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Biomedical subjects

I M Whyte

Publications and source records attributed to I M Whyte.

At least 37 records · Page 2Linked to original sources
PubMed2000

Lithium: thyroid effects and altered renal handling.

BACKGROUND: Lithium is frequently used in the treatment of bipolar affective disorder, and is widely known to affect thyroid function, most commonly resulting in hypothyroidism and goiter. Less well-known is the association between lithium therapy and hyperthyroidism and the potential for lithium to moderate the effects of thyroxine at a cellular level. Lithium excretion relates principally to glomerular filtration rate and proximal tubule function. Thyroxine, through its effects on tubular function, alters lithium clearance such that thyroid disease may cause retention of lithium and subsequent toxicity. CASE REPORTS: We report 2 cases with lithium toxicity, both of whom were later found to be hyperthyroid. One patient developed thyroid storm following dialysis to remove lithium. The other received antithyroid medication early. Both suffered a protracted multifactorial delirium requiring intensive inpatient care. CONCLUSION: In addition to altering thyroid function, lithium therapy may mask the signs of hyperthyroidism by inducing cellular unresponsiveness. In some lithium-treated patients with biochemical hyperthyroidism, early antithyroid treatment may be appropriate. Altered renal tubular function induced by hyperthyroidism may result in retention of lithium and systemic toxicity. We propose induction of the proximal tubule sodium hydrogen antiporter as the relevant mechanism.

Adult↗
PubMed2000

Acetaminophen causes an increased International Normalized Ratio by reducing functional factor VII.

Acetaminophen may increase International Normalized Ratio (INR) in patients taking anticoagulation medication, and in patients with acetaminophen poisoning without hepatic injury. The objective of this study was to describe and investigate the effect of acetaminophen on INR. The authors studied patients admitted to a regional toxicology treatment center with acetaminophen poisoning with INR and without potentially confounding coingestion or hepatic injury. Exposed and nonexposed (control) cohorts were recruited from admissions with acetaminophen poisoning and psychotropic drug poisoning, respectively. From 1,437 acetaminophen poisonings, after exclusions, there were 143 admissions with 205 estimations of INR. INR showed a time-dependent increase. Fifty percent of all patients and 66% of those with an extrapolated 4-hour acetaminophen concentration > or = 150 mg/L had an abnormal INR at some time. Dose ingested (p = 0.01) and nomogram-based risk (p for trend = 0.005) were correlated with the effect. N-acetylcysteine had a protective effect. Functional factor VII was lower (p = 0.005) in exposed patients (n = 30) than controls (n = 8), and less than antigenic factor VII in exposed patients (p = 0.03). Factor IX was lower (p = 0.02). Factor VIIIc was not significantly different. The authors concluded that an isolated, small rise in INR is common after acetaminophen poisoning without hepatic injury. It appears to be caused by inhibition of Vitamin K-dependent activation of coagulation factors. This effect suggests a possible mechanism for the observed interaction between acetaminophen and warfarin.

Acetaminophen↗
PubMed1999

Repetition of deliberate self-poisoning in an Australian hospital-treated population.

OBJECTIVES: To describe the hospital-treated prevalences for repeat deliberate self-poisoning (RDSP) and the demographic characteristics of the RDSP group, and to compare the RDSP and non-RDSP groups. DESIGN: Prospective longitudinal cohort study, with a one- to four-year follow-up. SETTING: The Hunter Area Toxicology Service (HATS), a regional toxicology treatment centre in New South Wales. SUBJECTS: 1238 consecutive DSP patients referred to hospital, 1992-1994, with follow-up through 1995. OUTCOME MEASURES: Deliberate self-poisoning (DSP) admissions within one year (RDSP-1), within six months (RDSP-6m), and within 28 days (RDSP-28d) of any other DSP admission by the same patient; length of stay; demographic characteristics; and drugs ingested. RESULTS: 175 patients (14.1%) repeated DSP during the study; 165 (13.3%) were classified as RDSP-1, giving a patient prevalence of hospitalisation in the range of 14.6 to 20.7 per 100,000 per year. Fifty-six RDSP-28d patients (33.9% of RDSP-1) accounted for 49.8% of the RDSP-1 admissions, and 123 RDSP-6m patients (74.5% of RDSP-1) accounted for 83.5% of RDSP-1 admissions. For RDSP-1, the male:female ratio was 1:1.9, with 35.7% unemployed, 29.1% pensioners and 15.8% married or in de facto relationships. RDSP-1 patients had a shorter length of stay (3 h), which was not clinically important. RDSP was more likely for the 25-34 years age group (odds ratio [OR], 2.24; 95% confidence interval [CI], 1.17-4.29) and the 35-44 years age group (OR, 2.12; 95% CI, 1.02-4.39) than the 10-18 years group, and more likely for women than men (OR, 1.69; 95% CI, 1.17-2.46). Being married/de facto reduced the risk for repetition (OR, 0.55; 95% CI, 0.31-0.96) compared with being single. Medications indicated for psychiatric illness were most commonly used for DSP. CONCLUSIONS: Many patients who repeat DSP do so after a very brief interval and account for a disproportionate number of hospitalisations. Availability of psychiatric medications for DSP patients is a possible area of intervention.

Adolescent↗
PubMed1999

Therapeutic drug monitoring in drug overdose.

The treatment of poisoned patients is still largely defined by history, clinical assessment and interpretation of ancillary investigations. Measurement of drug concentrations is clinically important for relatively few compounds. Most measurements form an adjunct to and should not be considered a substitute for clinical assessment. Drug concentrations are particularly important for those compounds where the concentration is predictive of serious toxicity in an otherwise asymptomatic patient.

Acetaminophen↗
PubMed1999

Activated charcoal reduces the need for N-acetylcysteine treatment after acetaminophen (paracetamol) overdose.

BACKGROUND: The evidence for efficacy of gastric lavage and activated charcoal for gastrointestinal decontamination in poisoning has relied entirely on volunteer studies and/or pharmacokinetic studies and evidence for any clinical benefits or resource savings is lacking. AIM OF STUDY: To investigate the value of gastrointestinal decontamination using gastric lavage and/or activated charcoal in acetaminophen (paracetamol) poisoning. PATIENTS AND METHODS: We analyzed a series of 981 consecutive acetaminophen poisonings. These patients were treated with gastric lavage and activated charcoal, activated charcoal alone, or no gastrointestinal decontamination. The decision as to which treatment was received was determined by patient cooperation, the treating physician, coingested drugs, and time to presentation after the overdose. RESULTS: Of 981 patients admitted over 10 years, 10% (100) had serum concentrations of acetaminophen that indicated a probable or high risk of hepatotoxicity. The risk of toxic concentrations for patients ingesting less than 10 g of acetaminophen was very low. In patients presenting within 24 hours, who had ingested 10 g or more, those who had been given activated charcoal were significantly less likely to have probable or high risk concentrations (Odds ratio 0.36, 95% CI 0.23-0.58, p < 0.0001). Gastric lavage, in addition to activated charcoal, did not further decrease the risk (Odds ratio 1.12, 95% CI 0.57-2.20, p = 0.86). CONCLUSIONS: Toxic concentrations of serum acetaminophen (paracetamol) are uncommon in patients ingesting less than 10 g. In those ingesting more, activated charcoal appears to reduce the number of patients who achieve toxic acetaminophen concentrations and thus may reduce the need for treatment and hospital stay.

Acetaminophen↗
PubMed1999

Oral or intravenous N-acetylcysteine: which is the treatment of choice for acetaminophen (paracetamol) poisoning?

BACKGROUND: The optimal route and duration of administration for N-acetyl-cysteine in the management of acetaminophen (paracetamol) poisoning are controversial. It has been stated on the basis of a selected post-hoc analysis that oral N-acetylcysteine is superior to intravenous N-acetylcysteine in presentations later than 15 hours. AIM OF STUDY: To investigate the efficacy of intravenous or oral N-acetylcysteine. PATIENTS AND METHODS: We analyzed a series of acetaminophen poisonings treated with a protocol including activated charcoal and intravenous N-acetylcysteine. The outcomes assessed included use of N-acetylcysteine, adverse effects of intravenous N-acetylcysteine, and the occurrence of hepatotoxicity (transaminase > 1000 U/L). We incorporated these results in a meta-analysis of previously reported series of acetaminophen poisonings to compare the outcomes from intravenous and oral N-acetylcysteine use. RESULTS: Of 981 patients admitted over 10 years, 4% (40) presented later than 24 hours and 10% (100) had concentrations of acetaminophen that indicated a probable or high risk of hepatotoxicity. The 30 patients who developed hepatotoxicity presented later, took larger amounts, had higher concentrations, and received N-acetylcysteine later than those who did not. No patients received a liver transplant but 2 patients died (one after referral to a transplant unit and one just before). Adverse reactions to intravenous N-acetylcysteine occurred in 6% (12/205) of patients but none prevented completion of the treatment. In the meta-analysis, those with probable or high risk concentrations had similar outcomes with intravenous (pooled n = 341) and oral N-acetylcysteine (pooled n = 1462) administration. Rates of hepatotoxicity for those treated within 10 hours (3 and 6%), late (10-24 hours: 30 and 26%), and overall (0-24 hours: 16 and 19%) were all similar. The proportion of patients classified as presenting later than 10 hours is much greater in the oral N-acetylcysteine studies (64%) than in many of the intravenous N-acetylcysteine studies (38%, 44%, and 63%). CONCLUSIONS: The differences claimed between oral and intravenous N-acetylcysteine regimes are probably artifactual and relate to inappropriate subgroup analysis. A shorter hospital stay, patient and doctor convenience, and the concerns over the reduction in bioavailability of oral N-acetylcysteine by charcoal and vomiting make intravenous N-acetylcysteine preferable for most patients with acetaminophen poisoning.

Acetaminophen↗
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

Serotonin syndrome resulting from drug interactions.

We describe six patients diagnosed with serotonin syndrome after exposure to drugs with serotonergic activity. Drug interactions occurred as a result of a combination of tricyclic antidepressants, selective serotonin reuptake inhibitors, selective noradrenaline reuptake inhibitors or monoamine oxidase inhibitors. Management included supportive care and the use of non-specific serotonin antagonists (cyproheptadine, benzodiazepines and chlorpromazine). All patients made uneventful recoveries.

Adolescent↗
PubMed1998

Features and toxicokinetics of clozapine in overdose.

One hundred patients were commenced on clozapine in the Hunter region of Australia from July 1993 to September 1995. Of these, one ingested clozapine as a self-poisoning on two occasions. Over the same period, there were four other self-poisonings with clozapine in the region. Another case from a different region is described. The cases were identified from the Hunter Area Toxicology Service Database and regional psychiatric hospitals. The severity of the poisoning is related to prior exposure and tolerance. Marked sedation at relatively low doses occurred in the absence of prior exposure. No reversible electrocardiographic changes or biochemical abnormalities were demonstrated. Anticholinergic effects were minimal. All seven cases made full recovery. A high-pressure liquid chromatography (HPLC) method for assaying clozapine and its major metabolite, norclozapine, in plasma is described. Approximate retention times were norclozapine, 3.8 minutes; clozapine, 5 minutes; and propyl-norclozapine, 7 minutes. The lower limit of analysis for this assay was 20 ng/ml for clozapine and the metabolite. Using the HPLC assay, serial clozapine and norclozapine plasma concentrations were measured in three of these cases of clozapine self-poisoning. Toxicokinetic modeling was conducted by simultaneous analysis of clozapine and norclozapine observations. A two-compartment model with a metabolite compartment attached to the central compartment was used. Clozapine metabolism to norclozapine was best described by linear elimination of norclozapine and nonlinear norclozapine formation. The Km (1918 +/- 2093 micrograms/l) relative to observed concentration (3396 +/- 962 micrograms/l) suggests that norclozapine formation was saturated at the time of the first observation.

Adult↗
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

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↗