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Biomedical subjects

Ian M Whyte

Publications and source records attributed to Ian M Whyte.

At least 19 recordsLinked to original sources
PubMed2006

Baclofen overdose: defining the spectrum of toxicity.

OBJECTIVES: To describe the spectrum of toxicity of baclofen in overdose, and investigate dose-related clinical effects. METHODS: Consecutive baclofen overdoses were identified from a prospective database of all poisoning admissions presenting to a regional toxicology service. Ingestion was corroborated on more than one occasion and from multiple sources. Demographic, clinical and outcome variables were extracted for each presentation for a retrospective review, and the data sets were divided into high dose (> or = 200 mg) and low dose (< 200 mg) groups for comparison of clinical effects. RESULTS: There were 23 presentations, of which eight patients ingested baclofen alone. Seizures were reported in four cases, a decreased level of consciousness (GCS < 9) occurred in eight patients and delirium was recorded in eight patients. Five patients had miosis and seven patients had dilated pupils, 13 patients had absent or depressed reflexes. The only arrhythmias were sinus bradycardia in six patients and sinus tachycardia in five. Hypertension occurred in 13 patients and hypotension in one. The reported total ingested dose of baclofen was known in 19 patients (Mean 630 mg, SD 730 mg; 80-2500 mg). A higher ICU admission rate, rate of mechanical ventilation and prolonged length of stay occurred in those ingesting 200 mg or more. Coma, delirium and seizures occurred only with doses of 200 mg or more, and hypertension was more common with higher doses. CONCLUSIONS: Baclofen overdose causes mainly neurological effects and excepting hypertension cardiovascular effects were uncommon. Doses greater than 200 mg were predictive of patients developing delirium, coma and seizures, requiring long hospital admissions and ICU admission.

Adolescent↗
PubMed2006

Psychiatric hospitalization after deliberate self-poisoning.

The decision for psychiatric hospitalization after deliberate self-poisoning (DSP) is not well understood. This study, a longitudinal cohort study of 3,148 consecutive DSP patients found 920 (29.2%) subjects were referred for psychiatric hospitalization, 576 (18.3%) on involuntary basis. A logistic regression analysis showed increased risk for: age 25 or older, homelessness, unemployment, previous self-harm, psychiatric inpatient treatment within 12 months, earlier psychiatric inpatient treatment, suicidal ideation or plan, mood or psychotic disorders, and lower clinician experience; and lower risk for being married/defacto, and after hours presentation. Recommendation for psychiatric hospitalization was based on complex decision making. These findings have implications for clinical practice guidelines, service costs, and service organization.

Adult↗
PubMed2005

Postcards from the EDge project: randomised controlled trial of an intervention using postcards to reduce repetition of hospital treated deliberate self poisoning.

OBJECTIVE: To determine whether an intervention using postcards (postcards from the EDge project) reduces repetitions of hospital treated deliberate self poisoning. DESIGN: Randomised controlled trial. SETTING: Regional referral service for general hospital treated deliberate self poisoning in Newcastle, Australia. PARTICIPANTS: 772 patients aged over 16 years with deliberate self poisoning. INTERVENTION: Non-obligatory intervention using eight postcards over 12 months along with standard treatment compared with standard treatment alone. MAIN OUTCOME MEASURES: Proportion of patients with one or more repeat episodes of deliberate self poisoning and the number of repeat episodes for deliberate self poisoning per person in 12 months. RESULTS: The proportion of repeaters with deliberate self poisoning in the intervention group did not differ significantly from that in the control group (57/378, 15.1%, 95% confidence interval 11.5% to 18.7% v 68/394, 17.3%, 13.5% to 21.0%: difference between groups -2%, -7% to 3%). In unadjusted analysis the number of repetitions were significantly reduced (incidence risk ratio 0.55, 0.35 to 0.87). CONCLUSION: A postcard intervention reduced repetitions of deliberate self poisoning, although it did not significantly reduce the proportion of individual repeaters.

Adolescent↗
PubMed2005

The Australasian Clinical Toxicology Investigators Collaboration randomized trial of different loading infusion rates of N-acetylcysteine.

STUDY OBJECTIVE: We determine whether the incidence of adverse events caused by intravenous N -acetylcysteine is significantly less when the initial dose is infused over a 60-minute period compared with the standard infusion period of 15 minutes. A secondary objective is to assess the efficacy of the 2 treatment arms. METHODS: This was a multicenter, randomized, prospective trial of patients who presented with acetaminophen poisoning and who were treated with N -acetylcysteine and had no history of hypersensitivity to N-acetylcysteine. Patients were randomly assigned to receive the initial dose of N-acetylcysteine over a 15-minute or 60-minute period. Baseline signs and symptoms and adverse events were serially evaluated before and during administration of N -acetylcysteine. Tests of liver injury and coagulation were collected at baseline and then at 12-hour intervals. RESULTS: The study was designed with an 80% power to detect a halving of the incidence of adverse events. Of 180 evaluable patients, 109 patients were randomized to the 15-minute group and 71 patients were randomized to the 60-minute group. The incidence of drug-related adverse events was 45% in the 15-minute group and 38% in the 60-minute group (95% confidence interval -8% to 22%). The study did not demonstrate a reduction of drug-related adverse outcomes with the 60-minute infusion. Incidence of maximum alanine aminotransferase levels indicating hepatotoxicity (serum level >1,000 IU/L) was 6.8% (5.6% for 15-minute, 8.7% for 60-minute). The difference did not attain statistical significance. CONCLUSION: This study did not demonstrate a reduction of drug-related adverse outcomes with the 60-minute infusion. The study also confirmed that early treatment with N -acetylcysteine (within 8 hours of ingestion) is more effective than later treatment.

Acetaminophen↗
PubMed2005

Clinical management for hospital-treated deliberate self-poisoning: comparisons between patients with major depression and borderline personality disorder.

OBJECTIVE: To compare the initial clinical management of hospital-treated deliberate self-poisoning patients with major depressive disorder (MDD) or borderline personality disorder (BPD) after controlling for demographic factors and level of suicide ideation. METHOD: This study compared sequential hospital treated deliberate self-poisoning patients (n = 570) with either MDD or BPD (but no major comorbid psychopathology) on four outcomes modelled using logistic regression: (i) length of stay in the general hospital; (ii) discharge to a psychiatric hospital; (iii) psychiatric follow-up; and (iv) general practitioner (GP) follow-up. RESULTS: BPD and MDD patients were discharged to psychiatric inpatient care at very similar rates (33%-35%) and almost all subjects with high levels of suicidal ideation were discharged to psychiatric hospital. However, for mild to moderate levels of suicidal ideation BPD patients were more likely to be discharged to psychiatric hospital than MDD patients. After controlling for demographics and suicidal ideation, BPD patients were more likely to be referred for psychiatric hospitalization on discharge (adjusted OR = 1.79, 95% CI = 1.01-3.18) and less likely to be referred to GPs if discharged to home (adjusted OR = 0.44, 95% CI = 0.24-0.81). There were no differences in general hospital length of stay or arrangements made for psychiatric follow-up for those discharged to home. CONCLUSIONS: This suggests that for mild to moderate suicidal ideation levels clinicians are more likely to choose to send BPD patients, after deliberate self-poisoning, to inpatient psychiatric care than MDD patients. Clinicians are also apparently more likely to choose to manage MDD patients in primary care settings, for those patients discharged to home. This has implications for service planning and clinical guidelines.

Adult↗
PubMed2005

Amphetamine-induced movement disorder.

Recreational use of amphetamines is common in Australia and New Zealand when compared with other developed nations. The clinical effects are variable because of the potential of these drugs to increase the proportion of different biogenic amines in the central nervous system (CNS). The substances affected are adrenaline, noradrenaline, serotonin and dopamine. Movement disorders represent one of the less common presentations of amphetamine toxicity but one that health care workers should be aware of nonetheless.

Amphetamine-Related Disorders↗
PubMed2005

Repeated self-poisoning: increasing severity of self-harm as a predictor of subsequent suicide.

BACKGROUND: Prediction of suicide risk is difficult in clinical practice. AIMS: To identify changes in clinical presentation predictive of suicide in patients treated for repeated episodes of self-poisoning. METHOD: A nested case-control study used the Hunter Area Toxicology Service database to identify exposure variables and the National Death Index to identify suicide. Cases were patients who had hospital treatment on more than one occasion between 15 January 1987 and 31 December 2000. RESULTS: There were 31 cases, for which 93 controls were selected. Study variables associated with an increased risk of subsequent suicide were an increase in the number of drugs ingested (odds ratio 2.59, 95% CI 1.48-4.51), an increase in the dose ingested (OR 1.33, 95% CI 1.01-1.76), an increase in coma score (OR 1.71, 95% CI 1.11-2.66), a decrease in Glasgow Coma Score (OR 1.21, 95% CI 1.03-1.43) and an increase in drug or alcohol misuse (OR 2.33, 95% CI 1.06-5.10). CONCLUSIONS: Patients who have escalating severity of self-poisoning episodes are at high risk of completed suicide.

Adolescent↗
PubMed2004

Posttraumatic stress disorder among deliberate self-poisoning patients.

This study explored posttraumatic stress disorder (PTSD) among suicide attempters. Participants were 330 hospital-treated deliberate self-poisoning (DSP) patients. Twelve-month prevalence of PTSD and comorbid psychiatric disorders was determined using the Composite International Diagnostic Interview (CIDI-A). Standard disability measures and demographic information were also obtained. PTSD prevalence was 32% among women and 15% among men. The PTSD group had significantly higher levels of affective disorder, anxiety disorders other than PTSD, psychiatric disability, and service utilization than DSP patients without PTSD. Logistic regression modeling showed that PTSD was associated with the type of traumatic event, number of events, affective disorder, and anxiety disorder other than PTSD.

Adult↗
PubMed2004

Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) have increasingly replaced tricyclic antidepressants (TCAs) in the treatment of depression. They appear to be safer in overdose, but there is little information on their spectrum of toxicity in overdose, or relative toxicity of each agent. OBJECTIVE: To determine the effect of SSRIs in overdose, as a group, and the relative toxicity of five different SSRIs. METHODS: A review of consecutive SSRI poisoning admissions to a single toxicology unit. Outcomes examined were length of stay [LOS], intensive care [ICU] admission rate, coma, seizures, electrocardiographic [ECG] abnormalities, and presence of serotonin syndrome [SS]. Logistic regression was used to model the outcome QTc >440 msec. RESULTS: There were 469 SSRI poisoning admissions analyzed after exclusions. The median LOS for all SSRI overdose admissions was 15.3 h (IQR: 10.5-21.3) and 30 of 469 (6.4%; 95% CI 4.3-9.0%) cases were admitted to ICU. The incidence of seizures was 1.9% and coma was 2.4%. Serotonin syndrome occurred in 14% of overdoses. Comparison of median QTc intervals of the five SSRIs was significantly different (p=0.0002); citalopram (450 IQR: 436-484) was individually different to fluoxetine (p=0.045), fluvoxamine (p=0.022), paroxetine (p=0.0002), and sertraline (p=0.001). The proportion of citalopram overdoses with a QTc >440 msec was 68%, differing significantly from sertraline (adjusted OR: 5.11 95% CI 2.32-11.27). Comparison of median QT intervals of the five SSRIs was statistically different (p=0.026); citalopram (400 IQR: 380-440) was individually different from sertraline (p=0.023). CONCLUSIONS: This study shows SSRIs are relatively safe in overdose despite serotonin syndrome being common. The exception was citalopram, which was significantly associated with QTc prolongation. We believe that cardiac monitoring should be considered in citalopram overdose, particularly with large ingestions and patients with associated cardiac disease.

Adolescent↗
PubMed2004

Aspiration pneumonitis in an overdose population: frequency, predictors, and outcomes.

OBJECTIVE: To characterize the frequency of aspiration pneumonitis in an unselected population of overdose patients and, further, to identify factors that predispose to aspiration pneumonitis and the outcomes of patients with aspiration pneumonitis compared with those without. DESIGN: Retrospective cohort study. SETTING: Toxicology unit of a tertiary referral hospital. PATIENTS: All poisoning admissions. MEASUREMENTS AND MAIN RESULTS: A total of 71 of 4,562 poisoning admissions to the Hunter Area Toxicology Service between January 1997 and October 2002 had definite aspiration pneumonitis (1.6%; 95% confidence interval, 1.2-2.0). Older age, Glasgow Coma Score of <15, spontaneous emesis, seizures, delayed presentation to hospital, and ingestion of tricyclic antidepressants were associated with an increased risk of aspiration pneumonitis. Paracetamol poisoning and female sex were associated with a decreased risk of aspiration pneumonitis with univariate analysis. Ingestion of alcohol, benzodiazepines, antipsychotics, and administration of activated charcoal were not associated with aspiration pneumonitis. A logistic regression model for predicting aspiration pneumonitis contained seven predictors: age, sex, Glasgow Coma Score of <15 (odds ratio, 3.14; 95% confidence interval, 1.87-5.27), emesis (odds ratio, 4.17; 95% confidence interval, 2.44-7.13), seizure, tricyclic antidepressant ingestion, and time from ingestion to presentation (delay of >24 hrs [odds ratio, 4.42; 95% confidence interval, 2.42-8.10]). The mortality for patients with aspiration pneumonitis was 8.5% compared with 0.4% for those without (odds ratio, 23; 95% confidence interval, 9-60; p <.0001), and they had a significantly higher intensive care unit admission rate. The median length of stay of patients with aspiration pneumonitis was 126 hrs (interquartile range, 62-210 hrs) compared with 14.7 hrs (interquartile range, 7-23 hrs) in patients without (p <.0001). CONCLUSIONS: Our study has shown a number of risk factors in overdose patients that are associated with aspiration pneumonitis that may allow the early identification of these patients for appropriate observation and management. Patients with aspiration pneumonitis have a significantly increased mortality and length of stay in the hospital.

Adult↗
PubMed2004

Alprazolam is relatively more toxic than other benzodiazepines in overdose.

AIMS: To describe alprazolam poisoning and the relative toxicity of alprazolam compared with other benzodiazepines. METHODS: A database of consecutive poisoning admissions to a regional toxicology service was searched to identify consecutive benzodiazepine deliberate self poisonings, which were coded as alprazolam, diazepam or other benzodiazepine. Major outcomes used were length of stay (LOS), intensive care (ICU) admission, coma (GCS < 9), flumazenil administration and requirement for mechanical ventilation. Prescription data were obtained for benzodiazepines for the study period. RESULTS: There were 2063 single benzodiazepine overdose admissions: 131 alprazolam overdoses, 823 diazepam overdoses and 1109 other benzodiazepine overdoses. The median LOS for alprazolam overdoses was 19 h which was 1.27 (95% CI 1.04, 1.54) times longer compared with other benzodiazepines by multiple linear regression. For patients with alprazolam overdoses, 22% were admitted to ICU which was 2.06 (95% CI 1.27, 3.33) times more likely compared with other benzodiazepines after multivariate analysis adjusting for age, dose, gender, time to ingestion and co-ingested drugs. Flumazenil was administered to 14% of alprazolam patients and 16% were ventilated, which was significantly more than for other benzodiazepine overdoses (8% and 11%, respectively). Twelve percent of alprazolam overdoses had a GCS < 9 compared with 10% for other benzodiazepines. From benzodiazepine prescription data, total alprazolam prescriptions in Australia increased from 0.13 million in 1992 to 0.41 million in 2001. Eighty five percent of prescriptions were for panic disorder, anxiety, depression or mixed anxiety/depression. CONCLUSIONS: Alprazolam was significantly more toxic than other benzodiazepines. The increased prescription of alprazolam to groups with an increased risk of deliberate self poisoning is concerning and needs review.

Adolescent↗
PubMed2004

Arsenic trioxide poisoning: a description of two acute overdoses.

Arsenic is a traditional poison that has a history extending back into ancient times, as a medicinal agent, a homicidal poison and more recently in deliberate and unintentional self-poisoning. We report two cases of acute poisoning with an unwettable formulation of arsenic trioxide. Both patients had early gastrointestinal toxicity and were treated with early whole bowel irrigation (WBI). Chelation therapy with dimercaptosuccinic acid (dimercaptosuccinate, DMSA) was commenced within 24 hours and serial blood and urine arsenic concentrations were measured. Neither patient suffered any adverse outcome in spite of very high blood and urine concentrations of arsenic. Arsenic quantification in blood, urine and faeces suggested that enhanced gastrointestinal decontamination was minimally effective for decontamination and that DMSA for at least two weeks was required.

Acute Disease↗
PubMed2003

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.

Adult↗
PubMed2003

Valproate overdose: a comparative cohort study of self poisonings.

AIMS: Based on individual case reports of massive overdoses, valproate is often regarded as having significant toxicity. This study aimed to describe the epidemiology of valproate poisoning and the spectrum of its clinical effects. METHODS: Consecutive valproate poisonings were identified and compared with other anticonvulsant overdoses and all other poisonings, from a prospective database of poisoning admissions presenting to a regional toxicology service. National prescription data for the same period were obtained. RESULTS: There were 79 patients with valproate poisoning from January 1991 to November 2001, 15 cases with valproate alone. Of the 15 cases, drowsiness occurred in two patients (both taking> 200 mg kg-1), vomiting occurred in four and tachycardia in five. In patients co-ingesting other medications, moderate to severe effects were consistent with the co-ingestants. There was one death not directly related to valproate. One patient had metabolic acidosis and thrombocytopaenia consistent with severe valproate toxicity. Comparison of valproate, carbamazepine, phenytoin and control groups showed that length of stay for both phenytoin and carbamazepine was significantly longer than for valproate (P < 0.0001), and there was a significantly increased risk of intensive care unit admission for carbamazepine vs valproate (OR 2.73; 95% CI 1.22, 6.28; P = 0.015). Although valproate prescriptions increased over the 10 years, there was relatively greater increase in the incidence of valproate poisoning. The odds of a valproate overdose in 1992 compared with carbamazepine were 0.29 (95% CI 0.07, 1.28; P = 0.141), but in 2001 were 2.73 (95% CI 1.38, 5.39; P = 0.004). CONCLUSIONS: Valproate causes mild toxicity in the majority of cases. Massive overdoses of greater than 400 mg kg-1 can cause severe toxicity, but these are uncommon. The older anticonvulsants phenytoin and carbamazepine remain a greater problem than valproate in overdose.

Adult↗