Pediatric Procedural Sedation, Analgesia, and Anxiolysis

Opioids

Opioids are commonly chosen for pediatric procedural sedation because of their short onset of action and ability to produce significant analgesia with varying amounts of sedation. Fentanyl and morphine are the most widely used opioid analgesics to manage moderate-to-severe procedural pain in children.

Morphine. Morphine remains the gold standard for pediatric opioid analgesia, partly because it can be administered SC, IV, intramuscularly (IM), and orally. Its properties are more quickly achieved via the IV route, as the onset of action is 4 to 6 minutes. The standard IV dose of morphine is 0.1 mg/kg per dose, and can provide analgesia for up to 4 hours.

Adverse effects of morphine include dependence (though not an issue with a single emergency dose), respiratory depression, nausea, vomiting, constipation, urinary retention, hypotension, and bradycardia. Naloxone can rapidly reverse these adverse effects.

Fentanyl. Fentanyl, which is 100 times more potent than morphine, can be administered IV, transdermally, or transmucosally. When given IV, the onset of action of fentanyl is 2 to 3 minutes, and duration of action of 30 to 60 minutes. For sedation and analgesia, the suggested IV dose of fentanyl in neonates and young infants is 1 to 4 mcg/kg every 2 to 4 hours as needed, and for older infants and children, 1 to 2 mcg/kg every 30 to 60 minutes as needed.

Adverse effects of fentanyl are respiratory depression and chest wall rigidity,⁹ which can be rapidly reversed with naloxone (the dose of naloxone by patient weight is the same as that given to reverse adverse effects of morphine and fentanyl).

Codeine. A weaker opioid analgesic, codeine is not recommended for routine pediatric use because of its significant potential to hypermetabolize to morphine in some children, leading to overdose.⁶

Benzodiazepines: Midazolam

Benzodiazepines, which act on the type A gamma-aminobutyric acid receptor, causing muscle relaxation, anxiolysis, and anterograde amnesia, are useful for pediatric procedural sedation. Due to its short half-life, midazolam is the most common benzodiazepine used in pediatric patients. Midazolam can be delivered via different routes of administration, including orally, IM, IV, and transmucosally.

Intramuscular Route. Intramuscular midazolam has been shown to cause deep sedation at doses of 0.3 mg/kg, with maximum sedation occurring at 45 minutes, recovery beginning by 60 minutes, and the most common side effect being euphoria.¹⁰

Intravenous Route. Intravenous midazolam is used extensively in pediatric procedural sedation and is usually given at a dose of 0.05 to 0.1 mg/kg, with a maximum dose of 2 mg.

Even among small children, midazolam is usually quite safe when given alone, but because it does not provide effective analgesia, it often requires combination with an opioid for effective procedural sedation. Flumazenil may be given for rapid reversal of known benzodiazepine-induced respiratory depression, but it should be avoided in children with seizure disorders.

Propofol

Propofol is now frequently employed for pediatric sedation outside of the operating room. Propofol has excellent sedation properties but, like midazolam, does not provide analgesia and necessitates a second agent such as ketamine or an opioid for successful completion of more painful procedures. However, for children in whom sedation is required to facilitate simple neuroimaging of the head or spine, propofol is a very useful agent given the child’s quick return to his/her baseline mental status following the procedure.

Regarding contraindications, since propofol contains egg lecithin and soybean oil, it was once considered inappropriate for use in patients with an egg or soy allergy. Recent data, however, have refuted this belief, and while the package insert for propofol still lists patient allergy to egg, egg products, soy, or soybeans as a contraindication to use,¹¹ the American Academy of Allergy, Asthma and Immunology recently concluded that patients with soy allergy or egg allergy can receive propofol without any special precautions.¹²

Since propofol is a powerful sedative and can cause a greater depth of sedation than that intended, providers must be comfortable with both monitoring and managing the pediatric airway. The induction dose of propofol is 1 mg/kg with repeated doses of 0.5 mg/kg to achieve the desired level of sedation. One emergency medicine-specific study by Jasiak et al¹³ found a mean cumulative propofol dose of 2.1 mg/kg for pediatric procedures given in a median of three boluses, with younger children requiring an overall higher mg/kg induction dose. Another study by Young et al¹⁴ showed an induction dose of 2 mg/kg to be well tolerated and without increased adverse events for pediatric procedural sedation.

When used properly, propofol has been shown to be safe and effective in pediatric patients. A recent review by Mallory et al¹⁵ looking at 25,433 cases of EP administration of propofol to pediatric patients noted serious complications in only 2% of patients, including one unplanned intubation, one cardiac arrest, and two aspirations.