No abstract

There are limited reliable data to guide clinicians managing patients with toxicity due to these substances. The harms associated with emerging recreational drugs are not fully documented, although it is clear that they are not without risk. Management of users with acute toxic effects is pragmatic and primarily extrapolated from experience with longer established stimulant or hallucinogenic drugs such as amfetamines, 3,4-methylenedioxymethamfetamine (MDMA) and lysergic acid diethylamide (LSD).

Chief Scientist Office of the Scottish Government.

Tricyclic antidepressants remain a common cause of fatal drug poisoning as a result of their cardiovascular toxicity manifested by ECG abnormalities, arrhythmias and hypotension. Dosulepin and amitriptyline appear to be particularly toxic in overdose. The principal mechanism of toxicity is cardiac sodium channel blockade, which increases the duration of the cardiac action potential and refractory period and delays atrioventricular conduction. Electrocardiographic changes include prolongation of the PR, QRS and QT intervals, nonspecific ST segment and T wave changes, atrioventricular block, right axis deviation of the terminal 40 ms vector of the QRS complex in the frontal plane (T 40 ms axis) and the Brugada pattern (downsloping ST segment elevation in leads V1-V3 in association with right bundle branch block). Maximal changes in the QRS duration and the T 40 ms axis are usually present within 12 hours of ingestion but may take up to a week to resolve. Sinus tachycardia is the most common arrhythmia due to anticholinergic activity and inhibition of norepinephrine uptake by tricyclic antidepressants but bradyarrhythmias (due to atrioventricular block) and tachyarrhythmias (supraventricular and ventricular) may occur. Torsade de pointes occurs uncommonly. Hypotension results from a combination of reduced myocardial contractility and reduced systemic vascular resistance due to alpha-adrenergic blockade. Life-threatening arrhythmias and death due to tricyclic antidepressant poisoning usually occurs within 24 hours of ingestion. Rapid deterioration is common. Level of consciousness at presentation is the most sensitive clinical predictor of serious complications. Although a QRS duration >100 ms and a rightward T 40 ms axis appear to be better predictors of cardiovascular toxicity than the plasma tricyclic drug concentration, they have at best moderate sensitivity and specificity for predicting complications.

Severe clinical toxicity may occur following recreational use of 25I-NBOMe, with stimulant and serotoninergic features predominating. Clinicians should be alert to this substance, in view of its emergence in Europe as well as in the United States.

No abstract

Several factors may affect the delivery of a nebulized aerosol to the lung through an endotracheal tube during mechanical ventilation. To study these factors in vitro, a model representing ventilation of an adult patient was constructed by linking a Servo 900C ventilator to a standard humidified circuit and an endotracheal (ET) tube positioned within a pipe representing the trachea. This was connected via a filter to a lung simulator. Nebulizers filled with 99mTc human serum albumin were positioned in the circuit, and the delivery of nebulized aerosol through the ET tube into the filter was measured using a gamma camera. With the use of an inspiratory phase-activated System 22 Acorn jet nebulizer, typical adult ventilator settings, and a 3-ml nebulizer solution volume, 5.4% of the nebulizer dose reached beyond the end of the ET tube. This was increased by increasing the inspiratory time, reducing the respiratory rate or respiratory minute volume, and by repositioning the nebulizer on the inspiratory limb of the Y-piece and was reduced by slowing the driving gas flow to the nebulizer. Under the same conditions, delivery was 3.1 and 4.4% using the Samsonic and Fisoneb ultrasonic nebulizers, respectively. Increasing the fill volume and the addition of an aerosol storage chamber increased delivery with all three nebulizers. These experiments suggest some simple ways of improving aerosol delivery during mechanical ventilation, including increasing the volume of nebulizer fill, repositioning the nebulizer in the ventilator circuit, adding an aerosol storage chamber, and adjusting ventilator settings to maximize delivery.

Torsades de pointes (TdP) is a characteristic polymorphic ventricular arrhythmia associated with delayed ventricular repolarization as evidenced on the surface electrocardiogram by QT interval prolongation. It typically occurs in self-limiting bursts, causing dizziness and syncope, but may occasionally progress to ventricular fibrillation and sudden death. Acquired long QT syndromes are mainly caused by cardiac disease, electrolyte abnormalities or exposure to drugs that block rectifying potassium channels, especially IKr. Management of TdP or marked QT prolongation includes removal or correction of precipitants, including discontinuation of culprit drugs and institution of cardiac monitoring. Electrolyte abnormalities and hypoxia should be corrected, with potassium concentrations maintained in the high normal range. Immediate treatment of TdP is by intravenous administration of magnesium sulphate, terminating prolonged episodes using electrical cardioversion. In refractory cases of recurrent TdP, the arrhythmia can be suppressed by increasing the underlying heart rate using isoproterenol (isoprenaline) or transvenous pacing. Other interventions are rarely needed, but there are case reports of successful use of lidocaine or phenytoin. Anti-arrhythmic drugs that prolong ventricular repolarization should be avoided. Some episodes of TdP could be avoided by careful prescribing of QT prolonging drugs, including an individualized assessment of risks and benefits before use, performing baseline and periodic electrocardiograms and measurement of electrolytes, especially during acute illnesses, using the lowest effective dose for the shortest possible time and avoiding potential drug interactions. These steps are particularly important in those with underlying repolarization abnormalities and those who have previously experienced drug-induced TdP.