Isopropanol poisoning.

INTRODUCTION: Isopropanol is a clear, colorless liquid with a fruity odor and a mild bitter taste. Most commonly found domestically as rubbing alcohol, isopropanol is also found in numerous household and commercial products including cleaners, disinfectants, antifreezes, cosmetics, solvents, inks, and pharmaceuticals. AIM: The aim of this review is to critically review the epidemiology, toxicokinetics, mechanisms of toxicity, clinical features, diagnosis, and management of isopropanol poisoning. METHODS: OVID MEDLINE and ISI Web of Science were searched to November 2013 using the words "isopropanol", "isopropyl alcohol", "2-propanol", "propan-2-ol", and "rubbing alcohol" combined with the keywords "poisoning", "poison", "toxicity", "ingestion", "adverse effects", "overdose", or "intoxication". These searches identified 232 citations, which were then screened via their abstract to identify relevant articles referring specifically to the epidemiology, toxicokinetics, mechanisms of toxicity, clinical features, diagnosis, and management of isopropanol poisoning; 102 were relevant. Further information was obtained from book chapters, relevant news reports, and internet resources. These additional searches produced eight non-duplicate relevant citations. EPIDEMIOLOGY: The majority of isopropanol exposures are unintentional and occur in children less than 6 years of age. Although isopropanol poisoning appears to be a reasonably common occurrence, deaths are rare. TOXICOKINETICS: Isopropanol is rapidly absorbed following ingestion with peak plasma concentrations occurring within 30 min. It can also be absorbed following inhalation or dermal exposure. Isopropanol is widely distributed with a volume of distribution of 0.45-0.55 L/kg. Isopropanol is metabolized by alcohol dehydrogenase to acetone, acetol and methylglyoxal, propylene glycol, acetate, and formate with conversion of these metabolites to glucose and other products of intermediary metabolism. The elimination of isopropanol is predominantly renal, though some pulmonary excretion of isopropanol and acetone occurs. In one case 20% of the absorbed dose was eliminated unchanged in urine, with the remainder excreted as acetone and metabolites of acetone. The elimination half-life of isopropanol is between 2.5 and 8.0 h, whereas elimination of acetone is slower with a half-life following isopropanol ingestion of between 7.7 and 27 h. MECHANISMS OF TOXICITY: While the exact mechanism of action of isopropanol has not been fully elucidated, brain stem depression is thought to be the predominant mechanism. While the clinical effects are thought to be mostly due to isopropanol, acetone may also contribute. CLINICAL FEATURES: The major features of severe poisoning are due to CNS and respiratory depression, shock, and circulatory collapse. The most common metabolic effects are an increased osmol (osmolal) gap, ketonemia, and ketonuria. Diagnosis. Poisoning can be diagnosed using the measurement of isopropanol serum concentrations, though these may not be readily available. Diagnosis is therefore more typically made on the basis of the patient's history and clinical presentation. An osmol gap, ketonemia, and/or ketonuria without metabolic acidosis, along with a fruity or sweet odor on the breath and CNS depression support the diagnosis. Management. Supportive care is the mainstay of management with primary emphasis on respiratory and cardiovascular support. Hemodialysis enhances elimination of isopropanol and acetone and should be considered in very severe poisoning. CONCLUSIONS: Severe isopropanol poisoning results in CNS and respiratory depression and circulatory collapse. Treatment primarily consists of symptom-directed supportive care. Although hemodialysis increases the elimination of isopropanol and acetone substantially, it should only be considered in severe life-threatening poisonings. Patients usually make a full recovery provided they receive prompt supportive care.

Activated charcoal supercedes ipecac as gastric decontaminant.

Syrup of ipecacuanha has previously been used to decontaminate patients following toxic or potentially toxic ingestions. The recent removal of this product from distribution in New Zealand has caused some concern to health professionals. This article outlines the relative merits of syrup of ipecacuanha and activated charcoal, and concludes that the latter is preferable in many respects. Details of its appropriate administration are discussed.

Cyanide poisoning: pathophysiology and treatment recommendations.

This paper aims to assess and compare currently available antidotes for cyanide poisoning. Such evaluation, however, is difficult. Thus, extrapolation from the results of animal studies has potential pitfalls, as significant inter-species differences in response may exist, and these experiments often involve administration of toxin and antidote almost simultaneously, rather than incorporating a more realistic time delay before initiation of treatment. Direct inference from human case reports is also problematic; either because of uncertainties over the exposure levels involved (and hence the likely outcome without treatment), or because of difficulties in identifying the specific contribution of a particular antidote within the overall treatment regimen. Certainly an effort to compare the relative efficacy of cyanide antidotes produces equivocal findings, with no single regimen clearly standing out. Indeed, factors such as the risks of antidote toxicity to various individuals and other practical issues, may be more important considerations. There is therefore no single treatment regimen which is best for all situations. Besides individual risk factors for antidote toxicity, the nature of the exposure and hence its likely severity, the evolving clinical features and the number of persons involved and their proximity to hospital facilities, all need to be considered. Clinically mild poisoning may be treated by rest, oxygen and amyl nitrite. Intravenous antidotes are indicated for moderate poisoning. Where the diagnosis is uncertain, sodium thiosulphate may be the first choice. With severe poisoning, an additional agent is required. Given the various risks with methaemoglobin formers or with unselective use of kelocyanor, hydroxocobalamin may be preferred from a purely risk-benefit perspective. However the former alternatives will likely remain important.

Enhanced elimination of piroxicam by administration of activated charcoal or cholestyramine.

This study has compared the effect of repeated administration of charcoal and cholestyramine on the elimination of piroxicam. Eight young adults were given piroxicam as a single dose of 20 mg, on 3 separate occasions. On one of the occasions charcoal was also given. On another occasion cholestyramine was also administered. The mean elimination half-life after piroxicam alone was 53.1 h. This was reduced to 40.0 h by charcoal administration and to 29.6 h after administration of cholestyramine. In the second phase of the study 7 elderly subjects received piroxicam 20 mg for 14 days on two occasions. Cholestyramine administration at the end of one of the periods reduced the mean elimination half-life of piroxicam from 52.3 h to 27.3 h.

Captopril: 4 years of post marketing surveillance of all patients in New Zealand.

The Intensive Medicines Monitoring Programme (IMP), a specialised part of the New Zealand Post Marketing Surveillance system, has been used to monitor captopril since it was first approved for marketing for the treatment of hypertension and heart failure. Monitoring has consisted of (1) spontaneous reporting for which doctors have been encouraged to report all clinical events, (2) a specific event recording survey at the end of the first year and (3) a controlled patient survey of taste disturbance. The IMP gathers prescription information on about 85% of all patients. There were 4,124 patients at the end of the first 4 years. Reported events involved 4% of patients, the majority being cutaneous (1%) and gastrointestinal (0.7%). The event recording survey gave an overall rate of adverse events of 2.2 per patient year. The taste survey showed a remarkably high incidence of taste disturbance in the control population and only taste loss was significantly higher (P less than 0.01) for captopril. This ongoing study has so far demonstrated a low incidence of adverse effects due to captopril, which is reassuring in view of its increasing use for mild hypertension and early cardiac failure.