Benzodiazepines includes midazolam diazepam and lorazepam Midazolam is the agent of choice due to its

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Drug

Clinical Effect

Indications

Dosea

Onset (min)

Duration (min)

Reversible

Comments

Sedative-

Sedation, sleep,

Imaging or pain

50-100 mg/kg

10-30

30-120

No

Works best in

Hypnotics

motion control

less diagnos

PO or PR

young infants

Chloral hydrate

tic studies (CT, EEG, ABR)

(max100 mg/kg or 2 g)

(<10 kg); unpredictable onset and duration; terrible taste Use lower doses

Midazolam

Sedation,

Shorter proce

IV 0.05-0.1

IV 1-2

IV 45-60

Yes (flumazenil)

in combina

anxiolysis

dures, anxiol

mg/kg

IN 2-5

IN 15-30

tion with nar

ysis, mild

IN 0.2-0.4

IM 5-15

IM 60-120

cotics; may

sedation when

mg/kg

PO 15-20

PO/PR 60-90

produce para-

mg/kg (Halve dose for >8 y, may repeat q5-10min to max of 0.5 mg/kg IV)

PR 10-15

Younger children are often restless

Pentobarbital

Sedation, sleep,

Longer painless

IV 2-6 mg/kg,

IV 3-5

IV 30-90

No

before sleep is

motion

procedures

titrated at 1-2

IM 10-15

IM 60-120

induced;avoid

control

(MRI, bone scan)

mg/kg (max 200 mg)

PO/PR 15-60

PO/PR 60-240

in patients with porphyria

Methohexital

Analgesics

Fentanyl

Ketamineb

Nitrous oxide (NO)

Reversal Agents

Naloxone

Flumazenil

Sedation, sleep, motion control

Analgesia

Analgesia, dissociation, amnesia, motion control

Mild analgesia, sedation, amnesia

Narcotic reversal

Benzodiazepine reversal

Shorter painless procedures (CT)

Shorter, moderately painful procedures

Shorter, moderately to severely painful procedures

Mildly painful procedures

IV 1-2 mcg/kg; may increase by 1 mcg/kg q3-5min to desired effect IV 1-1.5 mg/kg IM 4-5 mg/kg (use concentrated 100 mg/mL formulation) PO 10 mg/kg No reported max Inhaled 30-50% NO mixed with oxygen

IV/IM 0.1 mg/kg (max 2 mg/dose) May repeat q2min IV 0.02 mg/kg per dose May repeat q1min to max of 1 mg

IV 15-30 PR 30-60

IV 30-60

IV 15-30 IM 30-90

Yes (naloxone)

IV 20-40 IM 60-90

IV 30-60

Avoid in patients with temporal lobe epilepsy and porphyria

Chest wall rigidity may occur with rapid IV push

Contraindicated in patients with increased ICP, IOP, psychosis, thyroid disease

Contraindicated in patients with trapped gas pockets

Sedative may outlast reversal agent

Sedative may outlast reversal agent

ABR = auditory brainstem response; CT = computed tomography; EEG = electroencephalogram; ICP = intracranial pressure; IOP, intraocular pressure; MRI = magnetic resonance imaging.

3 " Doses are generalizations only; dosing must be individualized in all cases. Dosing may be altered by age or degree of illness. Neonatal dosing may differ. All PO/PR/IM 1 dosing is difficult to titrate—use caution and monitor for oversedation. Judicious use of local anesthetic may lessen dose requirements for systemic analgesia.

b Administer with atropine, 0.01 mg/kg (min 0.1 mg, max 0.5 mg), to blunt hypersalivation response. Some believe that administration with midazolam may ameliorate emergence phenomenon. All three drugs may be mixed together for IM administration.

pharmacokinetics and exceptional amnestic properties. Short-acting agent (varies by route of administration and dosage), with rapid onset (1-2 minutes IV, 2-20 minutes transmucosally or enterally). Given alone, it is unlikely to induce sleep, although it will create a relaxed state in most children. Serves as an excellent adjunct to local anesthetic or concomitant narcotic or dissociative agents for painful procedures. Midazolam, as with all benzodiazepines, produces dose-dependent respiratory depression that is significantly exaggerated by use with narcotics. Up to 10% of children experience a paradoxic hyperexcited, irritable state that can be blunted with increased dosing or flumazenil. Adolescents are more susceptible and should not be dosed on a per-kilogram basis (see Table I-24). Midazolam is reversible with flumazenil. 3. Barbiturates. Barbiturates depress reticular activating system and serve as very good sleep-inducing agents. Commonly used agents include pentobarbital, methohexital, and thiopen-tal. Pentobarbital has a slower onset and longer duration compared with methohexital. Thiopental is an ultra-short-acting agent with potential for significant hypotension and is generally reserved for situations requiring profound sedation, such as rapid sequence intubation. Barbiturates are not reversible.

B. Analgesics. Procedural analgesics include narcotics, ketamine, and nitrous oxide. Narcotics include fentanyl, morphine, and meperidine. Fentanyl has become the favorite due to its potency, lack of histamine release and hypotension, and pharmacokinetics.

1. Fentanyl. Agent is 100 times as potent as morphine, and careful attention should be paid to its microgram dosing.Takes effect within 1-2 minutes of IV administration and lasts for 30-60 minutes. Potential adverse effects include so-called stiff chest syndrome (rigidity of chest wall seen with rapid administration of large doses), requiring naloxone or neuromuscular blockade to reverse. Respiratory depression is very common, especially when administered with a benzodiazepine. Vomiting and facial pruritus are also common. Fentanyl is reversible with naloxone.

2. Ketamine. Dissociative anesthetic that induces a unique catatonic state with profound sedation, amnesia, and analgesia. Has a rapid onset (1-2 minutes IV) and short duration (15-30 minutes). Respiratory drive and protective airway reflexes are maintained. Side effects include hypersalivation, tachycardia, hypertension, and increased intracranial pressure, in addition to possibility (5-10%) of an "emergence reaction" with agitation on awakening. Vomiting on emergence has also been reported. Side effects may be blunted by concomitant administration of a benzodiazepine and an antisialagogue, such as atropine or glycopyrrolate. It is helpful to tell patient to expect a dreamlike state with changes in visual perception (double vision is common), and to tell parent to expect to see nystagmus and flushing. Ketamine is not reversible.

3. Nitrous oxide. The only inhaled sedative-analgesic commonly available outside of anesthesia department. Produces state of euphoria and mild sedation and analgesia within 2-3 breaths and wears off almost instantly as well. Administered using demand-valve mask via blender capable of administering up to 50% nitrous oxide and 50% oxygen. Due to environmental contamination and concerns about toxicity in health-care workers with chronic exposure, a scavenger system must be in place to retrieve stray gas. Side effects include nausea and potential for diffusion of nitrous oxide into enclosed cavities; thus, use is con-traindicated in patients with pneumothorax or obstructed bowel.

4. Reversal agents. Although these agents should be available whenever reversible agents are employed for procedural sedation, they are not routinely recommended at the conclusion of procedures. Duration of action of sedative-analgesic regimen may outlast that of reversal agent, raising risk of temporary reversal with later resedation. When a reversal agent is used in the setting of oversedation, patient should be monitored for duration of action of original agent, or at least 2 hours after administration of reversal agent. Reversal agents include naloxone, a narcotic antagonist that competes for opiate receptors, and flumazenil, which antagonizes effect of benzodiazepines. (See Table I-24 for dosing information.)

VI. Problem Case Diagnosis. The 4-year-old patient was screened and found to have no risk factors for sedation. He was monitored adequately; received midazolam, 2 mg IV (0.1 mg/kg), and fentanyl, 20 mcg (1 mcg/kg); and slept lightly through the procedure, which resulted in diagnosis of aseptic meningitis.

VII. Teaching Pearl: Question. What is the sedative agent of choice when a pediatric patient needs to be sedated for a long diagnostic imaging study (eg, MRI scan of spine)?

VIII. Teaching Pearl: Answer. Such procedures are painless, require complete immobilization, and take about 1 hour; therefore, IV pentobarbital at a dose of 3-6 mg/kg (maximum, 200 mg) is the agent of choice.

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