Therapeutic Intranasal Drug Delivery

Abstract: OBJECTIVE: Emergence agitation (EA), a short-lived, self-limiting phenomenon, arises frequently after the use of inhalational agents and hampers the implementation of pediatric ambulatory surgery in spite of using so many drugs with variable efficacy. METHODS: In this prospective, double-blinded, parallel group study (2008-2009), 80 children of both sex aged 3-7 years, with American Society of Anesthesiologists (ASA) physical status grade I-II, undergoing sevoflurane-based general anesthesia for elective day care surgery were randomly assigned into groups C or D. Group C received 4 mug/kg intranasal clonidine, whereas group D received 1 mug/kg intranasal dexmedetomidine, 45 min before induction of anesthesia. In postanesthesia care unit (PACU), the incidence of EA was assessed with Aonos four-point scale and the severity of EA was assessed with pediatric anesthesia emergence delirium scale upon admission (T0), after 5 min (T5), 15 min (T15), and 25 min (T25). Extubation time, emergence time, duration of PACU stay, dose and incidence of fentanyl use for pain control were noted. FINDINGS: Based on comparable demographic profiles, the incidence and severity of EA were significantly lower in group D as compared to group C at T0, T5, T15, and T25. But time of regular breathing, awakening, extubation, and emergence were significantly delayed in group D than C. The number and dose of fentanyl used in group C were significantly higher than group D. PACU and hospital stay were quite comparable between groups. CONCLUSION: Intranasal dexmedetomidine 1 mug/kg was more effective than clonidine 4 mug/kg in decreasing the incidence and severity of EA, when administered 45 min before the induction of anesthesia with sevoflurane for pediatric day care surgery. Dexmedetomidine also significantly reduced fentanyl consumption in PACU.

Web site Editorial comments:

Here is a study directly comparing IN clonidine to dexmedetomidine for preoperative sedation and suppression of post-operative agitation. For the most part, dexmedetomidine was superior but it also led to longer sedation time (which may be a positive or negative finding depending on the clinical situation).

Pubmed link: http://www.ncbi.nlm.nih.gov/pubmed/25710047

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Riediger C, Haschke M, Bitter C, et al. The analgesic effect of combined treatment with intranasal S-ketamine and intranasal midazolam compared with morphine patient-controlled analgesia in spinal surgery patients: a pilot study. J Pain Res 2015;8:87-94.

Abstract: OBJECTIVES: Ketamine is a well-known analgesic and dose-dependent anesthetic used in emergency and disaster medicine. Recently, a new formulation of S-ketamine, as an intranasal spray, was developed and tested in our institution in healthy volunteers. The authors investigated the effect of intranasal S-ketamine spray combined with midazolam intranasal spray in postoperative spinal surgery patients. MATERIALS AND METHODS: In this prospective, computer-randomized, double-blinded noninferiority study in spinal surgery patients, the effects of intranasal S-ketamine and midazolam were compared with standard morphine patient-controlled analgesia (PCA). The primary end point was the numeric rating scale pain score 24 hours after surgery. RESULTS: Twenty-two patients finished this study, eleven in each group. There were similar numeric rating scale scores in the morphine PCA and the S-ketamine-PCA groups at 1, 2, 4, 24, 48, and 72 hours after surgery during rest as well as in motion. There were no differences in the satisfaction scores at any time between the groups. The number of bolus demands and deliveries was not significantly different. DISCUSSION: In our study, we found that an S-ketamine intranasal spray combined with intra-nasal midazolam was similar in effectiveness, satisfaction, number of demands/deliveries of S-ketamine and morphine, and number/severity of adverse events compared with standard intravenous PCA with morphine. S-ketamine can be regarded as an effective alternative for a traditional intravenous morphine PCA in the postoperative setting.

Web site Editorial comments:

These authors conducted a small (22 patients) double blind RCT comparing the analgesic effect of intranasal ketamine/midazolam PCA to IV morphine PCA  in adult postoperative patients. They  chose this combination therapy because ketamine has analgesic effects but can cause psychotomiometic adverse effects, therefore they added midazolam to counter these adverse effects. They compared this combination to IV morphine which is considered by many to be the standard treatment for postoperative pain. The doses of each PCA were as follows: Ketamine/Midazolam 6 mg/0.75 mg every 20 minutes plus placebo IV PCA every 12 minutes as needed versus Intranasal placebo every 20 minutes plus IV morphine 2 mg every 12  minutes. Pain scores, satisfaction scores, number of PCA boluses, side effects, use of rescue medications were measured. The results showed no difference in pain scores, satisfaction, PCA boluses, side effects or use of rescue medications. In conclusion – here is yet another study supporting IN ketamine as an analgesic that is comparable to IV morphine, providing clinicians with another low tech option for caring for their patients who are in pain.

Pubmed link: http://www.ncbi.nlm.nih.gov/pubmed/25709497

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