Pharmacologic Considerations for Pediatric Sedation and Anesthesia Outside the Operating Room: A Review for Anesthesia and Non-Anesthesia Providers

Abstract

Understanding the pharmacologic options for pediatric sedation outside the operating room will allow practitioners to formulate an ideal anesthetic plan, allaying anxiety and achieving optimal immobilization while ensuring rapid and efficient recovery. The authors identified relevant medical literature by searching PubMed, MEDLINE, Embase, Scopus, Web of Science, and Google Scholar databases for English language publications covering a period from 1984 to 2017. Search terms included pediatric anesthesia, pediatric sedation, non-operating room sedation, sedation safety, and pharmacology. As a narrative review of common sedation/anesthesia options, the authors elected to focus on studies, reviews, and case reports that show clinical relevance to modern day sedation/anesthesia practice. A variety of pharmacologic agents are available for sedation/anesthesia in pediatrics, including midazolam, fentanyl, ketamine, dexmedetomidine, etomidate, and propofol. Dosing ranges reported are a combination of what is discussed in the reviewed literature and text books along with personal recommendations based on our own practice. Several reports reveal that ketofol (a combination of ketamine and propofol) is quite popular for short, painful procedures. Fospropofol is a newer-generation propofol that may confer advantages over regular propofol. Remimazolam combines the pharmacologic effects of remifentanil and midazolam. A variety of etomidate derivatives such as methoxycarbonyl-etomidate, carboetomidate, methoxycarbonyl-carboetomidate, and cyclopropyl-methoxycarbonyl metomidate are in development stages. The use of nitrous oxide as a mild sedative, analgesic, and amnestic agent is gaining popularity, especially in the ambulatory setting. Utilizing a dedicated and experienced team to provide sedation enhances safety. Furthermore, limiting sedation plans to single-agent pharmacy appears to be safer than using multi-agent plans.

Remimazolam tosilate in upper gastrointestinal endoscopy: A multicenter, randomized, non‐inferiority, phase III trial

“…As a result, the time to adequate sedation of patients treated with RT (2 min) was longer compared with propofol (1.3 min), which was consistent with unpublished result of phase IIc trial and other previous data 22 . Even so, the time to adequate sedation was only approximately 1/2 to 1/10 as long for RT (2 min) compared with other sedatives, such as dexmedetomidine (8.6–13 min), 24,25 etomidate (3–5 min) 25 and midazolam (16 min) 26 . This indicated that RT has the potential benefits to be used in short procedures, such as upper GI endoscopy.…”

Effectiveness and Safety of Intravenous Sedation with Propofol in Non-Operating Room Anesthesia (NORA) for Dental Treatment in Uncooperative Paediatric Patients

“…Another advantage is fewer side effects due to its anti-emetic effect (less postoperative nausea and vomiting) and less emergence delirium. The mechanism behind the anti-emetic effect is not very well understood, but it has been demonstrated that propofol interacts with dopaminergic (D2) receptors in the chemoreceptor trigger zone, inhibits the limbic system, thereby interacting with cortical reflexes reaching the vomiting centre [13][14][15]. Disadvantages of propofol use include hypotension, apnea and airway obstruction [14].…”

“…In fact, orotracheal intubation, length of the dental treatment and discharge duration are the main differences between IV and GA procedures [14]. The described complications of orotracheal intubation comprise of: sore throat, laryngeal edema, hoarseness, nerve injury, aspiration of oral or gastric contents, superficial laryngeal ulcers and laryngeal granuloma [16].…”

Psychomotor Recovery Following Remimazolam-induced Sedation and the Effectiveness of Flumazenil as an Antidote

“…3,4 However, the side effect of pain on injection and the notably narrow therapeutic window of propofol related to bradycardia, hypotension, and hypoventilation are the major disadvantages of this drug. 1,5 Remimazolam is an ester-type benzodiazepine acting on the GABA A receptor. It is designed to undergo rapid hydrolysis in the body by nonspecific esterase to an inactive carboxylic acid metabolite.…”