Bedside Snapshot

Use It For
Status epilepticus without IV access (IM first-line); home seizure-cluster rescue (Nayzilam); procedural sedation and amnesia; sedation of intubated patients
Adult Dose
  • Status epilepticus: 10 mg IM once (over 40 kg); IV only if lorazepam and diazepam are unavailable: 0.1 mg/kg (max 10 mg), repeat at 5 min
  • Procedural sedation: 1–2.5 mg IV, titrate
  • Intubated sedation: 0.02–0.1 mg/kg/hr IV
Pediatric Dose
Under 13 kg: 0.2 mg/kg IM or IN (max 10 mg); 13–40 kg: 5 mg IM; over 40 kg: 10 mg IM. Under 40 kg: repeat once at 5 min if still seizing (cumulative max 10 mg). Buccal 2.5–10 mg by age; IV/IO 0.1 mg/kg (max 10 mg)
Onset / Duration
IV: 3–5 min / recovery usually within 2 hr (up to 6 hr); IM: 15 min, peak 30–60 min (seizures stopped a median 3.3 min after IM injection); IN: peak level about 17 min
Do Not Give / Hold If
  • Do not give: hypersensitivity; acute narrow-angle glaucoma
  • Sedation: hold for shock, coma, alcohol with low vitals, SpO₂ <90%, SBP <90 mmHg or no airway kit
  • Seizing: never withhold for low SpO₂; give it and ventilate
Watch For
Apnea and hypoventilation (SpO₂, EtCO₂); hypotension, worse with opioids (BP every 5 min); paradoxical agitation (check for hypoxia); prolonged sedation after infusions
Reversal / Rescue
Airway, O₂ and bag-valve mask first. Flumazenil 0.2 mg IV every 1 min (max 1 mg) for iatrogenic oversedation only; not after midazolam for status epilepticus
Must Remember
1 mg/mL and 5 mg/mL vials look alike: 10 mg is 2 mL of 5 mg/mL but 10 mL of 1 mg/mL. Say the mg and the mL aloud and double-check every pediatric dose

Indications

Emergency & Prehospital

  • Convulsive status epilepticus without IV access: First-line is an IM benzodiazepine at 5 min. With no IV in place, IM works better than IV lorazepam (AES Level A in adults; RAMPART). The FDA label covers only the 10 mg IM autoinjector, in adults. The weight bands, IN use, IV use and the 5-minute repeat in children come from AES 2016, RAMPART and TREKK 2025.
  • Prolonged seizure in a child without IV access: IM, intranasal or buccal midazolam (AES Level B for children; IN and buccal use of the injection are off-label)
  • Seizure clusters at home: Nayzilam nasal spray, given by a caregiver, age 12 years and older (FDA-labeled)
  • Severe agitation: IM when there is no IV, or IV with droperidol (off-label)
  • Procedural sedation, anxiolysis and amnesia: cardioversion, pacing, fracture reduction; add an analgesic for painful procedures

ED / ICU / Transport

  • Sedation of intubated patients: FDA-labeled infusion. PADIS 2018 points to propofol or dexmedetomidine first. The 2025 focused update (Lewis et al., Crit Care Med 2025) conditionally suggests dexmedetomidine over propofol. It makes no recommendation on benzodiazepines for ICU anxiety.
  • Induction of general anesthesia: FDA-labeled; slower onset than standard agents used for rapid sequence intubation
  • Refractory status epilepticus: continuous IV infusion with continuous EEG after second-line drugs fail (off-label). See the status epilepticus condition page

Other Uses

  • Preoperative sedation and anxiolysis: IM or IV in adults; oral syrup for children before procedures

Dosing & Administration

Doses vary by protocol; follow local protocols and medical direction.

Available Forms

  • Injection 1 mg/mL: 2 mL and 5 mL vials; for slow IV titration
  • Injection 5 mg/mL: 1 mL (5 mg) and 2 mL (10 mg) vials; the EMS form for IM and IN dosing
  • Preservatives: some vials contain 1% benzyl alcohol. That rules them out for neonates and for intrathecal or epidural use. In neonates, use preservative-free midazolam
  • Premix: 1 mg/mL in 0.9% sodium chloride (50 mg/50 mL and 100 mg/100 mL)
  • Autoinjector: 10 mg/0.7 mL, IM only, for adult status epilepticus; cartons of 480. Seizalam (5 mg/mL IM vial) is discontinued
  • Nasal spray (Nayzilam): 5 mg in 0.1 mL single-use unit; do not prime or test
  • Oral syrup: 2 mg/mL, for pediatric premedication
High-Alert Medication: IV midazolam and pediatric oral midazolam are ISMP high-alert. Mixing up 1 mg/mL with 5 mg/mL is the classic error. 10 mg is 2 mL of 5 mg/mL or 10 mL of 1 mg/mL, so say the concentration out loud. Every pediatric dose and infusion gets a second clinician's check.

Adult Dosing

IndicationDose & RouteRepeat / MaxNotes
Status epilepticus, no IV (adults and children over 40 kg)
10 mg IM, mid-outer thigh (autoinjector or syringe)
Single dose. Still seizing at 5 min: 10 mg already meets the ESETT adequate dose, so give the second-line drug
High-alert RAMPART dose. Differs from FDA label: only the 10 mg IM autoinjector is labeled (adults); weight bands, IN use, IV use and the 5-minute repeat in children come from AES 2016, RAMPART and TREKK 2025. Give at 5 min; do not wait for an IV
Status epilepticus, IV/IO access
0.1 mg/kg IV/IO
Max 10 mg per dose; repeat once at 5 min; max 2 doses
High-alert Only if lorazepam and diazepam are unavailable (AES first-line IV drugs). Differs from FDA label (IV use not labeled). ESETT counted 10 mg IV as adequate (an enrollment threshold, not a target)
Seizure cluster, home rescue (Nayzilam, age 12 yr and older)
5 mg IN (one spray in one nostril)
One more 5 mg spray in the other nostril after 10 min if needed; max 2 doses per episode; max 1 episode every 3 days or 5 per month
No second dose for trouble breathing or unusual sedation. EMS: the home dose counts as dose 1
Procedural sedation, healthy adult under 60 yr
1–2.5 mg slow IV over at least 2 min
Wait 2 min, then small increments; total over 5 mg not usually needed
High-alert About 30% less with opioid premedication
Procedural sedation, age 60 yr and older or debilitated
1–1.5 mg slow IV over at least 2 min
Increments of no more than 1 mg; total over 3.5 mg not usually needed
High-alert At least 50% less with opioid or other CNS-depressant premedication
Preoperative sedation (IM)
0.07–0.08 mg/kg IM (about 5 mg), up to 1 hr before
Single dose
Reduce for age 60 yr and older, COPD, high-risk patients or opioid co-use
Induction of anesthesia
0.3–0.35 mg/kg IV over 20–30 sec (under 55 yr, no premedication); 0.3 mg/kg over 55 yr; 0.2–0.25 mg/kg in severe systemic disease
Increments of about 25% of the first dose; max 0.6 mg/kg total
High-alert Premedicated: 0.15–0.35 mg/kg. Onset 1.5–2.5 min; causes hypotension
Sedation of intubated patients (infusion)
Optional load 0.01–0.05 mg/kg IV (about 0.5–4 mg) slowly; then 0.02–0.1 mg/kg/hr (1–7 mg/hr)
Load may repeat every 10–15 min; no fixed max: titrate to the lowest rate that meets the target
High-alert Lowest doses with residual anesthetic, other sedatives or opioids. Reassess daily
Severe agitation, IM (off-label)
5 mg IM
Single 5 mg dose studied; no repeat interval set
High-alert Klein 2018 (Ann Emerg Med): more patients adequately sedated at 15 min than with IM haloperidol or ziprasidone in a large ED study. Lower doses in older adults or with alcohol or opioids. Capnography
Severe agitation, IV combination (off-label)
5 mg IV with droperidol 5 mg IV
Up to 2 more 5 mg doses (trial regimen; max 15 mg)
High-alert Taylor 2017 (Ann Emerg Med): studied in adults 18–65 yr in the ED. Capnography; airway equipment ready
Refractory status epilepticus, adult and child (off-label)
Load 0.2–0.5 mg/kg IV, then 0.1–2 mg/kg/hr
No fixed max: titrate to EEG seizure or burst suppression (5–15 sec interburst interval)
Range from the AES 2020 review (Table 1), not a label; the mg/kg/hr figures are the source's. The mcg/kg/min equivalent is calculated: 2 mg/kg/hr is about 33 mcg/kg/min (AES prints 2–40). Intubated, EEG-monitored patients only. Clearance slows with prolonged infusion

Pediatric Dosing

IndicationDose (per kg) & RouteMax Single / Max TotalNotes
Status epilepticus, no IV, under 13 kg
0.2 mg/kg IM (preferred) or IN
Max 10 mg per dose; repeat once at 5 min, cumulative max 10 mg
High-alert NASEMSO and TREKK 2025 dose. Not FDA-labeled in children (off-label)
Status epilepticus, no IV, 13–40 kg
5 mg IM, mid-outer thigh (over 40 kg: 10 mg, adult row)
Max 5 mg per dose; second 5 mg if still seizing at 5 min (cumulative max 10 mg)
High-alert Differs from FDA label. AES Fig 1 lists one dose; the repeat follows TREKK 2025. Cumulative 10 mg meets the ESETT adequate dose under 32 kg (0.3 mg/kg IM). TREKK 2025 writes the lower band as 13 kg or less, so at exactly 13 kg it also gives 0.2 mg/kg (about 2.6 mg)
Status epilepticus, intranasal
0.2 mg/kg IN, split between nostrils (5 mg/mL)
Max 10 mg; max 1 mL per nostril; repeat once at 5 min, cumulative max 10 mg
Off-label. IM needed less rescue therapy than IN in a 2026 meta-analysis
Status epilepticus, buccal
By age, between gum and cheek: 3 months–under 1 yr 2.5 mg; 1–under 5 yr 5 mg; 5–under 10 yr 7.5 mg; 10 yr and older 10 mg
Max 10 mg; single dose
Off-label in the US. Age bands from the EU Buccolam SmPC, section 4.2 (EU-licensed product, not sold in the US)
Status epilepticus, IV/IO access
0.1 mg/kg IV/IO
Max 10 mg per dose; repeat once at 5 min; max 2 doses
High-alert Only if lorazepam or diazepam is unavailable. Under 32 kg, ESETT counted 0.2 mg/kg IV or 0.3 mg/kg IM total as adequate (enrolled age 2 yr and older). Count caregiver doses
Refractory status epilepticus, IV infusion (off-label)
Load 0.2–0.5 mg/kg IV, then 0.1–2 mg/kg/hr
No fixed max: titrate to EEG endpoint
Same range as the adult row. A 2025 pediatric systematic review found effective rates clustered at 2–5 mcg/kg/min (0.12–0.30 mg/kg/hr), above the traditional start of 1 mcg/kg/min; data limited and heterogeneous
IV sedation, 6 months–5 yr
0.05–0.1 mg/kg slow IV
Total up to 0.6 mg/kg; usually no more than 6 mg
High-alert Under 6 months: dosing unclear; small increments with close monitoring
IV sedation, 6–12 yr
0.025–0.05 mg/kg slow IV
Total up to 0.4 mg/kg; usually no more than 10 mg
High-alert 12–16 yr: adult dosing, usually no more than 10 mg total
IM sedation (non-neonates)
0.1–0.15 mg/kg IM
Up to 0.5 mg/kg in anxious patients; total usually no more than 10 mg
Onset within 5 min; peak sedation 15–30 min
Oral premedication (syrup 2 mg/mL)
0.25–0.5 mg/kg PO, single dose
Max 20 mg. Up to 1 mg/kg (still max 20 mg) at 6 months–under 6 yr or in less cooperative children
High-alert 0.25 mg/kg may suffice at 6 to under 16 yr or in cooperative patients when sedation need not be deep (syrup label); use 0.25 mg/kg with cardiac or respiratory compromise or opioid co-use. Monitored settings only
Sedation of intubated patients (non-neonates)
Load 0.05–0.2 mg/kg IV over at least 2–3 min; then 0.06–0.12 mg/kg/hr (1–2 mcg/kg/min)
No fixed max: titrate to the sedation target
High-alert Hemodynamically compromised: small load increments. Neurotoxicity warning for repeated or prolonged exposure under 3 yr
Neonates (intubated, infusion only)
Under 32 weeks: 0.03 mg/kg/hr (0.5 mcg/kg/min). Over 32 weeks: 0.06 mg/kg/hr (1 mcg/kg/min)
No IV loading dose; never a rapid IV push
High-alert Hypotension and seizures with rapid injection, especially with fentanyl. Preservative-free midazolam only

Dosing weight: in obese children, base the mg/kg doses on ideal body weight (label). See pediatric weight-based dosing and Broselow tape.

Continuous Infusion

SettingExample ConcentrationStartTitrateUsual Range / Max
Adult ICU sedation (intubated)
1 mg/mL premixed bag, or 5 mg/mL diluted to 0.5 mg/mL (institution-specific)
0.02–0.1 mg/kg/hr (1–7 mg/hr)
Up or down by 25–50% of the initial rate; lower 10–25% every few hours to the minimum effective rate
No fixed max
Pediatric ICU sedation (intubated)
Institution-specific
0.06–0.12 mg/kg/hr (1–2 mcg/kg/min)
To the sedation target
No fixed max
Neonatal ICU sedation (intubated)
Institution-specific
0.03 mg/kg/hr (under 32 weeks) or 0.06 mg/kg/hr (over 32 weeks)
Slowly; no boluses
Lowest effective rate; reassess often

Preparation & Administration

  • IV push: over at least 2 min for sedation; wait 2 min (3–5 min to peak) before the next dose
  • Dilution: 0.9% sodium chloride or D5W; 0.5 mg/mL is stable 24 hr in D5W or saline and 4 hr in lactated Ringer's
  • Routes: IM in the mid-outer thigh (the autoinjector can go through clothing); IN with an atomizer, no more than 1 mL per nostril; buccal between gum and cheek, not toward the throat
  • Infusion: on a pump, dedicated or verified-compatible line
Dosing Notes:
  • Go lower for patients 60 yr and older, the debilitated, and anyone on opioids or other CNS depressants.
  • Count every benzodiazepine dose toward the status epilepticus total, caregiver doses included.

Contraindications & Precautions

Contraindications

  • Known hypersensitivity to midazolam (syrup: also cherry flavoring or excipient allergy)
  • Acute narrow-angle glaucoma; open-angle glaucoma only if the patient is on treatment
  • Benzyl alcohol-containing vials: premature infants; intrathecal or epidural use

Precautions

  • Setting: IV midazolam only with continuous respiratory and cardiac monitoring, bag-valve mask, intubation equipment and airway-skilled staff immediately available
  • Older adults, COPD, heart failure, opioid co-use: apnea, hypotension and rare deaths, mostly with other CNS depressants. Uncompensated illness, severe fluid or electrolyte disturbance and hypovolemia all add risk
  • Prolonged infusions (days to weeks): physical dependence; taper rather than stop abruptly
  • Nayzilam: consider a first dose under supervision, without a seizure, in patients at higher risk of respiratory depression; antiepileptic class warning for suicidal thoughts
  • Late pregnancy and children under 3 yr: neonatal sedation and withdrawal; brain-development warning with repeated or prolonged anesthetic exposure

Hold / Reassess If

  • Status epilepticus: hypoxia is expected during a convulsion. Don't hold the benzodiazepine for a low SpO₂. Give it and support the airway
  • Sedation or infusion: shock, coma, or acute alcohol intoxication with depressed vital signs: do not give. SpO₂ <90%, falling respiratory rate or EtCO₂ >50 mmHg: stop and support ventilation
  • SBP <90 mmHg in adults, or age-based hypotension in children (PALS: <70 + 2 × age in years, ages 1–10), after a dose: stop, give fluids, reassess before any further dose
  • Seizure has stopped: no more benzodiazepine. Two benzodiazepine doses already given (count caregiver doses) means no third. The airway is at high risk of compromise. Give the second-line drug (levetiracetam, fosphenytoin or valproate).
FDA Boxed Warning:
  • Injection and oral syrup: respiratory depression and arrest, sometimes fatal. Monitor continuously with airway equipment and skilled staff on hand. A deeply sedated child needs a dedicated observer, not the clinician doing the procedure. Individualize every dose (adult IV sedation starts at no more than 2.5 mg). Never a rapid IV push in neonates.
  • Opioids (all products): combined use can cause profound sedation, respiratory depression, coma and death.
  • IM autoinjector and nasal spray: abuse, misuse and addiction. Dependence and life-threatening withdrawal follow if it is used more often than recommended.

Adverse Effects & Toxicity

Common

  • Decreased tidal volume or respiratory rate (23% IV, 11% IM in adults) and apnea (15% after IV sedation doses)
  • Blood pressure and heart rate changes; hiccups (4%); injection-site pain (5%)
  • Nasal spray: sleepiness, headache, nasal discomfort, throat irritation, runny nose
  • Nausea (3%) and vomiting (3%); drowsiness and amnesia for hours
  • Children (IV): desaturation 4.6%, apnea 2.8%, hypotension 2.7%, paradoxical reactions 2%

Serious / Life-Threatening

EffectRecognitionManagement
Respiratory depression and apnea
Falling RR, SpO₂ <90%, rising EtCO₂ or flat waveform, snoring, obstruction
Stop dosing; jaw thrust, O₂, bag-valve mask; intubate if needed
Hypotension
BP drop after IV doses, induction or infusion; worse with opioids, hypovolemia, neonates on fentanyl
Stop or reduce; fluid bolus; vasopressor per protocol
Paradoxical agitation
Agitation, involuntary movements, combativeness
Rule out hypoxia first; stop midazolam
Delirium and prolonged ventilation
Positive CAM-ICU; slow waking after an infusion
Prefer propofol or dexmedetomidine for ventilated adults; daily sedation targets
Withdrawal after prolonged infusion
Tremor, agitation, hallucinations, seizures, vomiting, sweating
Taper; do not stop abruptly after days of infusion
Intra-arterial injection
Pain, blanching or color change distal to the site
Stop injection; treat as arterial injury

Overdose & Toxicity Management

  • Signs and care: sedation progressing to respiratory depression, apnea, hypotension and coma; markedly abnormal vitals suggest a co-ingestant such as alcohol or opioids. Airway, ventilation, IV fluids, glucose; Poison Control 1-800-222-1222
  • Flumazenil for sedation reversal: adult 0.2 mg IV over 15 sec, then 0.2 mg every 1 min (max 1 mg). Children 1 yr and older: 0.01 mg/kg (max 0.2 mg) every 1 min, max total 0.05 mg/kg or 1 mg
  • Flumazenil cautions: contraindicated after midazolam given for a life-threatening condition (status epilepticus, raised intracranial pressure). Avoid it in dependent patients and mixed overdoses. Resedation can occur.

Monitoring
ParameterWhen / How OftenTarget / Act If
Clinical: seizure activity and mental status
Continuously; time every dose and the total mg
Seizing 5 min after an adequate benzodiazepine dose: second-line drug. Not waking: suspect nonconvulsive status (EEG)
Clinical: SpO₂ and respiratory rate
Continuously from the first dose until awake
SpO₂ <90% or shallow breathing: reposition, O₂, bag-valve mask
Clinical: waveform EtCO₂
Continuously during sedation, after seizure doses and in transport
EtCO₂ >50 mmHg or loss of waveform: stimulate, ventilate, reassess airway
Clinical: BP and HR
Baseline, then every 5 min after IV doses and during infusion changes
SBP <90 mmHg in adults, or age-based hypotension in children: stop or reduce, fluids, reassess
Clinical: sedation depth and delirium
Before each dose; RASS on infusions; CAM-ICU each shift
Deeper than target: reduce the rate. Prolonged sedation after stopping: consider accumulation (renal or hepatic failure, CYP3A4 inhibitor). Positive CAM-ICU: reassess the need for benzodiazepines
Laboratory: glucose
Fingerstick on arrival in every seizure or altered patient
Hypoglycemia: treat before or alongside benzodiazepines
Clinical: after flumazenil
Continuous monitoring until resedation is unlikely
Resedation or hypoventilation: support ventilation; repeat flumazenil only per its label

Interactions & Compatibility

Clinically Significant Interactions

Drug / ClassEffectWhat To Do
Opioids (fentanyl, morphine, others)
Profound sedation, apnea, hypotension, death (boxed warning)
Reduce the midazolam dose (about 30% or more); titrate one drug at a time; continuous SpO₂ and EtCO₂
Propofol, barbiturates (phenobarbital), alcohol, other sedatives
Additive CNS and respiratory depression
Lower doses; expect airway support after a benzodiazepine plus phenobarbital load
Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin; ritonavir including Paxlovid; saquinavir)
Clearance falls (by 56% with saquinavir); prolonged, deep sedation
Avoid with the nasal spray. Oral midazolam is contraindicated with Paxlovid (PAXLOVID prescribing information). Injection: reduce doses, monitor closely
Moderate CYP3A4 inhibitors (erythromycin, diltiazem, verapamil); cimetidine
Half-life about doubles with erythromycin; longer sedation
Avoid with Nayzilam. Injection: lower or less frequent doses; watch for delayed oversedation
CYP3A4 inducers (phenytoin, phenobarbital, carbamazepine, primidone, rifampin)
Oral midazolam exposure falls by more than 90%
Oral premedication may fail; choose another route or agent
Flumazenil
Reverses sedation (flumazenil label); can precipitate withdrawal and seizures
Avoid after midazolam for status epilepticus and in dependent patients

IV Compatibility

  • Dilute with 0.9% sodium chloride or D5W; at 0.5 mg/mL it is stable 24 hr in either and 4 hr in lactated Ringer's (Hospira label).
  • Infuse on a pump through a dedicated or verified-compatible line; check every Y-site drug before connecting.
  • Verify with an institutional compatibility resource.

Special Populations
  • Pediatrics: the half-life runs 0.8–3.3 hr over age 1 yr. Expect more paradoxical reactions. Deep sedation needs a dedicated observer. Doses: Pediatric Dosing table.
  • Neonates: in seriously ill neonates the half-life runs 6.5–12 hr. Infusion only. No loading dose, and never a rapid push. For neonatal seizures: phenobarbital is first-line. The seizure autoinjector label says benzodiazepines should not be used for neonatal status epilepticus.
  • Pregnancy: use late in pregnancy or labor can cause neonatal sedation and withdrawal. Treat maternal status epilepticus without delay, then monitor the newborn. Seizing at 20 weeks' gestation or later, or up to 6 weeks postpartum? Treat it as eclampsia until proven otherwise. The first-line drug is magnesium sulfate (ACOG Practice Bulletin 222). A benzodiazepine is for a seizure that continues despite magnesium.
  • Lactation: it enters breast milk. After a procedural dose, the label suggests pumping and discarding milk for 4–8 hr.
  • Older adults: the half-life about doubles and clearance falls about 25%. Reduce IV and IM doses. Benzodiazepines sit on the AGS Beers list to avoid (falls, delirium). Acute seizure and procedural use remain appropriate.
  • Renal impairment: in ICU patients with acute renal failure on infusions, the half-life rose from 7.6 to 13 hr. The glucuronide built up to about 10 times the parent level. There is no fixed adjustment. Titrate to the lowest effective rate.
  • Hepatic impairment: in alcoholic cirrhosis the half-life runs about 2.5 times longer and clearance is halved. Use smaller doses at longer intervals.
  • Obesity: it raises the volume of distribution about 50% and lengthens the half-life (5.9 vs 2.3 hr). Clearance stays unchanged, so titrate infusions to the sedation target. Status epilepticus doses do not change (10 mg IM).
  • Heart failure: the half-life about doubles and clearance falls 25%. Start low. For ICU sedation strategy, see the analgosedation guide.

Field & Transport Considerations
  • Scope: Paramedics, RNs and critical-care transport teams can give IM, IN, IV and buccal doses. Caregivers give Nayzilam at home. Varies by state and agency protocol.
  • Storage & Stability: 20–25 °C (68–77 °F). The autoinjector and nasal spray tolerate 15–30 °C. Don't freeze the autoinjector. Schedule IV: secure storage, counts and witnessed waste.
  • Carried Concentration: 10 mg IM is 2 mL of 5 mg/mL. Draw IN doses from 5 mg/mL only. At 1 mg/mL you get too much volume for the nose.
  • Home rescue on scene: ask what was given (Nayzilam, Valtoco, Diastat, buccal midazolam), the dose and the time. That dose is dose 1.
  • Infusions in Transport: run it on a pump with the drug library. Confirm the concentration (1 mg/mL premix vs pharmacy mix), the rate in mg/hr and mg/kg/hr, and the bag volume for the trip. Every sedated patient gets capnography.
  • Handoff Essentials: seizure onset time; every benzodiazepine dose with time, route and mg (including caregiver doses); airway steps; glucose; current infusion rate and last titration; response and mental status.

Clinical Pearls
Know when the benzodiazepine phase is over: Still seizing at least 5 min after an adequate total dose? ESETT calls that benzodiazepine-refractory (midazolam 10 mg IV or IM; under 32 kg, 0.3 mg/kg IM or 0.2 mg/kg IV). Then give levetiracetam, fosphenytoin or valproate rather than a third benzodiazepine.
Timing, per AES 2016: 0–5 min is for stabilizing. At 5 min, give one benzodiazepine course, 2 doses at most in total, counting caregiver, EMS and ED doses. Still seizing 5 min after an adequate dose? Start a second-line drug at once, no later than the 20-min mark. Judge it at 40 min.
IM wins the race to the drug: In RAMPART, IM midazolam got in faster: median time to treatment was 1.2 min against 4.8 min for IV lorazepam. More IM patients arrived seizure-free (73% vs 63%).
IM may outperform IN in children: A 2026 meta-analysis, mostly of prehospital pediatric seizures, linked IM with less rescue therapy and seizures stopping about 24 sec sooner. Those are associations. They are not proof. Use IN when IM is not practical.
Exam discriminator (NREMT, CEN, FP-C):
  • No IV, active seizure: IM midazolam.
  • IV in place: IV lorazepam or diazepam first. IV midazolam 0.1 mg/kg (max 10 mg) only if neither is available.
  • Home rescue: Nayzilam (12 yr and older), Valtoco or rectal diazepam.
  • Ventilated ICU adult: propofol or dexmedetomidine before midazolam.
Agitation after sedation: think hypoxia first. Paradoxical reactions are uncommon: 2% of children. Before you give more midazolam, check SpO₂, EtCO₂ and the airway.
Infusions outlast the half-life: A single dose wears off in about 2 hr. Days of infusion in an older, obese or renal-failure patient are another story: the patient can stay sedated after the drip stops. Use daily sedation targets.

Pharmacology

Mechanism of Action

  • Binds the benzodiazepine site of the GABA-A receptor → more GABA-driven chloride entry → sedation, anxiolysis, amnesia and seizure termination. It modulates GABA. It does not open the channel itself.
  • Opioids act at mu receptors, a different site: with opioids (or propofol, barbiturates or alcohol) on board, respiratory depression and apnea become much more likely.
  • Hydrochloride salt at pH about 3 (up to about 25% open-ring form). At body pH it reverts to the lipophilic closed-ring form, which is why IM absorption is reliable and brain entry is fast.

Pharmacokinetics

RouteOnsetPeakDuration
IV
Sedation 3–5 min; induction 1.5–2.5 min
3–5 min
Recovery usually within 2 hr (up to 6 hr)
IM
Adults about 15 min (seizures stopped a median 3.3 min after injection in RAMPART); children within 5 min
30–60 min (adults); 15–30 min (children)
—
IN (Nayzilam)
—
Peak level median 17 min (8–28 min); bioavailability about 44%
—
PO (syrup)
Satisfactory sedation within 10 min in most children
—
—
  • Half-life: 1.8–6.4 hr in healthy adults (mean about 3 hr). It runs about twice as long in older adults and heart failure, 0.8–3.3 hr in children over 1 yr, and 6.5–12 hr in seriously ill neonates. It accumulates with prolonged infusion.
  • Metabolism and elimination: the liver's CYP3A4 turns 60–70% into 1-hydroxymidazolam, about as potent as the parent. Its glucuronide is renally cleared and builds up in renal failure. Urine carries 45–57% of an IV dose as that glucuronide. Under 0.5% comes out unchanged.
  • Protein binding / Vd: about 97% bound; Vd 1–3.1 L/kg; IM bioavailability over 90%.

Names & Classification
Generic Name
Midazolam hydrochloride (injection, syrup); midazolam (nasal spray)
Brand Names
Versed (discontinued in the US; the name is still widely used); Nayzilam (nasal spray); Seizalam (discontinued). Injection, syrup and the 10 mg autoinjector are generic
Pharmacologic Class
Short-acting benzodiazepine (GABA-A receptor positive allosteric modulator)
Therapeutic Class
Sedative-hypnotic; anxiolytic; amnestic; anticonvulsant; anesthesia adjunct
Controlled Substance
C-IV (DEA Schedule IV)
ISMP High-Alert
Yes: ISMP high-alert medication (moderate sedation agents, IV; oral sedation agents for children)
Look-Alike / Sound-Alike
No name pair commonly reported; the practical error is confusing the 1 mg/mL and 5 mg/mL concentrations

Related

References
  1. Hospira, Inc. (2026). Midazolam Injection, USP CIV: Prescribing information. DailyMed, U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1abda8b8-48a8-4995-af86-39220d1aa240
  2. UCB, Inc. (2023). NAYZILAM (midazolam) nasal spray, CIV: Prescribing information. DailyMed, U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2b29422e-54d5-4a49-8522-e9cf752368c3
  3. Glauser, T., Shinnar, S., Gloss, D., et al. (2016). Evidence-based guideline: Treatment of convulsive status epilepticus in children and adults: Report of the Guideline Committee of the American Epilepsy Society (landmark guideline; current AES guideline). Epilepsy Currents, 16(1), 48–61. https://doi.org/10.5698/1535-7597-16.1.48
  4. National Association of State EMS Officials, Medical Directors Council. (2022). National model EMS clinical guidelines (Version 3.0; Seizures, pp. 100–103). NASEMSO; copy hosted by Iowa Department of Health and Human Services. https://hhs.iowa.gov/media/198/download
  5. Silbergleit, R., Durkalski, V., Lowenstein, D., et al., for the NETT Investigators. (2012). Intramuscular versus intravenous therapy for prehospital status epilepticus (RAMPART; landmark trial). New England Journal of Medicine, 366(7), 591–600. https://doi.org/10.1056/NEJMoa1107494
  6. Kapur, J., Elm, J., Chamberlain, J. M., et al., for the NETT and PECARN Investigators. (2019). Randomized trial of three anticonvulsant medications for status epilepticus (ESETT; landmark trial). New England Journal of Medicine, 381(22), 2103–2113. https://doi.org/10.1056/NEJMoa1905795
  7. Devlin, J. W., Skrobik, Y., Gélinas, C., et al. (2018). Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU (PADIS). Critical Care Medicine, 46(9), e825–e873. https://doi.org/10.1097/CCM.0000000000003299
  8. Mohnkern, J. D., Khalid, A., Ibrahim, M., et al. (2026). Intranasal versus intramuscular midazolam in pediatric seizure control: A systematic review and meta-analysis. Prehospital Emergency Care. Advance online publication. https://doi.org/10.1080/10903127.2026.2658592
  9. Rafa Laboratories. (2022). Midazolam injection 10 mg/0.7 mL autoinjector: Prescribing information. DailyMed, U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d7362b4d-68a3-99a0-e053-2995a90a4f60
  10. TREKK/EIIC. (2025). Pediatric Status Epilepticus Algorithm, version 1.1 (May 2025). https://cms.trekk.ca/wp-content/uploads/2025/05/2025_07_08-Status-Epilepticus-Algorithm-v1.1-Final-1.pdf
  11. Vossler, D. G., Bainbridge, J. L., Boggs, J. G., et al. (2020). Treatment of refractory convulsive status epilepticus: A comprehensive review by the American Epilepsy Society Treatments Committee. Epilepsy Currents, 20(5), 245–264. https://doi.org/10.1177/1535759720928269
  12. Johnson, K. T., AlZadjali, A., Al Nasseri, D., et al. (2025). Midazolam infusions for therapeutic management of pediatric refractory status epilepticus: A systematic review. Frontiers in Pediatrics, 13, 1507325. https://doi.org/10.3389/fped.2025.1507325

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