wikitox:2.1.7.1.3.1_biguanides
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- | ===== CLINICAL EFFECTS ===== | ||
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- | ==== Metabolic effects ==== | ||
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- | A profound lactic acidosis is the most consistent reported finding in overdose. The pH is often less than 7.0 and high concentrations of lactate are observed. In some cases ketones are also high and account for some of the acidosis. The serum bicarbonate is low and there is usually a large [[: | ||
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- | ==== Cardiac effects ==== | ||
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- | Hypotension and tachycardia are common, as is reduced cardiac output. These may progress to cardiogenic shock. Patients may be dehydrated secondary to impaired consciousness and/or vomiting. All of these may contribute to the lactic acidosis (by reducing tissue perfusion) and should be corrected if possible. Myocardial infarction has occurred secondary to profound acidosis. | ||
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- | ==== Central nervous system effects ==== | ||
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- | Nausea and vomiting are common in the early stages; delirium, sedation, coma, and seizures may all occur secondary to the acidosis. | ||
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- | ==== Other effects ==== | ||
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- | Hypothermia, | ||
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- | ===== INVESTIGATIONS ===== | ||
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- | ==== Blood concentrations ==== | ||
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- | These are unhelpful in management. There is not a good correlation between blood concentrations of biguanides and outcome. In many of the series of acidosis occurring in chronic therapeutic use, the majority of patients have had undetectable concentrations at the time of presentation. | ||
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- | ==== Biochemistry ==== | ||
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- | Electrolytes, | ||
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- | ==== ECG ==== | ||
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- | A baseline ECG should be performed. Continuous ECG monitoring is advisable in patients with severe acidosis as complications secondary to either acidosis or hyperkalaemia may occur. | ||
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- | ===== DIFFERENTIAL DIAGNOSIS ===== | ||
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- | The differential diagnosis is of any agent that causes profound acidosis and CNS effects and would include [[: | ||
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- | ===== DIFFERENCES IN TOXICITY WITHIN THIS DRUG CLASS ===== | ||
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- | Lactic acidosis in therapeutic use is far more common with phenformin than metformin and phenformin has been removed from the market in most countries. There are insufficient data to determine if such differences are also true in overdose. | ||
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- | ===== DETERMINATION OF SEVERITY ===== | ||
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- | The following are associated with a less favourable outcome (mortality and morbidity): | ||
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- | * Elderly (age >60) | ||
- | * Complicating medical conditions (e.g. ischaemic heart disease, respiratory disease) | ||
- | * Renal failure | ||
- | * Hypotension (shock) | ||
- | * Diabetes | ||
- | * Low pH on presentation (pH<7.0) | ||
- | * Low bicarbonate on presentation (HCO3 < 6.0 mmol/L) | ||
- | * High lactate ( > 17 mmol/L) | ||
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- | However, none of these is a particularly good predictor of outcome. | ||
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- | ===== TREATMENT ===== | ||
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- | ==== Supportive ==== | ||
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- | All patients with significant acidosis should be admitted to intensive care. [[: | ||
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- | ==== GI Decontamination ==== | ||
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- | Oral [[: | ||
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- | ==== Treatment of specific complications ==== | ||
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- | **Acidosis** | ||
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- | Maintaining adequate tissue perfusion, oxygenation and glucose delivery and maximising compensatory hyperventilation are all important factors in the treatment of significant acidosis. The use of specific antidotes (including bicarbonate) to correct acidosis is controversial and may provide no additional benefit. We would recommend routine use of glucose and insulin, very slow and low doses of sodium bicarbonate if the pH is less than 6.9 - 7.0, and dichloroacetate if it is available. | ||
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- | ==== Antidotes ==== | ||
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- | **Bicarbonate** \\ Bicarbonate rapidly corrects acidaemia. Unfortunately, | ||
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- | ==== Elimination enhancement ==== | ||
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- | As these drugs are renally excreted, it is important to maintain a good urine output to facilitate renal clearance. Clearance is enhanced in acidic urine. So any effort to further increase renal clearance is likely to contribute to the metabolic acidosis and is thus contraindicated. \\ \\ **Haemodialysis** \\ The clearance of metformin may be enhanced by [[: | ||
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- | ===== LATE COMPLICATIONS, | ||
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- | Mortality in reported series of phenformin induced lactic acidosis is up to 50%. Long term sequelae do not appear to have been reported but it would be surprising if the hypotension, | ||
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- | ===== RESOURCES ===== | ||
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- | See PowerPoint presentation by Dr Rama Rao, New York Poisons Information Centre on hypoglycaemics . | ||
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- | ===== REFERENCES ===== | ||
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- | [[http:// | ||
wikitox/2.1.7.1.3.1_biguanides.txt · Last modified: 2019/07/05 20:09 by andrew