Ann Thorac Surg 2008;85:1002-1006. doi:10.1016/j.athoracsur.2007.10.036
© 2008 The Society of Thoracic Surgeons
Original Articles: Cardiovascular
Is Bonewax Safe and Does It Help?
Jörg Prziborowski, MD,
Martin Hartrumpf, MD,
Ulrich A. Stock, MD,
Ralf U. Kuehnel, MD,
Johannes M. Albes, MD, PhD*
Department of Cardiovascular Surgery, Heart Center Brandenburg, Bernau bei Berlin, Germany
Accepted for publication October 10, 2007.
* Address correspondence to Dr Albes, Department of Cardiovascular Surgery, Heart Center Brandenburg, Ladeburger Strasse 17, Bernau bei Berlin 16321, Germany (Email: j.albes{at}immanuel.de).
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Abstract
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Background: Bonewax is routinely used to seal sternal edges after median sternotomy. Adverse effects on sternal healing, however, have been proclaimed although clear evidence does not exist. We performed a study on coronary bypass patients with or without bonewax application to verify negative effects and risk factors for early rethoracotomy, wound healing problems, and mediastinitis.
Methods: In a prospectively randomized study on 400 patients undergoing isolated coronary bypass surgery, 200 patients with (bonewax) and 200 patients without bonewax (nonwax) application after median sternotomy were compared. Blood product consumption, early rethoracotomy, sternum stabilization, mediastinitis, and early mortality were compared. Risk factors such as age, sex, diabetes mellitus, and bonewax were analyzed by means of logistical regression analysis.
Results: Blood product consumption was almost identical in both groups (red blood cells, 3.9 ± 4.7 units in the bonewax group; 3.8 ± 3.4 units in the nonwax patients; fresh frozen plasma, 0.5 ± 1.6 units versus 0.5 ± 1.3 units; platelet concentrates, 0.07 ± 0.3 units versus 0.04 ± 0.2 units). Early rethoracotomy (bonewax 6.5%; nonwax 5%), sternal stabilization (bonewax 3%; nonwax 3%), and mediastinitis (bonewax 1%; nonwax 0.5%) did not differ significantly. Early mortality was 2.5% in the bonewax group and 0.5% in the nonwax cohort. Bonewax did not appear as an independent risk factor for adverse outcome.
Conclusions: Negative effects of bonewax on the percentage of postoperative complications and outcome were not shown. However, positive effects such as a reduction of blood product substitution were also not observed. Using bonewax on sternal edges is obviously safe but not particularly beneficial.
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Introduction
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Very early in cardiosurgical training the young resident becomes aware of the diametrically opposed opinion of surgical elders on the use of bonewax. While one group liberally apply beeswax to the sternal edges to reduce oozing, others express grave concern regarding consecutive wound healing problems or even mediastinitis [1]. Although used for many years in clinical practice worldwide, surprisingly little evidence has been accumulated so far addressing the issue of beneficial or adverse effects of the use of bonewax in cardiosurgical patients [2]. It is, however, necessary to overcome mere expert opinion on benefits and drawbacks of bonewax as the lowest degree of evidence. Therefore, we performed a prospective and randomized study on isolated coronary artery bypass patients who were either treated with or without bonewax after full median sternotomy.
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Material and Methods
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In a single institution, 400 patients (310 male, 90 female; mean age 67 ± 7 years) undergoing routine isolated coronary artery bypass grafting within a period of 1 year (July 2005 to June 2006) were enrolled in this study after giving informed consent. The study was approved by the state’s Ethical Committee. Risk factors were preoperatively assessed, including urgency status (elective: regular admission; urgent: transferral from other hospital). All patients received the left internal mammary artery (LIMA) and one or more venous grafts. All procedures were performed by means of full median sternotomy and institution of mild hypothermic cardiopulmonary bypass utilizing standard cross-clamping, blood cardioplegia, and side-clamping for proximal venous anastomoses. Demographic and procedural data are shown in Table 1.
Patients were divided into two groups. Randomized allocation to the groups was performed by drawing envelopes. In the bonewax group (n = 200), patients received bonewax sealing of the sternal edges directly after median sternotomy using one commercially available 2.5 g prefabricated strip (Bonewax; Johnson and Johnson, Beerse, Belgium). In the nonwax group (n = 200), no bonewax was used. During follow-up, blood and blood product substitution requirement was obtained (red blood cells, fresh frozen plasma, platelet concentrates). Percentages of early rethoracotomy for hemorrhage, sternum stabilization, superficial sternal infection, mediastinitis, and early mortality were assessed. Because of a low number of mediastinitis, the respective risk-factor analysis was carried out by combining the number of superficial sternal infections and mediastinitis in both groups (sternal infection).
Statistical Analysis
Statistical analysis was performed using SPSS Statistical Package for Windows (version 15; SPSS, Chicago, Illinois). For comparison of demographic data, numeric variables with normal distribution were analyzed by means of two-tailed, unpaired Student’s t test. Categorial variables were analyzed using cross-tabulation followed by a 
2 test. Logistical regression was then performed, yielding odds ratios for the influence of selected risk factors on binomial follow-up variables. Correlation of consumption of blood and blood products with risk factors and perioperative data was computed utilizing the general linear model of univariate analysis of variance (ANOVA) followed by linear regression analysis for assessing the correlation’s direction. Data are shown as mean percentages, means ± SD, odds ratios, or correlations. Significance was assumed if p was less than 0.05. Power sensitivity analyses were performed for the given sample size using G*Power 3 (Shareware; Institute of Experimental Psychology, Heinrich-Heine-University, Duesseldorf, Germany; Table 2) [3, 4].
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Results
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Patient groups did not differ statistically regarding age, sex, body mass index, and number of venous grafts. Risk for early mortality as assessed by EuroSCORE (European System for Cardiac Operative Risk Evaluation) was also equally distributed. Among the diabetic patients, however, insulin-dependency was more often observed in the nonwax subset than in the bonewax cohort (Table 1).
Perioperative data did not exhibit differences between both groups. Length of procedural periods such as operation time, total bypass time, as well as cross-clamp time did not show any statistically significant differences between both groups. Comparison of number of blood and blood products revealed no statistical differences between both cohorts. Number of early complications also did not exhibit differences, and hospitalization time was also similar in both groups. Early mortality did not differ between cohorts (Table 3).
No statistically significant risk factors for early rethoracotomy could be found, whereas body mass index was identified as risk factor for sternum stabilization (p < 0.05) and, with a tendency, for sternal infection (p = 0.085). Urgency status was also identified as risk factor for sternal infection. None of the analyzed risk factors, however, appeared to influence early mortality at statistically significant level (Tables 4 to 7).
A positive correlation of female sex as well as EuroSCORE greater than 6 with consumption of red blood cell units was observed, and operation time correlated positively with consumption of fresh frozen plasma and red blood cell units. Cross-clamp time correlated negatively with the number of fresh frozen plasma. No statistically significant correlation was detected concerning platelet concentrate consumption (Table 8).
Bonewax did not appear as an independent risk factor concerning early rethoracotomy, sternum stabilization, sternal infection, early mortality, and blood and blood product consumption (Tables 4 to 8).
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Comment
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Wax from honeybees is formed from a mixture of several compounds including hydrocarbons 14%, monoesters 35%, diesters 14%, triesters 3%, hydroxy monoesters 4%, hydroxy polyesters 8%, acid esters 1%, acid polyesters 2%, free acids 12%, and free alcohols 1%, with 6% remaining unidentified. The main components of beeswax are palmitate, palmitoleate, hydroxypalmitate, and oleate esters of long-chain (30 to 32 carbons) aliphatic alcohols, with a 6:1 ratio of the two prinicipal components triacontanylpalmitate CH3(CH2)29O-CO-(CH2)14CH3 and cerotic acid CH3(CH2)24COOH. Beeswax has a melting point range of 62°C to 64°C (144°F to 147°F). It does not boil in air, but continues to heat until burning at approximately 120°C (250°F). If beeswax is heated above 85°C (185°F), discoloration occurs. Density at 15°C ranges from 0.958 to 0.970 g/cm3 [5].
Bonewax is manufactured from sterilized, white-bleached honeybees’ wax (cera alba). Synthetic wax has not yet entirely displaced natural wax because of the still superior properties of beeswax as well as reasonable product costs. Consequently, 1 g bonewax is composed of 750 mg cera alba, 150 mg paraffinum sol., and 100 mg isopropylis palmitate [6]. Because of its texture, puttylike plastic properties, and temperature responsiveness, it has almost ideal qualities for application in bony structures to seal oozing from open bone marrow. Particularly after median sternotomy, sternal edges can be quite elegantly sealed with bonewax.
From first applications in orthopedic and cranial surgery in the 1950s [7, 8], beeswax has therefore been adopted for median sternotomy in cardiothoracic surgery [9]. Under the microscope, body parts of bees such as mandibles, wings, and legs can be found in commercially available bonewax. Fortunately, however, the sterilized product is not considered to carry harmful micro-organisms [10].
Beeswax was initially thought to be absorbed quite readily in the human body [1, 2]. However, subsequently, it became obvious that beeswax does not degrade in significant quantities in a reasonable period of time [9]. Instead, in animal experiment, it provokes a considerable inflammatory response, eliciting a foreign body reaction that consists of fibrous tissue infiltrated by macrophages, giant cells, and lymphocytes at the sites of the bone defects [10–12]. In other animal studies, it was shown that beeswax displaced the bone marrow and interfered with bone ingrowth into the defects, in contrast to other hemostyptic agents such as fibrin-collagen paste [13]. Purported adverse effects of bonewax entered the literature as early as 1978 [9, 14, 15]. Bonewax was considered to impede proper fusion after osteotomy and to provoke microbial infections. In a case series of 19 patients presenting with osteomyelitis of the sternum after cardiac surgery, Robicsek and colleagues [16] have postulated that bonewax applied as a sealant to the oozing sternum halves may have served as the possible cause of this problem. In a study on dogs, they could show that radioactively labelled bonewax did not entirely remain at the site of application but could be found in significant quantities in the lung [17]. However, very little further evidence was created demonstrating adverse effects of bonewax in cardiosurgical patients [18].
In 1994, Milano and colleagues [19] performed a large prospective clinical study on nearly 6,500 patients to elucidate influencing factors for postoperative mediastinitis. No impact of bonewax application on the development of mediastinitis was shown [19]. In 2003, Bhatti and Dunning [2] performed a literature review to find an influence of bonewax on the development of mediastinitis in cardiac surgery. Only the publication by Milano appeared as level 2b evidence (Cochrane classification). In 2006, Sudmann and coworkers [20] demonstrated the presence of bonewax granuloma in 17 of 18 cardiosurgical autopsies of patients who died of various causes. Weighing these surprisingly scarce data against the enormously accumulated consumption of bonewax worldwide, one may arrive at the conclusion that the substance is safe. However, not only adverse effects but also the potential benefit of bonewax require consideration.
Bonewax is cheap. Although prices may differ from country to country depending further on local negotiations and the number of packages ordered, costs for one sterilized ready-to-use 2.5-g strip may not range outside a single-digit dollar frame. At our institution, for instance, one strip costs 1.92
($2.50 US).
As an alternative to bonewax, a water soluble bone hemostasis material has recently been approved by the Food and Drug Administration. The agent is already commercially available as Ostene (Ceremed, Los Angeles, California). This material comprises a sterile mixture of water-soluble alkylene oxide copolymers, derived from ethylene oxide and propylene oxide. These copolymers have a long history in the medical and pharmaceutical fields, and they are considered inert. The compounds are not metabolized, but are eliminated from the body unchanged. The company hopes that increasing utilization of Ostene will eventually reduce the incidence of surgical bone infections, nonunion, and inflammatory complications. Evidence concerning median sternotomy, however, does not yet exist. In clinical use, the material has indeed similar properties as bonewax. However, the appearance is less puttylike but rather gluey. It is also noteworthy that Ostene is about 10 times as expensive as bonewax [11, 21].
Some groups have used fibrin glue to seal the open bone marrow of the sternal edges after median sternotomy, with some success in small series [1, 22]. However, fibrin glue is an expensive product. Assuming a minimum quantity of 1 mL per side to achieve the desired hemostatic effect, utilization of fibrin glue represents a very expensive treatment alternative.
Our study is the first prospectively randomized trial on a larger number of cardiosurgical patients that addresses both the issue of adverse findings and the possible beneficial effects. The size of our study population was determined to meet the requirements for a statistical power of 0.8 regarding small to medium effect sizes according to Cohen’s recommendations for medical studies [1, 2]. The minimal effect sizes to which the respective tests were sufficiently sensitive were indeed found in the small to medium effect size range (Table 2).
We could clearly demonstrate the absence of a negative influence of bonewax even after harvesting the left internal mammary artery, or in diabetic or obese patients. In contrast, however, we were not able to demonstrate a reduction of blood or blood product consumption as sequel of a presumably decreased perioperative blood loss when using bonewax [17]. Factors influencing sternal healing problems and mediastinitis have already been clearly identified. Insulin-dependent diabetes mellitus, bilateral use of the internal mammarian artery, and severe chronic obstructive lung disease are perhaps the best investigated factors [18, 23, 24]. Length of operative procedure, urgency, or obesity have not yet been identified as clear risk factors, although some evidence has been gained [19, 24]. Indeed, in our study, obesity, diabetes mellitus, and urgency did appear as risk factors for adverse outcome concerning various sternal healing problems, albeit not regarding early mortality. Furthermore, female sex, EuroSCORE greater than 6, and operation time did correlate with increased blood and blood product consumption. In contrast, however, bonewax did not appear as an independent risk factor for sternal healing, early mortality, or blood and blood-product consumption. We did not find any clinical evidence for pulmonary embolism in our patients. It therefore remains elusive whether embolization of bonewax into the lung as shown in animal experiments occurs on a significant scale in humans [17]. The absence of adverse pulmonary findings after bonewax application in the literature after more than 30 years of clinical use does indeed not support the assumption of pulmonary embolism being a clinically relevant problem.
In light of our findings, surgeons may readily use bonewax at their own discretion, risk factors or procedural characteristics notwithstanding. Although not supported by any evidence, a "dry" surgical field may outweigh only theoretical considerations regarding adverse effects of bonewax. However, one should bear in mind that using a mere "feel good" product does not in itself meet the patient’s demands. The bottom line is that bonewax is obviously not unsafe but it does not help much either.
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References
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Abstract
Introduction
