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A retrospective analysis of antidepressant poisonings in the emergency department: 11-year experience

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A retrospective analysis of antidepressant poisonings in the emergency department: 11-year experience
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  A retrospective analysis of antidepressantpoisonings in the emergency department:11-year experience P Unverir 1 , R Atilla 1 , O Karcioglu 1 , H Topacoglu 1 , Y Demiral 2 and Y Tuncok *,3 1 Department of Emergency Medicine, Dokuz Eylul University School of Medicine, Izmir, Turkey; 2 Department of Public Health, Dokuz Eylul University School of Medicine, Izmir, Turkey; 3 Department of Pharmacology, Dokuz Eylul University School of Medicine, Izmir, Turkey  Between 1993 and 2004, patients with antidepressantpoisoning admitted to an emergency department (ED)were analysed retrospectively with regard to demo-graphics, clinical findings and treatment attempts. Age,gender, suicide attempts, classification of antidepres-sants, Glasgow Coma Scale (GCS) score, ECG findings,need for endotracheal intubation, follow-up period andAntidepressant Overdose Risk Assessment (ADORA)criteria were analysed by SPSS software. A total of 356antidepressant poisoning cases were evaluated. Tricyclicantidepressants (TCA), especially opipramol and ami-triptyline, were the most common agents (58.4%). Themost frequent ECG finding was sinus tachycardia (40.7%,  n  /  145). Endotracheal intubation was required in 9.6% of cases. Patients with TCA ingestion had a longer observa-tion time in the ED, abnormal ECG findings, abnormalphysical examination findings and more ADORA criteria,than patients who ingested selective serotonin re-uptakeinhibitors (SSRI) (  P   /  0.008,  P   /  0.008,  P  B /  0.001,  P  B /  0.001). It was found that the patients who ingested TCA(  P   /  0.001), poisoned with amitriptyline (  P   /  0.001), pa-tients with GCS scores of 8 and less (  P   /  0.001), patientswith two or more ADORA criteria (  P   /  0.001), withseizures (  P   /  0.001), with abnormal ECG (  P   /  0.012), andpatients with a history of two or more suicide attemptswere intubated more frequently. Suicide attempts, classi-fication of the antidepressant, ECG findings, seizure, GCSscore and number of detected ADORA criteria affectthe need for intubation in patients with antidepressantpoisoning.  Human & Experimental Toxicology   (2006)  25, 605    612 Key words:  antidepressant; emergency department; intubation;tricyclic antidepressant poisoning Introduction According to a 2003 report of the American Associa-tion of Poison Control Centers (AAPCC), the rate of poisoning by antidepressant drugs is 8.2%. Inaddition, antidepressant poisoning takes third placein fatal poisonings, with a fatality rate of 0.2%. 1 According to the report of the Dokuz Eylul Drug andPoison Information Center in Izmir, between 1993and 1995, the rate of poisoning with antidepressantswas rather high (11.3%). 2 In a different study byAkkas  et al. , the most commonly ingested agentswere antidepressants (32%) in Ankara, Turkey. 3 In the evaluation of clinical findings for poisoning by antidepressant medications, the AntidepressantOverdose Risk Assessment (ADORA) criteria areused. These criteria are: prolongation of the QRSinterval, arrhythmias, altered mental status, seizure,respiratory depression, and hypotension. 4 Althoughthe percentages of antidepressant poisoning casesrequiring endotracheal intubation in the emergencydepartment (ED) and intensive care units (ICU) weregiven in the literature, 5    8 characteristics and out-comes of intubated patients cannot be found. There-fore, in this retrospective study, we evaluated theantidepressant poisoning cases admitted to the ED,with demographics, clinical signs and symptoms,treatment attempts and outcomes of patients requir-ing intubation, according to the ADORA criteria. Methods In this retrospective study, all patients over 18 years,who were admitted to Dokuz Eylul UniversityHospital ED for antidepressant ingestion from Jan-uary 1993 to June 2004, were enrolled. Concomitant *Correspondence: Yesim Tuncok, MD, Professor of Pharmacology,Department of Pharmacology, School of Medicine, Dokuz EylulUniversity, 35340, Balcova, Izmir, TurkeyE-mail: yesim.tuncok@deu.edu.trReceived 5 July 2005; revised 6 February 2006; accepted3 April 2006 Human & Experimental Toxicology  (2006)  25:  605    612www.sagepublications.com – 2006 SAGE Publications 10.1177/096032706072470  at Dokuz Eylul Universitesi on February 4, 2015het.sagepub.comDownloaded from   ingestion of antidepressants with other medicationsand other toxic substances were also included. Age,gender, recurrent suicide attempts, classification of antidepressants, Glasgow Coma Scale (GCS) score,ECG findings (arrhythmia, conduction block), needfor endotracheal intubation, follow-up period andADORA criteria (prolongation of the QRS interval,changes in mental status, seizure, breathing depres-sion, hypotension), performed treatment attempts(gastric emptying, activated charcoal, etc.), hospita-lization and discharging features were recorded andanalysed using the Statistical Package of SocialSciences for Windows 11.0. Treatment of all poi-soned patients has been provided by emergencymedicine residents and physicians, according to theconsultation to Dokuz Eylul Drug and Poison In-formation Center since 1993. However, some treat-ment attempts differed from the protocol in ourhospital because of referred patients to our hospitalfrom other healthcare facilities. Statistical analyseswere performed using the Student’s  t  -test for com-paring mean of groups and the  x 2 -test for non-parametric data. Statistical significance was takenat the 5% level. Logistic regression models wereused to predict the risk factors for endotrachealintubation and hospitalization in the ICU. Age,gender, antidepressant medicine groups, GCS score,seizure and prolongation of QRS interval were takenas the independent risk factors. In these factors,those with risks coded (female gender, take to thetricyclic antidepressant (TCA) group, 8 and B / 8 GCSscore, have seizure, prolongation of QRS interval)were numbered 1, and those without risk factorswere numbered 0. Multiple regression analysis wasalso used to predict risk factors for observation timein the ED. Results Demographic features From 1993 to 2004, 446 patients were admitted tothe ED with antidepressant ingestion. Ninety of thepoisoning cases were excluded from the study because of missing details on poisoning in thepatient charts. A total of 356 cases with antidepres-sant poisoning admitted to the ED were evaluated.Ingestion of antidepressants was most frequent in July and October (11 and 10.7%, respectively). Themajority of poisoning cases were aged between 21and 30 (40%), and the female:male ratio was 3:5(Table 1).Antidepressant poisoning cases were evaluated infive groups based on the contents of the medicationor toxic substance. TCAs were the most frequentlyingested antidepressants (58.4%), followed byselective serotonin reuptake inhibitors (SSRI)(22.5%; Table 2). Opipramol and amitriptyline ac-counted for the majority of TCAs (31.2%,  n  / 111and 23.3%,  n  / 83, respectively). Concurrent inges-tions, except antidepressants, were found in 35.7%( n  / 127) of the antidepressant poisoning patients.While the vast majority of the poisoning caseswere suicide attempts (97.5%,  n  / 347), 2.5% ( n  / 9)ingested antidepressants to sleep, relax, get rid of worries, or by accident.In the majority of poisoning cases, a first attemptto commit suicide was determined (78.6%,  n  / 280).Repeated suicide attempts accounted for 18.8% of patients ( n  / 67) (Table 1). Most of the patients withrepeated attempts to commit suicide were poisoned by TCAs (46.2%,  n  / 31) and SSRIs (29.8%,  n  / 20). GCS score In the first evaluation of the poisoning cases in theED, the GCS score was determined to be 14 9 / 2(range between 3 and 15). While most of the patientshad a GCS score of 15 (71.9%,  n  / 256), 4.2% ( n  / 15) had 8 and  B / 8. Ten of the 15 patients who had aGCS score of 8 or  B / 8, (66.7%,  n  / 10) suffered froma TCA overdose. ECG findings We obtained the ECG records of 295 patients(82.9%). ECG findings were evaluated to be normalin 121 of the 295 patients (41%). The followingabnormal ECG findings were observed: sinus tachy-cardia (40.7%,  n  / 145), right axis deviation Table 1  Presentation characteristics of the cases with antide-pressant poisoning Characteristics n % Female/male 277/79 77.8/22.2Age (years)Female (range) 28 9 / 10 (18    78)Male (range) 28 9 / 10 (18    63)Suicide attemptsFemale 270 97.5Male 77 97.5Depression history 118 33.1Patients presented within 2 hours 204 60Mean time of admission to EDafter ingestion (hour) (range)3.3 9 / 4.9 (0.1    48)Complaints on the presentationNausea/vomiting 103 61.7Vertigo 36 21.5Faintness 20 11.9Palpitation 6 3.6Syncope 2 1.2Total 167 100Concurrent ethanol consumption 42 11.8Concurrent ingestions other thanantidepressants127 35.7No. of suicide attempts1 280 78.6 ] / 2 67 18.8 Retrospective analysis of antidepressant poisonings in the ED P Unverir  et al  . 606  at Dokuz Eylul Universitesi on February 4, 2015het.sagepub.comDownloaded from   (10.7%,  n  / 38), prolongation of the QRS interval(7.9%,  n  / 28), incompatibility of R/S in aVRderivation (7.3%,  n  / 26), right bundle branch block (5.6%,  n  / 20), prolongation of the QT inter-val (4.5%,  n  / 16), prolongation of the PR interval(3.1%,  n  / 11), left bundle branch block (1.1%,  n  / 4), left axis deviation (0.8%,  n  / 3), premature atrialcontractions (0.8%,  n  / 3), premature ventricularcontractions (0.8%,  n  / 8), sinus bradycardia (0.8%, n  / 3), ST segment depression (0.3%,  n  / 1), sec-ond-degree atrioventricular block (0.3%,  n  / 1),atrial tachycardia (0.3%,  n  / 1), ventricular fibrilla-tion (0.3%,  n  / 1) and asystole (0.3%,  n  / 1). Mostof the patients with abnormal ECG findings in-gested TCA when compared to patients who in-gested SSRI ( n  / 119 (68.3%) versus  n  / 26 (14.9%), P   / 0.008). Clinical findings and ADORA criteria The physical examination findings of 39.6% of patients ( n  / 141) on admission were determinedto be normal. For the remainder of patients, tachy-cardia was the most frequent clinical finding(41.8%,  n  / 149). Physical examination findingswere seen more frequently in patients who ingestedTCA when compared to patients who ingested SSRIantidepressant agents ( P  B / 0.001, Table 3). Majorclinical findings could not be evaluated in 50patients (14%) because of missing data in theircharts. It was determined that 70.9% of the remain-ing 306 patients ( n  / 217) had major poisoningclinical findings related to the ADORA criteria(Table 3). Major clinical findings (ADORA criteria)were also seen more frequently in patients whoingested TCA when compared to patients whoingested SSRI antidepressant agents (66.8% (145)versus 14.7% (32),  P  B / 0.001, Table 3). Intubation and other treatment attempts It was determined that 34 of the 356 patients (9.6%)required endotracheal intubation. There was nosignificant difference in the mean ages between thepatients intubated (28.9 9 / 9.8) and patients notintubated (27.9 9 / 11.1) ( P   / 0.632). Reasons forendotracheal intubation were given as follows: alow GCS score (58.8%,  n  / 20), respiratory depres-sion (29.4%,  n  / 10) and failure to treat for seizures(1.1%,  n  / 4). Patients were intubated in a meantime of 4.9 9 / 4.3 hours (range: 0.5    24) after anti-depressant ingestion. All intubated patients hadintentional antidepressant ingestions. Poisoningcases with recurrent suicide attempts, abnormalECG findings, general tonic clonic seizures and aGCS score of 8 and  B / 8 had more intubations.Regarding the relationship between the number of ADORA criteria and intubation requirement, poi-soning cases with two or more ADORA criteria had areasonably higher frequency of intubation whencompared to the cases who had only one criterion(Table 4). While the majority of intubated patientswere suffering from TCA poisoning (70.5%, 24), Table 2  Medications responsible for anti-depressant poisonings Group Content n % 1 Tricyclic antidepressant (TCA) and/or other agents without antidepressants 208 58.42 Selective serotonin re-uptake inhibitors (SSRI) and/or other agents without antidepressants 80 22.53 Heterocyclic antidepressant (HCA) and/or other agents without antidepressants 28 7.94 Monoamine oxidase inhibitors (MAOI) and/or other agents without antidepressants 6 1.75 TCA 9 / SSRI 9 / HCA 9 / MAOI 9 / other agents without antidepressants 34 9.6Total 356 100 Table 3  The clinical features of the antidepressant ingestions Clinical feature n  %  P  Physical exam findingsNormal 141 39.6  B / 0.001Tachycardia 149 41.8Drowsiness 84 23.5Lethargia 22 6.1Mydriasis 19 5.3Dry skin/mucous membranes 18 5.0Coma 16 4.4Inadequate breathing effort 14 3.9Agitation 14 3.9Urinary retention 8 2.2Seizure 8 2.2Slow gastric motility 5 1.4Hallucination 3 0.8Rales in the lung oscultation 2 0.5Bradycardia 2 0.5Tremor 2 0.5Abdominal tenderness 1 0.2Asystole 1 0.2Dysmetria/dysdiadokokinesia 1 0.2Delirium 1 0.2Anxiety 1 0.2Persistent hypotension 21 5.9   / 0.05Metabolic acidosis 10 2.8   / 0.05ADORA criteriaArrhythmias 147 41.3  B / 0.001Altered mental status 127 35.7Conduction block 76 21.3Respiratory depression 28 7.9Hypotension 21 5.9Seizures 8 2.2Total 356 100 Retrospective analysis of antidepressant poisonings in the ED P Unverir  et al  . 607  at Dokuz Eylul Universitesi on February 4, 2015het.sagepub.comDownloaded from   nine (26.4%) had ingested more than one antide-pressant agent and only one (2.9%) was poisoned bya SSRI agent. Additionally, amitriptyline was thecausative agent in 23/24 poisoned patients intu- bated and ingested TCA (95.8%,  n  / 23).Endotracheal intubation risk increased 26-fold inpatients who had seizures (CI: 5.43    132.6; Table 5).However, other variables did not predict endotra-cheal intubation attempt.While gastric lavage alone was performed andactivated charcoal alone was administered in 3.9%( n  / 14) and 17.1% ( n  / 61) of patients, respectively,combined gastric lavage and activated charcoal wasperformed in 63.8% ( n  / 227) of patients. Combinedgastric lavage and activated charcoal was performedmore frequently in patients who ingested TCAswhen compared to patients who ingested SSRIs( P   / 0.001). Twenty-three patients (6.5%) weregiven sodium bicarbonate. Dopamine infusionwas administered in six patients (8.4%) due tohypotension. Observation time, hospitalization, ICU referral  Mean observation time in the ED for 356 patientsadmitted to hospital because of antidepressantpoisoning was 6.0 9 / 6.8 hours (range: 0.5    72). Thepercentage of patients who were observed B / 8 hourswas 62.1% ( n  / 221). Patients who were poisoned byTCAs were observed in the ED significantly longerthan those poisoned by SSRI agents (8.54 and 6.51hours, respectively,  P   / 0.008). Additionally, meanobservation time in the ED for patients who had been intubated was relatively longer than for pa-tients who had not been intubated (13.3 versus 7.5hours, respectively,  P   / 0.021). Observation timewas not affected by any variable in the multivariableanalysis.It was found that 13.5% of patients poisoned withantidepressants were hospitalized ( n  / 48). Hospita-lization rate due to poisoning by TCAs was signifi-cantly higher than those poisoned by SSRI agents(13.9% ( n  / 29) and 5% ( n  / 4), respectively, x 2  / 3.72,  P   / 0.038). While 10.1% of all patients( n  / 36) were admitted to ICU, 3.4% ( n  / 12) wereadmitted to the psychiatry ward. ICU referral ratewas 12.5% ( n  / 26) and 2.5% ( n  / 2) for TCA and Table 4  Endotracheal intubation rates in relation to the presentation characteristics of antidepressant ingestions Presentation characteristics Intubated Not intubated Total (n)  x 2 P n % n % GenderFemale 27 9.7 250 90.3 277 0.56 0.813Male 7 8.9 72 91.1 79 0.56 0.813No. of suicide attempts1 20 7.1 260 92.8 280 7.59 0.001 ] / 2 14 20.9 53 79.1 67Medication groupsGroup 1 24 11.5 184 88.5 208 6.40 0.001Group 2 1 1.3 79 98.8 80Amitriptyline ingestionYes 23 27.7 60 72.3 83 38.62 0.001No 11 4.0 262 96 273ECGNormal 5 4.1 116 95.9 121 9.80 0.012Abnormal 29 16.7 145 83.3 174SeizureYes 5 62.5 3 37.5 8 26.50 0.001No 29 8.3 319 91.7 348GCS 5 / 8 15 100 0 0 15 148.30 0.001 ] / 9 19 5.6 322 94.4 341No. of ADORA criteria1 0 0 102 100.0 102 33.55 0.001 ] / 2 34 5 81 95 115 Table 5  Logistic regression analysis of predictors for endotra-cheal intubation Risk factors Beta Standard error Oddsratio95%Confidenceinterval  Age   / 0.12 0.024 0.988 (0.1    1.03)QRSprolongation1.185 0.729 3.271 (0.8    13.6)Seizure 3.291 0.815 26.860 (5.43    132.6)TCAmedicine0.707 0.596 2.029 (0.63    6.53)Gender 0.568 0.705 1.765 (0.4    7.02)GCS 8 and  B / 8 12.063 25.005 173.371 (0.0    3.3) Retrospective analysis of antidepressant poisonings in the ED P Unverir  et al  . 608  at Dokuz Eylul Universitesi on February 4, 2015het.sagepub.comDownloaded from   SSRI poisoned patients, respectively. In addition,patients who had seizures or GCS scores 8 and  B / 8had a higher of risk of requiring ICU admission(Table 6). While 82.1% ( n  / 292) of patients weredischarged without any sequelae, 4.5% ( n  / 16)were referred to another hospital, according tohealth insurance status. Only one patient (0.3%),who ingested mianserin, sertralin and alprazolam,died in the ICU (Appendix). Discussion Our report confirms earlier reports that of allpatients presenting to hospitals with poisoning,young female patients are relatively over-re-presented. 2,6,8    17 According to previous studies,poisonings occur more frequently in June and July. 2,11,14,18 Our study, reflecting other studies,found that major hospitalization occurs in July.Information on the number of suicide attempts of poisoned patients is limited. Regarding the numberof suicide attempts, most of the poisoned cases hadfirst suicide attempt. In a study by Townsend  et al. ,repeated suicide attempts are reported as 18%. 19 Similarly, in our study, the rate of recurring suicideattempts was 19%.TCA is the most common group of medicationsencountered in antidepressant poisonings. 5    8,17,20 Similarly, in our study, the percentage of patientswho were poisoned by TCAs was higher than thepercentage of those poisoned with other antidepres-sants.Various reports have different information regard-ing the GCS score of antidepressant poisoningcases. 6,7,21 In a study by Whyte  et al. , patients whoingested TCAs excessively had a higher frequency tothose patients with a GCS score of 10 and under,when compared to patients who ingested SSRI. 10 Calkins  et al  ., reported that a GCS score of 8 andunder was 47% in TCA poisonings. 22 According toour study, mean GCS score was found to be 14 onfirst evaluation of the patients. Additionally, themajority of patients with a GCS score of 8 and underwere poisoned by TCAs and those patients wereintubated at a higher rate than patients with a GCSscore of 9 and over.An overdose of TCAs can cause life-threateningcardiac disturbances, 23  but sinus tachycardia is themost typical ECG change in patients poisoned withtricyclic and other antidepressants. 24    28 Relevant tothe literature, the most frequent ECG finding wassinus tachycardia in our patients. Additionally,most of the abnormal ECG findings, abnormalphysical examination findings and ADORA criteriawere found to be related to the TCA ingestions whencompared to SSRI ingestions. These aspects areimportant when prescribing TCAs for depression by physicians.In a study by Caravati  et al. , major toxicities weredetermined in 65 of 106 patients (61%) who hadTCA poisoning. 29 In our study, the percentage of patients with major toxicities was found to beslightly higher (70.9%) because of the various andconcomitant ingestions of antidepressant medica-tions. In different studies, rate of seizure, whichshows the seriousness of poisoning in antidepres-sant poisonings, is reported to be between 4 and24%. 4,6,10,22,30 Seizure was seen at a lower rate inour study (2.2%,  n  / 8). Seizures in antidepressantpoisonings depend on the content of the antidepres-sant classification and concomitant medications ortoxic substances ingested, which reduce the seizurethreshold.Endotracheal intubation requirement is evaluated by clinical signs and symptoms, GCS score andlaboratory findings for poisoned patients. Patientspoisoned with TCAs are reported to have higherintubation requirement percentages (23    68%). 28,31 It is known that patients poisoned by TCAs areintubated more frequently than patients poisoned bySSRIs or other antidepressants. 5,6,8 In our study aswell, intubation rate was higher in patients poi-soned by TCAs than other antidepressants. Addi-tionally, in our study, although confidence intervalswere found to be rather wide, intubation wasrequired relatively more for patients who hadseizures than patients those who did seize. Goodcare should be taken to prevent or treat seizures inpoisoned patients.In a study by Philips  et al. , gastric lavage wasperformed in 70% of TCA poisonings and activatedcharcoal was given to 96% of patients. 5 Bosch  et al  .,have also stated that gastric lavage was performed in71% of patients with antidepressant poisoning, 93%were given activated charcoal and 21% were admi-nistered sodium bicarbonate. 8 In the present study,similar to the previous reports, combined gastric Table 6  Multivariable analysis of predictors for hospitalizationto the ICU Risk factors Beta Standard error Oddsratio95%Confidenceinterval  Age 0.023 0.016 1.023 (0.1    1.05)QRSprolongation0.747 0.613 2.112 (0.63    7.02)Seizure 3.738 0.879 42.015 (7.5    235.4)TCA medicine 0.757 0.490 2.132 (0.8    5.56)Gender 0.435 0.556 1.545 (0.52    4.6)GCS 8 and  B / 8 3.382 0.656 29.431 (8.1    106.4) Retrospective analysis of antidepressant poisonings in the ED P Unverir  et al  . 609  at Dokuz Eylul Universitesi on February 4, 2015het.sagepub.comDownloaded from 
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