Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

all patients

1st line – supportive care and reassurance

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ACUTE
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all patients
1st line – 

supportive care and reassurance

If intoxication is mild, the patient may be best managed by monitoring and observation in a quiet environment.

Hospital services inclusive of vital signs, rectal temperature, cardiac telemetry (if chest pain, tachycardia, or arrhythmia present), available CPR including mechanical ventilation, and close one-on-one observation in severe toxicity.

Consider – activated charcoal

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ACUTE
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all patients
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within 1 hour of ingestion
Consider – 

activated charcoal

Treatment recommended for SOME patients in selected patient group

If the patient presents within 1 hour of drug ingestion and is cooperative, activated charcoal may be given.

Primary options

charcoal, activated: 50 g orally as a single dose, may repeat at 4-6 hour intervals

Plus – reassurance and oral sedation

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ACUTE
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all patients
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with mild agitation (Richmond Agitation-Sedation Scale +1 to 2)
Plus – 

reassurance and oral sedation

Treatment recommended for ALL patients in selected patient group

(+1 to 2): mildly aroused and cooperative, alert, may be irritable and pacing around but still willing to talk and cooperate with exam, normal vital signs. It is reasonable to give an oral benzodiazepine.

If an oral benzodiazepine is ineffective, repeated and higher doses of benzodiazepines or olanzapine can be given orally.

Haloperidol may also be given orally.[37][57][59]

Level of patient arousal guides sedation.

Primary options

diazepam: 10 mg orally as a single dose, may repeat if required

OR

lorazepam: 2 mg orally as a single dose, may repeat if required

Secondary options

olanzapine: 10 mg orally as a single dose

Tertiary options

haloperidol: 5 mg orally as a single dose

Plus – reassurance and oral or parenteral sedation

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ACUTE
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all patients
|
with moderate agitation (Richmond Agitation-Sedation Scale +2 to 3)
Plus – 

reassurance and oral or parenteral sedation

Treatment recommended for ALL patients in selected patient group

(+2 to 3): moderately aroused, restless, agitated, becoming more vocal, unreasonable, hostile, and uncooperative, tachycardia, hypertension.

Physical restraint of the patient may be required at this stage and should involve multiple staff members, preferably one per limb plus an additional staff member to establish intravenous access and administer sedatives.

Level of patient arousal guides sedation.

Primary options

diazepam: 10 mg orally as a single dose, may repeat if required; 5-10 mg intravenously as a single dose

OR

lorazepam: 2 mg orally as a single dose, may repeat if required; 1 mg intravenously as a single dose

Secondary options

olanzapine: 10 mg orally as a single dose; 10 mg intramuscularly as a single dose

OR

haloperidol: 5 mg orally as a single dose

OR

haloperidol lactate: 2.5 to 5 mg intramuscularly as a single dose

Tertiary options

midazolam: 5 mg intravenously/intramuscularly as a single dose

Plus – parenteral sedation

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ACUTE
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all patients
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with severe agitation (Richmond Agitation-Sedation Scale +3 to 4)
Plus – 

parenteral sedation

Treatment recommended for ALL patients in selected patient group

(+3 to 4): highly aroused, distressed, fearful, highly restless and agitated, noisy, abusive, uncooperative, and possibly violent. Presence of security personnel may be necessary until behavioral disturbance is under control.

If possible, QT interval should be measured prior to administration of either droperidol or intravenous haloperidol.

If benzodiazepines and/or antipsychotics are unsuccessful, rapid sequence intubation of the patient must be performed to protect patient and staff from harm.

Primary options

diazepam: 5-10 mg intravenously as a single dose, may repeat if necessary

OR

lorazepam: 1-2 mg intravenously/ intramuscularly as a single dose, may repeat if required

OR

midazolam: 5 mg intravenously/intramuscularly as a single dose, may repeat if required

Secondary options

haloperidol lactate: 2.5 to 5 mg intravenously/intramuscularly as a single dose

OR

olanzapine: 5-10 mg intramuscularly as a single dose

OR

droperidol: 2.5 to 5 mg intravenously/intramuscularly as a single dose

Plus – hydration

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ACUTE
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all patients
|
with volume depletion or rhabdomyolysis
Plus – 

hydration

Treatment recommended for ALL patients in selected patient group

The average patient may require 3-5 liters of intravenous fluids in the first few hours of admission.

Plus – sodium bicarbonate

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ACUTE
|
all patients
|
with metabolic acidosis
Plus – 

sodium bicarbonate

Treatment recommended for ALL patients in selected patient group

Sodium bicarbonate may be required to correct a severe metabolic acidosis.

Acid-base status should be rechecked after giving sodium bicarbonate.

Electrolytes should be monitored regularly because hypernatremia and hypokalemia are a risk if substantial amounts of bicarbonate have been given.

Dose is adjusted based on serum bicarbonate levels.

Plus – defervescence and muscle relaxation

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ACUTE
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all patients
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with hyperthermia >100°F (>38°C) but <103°F (<39.5°C)
Plus – 

defervescence and muscle relaxation

Treatment recommended for ALL patients in selected patient group

Active cooling is generally instituted when body temperature exceeds 100°F (38°C).[5][26][74] The simplest method to accomplish rapid cooling in any setting is the application of tepid mist and use of a fan for conductive, evaporative, and convective heat dissipation.[74] Additional measures include cooling blankets and ice packs. Care should be taken to monitor for hyponatremia.

Benzodiazepines are given to relax muscles.

Primary options

diazepam: 5-10 mg orally/intravenously as a single dose, may repeat if required

OR

lorazepam: 1-2 mg intravenously/intramuscularly as a single dose, may repeat if required

OR

midazolam: 5 mg intravenously/intramuscularly as a single dose, may repeat if required

Plus – defervescence and muscle paralysis

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ACUTE
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all patients
|
with hyperthermia >103°F (>39.5°C)
Plus – 

defervescence and muscle paralysis

Treatment recommended for ALL patients in selected patient group

Indicates severe, potentially life-threatening toxicity and mandates immediate cooling (e.g., cooled intravenous fluids, sponge baths, ice packs) and sedation. In general this is best done in the intensive care unit with paralysis and ventilation.[7]

Paralysis may need to be prolonged to prevent re-emergence of drug-induced hyperthermia and is usually accomplished with a nondepolarizing neuromuscular blocker with moderate duration of action, such as pancuronium. Patients must be intubated before initiation of paralysis.

Primary options

pancuronium: consult local specialist protocol for guidance on dose

OR

rocuronium: consult local specialist protocol for guidance on dose

OR

vecuronium: consult local specialist protocol for guidance on dose

Plus – benzodiazepine or beta-blocker

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ACUTE
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all patients
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with sinus tachycardia
Plus – 

benzodiazepine or beta-blocker

Treatment recommended for ALL patients in selected patient group

Most tachycardia is sinus in origin and resolves over several hours. However, treatment is beneficial because prolonged tachycardia places the patient at risk of myocardial ischemia from increased myocardial oxygen demand.[59]

Diazepam, lorazepam, or midazolam are first line for those patients not already receiving a benzodiazepine for agitation (or another indication). Doses should be titrated according to response; risk of respiratory depression and oversedation should be taken into consideration.

In normotensive patients, the beta-blocker metoprolol may be considered.[37] Metoprolol should be titrated according to heart rate and blood pressure.

Primary options

diazepam: 5-10 mg orally/intravenously as a single dose, may repeat if required

OR

lorazepam: 1-2 mg intravenously/intramuscularly as a single dose, may repeat if required

OR

midazolam: 5 mg intravenously/intramuscularly as a single dose, may repeat if required

Secondary options

metoprolol tartrate: 5 mg intravenously every 10-30 minutes

Plus – antiarrhythmic

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ACUTE
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all patients
|
with supraventricular tachycardia
Plus – 

antiarrhythmic

Treatment recommended for ALL patients in selected patient group

Supraventricular tachycardias associated with hemodynamic compromise are best treated with short-acting beta-blockade (e.g., intravenous esmolol).[7][54]

Primary options

esmolol: 50-200 micrograms/kg/min intravenously

Plus – antiarrhythmic

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ACUTE
|
all patients
|
with ventricular tachycardia
Plus – 

antiarrhythmic

Treatment recommended for ALL patients in selected patient group

May be treated conventionally with antiarrhythmic medication (e.g., amiodarone) or cardioversion.

Primary options

amiodarone: 300 mg intravenously over a period of not less than 3 minutes initially, followed by 15-20 mg/kg intravenously over 24 hours

Plus – anticonvulsant

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ACUTE
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all patients
|
with seizure
Plus – 

anticonvulsant

Treatment recommended for ALL patients in selected patient group

Seizures may be managed with intravenous benzodiazepines initially, and repeated as necessary.[37][54]

Barbiturates, and possibly general anesthesia, may be indicated for status epilepticus unresponsive to escalating doses of benzodiazepines.

Primary options

diazepam: 5-10 mg intravenously, may repeat if required

OR

lorazepam: 1-2 mg intravenously/intramuscularly, may repeat if required

Plus – neurosurgical consultation

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ACUTE
|
all patients
|
with subarachnoid hemorrhage
Plus – 

neurosurgical consultation

Treatment recommended for ALL patients in selected patient group

Subarachnoid hemorrhage may be treated conventionally by giving nimodipine and expedited transfer to a center for management of neurosurgical emergencies.[77]

Primary options

nimodipine: consult specialist for guidance on dose

Plus – vasodilator

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ACUTE
|
all patients
|
with hypertension
Plus – 

vasodilator

Treatment recommended for ALL patients in selected patient group

Benzodiazepines may not effectively mitigate hypertension in certain patients with amphetamine-related toxicity. If hypertension persists, the mixed alpha/beta-blocker labetalol has been shown to be safe and effective.[37][59]

Nitric oxide-mediated vasodilators such as nitroprusside and nitroglycerin are also useful for the treatment of isolated hypertension, as is the alpha-blocker phentolamine. The calcium-channel blocker nicardipine may also be useful.[78]

Primary options

labetalol: 10-20 mg intravenously every 10 minutes until desired blood pressure is achieved, maximum 300 mg/total dose

OR

nitroglycerin: 5-200 micrograms/min intravenously

OR

nitroprusside: 0.3 micrograms/kg/min intravenously initially, titrate to achieve desired blood pressure, maximum 10 micrograms/kg/min

OR

phentolamine: 5 mg intravenously every 2-4 hours until desired blood pressure is achieved

OR

nicardipine: 5 mg/hour intravenous infusion initially, increase by 2.5 mg/hour every 5-15 minutes until desired effect, maximum 15 mg/hour

Plus – Trendelenburg position and pressor agent

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ACUTE
|
all patients
|
with hypotension
Plus – 

Trendelenburg position and pressor agent

Treatment recommended for ALL patients in selected patient group

Hypotension is a late-stage phenomenon that may occur if the patient is severely dehydrated or has depleted catecholamines. An immediate temporizing effect may be obtained by placing the patient into the Trendelenburg position. Copious intravenous fluid administration is warranted.

Use of pressors such as dopamine or norepinephrine may be required in extreme cases.

Primary options

dopamine: 1-50 micrograms/kg/min intravenously

Secondary options

norepinephrine: 2-12 micrograms/min intravenously

Plus – supportive care and serotonin manipulation therapy

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ACUTE
|
all patients
|
with serotonin toxicity
Plus – 

supportive care and serotonin manipulation therapy

Treatment recommended for ALL patients in selected patient group

In patients with suspected serotonin toxicity, observation and supportive care in a hospital environment yields the best therapeutic results.

Specific treatment may include benzodiazepines or cyproheptadine (if available).[27][45]

Consultation with clinical staff at a poison center can prove critically important if serotonin toxicity is suspected.

Primary options

diazepam: consult specialist for guidance on dose

OR

cyproheptadine: consult specialist for guidance on dose

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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