PubMed Health⌕ Search

Biomedical subjects

Nicholas A Buckley

Publications and source records attributed to Nicholas A Buckley.

At least 19 recordsLinked to original sources
PubMed2005

Serotonin syndrome induced by fluvoxamine and oxycodone.

OBJECTIVE: To report a case of severe serotonergic symptoms following the addition of oxycodone to fluvoxamine. CASE SUMMARY: A 70-year-old woman developed severe serotonergic features, including confusion, nausea, fever, clonus, hyperreflexia, hypertonia, shivering, and tachycardia, following the addition of oxycodone 40 mg twice daily to fluvoxamine 200 mg/day, easily fulfilling diagnostic criteria for serotonin syndrome. Discontinuation of the offending drugs resulted in resolution of her symptoms over 48 hours, and no other cause of the syndrome was identified. Use of the Naranjo probability scale indicated a probable relationship between the serotonergic symptoms and the addition of oxycodone to fluvoxamine therapy. DISCUSSION: Serotonin syndrome is a serious adverse reaction usually due to interactions with serotonergic drugs. There have been only 3 previous reports involving oxycodone. Most previous reports of serotonin syndrome involving analgesics have been associated with meperidine, dextromethorphan, and tramadol. Unlike these synthetic opioids, however, oxycodone does not inhibit the reuptake of serotonin. In addition, there are a number of other possible pharmacologic mechanisms for the interaction we observed. CONCLUSIONS: Monitoring for serotonergic adverse events should be done when oxycodone is given to patients receiving serotonin-reuptake inhibitors.

Aged↗
PubMed2005

Life-threatening interaction between complementary medicines: cyanide toxicity following ingestion of amygdalin and vitamin C.

OBJECTIVE: To describe a case of severe accidental cyanide poisoning following a single ingestion of amygdalin with therapeutic intent. CASE SUMMARY: A 68-year-old patient with cancer presented to the emergency department shortly after her first dose (3 g) of amygdalin with a reduced Glasgow Coma Score, seizures, and severe lactic acidosis requiring intubation and ventilation. The patient also ingested 4800 mg of vitamin C per day. She responded rapidly to hydroxocobalamin treatment. The adverse drug reaction was rated probable on the Naranjo probability scale. DISCUSSION: Amygdalin and laetrile (a synthetic form of amygdalin) are commonly used as complementary or alternative medicine (CAM) for the treatment of cancer. Vitamin C is known to increase the in vitro conversion of amygdalin to cyanide and reduce body stores of cysteine, which is used to detoxify cyanide. Amygdalin has been used for decades by patients with cancer who are seeking alternative therapies, and severe reactions have not been reported with this dose. An interaction with vitamin C is a plausible explanation for this life-threatening response. CONCLUSIONS: This case highlights the fact that CAMs can produce life-threatening toxicity. This case also adds a further note of caution, namely, the potential for serious interactions between CAMs, particularly where there is no tradition of concomitant use.

Acidosis↗
PubMed2005

Hyperbaric oxygen for carbon monoxide poisoning : a systematic review and critical analysis of the evidence.

Poisoning with carbon monoxide (CO) is an important cause of unintentional and intentional injury worldwide. Hyperbaric oxygen (HBO) enhances CO elimination and has been postulated to reduce the incidence of neurological sequelae. These observations have led some clinicians to use HBO for selected patients with CO poisoning, although there is considerable variability in clinical practice. This article assesses the effectiveness of HBO compared with normobaric oxygen (NBO) for the prevention of neurological sequelae in patients with acute CO poisoning. The following databases were searched: MEDLINE (1966 to present), EMBASE (1980 to present), and the Controlled Trials Register of the Cochrane Collaboration, supplemented by a manual review of bibliographies of identified articles and discussion with recognised content experts. All randomised controlled trials involving people acutely poisoned with CO, regardless of severity, were examined. The primary analysis included all trials from which data could be extracted. Sensitivity analysis examined trials with better validity (defined using the validated instrument of Jadad) and those enrolling more severely poisoned patients. Two reviewers independently extracted from each trial, including information on the number of randomised patients, types of participants, the dose and duration of the intervention, and the prevalence of neurological sequelae at follow-up. A pooled odds ratio (OR) for the presence of neurological symptoms at 1-month follow-up was calculated using a random effects model. Bayesian models were also investigated to illustrate the degree of certainty about clinical effectiveness. Eight randomised controlled trials were identified. Two had no evaluable data and were excluded. The remaining trials were of varying quality and two have been published only as abstracts. The severity of CO poisoning varied among trials. At 1-month follow-up after treatment, sequelae possibly related to CO poisoning were present in 242 of 761 patients (36.1%) treated with NBO, compared with 259 of 718 patients (31.8%) treated with HBO. Restricting the analysis to the trials with the highest quality scores or those that enrolled all patients regardless of severity did not change the lack of statistical significance in the outcome of the pooled analysis. We found empiric evidence of multiple biases that operated to inflate the benefit of HBO in two positive trials. In contrast, the interpretation of negative trials was hampered by low rates of follow-up, unusual interventions for control patients and inclusion of less severely poisoned patients. Collectively, these limitations may have led negative trials to overlook a real and substantial benefit of HBO (type II error). There is conflicting evidence regarding the efficacy of HBO treatment for patients with CO poisoning. Methodological shortcomings are evident in all published trials, with empiric evidence of bias in some, particularly those that suggest a benefit of HBO. Bayesian analysis further illustrates the uncertainty about a meaningful clinical benefit. Consequently, firm guidelines regarding the use of HBO for patients with CO poisoning cannot be established. Further research is needed to better define the role of HBO, if any, in the treatment of CO poisoning. Such research should not exclude patients with severe poisoning, have a primary outcome that is clinically meaningful and have oversight from an independent data monitoring and ethics committee.

Carbon Monoxide Poisoning↗
PubMed2004

A meta-analysis of prognostic indicators to predict seizures, arrhythmias or death after tricyclic antidepressant overdose.

OBJECTIVES: To systematically review and summarize studies on the accuracy of ECG and tricyclic antidepressant (TCA) concentration as prognostic indicators of the risk of seizures, ventricular arrhythmia (VA) or death in patients with TCA overdose. METHODS: Articles were identified with MedLine and Cochrane register of controlled clinical trials searches and review of medical toxicology textbooks. Quality of the included studies was assessed. Pooled estimates of sensitivity, specificity, likelihood ratios and Summary Receiver Operating Characteristics (SROC) curves were generated. RESULTS: A total of 18 studies were included in the analysis. The pooled sensitivity (Se) and specificity (Sp) of the QRS for predicting seizures were 0.69 [95% CI 0.57-0.78] and 0.69 [95% CI 0.58-0.78] as compared to 0.75 [95% CI 0.61-0.85] and 0.72 [95% CI 0.61-0.81] for the TCA concentration. The Se and Sp of the QRS to predict VA were 0.79 [95% CI 0.58-0.91] and 0.46 [95% CI 0.35-0.59] compared to 0.78 [95% CI 0.56-0.90] and 0.57 [95% CI 0.46-0.67] for the TCA concentration. The Se and Sp of the QRS to predict death were 0.81 [95% CI 0.54-0.94] and 0.62 [95% CI 0.55-0.68] compared to 0.76 [95% CI 0.49-0.91] and 0.60 [95% CI 0.47-0.72] for the TCA concentration. Very few studies evaluated the accuracy of QTc, T 40 ms axis and the R/S ratio. CONCLUSIONS: Overall, the studies suggested that the ECG and TCA concentration have similar but relatively poor performance for predicting complications, such as seizures, VA or death, associated with TCA overdose.

Antidepressive Agents, Tricyclic↗
PubMed2004

Changes in fatalities due to overdose of anxiolytic and sedative drugs in the UK (1983-1999).

OBJECTIVE: To establish the frequency with which anxiolytic and sedative drugs result in fatal poisonings and to examine longitudinal changes in poisoning deaths. METHOD: The number of fatal poisonings between 1983 and 1999 in England, Scotland and Wales due to a single anxiolytic or sedative drug was obtained from the Department of Health in the UK. This was divided by the number of prescriptions for these drugs in England and Scotland to derive a fatal toxicity index (FTI) of deaths per million prescriptions. RESULTS: Chloral hydrate, clomethiazole, barbiturates, and related sedatives had much higher FTIs than benzodiazepines, buspirone, zolpidem and zopiclone. There has been a substantial reduction in the annual number of deaths from sedative drug poisoning between 1983 and 1999. This has been due to a sustained reduction in prescriptions for high toxicity drugs and more recently a major reduction in temazepam deaths that coincided with the withdrawal of gelatin capsule formulations. CONCLUSION: Deaths would be expected to be further reduced if there were reduced prescriptions of high toxicity drugs--and the continuing need for short-acting barbiturates, clomethiazole and chloral hydrate should be questioned.

Anti-Anxiety Agents↗
PubMed2003

The limited utility of electrocardiography variables used to predict arrhythmia in psychotropic drug overdose.

OBJECTIVE: The aim of the present study was to examine the relationship between serious arrhythmias in patients with psychotropic drug overdose and electrocardiography (ECG) findings that have been suggested previously to predict this complication. METHODS: Thirty-nine patients with serious arrhythmias (ventricular tachycardia, supraventricular tachycardia or cardiac arrest) after tricyclic antidepressant overdose or thioridazine overdose were compared with 117 controls with clinically significant overdose matched to each case for the drug ingested. These patients with psychotropic drug overdose had presented for treatment to the Department of Clinical Toxicology, Newcastle and to the Princess Alexandra Hospital, Brisbane. The heart rate, the QRS width, the QTc and QT intervals, the QT dispersion, and the R wave and R/S ratios in aVR on the initial ECGs were compared in cases and controls. RESULTS: The cases had taken dothiepin (16 patients), doxepin (six patients), thioridazine (five patients), amitriptyline (five patients), nortriptyline (three patients), imipramine (one patient) and a combination of dothiepin and thioridazine (three patients). In 20 of the 39 patients with arrhythmias, the arrhythmia had been a presumed ventricular tachycardia. Of the other 19 patients, 15 patients had a supraventricular tachycardia, two patients had cardiac arrests (one asystole, one without ECG monitoring) and two patients had insufficient data recorded to make classification of the arrhythmias possible. The QRS was >/= 100 ms in 82% of cases but also in 76% of controls. QRS >/= 160 ms had a sensitivity of only 13% and occurred in 2% of controls. QRS > 120 ms, QTc > 500 and the R/S ratio in aVR appeared to have a stronger association with the occurrence of arrhythmia: QRS > 120 ms (odds ratio [OR], 3.56; 95% confidence interval [CI], 1.46-8.68), QTc > 500 (OR, 3.07; 95% CI, 1.33-7.07), and R/S ratio in aVR > 0.7 (OR, 16; 95% CI, 3.47-74). Excluding thioridazine overdoses and performing the analysis for tricyclic antidepressant overdoses alone gave increased odds ratios for QRS > 120 ms (OR, 4.83; 95% CI, 1.73-13.5) and QTc > 500 (OR, 4.5; 95% CI, 1.56-13) but had little effect on that for the R/S ratio in aVR > 0.7 (OR, 14.5; 95% CI, 3.10-68). CONCLUSION: ECG measurements were generally weakly related to the occurrence of arrhythmia and should not be used as the sole criteria for risk assessment in tricyclic antidepressant overdose. The frequently recommended practice of using either QRS >/= 100 ms or QRS >/= 160 ms to predict arrhythmias is not supported by our study. R/S ratio in aVR > 0.7 was most strongly related to arrhythmia but had estimated positive and negative predictive values of only 41% and 95%, respectively. The use of these specific predictors in other drug overdoses is not recommended without specific studies.

Adolescent↗
PubMed2003

Of consents and CONSORTs: reporting ethics, law, and human rights in RCTs involving monitored overdose of healthy volunteers pre and post the "CONSORT" guidelines.

Randomized controlled trials (RCTs) of therapeutic interventions in acute drug overdose present a significant challenge for ethical, legal, and human rights protections of research subjects, particularly when healthy volunteers are involved. The CONSORT statement on the uniform reporting of clinical trials was published in 1996 with the overall aim of improving the reporting of RCTs, both individually and to facilitate their inclusion into systematic reviews. In CONSORT, reporting of ethical, legal, and human rights protections, including prior evaluation of the study by an ethics committee and provision of informed consent, was largely an implicit requirement. Those drafting CONSORT may have assumed such protections and the rights of study subjects were secured by existing doctor-patient relationships. Alternatively, CONSORT may have been viewed as likely to indirectly enhance such protections, as a flow-on effect of improved RCT design and reporting. We wished to examine whether such assumptions were justified by examining the reporting of RCTs of simulated overdose in healthy volunteers. We reviewed all reported RCTs involving activated charcoal in healthy human volunteersfor three years before the CONSORT statement (1989, 1990, and 1991) and three years afterwards (1999, 2000, 2001). Presence of documentation of inclusion and exclusion criteria, stopping rules, protocol deviations, information sheets, consent documentation, ethical approvals, conflicts of interest, understanding, refusal, inducements and coercion were recorded. We found a very poor level of reporting of some key ethical, legal, and human rights protections for healthy volunteers in toxicological RCTs. Reporting did not improve with the publication of CONSORT even in relation to requirements specifically included in the guidelines.

Antidotes↗
PubMed2003

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

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

Administration, Topical↗
PubMed2003

'Atypical' antidepressants in overdose: clinical considerations with respect to safety.

The 'atypical' antidepressants comprise a heterogenous class with wide variation in presentation and management during overdose, both when compared with each other and with more traditional agents.Further toxico-epidemiological data are required to make definitive predictions about the clinical effects of most of these agents in overdose. Here, however, we review the available information in a manner intended to benefit both prescribers and clinical toxicologists. Our conclusion is that there can be no generic response by medical practitioners as to the 'safety' of these new antidepressants. Though undoubtedly exhibiting fewer problems in specific areas than some of the older classes of agents (e.g. arrhythmias with tricyclic antidepressants) each nonetheless presents unique safety problems. We experienced great difficulty obtaining accurate information from the manufacturers about the animal toxicity data upon which their recommended human dose limits were set. This highlights the uncertainties involved with too readily making 'safety' claims about these agents. The decision to prescribe 'atypical' antidepressant medications alleged to be both efficacious and safe in overdose involves a medicolegal tension. This tension is between respecting patient autonomy through frank communication of the material risk of overdose and non-disclosure to avoid such harm.

Antidepressive Agents↗
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↗
PubMed2002

Should a lower treatment line be used when treating paracetamol poisoning in patients with chronic alcoholism?: a case for.

A lower threshold for treatment of paracetamol (acetaminophen) poisoning has been advocated in chronic heavy users of alcohol, based originally on animal studies indicating that chronic alcohol ingestion increased hepatotoxicity. This was attributed to increased production of the toxic metabolite, N-acetyl-p-benzoquinoneimine, by cytochrome P450 (CYP)2E1 induction. The clinical evidence for increased risk is limited to four retrospective studies with potential for referral and reporting bias and conflicting results. No study has specifically addressed the issue of the treatment threshold for acute paracetamol overdose in chronic alcohol users. However, animal studies in multiple species have consistently shown a lower dose of paracetamol is required to produce hepatotoxicity after chronic alcohol use. The knowledge of potential mechanisms has expanded to include effects of other alcohols, such as isopentanol, induction of CYP enzymes other than CYP2E1 and glutathione depletion. There are no convincing reasons or data to suggest these findings do not apply to humans. However, further human toxicokinetic and clinical research is required to quantify the extent of the interaction. Arguments about treating overdoses should not be confused with those about whether there is an alcohol-paracetamol interaction at therapeutic doses. Halving the threshold dose/concentration for treatment is a conservative educated guess that has been widely adopted. In overdose, the potential benefits of treatment at this lower threshold clearly outweigh the minimal risks of acetylcysteine.

Acetaminophen↗