Lorazepam (Ativan)

Benzodiazepine of choice in many ED/ICU settings for status epilepticus, acute agitation/anxiety, and alcohol withdrawal, and as part of sedation/amnestic regimens for procedures and mechanical ventilation.

• Mechanism: Positive allosteric modulator of GABA_A receptors → increased frequency of chloride channel opening in the presence of GABA, resulting in neuronal hyperpolarization and CNS depression
• IV onset: ~2–3 minutes; IM onset ~15–30 minutes; PO onset 15–60 minutes. Duration of effect from a single IV dose is typically 4–8 hours, but sedation and delirium can persist longer in ICU patients, especially with repeated doses
• Status epilepticus (adults): Lorazepam 0.1 mg/kg IV (max 4 mg per dose), given at ~2 mg/min; may repeat once in 5–10 minutes if seizures persist. In many protocols, 4 mg IV is given empirically in adults and may be repeated once
• Acute agitation/anxiety (adult): 0.5–2 mg IV/IM/PO, titrated every 10–20 minutes as needed; higher doses require close monitoring for respiratory depression and hypotension, especially with other sedatives or opioids
• Alcohol withdrawal: 1–4 mg IV/PO every 15–60 minutes as needed for agitation/tremor, or scheduled regimens (e.g., 1–2 mg IV/PO q4–6h with PRNs) depending on institutional protocol

• Generic Name: Lorazepam
• Brand Names: Ativan, various generics

Intermediate-acting benzodiazepine; anxiolytic, sedative-hypnotic, anticonvulsant, amnestic

Mechanism of Action:

• Lorazepam is a 1,4-benzodiazepine that binds to the benzodiazepine site on the GABA_A receptor complex at the interface of the α and γ subunits
• Enhances the effect of endogenous GABA by increasing the frequency of chloride channel opening, leading to neuronal hyperpolarization and decreased excitability
• Produces anxiolytic, amnestic, sedative, and anticonvulsant effects via widespread GABAergic modulation in cortical, limbic, and brainstem structures
• Does not directly activate GABA_A in the absence of GABA, which contributes to its relatively wide therapeutic index compared with barbiturates

Pharmacokinetics:

• Onset: IV 2–3 minutes (peak at ~5–10 minutes); IM 15–30 minutes; PO 15–60 minutes with peak 1–2 hours
• Duration: Clinical sedation often 4–8 hours after a single IV dose, longer with repeated dosing; anticonvulsant effect may be shorter than sedative effect
• Distribution: Relatively lipophilic but less so than diazepam; volume of distribution ~1–1.5 L/kg; ~85–90% protein bound
• Metabolism: Hepatic glucuronidation to inactive lorazepam-glucuronide; not dependent on CYP450, so fewer metabolic drug–drug interactions than many other benzos
• Elimination: Renally excreted as glucuronide conjugates; elimination half-life ~10–20 hours (often cited ~12–15 hours) in healthy adults; prolonged in elderly, obesity, or organ dysfunction
• IV formulation: Contains propylene glycol as a solvent, which can accumulate with high-dose or prolonged infusions, leading to metabolic acidosis, osmolar gap elevation, and renal dysfunction

• Status epilepticus and acute repetitive seizures - initial management
• Acute agitation, anxiety, or severe distress in the ED/ICU when rapid anxiolysis or sedation is necessary (e.g., severe panic, respiratory distress with high anxiety, palliative sedation)
• Alcohol withdrawal and delirium tremens - often as part of a symptom-triggered or fixed-dose benzodiazepine protocol
• Procedural sedation (usually in combination with opioids or other agents) for moderately painful procedures requiring anxiolysis and amnesia
• Adjunctive ICU sedation for mechanically ventilated patients when propofol or dexmedetomidine are contraindicated or insufficient on their own

Available Forms:

• IV/IM solution: commonly 2 mg/mL and 4 mg/mL in vials/ampules, containing propylene glycol
• Oral tablets: 0.5 mg, 1 mg, 2 mg tablets
• Oral solution: institution-specific or compounded formulations in some settings

Standard Adult Dosing:

Absolute Contraindications:

• Acute narrow-angle glaucoma or untreated open-angle glaucoma (class benzo warning)
• Severe respiratory insufficiency or sleep apnea without airway support, particularly when high doses are given
• Hypersensitivity to lorazepam or other benzodiazepines

Major Precautions:

• Respiratory depression and airway obstruction: Especially with opioids, other sedatives, or in patients with underlying lung disease
• Hypotension and hemodynamic instability: In patients with sepsis, hypovolemia, or cardiac dysfunction
• Delirium and prolonged sedation: With continuous infusions or repeated doses, particularly in the elderly and critically ill
• Tolerance, dependence, and withdrawal: Risk with prolonged use; taper gradually if used for more than several days
• Propylene glycol toxicity: With high-dose or prolonged IV infusions (osmolar gap metabolic acidosis, renal dysfunction, seizures)

Common:

• Sedation, drowsiness, fatigue
• Dizziness, confusion, ataxia
• Hypotension, especially with IV use
• Injection site pain or burning

Serious:

• Respiratory depression, apnea, and hypoventilation
• Severe hypotension, shock in unstable patients
• Paradoxical agitation or disinhibition (especially in pediatrics or elderly)
• Anaphylaxis or severe hypersensitivity reactions (rare)
• Withdrawal seizures with abrupt discontinuation after prolonged high-dose use

Clinical Monitoring:

• Continuous SpO₂ and frequent respiratory assessments when given IV/IM, especially when combined with opioids or sedatives
• Blood pressure and heart rate during IV dosing and in hemodynamically unstable patients
• Sedation depth (e.g., RASS) and delirium screening (e.g., CAM-ICU) for ICU patients
• Signs of benzodiazepine withdrawal if tapering after prolonged therapy

Laboratory Monitoring:

• Serum osmolal gap, anion gap, lactate, and renal function when high-dose infusions are used to evaluate for propylene glycol toxicity

• 1. Lexicomp. (2025). Lorazepam: Drug information. Wolters Kluwer. https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/6599
• 2. Glauser, T., Shinnar, S., Gloss, D., et al. (2016). Evidence-based guideline: Treatment of convulsive status epilepticus in children and adults. Epilepsy Currents, 16(1), 48–61. https://doi.org/10.5698/1535-7511-16.1.48
• 3. Barr, J., Fraser, G. L., Puntillo, K., et al. (2013). Clinical practice guidelines for the management of pain, agitation, and delirium in adult ICU patients. Critical Care Medicine, 41(1), 263–306. https://doi.org/10.1097/CCM.0b013e3182783b72
• 4. EMCrit Project. (2024). Status epilepticus (IBCC). https://emcrit.org/ibcc/sz/
• 5. DrugBank Online. (2024). Lorazepam (DB00186). https://go.drugbank.com/drugs/DB00186