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Biomedical subjects

N A Buckley

Publications and source records attributed to N A Buckley.

At least 37 records · Page 2Linked to original sources
PubMed1999

Preformatted admission charts for poisoning admissions facilitate clinical assessment and research.

STUDY OBJECTIVE: The assessment of patients with poisoning should include assessment of psychiatric details, the level of consciousness, and clinical features occurring in a number of toxidromes (toxicology syndromes). To ensure these aspects were routinely covered, we introduced a preformatted chart (PFC) to record our poisoning admissions. The aim of our study was to determine whether using a PFC improved the quality, accuracy, and completeness of the data obtained from admissions with poisoning. METHODS: Clinical details recorded on patients admitted with tricyclic antidepressant, neuroleptic, or carbamazepine poisoning between 1987 and 1994 were compared according to whether a PFC was used. A large number of items of history and examination of interest in poisonings were analyzed. The reproducibility of the findings recorded on the PFCs was measured in 20 patients. Findings initially recorded on the chart in the emergency department were compared with those recorded within the next 30 minutes by a second more experienced observer who did not have reference to the initial record. RESULTS: There were large and statistically significant differences in the completeness of recording of neurologic examination, such as pupil size (100% versus 68%), conjugate eye movements (97% versus 35%), deep tendon reflexes (97% versus 51%), and in the percentage that were reported as having abnormal signs, such as dilated pupils (26% versus 14%), nystagmus (12% versus 5%), and hyperreflexia (19% versus 8%). In all cases, more information was recorded when a PFC was used; however, the differences were small for items such as vital signs and drugs ingested. Agreement between 2 observers for history and examination was moderate to good, with items on history and level of consciousness generally recorded with greater agreement than other examination findings, perhaps reflecting fluctuations in these signs. CONCLUSION: Data collected prospectively with a PFC collects more information than can be obtained retrospectively from case records. In particular, the validity of data on clinical signs on presentation gained from retrospective chart review is questionable. Centers that are interested in collecting data on series of poisonings would benefit from using a PFC or some other systematic prospective method of data collection.

Emergency Service, Hospital↗
PubMed1998

Can the fatal toxicity of antidepressant drugs be predicted with pharmacological and toxicological data?

Antidepressant drugs are among the most common drugs involved in fatal poisoning and large variations between antidepressant drugs have been noted. Despite the fact that a large number of studies have calculated a fatal toxicity index (FTI) for antidepressants, no serious attempts have been made to compare the differences in fatal toxicity against known pharmacological and toxicological differences in receptor affinity. It is potentially from such data that screening of drugs during their pre-clinical development can be facilitated. We examined correlations between the FTI and noradrenaline (norepinephrine)/serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibition selectivity, the dose that is lethal to 50% of animals (LD50), lipid solubility, and antagonist activity at cholinergic, histaminergic, alpha-adrenergic and gamma-aminobutyric acid (GABA)A receptors or sodium and potassium channel blocking effects. We obtained data on the number of fatal poisonings between 1983 and 1992 in England and Wales caused by a single antidepressant drug from the Department of Health in the UK. This number was divided by the number of prescriptions in England for these drugs over this time to derive a FTI of deaths per million prescriptions. The highest FTIs were for amoxapine, viloxazine, desipramine and dothiepin. Lofepramine, paroxetine and fluoxetine had very low FTIs. Using Poisson regression, there was a significant positive relationship between the FTI of antidepressant drugs and their lethal toxicity in animals, and measures of their cardiac effects. The relative noradrenaline/serotonin reuptake inhibition, lipid solubility and their potency at histamine H1, muscarinic and alpha 1-adrenergic receptors had no substantial association with the FTI. Limited data suggest that some cardiac effects and potency as a GABAA antagonist may be important predictors of significant toxicity. Further data using standardised bio-assays are needed to compare the direct cardiac effects of antidepressants. Thus, the best current pre-clinical indicator of fatal toxicity in humans is the LD50 in animal studies. Clearly, there are humane and practical reasons for developing a better pre-clinical indicator of toxicity in overdose for this rapidly expanding group of drugs.

Animals↗
PubMed1997

Health care. A model for the management of self-poisoning.

OBJECTIVE: To describe the development and activity of a multidisciplinary service to manage self-poisoning. DESIGN: Descriptive, comparative study with prospective data collection. SETTING: Regional toxicology treatment centre in the Hunter area of New South Wales (NSW) with primary and secondary referral service to 385,000 people and tertiary referral service to a further 100,000. PATIENTS: All patients (1987-1995) with poisoning or envenomation presenting to the Hunter Area Toxicology Service (HATS). MAIN OUTCOME MEASURES: Average length of stay for HATS compared with national and NSW hospitals; mortality data for HATS compared with NSW. RESULTS: Average length of stay for HATS was 0.53-1.22 days shorter than for all Australian hospitals, potentially saving 518 bed-days, valued at $468,000 per year. Average length of stay was 0.94-3.39 days shorter than for all NSW hospitals, saving 1470 bed-days at $1.4 million per year. Inpatient mortality (0.2%; 95% confidence interval, 0.0-1.1) was not significantly different from NSW (0.5%; 95% CI, 0.2-0.8). Standardised mortality ratios showed no greater all-cause suicide mortality. CONCLUSIONS: In our centralised model for managing self-poisoning, all toxicology patients in an area health service are diverted to one hospital, where all patients with deliberate self-poisoning are admitted under the one multidisciplinary team, and all receive psychiatric assessment. This model has substantially reduced bed stay, with considerable savings to the Hunter Area Health Service manifested as an increase in beds available for other purposes.

Critical Pathways↗
PubMed1996

Interrater agreement in the measurement of QRS interval in tricyclic antidepressant overdose: implications for monitoring and research.

STUDY OBJECTIVE: To assess interobserver agreement when experienced clinicians measure QRS-interval duration in tricyclic antidepressant (TCA) overdose. METHODS: We studied the admission ECGs of 231 patients with ICA poisoning. Three of the authors, with experience in the management of TCA poisoning, independently measured QRS intervals manually. Each rater was blinded to patient outcome and the measurements made by the other raters. Our main outcome measure was agreement among raters, particularly as it applies to clinically used QRS cutoff points for the determination of treatment and disposition. RESULTS: Agreement on the measurement of QRS intervals was good (intraclass correlation coefficient, 60; 95% confidence interval [CI], 53 to .66) for transformed data and .82 (95% CI, 7B to .85) for raw data. When assigning patients to categories of QRS interval, the raters agreed on 169 of 231 patients (73%) (weighted kappa = 83; P < .0001). However, the raters did not agree unanimously on whether the QRS interval was less than 100 milliseconds or 100 milliseconds or greater in 45 of 231 of patients (19.5%) (kappa = 69; P < .0001). CONCLUSION: Reliance on the manually measured QRS interval to determine management in TCA poisoning is not justified because of substantial observer variation in the determination of whether the interval falls below the clinical cutoff point of 100 milliseconds. Agreement is sufficient to make the measurements useful as part of the overall assessment of toxicity.

Antidepressive Agents, Tricyclic↗
PubMed1996

An analysis of age and gender influences on the relative risk for suicide and psychotropic drug self-poisoning.

Psychiatric illness is a significant risk factor for both attempted and completed suicide and psychotropic medications account for 80% of all drug overdoses involving prescription medications. One challenge facing clinicians is to balance the benefit of treatment against the risk of drug overdose. The aim of the present study was to compare the age and gender distribution of patients prescribed psychotropic drugs with patients attempting and completing suicide with these drugs. Data were obtained from the Australian census and studies of general practitioner prescribing, patients who committed suicide or presented with self-poisoning within a defined geographic area. The characteristics of these populations were compared to calculate odds ratios for attempting or completing suicide with psychotropic drugs, before and after correction for rates of prescription, in different age and gender groups. The odds ratios (ORs) for self-poisoning were higher for those aged less than 45 years and yet this group was least likely to be prescribed psychotropic drugs. Men had a much higher rate of completed suicide using more lethal methods. The ORs for self-poisoning and suicide with psychotropic drugs, after correction for prescription rates, for those aged 15 to 24 years were 11.1 and 1.7, respectively. Those aged 25 to 44 years had ORs of 4.9 and 4.3, and, by contrast, those over 75 years had ORs of 0.03 and 0. Women were slightly more likely to poison themselves with psychotropic drugs (OR 1.2). However, the situation reversed after correction for prescription rates (OR 0.69). It is concluded that greater caution should be exercised in prescribing for those under 45 years of age, given their relatively higher risk of drug overdose, and that the least toxic compounds should be used. The risk (of self-poisoning) among the elderly may have been overstated, so that some patients may have been denied the benefit of adequate treatment.

Adolescent↗
PubMed1996

Effects of catecholamines and diazepam in chloroquine poisoning in barbiturate anaesthetised rats.

The recommended treatment of human chloroquine poisoning is diazepam and adrenaline but neither has been evaluated in controlled clinical trials. We investigated whether diazepam provided any added benefit over barbiturate anaesthesia and whether the protective effect of catecholamines in chloroquine poisoning was mediated through alpha or beta receptor stimulation. Rats, anaesthetised with thiobutobarbitone had a continuous intravenous infusion of 3 mg/kg/min of chloroquine. This caused a steady decline in pulse rate and blood pressure. When diazepam (3 mg/kg iv) was administered 5-10 min later, heart rates decreased at a faster rate (P = 0.005), blood pressure was consistently lower (P = 0.01) and there was a shorter time to arrhythmias and death (P < 0.05). Adrenergic agents were given by titration to attempt to maintain mean blood pressure > 75 mmHg. Compared with the phenylephrine (selective alpha agonist) group, the group treated with isoprenaline (selective beta agonist) had faster heart rates which decreased more slowly (P < 0.0001), higher blood pressure (P = 0.005) and longer time to arrhythmias and death (P = 0.005). Adrenaline and noradrenaline had intermediate effects. Thus beta agonist effect appears to explain the beneficial effects of adrenaline but alpha agonist activity may be harmful. This animal work suggests that a combination of barbiturate anaesthesia and isoprenaline may be better than the diazepam and adrenaline in combatting the effects of chloroquine.

Adrenergic Agents↗
PubMed1996

Relative toxicity of beta blockers in overdose.

OBJECTIVE: To compare the toxicity of beta blockers in overdose and to identify clinical features predictive of serious toxicity. DESIGN: Comparison of clinical data collected prospectively on a relational database of subjects presenting to hospital with self-poisoning, coroner's data and prescription data. SETTING: Newcastle and Lake Macquarie, Australia, 1987-1995. MAIN OUTCOME MEASURES: Death, seizure, cardiovascular collapse, hypoglycemia, coma and respiratory depression. SUBJECTS: Fifty-eight self-poisonings with beta blockers and two deaths investigated by the coroner with evidence of propranolol poisoning. RESULTS: All patients who developed toxicity did so within six hours of ingestion. The use of ipecac was temporally associated with cardiorespiratory arrest in one patient. Propranolol was the only beta blocker associated with seizure; of those who ingested more than 2 g of propranolol, two thirds had a seizure. There was a significant association between a QRS duration of > 100 ms and risk of seizures. Propranolol was over represented in beta blocker poisoning when prescription data were also examined. Propranolol was the only beta blocker associated with death. Propranolol was taken by a younger age group. CONCLUSIONS: Propranolol should be avoided in patients at risk of self-poisoning. Propranolol poisonings should be observed closely for the first six hours post ingestion. Syrup of ipecac should not be used to decontaminate the gastrointestinal tract after beta blocker overdose.

Adolescent↗
PubMed1995

Self-poisoning in Newcastle, 1987-1992.

OBJECTIVE: To examine the morbidity and mortality associated with self-poisoning with different drug classes. DESIGN: Prospective cohort study with limited follow-up. Retrospective analysis of coronial data. SETTING: Primary and tertiary referral toxicology centre covering Newcastle and Lake Macquarie, Australia, 1987-1992. RESULTS: There were 1969 admissions after ingestion of 3724 substances (2424 prescription drugs and 1300 non-prescription items). The coroner investigated 83 drug-related deaths. Only 12 of these people presented to hospital and, for most of these, death was inevitable at presentation. The most frequently ingested substances were benzodiazepines, alcohol, paracetamol, antidepressants, neuroleptics and anticonvulsants. Since 1980, the percentage of self-poisonings involving benzodiazepines has fallen, while it has risen for those involving antidepressants. Over 50% of deaths were due to tricyclic antidepressants or opioid analgesics. CONCLUSIONS: As death usually occurs out of hospital, interventions to decrease mortality from self-poisoning must focus on prevention, and targeting drugs that are frequently taken or frequently lethal in overdose. Consideration should be given to the use of antidepressants that are safer in overdose. The use of antidepressants, barbiturates or chloral hydrate as sedatives should be discouraged.

Adolescent↗
PubMed1995

Correlations between prescriptions and drugs taken in self-poisoning. Implications for prescribers and drug regulation.

OBJECTIVE: To compare prescription data for Australia with drugs ingested in self-poisoning and suicide, to determine which drugs are over-represented. DESIGN: Comparison of data on drugs taken in self-poisoning admissions and suicides with Australian prescription drug dispensing data from the Drug Utilization SubCommittee (DUSC). SETTING: Newcastle and Lake Macquarie, Australia, 1989-1992. SUBJECTS: Between July 1989 and June 1992, 1159 prescription drugs were taken in overdose. Eighty-three drug-related deaths were investigated by the coroner between 1987 and 1992. On 48 occasions a prescription drug was the primary cause of death. RESULTS: Drugs over-represented in self-poisoning (relative to Australian prescriptions) included not only those prescribed for psychiatric conditions (antidepressants, neuroleptics and lithium), but also benzodiazepines, barbiturates and other anticonvulsants. The highest odds ratios for death when adjusted for prescription numbers were for short-acting barbiturates (523.7; 95% confidence interval [CI], 207-1322), chloral hydrate (58.1; 95% CI, 18.1-187), colchicine (27.9; 95% CI, 3.8-202), dextropropoxyphene (20.8; 95% CI, 8.8-48.9), tricyclic antidepressants (13.3; 95% CI, 7.2-24.5) and anticonvulsants (11.6; 95% CI, 4.1-32.2). CONCLUSIONS: Short-acting barbiturates, chloral hydrate and dextropropoxyphene have little or no clinical advantage over alternatives and excessive toxicity in overdose. They should be removed from the market. The toxicity of anticonvulsants and colchicine should be considered when they are prescribed, and smaller amounts per prescription may be advisable for high risk patients using these and other toxic drugs.

Drug Prescriptions↗
PubMed1995

Relative toxicity of benzodiazepines in overdose.

OBJECTIVE: To assess the sedative effects in overdose of temazepam and oxazepam compared with other benzodiazepines to determine if this explains reported differences in fatal toxicity. DESIGN: Cohort study of patients admitted with benzodiazepine poisoning. SETTING: Newcastle, Australia. SUBJECTS: 303 patients who had ingested benzodiazepine alone or in combination with alcohol and presented to a general hospital which served a well defined geographical area. MAIN OUTCOME MEASURES: Degree of sedation: Glasgow coma score, McCarron Score, and whether patients were stuporose or comatose. RESULTS: Oxazepam produced less and temazepam more sedation than other benzodiazepines. Unadjusted odds ratios for coma with oxazepam and temazepam compared with other benzodiazepines were 0.0 (95% confidence interval 0.0 to 0.85) and 1.86 (0.68 to 4.77) respectively, chi 2 = 7.08, 2df, P = 0.03. After adjustment for potentially confounding effects of age, dose ingested, and coingestion of alcohol, the odds ratios were 0.22 (0.0 to 1.43) for oxazepam and 1.94 (0.57 to 6.23) for temazepam. Similar results were obtained for other measures of sedation. CONCLUSIONS: These results were in accordance with fatal toxicity indices derived from coroners' data on mortality and rates of prescription. The relative safety of benzodiazepines in overdose should be a consideration when they are prescribed.

Adolescent↗
PubMed1995

Barbiturate withdrawal--a nomogram for supplementary dosing after the phenobarbitone loading technique.

A case of a woman who presented with a multiple drug overdose and then subsequently had a withdrawal syndrome complicated by seizures and delirium highlights the seriousness of the barbiturate withdrawal syndrome. The patient had a short elimination half-life for phenobarbitone and required supplementary phenobarbitone doses to prevent and treat these complications. We have devised a nomogram which in conjunction with serum levels allows a rapid determination of whether and how much supplementary doses are required during barbiturate withdrawal.

Journal Article↗
PubMed1995

Hypertensive and normal pregnancy: a longitudinal study of blood pressure, distensibility of dorsal hand veins and the ratio of the stable metabolites of thromboxane A2 and prostacyclin in plasma.

OBJECTIVE: By combining serial measurements of the circulating concentrations of thromboxane A2 and prostacyclin with measurements of venous distensibility (taken during the pregnancies of both normal women and those with pregnancy induced hypertension or pre-eclampsia), to test the following hypotheses: 1. that changes in the venous plasma ratio of thromboxane (TXB2) and 6-keto-PGF1 alpha would correlate with changes in the blood pressure of women developing and recovering from pregnancy induced hypertension or pre-eclampsia and 2. that changes in venous distensibility would correlate with changes in arterial blood pressure in pregnancy induced hypertension or pre-eclampsia. DESIGN: Prospective, longitudinal cohort study. SETTING: John Hunter Hospital clinic, Newcastle, Australia. SUBJECTS: One hundred and sixty primiparous women, recruited when presenting for their first routine antenatal visit, were investigated at, or close to, 19, 28 and 37 weeks of gestation; a subgroup was also studied in the postnatal period. The measurements of the patients who developed pregnancy induced hypertension or pre-eclampsia were compared with those of controls selected from the cohort. MAIN OUTCOME MEASURES: Serial measurements of the circulating concentrations of the stable metabolites of thromboxane A2 and prostacyclin (TXB2 and 6-keto-PGF1 alpha, respectively), venous distensibility and immediate (no rest) and resting (for at least 30 min) blood pressures. RESULTS: There was no significant difference between the subject and control groups at any time during or after the pregnancy in the concentrations of prostaglandin metabolites, their ratio or venous distensibility. In contrast, there was a significant difference between the groups at 19 weeks for immediate and resting readings of diastolic pressure (6 mmHg (95% CI 1.5 to 10.5) and 4 mmHg (95% CI 0.1 to 7.9), respectively). These differences increased through the pregnancy but mean postnatal readings for the groups were almost identical suggesting that the subjects were not intrinsically hypertensive compared with controls. Blood pressures for the subject group, both immediate and resting, were significantly different from the 19 week readings at 28 weeks (diastolic) and at 37 weeks (systolic and diastolic). The only significant change from first readings among controls was in postnatal systolic pressure which was significantly higher than 19 week values, probably reflecting the vasodilatation, with accompanying hypotension, of early, normal pregnancy. This difference was not observed in those who subsequently developed pregnancy induced hypertension or pre-eclampsia. CONCLUSIONS: Our study was unable to demonstrate differences in circulating metabolites or venous distensibility between normotensive women and those with pregnancy induced hypertension or pre-eclampsia. If pregnancy induced hypertension or pre-eclampsia in humans represents not so much the presence of abnormal constrictor influences as a process initiated by failure of normal vasodilatation in early pregnancy, studies carried out later may detect mainly adaptive and secondary changes.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

Controlled release drugs in overdose. Clinical considerations.

The main characteristic of overdose with controlled release formulations is the delay in presentation and onset of clinical effects. There is a prolonged absorption phase which leads to a delayed time to maximum plasma concentration and usually a prolonged time with levels close to the peak concentration. Absorption may continue for more than 24 hours. Overdose with controlled release formulations of toxic drugs therefore requires a longer period of observation as the onset of symptoms may be as late as 16 to 20 hours after ingestion. Treatment nomograms calculated for standard formulations are not appropriate for controlled release formulations. The optimal gastrointestinal decontamination method is controversial, but in serious overdoses it should include gastric lavage and activated charcoal followed by whole bowel irrigation as a means of clearing whole tablets from the gastrointestinal tract. Pharmacobezoar formation should be suspected if, despite apparently effective gastrointestinal decontamination, there is evidence of continuing absorption. These are best diagnosed with endoscopy and the treatment options include endoscopic removal, whole bowel irrigation and surgery.

Biological Availability↗
PubMed1995

Cardiotoxicity more common in thioridazine overdose than with other neuroleptics.

On the basis of case reports and small non-comparative series it has been suggested that thioridazine has greater cardiotoxicity in overdose. Limited evidence also suggests an increased association with sudden death in therapeutic doses. The aim of our study is to examine the clinical and electrocardiographic features associated with neuroleptic poisoning and compare thioridazine with other neuroleptics. Consecutive adult patients with neuroleptic poisoning presenting to metropolitan hospitals in Newcastle between 1987 and 1993 were studied. The main outcome measures examined were ECG changes (QRS, QT and QTc intervals), arrhythmias, seizures, degree of sedation, heart rate and blood pressure. Two-hundred ninety-nine patients had ingested thioridazine (104), chlorpromazine (69), trifluoperazine (36), pericyazine (35), haloperidol (33), prochlorperazine (18), fluphenazine (8), or other neuroleptics (7). Sixteen patients had ingested more than one neuroleptic and were excluded from comparative analysis. Thioridazine was more likely to cause tachycardia (odds ratio 1.7, 95% CI 1.1-2.9, p = 0.03), a prolonged QT interval (odds ratio 5.2, 95% CI 1.6-17.1, p = 0.006), prolonged QTc > 450 ms1/2 (odds ratio 4.7, 95% CI 2.7-7.9, p = 0.001), a widened QRS (> 100 ms) (odds ratio 3.1, 95% CI 1.5-6.3, p = 0.001) and arrhythmias (odds ratio infinity, 95% CI 2.4- infinity, p = 0.004). There were no significant differences in the odds of coma (odds ratio 0.5 (0.2-1.5)), hypotension (odds ratio 0.9 (0.4-1.9)) or seizures (odds ratio 3.9 (0.3-43.5)). Adjustment for age, sex, dose ingested and co-ingestion of tricyclic antidepressants or lithium had no major effect on the odds ratios observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Magnesium sulfate in the treatment of ventricular arrhythmias due to digoxin toxicity.

Although digoxin antibodies are the definitive treatment of cardiac arrhythmias due to digoxin toxicity, magnesium can also be effective especially with low serum magnesium levels. The case report describes a patient with digoxin toxicity, ventricular tachycardia and a slightly elevated serum magnesium. Two 10 mmol doses of intravenous magnesium sulfate were associated with a more stable junctional rhythm with bigeminy. Magnesium is known to suppress early after depolarizations, and in supraphysiological doses, may act as an indirect antagonist of digoxin at the sarcolemma Na(+)-K(+)-ATPase pump. Intravenous magnesium may be used to treat cardiac arrhythmias due to digoxin poisoning where there is likely to be a delay in the availability of digoxin antibodies, even in the presence of elevated serum magnesium.

Aged↗