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A retrospective evaluation of analgesic exposures from Izmir, Turkey

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A retrospective evaluation of analgesic exposures from Izmir, Turkey
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  Human & Experimental Toxicology  (2007) 26:  629–636http://het.sagepub.com © 2007 SAGE Publications10.1177/0960327107076836 Introduction Paracetamol, aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are becoming increas-ingly available over-the-counter (OTC), thereforeside effects, misuse and poisonings of these agents are seen frequently. According to AmericanAssociation of Poison Control Centers ToxicExposure Surveillance System, analgesics were themost common medications that were responsible forthe drug overdose. 1 Analgesic ingestions are also themost common cause of drug overdose in other coun-tries. In UK, it was reported that 30 million pocketsof paracetamol were sold annually and 70000 peoplehad been poisoned with this drug and 150 of themdied. 2 It was also reported that analgesics were themost common agents among the drugs incriminatedin poisonings 3–5 and the most commonly identifiedmedications taken in fatal overdoses. 2,6 The aim of this study was to investigate the etio-logical, demographical and clinical characteristics of analgesic exposures reported to the Dokuz EylulUniversity Drug and Poison Information Center(DPIC), in Izmir, in a 12-year period. Epidemiologicaldata on analgesic exposures in Turkey are extremelylimited. Results of the analysis will give beneficialinformation to physicians for recent situation andcharacteristics of analgesic exposures in Turkey. Methods This study was approved by the Institutional EthicsCommittee of the Dokuz Eylul University, School of Medicine. A cross-sectional, descriptive review of all analgesic exposure cases reported to the DokuzEylul University DPIC in Izmir from 1993 to 2004 *Correspondence: Yesim Tuncok, MD, Professor of Pharmacology, Dokuz Eylul University School of Medicine,Department of Pharmacology, Balcova, 35340 Izmir, Turkey Tel.: 00-90-232-4123900; Fax: 00-90-232-2590541; E-mail: yesim.tuncok@deu.edu.trReceived 13 May 2006; revised 10 October 2006; accepted 9November 2006 A retrospective evaluation of analgesicexposures from Izmir, Turkey Nil Hocaoglu 1 , Sule Kalkan 1 , Aylin Akgun 2 , Sedat Capar 3 and Yesim Tuncok 1, * 1 Department of Pharmacology, School of Medicine, Dokuz Eylul University, Izmir, Turkey; 2 Department of Pharmacology, Health Sciences Institute, Dokuz Eylul University, Izmir, Turkey; 3 Faculty of Arts and Sciences, Department of Statistics, Dokuz Eylul University, Izmir, Turkey  The objective of this study is to analyze exposuresconcerning analgesics that were reported to Dokuz EylulUniversity Drug and Poison Information Center (DPIC)and admitted to the Department of Emergency Medicine inDokuz Eylul University Hospital (EMDEU) between 1993and 2004. Demographics of the patients, characteristics of analgesic exposures, performed treatment attempts andoutcome of the poisoned patients were recorded on stan-dard data forms and were then entered into a computer-ized database program. Statistical analysis was performed by using the chi-square test. The DPIC recorded 55962 poi-soning calls, 48654 (86.9%) of them related to medicines.Analgesics accounted for 16.3% (7939 cases) of all medi-cine-related exposures; among them 446 exposures wereadmitted to EMDEU. More than half of the analgesic expo-sure calls and admitted cases involved adults (55.9%,4440). Females dominated in all age groups (70.3%, 5578).Mean age was 20.2  11.8. The most involved analgesicswere paracetamol (47.9%), propionic acid derivatives(16.1%) and salicylates (13.7%). Most of the poisonings wereintentional (75.1%), especially in 19–29 years age group of adults and 13–18 years age group of children. Most of thepatients reported to DPIC and admitted to EMDEU wereasymptomatic (84.4% and 54.7%, respectively).Gastrointestinal decontamination methods were per-formed more frequently for admitted poisoning cases before hospital admission than reported poisoning cases(61% vs. 23%). Paracetamol ingestion was the most com-mon cause of analgesic exposures reported to our DPIC.Most of the analgesic exposures reported to DPIC wereasymptomatic or mild. DPICs have an important role forthe referral of analgesic exposures without unnecessarygastrointestinal decontamination procedures. Human & Experimental Toxicology  (2007) 26, 629–636 Key words: analgesic exposures; Drug and Poison InformationCenter; paracetamol; salicylate  at Dokuz Eylul Universitesi on February 4, 2015het.sagepub.comDownloaded from   Retrospective evaluation of analgesic exposures from Izmir, Turkey N Hocaoglu et al. 630 was conducted. We also evaluated the analgesicexposures reported to DPIC and admitted to theDepartment of Emergency Medicine of Dokuz EylulUniversity Hospital (EMDEU) in the second part of our study. Data regarding demographics, analgesicmedication type, distribution according to month andyear, route and reason for the exposure, time and cir-cumstances of poisoning (unintentional, intentionaland unknown), clinical effects, methods of manage-ment, length of hospital stay and outcome (completerecovery or death) were recorded from telephone consultations on standard data forms and were then entered into a computerized database program(Microsoft Access 2000, 9.0.2812, written by SedatCapar, 2001). Age of patients were categorized as  6 years, 7 to 12, 13 to 18 for children, 19 to 29, 30to 39, 40 to 49, 50 to 59, 60 to 69 and  69 years foradults. The analgesics were categorized into fivegroups: paracetamol, salicylates, non-steroidal anti-inflammatory drugs (NSAIDs, except paracetamoland salicylate), opioids and the others. The severityof clinical manifestations were graded into asympto-matic, mild, moderate or severe and assessed accord-ing to the EAPCCT/IPCS Poisoning Severity Score. 7 Clinical outcome is based on an assessment by thehealth personnel handling the call. Analgesic expo-sure cases admitted to EMDEU were followed by tele-phone calls, especially for clinical outcome and treat-ment attempts. Statistical analysis was performed byusing the chi-square test (SPSS 11.0 Standard VersionSPSS Inc). Results were considered statistically sig-nificant when P   0.05. Data in this paper are provid-ed as tables and charts using Microsoft Excel ® . Results Analgesic exposures reported to Dokuz Eylul University DPIC  During 1993 to 2004, the Dokuz Eylul UniversityDPIC in Izmir recorded 55962 calls concerning poi-soning, 48654 (86.9%) of them related to medicines.Analgesics accounted for 16.3% (7939 cases) of allmedicine-related exposures; among them 446poisoning cases were admitted to the EMDEU. Mostcases (83.7%) were from Izmir and the rest werereferred from other cities and rural areas. Telephonecalls came mainly from hospitals and clinics(94.9%), houses (3.8%) and workplaces (0.1%).Most of the analgesic poisonings who werereported to DPIC were adults (55.9%, 4440, Table 1).Females dominated in all age groups (70.3%, 5578).Women-to-men ratio was 2.5:1 (2.25 and 2.71% forchildren and adults, respectively). Mean age was20.2  11.8 (10.6  0.1 and 27.7  0.1 for childrenand adults, respectively, Table 1).The median number of reported analgesic expo-sures was 661 cases each year. The highest numberof analgesic exposure was reported in 2001 (1195),2003 (1095) and 2000 (1065). The seasonal distribu-tion in analgesic exposures showed a peak in spring(27.0%). Higher volumes for analgesic exposureswere reported in January and May (9.5% for each).Median time elapsed from analgesic exposure totelephone call was 1h (37.5%, mean 3.9  1.9h). In31.4% of cases, analgesic exposures occurred duringnight time (8 to 11 PM).Acute exposure was the main type of analgesicexposures in 93.9% of cases, followed in frequency by chronic (0.3%) and unknown (5.7%). The route of the exposure was ingestion in 7432 patients (93.6%).Intentional analgesic exposure (suicide attempt,misuse or abuse) predominance was found in all agegroups (75.1%), except in  6-years-old children whowere poisoned accidentally. Patients  6 years andyoung adults (19–29 years old) were the most vulner-able group in children and adults, respectively.Unintentional analgesic exposures were higher inthe   6-years-old group than in the 7- to 18-years-oldgroup of children significantly (   2  1471.0, P   0.0001). Most of the analgesic exposures were inten-tional, especially in 13- to 18-years-old group of chil-dren ( P   0.0001) and 19- to 29-years-old group of adults ( P   0.001). In the 19- to 29-years-old group, Table 1 The gender and age distribution of analgesic exposures ChildrenAdultsTotal No.(%)No.(%)No.(%) GenderMale1051(47.1)1181(52.9)2232(100.0)Female2374(42.6)3204(57.4)5578(100.0)Undetermined74(57.4)55(42.6)129(100.0)AgeMean  SD10.6  0.127.7  0.120.2  11.8Range1 month–18 years19–78 years1 month–78 years  at Dokuz Eylul Universitesi on February 4, 2015het.sagepub.comDownloaded from   Retrospective evaluation of analgesic exposures from Izmir, Turkey N Hocaoglu et al. 631 the rate of intentional analgesic exposures weresignificantly higher than that of 30- to 69-years-oldgroup (   2  10.085, P   0.0015). When the causes of poisoning were compared, intentional analgesicpoisonings were higher in adults than in the children(   2  1535.3, P   0.0001, Table 2).Intentional analgesic exposures were found to besignificantly higher in females than in males for allage groups (   2  258.43, P   0.0001, Table 3).Analgesic exposures were identified as paracetamol-related (47.9%), salicylate-related (13.7%), NSAIDs-related (except paracetamol and salicylate, 34.2%),opioid-related (0.2%) and the others (1.4%). Thefrequency distribution shows that paracetamol wasthe most frequent offending analgesic, followed byNSAIDs. The most common NSAIDs (except parac-etamol and salicylates) were propionic acidderivates, accounting for 16.1% of all analgesicexposures. The most frequently involved propionicacid derivate was naproxen (10.8%). Cough andcold preparations that consist of analgesic medica-tions accounted for more than one-third of theanalgesic exposures (37.5%, Table 4).When we looked at the amounts of analgesics,non-toxic amounts of analgesic exposures accountedfor 64.4% (5113) of all cases reported to DPIC. At thetime of telephone inquiry, 84.4% of patients (82.3and 85.6% for children and adults, respectively) hadeither developed no effect or had no symptoms of toxicity. The medical outcomes were graded as mild(14.0%), moderate (1.0%) or severe outcomes (0.5%)(Table 5). Clinical manifestations of analgesic expo-sures were nonspecific. Nausea was the most com-mon sign (25.2%), followed by tachycardia (15.5%)and headache (13.5%). When the clinical manifesta-tions of poisoning were compared, no difference was Table 2 Distribution of reason for analgesic exposure by age AgeIntentional Unintentional Total (year) No. (%) No. (%) No. (%) Children0–647(3.4)1344(96.6)1391(100.0)7–1280(50.9)77(49.1)157(100.0)13–181747(91.3)166(8.7)1913(100.0)Total187415873461Adults19–292750(93.3)198(6.7)2948(100.0)30–39924(91.3)88(8.7)1012(100.0)40–69386(89.7)49(10.3)435(100.0)  6919(95.0)1(5.0)20(100.0)Total40793364415 Table 3 Distribution of reason for analgesic exposure by age andgender Male Female Total No. (%) No. (%)No. Intentional1096(62.1)3486(91.3)4582Unintentional670(37.9)937(8.7)1607Total1766(100.0)4423(100.0)6189 Table 4 Distribution of major analgesics involved in analgesicexposures Analgesic Analgesic No. Percentage types subgrubs (%) AnilidsParacetamol380247.9Propionic acidIbuprofen2272.9derivatesNaproxen86110.8Ketoprofen200.3Fenbufen10.01Flurbiprofen1031.3Tiaprofenic acid670.8Total127916.1SalicylatesAcetylsalicylic acid107413.5Sodium salicylate30.03Diflunisal130.2Total109013.7Acetic asidIndometacin430.5derivatesTolmetin60.06Diclofenac6247.9Etodolac680.9Acemetacin730.9Ketorolac30.03Total81710.3OxicamsPiroxicam640.8Tenoxicam510.6Meloxicam550.7Total1702.1OpioidsMorphine110.1Dihydrocodeine10.01Tramadol70.07Total190.2Others7629.6Total7939100.0  at Dokuz Eylul Universitesi on February 4, 2015het.sagepub.comDownloaded from   Retrospective evaluation of analgesic exposures from Izmir, Turkey N Hocaoglu et al. 632 found on the presence of clinical signs and symp-toms in children and adults (   2  3.8, P   0.0513).Rates of recommended and performed decontami-nation procedures (mechanical emesis, gastric lavage,activated charcoal), specific antidotes and measuresof enhanced elimination (hemodialysis) in the treat-ment of patients reported to the DPIC are outlined inTable 6. These must be interpreted as minimum fre-quencies because of the limitations of telephone datagathering. At the time of telephone inquiry, mechani-cal emesis (ME, in 1.7% of cases), gastric lavage alone(GL, in 8.8% of cases), activated charcoal alone (AC,in 2.2% of cases) and gastric lavage with activatedcharcoal (GL  AC, in 9.9% of cases) were applied before calling to DPIC was determined. Specific anti-dote treatment (SA) and hemodialysis (H) wereapplied in only 0.3 and 0.04% of cases, respectively.Observation alone was recommended in 63.2%cases by DPIC. ME (0.2%), GL (0.9%) alone, AC(15.6%) alone and GL  AC (11.5%) were theothermethods recommended as gastrointestinaldecontamination methods. Additionally, the ratio of observation recommendation was found to behigher for non-toxic amounts of analgesic exposuresrecommended to DPIC than that of gastrointestinaldecontamination recommendations (   2  21.622, P   0.0001). In 2.7% of cases, for paracetamolpoisoning – N  -acetylcysteine – for opioids – nalox-one – were recommended as specific antidotes,respectively. Hemodialysis was recommended as anenhanced elimination procedure in 0.1% (fourcases) of all analgesic exposures (Table 6).Five analgesic exposure fatalities (0.06% of allanalgesic exposures) were reported to the DPIC: onecase was child and four cases were adults. Exceptfor the child, other four fatal poisoning cases (80%)were intentional. The most common class of analgesics primarily responsible for fatalities wasparacetamol and salicylate, accounting for twodeaths for each agent. One patient died from para-cetamol and salicylate ingestion together. Analgesic exposures admitted to EMDEU  Among analgesic exposures reported to DPIC, 446cases (5.6%) were admitted to EMDEU. Of the 446cases, 334 (72.6%) were female (77.6 and 69.6% forchildren and adults, respectively). The age rangedfrom 1 through 78 years with a median age of 21.9  9.8. Mean age of children and adults was10.6  0.1 and 27.7  0.1 years, respectively. Themajority of analgesic exposures were in the 13- to18-years-old (138, 81.2%) and 19- to 29-years-old(199, 72.1%) age groups for children and adults.Although the seasonal distribution in analgesicexposures who were admitted to EMDEU showed apeak in winter (26.2%) and spring (25.6%), most of the analgesic exposures occurred in August (10.3%).Approximately, in one-third of cases (33.5 and 36.6%for children and adults, respectively), analgesic expo-sures occurred during night time (8 to 11 PM).Suicide attempts were the major causes of analgesic exposures in all age groups (90.6%, 404cases), except in children  6-years-old. Most of thepoisonings were intentional, especially in 13- to 18-years-old group of children (133 cases, 78.2%)and 19- to 29-years-old group of adults (192 cases, Table 5 Distribution of medical outcome of analgesic exposures by age OutcomeChildrenAdultsTotal No.(%)No.(%)No.(%) No effect2281(82.3)4289(85.6)6570(84.4)Minor effect427(15.4)663(13.2)1090(14.0)Moderate effect38(1.4)43(0.9)81(1.0)Major effect24(0.9)16(0.3)40(0.5)Total2770(100.0)5011(100.0)7781(100.0) Table 6 Distribution of applied and recommended treatment attempts Treatment methodsApplied before calling DPICRecommended by DPIC No.(%)No.(%) Observation alone5105(64.3)5017(63.2)Mechanical emesis134(1.7)16(0.2)Gastric lavage alone699(8.8)71(0.9)Activated charcoal alone175(2.2)1238(15.6)Gastric lavage and786(9.9)913(11.5)activated charcoalSpecific antidote treatment24(0.3)214(2.7)Hemodialysis3(0.04)8(0.1)Others1013(12.7)462(5.8)Total7939(100.0)7939(100.0)  at Dokuz Eylul Universitesi on February 4, 2015het.sagepub.comDownloaded from   Retrospective evaluation of analgesic exposures from Izmir, Turkey N Hocaoglu et al. 633 69.6%). Female cases constituted the majority of intentional analgesic exposures (69.7%).Ingestion was the route of exposure in 99.6% of analgesic exposures. Amounts of analgesics ingestedwere graded as toxic (22.3%, 99), non-toxic (64.2%,286) and unknown (13.5%, 61) for cases admitted toEMDEU. Non-toxic analgesic exposures were themost part of paracetamol exposures (59%, 80), sali-cylate exposures (65.5%, 76) and NSAIDs exposures(68.2%, 105) for EMDEU cases.The most common symptoms of analgesic expo-sures admitted to EMDEU were nausea (8.7%), tachy-cardia (5.4%) and headache (4.7%). Clinical effectswere graded as mild (42.4%), moderate (2.7%) orsevere (0.2%) poisoning for cases admitted to EMDEUand 54.7% of them had no symptoms of toxicity.Paracetamol was the most frequent cause of anal-gesic exposures and accounted for 39.0% of allcases. NSAIDs (except paracetamol and salicylate,22.0%) were the second frequent cause of analgesicexposures, followed by salicylate (10.8%) and opi-oids (0.4%).While emesis was inducted mechanically in 0.7%of analgesic-ingested patients, in 5.6% of them GLalone, in 21.1% of them AC alone and in 33.2% of them GL  AC were already applied before beingadmitted to EMDEU. Specific antidote treatment wasalready applied in 2.5% of cases. After admitted toEMDEU, 37.6% of cases were observed alone. ME(0.7%), GL alone (2.2%), AC alone (17.3%) andGL  AC (17.9%) were the other performed gastro-intestinal decontamination methods in EMDEU. Nosignificant difference was found between ratios of observation recommendations for analgesic exposures reported to DPIC and admitted to EMDEU(   2  0.1395, P   0.7088). In all analgesic exposures,gastrointestinal decontamination methods were per-formed more frequently for admitted to EMDEU poi-soning cases before hospital admission than reportedto DPIC poisoning cases (61 and 23%, respectively).In the toxic analgesic exposures, gastrointestinaldecontamination procedure recommendations werehigher in the cases reported to DPIC than admitted toEMDEU (   2  6.755, P   0.0093).The follow-up period of hospitalization of thepatients were as follows: 31.6% for 2–6h, 30.6% for13–24h, 15.8% for 7–12h and 9.9% for  2h. Afterfirst medical aids, 24 cases (5.4% of all analgesicexposures) were hospitalized. The mean duration of hospitalization was 8.2h.Severe analgesic poisonings (4, 0.9%) were trans-ferred to the intensive care unit for further treat-ment. After stabilization, 1.3% of cases (6) weretransferred to the other hospitals due to their healthinsurance problems. Eighty seven percent of allcases (388) were cured and discharged fromEMDEU. After initial management, 7.2% of thecases left EMDEU either against medical advice orwithout notice. One 3-year-old child (0.2% of allcases) died from salicylate ingestion. Discussion This study analyzed the analgesic exposures reportedto the Dokuz Eylul University DPIC and patientsadmitted to the Dokuz Eylul University Hospital, inIzmir, during a 12-year period. In overdose, anal-gesics were reported to cause significant morbidityand mortality. Therefore, identification and docu-mentation of epidemiological aspects and othervariables in analgesic poisonings are of great impor-tance for the treatment plan and determination of proper preventive measures. 8 However, it is verydifficult to estimate the distribution of analgesicexposures in Turkey, as well as in most other devel-oping countries, due to the lack of centralized datacollection. Although DPIC calls based on the spontaneous reports of poisoning exposures give ageneral idea about the epidemiology of analgesicpoisonings in Turkey, our study was the biggestdescriptive research study up to date. In most devel-oped countries, analgesics top the list of the mostfrequent causes of poisonings. 2,9 The AmericanAssociation of Poison Control Centers reported over250000 telephone enquiries regarding children andadults who were thought to have been poisonedwith analgesics (11.3% of all poisonings) in 2003. 1 Similarly, analgesics were the most common med-ications that caused poisonings in Iran (11%). 10 Inour study, during a 12-year period, 7939 analgesicexposures reported for 16.3% of total calls to theDPIC. In other noteworthy Turkish epidemiologicalstudies conducted with a small number of poisonedpatients, percentages of analgesic exposures amongthe total number of emergency admissions due topoisonings were higher than that of our results(30.1%, 52 cases and 33%, 66 cases, respectively). 3,4 Such a high incidence of analgesic exposures may be due to the extensive prescribing of these medica-tions in Turkey. Furthermore, most of the analgesicsare sold without a prescription.Paracetamol was found to be the most commonpharmaceutical taken in overdose. Akkas et al. 11 found that 23% of the ingested medications wereparacetamol exposures in their study. In anotherstudy, Goksu et al. 5 reported that paracetamol wasthe most common cause of poisonings related tomedications in Turkey. In most Western countries,paracetamol is responsible for the greatest number of   at Dokuz Eylul Universitesi on February 4, 2015het.sagepub.comDownloaded from 
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