Sympathomimetic toxicity is commonly seen following recreation drug use, but may also result from excessive use or overdose of a number of pharmaceuticals.

It presents largely as one of adrenergic excess, with the CNS and CVS most notably effected. Treatment is largely supportive along with the provision of adequate sedation.

Agents causing sympathomimetic toxicity include:

Illicit substances:

• Amfetamines and their derivatives e.g. metafetamine, MDMA
• Cocaine
• Beta-adrenergic receptor agonists e.g. clenbuterol
• Novel psychoactives - including novel stimulants, novel hallucinogenic agents, and synthetic cannabinoid-receptor agonists.

Pharmaceuticals:

• Beta-adrenergic receptor agonists e.g. salbutamol
• Catecholamines e.g. adrenaline, noradrenaline, dopamine
• Psychostimulants e.g. modafinil
• Indirect sympathomimetics e.g. dexamfetamine, methylphenidate
• Monoamine inhibitors e.g. phenelzine
• Serotonin and Noradrenaline reuptake inhibitors (SNRIs) e.g. venlafaxine, atomoxetine
• Xanthines e.g. caffeine, theophylline

d

There is some variability depending on the causative agent but in general toxicity stems from the inhibition of monoamine reuptake transporters at the preganglionic synapse. They can also act to displace monoamines from presynaptic vesicles. The result is an increase in neurotransmitter presence in the synapse.

The increase in noradrenaline mostly leads to the cardiovascular signs, dopamine to the behavioural and psychotic symptoms and serotonin for the mood and some autonomic effects, although there is crossover of effects.

The sympathomimetic toxidrome can vary both in severity and the range of symptoms experienced based on whether the inciting agent has predominantly adrenergic, serotonergic or dopaminergic effects. Whilst several body symptoms are usually affected, the most notable signs are normally seen in the CNS and CVS.

• Central Nervous system
  • Excitation - agitation, anxiety, delirium
  • Acute behavioural disturbance - aggression, psychotic phenomena (commonly seen with metafetamine use)
  • Haemorrhagic or thrombotic strokes
• Cardiovascular effects
  • Tachycardia, arrhythmias
  • Hypertension
  • Acute coronary syndrome
  • Hypotension (with severe toxicity)
• Autonomic effects
  • Hyperthermia
  • Diaphoresis
  • Mydriasis
• Neuromuscular effects
  • Excitation - tremor, hyperreflexia
• Metabolic effects
  • Hypokalaemia
  • Lactic acidosis
  • Rhabdomyolysis

d

The main goal of treatment is to control agitation and aggression and identify and treat any complications including hypertheria, acute coronary/cerebrovascular syndromes and severe electrolyte derangements.

In most cases the paramount and often only treatment required is sedation, this is especially true of illicit recreational stimulant ingestion, which is the most common cause of sympathomimetic toxicity presenting to hospital.

When treating non-agitation related effects such as hypertension and hyperthermia, sedation should always be given first as this will commonly treat the problem before needing to consider more specific option.

Sedation

In those with mild symptoms, oral sedation may be adequate to control behaviour. Use:

• Diazepam 5-20mg (Child 0.2mg/kg up to 10mg). Repeat after 20 mins if required.
• Olanzapine 5-10mg, orally. Repeat at 20 mins if required.

In those with severe agitation or who fail to respond to oral sedation, parenteral sedation is often required: Options include:

• Droperidol 10mg (Child 0.2mg/kg max 10mg) intravenously or intramuscularly, repeat at 15 mins if required. Max 20 mg for a single event, 30mg in 24hrs.
• Midazolam 2.5-5mg intravenously (Child: 0.05-0.1mg/kg up to 5mg), repeat every 3-5 minutes until sedated but rousable.

Droperidol appears particularly effective in treating those affected by recreational stimulants. These agents tend to cause very high dopamine levels which droperidol likely treats due to it high dopamine receptor blocking effects.

Hyperthermia

It is common for patients with sympathomimetic toxicity to have a raised temperature. Severe hyperthermia however is uncommon and should prompt rapid treatment to control. In most cases provision of sedation will be sufficient, however if this is not effective then further measures should be taken. For further management options see here.

Hypertension

If hypertension is severe and does not respond to sedation, then use:

• glyceryl trinitrate 10 mcg/min by intravenous infusion. Increase by 10 mcg/min every 3 minutes until systolic blood pressure is less than 160mmHg up to a maxiumum rate of 100 mcg/min.

If blood pressure is not controlled despite this, then discuss with a clinical toxicologist for further advice (e.g. beta-blockade).

Other complications

Acute coronary syndrome, aortic dissection, stroke, tachyarrhythmias, rhabdomyolysis.

• These should be treated along standard treatment protocols
• Coronary artery spasm or dissection are more common in this group which should be a consideration when discussing with cardiology as primary angiogram is likely to be preferred in favour of thrombolysis in this group.
• Specific advice regarding drug induced rhabdomyolysis can be found here