Benzodiazepine · Antiepileptic · Alcohol withdrawal
Lorazepam (Ativan)
Also called Ativan
Indications
- Status epilepticus, the first-line IV benzodiazepine (label)
- Preanesthetic sedation, anxiolysis and amnesia (label)
- Alcohol withdrawal, a common choice in liver disease (off-label)
- Acute agitation and stimulant toxicity (off-label)
- ICU sedation when propofol and dexmedetomidine are unsuitable (off-label)
Dosing
| Where | Dose |
|---|---|
| Seizures and neuro | Lorazepam: 0.1 mg/kg IV (max 4 mg per dose), repeat once in 5–10 min |
| Seizures and neuro | Lorazepam: 0.5–2 mg IV/IM (alcohol withdrawal, stimulant toxicity) |
| Benzodiazepine equivalence | Lorazepam: 1 mg (IV onset 5–10 min; no active metabolites) |
On the quick cards
- Seizures and neuroPush and Emergency Meds: Status epilepticus, raised ICP and agitation
- Benzodiazepine equivalenceEquivalents and Conversions: Approximate equal doses
Mechanism of action
Lorazepam binds the benzodiazepine site in the GABA-A receptor's extracellular domain, between an α subunit (α1, α2, α3 or α5) and the γ2 subunit. It raises the receptor's affinity for GABA, so the chloride channel opens more often when GABA is released; without GABA it does nothing. High affinity and lower lipid solubility than diazepam mean it leaves the brain slowly, so one dose protects against seizures for hours.
Pharmacology
- CNS: sedation, anxiolysis and strong anterograde amnesia; anticonvulsant effect lasts hours, against 20–30 min for diazepam
- Respiratory: dose-related depression and airway obstruction, much worse with opioids, alcohol or other sedatives
- Cardiovascular: little effect at usual doses; hypotension with large doses or volume depletion
- Metabolic: high or prolonged IV doses can cause propylene glycol toxicity, with lactic acidosis, a rising osmolar gap, acute kidney injury and hypotension
- Other: a modifiable ICU delirium risk factor (PADIS 2018)
Pharmacokinetics
| Onset | IV 5–10 min, peak sedation about 15–30 min; IM absorption is complete, peaking within 3 h (label) |
|---|---|
| Duration | Usually 6–8 h (label) |
| Half-life | About 14 h (injection label; 12 h in the oral label) |
| Distribution | Vd about 1.3 L/kg; less lipophilic than diazepam, so slower into the brain and slower out |
| Protein binding | About 91% |
| Metabolism | Direct glucuronidation of the 3-hydroxy group to an inactive glucuronide; no CYP step, so liver disease, age and CYP drugs matter little |
| Clearance | About 1.1 mL/min/kg (label) |
| Elimination | Urine 88%, mostly as the glucuronide |
| Organ failure | Little change in liver disease (label); the glucuronide accumulates in kidney failure |
| Routes | IV (dilute first), IM, oral and sublingual |
Chemistry
- 7-chloro-5-(2-chlorophenyl)-3-hydroxy-1,3-dihydro-2H-1,4-benzodiazepin-2-one; the 3-hydroxy group allows direct glucuronidation, as with oxazepam and temazepam
- Un-ionized at body pH, less lipid-soluble than diazepam and almost insoluble in water
- Injection: 2 or 4 mg/mL in polyethylene glycol 400 (0.18 mL/mL) and propylene glycol (about 0.8 mL/mL) with 2% benzyl alcohol
- Viscous: dilute with an equal volume before IV push; refrigerate and protect from light
Adverse effects and cautions
In the one-pagers
- Mental Health: Meds and CommunicationBenzodiazepines and sedative withdrawal: Lorazepam: About 12 h; glucuronide inactive: Suits liver disease; IV form has propylene glycol
- End of Life, Brain Death and Organ DonationWithdrawing life support: Lorazepam: 1–3 mg: 0.5–4 mg/h
- Sedation, Pain and Delirium ScalesPharmacology and ICU pitfalls: Lorazepam: 0.01–0.1 mg/kg/h (≤10 mg/h): Propylene glycol: osmolar gap, acidosis
- ABG Interpretation in 6 StepsAnion gap, delta-delta and other gaps: The osmolar gap finds uncharged toxins. Calculated osmolality = 2 × Na⁺ + glucose ÷ 18 + BUN ÷ 2.8 (+ ethanol ÷ 3.7); the gap, measured minus calculated, is normally under 10 mOsm/kg (Berend 2014). Na⁺ 140, glucose 90 and BUN 14 give 290; a measured 320 is a gap of 30. Early after methanol or ethylene glycol the osmolar gap is high and the anion gap normal; a
- CEN Mental Health: Crisis, Suicide Risk, Eating Disorders and AbuseContinuous observation in a room that is not ligature-resistant: In the PSNet case, a woman on a hold after an alcohol and lorazepam overdose had a 24-hour sitter. Before a chest film she asked to go to the bathroom; the sitter was chatting outside, and she was found standing on an upside-down garbage can with her gown tied around her neck and the door hinge. The authors recommend clear orders tha
- Mass Casualty Triage and Incident CommandCBRNE: decontamination, nerve agents and radiation: Midazolam: 10 mg IM by autoinjector: Seizures; RAMPART: IM beat IV lorazepam, 73% vs 63%
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Sources
- FDA label: Lorazepam injection (Hikma, 2021)
- Yahwak 2008 (osmolar gap)
- PubChem: lorazepam
For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow the order, the label and your institution's protocols.