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Three Part Question

In [patients who undergo coronary artery bypass grafting] does [bilateral internal thoracic artery grafting] increase the risk of [mediastinitis]?

Clinical Scenario

You are seeing a 60-year-old man who has been referred for multivessel coronary artery bypass grafting (CABG). He is an insulin-treated diabetic with a body mass index of 27 and no previous myocardial infarction. His father also died of a heart attack when he was 65 years old. You tell him that the grafts with the best long-term patency are the internal thoracic arteries. You would like to perform CABG using bilateral internal thoracic arteries (BITA) and a vein graft. You inform the patient that this configuration of the procedure carries higher risk for mediastinitis, which is associated with about 20% in-hospital mortality and higher long-term mortality [Toumpoulis]. He is not that keen on the idea and asks if there are any other configurations that could have the same long-term results without the risks of mediastinitis. You wonder whether BITA would be performed in diabetics with low risk of mediastinitis

Search Strategy

Medline 1995 – July 2007 using the OVID interface.
[Coronary artery bypass OR CABG OR aortocoronary bypass OR off-pump bypass OR on-pump bypass.mp] AND [Internal thoracic OR internal mammary.mp] AND [double OR bilateral] AND [Mediastinitis OR deep sternal OR sternal infection OR chest infection OR surgical site infection.mp].

Search Outcome

One hundred and forty papers were found in Medline. Twenty-four were deemed to be relevant. The papers are documented in the table

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
The Parisian Mediastinitis group, 1996, France	CABG (n=960). BITA (n=126)		Deep sternal wound infection	3.3% deep sternal wound infection. BITA was an independent predictor (OR 4.78, 95% CIs 1.36–16.7, P=0.01)	No randomized, not double-blind. No evaluation of pedicled and skeletonized BITA
Ridderstolpe et al, 2001, Sweden	Cardiac surgery (n=3008). CABG (n=2108). BITA (n=87)		Deep sternal infection/mediastinitis	BITA was an independent predictor for deep sternal infection/mediastinitis (OR 4.23, 95% CIs 1.71–10.51, P=0.002)	Retrospective study. No propensity matching. Not only CABG patients analyzed
Stahle et al, 1997, Sweden	CABG patients (n=9989)		Mediastinitis	1.7% mediastinitis after CABG. BITA was an independent predictor (OR 3.3, 95% CIs 1.1–7.7)	Retrospective study. No evaluation of pedicled and skeletonized BITA
Toumpoulis et al, 2006 USA	Diabetics. Comparison of propensity matched BITA (n=490) with SITA (n=490)		Deep sternal wound infection	3.3% vs. 1.2% deep sternal wound infection in BITA vs. SITA (P=0.05)	Retrospective study. No evaluation of pedicled and skeletonized BITA
Kai et al, 2007 Japan	Insulin-dependent diabetics. Off-pump CABG with skeletonized BITA (n=162) vs on-pump CABG with pedicled BITA (n=23)		Deep sternal infection	0.6% vs. 13.0% deep sternal infection in off-pump vs. on-pump (P=0.01)	Small sample size. Retrospective study. No propensity matching
Peterson et al, 2003 Canada	Diabetics. Skeletonized BITA (n=79) vs. nonskeletonized BITA (n=36).		Deep sternal wound infection	1.3% vs. 11.1% deep sternal wound infection in skeletonized BITA vs. non-skeletonized BITA (P=0.03)	Small sample size. Retrospective study. No propensity matching
Tavolacci et al, 2003 France	CABG in diabetics (n=256). BITA (n=79)		Mediastinitis	1.7% vs. 10.1% mediastinitis in SITA vs. BITA (P<0.001). BITA was independent predictor for mediastinitis (OR 5.97, 95% CIs 1.63–21.93, P=0.004)	Small sample size. Retrospective study. No propensity matching
Endo et al, 2003 Japan	Non-diabetics: SITA (n=411) vs. skeletonized BITA (n=253). Diabetics: SITA (n=277) vs. skeletonized BITA (n=190)		Deep sternal wound infection	0.2% vs. 0.4% deep sternal wound infection in non-diabetics with SITA vs. BITA (P=0.99). 1.1% vs. 0.5% deep sternal wound infection in diabetics with SITA vs. BITA (P=0.65)	Small sample size. Retrospective study. No propensity matching
Pevni et al, 2003 Israel	Skeletonized BITA (n=1000). Diabetics (n=304)		Deep sternal wound infection	2.2% deep sternal wound infection. Diabetes was not an independent predictor	Retrospective study. No control group
Lev-Ran et al, 2004 Israel	Diabetics (oral-treated). BITA (n=228) vs. SITA (n=57)		Deep sternal wound infection	1.8% vs. 1.8% deep sternal wound infection in BITA vs. SITA (P=0.999)	Small sample size. Retrospective study. No propensity matching
Lev-Ran et al, 2004 Israel	Diabetics with skeletonized BITA (n=515). Oral-treated (n=468) and insulin-treated (n=47). In situ BITA was compared to T-grafting		Deep sternal infections	1.9% vs. 4.3% deep sternal infection in oral-treated vs. insulin-treated. 1.9% vs. 2.3% deep sternal infection in patients with in situ skeletonized BITA vs. T-graft skeletonized BITA (P=0.999)	Small sample size. Retrospective study. No propensity matching
Boodhwani et al, 2006 Canada	BITA (n=48) randomized to receive 1 skeletonized and 1 nonskeletonized Randomized, double blind, within patient comparison study		Postanastomotic flow, sternal perfusion	No significant different postanastomotic flows (p=0.16). Increased sternal perfusion with skeletonized BITA (p=0.03)	Small sample size. No comparison between groups with only skeletonized BITA vs only pedicled BITA. No evaluation of deep sternal wound infection
Stevens et al, 2005 Canada	Non-diabetics: SITA (n=2079) vs. BITA (1594). Diabetics: SITA (n=419) vs. BITA (n=214)		Deep sternal wound infection	1.2% vs. 1.2% deep sternal wound infection in non-diabetics with SITA vs. BITA. 2.2% vs. 1.4% deep sternal wound infection in diabetics with SITA vs. BITA	Retrospective study. No propensity matching
Momin et al, 2005 UK	Insulin-dependent diabetics. SITA (n=166) vs. BITA (n=95)		Deep sternal wound infection, sternal dehiscence	1.2% vs. 3.2% deep sternal infection in SITA vs. BITA (P=0.27). 1.2% vs. 3.2% sternal dehiscence in SITA vs. BITA (P=0.27)	Small sample size. Retrospective study
Bical et al, 2004 France	Patients <70 years. Diabetics BITA (n=164) vs. non-diabetics BITA (n=548)		Deep sternal wound infection	1.1% vs. 1.2% deep sternal wound infection in BITA diabetics vs. non-diabetics (P=NS)	Small sample size. Retrospective study. No propensity matching
Crabtree et al, 2004 USA	CABG patients (n=4004). Deep sternal wound infection (n=73)		Superficial and deep sternal wound infection	1.8% deep and 2.2% superficial sternal wound infection respectively. BITA was an independent predictor for superficial sternal wound infection (OR 7.55, 95% CIs 3.18–17.94, P<0.001)	Retrospective study. No evaluation of pedicled and skeletonized BITA
Ura et al, 2002 Japan	Pedicled BITA (n=558). Diabetics (n=143)		Mediastinitis	1.3% mediastinitis rate. 2.1% mediastinitis in diabetics. Diabetes was not an independent predictor for mediastinitis	Small sample size. Retrospective study. No control group
De Paulis et al, 2005 Italy	SITA (n=450) vs. pedicled BITA (n=300) vs. skeletonized BITA (n=150)		Deep sternal infection	1.1% vs. 3.3% vs. 4.7% deep sternal infection in SITA vs. skeletonized BITA vs. pedicled BITA (P=0.01)	Retrospective study. No propensity matching
Toumpoulis et al, 2005 USA	CABG patients (n=3760). BITA (n=2076). Deep sternal wound infection (n=40)		Deep sternal wound infection	1.4% vs. 0.7% deep sternal wound infection in BITA vs. non-BITA. BITA was an independent predictor for deep sternal wound infection (OR 2.6, 95% CIs 1.3–5.3, P=0.01)	Retrospective study. No evaluation of pedicled and skeletonized BITA
Walkes et al, 2002 USA	SITA (n=911) vs. BITA (n=158)		Mediastinitis	2.0% vs. 4.4% mediastinitis in SITA vs. BITA (P=0.06)	Small sample size. Retrospective study. No propensity matching

Comment(s)

Mediastinitis (or deep sternal wound infection) is an infrequent, yet potentially devastating complication after CABG, which is associated with increased cost of care, prolonged hospitalization, and increased morbidity and mortality. The reported incidence of mediastinitis range from 1.3% to 4.7% in patients with BITA grafting [2–6] and indeed BITA has been shown to be an independent predictor for mediastinitis with an odds ratio ranging from 2.6 to 4.8 [7–11]. Furthermore, in diabetic patients undergoing CABG the use of BITA has been associated with higher percentages of mediastinitis which can be as high as >10% [12–14]. There is a subgroup of patients in whom skeletonized BITA was used with lower rates of mediastinitis. Skeletonized use of BITA has been associated with mediastinitis ranging from 0.4% to 2.6% in the whole context of CABG [15–17] and from 0.5% to 3.3% in diabetic patients [4, 15, 16, 18, 19]. The beneficial effect of BITA skeletonization with respect to reduced rates of mediastinitis can be attributed to the statistically significant increased sternal perfusion with skeletonized BITA compared to pedicled BITA. This was shown clearly in a randomized, double-blind within-patient comparison study, in which patients were randomized to receive one skeletonized and one pedicled internal thoracic artery graft [20].

Editor Comment

BITA, bilateral internal thoracic artery; CABG, coronary artery bypass grafting; SITA, single internal thoracic artery.

Clinical Bottom Line

In general, the use of pedicled BITA grafts carries increased risk for mediastinitis after CABG and this is even higher among diabetic patients, thus rendering many surgeons reluctant in using BITA grafting in this subgroup of patients. However, the use of skeletonized BITA grafts can reduce this risk and both non-diabetics and diabetics can be operated on without increased risk of mediastinitis. The current available evidence shows that skeletonized BITA grafting can be safely applied in almost every patient. All cardiac surgeons should be trained efficiently in using skeletonized BITA.

References

1. The Parisian Mediastinitis group. Risk factors for deep sternal wound infection after sternotomy: a prospective, multicenter study. J Thorac Cardiovasc Surg 1996; 111:1200–1207.
2. Ridderstolpe L, Gill H, Granfeldt H et al. Superficial and deep sternal wound complications: incidence, risk factors and mortality. Eur J Cardiothorac Surg 2001; 20:1168–1175.
3. Stahle E, Tammelin A, Bergstrom R et al. Sternal wound complications – incidence, microbiology and risk factors. Eur J Cardiothorac Surg 1997; 11:1146–1153.
4. Toumpoulis IK, Anagnostopoulos CE, Balaram S et al. Does bilateral internal thoracic artery grafting increase long-term survival of diabetic patients. Ann Thorac Surg 2006; 81:599–606.
5. Kai M, Hanyu M, Soga Y et al. Off-pump coronary artery bypass grafting with skeletonized bilateral internal thoracic arteries in insulin-dependent diabetics. Ann Thorac Surg 2007; 84:32–36.
6. Peterson MD, Borger MA, Rao V et al. Skeletonization of bilateral internal thoracic artery grafts lowers the risk of sternal infection in patients with diabetes. J Thorac Cardiovasc Surg 2003;1314–1319.
7. Tavolacci MP, Merle V, Josset V et al. Mediastinitis after coronary artery bypass graft surgery: influence of the mammary grafting for diabetic patients. J Hosp Infect 2003; 55:21–25.
8. Endo M, Tomizawa Y, Nishida H. Bilateral versus unilateral internal mammary revascularization in patients with diabetes. Circulation 2003; 108:1343–1349.
9. Pevni D, Mohr R, Lev-Run O et al. Influence of bilateral skeletonized harvesting on occurrence of deep sternal wound infection in 1,000 consecutive patients undergoing bilateral internal thoracic artery grafting. Ann Surg 2003; 237:277–280.
10. Lev-Ran O, Braunstein R, Nesher N et al. Bilateral versus single internal thoracic artery grafting in oral-treated diabetic subsets: comparative seven-year outcome analysis. Ann Thorac Surg 2004; 77:2039–2045.
11. Lev-Ran O, Mohr R, Pevni D et al. Bilateral internal thoracic artery grafting in diabetic patients: short-term and long-term results of a 515-patient series. J Thorac Cardiovasc Surg 2004; 127:1145–1150.
12. Boodhwani M, Lam BK, Nathan HJ et al. Skeletonized internal thoracic artery harvest reduces pain and dysesthesia and improves sternal perfusion after coronary artery bypass surgery: a randomized, double-blind, within-patient comparison. Circulation 2006; 114:766–773.
13. Stevens LM, Carrier M, Perrault LP et al. Influence of diabetes and bilateral internal thoracic artery grafts on long-term outcome for multivessel coronary artery bypass grafting. Eur J Cardiothorac Surg 2005; 27:281–288.
14. Momin AU, Deshpande R, Potts J et al. Incidence of sternal infection in diabetic patients undergoing bilateral internal thoracic artery grafting. Ann Thorac Surg 2005;1765–1772.
15. Bical OM, Khoury W, Fromes Y et al. Routine use of bilateral skeletonized internal thoracic artery grafts in middle-aged diabetic patients. Ann Thorac Surg 2004; 78:2050–2053.
16. Crabtree TD, Codd JE, Fraser VJ et al. Multivariate analysis of risk factors for deep and superficial sternal infection after coronary artery bypass grafting at a tertiary care medical center. Semin Thorac Cardiovasc Surg 2004; 16:53–61.
17. Ura M, Sakata R, Nakayama Y et al. Bilateral pedicled internal thoracic artery grafting. Eur J Cardiothorac Surg 2002; 21:1015–1019.
18. De PR, de NS, Scaffa R, Nardella S et al. The effect of bilateral internal thoracic artery harvesting on superficial and deep sternal infection: the role of skeletonization. J Thorac Cardiovasc Surg 2005; 129:536–543.
19. Toumpoulis IK, Anagnostopoulos CE, DeRose JJ Jr et al. The impact of deep sternal wound infection on long-term survival after coronary artery bypass grafting. Chest 2005; 127:464–471.
20. Walkes JC, Earle N, Reardon MJ et al. Outcomes in single versus bilateral internal thoracic artery grafting in coronary artery bypass surgery. Curr Opin Cardiol 2002; 17:598–601.