New psychoactive substances (NPS): Emergency Department guidance

(eg: Bombay Blue, Annihilation, Clockwork Orange, Doctor Green Thumb, Exodus, Herbal Haze, Joker, Sensate, Pineapple Express, Spice, Herbal Incense)

These chemicals mimic the effects, and are often more potent than, the active component of cannabis (THC).

Method of Ingestion: Usually smoked but can be ingested

Desired effects: Similar to cannabis - relaxation, euphoria and dissociative state

Side Effects:

• CNS: Anxiety, hallucinations, change in perception, nystagmus, acute psychosis, convulsions, coma, hypertonia and myoclonus 
• GI: Nausea, vomiting
• CVS: tachycardia, tachyarrhythmias, palpitations and chest pain, QTc prolongation and syncope
• Other: Cold extremities, dry mouth, dyspnoea, mydriasis and hypokalaemia 
• Toxic effects generally last up to 4 hours, however, as with all NPS the effects are unpredictable and may last considerably longer

Management: See Toxbase ‘Synthetic Cannabinoid Receptor Agonists’

• Post Ingestion – 6 hours observation
• Post Inhalation – Asymptomatic patients do not require observations
• In symptomatic patients monitor heart rate and BP. Perform 12-lead ECG and take blood glucose measurement (BM)
• It is better to manage agitation without sedation. (Parents present. Nurse in quiet lowered light environment).
• Midazolam 0.05-0.1mg/kg if necessary for agitation.
• Manage seizures normally. Use Lorazepam 0.1mg/kg if required. 

Synthetics Cathinones & Phenylamines (Gogaine, Ching, Mr. White, Columbiana, Charly Sheen, Dust till Dawn, Ivory Wave, Blue Stuff, Bath Salts, Sniff)
Mephedrone (Magic, Bubbles, M-Cat, Meow Meow, Plant Food)

Method of Ingestion: Snorted as a powder, ingested in tablet form, ingested as powder wrapped in cigarette paper (‘bombing’), or injected

Desired Effects: Similar to that of amphetamines, cocaine and MDMA – euphoria, increased alertness, intensified emotions and boosted self-esteem

Side Effects:

• CNS: Tremor, sweating, dilated pupils, agitation, confusion, headache, anxiety, seizures, hallucinations or delusions.
• CVS: Chest pain, palpitations, dyspnoea, hypotension or hypertension may occur. Narrow-complex tachycardias are common; ventricular tachycardia or ventricular fibrillation may occur. Coronary Ischaemia
• GI: vomiting, abdominal pain
• Hyperpyrexia may be severe.
• Metabolic acidosis may also occur.
• Effects may have duration of 24-48 hours.

Management : See Toxbase under specific drug or ‘Amfetamines and other stimulants’ and Serotonin Toxicity

• Activated Charcoal if within 1 hour of ingestion.
• Observations - at least 4 hours. 30 minutely observations (HR, Rhythm, BP, GCS and T^o)
• ECG - Serial ECGs may be required in symptomatic patients
• Measure U&Es, LFTs, CK and Coag if features of toxicity are present.
• Agitation and delirium - Midazolam 0.05-0.1mg/kg if required
• Seizures – Normal management. Lorazepam 0.1mg/kg or Midazolam 0.1-0.15mg/kg
• Metabolic Acidosis – Correct any hypoxia and hypovolaemia. Consider 8.4% Soduim Bicarbonate
• Narrow Complex Tachycardias - best left untreated in uncompromised patients
• Hypotension – IV fluids. Discuss with ICU if hypotension unresponsive to fluids
• Hyperthermia – Aggressively cool patients. (See Serotonin Toxicity)

If Hyperthermia refer to Serotoxin Toxicity Guidance below

(Eg: Phenazepam, Etizolam, Diclazepam, Flubromazolam, Flubromazepam)

The primary toxicity of benzodiazepines ins CNS depression. These Benzodiazepinetype NPS may be many times more potent that Diazepam.

Desired Effects: Same as Diazepam - sedation, anxiolysis, hypnosis.

Side Effects:

• CNS: Drowsiness, ataxia, dysarthria and nystagmus, coma
• CVS: Bradycardia, Hypotension
• ECG Abnormalaties: 1nd/2nd degree block and QTc Prolongation
• Respiratory: Respiratory Depression

Management - see Toxbase under specific drug or drug class

• Consider Charcoal if <1 hr since ingestions
• Monitor Vital signs - will require at least 4 hours of observation post exposure
• Perform ECG

Flumazenil is an appropriate treatment in patients poisoned only by benzodiazepines who develop reduced ventilation and coma who would otherwise require mechanical ventilation. It should not be used as a diagnostic test and should not be use in patients who have co-ingested medicines that may cause seizures. (See toxbase)

Serotonin toxicity is a serious side effect of ingestion of NPS. Features may occur insidiously over a period of hours to minutes and are characterized by altered mental state, neuromuscular hyperactivity and autonomic instability.

• Altered Mental State – Agitation, confusion, delirium, hallucinations, drowsiness and coma
• Neuromuscular Hyperactivity – shivering, tremor, teeth grinding, myoclonus and hyperreflexia
• Autonomic Instability – Tachycardia, fever, hyper- or hypotension, flushing, diarrhoea and vomiting

In severe toxicity, uncontrolled hyperpyrexia leads to rhabdomyolysis, renal failure, acidosis, hypocalcaemia, hyperkalaemia, DIC and death. It is therefore paramount that it is diagnosed and treated early.

This flow chart can help aid diagnosis of Serotonin Toxicity (Formed from the Hunter Serotonin Toxicity Criteria (Sensitivity 84%, specificity 97%):

Isbister GK, Buckley NA, Whyte IM. Serotonin toxicity: a practical approach to diagnosis and treatment. Med J Aust 2007; 187:361-365

Serotonin Toxicity

*There is no evidence to support the use of Dantrolene effectivement in serotonin toxic patients.

Investigations: (Dictated to by presentation)

Mild toxicity - U&Es, CK, Glucose, VBG, ECG

Moderate / severe toxicity - U&Es, FBC, LFTS, Ca2+, Coag, CK, VBG, Glucose, ECG

Role of urine toxicology - Helpful for surveillance of agents only. Does not change management as most NPS NOT detected. 

Cooling:

• Cooled IV fluids and cooled fluids for bladder lavage
• Ice - applied by packing axilla and groin with ice
• Antipyretics have no role for serotonin toxicity induced hyperpyrexia
• Bair Hugger - on cool

RSI

Opiate - avoid Fentanyl/Alfentanil due to serotonergic action

Recommended induction agent:

• Thiopentone 3-5mg/kg (Avoid Ketamine)

Muscle relaxant - Rocuronium 1mg/kg for induction
Depolarising neuromuscular blockers (Suxamethonium) are contraindicated

Hyperkalaemia

• 0.5ml/kg Calcium Gluconate 10%
• Insulin/Dextrose infusion if blood sugar levels normal

Rhabdomyolysis

• IV fluids 
• Consider 3-5 mmol/kg of Sodium Bicarbonate (3-5mls/kg of 8.4% NaBic)

Drug Doses

• Midazolam: 0.05-0.1mg/kg IV
• Lorazepam: 0.1mg/kg (4mg max) IV
• Cyproheptadine: PO or crushed and administered via NG
  Adults and children aged 13 or more: 12 mg orally, followed by 4-8mg every 6hrs
  Children aged 12 years or less: 0.25mg/kg/day (max 12mg) in 4 divided doses 
• Chlorpromazine: 500mcg/kg IM 6-12 years, 25-50mg IM 12-18 years
• Dantrolene*: 2-3mg/kg IV

* There is no evidence to support the use of Dantrolene effectiveness in serotonin toxic patients.

Important points about management of serotonin toxicity management:

• Mortality is significantly raised in patients with a temperature >40^oC
• Cyproheptadine and chlorpromazine are unlicenced for this use. Their use treats symptoms but as yet do not alter mortality.
• Acute kidney injury, liver failure, disseminated intravascular coagulation, rhabdomyolysis are complications associated with moderate to severe serotonin toxicity.
• Toxicology studies of NPS are extremely limited.
• NPS have a greater duration of effect than ecstasy.

If the child has completed period of observation and is deemed medically fit for discharge please refer to the ‘intoxicated’ child/adolescent flow chart