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Biomedical subjects

Ian M Whyte

Publications and source records attributed to Ian M Whyte.

At least 37 records · Page 2Linked to original sources
PubMed2003

Moclobemide poisoning: toxicokinetics and occurrence of serotonin toxicity.

AIMS: To investigate the spectrum of toxicity of moclobemide overdose, the occurrence of serotonin toxicity, and to estimate toxicokinetic parameters. METHODS: All moclobemide overdoses presenting over a 10-year period to the Hunter Area Toxicology Service were reviewed. Clinical features, complications, length of stay (LOS) and intensive care (ICU) admission rate were extracted from a standardized, prospectively collected database. Comparisons were made between moclobemide alone and moclobemide with a serotonergic coingestant poisoning. Serotonin toxicity was defined by a combination of Sternbach's criteria and a clinical toxicologist's diagnosis. In five patients serial moclobemide concentrations were measured. Time to maximal plasma concentration (Tmax), peak plasma concentration (Cmax) and terminal elimination half-lives were estimated. RESULTS: Of 106 included patients, 33 ingested moclobemide alone, 21 ingested moclobemide with another serotonergic agent (in some cases in therapeutic doses) and 52 ingested moclobemide with a nonserotonergic agent. Eleven (55%) of 21 patients coingesting a serotonergic drug developed serotonin toxicity, which was significantly more than one (3%) of 33 moclobemide-alone overdoses (odds ratio 35, 95% confidence interval 4, 307; P < 0.0001). In six of these 21 cases severe serotonin toxicity developed with temperature >38.5 degrees C and muscle rigidity requiring intubation and paralysis. The 21 patients had a significantly increased LOS (34 h) compared with moclobemide alone overdoses (12 h) (P < 0.0001) and a significantly increased ICU admission rate of 57% vs. 3% (P < 0.0001). Time to peak plasma concentration was delayed in two patients where prepeak samples were obtained. Cmax increased slightly with dose, but all three patients ingesting > or = 6 g vomited or had charcoal. The mean elimination half-life of moclobemide in the five patients in whom serial moclobemide concentrations were measured was 6.3 h and elimination was first order in all cases. There was no evidence of a dose-dependent increase in half-life. CONCLUSIONS: The effects of moclobemide alone in overdose are minor, even with massive ingestions. However, moclobemide overdose in combination with a serotonergic agent (even in normal therapeutic doses) can cause severe serotonin toxicity. The elimination half-life is prolonged by two to four times in overdose, compared with that found in healthy volunteers given therapeutic doses. This may be a result of wide interindividual variation in overall elimination, also seen with therapeutic doses, but appears not to be due to saturation of normal elimination pathways.

Adult↗
PubMed2003

Presumed Angel's trumpet (Brugmansia) poisoning: clinical effects and epidemiology.

OBJECTIVE: To investigate the pattern and epidemiology of anticholinergic plant poisoning, and to characterize its time course and clinical features. METHODS: We reviewed all anticholinergic plant poisonings using a prospective database of all poisonings admitted to a major toxicology unit in Australia. All patients that presented with anticholinergic plant poisoning between July 1990 and June 2000 were included. Patient demographics, details of poisoning, diagnostic clinical features, adverse effects (seizures, arrhythmias, hypotension, accidental injury), and treatments required were obtained. Important diagnostic features were analysed and compared to previous studies. RESULTS: Thirty-three patients were presumed to have ingested Brugmansia spp. (Angel's trumpet) based on their description of the plant; median age 18 years (interquartile range 16-20); 82% males. Thirty-one ingested a brewed tea or parts of the plant (flower). Thirty-one used it recreationally. Common clinical features were: mydriasis (100%), mean duration 29 h (SD 13) and delirium (88%) with a mean duration of 18 h (SD 12). Tachycardia only occurred in 11 of the 33 patients (33%). In 24 patients where the time of ingestion was certain, 7 of 8 (88%) patients presenting within 5 h had tachycardia and only 5 out of 16 (31%) presenting after 5 h had tachycardia. There were no deaths, seizures or arrhythmias (excepting tachycardia). One patient had hypotension and two sustained accidental traumatic injuries. Nineteen patients required sedation, mainly with benzodiazepines. Physostigmine was used diagnostically in eight cases. CONCLUSIONS: Anticholinergic plant abuse is sporadic in nature. Most cases were moderate in severity, requiring sedation only, and severe toxicity was rare. Mydriasis and delirium were the commonest features, the later having important implications for management.

Adolescent↗
PubMed2003

Clinical toxinology--where are we now?

Clinical toxinology encompasses a broad range of medical conditions resulting from envenomation by venomous terrestrial and marine organisms, and also poisoning from ingestion of animal and plant toxins. Toxin-related disease is an important cause of morbidity and mortality worldwide, particularly in the tropical and subtropical continents. Snake bite is the single most important toxin-related disease, causing substantial mortality in many parts of Africa, Asia, and the Americas. The most important snake families are Viperidae and Elapidae, causing a range of clinical effects including local necrosis, neurotoxicity, coagulopathy and hemorrhage, myotoxicity and renal toxicity. These effects vary according to geography and group of snake. Arachnid envenomation results mainly in morbidity, particularly scorpion stings which can cause severe systemic envenomation. Spider bite is far less of a problem, and the majority of medically important cases can be attributed to widow spiders (Latrodectus spp.) and recluse spiders (Loxosceles spp.). Marine-related envenomations are common, but severe effects are less so. Plant and mushroom poisoning occur in most parts of the world, but the types and methods of poisoning vary considerably between continents. Management of toxin-related disease is often difficult, and in many cases meticulous supportive care is all that is available. The mainstay of treatment is the use of antivenoms for many envenomations and poisoning, although these do not exist for all dangerous organisms. Unfortunately antivenoms are not an economically viable product, so development and manufacture of these agents have been limited. This is now further worsened by a current shortage of antivenom. There is a need for improvement in the preventionand management of toxin-related disease. This will require well-designed studies to define the extent of the problem, initiatives to improve the prevention and management of these conditions, and development of new, and continuation of current, antivenom supplies.

Animals↗
PubMed2003

Intentional warfarin overdose.

Warfarin toxicity is common and usually results from dose changes or drug interactions. There are few reported cases of intentional overdose. The management of warfarin overdose is usually complicated by the patient using warfarin therapeutically, often for a mechanical heart valve or pulmonary embolus prophylaxis. Untreated patients have a significant bleeding risk, but treatment carries a significant risk of complete reversal of anticoagulation and consequent risk of thrombosis. The objective of this study was to describe warfarin overdoses and complications of treatment and develop a safe approach to management. Three patients are described. Two patients received a single 10-mg dose of vitamin K. Both required anticoagulation, and in one, warfarin resistance persisted for 2 weeks. In a third patient serial INR, factor levels and warfarin concentrations were measured, and incremental doses of vitamin K (up to 7.5 mg) were given based on INR. This patient did not require anticoagulation, and regular warfarin therapy was recommenced after 4 days. Patients intentionally overdosing on warfarin can be classified into three groups based on preexisting indications for warfarin: nontherapeutic, moderate risk, and major risk for thromboembolic complications. All patients should have regular INR measurements (6-hourly) to catch rapid rises. Patients not on warfarin therapeutically can be given 10 mg of vitamin K1 and repeat INRs as an outpatient. Titrating intravenous vitamin K with doses of 0.5 to 2.0 mg when INR > 5 is appropriate to reduce INR without causing warfarin resistance. The high-risk group must be kept anticoagulated, and warfarin resistance avoided.

Adult↗
PubMed2002

Paracetamol recall: a natural experiment influencing analgesic poisoning.

OBJECTIVES: To determine whether the occurrence of paracetamol and non-paracetamol analgesic deliberate self-poisoning (DSP) and accidental paediatric poisoning was affected by two periods of recall of paracetamol products. DESIGN: Retrospective, observational audit of proportions of poisonings with tablet and capsule formulations of paracetamol, ibuprofen and aspirin products during two recall periods compared with the number of poisonings during the same periods of the previous three years. SETTING: A national poisons information centre and a regional toxicology service. MAIN OUTCOME MEASURES: Rates of DSP and accidental paediatric poisoning with paracetamol, ibuprofen and aspirin. RESULTS: During the two recall periods, there was a significant increase in ibuprofen DSP calls to the poisons information centre (RR, 1.86; 95% Cl, 1.41-2.44; P = 0.001). There was no significant change in paracetamol or aspirin DSP calls over the two recall periods. However, there was a non-significant reduction in DSP calls with paracetamol in the first recall period alone (P = 0.057). There was a significant increase in the proportion of aspirin DSP presentations for the toxicology service (RR, 3.33; 95% CI, 0.97-11.4; P = 0.043), but no significant changes in paracetamol and ibuprofen DSP presentations. For accidental paediatric ingestions there was a significant increase in the proportion of ibuprofen calls (RR, 2.35; 95% CI, 1.85-2.98; P = 0.001), but no significant change in paracetamol or aspirin calls. CONCLUSIONS: Reduced paracetamol availability increased poisoning with alternative analgesics, but had little effect on the incidence of paracetamol poisoning. Restriction of paracetamol-containing products may inadvertently increase poisoning with potentially more toxic agents.

Acetaminophen↗
PubMed2002

Two cases of bites by the black-bellied swamp snake (Hemiaspis signata).

We report two cases of envenomation by the black bellied swamp snake, Hemiaspis signata, with expert identification of the snakes. In the first case a 12 year old boy, who after the removal of the pressure immobilisation bandage, developed decreased fibrinogen levels and positive cross-linked fibrinogen degradation products (XDPs), but normal prothrombin time and activated partial prothrombin time. These changes resolved over 8h with no treatment. In the second case a 7 year old boy had local pain, swelling and axillary lymphadenopathy following the bite. These cases indicate the potential for coagulopathy and local symptoms following bites by large specimens of H. signata in young children.

Animals↗
PubMed2002

Development of a Chinese herbal medicine toxicology database.

BACKGROUND: Use of Chinese herbal medicine has increased steadily in the West and adverse reactions have been reported. However, information is not readily available on the toxicity of the herbs and the management of poisoning. The goals of this project were to retrieve and evaluate scientific evidence on the toxicity of Chinese herbal medicine, to grade the toxicity of individual herbs, and to summarize relevant herb data via a searchable electronic database. METHODS: English and Chinese primary studies were systematically retrieved via journal abstracting databases and key toxicity texts. Partial translation of published research was achieved via an audited process utilizing data extraction forms. Methods for grading herb toxicity (in therapeutic use or overdose) were developed based on a combination of the quality of reports, severity of adverse reaction, supporting animal studies, extrapolation from pharmacology and empirical evidence. RESULTS: Good quality studies on the toxicity of Chinese herbs are lacking. In some cases there is insufficient scientific evidence to create an evidence-based grading of the toxicity of individual herbs. Available data have been summarized into detailed monographs. Twelve herb monographs (with a full toxicity profile and grading) have been completed and summary data for all adequate quality papers used in the grading are linked to the monographs. CONCLUSIONS: The resultant database and monographs represent the first reviews specifically on the toxicity of individual Chinese herbs with toxicological grades based on the evidence of published studies. The database and monographs should assist in promoting the safe and effective use of Chinese herbal medicine.

Databases, Factual↗
PubMed2002

Diagnostic data in clinical toxicology--should we use a Bayesian approach?

A number of toxidromes (toxicology syndromes) have been described for various poisonings and are promoted as a means of reaching a diagnosis in patients presenting with unknown poisonings. Many are based entirely on deductive reasoning from the known pharmacological effects of these drugs rather than on documented clinical experience. In this paper, we used our database, where we have recorded clinical signs on presentation in unselected poisonings to explore how clinical signs actually alter the odds of ingestion of different poisons. Many signs substantially altered the list of drugs likely to have been ingested. We found that the most important factor determining whether an unconscious patient had ingested a particular drug was how frequently that drug was taken generally (i.e., the a priori probability), rather than the presence of any particular physical sign. It also follows that our (or anyone else's) intuitive or deductive approach to diagnosis, derived from experience, will not necessarily be very useful at another place where predominantly different drugs are involved in poisoning. Our data were used to derive odds ratios as a measure of the strength of association of physical signs or investigations with ingested poisons. These can be used to develop simple diagnostic algorithms orflow charts to identify the most likely drugs ingested, or using more complicated programming, could also be used to calculate the precise probability of different drug-ingestion using Bayes' Theorem. The usefulness (i.e., external validity) of clinical research from other centers can also be determined.

Adolescent↗
PubMed2002

Data collection in clinical toxicology: are there too many variables?

The evidence base of clinical toxicology suffers in comparison to other clinical disciplines. There is an excess of case reports and case series with little in the way of case control or cohort studies, and very few randomized controlled trials. While randomized controlled trials are rightly regarded as the gold standard for interventional studies, they have limitations that are particularly evident in the practice of clinical toxicology. Properly conducted observational studies using quantitative, epidemiological methods [nonrandomized trials, cohort studies (prospective and retrospective), case control methods] can provide answers that may be impossible to obtain from randomized controlled trials. Development of a strong evidence base is essential for progress in clinical toxicology. Whether that evidence base is derived from randomized controlled trials or observational studies, it is essential to collect data. Important observations can be made from basic clinical data and systematic collection of those data into some form of electronic database has siginificant advantages. A clinical database provides accurate information in the areas of clinical practice, quality assurance (audit), and research. In the area of research, an appropriately designed database can be both a source of hypotheses as well as a vehicle to test them. It can also serve as a repository of research data in subsequent randomized controlled trials.

Confounding Factors, Epidemiologic↗