Evaluation of autologous PRP in Cardiovascular Surgery: Analysis of application results in 2000 patients
Entrance
Deep and superficial wound infections after cardiovascular surgery greatly increase morbidity, mortality and healing costs. Autologous platelet-rich plasma application (PRP) is a treatment method prepared from the patient's own blood and used to accelerate wound healing in other surgical interventions. The aim of this study was to analyze the effects of PRP therapy on standard wound healing for cardiac surgery procedures in all patients undergoing sternotomy.
Method
Over a 7-year period, 2000 patients requiring open heart surgery were evaluated. One thousand patients were left to recover with the standard sternal closure method. In the group of 1000 people, PRP was applied to the surgical area together with the sternal closure method. The results were evaluated in terms of wound healing status, infection, retreatment of the wound and disease costs.
Results
In 2000 patients, especially in the PRP group, greater ventricular benefit was observed in cardiac devices, heart transplants and emergency operations, other than that, no significant change was detected. It was observed that the use of PRP reduced deep wound infections from 2% to 0.6%, superficial wound infections from 8% to 2%, and re-wound treatment cases from 4% to 0.8%. In addition, the use of PRP reduced the healing expenditures in deep and superficial wound infections from $ 1,256,960 to $ 593,791.
Result
As a result, the use of PRP has significantly reduced the complications of sternal wounds related to cardiovascular surgery and related expenses. In cardiovascular surgery, it is important that sternotomy patients should regularly apply PRP.
ENTRANCE
Sternal complications such as wound dehiscence and infection after median sternotomy cases occur in 0.2% to 8% of patients [1]. These post-operative complications trigger a significant risk of death and cause long-term hospitalization, long-term antibiotic use, multiple surgical procedures and a high cost treatment process. There are several patient and surgical risk factors that cause the development of sternal wound complications[2, 3]: these are; obesity, bilateral harvest of internal mammary artery, diabetes (sugar), steroid therapy, aging, active smoking, osteoporosis disease and chronic lung disease. Several therapy modalities are used to minimize deep wound infections in high-risk patients [4]. However, deep infectionOnce an ion event occurs, debridement, continuous antibiotic irrigation, and vacuum-assisted closed therapy procedures reduce the incidence of deep wound infections with a fatal outcome [5–7]. A more conservative treatment method has just come to light. Local platelet-rich plasma (PRP) application, which is applied to support the early healing of the wound in various surgical cases, is becoming widespread [8]. According to recent scientific reports, the benefits of PRP application after median sternotomy have been clearly demonstrated [9–11]. However, most of these studies could not analyze the economic contribution of PRP use in detail due to economic inadequacies. Currently, Medicaid and Medicare health care centers do not reimburse deep infection treatment costs, which puts excessive costs on the patient. In this study, the infection status and recovery costs of 1000 patients who had sternotomy heart surgery and used PRP, and the infection status and health costs of 1000 patients who did not use PRP were compared in detail.
Method
Patients were enrolled in our study database of 2000 consecutive patients who had open heart surgery in the same health center between January 2005 and January 2013 with their consent (NCT00130377). University of Utah file admission number is 35242. The same information was collected prospectively as part of our institute's Society of Thoracic Surgeons database. From December 2009 to January 2013, there were 1000 consecutive patients who underwent standard sternal closure and PRP at the time of wound closure (PRP group). This group was compared with 1000 consecutive patients treated with the sternal closure method from January 2005 to December 2009 and treated only with antibiotics and the normal standard (gycemic treatment procedure) treatment (Control Group). All data were collected and analyzed sequentially. Surgery in terms of deep and superficial wound infections, retreatment and real costsResults were analyzed for 6 months post-intervention (See Fig. 1). Sternal wound infections are classified as follows by the Center for Disease Control and Prevention; Superficial, Deep or surgical site infections [12]. All patients were subjected to intravenous antibiotic administration for 60 minutes before the operation. During the whole study, preoperative antibiotic protocol and glycemic treatment were applied as standard for all patients. Standard surgical methods were used for all median sternotomies and sternal closure cases. All patients exposed to sternotomy, emergency patients, reoperated patients, ventricular assist device implantation, heart transplant patients, aortic dissection and standard coronary bypass were included in this study. Due to patient rights, comparison or control of subgroups was avoided. (Table 1)
fig. 1 Changes in the PRP Group according to the duration of infection
Patient profile of Table 1 PRP and Control Group
Postoperative infection time was reported as the number of patients with infection.
PRP DSWI- PRP applied deep wound infections,
Control DSWI – deep wound infections without PRP,
PRP SSWI- Superficial sternal wound infection applied to PRP,
Control SSWI – Superficial wound infection without PRP PRP platelet rich plasma,
COPD chronic obstructive pulmonary disease,
CABG coronary artery bypass surgery, BIMA Bilateral internal mammary artery,
PRBC-sorted red blood cells
Study design and endpoints
All data were collected and analyzed prospectively for this regular and haphazard patient group. Readmissions, sternal wound infections, and costs were independently evaluated and verified by the hospital infection committee and the finance office. All patients with sternotomy cases were included in this evaluation.
Definitions
A diagnosis of deep wound infection was made in all patients with one or more of the following findings:
1) Positive mediastinal tissue culture or fluid
2) Clinical evidence of mediastinitis during sternal operation
3) Chest pain, sternal imbalance, purulent discharge from the mediastinum with positive blood culture
Standard sternal wound closure
The entire sternotomy operation area was opened with a sternal saw blade. Postoperatively, the sternum was closed with 8 cut stainless wires. The wounds were closed with a stratified absorbable suture. The wounds were covered externally with sterile strips, gauze and paper tape. All surgeons at our institute actively participated in this study and were included in the wound closure procedure.
Preparation and application of platelet rich plasma (PRP)In the treatment application, 52 ml of blood was drawn from the central vein and mixed with 8 ml of citrate (anticoagulant). 60 ml of anticoagulant blood was processed with Magellan Autologous Platelet separation system. This PRP system is FDA approved and is only used to prepare PRP, and the price of 1 kit is $385. Platelet separation took 15 minutes without supervision. From this application, approximately 6 ml of rich PRP was prepared to be applied to the soft tissue and sternum during sternal wound closure. Analysis of growth factors in plasma content is shown in Table 2. Prepared PRP was mixed with 1 ml of calcium chloride and thrombin in 6 ml of plasma and applied to deep chest wounds and soft tissues during wound closure. PRP application time took 30 seconds in total.
Platelet Analysis
Platelet counts and growth factors were analyzed before and after centrifugation. PDGF platelet-derived growth factor, TGF transforming growth factor, VEGF vascular endothelial growth factor, FGF fibroblast growth factor, EGF endothelial growth factor.
Cost analysis
The costs of disposable consumables were also included in the cost of PRP. These are real PRP costs, not hospital expenses. These costs were also confirmed by the hospital room service director, the vendor, and the hospital finance department. Likewise, hospitalization and retreatment costs were approved by the same department. No separate cost was reflected for the 30-second PRP application. Likewise, the 30 seconds needed to draw blood from the intravenous line were not taken into account, only preoperative chemistry was included in the laboratory procedures.
Statistical Analysis
All patients undergoing open cardiovascular surgery between January 2005 and January 2013 were enrolled in this study. For the PRP applied group, patient treatment costs and treatment results were analyzed using Fisher's test. In addition, the clinical and cost benefits of the patients who were treated were calculated. Mean ± SD Basal (60 mL) PRP (mL) PDGF AB (ng/mL) 8.4 ± 2.1 96.1 ± 22.5 PDGF AA (ng/mL) 2.1 ± 0.4 25.4 ± 3.9 PDGF BB (ng/mL) 5.9 ± 1.2 61.3 ± 11.6 TGF B1 (ng/mL) 46.4 ± 4.4 278.2 ± 38.4 VEGF (ng/mL) 76.3 ± 19.5 801 ± 266.1 bFGF (ng/mL) 15.6 ± 2.9 55.1 ± 9.6 EGF (ng/mL) 13.4 ± 2.1 187 ± 29.4 Ethics, volunteerism and consents: all clinical studies with human content are carried out taking into account the ethical standards published by the national research committee and the 1964 Helsinki declaration and later publications.
Results
Two thousand consecutive patients completed this study. Of these, 1000 patients were those who received PRP application (PRP group), and the other 1000 patients were those who did not see PRP (Control Group). There were significant differences between the two groups in some respects, for example, age and body area were lower in the control group, heart transplant, emergency cases and blood transfusion use were higher in the PRP group. Compared to the control group, the use of PRP reduced deep wound infections from 2% to 0.6%, superficial wound infections from 8% to 2%, and hospital readmission and retreatment from 4% to 0.8%. Post-surgical infection time analysis showed that; Infections in the PRP group occurred within the first 2 months, whereas in the control group, the infection rate extended up to 4 months later (Fig. 1). Likewise, significant decreases were observed in treatment costs, while the costs in the Control Group were 1,256,960 dollars in deep and superficial wound infections, while it was 593,791 dollars in the PRP group (Table 3). Despite this reduction in sternal wound healing costs, the number of patients who needed the desired benefit was 71 people (confidence interval 41.8-244.5) with a 95% rate, and the money spent for 1 sternal deep wound infection was $27,000. However, the number of patients expected to heal superficial wounds was 95% (confidence interval 12.7-24.3) and the cost for 1 superficial infection was $6417. In total, the number of patients with expected recovery was 14 with a confidence interval of 10.5-18.9, 95%, and 5203 dollars were spent for 1 infection.
Table 3 Results
Evaluation
In most cardiovascular surgery, median sternotomy is the shortest way to reach the heart. However, deep central wound infection (DSWI) is a vital complication. Minimizing the formation of deep wound infection after the operation is of great importance for patients, caregivers, hospitals and payers. With the developments in surgical debridement, continuous antibiotic irrigation, modern wound closure methods have reduced the deep wound infection mortality rate for the last 30 years, but there has been no serious change in sternal wound complications since the 1980s. As a result, it is inevitable that the main goal is to prevent deep wound infections. There are various treatment approaches in this direction; such as closing the sternum more tightly, using more sutures. However, their contribution is limited. There are also several risk models used to predict the incidence of sternal wounds, but these estimates cannot prevent infections. The autologous PRP method to prevent deep wound infections has proven itself with very clear clinical data. The effect of growth factors in PRP on the rapid healing of the wound after median sternotomy is known. During inflammatory tissue healing, activated platelet cells secrete beneficial growth factors such as transforming BF, vascular endothelial BF, and endothelial BF (Table 2). These growth factors trigger cell proliferation, cell migration, cell differentiation and matrix synthesis. The same growth factors also positively affect chondrocyte metabolism, chondrogeny and bone strength [8]. This combination of growth factors in PRP activates and accelerates the healing mechanism in the wound. PRP is used extensively in many areas such as plastic, maxillofacial and orthopedic surgery to accelerate tissue healing [8, 18]. In addition, staphylococcus aureus, bacteria that cause deep wound infections, are inhibited by PRP administration [19]. Some studies have also shown that PRP applied to wounds in cardiac surgery produces different and mixed results [20–23]. Although these studies were properly designed and performed, they were insufficient to assess post-use effects due to the small number of patient enrollments. Previous studies have reported that different growth factor ratios were obtained with different preparation methods of PRP [24]. At the same time, positive results of antibiotic administration in addition to PRP have been revealed, but it has not been clinically proven how much and to what extent PRP increases the effect [25]. Just like the PRP Kit used in this application, the use of a disposable, closed and sterile PRP Kit is important both in terms of platelet concentration to be obtained and in terms of giving the same result, and it eliminates the risk of air contamination. This is the first major clinical study to include all patients entering a median sternotomy case and independent of emergencies, heart transplant cases, ventricular device implantation cases, dialysis, steroid use, emphysema, and reoperation cases. Despite the reports by the Society of Thoracic Surgeons that the rate of deep wound infections was reduced to 0.3%, this is not the case in sternotomy cases. Most of the patients in this report are intended for patients undergoing bypass surgery or isolated valve surgeries. Also, many clinical studies, unlike ours, do not consider the 6-month postoperative period. However, many infections begin to occur 30 days after surgery, which reveals the inadequacy of such studies. In addition, the number of sutures used in wound closure has no effect on wound healing. In addition, no complications were encountered in any patient in whom PRP was used. This study also showed that all infections in the PRP group occurred only within the first 2 months, while infection was observed in the control group even after 4 months. Although it was not observed during the study, it was understood from this study that PRP plays an active role in the early diagnosis and rapid elimination of the infection case. The economic analysis of PRP in sternal wounds is very interesting, because if you prevent even one deep wound infection with PRP, it will save you from a great economic loss, because the cost for one deep wound infection is much more expensive than 1 PRP application. The number of patients requiring PRP (NNT) calculation and the benefit to be obtained are effective only in deep wounds and their combinations. Because the cost of superficial wound treatment is lower than the cost of PRP application. If NNT was 17 instead of 3.5 for superficial wound infections, PRP application would be cheaper. This study had some limitations as the patients were not randomly selected from multiple centers. However, due to the high number of patients in the study, it is clear that cardiovascular surgery gives clear and verifiable results in terms of both cost and treatability. Complications related to wound infection were also evaluated by different healthcare professionals, such as nurses, physical therapists, plastic surgeons, and cardiologists, who had no previous experience with PRP. This has eliminated the prejudice that may arise from the evaluation of the same disease by the same people all the time. Patients were not considered as part of this study and all patients undergoing cardiovascular surgery were included in the study. However, a study group of 2000 patients, including surgeons and their attendants, was included in the complete evaluation, allowing patients undergoing cardiac surgery to be evaluated in real hospital conditions without any extra precautions. Cost analysis was likewise performed and verified by independent hospital and financial analysts unrelated to this study. Medicaid and Medicare services center do not reimburse the treatment costs of deep wound infections that exceed the limits.
Result
In conclusion, this study showed that regular use of PRP reduced the incidence of deep and superficial infections by 7.41%, taking into account the overall cost benefits. For the 2000 patients included in this study, PRP application at the time of wound closure during the surgical operation was reported to be both safe and reducing the risk of post-surgical infection. PRP is a reliable, simple and easy-to-prepare therapy that provides both clinical and financial benefits for the patient undergoing open heart surgery. PRP applied at the time of wound closure after open heart surgery has created added value both in accelerating the treatment and in reducing the costs.
Release permission
The necessary permissions for the publication of this study were obtained from the relevant institution. Declaration
Thanks
Utah EÄŸitim ve ArÅŸt., who contributed to this study and contributed to financial and cost analysis. Special thanks to Kathy Adamson, hospital director, Shirley Noon, director of the Society of Thoracic Surgeons for database support, and our nurses, anesthesiologists and perfusionists for their interest in our cardiovascular patients and their contribution to cost validation, Dr. Many thanks to Richard Nelson.
Funding
The costs of this study were covered by the State of Ohio- 3rd Frontier Fund. Open Access This article is published with Creative Commons Attribution permission.
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