Evaluation of Platelet Rich Plasma in Reducing Sternal Wound Complications in CABG Surgery With Median Sternotomy
Phase: NA
Conditions: Surgical Site Infection (SSI), Mediastinitis, Delayed Wound Healing
Sponsor: Shaheed Zulfiqar Ali Bhutto Medical University

EVALUATION 
OF 
PLATELET 
RICH 
PLASMA 
IN 
REDUCING STERNAL WOUND COMPLICATIONS IN 
CABG SURGERY WITH MEDIAN STERNOTOMY 
 
SYNOPSIS 
By  
Dr. Sangeen Khan Wazir 
ClinicalTrials.gov Identifier (NCT Number): 
(NCT number not assigned yet) 
Version/Date of Protocol: 
Version 1.0 / July 7, 2022 
Sponsor: 
Shaheed Zulfiqar Ali Bhutto Medical University (SZABMU) 
Principal Investigator: 
Dr. Sangeen Khan Wazir, MBBS 
Pakistan Institute of Medical Sciences (PIMS) 
Ibn-e-Sina Road, G-8/3, Islamabad, Pakistan 
Phone: +92-334 -8123491  
Email: sangeenkhanwazir@outlook.com 
Purpose of Document: 
This document contains the full study protocol for the interventional clinical trial evaluating 
the use of autologous platelet-rich plasma (PRP) for improving sternal wound healing after 
coronary artery bypass surgery. It includes background, methods, discussion, keywords, 
rationale, research question, population, intervention, comparison, outcomes, study 
objectives, operational definitions, hypothesis, study design, study setting, duration, sample 
selection (inclusion and exclusion criteria), sample size, sampling technique, data collection 
procedure, data analysis, ethical considerations and references. 
Confidentiality Statement: 
This document contains confidential information for the purpose of clinical research and does 
not include names of study participants. 
 
  
  
 

1 
 
TABLE OF CONTENTS 
ABSTRACT                                                                                                                         1 
 Background 
2 
Methods 
2 
Discussion 
2 
Keywords 
3 
INTRODUCTION 
4 
Rationale 
5 
Research Question 
6 
Population 
6 
Intervention 
6 
Comparison 
6 
Outcome 
6 
Objective 
6 
Operational Definitions 
7 
Hypothesis 
8 
MATERIAL AND METHODS 
8 
Study Design 
8 
Study Setting 
8 
Duration 
8 
Sample selection 
8 
Inclusion criteria 
8 
Exclusion criteria 
9 
Sample size 
9 
Sampling technique: 
10 
Data Collection Procedure 
10 
Data Analysis 
11 
Ethical considerations: 
11 
References 
12 

2 
 
ABSTRACT 
Background 
Deep and superficial wound infections following cardiac surgery increases morbidity, 
mortality and cost. Autologous platelet rich plasma PRP derived from patients own blood has 
been used in other surgical settings to promote successful wound healing. The goal of this 
study is to analyze the effect of PRP during sternal closure in addition to standard wound care 
for reducing the frequency of postoperative complications.  
Methods 
Over a period of six months, all consecutive consenting patients undergoing on pump coronary 
bypass grafting surgery requiring sternotomy will be enrolled. The patients will be randomized 
into two groups. The control group will receive standard of care sternal closure. The study 
group will receive standard of care sternal closure plus PRP applied to the sternum and the 
surrounding tissue at the time of closure.  Participants and outcome assessors are blinded to 
group assignment, while surgeons performing the procedure are aware of the intervention. The 
patients will be followed up for a period of 30 days post-surgery. Wound healing, deep and 
superficial infection including mediastinitis, and readmissions within 30 days will be 
documented as primary outcomes. Secondary outcome will be the overall cost burden for the 
30-days post-surgery period. Other outcomes will be ICU stay (days), blood transfusions more 
than 4 units and platelets transfusions more than 4 units. 
 
Discussion 
Wound dehiscence and infection in post cardiac surgery period are a significant source of 
morbidity and mortality. Treatment of these complications may cause prolonged 
hospitalization, prolonged antibiotic therapy, and revisions of operative procedures. In 
addition to burden on physical health, the complications associated with cardiac surgery can 
portend a high financial cost to the patient. The PRP has been shown to decrease the incidence 
of sternal wound complications following cardiac surgery and routine use of platelet rich 
plasma has been advocated for all patients undergoing sternotomy for cardiac surgical 
procedures. 
 
 

3 
 
Keywords 
Sternal wound infection, Superficial sternal wound infection, Deep sternal wound infection, 
Surgical site infection, Delayed wound healing, Median sternotomy, Cardiac surgery, 
Postoperative wound complications, Hospital length of stay, Cost analysis, Platelet rich 
plasma, coronary artery bypass grafting, wound healing, CABG, readmission rate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

4 
 
INTRODUCTION 
 
Median sternotomy in cardiac surgery is considered to be the gold standard incisional approach 
for the majority of cardiac operative procedures resulting in a low failure rate and excellent 
long-term outcomes [1].  
Although the incidence of sternal complications after cardiac operations through median 
sternotomy is relatively low, ranging from 0.4% to 8%, it is associated with a comparatively 
high mortality rate of up to 47% if left undetected. Indicative of this, the 4-year survival rate 
of patients diagnosed with sternal complications is 65% compared with 85% in patients who 
heal without such complications [2]. Median sternotomy can have many complications like 
wound dehiscence and infection in 0.2 to 8 % of the patients [3, 4]. Some of the serious 
complications of sternotomy include Deep sternal wound problems DSWP following cardiac 
surgery, ranging from 0.4–3% in unselected patients [5]. DSWP are rare, but can have serious 
complications, as it is associated with prolonged hospital stays, long-term antibiotic therapy, 
multiple surgical procedures, higher mortality and morbidity, and increased patient suffering 
and costs [6]. This complication can be avoided by using protein rich plasma PRP, since 
platelets upon activation will excrete growth factors and attractants for tissue stem cells, thus 
promoting tissue healing [5].  
 The literature has identified a range of preoperative, perioperative, and postoperative risk 
factors that are suggested to contribute to the development of sternal complications [2] . Risk 
factors known for postoperative complications in patients going through cardiac surgery 
include obesity, bilateral harvesting of the internal mammary artery, unilateral LIMA 
harvesting, diabetes, steroid therapy, history of active smoking, osteoporosis, and chronic lung 
diseases [2, 7, 8, 9]. Two studies listed the postoperative requirement for blood products as an 
independent risk factor for sternal infection [2] . The replacement of blood products may lead 
to host immunosuppression and increase the risk of sternal infection [2] . Insulin-dependent 
diabetes mellitus is considered the most serious predisposing factor for deep infections [4]. 
Given that the IMA is a major blood supply to the sternum, some studies report mobilization 
of these arteries may lead to sternal hypoperfusion and increase the risk of sternal infection 
[2]. 
 Complications in the post-surgery period are a significant source of mortality. Treatment of 
these complications may cause prolonged hospitalization, prolonged antibiotic therapy, and 

5 
 
revisions of operative procedures [10]. Centrifugal-based platelet concentration methods have 
been developed separating whole blood in a red blood cell (RBC) layer, a platelet rich plasma 
(PRP) layer and a platelet poor plasma (PPP) layer. The PRP layer also contains a high 
concentration of leukocytes, which might provide additional protection against infection. 
Numerous growth factors and chemoattractants are excreted from activated platelets, in 
sufficient amounts to stimulate vascular proliferation and attract tissue stem cells and in 
addition platelets also appear to have antimicrobial properties [5]. During the inflammatory 
phase of wound healing, PRP stimulates the release of growth factors such vascular endothelial 
growth factor and transforming growth factor beta, which are believed to stimulate cell 
proliferation, migration, differentiation, and matrix synthesis. These same growth factors can 
positively affect chondrocyte metabolism, increase chondrogenesis, and improve bone healing 
and regeneration. PRP wound irrigation was found to be safe and cost-effective, improving 
healing and leading to a lower incidence of sternal infections [6].  Nowadays, PRP is being 
used in many specialties to promote speed-up tissue healing and hence less complications . 
Furthermore, PRP inhibits in vitro the growth of Staphylococcus aureus, the most common 
bacteria responsible for DSWI, and Escherichia coli, whereas it was ineffective against 
Pseudomonas aeruginosa, Enterococcus faecalis and Klebsiella pneumoniae [9]. PRP can be 
injected in the LIMA bed, hence increasing neovascularization, speeding up the healing 
process, as a result can avoid deep sternal wound infection, sternal dehiscence and reoperation 
secondary to postoperative complications. 
 The PRP has found multiple uses in many fields, including oral, maxillofacial, and plastic 
surgery [8,10]. In cardiac surgery patients, PRP has been shown to decrease the incidence of 
sternal wound complications [10]. Although it is  not used routinely, some authors suggest 
regular use of PRP based on preliminary results from studies on reducing complications in 
patients undergoing cardiac surgery with median sternotomy [8].  
Rationale 
Postoperative complications cause significant morbidity in post cardiac surgery patients. The 
PRP has been proposed in clinical trials to reduce the frequency of complications in patients 
undergoing median sternotomy for cardiac operative procedures. The purpose of our study is 
to evaluate whether there is any beneficial effect of use of PRP in addition to standard care 
after on pump CABG, cardiac surgery.  

6 
 
Research Question 
Does application of PRP after CABG, cardiac surgery reduce the frequency of sternal wound 
complications?  
 
Objective 
To compare the complication rates of application of PRP in addition to standard sternal wound 
closure versus standard sternal wound closure alone. 
Population 
All consecutive patients of age 45 to 72, undergoing CABG, cardiac surgery with median 
sternotomy will be included in the study.  
Intervention 
Application of 6 mL of autologous PRP to sternum and soft tissue during sternal closure. 
 
Comparison 
The control group will undergo midline sternotomy with a sternal saw blade. The sternum will 
be closed with a simple interrupted or figure of eight stainless steel wire. The wounds will be 
closed in a layered manner with absorbable suture and dressed with Steri-Strips, gauze and 
paper tape. The study group will additionally receive 6 mL of autologous PRP applied to 
sternum and soft tissue during sternal closure. 
 
Outcome 
(i) Primary Outcome; 
Primary outcome will be measured as frequency of sternal wound complications in terms of 
delayed healing, superficial infection, deep infections, and readmission rate including 
mediastinitis in 30-days period post-surgery.  
(ii) Secondary outcome; 
Secondary outcome will be the overall cost burden for the 30-days post-surgery period.  
(iii) Other outcomes; 

7 
 
Other outcomes will be ICU stay (days), blood transfusions more than 4 units and platelets 
transfusions more than 4 units within 30 days. 
 
OPERATIONAL DEFINITIONS 
 
1-Cardiac Surgery: Cardiac surgery, also called heart surgery, involves surgical operations 
performed on the heart to correct life-threatening conditions. The surgery can be either open-
heart surgery or minimally invasive surgery depending on the condition to be corrected. 
 
2-PRP: Platelet-rich plasma (PRP) is defined as a portion of the plasma fraction of autologous 
blood having a platelet concentration above baseline. 
 
3-Study Outcome 
Study Outcome will be measured as frequency of sternal wound complications in terms of 
delayed healing, superficial infection, deep infections, and readmission rate including 
mediastinitis in 30-days period post-surgery. Secondary outcome will be the overall cost 
burden for the 30-days post-surgery period. Other outcomes will be ICU stay (days), blood 
transfusions more than 4 units and platelets transfusions more than 4 units within 30 days. 
 
4- DSWI: DSWI diagnosis will be made, based on the guidelines of the CDC, in patients who 
developed one or more of the following: [1] positive culture of mediastinal tissue or fluid; [2] 
clinical evidence of mediastinitis during sternal reoperation; or [3] chest pain, sternal 
instability, purulent discharge from the mediastinum associated with a positive blood culture. 
DSWI presenting in the first 30 days after operation will be included in the study.  
 
5- SWI: All the infections will be considered positive that will involve skin and subcutaneous 
tissue within the first 30 postoperative days, not reaching the sternum, requiring local surgical 
intervention with regular wound care, accompanied by antibiotic therapy and/or Vacuum 
Assisted Closure (VAC) therapy.  
 
6- Delayed Healing:  Healing is a complex biochemical process of tissue repair after it has 
been damaged. It has three stages which are inflammation, proliferation and remodelling. Delay 
in the specific time period or in the biochemical process is called delayed healing. Skin, 

8 
 
subcutaneous tissue or sternum which is unable to heal within two weeks of surgery will be 
considered delayed wound healing. 
 
7- Readmission: It is defined as any hospital readmission within 30 days of discharge related 
to the index surgery.  
 
8- ICU stay: Stay that refers to the duration, in days, spent in the intensive care unit, within 30 
days postoperatively.  
 
9- Blood transfusion: It is defined as the requirement of more than 4 units of packed red blood 
cells (PRBC) or platelets within 30 days postoperatively. 
 
Hypothesis  
Administration of platelet rich plasma during sternal wound closure reduces the frequency of 
complications in the 30-days post-surgery period. 
 
MATERIAL AND METHODS 
Study Design 
Randomized control trial 
Study Setting 
The Department of Cardiac Surgery, Cardiac Center, Pakistan Institute of 
Medical Sciences (PIMS), Islamabad. 
Duration 
06 months after acceptance of synopsis 
Sample selection; 
Inclusion criteria 
 
                                   Patients from 45 to 72 years of age, undergoing on pump CABG,  

9 
 
                                   cardiac surgery with median sternotomy.  
                                   Patients who provide consent. 
Exclusion criteria 
●    BMI less than 18.5 or more than 24.9 
●    Bilateral harvesting of the internal mammary artery,  
●    Steroid therapy,  
●     Known Diabetic,  
●      Active smoker,  
●      Osteoporosis,   
●      Chronic lung disease, 
●      CPB time more than 72.5 minutes 
●       Platelet Rich Plasma cannot be obtained. 
●       Patients who are not candidates for blood bank donations. 
Sample size 
The sample size has been calculated by using WHO size calculator with the statistical 
assumptions as following: 
 
(Level of significance = 5%), (Power of test = 80%), (Population standard deviation = 3.0) 
(Anticipated population, rate of oedema and infiltration in prp group, P1= 18%) 
Anticipated population, rate of oedema and infiltration in control group, P2= 44%Sample size 
comes out to be 49 cases in each study group and a total of 98 patients will be included in the 
study. 

10 
 
Sampling Technique  
Participants will be recruited using non-probability consecutive sampling and randomly 
assigned to one of two groups.  
Data Collection Procedure 
The study protocol will be first submitted for approval to the hospital ethics committee and 
Advance Research committee. A written informed consent will be taken from all parents/ 
caretakers. The subjects fulfilling inclusion will be enrolled from Cardiac Center. Participants 
will be recruited using non-probability consecutive sampling and randomly assigned to one of 
two groups. The antibiotic prophylaxis will be given 60 min before incision. The preoperative 
antibiotics protocol and glycemic management protocol will be standard and  will remain the 
same for all patients throughout the study. Patients will be given general anesthesia. This will 
ensure that they are asleep and pain free through the whole surgery. An incision of 8- to 10-
inch will be made in the chest. A midline sternotomy with a sternal saw blade will be done. 
Bleeding sites will be secured followed by pericardiectomy. Once the heart is visible, 
cannulation will be done and the patient will be connected to a heart-lung bypass machine. 
The machine will move blood away from the heart so that the surgeon can operate. Surgery 
will be performed according to local guidelines. Patients will be heparinized using an initial 
dose of 300 IU/kg unfractionated heparin. During surgery the activated clotting time (ACT) 
will be maintained at least 480 s. All patients undergoing sternotomy will be included in the 
study including emergencies, reoperations, ventricular assist device implantations, heart 
transplants, aortic dissections and standard operations (i.e. coronary artery bypass grafting and 
valve repairs or replacements). Following sternotomy, the use of bone wax on the sternum will 
be avoided, as this might form an intrasternal barrier and interfere with PRP augmented 
healing. Targeted flow rates during cardiopulmonary bypass were 2.6 L/min/m2 , yielding a 
venous saturation of 70−80%. After heparin reversal is achieved with protamine, all the 
bleeding spots will be identified and stopped i.e. haemostasis will be secured. The control 
group will undergo midline sternotomy with a sternal saw blade. The sternum will be closed 
with a simple interrupted or figure of eight stainless steel wire. The wounds will be closed in 
a layered manner with absorbable suture and dressed with Steri-Strips, gauze and paper tape. 
The study group will additionally receive 6 mL of autologous PRP applied to sternum and soft 

11 
 
tissue during sternal closure. Participants and outcome assessors will be blinded to group 
assignment, while surgeons performing the procedure will be aware of the intervention 
Primary outcome will be measured as frequency of sternal wound complications in terms of 
delayed healing, superficial infection, deep infections, and readmission rate including 
mediastinitis in 30-days period post-surgery. Secondary outcome will be the overall cost 
burden for the 30-days post-surgery period. Other outcomes will be ICU stay (days), red cell 
concentrate (RCC) more than 4 units and platelets transfusions more than 4 units. 
All the information will be entered on the predesigned Performa by the researcher himself to 
comply with the study protocol attached as Annexure-I. 
Data Analysis 
Quantitative variables (age, hospital stay, ICU stay, cost) will be summarized as mean ± SD or 
median (IQR) and compared using t-test or Mann–Whitney U test. Categorical variables 
(superficial/deep wound infections, delayed healing, readmissions, transfusion requirements, 
residence (urban\rural), education status and socioeconomic background (low\middle) will be 
reported as counts and percentages and compared using chi-square or Fisher’s exact test. A p-
value <0.05 will be considered significant. Missing data will be handled using complete case 
analysis. All analyses will be performed using [SPSS/R]. 
Ethical Considerations 
From ethical point of view: 
● Those patients will be included in the study that will be willing to participate in the 
study. 
● A written informed consent will be taken from the patients and they will be ensured 
that their confidentiality will not be breached. 
● There will be no compromise on the standard care and treatment for study purposes. 
 
 
 

12 
 
References 
[1]  Reser, Diana, et al. "Median sternotomy." Multimedia manual of cardiothoracic surgery: 
MMCTS 2015 (2015). 
[2]  Balachandran, Sulakshana, et al. "Risk factors for sternal complications after cardiac 
operations: a systematic review." The Annals of thoracic surgery 102.6 (2016): 2109-2117. 
[3]  Patel, Amit N., et al. "Evaluation of autologous platelet rich plasma for cardiac surgery: 
outcome analysis of 2000 patients." Journal of cardiothoracic surgery 11.1 (2016): 1-6. 
[4]  Heilmann, Claudia, et al. "Wound complications after median sternotomy: a single-centre 
s  
[5]  Vermeer, Harry, et al. "Platelet-leukocyte rich gel application in the prevention of deep 
sternal wound problems after cardiac surgery in obese diabetic patients." Journal of thoracic 
disease 11.4 (2019): 1124. 
[6]  Schiraldi, Luigi, et al. "Deep sternal wound infections: Evidence for prevention, treatment, 
and reconstructive surgery." Archives of plastic surgery 46.4 (2019): 291. 
[7]  Kirmani BH, Jones SG, Datta S, McLaughlin EK, Hoschtitzky AJ. A meta-analysis of 
platelet gel for prevention of sternal wound infections following cardiac surgery. J. Blood 
Transfus. 2017 Jan;15(1):57. 
[8]  Yao D, Feng G, Zhao F, Hao D. Effects of platelet-rich plasma on the healing of sternal wounds: A 
meta-analysis. Wound Repair Regen. 2021 Jan;29(1):153-167. 
[9]  Serraino, Giuseppe F., et al. "Platelet‐rich plasma inside the sternotomy wound reduces the 
incidence of sternal wound infections." International wound journal 12.3 (2015): 260-264.  
[10]  Dominijanni, Andrea, et al. "Platelet gel in oral and maxillofacial surgery: a single-centre 
experience." Blood Transfusion 10.2 (2012): 200.