Lorazepam
- 4mg/2ml, 4mg/1ml and 2mg/1ml ampoules (IV, IM)
- 0,5mg, 1mg and 2mg tablets (PO and sublingual alternatives)
Executive Summary
(November 2022)
Emergency Medicine Executive Summary
Lorazepam is an intermediate acting benzodiazepine (BDZ) –a GABA receptor enhancer– with CNS depressant effects including sedative, hypnotic, skeletal muscle relaxing and anticonvulsant activity. It can be administered either by intravenous, intramuscular, sublingual or oral routes. Along with midazolam and clonazepam, lorazepam is one of the most frequently indicated BDZ in the ED.
Sedation timing with single 2-4mg dose:
Intravenous
Onset (IV): 5-10 minutes*
Peak Effect (IV): 30 minutes
Duration (IV): 2-6 hours
(*shorter to terminate seizures)
Intramuscular
Onset (IM) 15 minutes
Peak Effect (IM) 60 minutes
Duration (IM) 6-8 hours
Dosing
Adult dose for status epilepticus:
0.1mg/kg IV (max 4mg/dose).
Repeat every 5-10 min until the crisis has ceased.
Consider initiating an antiepileptic if a second lorazepam dose is required.Adult dose for undifferentiated agitation:
2-4mg sublingual, IV or IM as needed (if severely agitated, IM route is preferred).
Repeat every 20-30 min if necessary.
The BDZ of choice to treat severe undifferentiated agitation is considered to be midazolam IM for its faster onset of action (22).Acute anxiety disorder:
0.5-2mg sublingual, PO or IV as needed.
Repeat every 20-30 minutes if necessary.
Indications
FDA approved, frequently elected as the first-line BDZ (6):
Status epilepticus (IV)
Anxiety disorders (sublingual, IV)
FDA not approved, frequently elected BDZ (16, 17, 20):
Undifferentiated agitation (sublingual, IM, IV)
FDA not approved, sometimes elected amongst other BDZ (3, 8, 17, 24):
Sympathomimetic toxicity (cocaine, methamphetamines)
Alcohol withdrawal
Vertigo
Usage
Introduction
Benzodiazepines (BDZs) are used for a significant variety of conditions in the ED; their different pharmacological properties allow emergency clinicians to have a wide arsenal to treat each particular patient.
The most frequently used BZDs in the ED are lorazepam, diazepam, midazolam and clonazepam; and there is an overall deficit of comparative studies between BDZs to support one preference over another for most disorders.
In the case of lorazepam, it is the BDZ of choice (for IV use) to treat status epilepticus and seizures. For every other condition, the decision-making process of which BDZ to use mostly depends on individual pharmacokinetic profile and its appropriateness on the desired effect.
Seizures and Status Epilepticus (SE):
IV lorazepam is superior to other IV BDZs to treat SE.
There is an established consensus of using lorazepam as the first-line IV BDZ, with a high level of evidence and recommendation for both children and adults (1, 2, 3, 5, 7, 8, 10, 11, 12, 14).
In case of unavailable IV access, midazolam 10mg IM is preferred because it is at least comparable in efficacy to IV lorazepam and is easier to administer (1, 9, 11, 13). In the case of unavailable midazolam, lorazepam is a good alternative for IM route as it has good bioavailability as well. Do not administer diazepam by IM route because of its erratic response (13).
Anxiety disorders, acute anxiety states:
Benzodiazepines have a dominant role for short-term, acute management of anxiety disorders in the ED (3). Amongst them, lorazepam is a good alternative between other BDZ for the management of anxiety disorders in the ED, considering its rapid onset of action and long lasting effect.
Agitation:
Lorazepam is indicated as an adjunctive or single medication to treat undifferentiated agitation in the ED, but midazolam (IM) is considered to be the BDZ of choice to treat severe undifferentiated agitation for its faster onset of action compared with lorazepam (22).
Historically some clinicians have considered lorazepam as a first-line medication, usually in combination with a first generation (typical) antipsychotic such as haloperidol (3), but the latest evidence shows preference for olanzapine and droperidol over haloperidol (22).
Studies have shown lorazepam to have a similar efficacy compared with haloperidol but inferior to the combination of both (15, 21).
It can be administered with haloperidol in the same syringe, a feature that could be useful in the ED compared with other BDZ (20).
Hyperadrenergic states:
This wide spectrum of conditions can be divided into (i) pathological sympathetic stimulation (eg. thyroid storm, tetanus disease, pain, etc), (ii) exogenous sympathomimetic toxicity and (iii) substance withdrawal response. Caution should be taken as these condition’s syndromic presentations can frequently overlap with undifferentiated agitation, and many of them have serious short-term morbidity and mortality.
Benzodiazepines are part of the standard therapy for acute cocaine intoxication (23, 24, 26). Diazepam and lorazepam are the most studied BDZ for cocaine-associated chest pain, and both are considered as first-line alternatives (3, 4, 26).
For Alcohol Withdrawal Syndrome lorazepam and diazepam are considered the best alternatives (3), but most authors recommend escalating doses of diazepam as the BDZ of choice (4, 25).
⚠ Cautions
Caution should be taken with profound sedation, coma and respiratory depression; particularly when repeated doses are administered, or combined with other CNS depressants and/or opioids.
Benzodiazepines are prone to develop dependence, they should be administered for immediate or short-term therapy in the ED; it is recommended not to prescribe more than a 7-days course of BDZ in this setting (1, 3). Adequate outpatient follow-up should be planned to establish a long-term therapeutic approach to patients who have required BDZs in the ED.
Adult dose
Status epilepticus and seizures:
0.1mg/kg IV (max 4mg/dose).
Repeat every 5-10 min until crisis cessation.
Initiate load with antiepileptic agent if a second lorazepam dose is required.Acute anxiety disorder:
0.5-2mg sublingual, PO or IV as needed.
Repeat every 20-30 minutes if necessary.Agitation:
2-4mg sublingual or IM as needed.
Consider as an adjunct with 1st generation antipsychotic (droperidol).
Repeat every 20-30 min if necessary.Hyperadrenergic states (cocaine and other sympathomimetic toxicity, substance withdrawal, neuroleptic malignant syndrome, serotonin syndrome, tetanus, etc):
2-4mg IV.
Repeat every 10-20 min as needed.Vertigo:
1-2mg sublingual or IV.
BDZ are given as an adjunctive therapy along with other vestibular- inhibiting medications and non-pharmacological interventions depending on the cause of vertigo.Procedural sedation:
EMDrugs do not recommend lorazepam for procedural sedation.
Short acting BDZ (eg. midazolam) or ketamine are the most often appropriate alternatives.
Pediatric dose
Status epilepticus and seizures (1, 2, 7, 12):
0.1mg/kg IV (max 4mg per dose)*.
Repeat every 5 minutes if necessary.
*If unavailable IV access, consider diazepam 0.5mg/kg rectal (max 20mg per dose).Acute anxiety disorder (3):
A comprehensive approach is essential to treat anxiety in children (non-pharmacological interventions).
0.05mg/kg sublingual, IV depending on severity.
Repeat every 30 minutes if necessary.Undifferentiated Agitation (18, 19):
0.05-0.1mg/kg, usual dose 0.5-2mg sublingual, IV, IM depending on severity.
Combined therapy with first generation antipsychotics (eg. haloperidol) is more effective. Consider monotherapy with second generation antipsychotic (eg. olanzapine).Agitation due to substance intoxication or withdrawal (19):
0.05-0.1mg/kg (max 4mg/dose) sublingual, PO, IV, IM depending on severity.Procedural sedation:
EMDrugs do not recommend lorazepam for procedural sedation.
Short acting benzodiazepines are the most appropriate alternatives (eg. midazolam).
References
Overview:
Walls RM, Hockberger RS, Gausche-Hill M. Rosen’s Emergency Medicine : Concepts and Clinical Practice. 9th edition. Philadelphia, PA: Elsevier; 2018
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PubmedNIH-NLM (National Institutes of Health National Library of Medicine). DailyMed. Label: Ativan - lorazepam injection. Updated in March 2021
DailyMed
Seizures and Status Epilepticus
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Agitation
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Sympathomimetic toxicity, alcohol withdrawal
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