Children undergoing surgery may experience significant and understandable anxiety in the preoperative period; helping manage this anxiety not only creates a calmer and safer environment for anesthesia induction, but has also been associated with better postoperative pain management and a lower incidence of postoperative nausea and vomiting, issues with feeding, postoperative delirium, sleep and behavioral disturbances [4]. The goal of premedication is to control this preoperative anxiety, especially in pediatric patients, with secondary goals including aiding with sedation, amnesia, analgesia and antiemesis [4]. Premedication in pediatric patients can utilize clonidine, midazolam, or dexmedetomidine.

While most studies have found that the level of sedation is stronger with the alpha-2-agonists like clonidine and dexmedetomidine, there is conflicting evidence regarding which agent is best for all of the other goals of premedication in pediatric patients as outlined in the paragraph above. An older study published in 2007 found that overall, children undergoing mask-induction of anesthesia responded more favorably to clonidine compared to midazolam [1]. They more readily accepted the taste of clonidine and were found to have improved post-operative anxiolysis (reduction of anxiety), decreased incidence of emergency agitation and better parental satisfaction scores than patients who received midazolam [1]. However, a more recent double-blinded randomized control study in 2021 found the opposite; in the 90 patients ages 2-6 undergoing ENT surgery that were included in the trial, patients who received midazolam had better anxiolysis compared to those who received clonidine and dexmedetomidine [2]. And a 2022 meta-analysis looking at aggregate data from 48 different randomized control trials found that, while all three agents provide adequate sedation and anxiolysis, dexmedetomidine was preferred over midazolam and clonidine due to the side effects of each medication, perhaps related to the intranasal administration of dexmedetomidine, versus oral administration of the other two agents [5].

While premedication helps to decrease preoperative anxiety in pediatric patients, clonidine, midazolam, and dexmedetomidine all affect cardiorespiratory status in some way. In 2023, a group of researchers performed a secondary analysis of the 2021 paper mentioned earlier in this article to investigate whether clonidine, dexmedetomidine or midazolam cause hemodynamic instability in children ages 2-6 years old undergoing elective ENT surgery [3]. Consistent with results from past studies, clonidine and dexmedetomidine cause deeper sedation than midazolam [3]. However, while all three were found to be safe in this cohort, midazolam was found to be the most effective at maintaining baseline cardiorespiratory status, with the fastest recovery after emergence from anesthesia [3]. In fact, contrary to findings from past studies, this study found that midazolam was associated with faster weaning of oxygen supplementation than both clonidine and dexmedetomidine [3].

While there is a lot that still needs to be understood about the risks and benefits of clonidine or other premedication prior to surgery, the fact remains that treating preoperative anxiety in pediatric patients improves surgical outcomes.

References

1. Almenrader N, Passariello M, Coccetti B, Haiberger R, Pietropaoli P. Premedication in children: a comparison of oral midazolam and oral clonidine. Paediatr Anaesth. 2007 Dec;17(12):1143-9. doi: 10.1111/j.1460-9592.2007.02332

2. Bromfalk Å, Myrberg T, Walldén J, Engström Å, Hultin M. Preoperative anxiety in preschool children: A randomized clinical trial comparing midazolam, clonidine, and dexmedetomidine. Paediatr Anaesth. 2021 Nov;31(11):1225-1233. doi: 10.1111/pan.14279.

3. Bromfalk Å, Hultin M, Walldén J, Myrberg T. Cardiorespiratory Response to Sedative Premedication in Preschool Children: A Randomized Controlled Trial Comparing Midazolam, Clonidine, and Dexmedetomidine. J Perianesth Nurs. 2023 Jan 3:S1089-9472(22)00452-X. doi: 10.1016/j.jopan.2022.08.009.

4. Dave NM. Premedication and Induction of Anaesthesia in paediatric patients. Indian J Anaesth. 2019 Sep;63(9):713-720. doi: 10.4103/ija.IJA_491_19.

5. Yang CQ, Yu KH, Huang RR, Qu SS, Zhang JM, Li YL. Comparison of different sedatives in children before general anaesthesia for selective surgery: A network meta-analysis. J Clin Pharm Ther. 2022 Oct;47(10):1495-1505. doi: 10.1111/jcpt.13763.