Accepted Manuscript Surgical treatment of jaw osteonecrosis in “krokodil” drug addicted patients Yuri M. Poghosyan , D.Sc. Koryun A. Hakobyan , Anna Yu. Poghosyan , D.Sc. Eduard K. Avetisyan , PhD PII:
S1010-5182(14)00161-9
DOI:
10.1016/j.jcms.2014.05.005
Reference:
YJCMS 1812
To appear in:
Journal of Cranio-Maxillo-Facial Surgery
Received Date: 3 September 2013 Revised Date:
1 April 2014
Accepted Date: 8 May 2014
Please cite this article as: Poghosyan YM, Hakobyan KA, Poghosyan AY, Avetisyan EK, Surgical treatment of jaw osteonecrosis in “krokodil” drug addicted patients, Journal of Cranio-Maxillofacial Surgery (2014), doi: 10.1016/j.jcms.2014.05.005. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT SURGICAL TREATMENT OF JAW OSTEONECROSIS IN “KROKODIL” DRUG ADDICTED
RI PT
PATIENTS
Yuri M. Poghosyana D.Sc., Koryun A. Hakobyana, Anna Yu. Poghosyanb D.Sc., Eduard K. Avetisyanb PhD
a
Chair of Postgraduate Maxillofacial Surgery of YSMU (Head: Prof. Yu.Poghosyan D.Sc.), 2 Koryun Str,
SC
Yerevan, Armenia, 0025 b
Department of Maxillofacial and ENT Surgery (Head: Assoc. Prof. A.Poghosyan D.Sc.) "Heratsy" №1
M AN U
University Hospital, 60 Abovyan Str., Yerevan, Armenia, 0025
Co-author responsible for correspondence: Anna Poghosyan, 13 Avag Petrosyan Str., 18 apt, Yerevan, Armenia, 0001 Tel. (+374 91) 474 169
AC C
EP
TE D
e-mail: [email protected]
ACCEPTED MANUSCRIPT ABSTRACT Retrospective study of jaw osteonecrosis treatment in patients using the “Krokodil” drug from 2009-2013
On the territory of the former USSR countries ther is widesoread use of a self-produced drug called “Krokodil”. Codeine
RI PT
containing analgesics ("Sedalgin", "Pentalgin" etc), red phosphorus (from match boxes) and other easyily acquired chemical components are used for synthesis of this drug, which used intravenously. Jaw osteonecrosis develops as a complication in patients who use “Krokodil”. The main feature of this disease is jaw bone exposure in the oral cavity.
SC
Surgery is the main method for the treatment of jaw osteonecrosis in patients using “Krokodil”.
40 “Krokodil” drug addict patients with jaw osteonecrosis were treated. Involvement of maxilla was found in 11
M AN U
patients (27.5%), mandible in 21(52.5%), both jaws in 8(20%) patients. 35 lesions were found in 29 mandibles and 21 lesions in 19 maxillas. Main factors of treatment success are: cessation of “Krokodil” use in the pre- (minimum 1 month) and postoperative period and osteonecrosis area resection of a minimum of 0.5cm beyond the visible borders of osteonecrosis towards the healthy tissues. Surgery was not delayed until sequestrum formation. In the mandible marginal or segmental resection (with or without TMJ exarticulation) was performed. After surgery recurrence of
TE D
disease was seen in 8 (23%) cases in the mandible, with no cases of recurrence in the maxilla. According to our experience in this case series, surgery is the main method for the treatment of jaw osteonecrosis in
EP
patients using “Krokodil”. Cesation of drug use and jaw resection minimize the rate of recurrences in such patients.
AC C
Keywords: drug “Krokodil”, desomorphine, jaw osteonecrosis, jaw resection
INTRODUCTION
ACCEPTED MANUSCRIPT Social and economic problems, and strict control over heroin drug mafia, leads to drug abusers obtaining drugs which are cheaper, more easily available and equal to heroin in effect. Among them home-made drugs such as “Krokodil” and “Vint” are widely used over the territory of the former USSR (Russia, Ukraine, Armenia and others). The active substance of the “Krokodil” is desomorphine, which belongs to opiate group. Drug abusers synthesize the
RI PT
desomorphine drug themselves using cheap commonly available substances which are easily obtained in the drugstores or various shops. Codeine containing analgesics ("Sedalgin", "Pentalgin" etc), iodine, soda, red phosphorus (from match boxes), hydrochloric acid, petrol and similar sustances are used for this purpose. During intravenous use of the
SC
drug other highly toxic components of the mixture gain entrance into the bloodstream along with desomorphine. They have a destructive effect on the organism, including in the maxillofacial area, resulting in the development of jaw
M AN U
osteonecrosis. This is characterized by pain, exposure of the alveolar process of the jaws (92,2% of cases) (Hakobyan, 2013), swelling of the surrounding soft tissues and intra- and extra oral fistulas in the affected area (Malanchuk et al., 2007; Poghosyan and Hakobyan, 2012). In spite of complex surgical and medical treatment a high percentage of postoperative recurrence and complications persist (Malanchuk et al., 2007; Saberov and Drobishev, 2011, Poghosyan and Hakobyan, 2013).
TE D
The aim of this study was to assess surgical treatment options for jaw osteonecrosis in “Krokodil” drug addicted
EP
patients
AC C
MATERIAL AND METHODS
Forty “Krokodil” drug addict patients with jaw osteonecrosis were referred for treatment in the Department of Maxillofacial surgery of “Kanaker-Zeytun’’ m/c (Yerevan, Armenia), between September 1, 2009 and May 30, 2013. There were 39 male and 1 female patients with a mean age of 41±1 (range 26-54). All patients had used “Krokodil” in the past, and all of them had stopped its use a minimum of 1 month before surgery. Involvement of maxilla was found in 11 patients (27.5%), mandible in 21(52.5%), both jaws in 8(20%) patients. Extra- and intraoral fistulas were present in 16 (40%) patients (fig.1). The number of lesions in one patient varies from 1 to 3. 56 lesions were found in 40 patients: 35 lesions were found in 29 mandibles, 21 lesions in 19 maxillas. Exposed area of necrotic bone included
ACCEPTED MANUSCRIPT from 1 – 3 dental sockets (fig.2 a) up to the whole alveolar process (fig.2 b). The exposed bone is of dim greyishyellowish shade and covered with greyish plaque. The empty dental sockets which could be filled with purulent discharge are observed. The surrounding mucosa is, as a rule, in pale pink colour, rarely hyperemic. Clinically intact teeth are often seen in the necrotic jawbones (fig.2 b).
RI PT
In up to 92.3% of cases (131 lesions from 142, in 90 patients) jaw osteonecrosis develops after tooth extraction, either by the dentist or the patient himself (Hakobyan, 2013). The patients experience bone exposure either immediately after the tooth removal orafter 1-12 months. Among other causes of jawbone osteonecrosis development are poor
SC
quality removable and fixed dentures, failed endodontic treatment, marginal or apical periodontitis, oral cavity mucosa acute or chronic trauma, bone trauma, anatomical features of the jaws (exostoses, palatal torus) and poor oral
used “Krokodil” (Hakobyan, 2012).
Surgery tactics A. Presurgical preparation
M AN U
hygiene. Caries and periodontal disease was present in 100% of drug addicted patients with jaw osteonecrosis who
TE D
Besides routine examination for general anaesthesia, all patients were tested for hepatitis C, B, and HIV. Hepatitis C was diagnosed in 37(92.5%) patients, Hepatitis B in 2(5%) and HIV in 1(2.5%). Patients were operated on a minimum one month after the termination of drug use. If the period of drug withdrawal
which included: 1.oral hygiene
EP
was less than one month non radical surgery (if complications were found) and conservative treatment was done,
AC C
2.removal of mobile parts of necrotisized bone 3.abscess and inflammatory mass surgery 4.detoxication therapy (isotonic saline solution, 5% glucose solution, Ringer's solution, lasix) 5.antibacterial and antifungal therapy – in case of necrotisic bone suppuration 6.treatment in drug addiction clinic B. Surgery Surgeries was not delayed until sequestrum formation. During surgery resection wasextended to 0.5 cm beyond the visible limits of osteonecrosis.
ACCEPTED MANUSCRIPT When operating on the maxilla if perforation of the floor of maxillary sinus formed, our approach was: 1. If the perforation was less than 1cm, hypertrophic mucosa of maxillary sinus floor was not removed and the wound was closed tightly 2. If the perforation was more than 1cm, pathological mucosa of maxillary sinus was removed (only from the
RI PT
perforated area, because the removal of whole maxillary sinus pathological or intact mucosa may cause development of osteonecrosis in the sinus walls) and then the maxillary sinus was packed with iodoform gauze and the end of gauze was taken out from ostium in the inferior nasal meatus. The wound in oral cavity was closed tightly.
SC
In the mandible marginal (fig.3b) or segmental resections (with or without TMJ exarticulation) (fig.4) were performed. If after marginal resection the height of the remaining bone was less than 0.5 cm, segmental resection was performed.
M AN U
If a sequestrum was found during surgery on the mandible , the intraoral wound was closed partly and the bone wound was left to heal by secondary intention using iodoform gauze. In other cases of surgery on both jaws intraoral wounds were closed tightly, with local flaps without tension.
C.
Postoperative period
TE D
In the postoperative period conservative treatment was continued. Sutures were removed on the 10th day. If failure of sutures was found after 3-6 postoperative days, the wound was left to heal with secondary intention using iodoform gauze for 1-1.5 months. Recurrence of disease wascharecterised by bone exposure, intra-, extraoral suppuration if found 1-1.5 months after radical surgery.
EP
Patients were considered as recovered if local signs of inflammation (intra-, extraoral suppuration, soft tissue abscesses and inflammatory masses) and exposed bone were absent.
AC C
Statistical analysis
Data are expressed as means±SEM. IBM SPSS Statistics 20 is used for statistical analysis. RESULTS
Main predictive factors for treatment success was: termination of “Krokodil” drug use in pre- and postoperative period and resection of necrotic bone for 0.5 cm beyond the visible borders of osteonecrosis towards the healthy tissues. Results of surgery on the mandible are shown in Table 1. We had 8(23%) cases of recurrence in the mandible. In all cases the main cause of recurrence was failure of intraoral sutures in the first 3-6 postoperative days.
ACCEPTED MANUSCRIPT 2 cases total resection of alveolar process with hard palate and partial resection of zygomatic bone were performed in the maxilla.. In other cases partial resection of the alveolar process, hard palate and zygomatic bone was done. No cases of recurrence were seen after surgery on the maxilla. In 8 (38%) cases from 21 lesions in the maxilla an oroantral communication was formed.
RI PT
In 13(23%) sequestra were found: 8 in the maxilla, 5 in the mandible. These were in patients who had stopped using “Krokodil’’ 12.6±1.7 (from 5 to 18) months before surgery, with onset of the disease 10±1.1 (from 7 to 15) months before surgery.
SC
In all cases diagnosis of jaw osteonecrosis was confirmed histologically. Histological study of the resected jaw areas revealed osteonecrosis with insignificant inflammatory background and without visible regeneration processes: the
M AN U
processes of osteolysis, osteoporosis, tissue necrosis without obvious borders with the saved tissues and weak inflammatory infiltration. There was a lack of a significant number of dilated vessels or granulation tissue in the areas adjacent to the necrotic bone tissues (Poghosyan et al., 2012).
TE D
DISCUSSION
Atypical jaw osteomyelitis, characterized by a severe chronic course and which is resistant to common medical treatment, can develop in maxillofacial region in patients who have used synthetic, intravenous, narcotic drugs which contain red phosphorus.
EP
This form of atypical jaw osteomyelitis closely resembles phosphoric jaw necrosis, widely described in the literature (Malanchuk et al., 2007; Tymofeev and Lesovaya, 2009; Tymofeev and Dakal, 2010). According to Timofeyev's data
AC C
(2009) poisoning by phosphorus compounds is seen in patients using home-made narcotics which contain red phosphorus. The history and clinical manifestations of the disease allow us to refer to this as the phosphoral jaw necrosis. Thorough history taking is one of the main diagnostic techniques of diagnosing facial bone osteonecrosis. Many authors pay attention to the accompanying pathology in drug addicted patients. Based on the case history data Malanchuk (2010) mentioned that 50% of the patients examined previously suffered from viral hepatitis A, B, C; 6.6% tuberculosis, and 10 % were HIV- infected. 16.6% had severe accompanying diseases: chronic bronchitis, pneumonia and chronic renal failure. Basin and Medvedev (2013) noted 97.7% had hepatitis C, 13,3%-HIV and 6,6% tuberculosis in
ACCEPTED MANUSCRIPT 45 drug addicted patients. In our practice, from the 90 patients with jaw osteonecrosis hepatitis C was seen in 96.7% patients, hepatisis B – 5.6%, HIV – 7.8% (Hakobyan, 2013). Malanchuk (2007) stated the clinical picture had a severe chronic course, diffuse type, rapid spreading of the process, prolonged chronic intoxication, relapses, high rate of septic complications in drug addicted patients. Morozova et al.
RI PT
(2013) reported the following clinical manifestations of chronic osteomyelitis against the background of chronic intoxication: sluggish course, expressed intoxication, progressive bone destruction with repeated sequestration, pathological jaw fractures, diffuse osteonecrosis with demarcation zone absence, expressed immunodeficiency.
SC
Timofeev (2010), Morozova et al. (2013) described the abscesses and inflammatory masses of the soft tissues of the maxillofacial region and the neck. We saw combined involvement of the nasal bones in 1,1% patients, of the zygomatic
M AN U
bones in 4,4%, and the hard palate in 6.7% patients (Hakobyan, 2013).
Timofeev (2010) mentions the rarefied bone tissue areas of various size with huge sequestrum formation on the X-ray pictures of the mandible against the background of osteoporosis foci. According to the author’s data the terms of sequestrum formation in drug addicted patients who used "Pervitin" exceed these terms in traditional forms of the disease on 2-3 weeks. He refers to the specificity of the osteomyelitis X-ray pictures the fact that sequestra are
TE D
revealed against the background of numerous osteoporosis foci of the jaw. According to Malanchuk’s data (2007), in drug addicted patients the exact sequestration is absent and focal resorbtion is without exact borders resembling the picture of radial osteomyelitis seen in X-ray studies. Tymofeev and Lesovaya (2009) describes bone necrosis without demarcation zone and traditional formation of the sequestra as typical signs of odontogenic osteomyelitis of atypical
EP
course in drug addicted patients.
Our practice has shown, that radiologic signs of jaw osteonecrosis in “Krokodil” addicted patients depend on the terms
AC C
of drug use withdrawal and the onset of the disease (Poghosyan and Hakobyan, 2013). In the early stages of the disease radiographic examination can be uninformative as nonspecific signs are often revealed: osteosclerosis, destruction, empty dental alveoli without demarcation of osteonecrosis zone (fig.4a) and the clinical signs do not correspond to the radiological ones. In X-ray study, patients who discontinued “Krokodil” usage during 8.3 ±1.6 months and the onset of the disease was noted 10.6±1.8 months before the examination had osteonecrosis foci with demarcation (fig.3a). Demarcation revealed in X-ray study is not a sensitive sign of sequestrum formation (Poghosyan and Hakobyan, 2013).
ACCEPTED MANUSCRIPT Based on experience of facial bone osteomyelitis treatment in drug addicted patients Malanchuk (2010) supposes that in surgical treatment of such patients it is not worth considering the presence of demarcation processes as the pathological process spreads quickly and the demarcation zone has not been formed. In sequesterectomy it is necessary to remove all the dead bony tissue up to revealing multiple various-sized blood vessels of the bone.
RI PT
Timofeev (2010) recommended closure of the osseous defect with local soft tissues. According to the study conducted by Saberov (2011) the patients underwent radical surgical interventions such as jaw resection within the limits of healthy osseous tissue. Removal of obviously necrotic bone was considered to be the treatment. In Timofeev’s opinion
SC
traditional conservative treatment of post-operative wounds is not effective enough to prevent the enlargement of the inflammatory changed soft tissue size, new fistula appearance with scarce purulent discharge.
M AN U
Despite complex treatment and radical surgical interventions including extended removal of necrotic tissue and partial resection up to visually healthy osseous tissue, Malanchuk (2007) mentioned the relapses of the disease and septic complications. Saberov (2011) and Morozova (2013) stated the necessity of a surgical approach and patient’s immune state correction.
In our opinion the surgical method is the main treatment for patients with jaw osteonecrosis who use home-made
TE D
narcotic drug such as “Krokodil” containing red phosphorus (Poghosyan and Hakobyan, 2013). The main criteria for the treatment are: pre- and postoperative discontinuation of “Krokodil” use and resection of osteonecrotic tissue for a minimum in 0.5 cm beyond the visible borders of osteonecrosis towards the healthy tissues (Poghosyan and Hakobyan, 2013). A positive outcome is seen in 100% of the upper jaw cases. In the mandible the rate of recurrence is
EP
23%.. The formation of an oroantral communication is a complication of the treatment of upper jaw osteonecrosis in 38% of cases. Sequestrum formation is seen in 23% of cases of the patients who discontinued the use of the drug. In
AC C
regular drug use the sequestrum formation could fail, even 2 years after the onset of the disease (Poghosyan and Hakobyan, 2013). Malanchuk (2007) observed high rate of septic complications (8.33%) and low efficacy of medical and surgical treatment if narcotic drug usage is continued. CONCLUSION
Jaw osteonecrosis develops as a complication in patients who use the drug “Krokodil”. According to our experience for this case series surgery is the main method for the treatment of jaw osteonecrosis in patients using “Krokodil”. Drug withdrawal and jaw resection for aminimum in 0.5cm beyond the visible borders of osteonecrosis towards the healthy tissues minimizes the rate of disease recurrences in such patients.
ACCEPTED MANUSCRIPT CONFLICT OF INTEREST
RI PT
There is no conflict of interest that has to be indicated by the authors.
REFERENCES 1.
Basin E.M., Medvedev Yu.A: Principles of maxilla osteonecrosis in patients with drug abuse, Pacific Medical Journal. 1: 87–89, 2013.
Hakobyan K.A. Clinical picture, diagnosis and treatment of facial bones osteonecrosis at patients who use the
SC
2.
drug // Autoref. Diss. Cand. Med. Sci. Yerevan, 2013.
Hakobyan K.A. The state of oral cavity in drug addicted patients with jaw osteonecrosis who use the drug
M AN U
3.
"Crocodile" (desomorphine). Bulletin of Stomatology and Maxillofacial Surgery 1:16-19, 2012. 4.
Malanchuk V.O. Brodetskiy I.S: Complex treatment of patients with osteomyelitis of the jaws against drug addiction // Recent advances and prospects of development of oral surgery and maxillofacial surgery: a mat. Republican scientific-practical conference with international participation. Harkov: 51–53, 2010. Malanchuk VA, Kopchak AV, Brodetsky IS: Clinical features of jaw osteomyelitis in drug addicted patients. Ukr.
TE D
5.
Med. Jour. 4(60): 111-117, 2007. 6.
Medvedev Yu., Basin E: Facial osteonecrosis in persons with drug addiction; clinical picture, diagnosis,
7.
EP
principles of treatment. J.Vrach. 2: .55-60, 2012 Morozova M. N., Lupersolsky M. U., Boyarintsev S: Experience of surgical treatment of atypical chronic
AC C
osteomyelitis of the jaws in patients who recovered from drug abuse. Journal of problems of biology and medicine. 2(100): 309-313, 2013.
8.
Poghosyan Yu.M, Hakobyan K.A, Manukyan E.V: Pathomorphological features of jaw osteonecrosis in drug
addicted patients who use the drug "Crocodile" (desomorphine). Medicine Science and Education №12:103108,2012.
9.
Poghosyan Yu.M., Hakobyan K.A: Clinical-laboratory features of jaw osteonecrosis in drug addicted patients who use the drug "Crocodile" (desomorphine). Issues in Theoretical and Clinical Medicine №2 (69):69-72, 2012.
ACCEPTED MANUSCRIPT 10. Poghosyan Yu.M, Hakobyan K.A: Treatment of jaw osteonecrosis in patients who use self-produced drugs. Issues in Theoretical and Clinical Medicine № 1(77):48-51, 2013. 11. Saberov R.Z., Drobishev A.Yu: The osteonecrosis of the jaw in patients with immune deficiency in patients
Maxillofacial Surgeons. SPb., 157, 2011.
RI PT
receiving narcotic drugs // New technologies in dentistry: Proceedings of the XVI International Conference of
12. Tymofieiev A.A., Dakal AV: Clinical course of purulent inflammatory diseases of the jaws and soft tissues of the maxillofacial area in patients using "Vint" drug. Modern Stomatology.1: 96-102, 2010.
SC
13. Tymofieiev A.A., Lesova I.G: Phosphoric necrosis of jaws at narcodependent patients using substitute
AC C
EP
TE D
M AN U
awareness-inducing "Screw". Modern Stomatology.5 (49): 94-98, 2009.
ACCEPTED MANUSCRIPT Table 1 Results of surgery on mandible Amount of operated
Amount of recurrences
lesions 21
5
Segmental resection
14 (TMJ exarticulation–2
3
AC C
EP
TE D
M AN U
SC
cases)
RI PT
Marginal resection
ACCEPTED MANUSCRIPT
RI PT
Fig.1. Fistulae in the right submandibular and submental areas (black arrows) at patient A.
Fig.2. Oral cavity view of “Krokodil” drug user patients. (a) the mandible right side partial exposure at patient B. (b) exposure of whole alveolar process of mandible at patient A.
Fig.3. Patient B (a) preoperative orthopanthomogramm: there is demarcation of the osteonecrosis
M AN U
(c) orthopanthomogramm 1 month postoperatively
SC
zone, (b) postoperative view of the intraoral wound after mandible marginal resection (7th day),
Fig.4. Patient A (a) preoperative orthopanthomogramm: no sign of demarcation of osteonecrosis zone, (b) intraoperative view, (c) resected part of mandible, (d), (e) external view 11 months
AC C
EP
TE D
postoperatively, (f) Orthopanthomogramm 11 months postoperatively
AC C
EP
Figure 1
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
Figure 2a
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
Figure 2b
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
Figure 3a
AC C
EP
Figure 3b
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
Figure 3c
Figure 4a
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
Figure 4b
AC C
EP
Figure 4c
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
Figure 4d
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
Figure 4e
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
Figure 4f
S1010-5182(14)00161-9
DOI:
10.1016/j.jcms.2014.05.005
Reference:
YJCMS 1812
To appear in:
Journal of Cranio-Maxillo-Facial Surgery
Received Date: 3 September 2013 Revised Date:
1 April 2014
Accepted Date: 8 May 2014
Please cite this article as: Poghosyan YM, Hakobyan KA, Poghosyan AY, Avetisyan EK, Surgical treatment of jaw osteonecrosis in “krokodil” drug addicted patients, Journal of Cranio-Maxillofacial Surgery (2014), doi: 10.1016/j.jcms.2014.05.005. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT SURGICAL TREATMENT OF JAW OSTEONECROSIS IN “KROKODIL” DRUG ADDICTED
RI PT
PATIENTS
Yuri M. Poghosyana D.Sc., Koryun A. Hakobyana, Anna Yu. Poghosyanb D.Sc., Eduard K. Avetisyanb PhD
a
Chair of Postgraduate Maxillofacial Surgery of YSMU (Head: Prof. Yu.Poghosyan D.Sc.), 2 Koryun Str,
SC
Yerevan, Armenia, 0025 b
Department of Maxillofacial and ENT Surgery (Head: Assoc. Prof. A.Poghosyan D.Sc.) "Heratsy" №1
M AN U
University Hospital, 60 Abovyan Str., Yerevan, Armenia, 0025
Co-author responsible for correspondence: Anna Poghosyan, 13 Avag Petrosyan Str., 18 apt, Yerevan, Armenia, 0001 Tel. (+374 91) 474 169
AC C
EP
TE D
e-mail: [email protected]
ACCEPTED MANUSCRIPT ABSTRACT Retrospective study of jaw osteonecrosis treatment in patients using the “Krokodil” drug from 2009-2013
On the territory of the former USSR countries ther is widesoread use of a self-produced drug called “Krokodil”. Codeine
RI PT
containing analgesics ("Sedalgin", "Pentalgin" etc), red phosphorus (from match boxes) and other easyily acquired chemical components are used for synthesis of this drug, which used intravenously. Jaw osteonecrosis develops as a complication in patients who use “Krokodil”. The main feature of this disease is jaw bone exposure in the oral cavity.
SC
Surgery is the main method for the treatment of jaw osteonecrosis in patients using “Krokodil”.
40 “Krokodil” drug addict patients with jaw osteonecrosis were treated. Involvement of maxilla was found in 11
M AN U
patients (27.5%), mandible in 21(52.5%), both jaws in 8(20%) patients. 35 lesions were found in 29 mandibles and 21 lesions in 19 maxillas. Main factors of treatment success are: cessation of “Krokodil” use in the pre- (minimum 1 month) and postoperative period and osteonecrosis area resection of a minimum of 0.5cm beyond the visible borders of osteonecrosis towards the healthy tissues. Surgery was not delayed until sequestrum formation. In the mandible marginal or segmental resection (with or without TMJ exarticulation) was performed. After surgery recurrence of
TE D
disease was seen in 8 (23%) cases in the mandible, with no cases of recurrence in the maxilla. According to our experience in this case series, surgery is the main method for the treatment of jaw osteonecrosis in
EP
patients using “Krokodil”. Cesation of drug use and jaw resection minimize the rate of recurrences in such patients.
AC C
Keywords: drug “Krokodil”, desomorphine, jaw osteonecrosis, jaw resection
INTRODUCTION
ACCEPTED MANUSCRIPT Social and economic problems, and strict control over heroin drug mafia, leads to drug abusers obtaining drugs which are cheaper, more easily available and equal to heroin in effect. Among them home-made drugs such as “Krokodil” and “Vint” are widely used over the territory of the former USSR (Russia, Ukraine, Armenia and others). The active substance of the “Krokodil” is desomorphine, which belongs to opiate group. Drug abusers synthesize the
RI PT
desomorphine drug themselves using cheap commonly available substances which are easily obtained in the drugstores or various shops. Codeine containing analgesics ("Sedalgin", "Pentalgin" etc), iodine, soda, red phosphorus (from match boxes), hydrochloric acid, petrol and similar sustances are used for this purpose. During intravenous use of the
SC
drug other highly toxic components of the mixture gain entrance into the bloodstream along with desomorphine. They have a destructive effect on the organism, including in the maxillofacial area, resulting in the development of jaw
M AN U
osteonecrosis. This is characterized by pain, exposure of the alveolar process of the jaws (92,2% of cases) (Hakobyan, 2013), swelling of the surrounding soft tissues and intra- and extra oral fistulas in the affected area (Malanchuk et al., 2007; Poghosyan and Hakobyan, 2012). In spite of complex surgical and medical treatment a high percentage of postoperative recurrence and complications persist (Malanchuk et al., 2007; Saberov and Drobishev, 2011, Poghosyan and Hakobyan, 2013).
TE D
The aim of this study was to assess surgical treatment options for jaw osteonecrosis in “Krokodil” drug addicted
EP
patients
AC C
MATERIAL AND METHODS
Forty “Krokodil” drug addict patients with jaw osteonecrosis were referred for treatment in the Department of Maxillofacial surgery of “Kanaker-Zeytun’’ m/c (Yerevan, Armenia), between September 1, 2009 and May 30, 2013. There were 39 male and 1 female patients with a mean age of 41±1 (range 26-54). All patients had used “Krokodil” in the past, and all of them had stopped its use a minimum of 1 month before surgery. Involvement of maxilla was found in 11 patients (27.5%), mandible in 21(52.5%), both jaws in 8(20%) patients. Extra- and intraoral fistulas were present in 16 (40%) patients (fig.1). The number of lesions in one patient varies from 1 to 3. 56 lesions were found in 40 patients: 35 lesions were found in 29 mandibles, 21 lesions in 19 maxillas. Exposed area of necrotic bone included
ACCEPTED MANUSCRIPT from 1 – 3 dental sockets (fig.2 a) up to the whole alveolar process (fig.2 b). The exposed bone is of dim greyishyellowish shade and covered with greyish plaque. The empty dental sockets which could be filled with purulent discharge are observed. The surrounding mucosa is, as a rule, in pale pink colour, rarely hyperemic. Clinically intact teeth are often seen in the necrotic jawbones (fig.2 b).
RI PT
In up to 92.3% of cases (131 lesions from 142, in 90 patients) jaw osteonecrosis develops after tooth extraction, either by the dentist or the patient himself (Hakobyan, 2013). The patients experience bone exposure either immediately after the tooth removal orafter 1-12 months. Among other causes of jawbone osteonecrosis development are poor
SC
quality removable and fixed dentures, failed endodontic treatment, marginal or apical periodontitis, oral cavity mucosa acute or chronic trauma, bone trauma, anatomical features of the jaws (exostoses, palatal torus) and poor oral
used “Krokodil” (Hakobyan, 2012).
Surgery tactics A. Presurgical preparation
M AN U
hygiene. Caries and periodontal disease was present in 100% of drug addicted patients with jaw osteonecrosis who
TE D
Besides routine examination for general anaesthesia, all patients were tested for hepatitis C, B, and HIV. Hepatitis C was diagnosed in 37(92.5%) patients, Hepatitis B in 2(5%) and HIV in 1(2.5%). Patients were operated on a minimum one month after the termination of drug use. If the period of drug withdrawal
which included: 1.oral hygiene
EP
was less than one month non radical surgery (if complications were found) and conservative treatment was done,
AC C
2.removal of mobile parts of necrotisized bone 3.abscess and inflammatory mass surgery 4.detoxication therapy (isotonic saline solution, 5% glucose solution, Ringer's solution, lasix) 5.antibacterial and antifungal therapy – in case of necrotisic bone suppuration 6.treatment in drug addiction clinic B. Surgery Surgeries was not delayed until sequestrum formation. During surgery resection wasextended to 0.5 cm beyond the visible limits of osteonecrosis.
ACCEPTED MANUSCRIPT When operating on the maxilla if perforation of the floor of maxillary sinus formed, our approach was: 1. If the perforation was less than 1cm, hypertrophic mucosa of maxillary sinus floor was not removed and the wound was closed tightly 2. If the perforation was more than 1cm, pathological mucosa of maxillary sinus was removed (only from the
RI PT
perforated area, because the removal of whole maxillary sinus pathological or intact mucosa may cause development of osteonecrosis in the sinus walls) and then the maxillary sinus was packed with iodoform gauze and the end of gauze was taken out from ostium in the inferior nasal meatus. The wound in oral cavity was closed tightly.
SC
In the mandible marginal (fig.3b) or segmental resections (with or without TMJ exarticulation) (fig.4) were performed. If after marginal resection the height of the remaining bone was less than 0.5 cm, segmental resection was performed.
M AN U
If a sequestrum was found during surgery on the mandible , the intraoral wound was closed partly and the bone wound was left to heal by secondary intention using iodoform gauze. In other cases of surgery on both jaws intraoral wounds were closed tightly, with local flaps without tension.
C.
Postoperative period
TE D
In the postoperative period conservative treatment was continued. Sutures were removed on the 10th day. If failure of sutures was found after 3-6 postoperative days, the wound was left to heal with secondary intention using iodoform gauze for 1-1.5 months. Recurrence of disease wascharecterised by bone exposure, intra-, extraoral suppuration if found 1-1.5 months after radical surgery.
EP
Patients were considered as recovered if local signs of inflammation (intra-, extraoral suppuration, soft tissue abscesses and inflammatory masses) and exposed bone were absent.
AC C
Statistical analysis
Data are expressed as means±SEM. IBM SPSS Statistics 20 is used for statistical analysis. RESULTS
Main predictive factors for treatment success was: termination of “Krokodil” drug use in pre- and postoperative period and resection of necrotic bone for 0.5 cm beyond the visible borders of osteonecrosis towards the healthy tissues. Results of surgery on the mandible are shown in Table 1. We had 8(23%) cases of recurrence in the mandible. In all cases the main cause of recurrence was failure of intraoral sutures in the first 3-6 postoperative days.
ACCEPTED MANUSCRIPT 2 cases total resection of alveolar process with hard palate and partial resection of zygomatic bone were performed in the maxilla.. In other cases partial resection of the alveolar process, hard palate and zygomatic bone was done. No cases of recurrence were seen after surgery on the maxilla. In 8 (38%) cases from 21 lesions in the maxilla an oroantral communication was formed.
RI PT
In 13(23%) sequestra were found: 8 in the maxilla, 5 in the mandible. These were in patients who had stopped using “Krokodil’’ 12.6±1.7 (from 5 to 18) months before surgery, with onset of the disease 10±1.1 (from 7 to 15) months before surgery.
SC
In all cases diagnosis of jaw osteonecrosis was confirmed histologically. Histological study of the resected jaw areas revealed osteonecrosis with insignificant inflammatory background and without visible regeneration processes: the
M AN U
processes of osteolysis, osteoporosis, tissue necrosis without obvious borders with the saved tissues and weak inflammatory infiltration. There was a lack of a significant number of dilated vessels or granulation tissue in the areas adjacent to the necrotic bone tissues (Poghosyan et al., 2012).
TE D
DISCUSSION
Atypical jaw osteomyelitis, characterized by a severe chronic course and which is resistant to common medical treatment, can develop in maxillofacial region in patients who have used synthetic, intravenous, narcotic drugs which contain red phosphorus.
EP
This form of atypical jaw osteomyelitis closely resembles phosphoric jaw necrosis, widely described in the literature (Malanchuk et al., 2007; Tymofeev and Lesovaya, 2009; Tymofeev and Dakal, 2010). According to Timofeyev's data
AC C
(2009) poisoning by phosphorus compounds is seen in patients using home-made narcotics which contain red phosphorus. The history and clinical manifestations of the disease allow us to refer to this as the phosphoral jaw necrosis. Thorough history taking is one of the main diagnostic techniques of diagnosing facial bone osteonecrosis. Many authors pay attention to the accompanying pathology in drug addicted patients. Based on the case history data Malanchuk (2010) mentioned that 50% of the patients examined previously suffered from viral hepatitis A, B, C; 6.6% tuberculosis, and 10 % were HIV- infected. 16.6% had severe accompanying diseases: chronic bronchitis, pneumonia and chronic renal failure. Basin and Medvedev (2013) noted 97.7% had hepatitis C, 13,3%-HIV and 6,6% tuberculosis in
ACCEPTED MANUSCRIPT 45 drug addicted patients. In our practice, from the 90 patients with jaw osteonecrosis hepatitis C was seen in 96.7% patients, hepatisis B – 5.6%, HIV – 7.8% (Hakobyan, 2013). Malanchuk (2007) stated the clinical picture had a severe chronic course, diffuse type, rapid spreading of the process, prolonged chronic intoxication, relapses, high rate of septic complications in drug addicted patients. Morozova et al.
RI PT
(2013) reported the following clinical manifestations of chronic osteomyelitis against the background of chronic intoxication: sluggish course, expressed intoxication, progressive bone destruction with repeated sequestration, pathological jaw fractures, diffuse osteonecrosis with demarcation zone absence, expressed immunodeficiency.
SC
Timofeev (2010), Morozova et al. (2013) described the abscesses and inflammatory masses of the soft tissues of the maxillofacial region and the neck. We saw combined involvement of the nasal bones in 1,1% patients, of the zygomatic
M AN U
bones in 4,4%, and the hard palate in 6.7% patients (Hakobyan, 2013).
Timofeev (2010) mentions the rarefied bone tissue areas of various size with huge sequestrum formation on the X-ray pictures of the mandible against the background of osteoporosis foci. According to the author’s data the terms of sequestrum formation in drug addicted patients who used "Pervitin" exceed these terms in traditional forms of the disease on 2-3 weeks. He refers to the specificity of the osteomyelitis X-ray pictures the fact that sequestra are
TE D
revealed against the background of numerous osteoporosis foci of the jaw. According to Malanchuk’s data (2007), in drug addicted patients the exact sequestration is absent and focal resorbtion is without exact borders resembling the picture of radial osteomyelitis seen in X-ray studies. Tymofeev and Lesovaya (2009) describes bone necrosis without demarcation zone and traditional formation of the sequestra as typical signs of odontogenic osteomyelitis of atypical
EP
course in drug addicted patients.
Our practice has shown, that radiologic signs of jaw osteonecrosis in “Krokodil” addicted patients depend on the terms
AC C
of drug use withdrawal and the onset of the disease (Poghosyan and Hakobyan, 2013). In the early stages of the disease radiographic examination can be uninformative as nonspecific signs are often revealed: osteosclerosis, destruction, empty dental alveoli without demarcation of osteonecrosis zone (fig.4a) and the clinical signs do not correspond to the radiological ones. In X-ray study, patients who discontinued “Krokodil” usage during 8.3 ±1.6 months and the onset of the disease was noted 10.6±1.8 months before the examination had osteonecrosis foci with demarcation (fig.3a). Demarcation revealed in X-ray study is not a sensitive sign of sequestrum formation (Poghosyan and Hakobyan, 2013).
ACCEPTED MANUSCRIPT Based on experience of facial bone osteomyelitis treatment in drug addicted patients Malanchuk (2010) supposes that in surgical treatment of such patients it is not worth considering the presence of demarcation processes as the pathological process spreads quickly and the demarcation zone has not been formed. In sequesterectomy it is necessary to remove all the dead bony tissue up to revealing multiple various-sized blood vessels of the bone.
RI PT
Timofeev (2010) recommended closure of the osseous defect with local soft tissues. According to the study conducted by Saberov (2011) the patients underwent radical surgical interventions such as jaw resection within the limits of healthy osseous tissue. Removal of obviously necrotic bone was considered to be the treatment. In Timofeev’s opinion
SC
traditional conservative treatment of post-operative wounds is not effective enough to prevent the enlargement of the inflammatory changed soft tissue size, new fistula appearance with scarce purulent discharge.
M AN U
Despite complex treatment and radical surgical interventions including extended removal of necrotic tissue and partial resection up to visually healthy osseous tissue, Malanchuk (2007) mentioned the relapses of the disease and septic complications. Saberov (2011) and Morozova (2013) stated the necessity of a surgical approach and patient’s immune state correction.
In our opinion the surgical method is the main treatment for patients with jaw osteonecrosis who use home-made
TE D
narcotic drug such as “Krokodil” containing red phosphorus (Poghosyan and Hakobyan, 2013). The main criteria for the treatment are: pre- and postoperative discontinuation of “Krokodil” use and resection of osteonecrotic tissue for a minimum in 0.5 cm beyond the visible borders of osteonecrosis towards the healthy tissues (Poghosyan and Hakobyan, 2013). A positive outcome is seen in 100% of the upper jaw cases. In the mandible the rate of recurrence is
EP
23%.. The formation of an oroantral communication is a complication of the treatment of upper jaw osteonecrosis in 38% of cases. Sequestrum formation is seen in 23% of cases of the patients who discontinued the use of the drug. In
AC C
regular drug use the sequestrum formation could fail, even 2 years after the onset of the disease (Poghosyan and Hakobyan, 2013). Malanchuk (2007) observed high rate of septic complications (8.33%) and low efficacy of medical and surgical treatment if narcotic drug usage is continued. CONCLUSION
Jaw osteonecrosis develops as a complication in patients who use the drug “Krokodil”. According to our experience for this case series surgery is the main method for the treatment of jaw osteonecrosis in patients using “Krokodil”. Drug withdrawal and jaw resection for aminimum in 0.5cm beyond the visible borders of osteonecrosis towards the healthy tissues minimizes the rate of disease recurrences in such patients.
ACCEPTED MANUSCRIPT CONFLICT OF INTEREST
RI PT
There is no conflict of interest that has to be indicated by the authors.
REFERENCES 1.
Basin E.M., Medvedev Yu.A: Principles of maxilla osteonecrosis in patients with drug abuse, Pacific Medical Journal. 1: 87–89, 2013.
Hakobyan K.A. Clinical picture, diagnosis and treatment of facial bones osteonecrosis at patients who use the
SC
2.
drug // Autoref. Diss. Cand. Med. Sci. Yerevan, 2013.
Hakobyan K.A. The state of oral cavity in drug addicted patients with jaw osteonecrosis who use the drug
M AN U
3.
"Crocodile" (desomorphine). Bulletin of Stomatology and Maxillofacial Surgery 1:16-19, 2012. 4.
Malanchuk V.O. Brodetskiy I.S: Complex treatment of patients with osteomyelitis of the jaws against drug addiction // Recent advances and prospects of development of oral surgery and maxillofacial surgery: a mat. Republican scientific-practical conference with international participation. Harkov: 51–53, 2010. Malanchuk VA, Kopchak AV, Brodetsky IS: Clinical features of jaw osteomyelitis in drug addicted patients. Ukr.
TE D
5.
Med. Jour. 4(60): 111-117, 2007. 6.
Medvedev Yu., Basin E: Facial osteonecrosis in persons with drug addiction; clinical picture, diagnosis,
7.
EP
principles of treatment. J.Vrach. 2: .55-60, 2012 Morozova M. N., Lupersolsky M. U., Boyarintsev S: Experience of surgical treatment of atypical chronic
AC C
osteomyelitis of the jaws in patients who recovered from drug abuse. Journal of problems of biology and medicine. 2(100): 309-313, 2013.
8.
Poghosyan Yu.M, Hakobyan K.A, Manukyan E.V: Pathomorphological features of jaw osteonecrosis in drug
addicted patients who use the drug "Crocodile" (desomorphine). Medicine Science and Education №12:103108,2012.
9.
Poghosyan Yu.M., Hakobyan K.A: Clinical-laboratory features of jaw osteonecrosis in drug addicted patients who use the drug "Crocodile" (desomorphine). Issues in Theoretical and Clinical Medicine №2 (69):69-72, 2012.
ACCEPTED MANUSCRIPT 10. Poghosyan Yu.M, Hakobyan K.A: Treatment of jaw osteonecrosis in patients who use self-produced drugs. Issues in Theoretical and Clinical Medicine № 1(77):48-51, 2013. 11. Saberov R.Z., Drobishev A.Yu: The osteonecrosis of the jaw in patients with immune deficiency in patients
Maxillofacial Surgeons. SPb., 157, 2011.
RI PT
receiving narcotic drugs // New technologies in dentistry: Proceedings of the XVI International Conference of
12. Tymofieiev A.A., Dakal AV: Clinical course of purulent inflammatory diseases of the jaws and soft tissues of the maxillofacial area in patients using "Vint" drug. Modern Stomatology.1: 96-102, 2010.
SC
13. Tymofieiev A.A., Lesova I.G: Phosphoric necrosis of jaws at narcodependent patients using substitute
AC C
EP
TE D
M AN U
awareness-inducing "Screw". Modern Stomatology.5 (49): 94-98, 2009.
ACCEPTED MANUSCRIPT Table 1 Results of surgery on mandible Amount of operated
Amount of recurrences
lesions 21
5
Segmental resection
14 (TMJ exarticulation–2
3
AC C
EP
TE D
M AN U
SC
cases)
RI PT
Marginal resection
ACCEPTED MANUSCRIPT
RI PT
Fig.1. Fistulae in the right submandibular and submental areas (black arrows) at patient A.
Fig.2. Oral cavity view of “Krokodil” drug user patients. (a) the mandible right side partial exposure at patient B. (b) exposure of whole alveolar process of mandible at patient A.
Fig.3. Patient B (a) preoperative orthopanthomogramm: there is demarcation of the osteonecrosis
M AN U
(c) orthopanthomogramm 1 month postoperatively
SC
zone, (b) postoperative view of the intraoral wound after mandible marginal resection (7th day),
Fig.4. Patient A (a) preoperative orthopanthomogramm: no sign of demarcation of osteonecrosis zone, (b) intraoperative view, (c) resected part of mandible, (d), (e) external view 11 months
AC C
EP
TE D
postoperatively, (f) Orthopanthomogramm 11 months postoperatively
AC C
EP
Figure 1
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
Figure 2a
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
Figure 2b
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
Figure 3a
AC C
EP
Figure 3b
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
Figure 3c
Figure 4a
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
Figure 4b
AC C
EP
Figure 4c
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
Figure 4d
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
Figure 4e
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
Figure 4f
