Introduction
Bone wax, a commonly used haemostatic and mechanical sealant in surgical practice, was described as ‘antiseptic wax’ by Victor Horsley in the 1800s.Reference Horsley1 The composition of bone wax has changed over the ages. Although it was initially described as consisting of beeswax, almond oil and salicylic acid,Reference Horsley1 its composition currently consists of white beeswax (85 to 90 per cent) and isopropyl palmitate (10–15 per cent) with or without pure paraffin wax.Reference Nooh, Abdullah, Grawish, Ramalingam, Javed and Al-Hezaimi2
This material has quickly grown in popularity because of its non-reactive and non-absorbable properties, but these very properties do, occasionally, result in complications. Animal experiments have shown that bone wax remains as a foreign body for years and reduces the ability of cancellous bone to clear bacteria.Reference Johnson and Fromm3 Bone wax also inhibits new bone formation, thereby delaying healing.Reference Nooh, Abdullah, Grawish, Ramalingam, Javed and Al-Hezaimi2 Commonly described complications of bone wax usage are foreign body granuloma and bacterial infection.Reference Katz and Rootman4–Reference Fahradyan, Ohanisian, Tsuha, Park and Hammoudeh9 Additionally, there are reports of delayed migration of bone wax to adjacent areas.Reference Baird, Teh, Lim and Campbell8–Reference Zhou, Li, Wei, Yang, Zhang and Qi11
As bone wax is a frequently used material in both otorhinolaryngological and neurosurgical procedures and because we noted certain rare post-operative complications as a result of its use in our practice, we decided to perform a retrospective review of all patients treated by us who had developed complications because of bone wax usage at the skull base. We also highlight the diverse infection profile and site-specific management of these complications.
Materials and methods
We conducted a retrospective study of all patients attending the ENT and neurosurgery sections of our hospital over the last 15 years and who had intra-operative evidence of complications following the use of bone wax at the primary surgery.
Our search strategy was to screen all patients who had post-operative wound infections during the study period from 2005 to 2019. Only those patients who had infections associated with bone wax at the skull base (as determined by the operation notes) were finally included. Data from the electronic medical records of these patients were extracted to note the clinical presentation, prior medical and surgical history, imaging findings, operative details at revision surgery, microbiology reports, histopathology results, treatment, and final outcomes.
Results
A total of five patients were found to have complications of bone wax use at the primary surgery. There were three males and two females, with ages ranging from 21 to 57 years (Table 1). A common feature in all five patients was the presence of copious amounts of bone wax at the surgical site. The wax was present in proximity to adjacent bone and lay interspersed with granulation tissue and bone in four cases (cases 1, 3, 4 and 5) and within the ethmoid sinuses in one case (case 2).
* n = 5. CSF = cerebrospinal fluid; MRI = magnetic resonance imaging; MRCT = magnetic resonance imaging with computed tomography; CT = computed tomography
Clinical presentation
In three patients who had the primary surgery performed elsewhere, operative details were unavailable. These patients presented for the first time to our hospital with discharging wounds (cases 1 and 3) and with cerebrospinal fluid (CSF) rhinorrhoea and recurrent meningitis in one patient (case 2). In all of these cases, the finding of large amounts of bone wax along the skull base was an unexpected finding.
Two other patients (cases 4 and 5) were operated on in our hospital: both had required the use of bone wax intra-operatively, one for sealing the mastoid air cells during retrosigmoid craniectomy for vestibular schwannoma excision and the other for haemostasis during removal of a part of the foramen magnum for excision of a C1-2 schwannoma. While one patient (case 3) presented with a discharging postaural fistula, which persisted for several months after the primary surgery, another patient (case 5) developed persistent fever one month after the primary surgery. Only one of the five patients (case 4) was asymptomatic at presentation and the presence of the complication was shown on a routine post-operative CT scan of the brain (Table 1).
Imaging findings
Contrast-enhanced magnetic resonance imaging (MRI) of the brain provided a pre-operative diagnosis of the extent of the complication in all patients (Table 1). In case 1, there was an abscess in the temporal lobe (Figure 1), and the extent of tegmen breach was well visualised on a combination of high-resolution computed tomography (CT) and MRI images of the temporal bone. In case 2, several anterior skull base defects were present (Figure 2a and b), and because there was reactive sinusitis, the site of the meningocele was better demonstrated on high-resolution CT scan of the skull base (Figure 2a) than on MRI scan. In case 3, osteomyelitic bone in close proximity to the sigmoid sinus was evident on a high-resolution CT scan of the temporal bone, whereas the tract and its course as well as bone wax were well visualised on an MRI scan (Figure 3a and b). In case 4, there was an enhancing lesion in the cerebellopontine angle cistern mimicking a tumour with oedema of the adjacent brain stem not seen in an earlier post-operative MRI scan done six months after excision (Figure 4a–d). In case 5, there was enhancement adjacent to the foramen magnum, suggesting an infective process (Figure 5a and b).
Bacteriology and mycology
Staphylococcus aureus was the commonest organism isolated with methicillin resistant S aureus (MRSA) isolates seen in two patients. Case 3, who had MRSA cultured from the pre-operative swab, underwent a two-week course of linezolid and cotrimoxazole pre-operatively, and re-exploration was performed after the repeat swab was negative. A negative culture was seen in one patient (case 4) (Table 2).
* n = 5. CSF = cerebrospinal fluid; MRSA = methicillin resistant Staphylococcus aureus
Fungal infections were noted in two of the five cases. In case 1, Aspergillus flavus was isolated from the brain abscess. Intra-operative findings in this patient included the presence of a 20 × 12 mm thick walled temporal lobe abscess full of thick, gelatinous pus which prompted us to request bacterial, fungal and mycobacterial cultures. In case 5, Trichosporon beigelii, a yeast-like fungus, was grown in culture from the granulation tissue.
Histopathology results
Histopathology showed granulation tissue with chronic inflammation in all patients. In case 1, with the fungal brain abscess, filamentous fungal forms were seen in the abscess wall, and in the patient with fungal osteomyelitis, yeast-like forms were seen to infiltrate bone.
Treatment and outcome
Re-exploration of the surgical site with removal of bone wax was performed in all patients (Table 2). In case 2, this was done twice. Following endoscopic repair of a right-sided foveal defect and excision of bone wax in the sinuses, the patient presented three months later with bilateral grade 2 sinonasal polyposis. He underwent bilateral endoscopic polyp excision and was noted to have bone wax in the frontal recesses bilaterally, which appeared to have been left behind at the previous surgery. After removal of this residual bone wax and polyps and commencing steroid nasal sprays, the patient was asymptomatic at five years’ follow up.
Case 3, whose culture from the postaural fistula had grown MRSA, was given oral linezolid and cotrimoxazole for two weeks pre-operatively and one week post-operatively. Based on intra-operative bacterial culture reports of Klebsiella species growth, antibiotics were changed post-operatively to intravenous cefoperazone and amikacin for one week followed by oral amoxicillin clavulanate for two weeks. Case 4 had a cerebellopontine angle mass that mimicked a recurrent tumour but was actually a sterile foreign body granuloma in the cerebellopontine angle cistern. After partial excision, the mass disappeared at the follow-up visit.
With regard to antifungal therapy, case 1 responded well to a three-month course of itraconazole at a dose of 200 mg twice daily; however, case 5 refused antifungal therapy and was lost to the follow up.
Discussion
Traditionally, during mastoid surgery or craniotomy, a small amount of bone wax has been used by surgeons to provide a haemostatic seal when there is bleeding from emissary veins or bone which cannot be controlled by pressure or the use of cautery. Its use is not free from complications, however, as outlined by several authors.Reference Katz and Rootman4–Reference Zhou, Li, Wei, Yang, Zhang and Qi11
Bone wax may also be used as a mechanical sealant in some cases. In four patients (cases 1 to 4), despite the lack of operative details in three, it appeared that bone wax had been used as a mechanical sealant to prevent CSF leak rather than for haemostasis. In case 5, however, it was used as a haemostatic agent. Neurosurgeons describe the use of a thin layer of bone wax as a mechanical sealant to plug the small mastoid cells that are inadvertently opened during retromastoid craniectomy or temporal craniotomy.Reference Byrns, Khasgiwala and Patel10 If larger exposure of cells is encountered, plugging with fat or muscle is advised, rather than bone wax.Reference Lüdemann, Stieglitz, Gerganov, Samii and Samii12 In our series, the use of excessive bone wax appears to be the predisposing cause for complications in all the cases. Further, the use of bone wax as a layer of repair to prevent CSF leak is not advisable. This appears to have been the cause for complications in cases 1 and 2.
Migration of bone wax with resultant development of complications has been described by some authors.Reference Baird, Teh, Lim and Campbell8–Reference Zhou, Li, Wei, Yang, Zhang and Qi11 In one of our patients (case 4), bone wax that was used to seal mastoid cells that were opened during vestibular schwannoma surgery was found to have migrated intradurally causing an inflammatory reaction and granuloma formation that required subsequent surgery. Bone wax present at the internal auditory meatus causing cerebellopontine angle granuloma formation has been reported earlier,Reference Patel, Kwartler and Hodosh5 but there was no mention of intradural migration from the mastoid air cells as was observed in our case in that report.
In our patient, although the location and appearance of the enhancing lesion mimicked a recurrent schwannoma, we felt that it was important to recognise the possibility of an inflammatory pathology too as it was unlikely that a schwannoma would have recurred at this size when an MRI scan done one year earlier had shown no evidence of residual tumour. Further, the presence of new onset oedema in the repeat MRI scan is atypical for a recurrent schwannoma. We thus decided to re-explore the previous surgical site. Failure to consider the possibility of a new pathology in this patient may have resulted in him being unnecessarily subjected to stereotactic radiosurgery that may have worsened his neurological status. Foreign body granuloma formation in the medulla, secondary to bone wax inadvertently being left behind in the subarachnoid space, has also been reported.Reference Ates, Cayli and Gurses13 In case 2, inadequate primary repair and excessive bone wax in the anterior skull base caused a triad of complications of infection leading to recurrent meningitis, sinonasal polyposis and wax migration into the ethmoid sinuses.
• Bone wax use during skull base surgery may result in infection, foreign body granuloma or migration, but the complication may occur several weeks later
• All cases require surgical re-exploration with excision of bone wax and infected tissue
• Excised pus and granulation should be sent for bacterial, fungal and mycobacterial cultures
• Asymptomatic, sterile foreign body granuloma mimicking a tumour is, rarely, seen too
• Methicillin resistant Staphylococcus aureus infection, which is common, also requires appropriate combination antibiotic therapy
• Invasive fungal infection is a rare complication that requires appropriate antifungal therapy in addition
One of the prime complications of bone wax use is surgical site infection with staphylococcal infections being predominant. Bone wax has been shown to impair clearance of staphylococcal bacteria when compared with either a synthetic polymer or controls in a rabbit model, wherein defects created in the tibia were inoculated with S aureus. All the animals who received bone wax developed features of osteomyelitis compared with controls or the polymer group.Reference Wellisz, An, Wen, Kang, Hill and Armstrong14 Intraventricular migration of bone wax from the burr hole site, found during placement of a ventricular catheter, had been reported to result in repeated episodes of Staphylococcus epidermidis meningitis and shunt infections that abated only once the bone wax was removed endoscopically.Reference Spennato, Escamilla-Rodrìguez, Di Martino, Imperato, Mirone and Cinalli7 The retrieved bone wax, which had also been cultured, was found to be positive for S epidermidis. Reference Spennato, Escamilla-Rodrìguez, Di Martino, Imperato, Mirone and Cinalli7 In our series, while MRSA was the infecting organism in two patients, a sterile granuloma was also seen in one patient (case 4).
A unique feature in our series was the presence of serious fungal infections in two patients. In fact, case 1 is the first report in the literature of a fungal brain abscess as a result of A flavus and case 5 is the first case of T beigelii infection, both secondary to the use of bone wax. A high index of suspicion because of the viscous appearance of the pus within the abscess led to the request for fungal culture in addition to bacterial and mycobacterial culture along with histopathology. Invasive fungal infections may be introduced by the use of in-dwelling catheters and devices around which fungi can form a biofilm.Reference Colombo, Padovan and Chaves15 Although this has not been described before, it is possible that fungal biofilm development occurs with the use of bone wax too, and cases 1 and 5 are illustrative of this phenomenon. While Aspergillus species usually respond well to the administration of azoles (as seen in case 1), the treatment of T beigelii is more challenging. Triazoles appear to have better in vitro and in vivo activity against the organism than amphotericin B.Reference Colombo, Padovan and Chaves15 Unfortunately, our patient (case 5) was lost to follow up and hence his response could not be assessed.
Conclusion
Excessive use of bone wax in the skull base for haemostasis or as a sealant for mastoid air cells can result in infective and non-infective complications that may mimic a tumour. Fungal pathogens may be a cause for serious, invasive infection, and it is mandatory to send fungal and bacterial cultures in all cases. Treatment of the complication will require re-exploration and removal of bone wax along with appropriate antibiotic or antifungal therapy.
Competing interests
None declared