylopathy and were treated by surgery. According to the inclusion and exclusion criteria, 186 patients were included in the HC group and 265 patients were included in the FGHM group. The details of patient inclusion and exclusion are illustrated in Figure 1.

The large volume of real-world cases of ACSS using FGHM (SURGIFLO) from 2015 to 2016 in our site allowed us to create sufficient propensity-score matched pairs and demonstrate the clinical and economic benefits associated with hemostasis. This is the first known study that assessed the impact of FGHM on cervical–spine perioperative benefits associated with hemostasis and hospital cost by using hospital medical records.

Every patient in the matched FGHM group received gelatin sponge but in significantly lower amounts compared with patients in matched HC group. According to the surgeons of the included patients, the gelatin sponge was usually used first for bleeding control in the FGHM group. Gelatin sponge can soak blood and provide a matrix for clot formation [13,14]. The spongey physical property renders it effective at stopping continuous oozing of visualized and even sites. However, it could be challenging when applying cauterization and high-swell TAH agents to stop bleeding of epidural veins, because these veins are a plexus of vessels surrounding the spinal cord and spinal nerves. Gelatin sponge is a mass-occupying agent and could considerably swell up once saturated with blood, which may potentially lead to neurological compression [15]. Flowable gelatin provides an environment for platelets to adhere and has a distinctly smaller swelling factor compared with gelatin sponge [7]. Also, flowable gelatin better conforms to irregular and deep surgical surface than performed nonflowable TAH agents [12,16]. These characteristics bring advantages to flowable gelatin for stopping venous bleeding from the spinal epidural space in ACSS when the conventional hemostatic agents did not work well in the first line setting. The lower amount of gelatin sponge in the matched FGHM group reflected that the improved hemostasis brought by FGHM reduced the needs of traditional hemostatic agents and offset some costs for gelatin sponge. Thus, the generated clinical evidence in our study confirmed that previously reported superior hemostasis effects of FGHM [17–20] could also occur in the Chinese setting.

Unlike a prospective study, patients in this observational study were not randomly assigned for treatment in clinical pathway. This limitation of retrospective studies necessitates other methods to minimize confounders on hemostatic agents and outcomes [21]. Therefore, this study applied propensity score matching to manage the treatment-selection bias. The low intraoperative blood transfusion rate and volume may be a result of the characteristics of ACSS. Compared with posterior lumbar spinal surgery, there is often less resection of the posterior longitudinal ligament in ACSS, causing less damage to tissue and blood vessel. Thus, the bleeding volume in ACSS was much less compared with the average 600 ml blood loss in lumbar spinal surgery [22]. The improved hemostasis effect of FGHM can also be supported by the statistical significance for the reduced operation time. When the anterior approach is used in cervical spinal discectomy, the operative field is narrow: mild intraoperative bleeding can reduce visibility, degrading accuracy and safety of the surgical technique. In other words, surgeons tend to conduct each step in the surgical procedure followed by prompt hemostasis, though it is time consuming. The prompt hemostasis achieved by FGHM could improve the flow and duration of procedure execution, which may bring better perioperative outcomes including shorter postsurgery LOS and lower risk of drainage tube placement. The operation time could have an impact on other outcomes, such as infection [23] and complications after hospital discharge [24], but these indicators were not measured in our study.

The cost of implanted fixation devices was separated mainly for two reasons: these devices in China are notably more expensive than other medical resources, and their prices vary from brand to brand. Cost of implanted fixation devices could be a confounder if the total medical cost is directly used for comparisons. Therefore, ‘hospital costs, except cost of TAH and implanted fixation’ was used to measure the economic impact associated with FGHM. This study showed that the cost savings associated with improved hemostasis by FGHM could offset the increased acquisition costs of FGHM (SURGIFLO). The comparisons of the cost distribution between matched groups showed that the reduction of medical costs in the matched FGHM group was driven primarily by the decreased cost of disposable medical consumables, which are mainly charged during blood transfusion and postsurgery care. For example, the lower requirement on intraoperative transfusion could result in less frequent usage of disposable blood-transfusion sets; the decreased risk for drainage could save the cost on disposable drainage tubes. Additionally, the economic impacts associated with the shortened postsurgery LOS was reflected through a lower cost of hospital bed, nursing service as well as laboratory tests that were used for postoperative infection and complications monitoring. Thus, this study could be a good example to demonstrate the economic impact associated with improved hemostasis. Though a significant reduction of blood transfusion in matched FGHM was observed, cost savings on blood transfusion were not observed, likely due to the already low blood transfusion rate/volume in ACSS and relatively low price of packed red blood cell (¥210/200 ml) in China. It also should be noted that the economic impact of reduced operation time associated with FGHM could be minimal because of the low service fee for operation rooms in China. This study also observed the costs of clinically relevant outcomes, including reduced blood transfusion, operation time, drainage tube placement and postsurgery LOS. Cost comparison results demonstrated that the increased cost for FGHM could be completely offset by the savings for other medical resources.

This study has limitations that could compound the generalizability of the results. First, this study was conducted in a single tertiary care hospital. Clinical outcomes associated with FGHM should be further explored in other medical settings. Second, due to the retrospective nature of this study, direct clinical measures, such as accurate bleeding volume to assess the hemostatic effects of FGHM, were not possible. Thus, future studies are needed to confirm the findings herein. Finally, our study excluded patients who received thrombin in surgery in order to minimize the potential confounding effects associated with thrombin in the control of bleeding. In real clinical practices, thrombin could be mixed with FGHM to further improve the hemostatic effects. Because the cost of thrombin is relatively low, future studies should further evaluate the hemostatic effects associated with FGHM mixed with thrombin that could gain more clinical and economic benefits.

In summary, this observational study identified a large number of propensity score-matched patients to demonstrate the favorable impact of FGHM on outcomes related to hemostasis in ACSS. Moreover, medical resources savings related to improved surgical outcomes could completely offset the acquisition costs of FGHM. These findings suggest that the adoption of FGHM beyond basic gelatin sponge would bring more favorable outcomes than gelatin sponge alone for hemostasis in ACSS. Future studies using direct outcome measures are warranted to confirm cost-effectiveness dominance of FGHM in ACSS.

Z Wang formulated the research idea and worked with Yunchang Wu; Yiqing Wu, G Gangoli, A Bourcet, W Danker III and W Chen drafted the study protocol, which was verified by Z Wang. Yunchang Wu and Q Gong coordinated the data acquisition. W Chen and H Zhan structured the collected data into the database, developed the data analysis plan, and conducted data analysis. Yunchang Wu and Z Wang interpreted the results from clinical perspective. Z Wang, Yunchang Wu, Yiqing Wu, G Gangoli, A Bourcet, W Danker III and W Chen were fully involved with the development of this manuscript. All authors critically reviewed the manuscript and approved the submission of this manuscript.

This study was funded by Johnson & Johnson Medical Devices Companies, Somerville, NJ, USA. Yiqing Wu, A Bourcet, G Gangoli and W Danker are employees of Johnson & Johnson Medical Devices Companies. Q Gong, H Zhan and W Chen are the employees of Normin Health, a consulting firm receiving industry to conduct health outcomes and economics research.

No writing assistance was utilized in the production of this manuscript.

The authors state that they have obtained appropriate institutional review board approval for this work.