Lorazepam Macure
Injectable benzodiazepine for emergency treatment of status epilepticus and procedural sedation
Lorazepam Macure is a concentrated injectable formulation of lorazepam (4 mg/ml), a benzodiazepine used primarily in hospital and emergency settings. It is the first-line treatment for status epilepticus (prolonged seizures) and is also used for pre-operative sedation, acute anxiety management, and procedural sedation. Lorazepam Macure must be administered by trained healthcare professionals with appropriate monitoring and resuscitation equipment immediately available. It is a prescription-only controlled substance in most countries worldwide.
Quick Facts
Key Takeaways
- Lorazepam Macure is an injectable benzodiazepine (4 mg/ml) used primarily for the emergency treatment of status epilepticus, with an IV onset of action of 1–5 minutes.
- It is the internationally recommended first-line benzodiazepine for convulsive status epilepticus, with efficacy demonstrated in landmark randomised controlled trials.
- Administration must occur in a clinical setting with continuous monitoring of respiratory function, blood pressure, and level of consciousness.
- Concomitant use with opioids or other CNS depressants significantly increases the risk of respiratory depression, profound sedation, and death.
- The injection contains propylene glycol and polyethylene glycol as solvents; rapid IV administration must be avoided to minimise the risk of cardiovascular adverse effects.
What Is Lorazepam Macure and What Is It Used For?
Lorazepam Macure belongs to the benzodiazepine class of medications, which act on the central nervous system by enhancing the activity of gamma-aminobutyric acid (GABA), the brain’s primary inhibitory neurotransmitter. By potentiating GABA activity at GABA-A receptors, lorazepam produces anticonvulsant, anxiolytic (anxiety-reducing), sedative, muscle relaxant, and amnestic effects. The injectable formulation is specifically designed for situations requiring rapid onset of action, where oral administration is either impractical or too slow.
The primary clinical indication for Lorazepam Macure is the treatment of status epilepticus, a medical emergency defined as a seizure lasting longer than 5 minutes or two or more seizures occurring without full recovery of consciousness between them. Status epilepticus affects approximately 12–41 per 100,000 people annually and carries a mortality rate of 7–39% depending on the underlying aetiology and treatment delays. Lorazepam has been established as the first-line treatment based on robust evidence from multiple randomised controlled trials, including the landmark Veterans Affairs Status Epilepticus Cooperative Study published in the New England Journal of Medicine.
Beyond status epilepticus, Lorazepam Macure is used for premedication before surgical or diagnostic procedures, where it provides anxiolysis, sedation, and anterograde amnesia. This is particularly valuable in procedures that may cause significant patient anxiety, such as endoscopy, bronchoscopy, or minor surgical interventions. The amnestic properties of lorazepam are often considered advantageous in this context, as patients may have reduced recall of potentially distressing procedural experiences.
Lorazepam Macure may also be used in the acute management of severe anxiety or agitation when oral administration is not feasible, such as in patients who are unable to swallow or who require immediate pharmacological intervention. In critical care settings, it may be employed for short-term sedation of mechanically ventilated patients, although current critical care guidelines generally favour shorter-acting agents such as propofol or dexmedetomidine for prolonged ICU sedation due to concerns about accumulation and prolonged sedation with lorazepam.
Mechanism of Action
Lorazepam binds with high affinity to the benzodiazepine binding site located at the interface between the alpha and gamma subunits of GABA-A receptors. This binding does not directly activate the chloride channel but instead allosterically modulates the receptor, increasing the frequency of chloride ion channel opening events in response to GABA binding. The resulting enhanced chloride influx hyperpolarises the neuronal membrane, making neurons less excitable and less likely to fire action potentials.
The anticonvulsant efficacy of lorazepam in status epilepticus relates to this mechanism: by rapidly enhancing GABAergic inhibition throughout the brain, lorazepam can terminate the sustained, synchronised neuronal firing that characterises epileptic seizures. Importantly, lorazepam has a particularly high affinity for GABA-A receptors and a slow dissociation rate from the benzodiazepine binding site, which contributes to its prolonged duration of anticonvulsant action compared to other benzodiazepines such as diazepam.
What Should You Know Before Receiving Lorazepam Macure?
Before any administration of Lorazepam Macure, the prescribing clinician must carefully evaluate the patient’s medical history, current medications, and clinical status to identify potential contraindications and risk factors. Benzodiazepines as a class carry significant risks, and the injectable route of administration adds additional considerations related to cardiorespiratory monitoring and the solvent system used in the formulation.
Contraindications
Lorazepam Macure is contraindicated in the following situations:
- Hypersensitivity to lorazepam, other benzodiazepines, or any of the excipients (including propylene glycol and polyethylene glycol 400)
- Severe respiratory insufficiency, including acute or severe chronic obstructive pulmonary disease (COPD) exacerbations
- Sleep apnoea syndrome (obstructive sleep apnoea)
- Myasthenia gravis – benzodiazepines may worsen muscle weakness
- Severe hepatic insufficiency – risk of encephalopathy
- Acute narrow-angle glaucoma – unless the patient is already receiving appropriate treatment
- Intra-arterial injection – must never be administered by this route due to the risk of arterial spasm and gangrene
Concomitant use of Lorazepam Macure with opioids (such as morphine, fentanyl, oxycodone, or codeine) may result in profound sedation, respiratory depression, coma, and death. If co-administration is judged medically necessary, the lowest effective dose should be used for the shortest possible duration, and the patient must be closely monitored for signs and symptoms of respiratory depression and sedation.
Warnings and Precautions
Several important warnings and precautions apply to the use of Lorazepam Macure:
Respiratory depression: This is the most clinically significant risk associated with injectable lorazepam. The risk is dose-dependent and is substantially increased when lorazepam is combined with other CNS depressants, including opioids, barbiturates, other sedatives, alcohol, or general anaesthetics. Resuscitation equipment and personnel trained in airway management must be immediately available during and for at least 8 hours following administration.
Paradoxical reactions: In some patients, particularly elderly individuals and children, benzodiazepines may produce paradoxical reactions including agitation, restlessness, irritability, aggression, rage, hallucinations, and psychosis. If these occur, Lorazepam Macure should be discontinued.
Propylene glycol toxicity: The injectable formulation contains propylene glycol as a solvent. Prolonged or high-dose use may lead to propylene glycol accumulation, causing metabolic acidosis, acute kidney injury, and cardiovascular instability. This is particularly relevant in patients receiving continuous infusions in critical care settings and in patients with renal impairment.
Dependence and withdrawal: Even with short-term use, physical dependence on benzodiazepines can develop. Abrupt discontinuation after repeated dosing may precipitate withdrawal symptoms, including rebound anxiety, insomnia, tremor, and in severe cases, seizures. When discontinuing after repeated doses, gradual dose tapering is recommended.
Elderly patients: Older adults are significantly more sensitive to the effects of benzodiazepines due to age-related changes in pharmacokinetics (reduced clearance, increased volume of distribution) and pharmacodynamics (enhanced receptor sensitivity). Lower doses should be used, and monitoring should be more intensive. The risk of falls, fractures, and over-sedation is substantially elevated in this population.
Pregnancy and Breastfeeding
Lorazepam Macure should generally be avoided during pregnancy, particularly during the first trimester, due to an increased risk of congenital malformations. Benzodiazepines cross the placental barrier, and use during the third trimester or labour may cause neonatal effects including hypothermia, hypotonia (floppy infant syndrome), respiratory depression, and feeding difficulties. Neonates exposed to benzodiazepines in utero may also develop withdrawal symptoms after birth.
However, in the specific context of status epilepticus during pregnancy, the immediate risk to both mother and foetus from uncontrolled seizures outweighs the potential drug-related risks. In this situation, lorazepam remains the first-line treatment as recommended by international guidelines.
Lorazepam is excreted in breast milk, and therefore breastfeeding is not recommended during treatment. If a single dose has been administered in an emergency, the clinician should provide guidance on the appropriate duration for withholding breastfeeding based on the elimination half-life (typically 24–48 hours to allow for substantial drug clearance).
How Does Lorazepam Macure Interact with Other Drugs?
Understanding drug interactions is critical for the safe use of Lorazepam Macure, particularly in the acute care setting where patients are often receiving multiple concurrent medications. Lorazepam is primarily metabolised by hepatic glucuronidation (UGT enzymes) rather than the cytochrome P450 system, which reduces its interaction profile compared to some other benzodiazepines. However, pharmacodynamic interactions with other CNS depressants are highly significant and potentially life-threatening.
Major Interactions
| Interacting Drug | Mechanism | Clinical Effect | Action Required |
|---|---|---|---|
| Opioid analgesics (morphine, fentanyl, remifentanil, oxycodone) | Additive CNS depression | Profound sedation, respiratory depression, coma, death | Avoid unless essential; use lowest effective dose; intensive monitoring |
| Clozapine | Additive CNS and respiratory depression | Marked sedation, excessive salivation, hypotension, respiratory arrest | Combination generally contraindicated |
| General anaesthetics (propofol, sevoflurane) | Synergistic CNS depression | Enhanced sedation, prolonged recovery, respiratory depression | Reduce anaesthetic doses; extended post-operative monitoring |
| Barbiturates (phenobarbital, thiopental) | Additive GABA-A receptor modulation | Excessive sedation, respiratory depression, cardiovascular collapse | Extreme caution; dose reduction of both agents |
| Alcohol (ethanol) | Additive CNS depression | Severe respiratory depression, loss of consciousness, death | Alcohol must be avoided; assess patient alcohol intake before dosing |
Pharmacokinetic and Minor Interactions
| Interacting Drug | Mechanism | Clinical Effect | Action Required |
|---|---|---|---|
| Valproic acid / Sodium valproate | Inhibits lorazepam glucuronidation | Increased lorazepam plasma levels by up to 2-fold; prolonged half-life | Reduce lorazepam dose by 50% when co-administered |
| Probenecid | Inhibits glucuronidation and renal excretion | Increased lorazepam half-life and AUC; enhanced sedation | Reduce lorazepam dose by 50% |
| Sedating antihistamines (promethazine, diphenhydramine) | Additive CNS depression | Enhanced sedation and cognitive impairment | Monitor for excessive sedation |
| Loxapine (inhaled) | Additive CNS and respiratory depression | Excessive sedation, respiratory depression | Avoid co-administration within 1 hour |
| Muscle relaxants (baclofen, tizanidine) | Additive CNS depression and muscle relaxation | Enhanced sedation, increased fall risk | Monitor closely; dose adjustment may be needed |
Unlike many other benzodiazepines (such as diazepam and midazolam), lorazepam is primarily metabolised by direct glucuronidation rather than oxidative metabolism via the cytochrome P450 enzyme system. This means that lorazepam has fewer pharmacokinetic interactions with CYP3A4 inhibitors and inducers, making it a preferable choice in patients taking multiple medications that affect CYP450 enzymes, including azole antifungals, macrolide antibiotics, and HIV protease inhibitors.
What Is the Correct Dosage of Lorazepam Macure?
Dosing of Lorazepam Macure must be carefully individualised based on the clinical indication, the patient’s age, body weight, clinical condition, concomitant medications, and response to treatment. The concentrated 4 mg/ml solution must be diluted before IV administration. For IV use, it should be diluted 1:1 with a compatible diluent (0.9% sodium chloride or 5% dextrose). The maximum rate of IV injection should not exceed 2 mg per minute to minimise the risk of apnoea, hypotension, and cardiovascular adverse effects.
Adults
Status Epilepticus (Emergency)
Initial dose: 4 mg IV, administered over 2 minutes (at a rate not exceeding 2 mg/min).
Repeat dose: If seizures continue or recur after 10–20 minutes, a second 4 mg dose may be administered.
Maximum dose: 8 mg in a 12-hour period for status epilepticus.
IM route: 4 mg as a deep intramuscular injection. The IM route should only be used when IV access is not immediately available, as the onset is slower (15–30 minutes).
Pre-operative Sedation (Premedication)
IV route: 0.044 mg/kg (up to a maximum of 2 mg), administered at least 15–20 minutes before the procedure.
IM route: 0.05 mg/kg (up to a maximum of 4 mg), administered 2 hours before the procedure.
For most adults weighing 50–80 kg, this corresponds to approximately 2–4 mg.
Acute Anxiety / Agitation
IV or IM: 0.025–0.05 mg/kg, with doses repeated every 6 hours as needed.
Usual range: 1–4 mg per dose.
Treatment should be limited to the shortest duration possible.
Children
Status Epilepticus (Paediatric)
Neonates: 0.05 mg/kg IV over 2–5 minutes. May be repeated after 10–15 minutes if necessary.
Infants and children (1 month – 11 years): 0.1 mg/kg IV (maximum 4 mg per dose) given over 2–5 minutes. A second dose of 0.1 mg/kg may be given after 10 minutes if seizures persist.
Adolescents (12–17 years): Adult dosing applies; 4 mg IV over 2 minutes.
Paediatric dosing must account for the child’s weight, and the injection should be administered slowly with continuous monitoring.
Elderly Patients
Dose Adjustments in Older Adults
Elderly patients (aged 65 years and over) should receive 50% of the standard adult dose as a starting point, with careful upward titration based on clinical response.
Status epilepticus: Initial dose of 2 mg IV (rather than 4 mg), repeated as necessary with close monitoring.
Premedication: 0.02–0.03 mg/kg (approximately 1–2 mg for most elderly patients).
Elderly patients require extended monitoring periods due to slower drug metabolism and increased sensitivity to CNS-depressant effects.
Missed Dose
Lorazepam Macure is administered by healthcare professionals in acute care settings and is not subject to regular scheduled dosing by the patient. There is no concept of a “missed dose” in the traditional sense. If the clinical situation requires treatment and the previous dose has worn off, the healthcare team will assess the need for additional dosing based on the patient’s current clinical status, time since last dose, and response to previous administration.
Overdose
Overdose with injectable lorazepam presents primarily as excessive CNS depression, manifesting as profound sedation, confusion, diminished reflexes, respiratory depression, hypotension, and potentially coma. In severe cases, particularly when combined with other CNS depressants, respiratory arrest and cardiovascular collapse may occur.
Treatment of overdose is primarily supportive:
- Maintain patent airway and ensure adequate ventilation; intubation and mechanical ventilation may be required
- Continuous monitoring of vital signs (respiratory rate, oxygen saturation, blood pressure, heart rate)
- Intravenous fluids and vasopressors for hypotension if necessary
- Flumazenil (the specific benzodiazepine antagonist) may be considered, but should be used with extreme caution in patients with epilepsy (as it may precipitate seizures) and in patients with known or suspected benzodiazepine dependence (as it may precipitate acute withdrawal)
Flumazenil should be used with extreme caution in patients being treated for status epilepticus, as reversal of benzodiazepine effects may trigger recurrent or worsening seizures. In the context of benzodiazepine overdose with concurrent tricyclic antidepressant ingestion, flumazenil may unmask the proconvulsant effects of the tricyclic, precipitating seizures.
What Are the Side Effects of Lorazepam Macure?
Like all benzodiazepines, Lorazepam Macure can cause a range of adverse effects, most of which are extensions of its pharmacological activity as a CNS depressant. The severity and incidence of side effects are influenced by the dose administered, the rate of injection, the patient’s age and clinical condition, and the presence of concomitant CNS-depressant medications. Healthcare professionals administering this medication must be aware of the full adverse effect profile to enable prompt identification and management.
The following side effects have been reported in clinical trials and post-marketing surveillance. Frequencies are classified according to the MedDRA convention:
Very Common (>1/10)
- Sedation and drowsiness
- Fatigue and lethargy
- Injection site pain or discomfort
Common (1/10 – 1/100)
- Dizziness and unsteadiness
- Muscle weakness (asthenia)
- Confusion and disorientation
- Anterograde amnesia (inability to form new memories)
- Headache
- Nausea
- Respiratory depression (dose-dependent)
- Hypotension (particularly with rapid IV injection)
- Injection site redness (erythema)
Uncommon (1/100 – 1/1,000)
- Visual disturbances (blurred vision, diplopia)
- Paradoxical reactions (agitation, restlessness, aggression, rage)
- Changes in libido
- Dysarthria (slurred speech)
- Ataxia (impaired coordination)
- Constipation
- Changes in appetite
- Thrombophlebitis at injection site
Rare (<1/1,000)
- Respiratory arrest (particularly with rapid IV injection or in elderly)
- Severe hypotension and cardiovascular depression
- Hallucinations and psychosis
- Allergic reactions (rash, urticaria, anaphylaxis)
- SIADH (syndrome of inappropriate antidiuretic hormone secretion)
- Blood dyscrasias (thrombocytopenia, agranulocytosis)
- Hepatic dysfunction
- Propylene glycol toxicity (metabolic acidosis, renal failure – with prolonged high-dose infusions)
Patients should be informed that sedation and impaired psychomotor function are expected after receiving Lorazepam Macure. Following injection, patients must not drive, operate machinery, or make important legal or financial decisions for at least 24 hours, and ideally until they feel fully alert. The amnestic effects may persist for several hours, during which patients may not reliably recall conversations or instructions – important information should be provided in writing and to an accompanying person.
Contact healthcare providers immediately if you experience: severe difficulty breathing or very slow breathing, loss of consciousness, persistent confusion, signs of allergic reaction (rash, swelling, difficulty breathing), or chest pain. These may indicate serious adverse effects requiring urgent intervention.
How Should You Store Lorazepam Macure?
Proper storage of Lorazepam Macure is essential to maintain the chemical stability, sterility, and efficacy of the product. Injectable lorazepam is more sensitive to storage conditions than oral formulations due to its solution-based formulation and the presence of organic co-solvents.
Recommended storage conditions:
- Temperature: Store at 2–8°C (in a refrigerator). Lorazepam injection is sensitive to elevated temperatures, which can accelerate degradation.
- Light protection: Keep ampoules in the original carton to protect from light. Lorazepam is photosensitive and may degrade on exposure to ultraviolet light.
- Do not freeze: Freezing may cause crystallisation of the solution, rendering it unsuitable for use.
- After dilution: Diluted solutions should be used within 24 hours if stored at 2–8°C, or used immediately if prepared at room temperature. However, local hospital pharmacy guidelines may specify shorter in-use stability periods.
Before administration, inspect the solution visually. Do not use if the solution is discoloured, contains visible particles, or if the ampoule appears damaged. A slight yellow tint is normal for the concentrated solution, but any cloudiness, precipitate, or colour change beyond light yellow indicates degradation and the product must be discarded according to local pharmaceutical waste protocols.
As with all medicines, Lorazepam Macure should be kept out of the sight and reach of children. As a controlled substance, it must be stored in a locked controlled drugs cabinet in accordance with applicable national and institutional regulations for the handling and storage of controlled medicines.
Do not use Lorazepam Macure after the expiry date printed on the ampoule and outer carton. The expiry date refers to the last day of that month. Unused or expired medicine should not be disposed of via household waste or wastewater. Return expired or unwanted stock to the pharmacy or appropriate disposal facility in accordance with local regulations for controlled substance disposal.
What Does Lorazepam Macure Contain?
Understanding the full composition of Lorazepam Macure is important for identifying potential sensitivities and for safe clinical practice, particularly given the excipients used in injectable benzodiazepine formulations.
Active substance:
- Lorazepam – 4 mg per ml. Lorazepam is a 3-hydroxy benzodiazepine with the chemical name 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one. Its molecular formula is C15H10Cl2N2O2 and its molecular weight is 321.16 g/mol.
Excipients (inactive ingredients):
- Propylene glycol – Acts as a co-solvent to maintain lorazepam in solution. This excipient is clinically relevant as it can accumulate with prolonged or high-dose use, causing metabolic acidosis, osmolar gap elevation, and renal injury. Monitoring of serum osmolality and anion gap is recommended during prolonged infusions.
- Polyethylene glycol 400 (macrogol 400) – Co-solvent that aids in maintaining solubility of the active ingredient.
- Benzyl alcohol (in multi-dose formulations) – Used as a preservative. Products containing benzyl alcohol must not be used in neonates or premature infants due to the risk of “gasping syndrome”, a potentially fatal condition characterised by metabolic acidosis, respiratory distress, and CNS depression. Benzyl-alcohol-free formulations should be used for neonatal and paediatric patients whenever available.
Pharmaceutical form: Clear, colourless to slightly yellow solution for injection in glass ampoules. Each ampoule typically contains 1 ml of solution (4 mg lorazepam). The product is intended for single use; any unused solution remaining in the ampoule after withdrawal of the required dose must be discarded.
Frequently Asked Questions
Lorazepam Macure is an injectable benzodiazepine (4 mg/ml solution) used in hospital and clinical settings for the emergency treatment of prolonged seizures (status epilepticus), pre-operative sedation (premedication before surgery), and acute management of severe anxiety or agitation. It is administered by intravenous (IV) or intramuscular (IM) injection by healthcare professionals only. It is the internationally recognised first-line pharmacological treatment for convulsive status epilepticus.
When given intravenously, Lorazepam Macure produces effects within 1 to 5 minutes, making it one of the fastest-acting treatments for status epilepticus. When administered intramuscularly, the onset of action is approximately 15 to 30 minutes. The anticonvulsant effect typically lasts 12 to 24 hours, while the sedative effect lasts approximately 6 to 8 hours. This prolonged duration of anticonvulsant action is one of the reasons lorazepam is preferred over diazepam for treating status epilepticus.
Lorazepam Macure is a concentrated injectable formulation (4 mg/ml) designed exclusively for intravenous or intramuscular administration in clinical settings. Unlike oral lorazepam tablets, the injectable form provides a much faster onset of action (1–5 minutes IV versus 15–30 minutes oral), making it essential for emergency situations. The injection must be administered by trained healthcare professionals and requires monitoring of vital signs. Both contain the same active substance but differ in their route of administration, onset time, excipients, and clinical applications.
Yes, respiratory depression is one of the most clinically significant adverse effects of Lorazepam Macure injection. The risk is particularly elevated when the drug is administered too rapidly intravenously, at higher doses, or in combination with other central nervous system depressants such as opioids, barbiturates, or alcohol. This is why Lorazepam Macure must always be administered in a setting with resuscitation equipment available, and patients must have continuous monitoring of respiratory function, oxygen saturation, and blood pressure.
Lorazepam is considered the first-line treatment for status epilepticus based on multiple randomised controlled trials and international guidelines from the ILAE, AES, and NICE. Compared to diazepam, lorazepam has a longer duration of anticonvulsant action (12–24 hours versus 15–30 minutes), lower risk of seizure recurrence, and comparable speed of onset when given intravenously. The VA Status Epilepticus Cooperative Study demonstrated that lorazepam terminated seizures in 64.9% of patients. Its favourable pharmacokinetic profile makes it the preferred initial benzodiazepine for convulsive status epilepticus.
During and after Lorazepam Macure administration, continuous monitoring is essential. This includes pulse oximetry (oxygen saturation), blood pressure, heart rate, respiratory rate, and level of consciousness. Resuscitation equipment, including airway management devices and flumazenil (the benzodiazepine antagonist), must be immediately available. After IV administration, patients should be monitored for at least 8 hours. In elderly patients and those with compromised respiratory function, more intensive monitoring may be required.
References & Sources
All information in this article is based on international medical guidelines, peer-reviewed research, and approved prescribing information. Evidence Level 1A.
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- Alldredge BK, Gelb AM, Isaacs SM, et al. A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus. N Engl J Med. 2001;345(9):631-637. doi:10.1056/NEJMoa002141
- Glauser T, Shinnar S, Gloss D, et al. Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr. 2016;16(1):48-61.
- National Institute for Health and Care Excellence (NICE). Epilepsies in children, young people and adults. NICE guideline [NG217]. Updated 2024.
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- European Medicines Agency (EMA). Lorazepam – Summary of Product Characteristics. Available at: www.ema.europa.eu
- World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd List, 2023. Lorazepam listed for treatment of status epilepticus.
- British National Formulary (BNF). Lorazepam. London: BMJ Group and Pharmaceutical Press. Accessed January 2026.
- Greenblatt DJ, Shader RI, Franke K, et al. Pharmacokinetics and bioavailability of intravenous, intramuscular, and oral lorazepam in humans. J Pharm Sci. 1979;68(1):57-63.
- Silbergleit R, Durkalski V, Lowenstein D, et al. Intramuscular versus intravenous therapy for prehospital status epilepticus (RAMPART). N Engl J Med. 2012;366(7):591-600. doi:10.1056/NEJMoa1107494
About This Article
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iMedic Medical Editorial Team
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