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Three Part Question

In [patients undergoing cardiac surgery] does liberal use of [bone wax] increase the risk of [mediastinitis]?

Clinical Scenario

You are a registrar performing the sternotomy on a 65 year-old patient who is undergoing an aortic valve replacement, supervised by your consultant. You open the chest and start liberally applying bone wax to the sternal edges. Your Consultant is greatly alarmed and tells you that bone wax is 'poison' and should only be used for friable, bleeding sternums. You heed his advice but wonder what evidence exists for his strongly held views.

Search Strategy

Medline 1966-07/03 using the OVID interface
[(exp mediastinitis or mediastinitis.af) AND (exp waxes or wax.af)] OR [bone wax.af] LIMIT to review articles.

Search Outcome

276 papers were found of which 5 were deemed to be relevant.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Robicesk et al, 1978, USA	Case series of 19 patients who presented in a short period with Mycobacterium fortuitum osteomyelitis in the sternum, 2-3 weeks after cardiac surgery	Case series (4)	Outcome	3 deaths. 15 required reoperation including sternectomy.	No evidence for hypothesis that bone wax caused the outbreak was presented
			Possible causes	Bone wax was postulated as a possible cause of the outbreak
Robicsek et al, 1981, UK	Radiolabelled bone wax (5g) was applied to the edges of sternotomies made in 6 dogs. Sternotomy closed with steel wires Lung biopsies were then taken at 15, 30 and 60 mins	Experimental study	Lung radioactivity	Radioactivity in the lungs doubled from 15mins after bone wax application. Samples from the liver kidney and spleen did not change.	Non-human model
			Contrast injection to sternum during angiography of a dog	Contrast moves rapidly into the azygos and hemiazygos system and then into the venae cavae and right heart
Nelson et al, 1990, USA	Study to determine the inoculum of S aureus required to induce osteomyelitis in the tibial metaphysis of 84 rats 39 rats had a 1mm hole in tibia inoculated and then the skin closed 45 rats had a 1mm hole with innoculum and then bone wax applied and the skin closed Rats killed at times up to 21 days	Experimental Study	Inoculum of S. aureus required to infect 50% of animals	Bone wax reduced the amount of inoculum from log 6.9 to log 2.6 bacteria This is a 99.99% smaller inoculum	Non-human non-sternal model used No perioperative anti biotics used
Solheim et al, 1992, Norway	The tissue response and effect on bone induction was assessed in 150 rats when either bone wax, absorbable fibrin-collagen paste, or a biodegradeable polyorthoester was applied A demineralised bone matrix was inserted into the rectus muscles for 4 weeks. The rats were then killed and the bone samples assessed	Experimental study	Level of resorbtion	Large amounts of bone wax remained at 4 weeks. Some small amounts of collagen paste remained	Non human trial on non sternal, demineralised bone model in rats
			Inflammatory reaction	Bone wax induced a much stronger chronic inflammatory reaction
			Measurements of bone growth	Bone wax significantly reduced bone growth compared to other haemostatics or bone alone
Milano et al, 1994, USA	Study of 6459 consecutive cardiac surgery patients of which 83 developed mediastinitis Also performed a literature search of Medline for risk factors in mediastinitis, 1966-1994	Prospective Cohort study and review (2b)	Multivariate analysis of factors implicated in causing mediastinitis	Obesity, NYHA score, Cardiopulmonary Bypass time and previous surgery identified. Presence of bone wax not investigated. Poor haemostasis of sternum was not significant	Bone wax data was not prospectively collected in this study
			Literature review: Identified 13 studies that described 48 risk factors	Only 1 paper found that poor sternal haemostasis was a significant factor. No studies found bone wax to be significant

Comment(s)

There are no human cohort studies that have made the link between bone wax and mediastinitis. One 1978 case series postulated that bone wax may have been a causal factor in an outbreak of Mycobacterium fortuitum mediastinitis, although no evidence was presented to support this. a review by Milano et al. looking for risk factors associated with mediastinitis found no evidence for bone wax causing mediastinitis and in fact associated poor haemostasis with an increased risk. However animal studies have shown that bone wax can embolise to the lungs, that bone wax markedly reduces the inoculum of Staphlococcus aureus required to cause osteomyelitis, and that bone wax is still present in large quantities 4 weeks post-operatively. Bone wax is still routinely used in clinical practice and thus a clinical trial is urgently needed in this area to investigate whether these troubling pre-clinical findings cause harm to patients in the clinical setting.

Clinical Bottom Line

Animal studies indicate that there are strong reasons for concern over the liberal usage of bone wax.

References

1. Robicsek F, Daugherty HK, Cook JW, et al. Mycobacterium fortuitum epidemics after open-heart surgery. J Thorac Cardiovasc Surg 1978;75(1):91-6.
2. Robicsek F, Masters TN, Littman L, et al. The embolization of bone wax from sternotomy incisions. Ann Thorac Surg 1981;31(4):357-9.
3. Nelson DR, Buxton TB, Luu QN, et al. The promotional effect of bone wax on experimental Staphylococcus aureus osteomyelitis. J Thorac Cardiovasc Surg 1990;99(6):977-80.
4. Solheim E, Pinholt EM, Bang G, et al. Effect of local hemostatics on bone induction in rats: a comparative study of bone wax, fibrin-collagen paste, and bioerodible polyorthoester with and without gentamicin. J Biomed Mater Res 1992;26(6):791-800.
5. Milano CA, Kesler K, Archibald N, et al. Mediastinitis after coronary artery bypass graft surgery: Risk factors and long-term survival. Circulation 1995;92(8):2245-51.