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A T Proudfoot

Publications and source records attributed to A T Proudfoot.

At least 19 recordsLinked to original sources
PubMed2004

Position Paper on urine alkalinization.

This Position Paper was prepared using the methodology agreed by the American Academy of Clinical Toxicology (AACT) and the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT). All relevant scientific literature was identified and reviewed critically by acknowledged experts using set criteria. Well-conducted clinical and experimental studies were given precedence over anecdotal case reports and abstracts were not considered. A draft Position Paper was then produced and presented at the North American Congress of Clinical Toxicology in October 2001 and at the EAPCCT Congress in May 2002 to allow participants to comment on the draft after which a revised draft was produced. The Position Paper was subjected to detailed peer review by an international group of clinical toxicologists chosen by the AACT and the EAPCCT, and a final draft was approved by the boards of the two societies. The Position Paper includes a summary statement (Position Statement) for ease of use, which will also be published separately, as well as the detailed scientific evidence on which the conclusions of the Position Paper are based. Urine alkalinization is a treatment regimen that increases poison elimination by the administration of intravenous sodium bicarbonate to produce urine with a pH > or = 7.5. The term urine alkalinization emphasizes that urine pH manipulation rather than a diuresis is the prime objective of treatment; the terms forced alkaline diuresis and alkaline diuresis should therefore be discontinued. Urine alkalinization increases the urine elimination of chlorpropamide, 2,4-dichlorophenoxyacetic acid, diflunisal, fluoride, mecoprop, methotrexate, phenobarbital, and salicylate. Based on volunteer and clinical studies, urine alkalinization should be considered as first line treatment for patients with moderately severe salicylate poisoning who do not meet the criteria for hemodialysis. Urine alkalinization cannot be recommended as first line treatment in cases of phenobarbital poisoning as multiple-dose activated charcoal is superior. Supportive care, including the infusion of dextrose, is invariably adequate in chlorpropamide poisoning. A substantial diuresis is required in addition to urine alkalinization in the chlorophenoxy herbicides, 2,4-dichlorophenoxyacetic acid, and mecoprop, if clinically important herbicide elimination is to be achieved. Volunteer studies strongly suggest that urine alkalinization increases fluoride elimination, but this is yet to be confirmed in clinical studies. Although urine alkalinization is employed clinically in methotrexate toxicity, currently there is only one study that supports its use. Urine alkalinization enhances diflunisal excretion, but this technique is unlikely to be of value in diflunisal poisoning. In conclusion, urine alkalinization should be considered first line treatment in patients with moderately severe salicylate poisoning who do not meet the criteria for hemodialysis. Urine alkalinization and high urine flow (approximately 600 mL/h) should also be considered in patients with severe 2,4-dichlorophenoxyacetic acid and mecoprop poisoning. Administration of bicarbonate to alkalinize the urine results in alkalemia (an increase in blood pH or reduction in its hydrogen ion concentration); pH values approaching 7.70 have been recorded. Hypokalemia is the most common complication but can be corrected by giving potassium supplements. Alkalotic tetany occurs occasionally, but hypocalcemia is rare. There is no evidence to suggest that relatively short-duration alkalemia (more than a few hours) poses a risk to life in normal individuals or in those with coronary and cerebral arterial disease.

Alkalies↗
PubMed2000

Mechanisms of toxicity, clinical features, and management of acute chlorophenoxy herbicide poisoning: a review.

INTRODUCTION: Chlorophenoxy herbicides are used widely for the control of broad-leaved weeds. They exhibit a variety of mechanisms of toxicity including dose-dependent cell membrane damage, uncoupling of oxidative phosphorylation, and disruption of acetylcoenzyme A metabolism. Between January 1962 and January 1999, 66 cases of chlorophenoxy herbicide poisoning following ingestion were reported in the literature. FEATURES FOLLOWING INGESTION: Adjuvants in the formulations may have contributed to some of the features observed. Vomiting, abdominal pain, diarrhea, and, occasionally, gastrointestinal hemorrhage were early effects. When present, hypotension was predominantly due to intravascular volume loss, although vasodilation and direct myocardial toxicity may have contributed in some cases. Neurotoxic features included coma, hypertonia, hyperreflexia, ataxia, nystagmus, miosis, hallucinations, convulsions, fasciculation, and paralysis. Hypoventilation occurred not infrequently, usually in association with central nervous system depression, but respiratory muscle weakness was a factor in the development of respiratory failure in some patients. Myopathic symptoms including limb muscle weakness, loss of tendon reflexes, and myotonia were observed and increased creatine kinase activity was noted in some cases. Other clinical features reported included metabolic acidosis, rhabdomyolysis, renal failure, increased aminotransferase activities, pyrexia, and hyperventilation. Twenty-two of 66 patients died. FEATURES FOLLOWING DERMAL AND INHALATIONAL EXPOSURE: Substantial dermal or inhalational 2,4-dichlorophenoxyacetic acid exposure has occasionally led to systemic features but no such reports have been published in the last 20 years and no fatalities have been reported at any time. Substantial dermal exposure has been reported to cause mild gastrointestinal irritation after a latent period followed by progressive mixed sensory-motor peripheral neuropathy. Mild, transient gastrointestinal and peripheral neuromuscular symptoms have also occurred after occupational inhalation exposure, with or without dermal exposure. MANAGEMENT: In addition to supportive care, alkaline diuresis to enhance herbicide elimination should be considered in all seriously poisoned patients. Limited clinical data suggest that hemodialysis produces similar herbicide clearance to alkaline diuresis without the need for urine pH manipulation and the administration of substantial amounts of intravenous fluid in an already compromised patient. CONCLUSIONS: While chlorophenoxy herbicide poisoning is uncommon, ingestion of a chlorophenoxy herbicide can result in serious and sometimes fatal sequelae. In severe cases of poisoning, alkaline diuresis or hemodialysis to increase herbicide elimination should be considered.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1995

Antidotes: benefits and risks.

The ability of naloxone and flumazenil to reverse serious toxicity due to their respective agonists is well known. Their adverse effects are minor and few but flumazenil administration may unmask seizures in poisoning with combinations of benzodiazepines and tricyclic antidepressants. The desferrioxamine challenge test is frequently falsely negative and should be abandoned. In addition to being cytoprotective, N-acetylcysteine has potent vasodilator and positive inotropic actions which may be partly responsible for its beneficial effect in late-presentation paracetamol overdosage with hepatic damage and failure.

Acetylcysteine↗
PubMed1993

Toxicological index of paraquat: a new strategy for assessment of severity of paraquat poisoning in 128 patients.

A new assessment of the severity of paraquat poisoning in 128 patients has been developed. It involves toxicological index of paraquat and discriminant function score. This system not only allows a more accurate assessment of severity of the poisoning, but also provides a more reliable prediction of the outcome in an early stage for the purpose of forensic and clinical toxicology.

Discriminant Analysis↗
PubMed1990

Intravenous N-acetylcysteine, hepatotoxicity and plasma glutathione S-transferase in patients with paracetamol overdosage.

The concentration of glutathione S-transferase B1 (GST B1) subunits was measured in sequential plasma samples taken at frequent intervals for 48 h from ten patients with severe paracetamol poisoning who were treated with intravenous N-acetylcysteine. No significant increase in plasma GST B1 concentration was observed over the study period and with 4 h of starting treatment with N-acetylcysteine there were significant decreases in plasma GST B1 concentrations. None of the patients subsequently developed significant liver damage. At the dose used for the treatment of paracetamol poisoning, N-acetylcysteine has no hepatotoxic effects.

Acetaminophen↗
PubMed1989

The disposition and kinetics of intravenous N-acetylcysteine in patients with paracetamol overdosage.

Seventeen patients received standard treatment with intravenous N-acetylcysteine for 18 episodes of severe poisoning with paracetamol (acetaminophen). The dose of N-acetylcysteine was 150 mg/kg given in 15 min followed by 50 mg/kg in 4 h and 100 mg/kg over the next 16 h. Liver damage was absent or mild on 13 occasions (ALT greater than 500 mu/l) and severe on 5 (ALT less than 1000 mu/l). Total plasma N-acetylcysteine was estimated by HPLC. The mean maximum plasma concentration after the initial loading dose was 554 mg/l. Concentrations then fell rapidly and after 12 h a mean steady-state level of about 35 mg/l was maintained. When the infusion was discontinued N-acetylcysteine disappeared with a half-life of 5.7 h. The mean steady-state volume of distribution, AUC, mean residence time and total clearance were 536 ml/kg, 1748 mg.h.l-1, 2.91 h and 3.18 ml.min-1.kg-1. These values are generally consistent with those previously reported with much smaller doses and the disposition of N-acetylcysteine does not appear to be dose-dependent. The elimination of N-acetylcysteine was not impaired in the patients with severe liver damage, and the pharmacokinetic variables and plasma concentrations were similar in patients with and without hepatotoxicity. The dosage schedule for intravenous N-acetylcysteine should probably be modified since adverse reactions invariably occur early when plasma concentrations are at their highest, and liver damage was prevented just as effectively at the lowest as at the highest Cmax. High initial concentrations of N-acetylcysteine can be avoided with simple alternative regimens based on the kinetic data of this study.

Acetaminophen↗
PubMed1989

Plasma glutathione S-transferase and F protein are more sensitive than alanine aminotransferase as markers of paracetamol (acetaminophen)-induced liver damage.

Concentrations of glutathione S-transferase (GST; glutathione transferase; EC 2.5.1.18) B1 subunits, F protein, and the activity of alanine aminotransferase (ALT; EC 2.6.1.2) were measured in sequential plasma samples taken from nine patients with self-administered paracetamol (acetaminophen) poisoning. GST exceeded the reference interval in all patients at the time of admission, and F protein was increased in seven. In contrast, abnormal activities of ALT in plasma were found in only one of the nine on admission, a patient admitted 12 h after poisoning. Subsequent to admission nine, eight, and five patients, respectively, had abnormal concentrations of GST, F protein, and ALT. When expressed as multiples of the upper reference limit, the highest values for GST measured in each patient always far exceeded the greatest abnormalities in ALT; this was true for F protein in only five patients. Patients in whom the concentration of GST exceeded 10 micrograms/L on admission subsequently went on to develop moderate or severe liver damage, despite treatment with N-acetylcysteine. F protein and ALT measurements on admission were not as efficient as GST at predicting the clinical outcome of the patients. We conclude that GST and F protein offer clear advantages over ALT for detecting minor degrees of acute liver dysfunction, particularly when only centrilobular damage may be involved.

Acetaminophen↗
PubMed1989

Adult salicylate poisoning: deaths and outcome in patients with high plasma salicylate concentrations.

The clinical features, plasma salicylate concentrations, acid-base abnormalities and other biochemical findings are presented for 97 patients who either died from acute salicylate overdosage or survived maximum recorded plasma salicylate concentrations of 700 mg/l or greater. These patients comprised 4 per cent of 2204 cases of salicylate poisoning admitted during the period 1975 to 1985 inclusive. Seven patients died (overall mortality 0.3 per cent); they were significantly older than the survivors, the mortality being as high as 33 per cent in patients over the age of 70 years. Delayed presentation, coma, hyperpyrexia, pulmonary oedema and acidaemia were more common in the fatal cases. Failure to hyperventilate appropriately may contribute to the development of acidaemia. The prognosis of acute salicylate poisoning cannot be determined from the plasma concentration of the drug alone. Clinical features, particularly impaired consciousness, and the arterial hydrogen ion concentration must be taken into consideration. Haemodialysis is the treatment of choice for severe salicylate intoxication and should be used more liberally than it is at present.

Adult↗
PubMed1988

Poisoning treatment centre admissions following acute incidents involving pesticides.

1. Adult hospital admissions following acute exposures to pesticides are very uncommon and are more often due to parasuicide than to accidents. 2. Most accidental pesticide incidents are work-related. 3. Males are more likely to be involved than females (2.9:1). 4. Life-threatening and fatal consequences developed in 24% of 54 incidents. 5. Of the 10 fatalities, eight were caused by paraquat, eight were due to parasuicide and two to non-work related accidents.

Accidents↗
PubMed1988

Clinical toxicology--past, present and future.

1. The alarming increase in the incidence of self-poisoning in Western countries in the 1950s prompted the establishment of the National Poisons Information Service in the UK and the designation of certain Regional Poisoning Treatment Centres. 2. The substances taken in acute poisoning episodes largely reflect the poisons available in the community and, in the UK at least, have changed with fashions in prescribing although psychotropic drugs and analgesics always predominate. 3. Intensive supportive care with repeat-dose oral activated charcoal and even haemoperfusion has been proved effective in acute poisoning with central nervous depressant drugs such as barbiturates even though these latter drugs are now rarely encountered in overdose. 4. Other advances in clinical toxicology include the introduction of the opiate antagonist naloxone, Fab antibody fragments for life-threatening digoxin overdosage and proven treatment for paracetamol poisoning. Analytical toxicology has also made a major contribution. 5. On the debit side, formal psychiatric assessment of patients after acute poisoning remains contentious, tricyclic antidepressants are still a major problem and there is no effective treatment for poisoning with paraquat or for paracetamol when presentation is delayed. 6. As to the future, although the 'epidemic' of serious acute poisoning of the 1960s and 70s appears to be past its peak, there will always be unusual and serious problems and the UK poisons information services must develop to make the best use of computer-based technology.

Humans↗