405

Therapeutic

Class Medication

Mechanism of

Action Metabolism

Route of

Administration

(neonates) Dose and Frequency Reversal

Agent Comments

Propofol Alkylphenol

sedative–

hypnotic.

Increases responsiveness of

GABA receptor

to GABA, potentiating glycine

activity (mediates

response to noxious stimuli).

Hepatic:

Extensive metabolism

via CYP, with glucuronide and sulfate conjugation.

IV IV: 200–300 mcg/kg/min

initial dose.n

Usual dose rangen

:

125–150 mcg/kg/min

Effective, safe dose range

for neonates needs further study.

None

Discontinue infusion, Support respiration, cardiac

function, correct

acid-base status.

Advantages: Rapid onset, short t1/2.

SE: Pain at injection site, hypotension,

apnea.

Generics: Contain benzyl alcohol,

sodium benzoate.

No analgesic properties/ assess sedative

effect.

↓ doses required when used with

opioids.n

Monitor lipids, metabolic status during

infusion.

Benzodiazepines Diazepam Binds to GABA

receptors in

CNS decreasing

excitability of

neuronal cells

Hepatic:

CYP P450 oxidation and

demethylation to

active metabolites

(oxazepam).

Half-life: Diazepam

Infants (40–50 h)

Neonates (50–100 h)

IV, Oral IV: 0.1–0.3 mg/kg dose

over 3–5 min, maximum total dose of

2 mg.

Oral: 0.2–1 mg/kg q6–8h

for NAS

Flumazenil 0.01

mg/kg IV (total

dose 0.05 mg/kg)

Not first-line IV due to: benzoic acid,

benzyl alcohol, sodium benzoate.

Extravasation may cause necrosis.

Complications of: all benzodiazepines:

myoclonic jerking, excessive sedation,

respiratory depression.

Lorazepam Binds to GABA

receptors in

CNS decreasing

excitability of

neuronal cells

Hepatic:

Glucuronide conjugation to inactive metabolite: lorazepam glucuronide

IV, Oral IV/Oral: 0.05–0.1 mg/kg

q4–8h as needed.

IV continuous infusion:

0.05–0.1 mg/kg/h

Dilute with sterile water

1:1 prior to infusion

Flumazenil 0.01

mg/kg IV (total

dose 0.05 mg/kg)

Risk of withdrawal (irritability, agitation,

tremors, sleep problems) after

long-term sedation with IV benzodiazepines.

Slower BBB penetration vs. diazepam.

Caution: Monitor for propylene glycol

toxicity with continuous infusion.

Oral solutions contain propylene glycol

+/– benzyl alcohol (“gasping syndrome”)

↓ dose for hepatic dysfunction.

Incompatible with TPN

Midazolam Binds to GABA

receptors in

CNS decreasing

excitability of

neuronal cells

Hepatic:

CYP-P450

hydroxylation followed

by glucuronide

conjugation, highly

protein bound

Rapid onset:

1–5 min IV

<5 min intranasal

Peak sedative action:

<20 min

IV, Oral, intranasal IV (slow): 0.05–0.15 mg/kg/dose

Intranasal:

0.1–0.3 mg/kg/dose

Oral:

0.15–0.45 mg/kg/dose

Continuous infusion:

0.03–0.06 mg/kg/h =

0.5–1 mcg/kg/min

Flumazenil 0.01

mg/kg IV (total

dose 0.05 mg/kg)

No analgesic effect. Anxiolytic, sedative,

muscle relaxant, anticonvulsant

Not recommended for continuous intravenous infusion in neonates. Caution

in hepatic impairment.

Monitor for hypotension, respiratory

depression, and seizure-like activity.

Decreases cerebral blood flow velocities

Decrease dose in neonates with

decreased cardiac output.

Table

A.2 Sedative and Analgesic Agents Commonly Used in Pediatrics (Continued)

406