ASK DIS: Promethazine For Procedural Sedation

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General

phenothiazine antihistamine with sedative, antiemetic, and anticholinergic effects. It is a competitive histamine (H1) and alpha-adrenergic receptor antagonist
The clinical effects of promethazine generally occur within 5 minutes after an IV dose and 20 minutes after an IM dose in adults.
The average duration of action is 4 to 6 hours, but effects may persist for up to 12 hours
Use of promethazine as a sedative agent spread rapidly after its approval.
While often producing a satisfactory level of sedation, the combination was associated with respiratory depression, hypotension, extrapyramidal effects, and prolonged recovery times.
Due to this, American Academy of Pediatrics published a statement in 1995 discouraging the use of these agents as sedatives in children

Apnea and Respiratory Depressant

direct central respiratory depressant effect, antagonism of central dopaminergic receptors resulting in increased levels of endogenous opioids capable of producing respiratory depression, or potentiation of the respiratory depressant effects of concomitantly administered opioids
Respiratory depression may be more pronounced in infants, particularly premature neonates, who may not be able to metabolize promethazine as well as older children and adults due to lower levels of CYP2D6 activity or reduced sulfur stores

Tissue Injury

Promethazine injection has a pH of 4 to 5.5 and IV administration may lead to severe injection site reactions.
These range from burning, pain, and erythema at the site of injection to thrombophlebitis, venous thrombosis, abscess formation, tissue necrosis, and gangrene.
Nerve injury, including paralysis, has been reported after parenteral administration into or near a nerve.
Subcutaneous (SC) administration has also resulted in chemical irritation of the tissues with subsequent necrosis. The SC route is now contraindicated

Others

the most frequently observed adverse effects are sedation, somnolence, blurred vision, dry mouth, and confusion.
Extrapyramidal adverse effects may present as oculogyric crisis, torticollis, and tongue protrusion.
These effects are typically the result of an acute overdose, but may occur after therapeutic doses
Other side effects such as thickening of bronchial secretions, and pharyngitis have been reported with the use of this medication

Evidences Against Use

Ketamine/Midazolam combination provided sufficient sedative effect in lower doses compared to Midazolam/Promethazine (sedative agents in pediatric dentistry)
chloral hydrate can be considered as a safe and more effective drug in sedation induction for sleep EEG in children compared to Promethazine (orally 70 mg/kg chloral hydrate VS promethazine 1 mg/kg for sedation during electroencephalography (EEG) in children). However, in terms of side effects, both results were comparable.

Evidences Supporting Use

combination of midazolam and promethazine not only speeds up the sedation induction, but also decreases unresponsiveness to the treatment and the need for a rescue dose (oral midazolam + Promethazine vs Oral Midazolam only)
Preanesthetic sedation of preschool children: Comparison of intranasal midazolam versus oral promethazine showed both were comparable for numerous elective surgery
Chloral hydrate and promethazine, when used in combination, have been shown to be more effective than i.v. midazolam in providing maintenance sedation in critically ill children

Usual Pediatric Dose for Sedation (>2 years)

Sedation: oral, IM, IV, or rectal: 0.5 to 1 mg/kg/dose (not to exceed 25 mg) every 6 hours as needed
Preoperative analgesia/hypnotic adjunct: IM, IV: 1.1 mg/kg once in combination with an analgesic or hypnotic (at reduced dosage) and with an atropine-like agent (at appropriate dosage).
Note: Promethazine dosage should not exceed half of suggested adult dosage

References:

http://www.medscape.com/viewarticle/720608_10
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3283976/
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3574988/
http://ispub.com/IJA/12/2/6492
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4173384/
http://www.drugs.com/dosage/promethazine.html
http://www.accessdata.fda.gov/drugsatfda_docs/label/2004/07935s030lbl.pdf
http://dentistryasleepny.com/pdf/Article3_Considerations_for_the_Use_of_Enteral_Sedation_in_Pediatric_Dentistry

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