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SAFE Nail. Use of a Interlocking nail with a long acting antibiotic releasing core in patients with high
infection risk. Prospective study in 27 cases.
Nuno Craveiro Lopes *, Carolina Escalda*,
*- Senior Orthopedic surgeon, Orthopedic Department, Garcia de Orta Hospital
Correspondence to:
Nuno Craveiro Lopes
Servio de Ortopedia e Traumatologia
Hospital Garcia de OrtaAv. Prof. Professor Torrado da Silva, Pragal
2801-951 Almada
PortugalFax: 351-212957004
Tel: 351-212727153
E-mail: nuno.lopes@netvisao.pt
Conflito of interests:
Nothing to declare
ABSTRACT
Introduction
The use of interlocking na
ils with PMMA cement impregnated with antibiotics is an attractive method for
treating or preventing infections of long bones. After conducting a in vitro pilot experimental study to evaluatethe stiffness of the nails, the levels of release of antibiotic and clinical efficacy of a modified interlocking nail,
with a core of PMMA cement impregnated with vancomycin, the Authors present the experience with the use
of a modified nail, filled with polymethylmethacrylate cement impregnated with 2 g of vancomycin (SAFE
Nail) to prevent and control infection in 27 cases at high risk.Material and Method
We prospectively evaluated 27 cases (8 femurs, 16 tibias and 3 knee arthrodesis), including 8 women and19 men, average age 42 years (range 15-69 years). 8 cases had open fractures, 11 presented with treatment with
external fixators that were converted into SAFE nail, 4 had limb length discrepancy and underwent lengtheningover a SAFE nail and 4 had osteomyelitis with fracture or nonunion.
In all cases it was used a Grosse nail with two longitudinal series of 5 mm holes, filled with 20 to 40 gr of
polymethylmethacrylate cement with 2 grams of vancomycin.The mean follow-up was 14 months (range 8-29 months). It was noted the time until consolidation, the
emergence of infection and intercurrences.Results
In 23 cases cultures were made prior to the nailing and potentially very aggressive bacteria was found in 17of these cases (74%).
In the overall of cases, there were two problems, five obstacles and no complications.In the group of 8 cases with open fractures, one developed a delayed consolidation, coming to fracture the
nail after 3 months. Substitution with SAFE DualCore nail (2nd generation), a reinforced nail, achievedconsolidation. Another patient developed a infection with MSSA resistant to vancomycin. Substitution with a
SAFE DualCore nail, loaded with cement with flucloxacilin achieved the consolidation and cure of the
infection.
In the group of 11 cases where conversion of external fixation to SAFE nail was done, consolidation wasachieved without the appearance of infection in all cases.
Of the 4 cases undergoing lengthening over SAFE nail, regenerated bone took more than three months to
consolidate in two cases and a fracture of the nail occurred. We proceeded to the replacement by a SAFEDualCore nail, resulting in the consolidation of the regenerate without the occurrencee of infection.
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Finally, 4 cases with osteomyelitis of the tibia treated with a SAFE nail healed their infection.
Conclusions
The SAFE nail has proved extremely effective in the prevention and treatment of bone infection, when the
appropriate antibiotic can be used. Currently in cases where the bacteria is not known, we use two antibiotics,flucloxacillin and vancomycin.
In relation to its strength, it was observed that the SAFE nail supports 10% more load than Grosse nail and the
same 450,000 load cycles, corresponding to 3 months of use in ambulatory patients, what proved to be
insufficient for some patients who present late consolidation. To remedy this fact, changes were introduced in
order to reinforce the nail, creating the 2nd generation of SAFE nail called SAFE DualCore nail, whichsupports about 900.000 load cycles.
Keywords: Antibiotic; pin; infection, osteomyelitis, cement, PMMA, open fracture, bone lengthening
INTRODUCTION
The use of interlocking na
ils with PMMA cement impregnated with antibiotics is an attractive method fortreating or preventing infections of long bones. After conducting a in vitro pilot experimental study to evaluate
the stiffness of the nails, the levels of release of antibiotic and clinical efficacy of a modified interlocking nail,
with a core of PMMA cement impregnated with vancomycin, the Authors present the experience with the use
of a modified nail, filled with polymethylmethacrylate cement impregnated with 2 g of vancomycin (SAFE
Nail) to prevent and control infection in 27 cases at high risk.
Fig.1 - Injection of cement with antibiotics inside the nail involved with a
Esmach band.
MATERIAL AND METHODS
Twenty-seven consecutive cases who presented for treatment at our institution between January 2009 andDecember 2010 were included in this prospective study. The patients suffered from situations in which the
usual methods of treatment had a high risk of infection, for which, at the responsibility of the surgeon nail were
modified in order to be adapted to the particular situation of the patient.
It was eight women and 19 men with mean age of 42 years, ranging from 15 to 69 years. 8 femurs weretreated, 16 tibias and 3 arthrodesis of the knee. All patients were at high risk of infection or with current
infection, including 8 cases of open fractures, 11 cases of treatment with external fixators that were converted
into nailing, four cases of limb shortening where lengthening with external fixators over nail was and 4 cases of
osteomyelitis with fracture or bone loss(Table I).Of the eight open fractures (Fig. 2), 3 were Gustillo grade I, two grade II and 3 grade III [5]. The group of 11
cases treated with external fixation (Fig. 3) had the fixator on average 19 weeks (4-48 weeks). The group of 4
cases underwenting lengthening with external fixator over nail (Fig. 4) maintained the fixator for 12 to 16weeks for 4 and 5 cm lenghtenings. Of the four cases with osteomyelitis, three were secondary to nailing after
open fractures (Fig. 5) and one to a hematogenous osteomyelitis lasting between 2 months and 3 years. In all
cases presenting high debit drainage
. In three cases a Staphylococcus aureus was isolated, two methicillin-resistant
and on another patient a serracia marescencis.
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Fig.2 - H.C., male, 47 years. Open fr GIII comminuted with 3 days of evolution. Nailing with SAFE Nail.
Appearance at 10 months.
In all cases a Grosse Stryker nail was used, adapted to the bone structure to be treated. The selected nail was
prepared in the workshops of the hospital with transfixing perforations of 5mm in diameter in the frontal plane
every 4 cm along the nail. At the beginning of the intervention in a sterile environment, the nail was involved in aEsmach band in tension and well reinforced in its proximal part. The cement is prepared in the usual way using 20
to 40gr of PMMA powder according to the internal volume of the nail to be used. 2 g of vancomycin and all of the
liquid component was added. Using a cement gun with the application tube cutted short and adapted solidly in theproximal nail hole, the cement was injected slowly inside the nail until it exit through the distal hole (Fig. 1). Then
the screw support of the proximal guide is screwed in in order to push the cement in the threaded area. Once the
cement gets pasty and before polymerization and heating, the screw is removed and the locking holes are cleaned
with a 4-5mm Steinmann pin.
Fig.3 - M.Q., female, 58 years. Reconstruction with the Ilizarov apparatus in a pseudoarthrosis after nail
failure. Reconversion to SAFE nail after 5 months of external fixation. Appearance at 15 months.
The technique of nailing and locking screws is similar to a normal interlocking nail, except that its introductioninto the medullary canal can not be made over the guide wire.
All patients received systemic antibiotic therapy, including 2 g of cefazolin and 80 mg of gentamicin every 8
hours for 3 days to prevent postoperative bacteremia.Patients leaved the hospital between the 3rd and 5th postoperative day and was controlled at the outpatient
clinic every 15 days and then monthly until consolidation. It was noted the time until the consolidation, the
emergence of infection and other intercurrences.
RESULTS
Exsudate cultures were performed prior to nailing in 25 cases, presenting 18 of these cases, potentially very
aggressive bacteria (74%). MSSA was isolates in 10 (40%), two MRSA, 2 Serratia, 2 Shigella (8% each), aPseudomonas, 1 Enterococcus (4% each), 5 cases had mixed skin flora (20%) and two cultures resulted negative.
All patients in the osteomyelitis group had positive cultures with aggressive bacteria, 37.5% of the open fractures,
54% of the conversions group and 75% of the lengthening group.
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The mean follow-up was 14 months (range 8-29 months).
Fig.4 - F.H., male, 37 years. Failed TSRH self lengthening nail. Lengthening with external fixator over
nail. SAFE nail conversion after 3 months of external fixation. Appearance at 22 months.
In the group of 8 cases with open fractures (Fig. 2), we observed the development of delayed union in three
cases. In one case SAFE nail brooked at 3 months. A exchange with a SAFE DualCore nail was done (2nd
generation, reinforced with metal core and impregnated with 2gr of Vancomycin and 2gr of flucloxacillin),achieving consolidation. The remaining two cases had at the last follow up a delayed union with no signs of
infection (at 4 and 6 months). Another patient developed infection with vancomycin-resistant MSSA. Nailsubstitution was made with a SAFE DualCore nail, achieving the consolidation and cure of the infection.
In the group of 11 cases where reconversion of external fixation to SAFE nail was done (Fig.3), there wasdelayed union in two cases with infection control in all cases.
Fig.5 - J.N., male, 27 years. Osteomyelitis after nailing of a open fracture. Nailling with SAFE nail one
year after infection. Appearance at 2 and a half years of evolution
Of the four cases undergoing lengthening over a SAFE nail (Fig. 4), we detected delayed consolidation of the
regenerate with nail failure in 2 cases. A nail exchange with SAFE DualCore nail with bone graft in one patient,
lead to consolidation of the regenerate, with no occurrence of infection.
Finally, 4 cases with osteomyelitis of the tibia treated with SAFE nail (Fig. 5), achieved consolidation andhealed their infection without complications.
In the overall of the cases, there were two problems, 5 obstacles and no complications [26]: 3 cases had residual
infection of soft tissues appearing between 2 and 4 weeks after nailing, two with superficial lesions were treatedwith systemic antibiotic therapy with gentamicin and the third with a deep fistula, by surgical debridement and
placement of PMMA beads with Meropeneme. All have evolved to progressive closure of the lesions. A patient
with open fracture progressed to osteomyelitis by bacterial resistance to Vancomycin. He was treated withexchange of the SAFE nail to a SAFE DualCore nail with flucloxacillin, the antibiotic that the bacteria was
sensitive, and evolved to the cure of the infection. Finally, 3 cases (11%) developed delayed consolidation with a
failure of the SAFE nail. They have been treated with replacement with a SAFE DualCore nail, one of which with
cancellous bone graft taken from the contralateral femur with the RIA system [27].
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DISCUSSIONBone infection requires a sequence of surgical procedures for infection control, to provide stability of the bone
structure and to promote the consolidation of the fracture, fragility, or bone loss. Traditional treatment includes serial
surgical debridement, various forms of systemic and local antibiotics and bone stabilization with external fixators, which
can later be converted into internal fixation once the infection had cleared [8,9,10]
The PMMA cement as spacers or beads impregnated with antibiotics has been used since 1970 [8,15,28,29] in the
treatment of bone infection, and has proved an effective method for long term local administration of high doses of
antibiotics [ 30], keeping minimal or undetectable systemic levels [6.12]. However, a second surgical procedure isneeded to remove the spacers or beads. Other type of carriers of antibiotics have been investigated to prevent the
need for a second surgical intervention and in some cases, to facilitate bone healing, including calcium sulfate and
various synthetic resorbable polymers [18,19,31,32,33, 34,35,36,37].
The safety of local treatment with PMMA cement loaded with antibiotics is well documented in clinical studies[8,15,18,19,28,29]. It is not available commercially PMMA cement with sufficient concentration of antibiotics for
local control of infections, the surgeon has to prepare it using most of the time, several antibiotics in high doses.
flucloxacillin and vancomycin proved to be the best combination in our midst because they have a broad spectrum
of action adapted to the most common bacterial flora, to be available in the market in powder form, having goodheat stability, good release properties and no effect on bone consolidation [18,31,38,39,40,41]. In addition to local
treatment, we administer parenteral antibiotics, including cefazolin and gentamicin for 3 to 4 days to prevent
postoperative bacteriemia.Most of our patients were treated with procedures that required the use of external fixators for prolonged periods. Itis well known in the literature [42,43,44,45], that in these situations there is a high prevalence of infection around
threaded pins and wires, muscle contractures and joint stiffness, pain and functional disability, and many patients
refuse treatment, they create intolerance to external fixators or are not good candidates because of exaggeratedobesity, intolerance or psychological instability. In these cases, the use of the SAFE nail brings an invaluable added
value.
Several authors reported other methods of combining an intramedullary device with PMMA cement
impregnated with antibiotics, including nails with beads [46.47], guide wires [26], Ender [16], Kntscher [48]andinterlocking nails[17] covered with PMMA cement with antibiotics. However they all had problems, obstacles and
complications in large number, including necessity to remove the beads, to include other mean of stabilization with
external immobilization, replacement with a more stable nail in a second timing or because of debonding of thecement outside the nail during insertion or extraction, leading to blockage of the nail and cement inside themedullary canal.
The SAFE nail was easy to manufacture and the procedure of filling it with cement impregnated with
antibiotics is fast and easy to perform by one of the surgeons, taking about 10 minutes, while the other surgeonprepare the implant site.
In this group of patients, the SAFE nail has been very effective in preventing infection and treating open
fractures, conversion of external fixation into internal, to do lengthening over nail and to treat osteomyelitis of long
bones with bone fragility. All these situations usually require long periods of external fixation and often serialsurgeries.
It is well documented that the placement of intramedullary PMMA cement impregnated with antibiotics is very
effective in the prevention and treatment of osteomyelitis, because it releases locally prolonged and high doses ofantibiotics [8,9,18,28,29,31,38,39,40,41]. However the fact that systemic levels of antibiotics are minimal orundetectable [20,21], makes this form of administration by itself insufficient to control the residual soft tissue
infection. These infections, which often accompany the process of osteomyelitis, become isolated from the
intramedullary environment after 2 weeks of treatment through the bone healing process. So it is necessary tosupplement the treatment with appropriate antibiotics, administered systemically or locally in the form of PMMA
cement beads with antibiotics.
Table I pre and posoperative patient data
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N Name Age/Sex Date Segment Observations Initial Treat. Contamination FW Result
Grup 1 (Open Fractures)
1 JM 57/M 08/2009 Tibia Distal GII SAFE 3 weeks 22 Consolidation. No Infection
2 GW 51/M 11/2009 Tibia Segmental GI SAFE
9 days
MSSA
Flucloxacylin
19 Infection Strep B Hem
Substitution SAFE DualCore
Consolidation
3 MS 61/F 07/2010 TibiaMedial Cominutive GIII
ObeseSAFE
7 days
Pseud. Aerug.
Gentamycin
11 Late Consolidation
# nail - 3 months No Infection
Substitution SAFE DualCore
4 TS 23/M 07/2010 Tibia Distal Cominutive GI SAFE 2 days 11 Consolidation. No Infection
5 HC 47/M 08/2010 Tibia Medial Cominutive GIII SAFE
3 days
MSSA
Entero.Cloacae
Fluclo+Genta
10 Consolidation.
No Infection
6 LS 38/M 08/2010 Femur Diafisal. Gun fire GI SAFE4 days 10 Consolidation.
No Infection
7 PC 35/M 08/2010 Tibia Medial GII SAFE2 days
Mix flora
2 Infection soft tissues
Late Consolidation
No Infection ssea
8 CF 17/M 12/2010 Tibia Distal GIII SAFE15 days
Negativo
4 Late Consolidation
No Infection
Grup 2 (Reconversion from External Fixation)
9 MS 37/F 03/2010 Femur Pseudartrose
Shortening. 3cm
Ilizarov
4 months
Shigella Spp.
MSSAMeropenem
15 Consolidation.
No Infection
10 JS 42/M 12/2010 Tibia Fr. segmentar GIII Fix.Ex.AO5 months
Mix flora
13 Late Consolidation
No Infection
11 AR 49/M 04/2009 Tibia Fr. segmentar GIII ExFixAO1 Month
Mix flora
26 Consolidation.
No Infection
12 CF 66/M 11/2010 Knee
Inf. PTK. Spacer + revision
+ ExFix AO.
Shortening 6 cm
Ilizarov
8 months
MSSA
Flucloxacylin
7 Consolidation.
No Infection
13 JO 69/M 12/2010 Knee
Inf. PTK. Spacer + revision
+ ExFix MonoTube.
Shortening 5 cm
Ilizarov
4 months
Serrat. Maresc
Gentamycin
4 Infection soft tissues
Late consolidation
No bone Infection
14 EJ 48/F 02/2010 KneeKnee Instability.
PoliomyelitisIlizarov
3 months
MSSA
Flucloxacylin
16 Consolidation.
No Infection
15 MQ 58/F 03/2010 Femur Pseudartrose distal
Shortening. 5cmIlizarov
5 months
Negative
15 Consolidation.
No Infection
16 CG 56/M 10/2009 Tibia Fr. Distal GII Ilizarov2 months
Mix flora
20 Consolidation.
No Infection
17 JS 42/M 12/2010 Femur Cominutive . distal GII Ilizarov5 months
Mix flora
13 Consolidation.
No Infection
18 SR 25/F 10/2010 Femur Distal Pseudartrosis.
ObeseIlizarov
4 months
MSSA
Flucloxacylin
8 Consolidation.
No Infection
19 MS 38/F 12/2010 Tibia Bone loss 10cm Ilizarov
1 ano
Shigella Spp
Meropeneme
6 Infection soft tissues
Consolidation
No bone Infection
Grup 3 (Bone lenghtening)
20 AC 18/F 11/2010 Femur
Shortening after osteomielytis
Shortening 4 cm ExFix+ SAFE 3 months
7 Consolidation.
No Infection
21 VA 15/M 09/2010 Femur Resseco de Ewing
Shortening 4cmExFix+ SAFE
3 months
MSSA
Flucloxacylin
9 Late Consolidation
# nail - 3 months No Infection
Substitution SAFE DualCore
22 SD 51/M 11/2010 Femur Pseudartrose. proximal
Shortening 5cmExFix+ SAFE
4 months
MRSA
Vancomicina
7 Atrophic regenerate
# nail - 3 months No Infection
Substitution SAFE DualCore
and bone graft
23 FH 37/M 08/2009 Femur Aneurismatic bon cyst
Shortening 4cmTSRH nail
3 months
MSSA
Flucloxacylin
22 Consolidation.
No Infection
Grup 4 (Osteomyelitis with bone fragility)
24 FR 36/F 01/2009 Tibia Open fracture nailing. Medial Grosse nail
4 months
MSRA
Gentamycin
29 Consolidation.
No Infection
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N Name Age/Sex Date Segment Observations Initial Treat. Contamination FW Result
25 CR 16/F 09/2009 Tibia Hematogenic Proximal SAFE nail
3 years
MSSA
Flucloxacylin
21 Consolidation.
No Infection
26 JN 27/M 01/2009 Tibia Open fracture nailing. Medial Ilizarov
1 year
Serracia Mares
Gentamycin
29 Infection soft tissues
Consolidation
No Infection ssea
27 GT 51/M 01/2010 Tibia Open fracture nailing. Medial Grosse nail
3,5 months
MSSA
Flucloxacylin
17 Consolidation.
No Infection
In three cases we observed the reappearance of active soft tissue fistula after 2 weeks of treatment, whichprogressed to healing with systemic antibiotic therapy in two cases and the other case with use of PMMA cementbeads impregnated with antibiotic.
The levels of the bending forces that are exerted on the femur and tibia of an adult in their normal activities
represents up to 0.6 times the body weight when walking (40 kg) and 1.3 times when climbing stairs (100 kg) [24].
These bending forces never are reached in a patient with lower limb pathology underwent a nailling of the femur ortibia and using cruches. On the other hand, it is described that intramedullary nails have a lifespan of about 450 to
500,000 load cycles, which corresponds to about 3 to 4 months of use, leading to its failure in the meantime if there
is no bone consolidation [25 ].
The rate of delayed consolidation and pseudarthrosis after internal fixation of the closed fractures of the tibia,varies from 5 to 13%. It is known that this rate increases exponentially when it comes to an open fracture, reaching
up to 47% in Gustillo grade I and II and 74% in grade III [49].
In the group of 27 cases we treated, there was need for a second surgery procedure in 5 cases (18.5%),including 3 nail failures (11%) after 3 months in patients with delayed consolidation . This number is acceptable
and low comparatively to the data of other authors and given the severity and high risk of complications and
additional surgeries associated with alternative treatment with prolonged external fixation. [45].
Fig.6 Method for extraction of broken nail, using:
a) a retrograde 3mm Kirschner wire to push, or
b) an anterograde 5mm threaded pin to pull
In three cases it was necessary to remove broken SAFE nails, the procedure was easy to perform using a 3mm
Kirschner wire inserted retrograde, through the intercondylar notch of the femur or the calcaneus, to push
proximally the distal fragment of the broken nail, or a threaded pin, anterograde, to pull the distal fragment (Fig.6).In the overall of the 27 cases, there were two problems, 5 obstacles and no complications.
To avoid the obstacles that arose, modifications were introduced to the nail to reinforce it and give more
resistance to fatigue and simultaneously to increase the spectrum of action and dose of antibiotics, leading to the
2nd generation of SAFE nails, called SAFE DualCore nail.
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CONCLUSIONS
The authors conclude that this device, an example of a new class of implants - implants biologically active, can
represent an added value compared to current methods of treatment of open fractures, conversions of externalfixation in internal fixation and treatment of bone infections with weakening or bone loss. The procedure is simpler
and faster, the nail is more resistant than the normal nails, allowing the choice of appropriate antibiotic with local
release of high doses and prolonged treatment, able to establish a suppressive antibiotic therapy, thus avoiding the
recurrence of infection, with less intercurrences than similar methods.
In the treated patients, the SAFE nail has proved extremely effective in the prevention and treatment of boneinfection, when the appropriate antibiotic can be used. Currently in cases where the bacteria are not known, we use
two antibiotics, flucloxacillin and vancomycin.
In relation to its strength, it was observed that with a bending load of 40 to 80 kg, it is 10% stronger than thecorrespondent standard Grosse nail. Its resistance to fatigue showed, however, to be insufficient for some patients
who have delayed consolidation. To remedy this fact, modifications were introduced to the nail so as to reinforce it
and give more resistance to fatigue, giving rise to the 2nd generation of SAFE nails, called SAFE DualCore nail.
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