Corrine R Balit

Quetiapine Poisoning: A Case Series

STUDY OBJECTIVE We describe the effects of quetiapine in overdose. METHODS Quetiapine poisonings were identified from a prospective database of poisoning admissions to a regional toxicology service. Data extracted included details of ingestion, clinical features, investigations (including ECG), and other outcomes (length of stay and ICU admission rate). RESULTS There were 45 cases of quetiapine overdose, of which 18 patients with quetiapine assay results were included. Median length of stay was 35 hours (interquartile range [IQR] 14 to 42 hours) for the 18 patients, and 9 were admitted to the ICU. The median ingested dose was 3.5 g (IQR 1.7 to 6.2 g), and reported ingested dose was highly correlated with estimated peak drug concentration (r(2)=0.84; P<.0001), confirming patient-provided history of ingestion. Seizures occurred in 2 patients, delirium occurred in 3 patients, and mechanical ventilation was required in 4 patients. No arrhythmias or deaths occurred. Six of the 18 patients ingested quetiapine alone, with a median length of stay of 35 hours, and 3 were admitted to the ICU. In 1 patient who ingested 24 g, hypotension and seizures occurred. For 10 patients for whom ECGs were available and who had ingested no cardiotoxic drugs, tachycardia occurred in 8 patients. For these 10 patients, the mean corrected QT (QTc) interval was increased at 487 ms, but the mean uncorrected QT interval was 349 ms. Reported dose and peak quetiapine concentrations were significantly associated with ICU admission and length of stay more than 24 hours. A reported dose less than 3 g and a Glasgow Coma Scale score not less than 15 predicted patients not requiring ICU admission or length of stay more than 24 hours. CONCLUSION Quetiapine overdose causes central nervous system depression and sinus tachycardia. In large overdoses, patients may require intubation and ventilation for associated respiratory depression. Although a prolonged QTc occurs, its clinical significance is unclear because it is most likely caused by an overcorrection caused by the tachycardia. In our experience, a reported dose of less than 3 g for patients who are not drowsy (with a Glasgow Coma Scale score of 15) at least 4 hours after ingestion and who did not coingest another toxic agent defined a group not requiring ICU admission or inpatient admission greater than 24 hours.

Bupropion Overdose: QTc Prolongation and its Clinical Significance

OBJECTIVE: To investigate the cardiotoxicity of bupropion hydrochloride in deliberate self-poisoning. METHODS: A prospective study was conducted in a national poisons information center (PIC) of cases of adult deliberate self-poisoning with medical record follow-up of the patients. Fifty-nine cases of bupropion deliberate self-poisoning managed in the hospital, in which the New South Wales PIC was contacted for advice, were evaluated from November 2000 through July 2001. Clinical effects and electrocardiographic (ECG) parameters (QRS, QT, QTc) were the main outcome measures. RESULTS: ECGs were available for 17 of the 59 patients for analysis, 9 patients (53%) were women, and median patient age was 28 years (interquartile range 22–37). The mean ± SD ingested bupropion dose was 3.8 ± 3.1 g. Tachycardia occurred in 13 patients (76%; 95% CI 50 to 93) and hypertension in 8 patients (47%). There were no reports of hypotension or arrhythmias. There was a significantly increased QTc of 461 ± 34 msec in the patients with bupropion overdose compared with previously developed controls; 13 of the 17 cases had a QTc >440 msec (76%; 95% CI 50 to 93). The uncorrected QT interval did not differ from that of controls. CONCLUSIONS: A moderately prolonged QTc (>440 msec) is common in bupropion overdose. However, this may not be a result of intrinsic cardiac toxicity, but overcorrection of the QTc due to the tachycardia that occurs. It is important that the QTc is interpreted with caution in overdoses of agents that cause significant tachycardia (>100 beats/min).

Amisulpride overdose is frequently associated with QT prolongation and torsades de pointes.

This study aimed to describe the effects of the antipsychotic amisulpride in overdose, including the frequency of QT prolongation and torsades de pointes. Cases of amisulpride overdose (>1 g) were recruited from 2 state poison centers and a tertiary toxicology unit over 5 years. A 1-page clinical research form was used to collect clinical information. Copies of all electrocardiograms were obtained. Electrocardiogram parameters (QRS and QT intervals) were manually measured as previously described, and plots of QT-heart rate (HR) pairs were compared with the QT nomogram. There were 83 patients with amisulpride overdoses with a median age of 29 years (interquartile range [IQR], 23-40 years), and 42 (51%) were female. The median dose ingested was 6 g (IQR, 3-13 g, range, 1.2-120 g). The median HR was 66 beats/min (IQR, 60-81 beats/min). Bradycardia occurred in 20 cases (24%), and hypotension in 19 (23%). From 440 electrocardiograms (average of 5 per case; range, 1-15), an abnormal QT-HR pair occurred in 61 cases (73%). Torsades de pointes developed in 6 cases (7%), with doses of 4, 4.6, 18, 24, 32, and 80 g. The patient taking 32 g died after a cardiac arrest. Widened QRS did not occur except transient rate-dependent bundle-branch block in 3 cases. There were significant associations of bradycardia, hypokalemia, and hypocalcaemia, with QT prolongation and torsades de pointes. Central nervous system effects were uncommon with coma in 7 cases, seizures in 2, and dystonic reactions in 2. Amisulpride overdose commonly causes QT prolongation, bradycardia, and hypotension. Torsades de pointes occurred commonly enough to suggest that amisulpride is highly cardiotoxic in overdose.

Australian scorpion stings: a prospective study of definite stings

There is little information on scorpion stings in Australia. The aim of this study is to describe the circumstances and clinical effects of stings by Australian scorpions. Cases of scorpion stings were collected prospectively from calls and presentations to Australian poison information centres and emergency departments from February 2000 to April 2002. Only definite scorpion stings where the scorpion was immediately collected and expertly identified were included. There were 95 patients, 33 males and 62 females, with a mean age of 32 (SD 19.5; range 1-71) and 23 children (age<15 years). Three families of scorpions caused all stings: Buthidae (79), Bothruiridae (11, all Cercophonius spp.) and Urodacidae (five, all Urodacus spp.). The majority of stings (76%) were by one genus of scorpion Lychas spp. Seventy one percent of stings occurred between 6pm and 8am and 82 (86%) occurred indoors. Sixty percent of stings occurred on distal limbs. The median duration of effects was 6 h (interquartile range (IQR): 1-24 h). Immediate localised pain occurred in all cases and was severe in 76 cases (80%). Other local effects included red mark/redness (66%), tenderness (35%), numbness (12%) and paraesthesia (11%). Minor systemic effects (nausea, headache and malaise) occurred in 11% of cases. There were no deaths or major systemic envenoming. Less severe effects were observed for the larger Urodacus species, compared to Lychas spp. Scorpion stings in Australia do not appear to cause severe or life-threatening effects, even in children. This differs from other parts of the world, where severe envenoming is reported. The major clinical effect is severe pain, consistent with other scorpion stings. Most stings occurred indoors and at night.

Prospective Study of Centipede Bites in Australia

Background: There are limited reports of definite bites by centipedes with expert identification, which are required for attribution of particular clinical effects to different species. Objective: To describe the clinical effects of centipede bites in Australia. Methods: Prospective study of calls regarding centipede exposures to a state poison information center, from December 2000 to March 2002. Information collected included demographics, details of the exposure, local effects, systemic effects, and treatment. Collected centipedes were identified by an expert. All subjects were followed until clinical effects had resolved. Results: Of 48 centipede exposures 3 were centipede ingestions with no adverse effects and one was a contact reaction to the centipede that resulted in erythema and delayed itchiness. Of 44 definite centipede bites, the centipedes obtained and formally identified in 14 cases were from the genera Scolopendra (5), Cormocephalus (6), and Ethmostigmus (3). Of these 14 bites, 13 occurred distally (hands or feet). Pain occurred in all 14 cases and was severe in 7 patients. Redness/red mark occurred in 53%, swelling/raised area in 43%, and itchiness in 14%. No systemic effects were reported. Ethmostigmus spp. and Scolopendra spp. caused more severe effects. Of the bites, 57% occurred indoors and 50% at night. Treatment consisted of supportive measures including ice packs and simple analgesia, and 4 patients reported pain relief after immersing the bite area in hot water. Similar clinical effects were reported in the other 30 definite centipede bites. Conclusions: Australian centipede bites cause minor effects with moderate to severe pain, associated with localized swelling and erythema in bites by the genera Ethmostigmus and Scolopendra. Hot water immersion may potentially be beneficial for centipede bites. The genus Scolopendra occurs worldwide and the results may have international applicability.

Antipsychotic Poisoning in Young Children: A Systematic Review

The aim of this review was to determine the spectrum and severity of effects of unintentional antipsychotic poisoning in children. A computerised literature search of MEDLINE (1966 to February 2005) and EMBASE (1980 to February 2005) was undertaken. The Internet was searched using URL: http://www.google.com. The proceedings of the North American Congress of Clinical Toxicology (NACCT) and the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) were hand searched. All cases of unintentional antipsychotic (all classes) poisoning in children aged 0–6 years were included. The data extracted included the age, weight, antipsychotic, dose, clinical effects, treatment and outcomes. The toxic dose was estimated as the lowest dose causing objective adverse effects.Sixty-eight reports were identified. Few contained all of the required information. Most of the case series included multiple antipsychotics with limited information on individual drugs or all ages with limited paediatric information. For most antipsychotics the ingestion of one tablet caused symptoms that were sometimes severe and usually lasted from 1 to 3 days. Extrapyramidal symptoms (EPS) were often delayed for up to 12–24 hours. Chlorpromazine caused CNS depression, hypotension and miosis; EPS and cardiac effects were rare, and the toxic dose was estimated to be 15 mg/kg. Haloperidol caused drowsiness (rarely coma) and over one-half of patients had neuromuscular effects (mainly EPS), with a toxic dose estimated at 0.15 mg/kg. Thioridazine caused CNS depression and potentially cardiac effects, with a toxic dose of 1.4 mg/kg. Atypical antipsychotics caused significant CNS depression (except risperidone); EPS were less common. Toxic doses were clozapine 2.5 mg/kg, olanzapine 0.5 mg/kg and aripiprazole 3 mg/kg. EPS responded to anticholinergic drug treatment.In summary, unintentional antipsychotic ingestion in children can cause severe effects that last 1–3 days, often with one tablet. Children potentially ingesting a toxic dose or who are symptomatic should be considered for assessment in hospital. Most cases resolve with good supportive care. Toxic doses are only estimates that are based on limited data and should be used with caution until prospective studies are undertaken.

Randomized controlled trial of topical aspirin in the treatment of bee and wasp stings

Abstract Background: The New South Wales Poisons Information Centre (NSW PIC) has been recommending the use of topical aspirin paste for bee and wasp stings since the early 1980s. Anecdotal evidence from calls suggested it was effective in reducing the swelling and duration of pain, but a literature search found no evidence to support this. Objective: The objective of this study was to assess the effectiveness of advice given by a PIC to apply topical aspirin for the treatment of bee and wasp stings. Methods: Patients were recruited from callers to the NSW PIC who reported a bee or wasp sting. They were randomly assigned, using a 2:1 ratio, to two different treatment advices: to apply an ice pack (control group), or to apply an ice pack and topical aspirin paste (treatment group). Initial follow‐up was within 24–48 hours. Primary outcome was the presence of swelling at 12 hr. Secondary outcomes included the presence of pain at 12 hr, the presence of itchiness, and duration of redness. Results: There were 37 patients who received treatment advice and 19 in the control group. Of the 37 patients advised to apply aspirin, 21 (57%) had no swelling at 12 hr compared with 14 of the 19 (74%) patients with ice alone (difference −17%; 95% CI: −47–12%; p = 0.26). Eighty‐one percent (30/37) of patients advised to apply aspirin had no pain at 12 hr compared with (18/19) 95% of the others (−14%; 95% CI: −39–14%; p = 0.34). The median duration of redness was 6 hr [interquartile range (IQR): 2–48 hr] in those advised to apply aspirin paste compared with 2 hr (IQR: 0–10 hr) in those that only applied ice (p = 0.04). Conclusions: Topical aspirin paste was not effective in reducing the duration of swelling or pain in bee and wasp stings, and significantly increased the duration of redness. Symptoms rapidly subsided with ice alone as treatment.

Unintentional paediatric ingestions of angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists

Aims:  There is limited information on safety of angiotensin coverting enzyme (ACE) inhibitors and angiotensin II (AII) receptor antagonists in unintentional paediatric ingestions. This study was conducted with the aim of developing referral guidelines for poison information centres.