Stuffed, Speeding and Busted!

Metamphetamine is a centrally acting sympathomimetic psychostimulant.

Amphetamines have direct and indirect actions.

•  Direct stimulation of the central nervous system and peripheral vascular system via adrenoreceptors, as well as dopaminergic and serotonergic receptors.
• Indirect sympathomimetic action through enhanced catecholamine release, decreased catecolamine reuptake and inhibition of monoamine oxidase (an enzyme that metabolises biogenic amines).

ADME for metamphetamine:

• Absorption:
  — Rapidly absorbed following oral administration. Time to peak levels is 2 hours. Extremely fast absorption following smoking/ inhalation.
• Distribution:
  — Moderate volume of distribution (3-7L/kg) as they are lipid soluble weak bases.
  — Crosses blood brain barrier.
• Metabolism:
  — Undergoes hepatic metabolism by aromatic hydroxylation and N-demethylation.
• Excretion:
  — Majority excreted unchanged in the urine.

Patients often present accompanied by the authorities, whether Border/Customs or Police. Clinical features may include:

• CNS effects
  — anxiety, agitation, paranoia, bruxism, hyperthermia, delirium, seizures
  — rigidity, myoclonus, coma, ischemic stroke and intracranial hemorrhage
  — post-amphetamine psychosis
• Cardiovascular effects
  — Tachycardia, hypertension
  — acute coronary syndrome, cardiac dysrythmia, carotid or aortic dissection, mesenteric ischemia, cardiomyopathy, acute pulmonary edema
• Peripheral sympathomimetic effects
  — mydriasis, diaphoresis, tremor
• Metabolic and renal effects
  — dehydration, rhabdomyolysis and hyperkalemia, acute renal failure, metabolic acidosis

Death in these patients is usually due to myocardial infarction, dysrhythmia, seizures or intracerebral hemorrhage.

Suspect a vascular catastrophe in an amphetamine intoxicated patient with a significant headache.

The patient currently has features of mild amphetamine toxicity as a result of ‘body stuffing’

There is potential for life-threatening deterioration due to ongoing absorption of methamphetamine. Unlike ‘body packers’, ‘body stuffers’ often can’t be sure how much drug they have ingested, or exactly what drugs were in the the package. It is also difficult to predict how rapidly the drug with egress from the packaging and be absorbed.

Amphetamine toxicity can be graded as follows:

• Mild
  — euphoria, increased alertness, bruxism, tachycardia, hypertension
• Moderate
  — agitation, paranoia, hallucinations, diaphoresis, vomiting, abdominal pain, palpitations, chest pain
• Severe
  — hyperthermia, metabolic acidosis, rhabdomyolysis, hyperkalemia, coma

Most presentations have mild or moderate toxicity, but the potential for badness should not be underestimated.

ʻBody packingʼ is  the internal concealment of illicit drugs (usually in large quantities) for transportation across international borders. ʻBody stuffingʼ, on the other hand, is the rushed, unplanned internal concealment of illicit drugs to avoid detection just before capture by law enforcement officers.

In the latter case the drugs present may be unknown, the doses unknown, there may be multiple types of drug and the stuffed package is more likely to leak.

Always ask suspected body packers/ stuffers:

• What drugs were internally concealed and how much?
• What type of packaging and how many layers? Was there a package within a package?
• What were the circumstances of internal concealment? (planned or impulsive?)
• What route of internal concealment was used? (as well as oral, toxicity can also result from rectal or vaginal internal concealment — the patient may even directly aspirate the package into his or her lungs)

Use the Resus-RSI-DEAD approach and you can’t go wrong.

Methamphetamine overdoses can present challenging behavioural, cardiovascular and metabolic emergencies.

Resuscitation

• Identify and immediately manage potential life threats:
  — Agitated delirium
  — Seizures (about 4% of ED presentations)
  — Hypertensive emergencies
  — Hyperthermia
• Treat agitation and seizures with benzodiazepines
  — Severe agitation and seizures can be treated with IV benzodiazepines (e.g. 10mg of midazolam or diazepam IV) with repeat doses of diazepam 10-20mg IV every 5-10 minutes as needed up to a maximum dose of 60mg.
  — Agitated patients refractory to diazepam can be given droperidol 2.5mg IV or olazepine 10mg IM.
• Treat hypertension that is non-responsive to benzodiapine sedation with either phentolamine (1mg IV q5min) or a titrated infusion of GTN or sodium nitroprusside.
  Avoid beta-blockers as this can lead to vasoconstriction through unopposed alpha adrenergic stimulation.
• Hyperthermia
  — T>38.5 is treated with ongoing benzodiazepine sedation, IV fluids and temperature monitoring.
  — If T>39.5C external cooling is required to prevent rhabdomyolysis and multi-organ dysfunction so intubation and neuromuscular blockade is often necessary.
•  As with most toxic arrests good neurological outcomes are possible following even hours of prolonged CPR (unless the arrest is due to a vascular catastrophe.

Supportive care and monitoring

• A “settled” calm environment and close observation is optimal.
• Benzodiazepines are recommended for agitation and seizures. A cooperative agitated patient may have 10-120 mg diazepam orally, with a further 10mg diazepam every 20 minutes until calm.
• Cardiac monitoring and serial ECGs  should continue until tachycardia resolves.
• Remember FASTHUGS IN BED Please!

Investigations

• Screening tests recommended for all intentional overdoses:
  — ECG
  —Paracetamol level
  — blood glucose
• Bloods tests are guided by the clinical presentation:
  — VBG (metabolic acidosis)
  — UEC (renal dysfunction, dehydration, hyerkalemia)
  — CK (rhabomyolysis)
  —Troponin (acute coronary syndrome)
• Imaging is guided by the clinical presentation:
  — CTA (suspected dissection)
  — CT head (suspected intracranial haemorrhage)
• Consider levels possible co-ingestants

Decontamination

• Activated charcoal can be considered for body stuffers who present within 1 hour of oral ingestion and are cooperative, but amphetamines are rapidly abosrbed and there is risk of seizures.
• Upper GI endoscopy or laparotomy for decontamination is rarely necessary in body stuffers.

Enhanced elimination

• Whole bowel irrigation, which may be useful in selected cases of body packing, is not used for body stuffers.
• Acidification of urine is mentioned in textbooks as helping to increase excretion of amphetamines, but may precipitate acute renal failure and have adverse systemic effects so is contraindicated

Antidotes

• Nil

Disposition

• Patients who are asymptomatic or exhibit mild toxicity can often be monitored in a ward environment.
• More severe toxicityrequires ongoing care in an HDU/ ICU setting.
• Patients who are asymptomatic 8 hours after ‘body stuffing’ can usually be ‘medically cleared’.

The patient was administered activated charcoal.

It was taken with some encouragement by the local constabulary: “sympathy, you want sympathy? Look in the dictionary its between sh!t and syphilis”. An ABG was performed: pH 7.32, Pa02 128 mmHg, PaCO2 39 mmHg, Base Excess -6, Sats 99%. He was admitted to CCU for observation and telemetry and was given diazepam 20mg po to help him settle for the night. There was no increase in agitation over the following hours, and his tachycardia settled overnight. The patient absconded the following day, but was arrested few days later when he returned to his home…

The decision to decontaminate is always a 3-way balancing act based upon the:

• risk assessment for the ingestion
• current clinical status and risk of adverse effects
• potential benefits of decontamination

Pros

• Activated charcoal may (theoretically) reduce metamphetamine absorption leading to a more benign clinical course
• Potential for improved outcomes and shorter length of stay (but unproven)

Cons

• Risk of aspiration (30% of patients given activated charcoal vomit within one hour, 4% of amphetamine presentations to ED have seizures)
• Numerous other complications of activated charcoal (from GI complications such as bowel obstruction or perforation to corneal abrasions!)
• Metamphetamines are rapidly absorbed, decreasing the likelihood of significant benefit from activated charcoal
• Requires a cooperative patient
• Requires a protected airway
• Administration is messy and time consuming and may distract from other priorities such resuscitation
• Diversion of resources to an intervention with unproven benefit