European Review for Medical and Pharmacological Sciences 2018; 22: 217-222 Intranasal drug administration for procedural sedation in children admitted to pediatric Emergency Room C. FANTACCI1, G. C. FABRIZIO1, P. FERRARA1, F. FRANCESCHI2, A. CHIARETTI1 1Department of Pediatrics, Catholic University of the Sacred Heart, School of Medicine, Gemelli Hospital Foundation, Rome, Italy 2Institute of Internal Medicine, Catholic University of the Sacred Heart, School of Medicine, Gemelli Hospital Foundation, Rome, Italy Abstract. – OBJECTIVE: Pain relief is a very sometimes be overlooked because pain is often important aspect in Pediatrician’s clinical prac- underestimated in childhood. This is due to the tice. It is often thought that young children, par- common belief that young children, particularly ticularly infants, do not perceive as much pain as infants, do not perceive as much pain as adults adults because of their immature nervous sys- because of their immature nervous system and tem and that untreated pain would not have ad- verse long-term consequences. Instead, it has that untreated pain would not have adverse 1,2 been demonstrated that infants and children ex- long-term consequences . On the contrary, it perience pain in a similar manner to adults. Ma- has been shown that infants and children ex- ny factors, particularly emotional factors, can in- perience pain in a similar manner to adults3. crease the child’s pain perception. Children live Furthermore, high levels of pain in children may with anxiety even minor procedures. This sug- have significant neurophysiological and physio- gests the need for an adequate sedation and the 4,5 way of sedation should be free of pain itself. We logical effects . Inadequately managed pain in believe the route to be followed may be the intra- children can also have detrimental psychological nasal (IN) administration of sedative drugs. consequences, which can in turn lead to higher MATERIALS AND METHODS: We have con- levels of pain during medical treatments. For ex- ducted a brief review of the literature by Pubmed ample, emotional factors – such as elevated anx- about the most commonly used sedative drugs: iety, distress, anger and low mood – can increase sufentanyl, fentanyl, midazolam, ketamine, ni- trous oxide and dexmedetomidine. We have in- the child’s pain perception and make subsequent vestigated in the literature the type of adminis- medical procedures and pain management more tration of IN drugs: drop instillation or by a mu- difficult6,7. In addition, a large-scale early re- cosal atomizer device (MAD). searche found that as many as one third of chil- RESULTS: In our study, it was noted that IN dren who experienced medical procedures for drugs administration is an effective and safe method to reduce anxiety and to deliver anal- diagnosis or treatment showed some evidence of 8 gesia because it is practical and non-invasive. subsequent psychological adjustment problems . Moreover, therapeutic levels of sedatives are Moreover, reports of fear and pain experienced low due to the presence of a rich vascular plex- during medical procedures in childhood are us in the nasal cavity, which communicates with predictive of fear and pain during medical pro- the subarachnoid space via the olfactory nerve 9 and reduce the time of medication delivery, that cedures in young adulthood . is, the onset of action. The use of MAD even Children often live with many anxiety and gives as better bioavailability of drugs. anguish even minor procedures, most notably CONCLUSIONS: IN sedation via MAD is ef- the placement of a venous access, and even more fective and safe and should be one of the first seizure control, laceration repair, dental and oph- choices for procedural sedation in children. thalmologic procedures. Usually, children’s fear Key Words: and anticipatory anxiety increase the likelihood Intranasal sedation, Procedures, Pain, Children. of experiencing more pain and distress during the actual procedures; in addition, children typically Introduction report having overly negative expectations prior to medical procedures, regardless of whether a Pain relief is a very important aspect in Pe- pharmacologic or behavioral pain management diatrician’s clinical practice, although it may intervention will be employed10. Corresponding Author: Claudia Fantacci, MD; e-mail: [email protected] 217 C. Fantacci, G.C. Fabrizio, P. Ferrara, F. Franceschi, A. Chiaretti This entails the need to propose not only ade- quate sedation but also a way of sedation free of pain itself as much as possible11. The benefits of providing adequate proce- dural sedation for children include decreasing patient anxiety and emotional trauma, decreas- ing parental emotional discomfort, and facili- tating ease and/or completion of the procedure. A desirable sedating agent has a rapid onset with short duration of action; it is effective and safe12. In recent years, the use of intranasal (IN) ad- ministration of sedative drugs before perform- ing the procedures has taken hold, because it is a practical and non-invasive route of adminis- tration. Therapeutic levels of sedatives can be reached via IN administration due to the rich Figure 2. With the use of MAD, the drug is delivered via a fine spray over a broad surface area in the nasal cavity, vascular plexus cavity which communicates favoring its absorption. with the subarachnoid space via the olfacto- ry nerve13,14. In the recent past many authors preferred IN midazolam administer by drop Materials and Methods instillation; nowadays many studies investigate new methods such as the use of spray devices. Relevant studies were identified from two A mucosal atomizer device (MAD, Figure 1) sources: a key word search including intranasal, delivers drug via a fine spray over a broad sur- drugs, sedation, children, medication, sufentanil, face area in the nasal cavity (Figure 2). It also fentanyl, midazolam, ketamine, nitrous oxide, reduces sneezing and coughing compared to dexmedetomidine; a review of the references other devices15-17. from each identified article. We included in this Different drugs have been used for IN seda- review only pediatric articles. tion for procedural sedation in children; this review aims to re-evaluate this method of se- dation and the drugs most commonly used for Results its usage. Ketamine Ketamine is usually administered intravenous- ly (IV) or intramuscularly (IM), but it may also be administered nasally18. The dose required to achieve a state of dissociative sedation in children is typically 1.0 to 1.5 mg/kg IV or 3 to 4 mg/kg IM19. When used nasally, the recommended ad- ministration dose is 9 mg/kg18. In 2001, Acworth et al20 compared IN mid- azolam vs. ketamine IV plus midazolam IV in children requiring minor procedures, such as laceration repair or foreign body removal, in the ambulatory setting, and concluded that the combination is higher to IN midazolam alone in terms of speed of onset and consistency of effect. In 2013, Nielsen et al21 studied the association of ketamine with sufentanil administered IN. They did not report any serious adverse events; oxygen saturation and heart rate remained sta- Figure 1. MAD (Mucosal Atomizer Device). ble. The reported adverse effects were mild and 218 IN drug administration for procedural sedation in children admitted to Pediatric Emergency Room mostly related to an unpleasant bitter taste imme- received sufentanil had a marked decreased ven- diately after the administration of the nasal spray, tilatory compliance during the induction of an- which disappeared after drinking. esthesia and had a higher incidence of vomiting during the first postoperative day24. Midazolam The bioavailability of IN route ranges from Nitrous Oxide and Fentanyl 50-83%22. It can be administered orally, nasally, Seith et al26 administered a continuous flow of rectally, IV or IM. In a randomized, double-blind, nitrous oxide of 50 to 70% via a full-face mask in placebo control study, Shapiro et al11 showed that association with a pre-calculated dose of 1.5 µg/ midazolam spray offers relief to children anxious kg of IN fentanyl that was administered through about minor medical procedures, such as inser- MAD26-30. A nitrous oxide alone agent has been tion of a needle in a subcutaneously implanted associated with higher levels of emesis; instead, intravenous port, venous blood sampling and according to Seith et al26, the association with venous cannulation. A double-blind, randomized, IN fentanyl reduces the incidence of vomiting. controlled trial conducted by Rakaf et al22 in 2011 Fentanyl is an opiate analgesic with the most reported a success rate of 91% to 100% for com- evidence to support IN route. It is most used for pleting dental procedures following IN midazol- acute pain management like orthopedic fractures am administration. or burns because it controls at relatively high The dose of intranasal midazolam used in doses the pain. Its usage in pediatric patients has the different studies range between 0.2 mg/ shown comparable effectiveness with the IV ad- kg and 0.4 mg/kg or 0.5 mg/kg11-15. The most ministration31. common adverse effects reported following IN midazolam are burning or irritation in the nose Dexmedetomidine and a bitter taste in the mouth. It can determine Recently, some Emergency Pediatric Depart- respiratory and circulatory depression, but these ments have gained a useful experience of this IN side effects are unlikely when midazolam is medication for short procedures in pediatric out- used as a single drug, while they increase when patient. Intranasal route is more rapidly absorbed it is used with opioids or other sedatives. In in blood stems compared to oral form and it pre- their work, Lane et al12 had 1/205 children who serves the airway reflexes and respiratory drive32. received IN administration of midazolam with Generally, this drug is administered at dose of an adverse event. This was a minor desatura- 2-4 µg/kg. Patel et al33 described an 11-year-old tion episode following ketamine administration girl sedated with 2.4 µg/kg of IN dexmedeto- requiring brief blow by oxygen.