Faculty of medicine Department of cardiology

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Faculty of medicine

Department of cardiology

Treatment of deep sternal wound infection after cardiac surgery

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1. Summary

Deep sternal wound infection is one of the main complications after major cardiac surgery globally. Dealing with the infection and getting completely cured is very challenging, time-consuming and a costly process. Mortality and morbidity are still high after decades despite modern surgical techniques, drugs and protocols of prevention of infection preoperatively. Many different protocols and methods are performed and reported for the treatment of deep sternal wound infections.

This study will review articles about the treatment of deep sternal wound infection that are presented in [Table 1]. The aim is to see how deep sternal wound infection is treated and what methods are performed. Risk factors that may increase or contribute to getting this complication since deep sternal wound infection is a complication of major cardiac surgery will also be reviewed. The study will analyse the methods that had the best outcome of surgery procedures. The search was performed on the database PubMed. All selected articles were downloaded, read and analysed.

The objective is to perform a systematic search and to identify articles and publications relevant to the main thesis. By reviewing and detailed analysing various studies, articles that are specifically related to the thesis were found and implemented. The evaluation of different treatment methods outcome was performed.

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2. Conflicts of interest

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3. Abbreviations

AVD Atherosclerotic vascular disease AVR Aortic valve replacement

BMI Body mass index

BPMMF Bilateral pectoralis major muscle flap

BT Blood transfusion

CABG Coronary artery bypass grafting CAD Coronary artery disease

COPD Chronic obstructive pulmonary disease CRF Chronic renal failure

DM Diabetes mellitus

DSWI Deep sternal wound infection HBU Homogenous blood usage HO2T Hyperbaric oxygen therapy

HT Hypertension

IABP Intra-aortic balloon pump IMA Internal mammary artery

LF-UAW Low Frequency-Ultrasound assisted wound debridement LVEF Left ventricular ejection fraction

MCFC Musculocutaneous flap closure MFC muscle flap closure

MI Myocadiac infarction

MPMF Mono-lateral pectoralis muscle flap

MRSA Methicillin-resistant Staphylococcus aureus MVR Mitral valve replacement

OF Omental flap

OP Operation

PAD Peripheral artery disease PMF Pectoralis muscle flap PVD Peripheral vascular disease

RF Renal failure

RV Right ventricle

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TPF Titanium plate fixation

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4. Terms

Debridement: The removal of damaged tissue or foreign objects from a wound.

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5. Introduction

Deep sternal wound infection (DSWI) is a life-threatening condition that occurs mainly in patients undergoing major cardiac surgery with an incidence between 0.6 and 5 %. A procedure called sternotomy in which an incision is made vertically to be able to divide sternum in two halves and separate them to be able to easily access the heart or mediastinum. This infection is also called post-sternotomy infection or mediastinitis in which a deeper layer of the sternum is involved or mediastinal space and that is why antibiotic are usually accompanied in all these procedures [1-2]. Many risk factors are known, and some are yet to be discovered. Most of the patients who develop DSWI after major cardiac surgery are diagnosed with obesity or diabetes mellitus type 2 which are two of the major risk factors [3].

Identifying high-risk factor patients and then managing the risk factors in addition to choosing an appropriate method of surgery or strategy of management will have a significant impact on the reduction of the DSWI incident [4].

To diagnose DSWI, the clinical presentation, laboratory results, and radiological findings must be known. For the more precise diagnosis of mediastinitis, the diagnosis must also include at least one of the following criteria:

1) A positive culture from the wound.

2) Evidence that show signs of mediastinitis in a pathohistological examination or during the surgery procedure.

3) Either fever >38, chest pain or sternal instability [4].

One of the preventive methods that reduces the incident of DSWI is applying Platelet-leukocyte rich gel on the sternum halves before closure. This gel promotes tissue healing leading to reduced risk of infection after cardiac surgery in obese or diabetic patients [1].

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There are many methods for the treatment of DSWI such as TPF. As an example, in [Fig. 1] titanium plates were placed transversally to achieve complete sternal integrity as well as one “H” shape short plate as a very limited muscular-cutaneous flap could develop in this area [7]. The treatment can be a combination of procedures as well. In [Fig. 2] the wound closure is achieved by using OF to cover the dead spaces in the mediastinum. This procedure is done by making a tunnel in the anterior surface of the diaphragm to transport an omental pedicle to anterior mediastinum followed by PMF to achieve a tension-free skin closure [6].

Other methods are bilateral pectoralis major muscle flap (BPMMF), omental flap (OF), unilateral pectoralis muscle flap (UPMF), antibiotics, vacuum-assisted closure (VAC), titanium sternal plate fixation (TSPF)/(TPF) or a combination of some of these methods. Choosing a surgical method can depend on a patient’s age or risk factors. In patients’ who do not have sternal bone necrosis and are younger than 70 years old, BPMMF could be a better option than other techniques such as OF due to its lower mortality rate and recurrence [6].

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6. Aim and objectives

This study will review articles about the treatment of deep sternal wound infection which is not older than five years. The aim is to see how deep sternal wound infection is treated and what methods are performed. Risk factors that may increase or contribute to getting this complication since deep sternal wound infection is a complication of major cardiac surgery will also be reviewed. The study will analyse the methods that had the best outcome of surgery procedures. The search was performed on the database PubMed by these following steps:

1. Perform a systematic search of the literature using a database to identify articles and publications relevant to the main thesis.

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7. Literature review

7.1 Definition and diagnosis of DSWI

Centers for Disease Control and Prevention, defined DSWI as an infection that must include at least one of the following criteria:

1) A positive culture from the wound.

2) Evidence that shows signs of mediastinitis in a pathohistological examination or during the surgery procedure.

3) Either fever >38, chest pain or sternal instability. The diagnosis is based on the above-mentioned criteria as well as clinical examination and radiological findings. The diagnosis is confirmed by microbiological findings [2] [5] [9-11].

7.2 Incident

DSWI is a serious condition that is life-threatening and has a high mortality rate despite modern technique and proper treatment. The incident of DSWI varies depending on the year of publication, study methodology and patient population [4]. In some studies, the incidence of DSWI is somewhere between 0.6%-5% with a mortality rate between 10%-47% [9]. In some other studies the DSWI incident is between 1% to 3% with a mortality rate of 19%-29% [12] or in additional study 0.2%-3% and a mortality rate of 1.1%-19% [4].

One of the factors that strongly influence on the incident of DSWI is the type of procedure and duration of it. The lowest incident of DSWI was in patients undergoing isolated valvular surgery which had an incident rate of 1.3% and the highest rate was in patients undergoing concomitant coronary artery bypass grafting CABG with thoracic aortic surgery which had a rate of 3.4% according to Liverpool hospital, NSW, Australia [13].

7.3 Risk factors

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complexity of procedure play an important role [13]. There are several patient-related risk factors such as the patient’s comorbidities, age, obesity and habits such as smoking [1] [5] [7]. Not all the risk factors are manageable, but some of the patient-related risk factors such as diabetes could be controlled preoperatively. Continuously insulin infusion to a diabetic patient intraoperatively and maintaining the infusion through the first two postoperative days could reduce the risk of DSWI in the patient undergoing major cardiac surgery [13].

In addition, Pankaj Kaul mentioned tissue strangulation in tissue closure or use of excessive rewiring material, sternal plates, COPD [14], nosocomial infection, dialysis, prolonged mechanical ventilation as other risk factors for DSWI [15]. Another study shows that chronic infections could be also a risk factor for DSWI such as human immunodeficiency virus, hepatitis B virus, hepatitis C virus and a bacterial illness for more than 4 weeks [11].

7.4 Classification of sternal wound infection

El Oakley and Wright classified sternal wound infection (SWI) into two separate classifications. The first classification is according to risk factors and time of presentation after surgery which they presented DSWI in five major types and their subtypes, I, II, IIIa-IIIb, IVa-IVb and V. Type I is when the infection occurs within 2 weeks after surgery with no risk factors. Type II within 2-6 weeks with no risk factors. Type IIIa within 2 weeks and with >1 risk factor and IIIb 2-6 weeks with <1 risk factor. Type IVa is when the therapeutic trials failed one time in type I-III and IVb when therapeutic trials failed two times or more. Type V is when the presentation after surgery is more than six weeks. The second classification is according to anatomical region involvement which also has 5 types. Type 1, 2A, 2B, 2C, 2D. Type 1 is only a superficial sternal infection which is not extended beyond the skin and subcutaneous layer followed by type 2A without bone and retrosternal involvement whereas in type 2B retrosternal tissue is involved followed by type 2C which has the involvement of bone as well and type 2D which is osteitis [11].

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cellulitis and purulent wound drainage. Osteomyelitis is common and costochondritis can also occur but it’s not common. Type 3 infection is a chronic infection that develop within a few months after cardiac surgery and it involves draining sinus tract into the sternum or costochondral arches [9].

Rupprecht and Schmid presented another classification that is integrated with El Oakley and Wright classification. This classification allows one to choose the right treatment according to clinical findings. The classification is presented as followed:

Sternal instability without infection: Instability occurs when a high traction force is applied on the sternum edges after surgery and do not let the sternum to heal properly. This can cause gliding trauma and eventually cause chronic pain syndrome. Severe cough is an example of such a force.

DSWI without sternal instability: When there is significant tension on the skin and soft tissue, this tension does not allow the wound to heal properly due to wound dehiscence that occurs despite a good sternum structure. This condition is usually seen in patients with large breasts, obese or diabetic patients.

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8. Method

All selected articles were downloaded, read and analysed. A systematic search of the literature was performed by using PubMed to identify articles and publications relevant to the main thesis. The following keywords were used either alone or in a combination: “Deep sternal wound infection treatment”, “vacuum-assisted closure”, “mediastinitis” and “surgical”. [Fig. 3] demonstrate how the 24 articles that were used for writing this master thesis were selected. By reviewing and detailed analysing various studies, articles that are specifically related to the main thesis were found as well as some other articles that contributed indirectly. The treatment outcome of different treatment methods was evaluated.

Figure 3. Systematic search on PubMed. By reading the title of articles, abstract and later reading the full text article, only 24 articles were selected for this thesis. Nine of 24 selected articles where used as a complementary and 15 of 24 were used for the purpose of study of DSWI treatment which are presented in the result.

Articles identified through database searching on PubMed using key

words (n = 714)

Articles removed due to lack of access to full text

(n = 5) Selected articles with title related to

the main thesis (n = 62)

Full-text articles assessed for eligibility

(n = 57)

Full-text articles excluded; the articles were not useful for the purpose of the

thesis (n = 33)

Studies included in this thesis (n = 24)

Studies included in quantitative synthesis (meta-analysis)

(n = 15)

Articles removed due to unrelated title to the main thesis

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9. Results

Table 1:

The results of the reviewed articles are presented in this table.

Stud y nr of cases sex _M/F age Comorbidities /Risk-factors Type of study The primary type of surgery Type of Tx-procedure for DSWI Follow

up Outcome and additional information Mortality

[2] 15 7/8 65 DM CRF retro prospecti ve CABG, valvular replacement, aortic replacement surgical debridement and VAC then Dalbavancin as definitive Tx

6m 14 patients did not show any sign of DSWI or any other problems anymore. 1 patient had a relapse after 97 days. 0 [16] 56 40/16 64 DM COPD PVD Obesity retro prospecti ve CABG IMA

VAC and AB before surgical reconstruction. 23 pts with conventional sternal rewiring and 33 with other interventions (PMF) but no sternal refixation

12m Readmission was higher in the sternal rewiring group than others as well as 5 cases of mortality in the rewiring group with no mortality in others. PMF is a better option for the treatment of DSWI.

5 (90 days) [8] 42 30/12 71.5 DM, COPD, HT, PVD, MI, OP

cohort VAC and AB and then TSFS or MFC as a final treatment 36.6 m for TSFS and 23.6 m for MFC group

TSFS had shorter operation time and hospitalization as well as a lower mortality rate. Even the quality of life was better in patients undergoing TSFS procedure, but patients with muscle flap closure (MFC) had lesser chest pain and could breathe freely. Due to better tissue perfusion in MFC patients, the MFC procedure is a better option in complicated DSWI. Because in perfused tissue, the infection could be better controlled.

3 (TSFS) 9 (MFC) [17] 1 male 60 DM, obesity, HT COPD, AVD, case report

CABG When all other ABs were insufficient, Dalbavancin was used which was effective as well as sternum refixation

Treatment was successful as the patient was discharged 27 days after admission or 15 days after surgery. The wound was completely healed, and the sternum was stable.

0 [18] 34 66.1 DM, previous cardiac op, BMI >30, IABP, HBU, Obesity. cohort CABG, AVR, MVR, CABG+AVR Aortic dissection. conservative management with AB 1 patient. surgical debridement with or without rewiring 13 patients. MFC 16 patients. mean follo w up 3.2 years

There was no mortality in patients 16/30 who underwent MFC. But 4/16 had complications. 3 patients passed away during the follow-up period, but it was not related to DSWI treatment. BPMMF was the most common surgical treatment with the best outcome.

4 in hospital 3 follow up period [19] 10 6m 4f 63 DM, HT, COPD, RF, PVD, retrospec tive CABG CABG+AVR CABG+MVR Debranching Hyperbaric oxygen therapy as an additional treatment 3 months after conventional treatment being insufficient. 5 days/week, 20 sessions 92 minutes

7/10 patients were completely healed. 1 patient had to do another cycle of HO2T which resulted in complete wound healing. Two other patients, the HO2T was interrupted and they underwent muscle flap reconstruction.

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uncontrolled DM, Parkinson, Smoking, Obesity and hypercholest erolemia. Extra-abdominal-pedicled omental flap and BPMMF.

myocardial infarction following TKA 1 week prior to bypass grafting. 3 weeks postoperatively patient readmitted and was diagnosed with DSWI. The initial treatment of DSWI with AB and VAC failed. 2 days later the patient was readmitted again due to total sternal dehisced and AKF. After performing other methods as well as surgical debridement and VAC again patient developed RV perforation. The patient was discharged without complication to the rehabilitation unit 2 weeks after extra-abdominal pedicle omental flap and BPMMF procedure. [20] 107 101m 6f 65 advanced age, male gender, left-main stenosis, BMI >30, COPD, DM, BT, HT, Obesity. case-control and retrospec tive cohort CABG Surgical debridement, irrigation, sternum rewiring and if this method failed, then MFC was performed.

10.3 years

There was no increased early mortality risk in DSWI patient but there was an increased risk of morbidity (stroke, Intra-aortic balloon pump, arrhythmia, and myocardial infarction). Long term mortality in mediastinitis patients (37% cardiac-related and 17.8% non-cardiac-related) was much higher compared to non-mediastinitis patients (21.4% cardiac-related and 15.8 non-cardiac related).

2 [21] 14 10m 4f 75 DM, hyperlipidae mia, smoking, BMI >30, HT, COPD and Dialysis Obesity. Retrospe ctive CABG, AVR, MVR or a combination of these. Surgical debridement. Greater OF. The OF was performed majorly combined with split skin graft then the wound was closed using VAC for 7 days. One patient had muscle flap.

2 years

All the patients with OF procedure as a treatment of DSWI had a full recovery and the wound was completely healed. In these populations, death was not related to OF procedure, rather it was due to cardiovascular failure due to multimorbidity of this population. 0 [10] 45 25m 20f 66.6 A 65.4 B DM, Smoking, COPD, PAD BMI >30 Obesity. Retrospe ctive

CABG LF-UAW and VAC (23 patients, group A), VAV (22 patients group B). Both groups had musculocutaneous flap closure (MCFC) as a final step. 7.3 m group A 8.7m group B.

The hospital stay was significantly shorter in group A as well as wound healing was faster. The recurrence of SWI was much lower in the group A 1/23 compare to group B which was 7/22

0 [6] 60 38m 22f 63A 70B 70C DM, advanced age, male gender, PAD, BMI >30, COPD, RF, BT, Obesity. Cohort CABG, AVR, or combinations

All patients had surgical debridement and VAC. For secondary closure of the wound. Group A, B had BPMMF, group C had OF following VAC.

Group A (n=21) had type II DSWI, group B (n=20) type III and both with BPMMF as a treatment whereas group C (n=19) with type III had OF as a treatment following VAC.

Group A had the best outcome with no mortality or morbidity. In group B, death occurred in 1/20 patients and treatment failed in 2/20 cases in the post-discharge period. But after further treatment, the wound was healed in both patients and they were discharged. The hospital stay was almost twice longer in group C compared to group B as well as in-hospital mortality 3/19 in group C compared to group B 1/20.

BPMMF is superior to OF when the patient is younger than <70 and has no sternal bone necrosis.

A=0 B=1 C=3 [7] 36 TPF 26 cont rol. 23m 13f 63.9 DM, advanced age, male gender, Hyperlipidae mia BMI >30, COPD, RF, BT, LVEF, Retrospe ctive non-specific cardiac surgery Surgical debridement and removal of the previous wires and then VAC. Titanium plate fixation mean 15.92 m

In this study, besides having 36 patients receiving TPF with had a control group of 26 patient who received conventional therapy which had a failure rate of 43.3% (unstable sternum) and they had to go through MF reconstruction procedure whereas in the TPF group had no failure (sternum was stable). Multiple debridement’s were lower in the TPF group. Even if the mortality rate was lower in the TPF group compare to the control group, the statistical data doesn’t show any significant difference. Overall the TPF is a better treatment option for DSWI compare to conventional treatment due to low multiple debridement procedures and lower failure rate

4 =TPF 5 =control

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70f hyperlipidae mia, smoking, BMI >30, HT, Obesity, COPD and CRF. ctive replacement and also a combination of both. debridement, VAC and then mono-lateral pectoralis muscle flap (MPMF) for 86 patients (group A) and for the remaining 81 patients (group B) BPMF.

whereas in group B 30/81 patient had complications. 8 patients in group A needed wound revision and 14 patients in group B. In the overall group, A had lower hospital stay time as well as time spent in ICU was lower in group A. Group B=1 [23] 106 69m 37f 69 HT, DM, Obesity Retrospe ctive CABG, valve replacement and also a combination of both. Aortic bow replacement, heart/lung transplantatio n.

VAC and surgical debridement. Latissimus dorsi flap

18m Latissimus dorsi flap reconstruction is a good option for the treatment of DSWI. Our patients overall had a better quality of life compared to those with heart insufficiency and diabetes although physical functioning was reduced. The graph of self-evaluation presents that 35 percent of the patients didn’t feel any significant difference post-surgically in acute state and 20 percent felt much better.

21 (within thirty days), 50 (after one year) 58 (follow up) [24] 52 36m 16f 53 DM, Smoking, COPD, Prolonged ventilator, Retrospe ctive CABG, VR or combination. Aortic dissection. Repairment of the defected septum. Surgical debridement. VAC and BPMMF.

12m 4 patients had complications of which 1 died due to respiratory failure and the other 3 were cured. 51/52 patients were cured to discharged. 1 patient died during 12 months follow up due to acute cerebral haemorrhage.

1 died (in hospital) 1 died in follow up

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10. Discussion of the results

In the report by Michele Bartoletti et al. (2019), the 15 patients with DSWI were treated with dalbavancin which had very good results with no mortality [2]. There is also a single case report using the same antibiotic with similar outcome [17]. The use of Dalbavancin is the best choice since it has better bone tissue penetration which means it could be used for the treatment of osteomyelitis. Dalbavancin covers Gram-positive strains and MRSA and it’s 16 times more effective compared to vancomycin when treating DSWI caused by Streptococcus pneumoniae [17]. More trials are needed for better understanding and if this treatment really has such a good result, then maybe dalbavancin could be used as a definitive treatment in DSWI.

In some other cases, the surgical technique is used as well as vacuum-assisted therapy (VAT) before plastic reconstruction due to its provision of negative pressure that reduces wound oedema and ameliorate wound granulation and healing [7].

Since DSWI can lead to a bone infection, it is necessary for the surgeon to perform a radical debridement. Survival benefit for patients undergoing VAT has been shown in some studies. This is a reason why most heart surgery procedures use VAT in the interval between debridement and final closure of the wound [21].

One of the plastic reconstructions methods is using the omental flap (OF) or muscle flap which in both cases, VAT is done [15]. In the case of recurrent infection, persistent infection or remaining potentially infected artificial material, muscle flap closure (MFC) is not sufficient for defect coverage. That is why OF is a better choice [21]. Since the muscle flap will get stiff and become more like a scar tissue it will be difficult to use the same flap for coverage after transplantation. On the other hand, greater OF can cover all the dead spaces and cavities even artificial materials. OF has also anti-infection activity and immunologic capacity. But the disadvantage of the greater OF is the risk of hernia in the abdomen as well as infection due to its site being near the already existing infection source [21].

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seems to be higher in group C, one should note that, out of the three patients’ who died, only one patient died due to mediastinitis-related endocarditis and the other two died due to unrelated causes [6].

The study performed by Rashed et al. (2016), had the best result with MFC compare to patients who had sternal rewiring plus wound closer [16]. Spindler et, al. had MFC as the first-choice treatment for DSWI, but since they got better results with OF, they changed their strategy in the hospital [21].

In the study by Wei Wang et al. (2016), they compared TPF with conventional treatment. TPF patients had stable sternum whereas 42.3% of patients with conventional treatment had rewiring failure and they had MF reconstruction by plastic surgery. This study also shows that TPF makes the chest wall much more stable. In the patients who underwent rewiring despite multiple debridement’s, treatment didn’t succeed and required plastic surgery. TPF is the best procedure for the treatment of severe DSWI [7]. The amount of perfused tissue helps for control of infection and that is why MFC is a better option for treatment of complicated DSWI compare to TSF [8].

In the study by Litwinowicz et al. (2016), HO2T was successful in 80% of patients. HO2T is an additional therapy for DSWI and can improve sternal stabilization, wound sterilization and final healing. This therapy can specially be used when pharmacotherapy and VAC have failed [19].

In the study by Federico Lo Torto et al. (2010), MPMF had better results compare to bilateral. Because the surgery time is less as well as the complication rate is lower. The effectiveness of coverage and mortality is comparable to BPMMF. One of the advantages of the MPMF procedure is that the contralateral pectoralis muscle is preserved and could be used in case of failure [22].

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11. Conclusions

PMF is the better option for the treatment of DSWI. When the wound is bigger both pectoral muscles could be used. By using this method both flaps together can cover the dead spaces. OF is a risky procedure due to its site being near the infectious site. Additionally, by making an incision in the lower part of the sternum in order to bring it out to lay it over the sternum, this will cause a path for pathogens to get into the abdominal cavity. This procedure is therefore better as a backup when other procedures fail or because OF has an immunologic capacity. It might be a better option in the patients who are going to have artificial material. TSF has lower multiple debridement’s and lowers failure rate as well as it makes the sternum stable. However, in patients with complicated DSWI, PMF is still a better option because the tissue will have better perfusion and the infection could be controlled.

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12. References

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2. Bartoletti M, Mikus E, Pascale R, Giannella M, Tedeschi S, Calvi S, et al. Clinical experience with dalbavancin for the treatment of deep sternal wound infection. J Glob Antimicrob Resist. 2019 Sep;18:195–8.

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16. Rashed A, Gombocz K, Alotti N, Verzar Z. Is sternal rewiring mandatory in surgical treatment of deep sternal wound infections? J Thorac Dis. 2018 Apr;10(4):2412–9. 17. Guzek A, Suwalski G, Tomaszewski D, Rybicki Z. Dalbavancin treatment in a deep

sternal wound MRSA infection after coronary artery bypass surgery: a case report. J Cardiothorac Surg. 2018 Dec;13(1):3.

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21. Spindler N, Etz C, Misfeld M, Josten C, Mohr F-W, Langer S. Omentum flap as a salvage procedure in deep sternal wound infection. Ther Clin Risk Manag. 2017 Aug;Volume 13:1077–83.

22. Lo Torto F, Turriziani G, Donato C, Marcasciano M, Redi U, Greco M, et al. Deep sternal wound infection following cardiac surgery: A comparison of the monolateral with the bilateral pectoralis major flaps. Int Wound J. 2020 Feb 17;iwj.13324.

23. Spindler N, Kade S, Spiegl U, Misfeld M, Josten C, Mohr F-W, et al. Deep sternal wound infection – latissimus dorsi flap is a reliable option for reconstruction of the thoracic wall. BMC Surg. 2019 Dec;19(1):173.

Faculty of medicine Department of cardiology