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High rates of midazolam injection among drug users in Bangkok, Thailand Kerr, Thomas; Kiatying-Angsulee, Niyada; Fairbairn, Nadia; Hayashi, Kanna; Suwannawong, Paisan; Kaplan, Karyn; Lai, Calvin; Wood, Evan Mar 26, 2010

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RESEARCH Open AccessHigh rates of midazolam injection among drugusers in Bangkok, ThailandThomas Kerr1,2*, Niyada Kiatying-Angsulee3, Nadia Fairbairn1, Kanna Hayashi1, Paisan Suwannawong4,Karyn Kaplan4, Calvin Lai1, Evan Wood1,2AbstractBackground: Reports from Thailand suggest that a growing number of people who inject drugs (IDU) are nowinjecting midazolam, a legal benzodiazepine with potent amnestic and ventilatory depressant effects. We thereforesought to examine midazolam injection among a community-recruited sample of Thai IDU.Methods: We examined the prevalence and correlates of midazolam injection among 252 IDU participating in theMitsampan Community Research Project, Bangkok, using multivariate logistic regression. We also examined the useof midazolam in combination with other drugs.Results: 252 IDU participated in this study, including 66 (26.2%) women. In total, 170 (67.5%) participants reportedever having injected midazolam, and 144 (57.1%) reported daily midazolam injection in the past six months. Inmultivariate analyses, a history of midazolam injection was independently associated with using drugs incombination (adjusted odds ratio [AOR] = 5.86; 95% confidence interval [CI]: 2.96-11.60), younger age (AOR = 0.43;95%CI: 0.22-0.83), having a history of methadone treatment (AOR = 3.12, 95%CI: 1.55-6.90), and binge drug use(AOR = 2.25, 95%CI: 1.09-4.63). The drugs most commonly used in combination with midazolam were heroin(72.3%) and yaba (methamphetamine) (30.5%).Conclusion: We observed a high rate of midazolam injection among Thai IDU. Midazolam injection was stronglyassociated with polysubstance use and binge drug use, and was most commonly used in combination with bothopiates and methamphetamines. Our findings suggest that midazolam injection has become increasingly commonwithin Thailand. Evidence-based approaches for reducing harms associated with midazolam injection are needed.BackgroundThailand, like many other countries globally has beenexperiencing shifting patterns of drug supply and use[1-7]. Studies undertaken during the past decade suggesta number of Thai people who inject drugs (IDU) arenow injecting midazolam (Thai trade name: Dormi-cum®), a legal, rapid onset, short duration benzodiaze-pine with potent sedative, amnestic and ventilatorydepressant effects [8-10]. Midazolam is prescribed intablet form, although it is often administered intrave-nously for sedation in hospital settings [9]. However, ithas been reported anecdotally that some Thai physiciansalso prescribe midazolam for the treatment of withdra-wal from opiate use [11]. A study indicated risingmidazolam injection among Thai IDU, with 30% of anIDU sample reporting midazolam injection during 1999-2000 [9]. This trend was believed to coincide with theThai government’s increasing focus on drug enforce-ment and the declining availability and rising price ofheroin in Thailand. Midazolam is much less expensive(approximately $3 USD per tablet) to acquire than her-oin [8].It has been suggested that midazolam injection, partlybecause of the associated amnestic effects, can result inelevated rates of risk behaviour, including syringe shar-ing [9]. The injection of midazolam filtrate is believed toincrease risk for soft-tissue infections, gangrene, andthromboembolic events [8]. Withdrawal effects are typi-cal of benzodiazepines and include headaches, insomnia,agitation and seizures and can be fatal [8]. Further, con-cerns have been expressed regarding high rates of poly-substance use among IDU who inject midazolam,* Correspondence: uhritk@cfenet.ubc.ca1British Columbia Centre for Excellence in HIV/AIDS, St Paul’s Hospital,Vancouver, CanadaKerr et al. Harm Reduction Journal 2010, 7:7http://www.harmreductionjournal.com/content/7/1/7© 2010 Kerr et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.prompting calls for more research on midazolam injec-tion [9]. Given these concerns, the ongoing “drug war”in Thailand, and the paucity of research on midazolamuse, we sought to examine the prevalence and correlatesof midazolam injection, as well as patterns of midazo-lam-related polysubstance use, among a community-recruited sample of IDU in Bangkok, Thailand.MethodsThe Mitsampan Community Research Project is a colla-borative research project involving the British ColumbiaCentre for Excellence in HIV/AIDS (Vancouver,Canada), the Mitsampan Harm Reduction Center (Bang-kok, Thailand), the Thai AIDS Treatment Action Group(Bangkok, Thailand), and Chulalongkorn University(Bangkok, Thailand). During July-August 2008, the part-ners undertook a cross-sectional study involving 252community-recruited IDU. The primary aims of thestudy were to assess drug use and HIV risk behaviorsand to assess barriers to access to healthcare amonglocal IDU. Potential participants were recruited throughpeer-based outreach efforts and word of mouth. Studyparticipants were invited to attend the Mitsampan HarmReduction Center (MSHRC) to participate in the study.The Mitsampan Center was established in the Mitsam-pan neighborhood, which is home to large number ofillicit drug users and low-income residents. Individualswere eligible for participation in this study and definedas an “IDU” if they reported injection of illicit drugs inthe past six months. All participants provided informedconsent and completed an interviewer-administeredquestionnaire eliciting information about demographiccharacteristics, drug use, HIV risk behaviour, criminaljustice system exposure, and experiences with healthcare. All participants were given 250 Baht (approxi-mately $7 USD) upon completion of the questionnaire.The study has been approved by the Research EthicsBoards of the University of British Columbia and Chula-longkorn University.Using univariate statistics and multivariate logisticregression, we compared IDU who did and did notreport a history of midazolam injection. Variables con-sidered included: median age (< 36.5 years or ≥ 36.5years), gender, education level (< secondary school vs. ≥secondary school), heroin injection (yes vs. no), yaba(i.e., methamphetamine) injection (yes vs. no), use ofdrugs in combination (yes vs. no), syringe borrowing(yes vs. no), syringe lending (yes vs. no), non-fatal over-dose (yes vs. no), binge drug use (yes vs. no), havinghad drugs planted on oneself by police (yes vs. no),incarceration (yes vs. no), compulsory treatment experi-ence (yes vs. no), and methadone treatment (yes vs. no).Use of drugs in combination refers to use of more thanone drug at the same time (i.e., not the simple use oftwo drugs in the same day or week). We consideredexperiences of drug planting by police given that thistype of contact with police could potentially promptsome IDU to obtain midazolam, given that the drug canbe obtained “over-the-counter” in selected pharmaciesand acquiring it may involve little or no contact withthe illicit drug market. This variable was ascertained byasking participants “Have police ever planted drugs onyou?” Binge drug use refers to periods when drugs areused more often than usual. All behavioural variablesrefer to lifetime history (e.g., ever injected yaba). Toexamine the bivariate associations, we used the Pearsonc2 test. We then examined factors independently asso-ciated with a history of midazolam injection use by fit-ting a multivariate logistic regression model thatincluded all variables that were associated with midazo-lam injection at the p ≤ 0.05 level in univariate analyses.All p-values were two-sided. We also asked participantswho reported midazolam injection about the frequencyof their midazolam injecting in the previous six months,and the drugs they used (if any) in combination withmidazolam.ResultsIn total, 252 IDU participated in this study, including 66(26.2%) females. The median age of participants was36.5 years. Two hundred and thirty-eight (94.4%) parti-cipants were born in the Bangkok Metropolitan Area. Intotal, 170 (67.5%) participants reported that they hadinjected midazolam previously and, of these, 144 (81.4%,57% of the total sample) reported daily midazolam injec-tion in the past six months. As indicated in Table 1, inunivariate analyses, factors positively associated withMSHRC use included use of drugs in combination(odds ratio [OR] = 7.53, 95% confidence interval [CI]:4.14-13.71), syringe borrowing (OR = 1.94, 95%CI: 1.08-3.47), having drugs planted on oneself by police (OR =3.03, 95%CI: 1.73-5.30), incarceration (OR = 2.05, 95%CI: 1.11-3.78), methadone treatment (OR = 4.29, 95%CI:2.35-7.86), and binge drug use (OR = 2.90, 95%CI: 1.60-5.26). Younger age (OR = 0.52, 95%CI: 0.30-0.89) andfemale gender (OR = 0.43, 95%CI: 0.24-0.76) were nega-tively associated with midazolam injection. As indicatedin Table 2, in multivariate analyses, midazolam injectionwas positively associated with use of drugs in combina-tion (adjusted odds ratio [AOR] = 5.86; 95%CI: 2.96-11.60), binge drug use (AOR = 2.25; 95%CI: 1.09-4.63),methadone treatment (AOR = 3.12; 95%CI: 1.55-6.90),and was negatively associated with younger age (AOR =0.43; 95%CI: 0.22-0.83). Among midazolam injectors,65% reported using drugs in combination with othersubstances, with the substances most commonly used incombination with midazolam being heroin (72.3%), yaba(30.5%), methadone (7.6%), and alcohol (4.7%).Kerr et al. Harm Reduction Journal 2010, 7:7http://www.harmreductionjournal.com/content/7/1/7Page 2 of 6DiscussionIn the present study, we found that approximately 68% ofa community-recruited sample of IDU in Bangkok hadinjected midazolam previously. Fifty-seven percent of thesample had injected midazolam at least once a day in thepast six months. Midazolam injectors were more likely toreport using drugs in combination, binge drug use, and ahistory of methadone treatment. Midazolam injectorstended to be older, and were less likely to be female.Sixty-five percent of midazolam injectors reported use ofdrugs in combination, with heroin and yaba being thedrugs most commonly used with midazolam.Table 1 Factors associated with a history of midazolam injection among IDU in MSCRP (n = 252)Characteristic Yes67.5 (%)n = 170No29.8 (%)n = 82Odds Ratio (95% CI) p valueMedian age< 36.5 years 76 (45) 50 (61) 0.52 (0.30 - 0.89) 0.02≥ 36.5 years 94 (55) 32 (39)Genderfemale 35 (21) 31 (38) 0.43 (0.24 - 0.76) < 0.01male 135 (79) 51 (62)Education≥ secondary 106 (62) 43 (52) 1.50 (0.88 - 2.56) 0.14< secondary 64 (38) 39 (48)Ever injected heroinyes 161 (95) 73 (89) 2.21 (0.84 - 5.79) 0.11no 9 (5) 9 (11)Ever injected yaba (methamphetamine)Yes 109 (64) 52 (63) 1.03 (0.60 - 1.78) 0.91no 61 (36) 30 (37)Ever used drugs in combinationyes 142 (84) 33 (40) 7.53 (4.14 - 13.71) <0.01no 28 (16) 49 (60)Binge drug useyes 80 (47) 19 (24) 2.90 (1.60 - 5.26) < 0.01no 90 (53) 62 (76)Ever borrowed used syringesyes 68 (40) 21 (26) 1.94 (1.08 - 3.47) 0.03no 102 (60) 61 (74)Ever lent used syringesyes 62 (36) 30 (37) 1.00 (0.58 - 1.72) 0.99no 108 (64) 52 (63)Ever overdosedyes 59 (35) 16 (20) 2.19 (1.17 - 4.12) 0.02no 111 (65) 66 (80)Ever had drugs planted on you by policeyes 97 (57) 25 (30) 3.03 (1.73 - 5.30) <0.01no 73 (43) 57 (70)Ever been in prisonyes 140 (82) 57 (70) 2.05 (1.11 - 3.78) 0.02no 30 (18) 25 (30)Ever been in forced drug treatmentyes 56 (33) 24 (29) 1.19 (0.67 - 2.11) 0.56no 114 (67) 58 (71)Ever on methadone treatmentyes 93 (55) 18 (22) 4.29 (2.35 - 7.86) <0.01no 77 (45) 64 (78)Kerr et al. Harm Reduction Journal 2010, 7:7http://www.harmreductionjournal.com/content/7/1/7Page 3 of 6The prevalence of midazalom injection found in thepresent study is much higher than most previouslyreported rates [9,12]. Van Griensven et al. reported a risein self-reported midazolam injection in the previous sixmonths, from approximately 10% in 1999 to 30% in 2000[9], and a report from 2005 found that 73% of IDU inBangkok had a history of midazolam injection [13]. How-ever, while approximately 16% of the total sample in thelatter study reported injecting midazolam on a daily basisin the previous month, 57% of IDU participating in ourstudy said they injected the drug on a daily basis in theprevious six months. Collectively these findings suggestthat the prevalence, and more notably the intensity ofmidazolam injection have continued to increase steadilysince 1999. It is believed that midazolam is often used asa cheaper and more accessible alternative to heroin, par-ticularly when heroin availability declines and heroinprice increases [8,9]. Previous studies have indicated thatthe prevalence of midazolam injecting increased follow-ing the initiation of Thailand’s “War on Drugs” in Febru-ary 2003 [7,14]. This initiative involved scaling up effortsto seize drugs, arrest drug dealers, and force drug usersinto military-style boot camps [7]. It has been reportedthat over 2,200 suspected drug dealers were killed viaextrajudicial execution during its implementation [15].The precise role of Thailand’s drug war on the drug pat-terns observed herein is difficult to determine. However,previous studies have found that transitions in injectiondrug use as well as an initiation of, or increase in, misuseof more licit drugs may occur among drug using popula-tions exposed to an increase in drug enforcement [16,17].Midazolam injection was strongly associated with theuse of drugs in combination and was reportedly mostcommonly used in combination with both heroin andmethamphetamine. This raises concern regarding thepotential elevated risk for overdose as a result of poly-substance use [18]; however, it is notable that whilemidazolam was associated with non-fatal overdose, thisassociation did not persist in a multivariate analysis.Midazolam injection was also associated with bingedrug use, which is concerning given that binge drug usehas been associated with HIV infection among IDU[19]. Although concern has been expressed regardingthe impact of midazolam injection on syringe sharing[9], in particular as a result of the amnestic effects ofthe drug, the association between syringe borrowing andmidazolam injection also did not persist in our multi-variate analysis.The findings of this study have implications for harmreduction practice. First, because midazolam filtrate ishighly acidic and damaging to veins, midazolam injec-tors are known to resort to groin injection when periph-eral veins are no longer usable. Groin injection carriessignificant risk, including risk for deep vein thrombosis,pulmonary embolus, abscesses, and puncture of thefemoral artery, vein, or nerve [20]. Therefore establishedharm reduction approaches specific to groin injectingshould be applied in work with midazolam injectors[20], including encouraging midazolam injectors toavoid initiating groin injecting by exercising proper veincare to maintain peripheral veins, or by switching to analternate route of drug consumption when peripheralTable 2 Multivariate logistic regression analysis of factors associated with a history of midazolam injection in MSCRPcohort (n = 252)Variable Adjusted Odds Ratio (AOR) 95% Confidence Interval (CI) p - valueMedian age(< 36.5 years vs. ≥ 36.5 years) 0.43 (0.22 - 0.83) 0.01Gender(female vs. male) 0.61 (0.29 - 1.3) 0.18Binge drug use(yes vs. no) 2.25 (1.09 - 4.63) 0.03Ever used drugs in combination(yes vs. no) 5.86 (2.96 - 11.60) < 0.01Ever borrowed used syringes(yes vs. no) 1.30 (0.64 - 2.65) 0.48Ever overdosed(yes vs. no) 1.23 (0.55 - 2.78) 0.62Ever had drugs planted on you by police(yes vs. no) 1.95 (0.95 - 3.98) 0.07Ever been in prison(yes vs. no) 1.40 (0.59 - 6.27) 0.48Ever on methadone treatment(yes vs. no) 3.12 (1.55 - 6.90) < 0.01Kerr et al. Harm Reduction Journal 2010, 7:7http://www.harmreductionjournal.com/content/7/1/7Page 4 of 6veins are no longer accessible (i.e., non-intravenous use).Second, given that midazolam injectors frequentlyexperience abscesses and other soft-tissue infections,efforts should be made to ensure early and appropriatecare for such infections. This may require providingaccess to low-threshold care for soft-tissue infections.Third, given the lack of access to sterile injecting sup-plies in Thailand [21], efforts should be made to providemidazolam injectors with appropriate injecting supplies,including syringes and alcohol swabs. Lastly, because ofthe amnesic effects of midazolam and the risks asso-ciated with binge and combination drug use amongmidazolam injectors, educational efforts should includeencouraging midazolam injectors to avoid injecting mid-azolam when alone.This study has limitations. Previous studies have indi-cated that the majority of midazolam is distributed inBangkok [11], and the rates of midazolam injectionreported here may not generalize to other settings inThailand. As well, the data pertaining to midazolaminjection in Thailand is limited, and therefore conclu-sions concerning changes in the prevalence of midazo-lam injection should be interpreted with caution. Thispoints further to the outstanding need for more sys-tematic surveillance of drug use trends in Thailand, aswell as data on the harms of illicit drug use, includingmidazolam injection. Further, the study sample was notrandomly selected and therefore may not be representa-tive of local IDU. We should also note that we relied onself-report, and therefore our data may have beenaffected by socially desirable responding or recall bias.Finally, we identified a number of associations with mid-azolam injecting, such as syringe sharing, which did notpersist in multivariate analyses. Because of the limitedsample size in our study, future research will berequired before we can conclude that midazolam injec-tion is not associated with elevated risk behaviour.In summary, we found extremely high rates of mida-zolam injection among a cohort of Thai IDU in Bang-kok. Midazolam injection was strongly associated withthe use of various drugs in combination and binge druguse. Given the many adverse effects of midazolam injec-tion, evidence-based pubic health interventions areurgently needed to reduce the harms associated withthis form of drug use.AcknowledgementsWe would particularly like to thank the staff and volunteers at theMitsampan Harm Reduction Centre for their support. We also thank DanielMiles Kane and Deborah Graham for their assistance with data management,and Prempreeda Pramoj Na Ayutthaya and Donlachai Hawangchu for theirassistance with data collection. Dr. Kerr is supported by the Michael SmithFoundation for Health Research (MSFHR) and the Canadian Institutes ofHealth Research (CIHR).Author details1British Columbia Centre for Excellence in HIV/AIDS, St Paul’s Hospital,Vancouver, Canada. 2Department of Medicine, University of British Columbia,Vancouver, Canada. 3Social Pharmacy Research Unit, ChulalongkornUniversity, Bangkok, Thailand. 4Thai AIDS Treatment Action Group, Bangkok,Thailand.Authors’ contributionsTK, NKA, NF, KH, PS, KK and EW designed the study. CL conducted thestatistical analyses. TK drafted the manuscript and incorporated allsuggestions from co-authors. All authors made significant contributions tothe conception of the analyses, interpretation of the data, and drafting ofthe manuscript. All authors have read and approved the final manuscript.Competing interestsThe authors declare that they have no competing interests.Received: 9 September 2009 Accepted: 26 March 2010Published: 26 March 2010References1. 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Kobe,Japan 2005.14. Vongchak T, Kawichai S, et al: The influence of Thailand’s 2003 ‘war ondrugs’ policy on self-reported drug use among injection drug users inChiang Mai, Thailand. International J Drug Policy 2005, 16(2):115-21.15. Cohen J: Not enough graves. New York: Human Rights Watch 2004.16. Strathdee SA, Zafar T, Brahmbhatt H, Baksh A, ul Hassan S: Rise in needlesharing among injection drug users in Pakistan during the Afghanistanwar. Drug and Alcohol Dependence 2003, 71(1):17-24.17. Daosodsai P, Bellis MA, Hughes K, Hughes S, Daosodsai S, Syed Q: Thai Waron Drugs: measuring changes in methamphetamine and othersubstance use by school students through matched cross sectionalsurveys. Addictive Behaviors 2007, 32(8):1733-1739.18. Darke S, Hall W: Heroin overdose: research and evidence-basedintervention. J Urban Health 2003, 80(2):189-200.19. Miller CL, Kerr T, Frankish JC, Spittal PM, Li K, Schechter MT, Wood E: Bingedrug use independently predicts HIV seroconversion among injectiondrug users: implications for public health strategies. Substance Use &Misuse 2006, 41(2):199-210.20. Australian Injecting and Illicit Drug Users League: Femoral Injecting: AGuide to Injecting in the Groin Using the Femoral Vein. [http://www.aivl.org.au].21. Kerr T, Fairbairn N, Hayashi K, Suwannawong P, Kaplan K, Zhang R, Wood E:Difficulty accessing syringes and syringe borrowing among injectiondrug users in Bangkok, Thailand. Drug and Alcohol Review 2010,29:157-161.doi:10.1186/1477-7517-7-7Cite this article as: Kerr et al.: High rates of midazolam injection amongdrug users in Bangkok, Thailand. Harm Reduction Journal 2010 7:7.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color figure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submitKerr et al. Harm Reduction Journal 2010, 7:7http://www.harmreductionjournal.com/content/7/1/7Page 6 of 6


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