Intranasal Sufentanil/Midazolam Versus Ketamine/ Midazolam for Analgesia/Sedation: DISCUSSION

In: Anesthesia

21 Sep 2009

Analgesia Sedation DISCUSSION

The intranasal route of administration shows promise. The intranasal route is one of the most permeable and highly vascularized sites for drug administration, ensuring rapid absorption into the systemic circulation and onset of therapeutic action. In general, it has been potentially explored as an alternative route for drugs with poor bioavailability and for the delivery of biosensitive and high molecular-weight compounds such as proteins, peptides, steroids, and vaccines. Direct systemic absorption bypasses the portal circulation (hepatic first-pass effect) and may increase the bioavailability of nasally absorbed drugs. Added absorption enhancers, such as cyclodextrins, phospholipids, bioadhesive powder systems, and chitosan, improve nasal delivery. Intranasal delivery devices include drops (eg, dripped in using a tuberculin syringe), sprays, aerosols, and microsphere formulations. Atomization of aqueous polymer solutions is a key step in the formulation of several pharmaceutical products. For example, in pediatric dental patients, intranasal midazolam spray administered using an atomizer has been found to be safe. Nasal drug delivery may be assessed by a variety of means, but high reliance is often placed on in vitro testing methodology (emitted dose, droplet or particle size distribution, spray pattern, and plume geometry). Spray pattern and plume geometry define the shape of the expanding aerosol cloud, while droplet size determines the likelihood of deposition within the nasal cavity by inertial impaction. Aerosols are deposited mainly in the anterior and turbinate regions, with little passing beyond the nasopharyngeal region. Spray droplets are deposited in spots of the middle and posterior portions of the turbinate region as well.

Intranasal administration of sedatives and opioid analgesics provides a mechanism for more rapid drug absorption and more rapid onset of pain relief compared with oral dosing. Although the pharmacokinetics of intranasal sufentanil have not been worked out, lipophilic agents with a low molecular weight produce plasma levels similar to those achieved by the intravenous route. While previous work has demonstrated the efficacy and safety of preanesthetic sedation of children with intranasal sufentanil or midazolam, there has been no direct comparison of a combination of sufentanil/ midazolam and intranasal ketamine/midazolam to determine which drug combination is preferable for sedation and postoperative pain relief in preschool children. The Go Medical nasal spray is a portable 0.18mL patient-controlled analgesic device that is a hand-activated spray. It incorporates a 3-minute fill time (during which another full dose cannot be delivered). The spray is delivered in small-droplet form (80 |xm). It is simple to use. nexium medication

In this study, patients had similar weight distributions in both groups (S/M group, mean = 17.8 kg; K/M group, mean = 17.17 kg). As drugs are administered according to weight, bias according to this variable was not introduced. The presurgery behavior was reflected in the baseline anxiety scale (Figure 2), in the preanesthetic sedation (in which both groups were equally calm, drowsy, and peaceful), as well as in an uneventful and smooth mask induction of anesthesia in the majority of children.

Despite the potentially additive effects that a benzodiazepine with an opioid may have on respiratory depression, no such event was detected. Preanesthetic and postanesthetic oxygen-saturation levels were the same for both groups, at mean values of 97-98%. The study demonstrated that the drug combinations chosen had no negative effects on behavior during the perioperative period. There was an absence of adverse effects (such as nausea and respiratory depression), and no abnormal physiological responses during the perioperative period.

Dental practitioners specifically referred these patients for extractions. Single dental extractions are not usually associated with severe pain. Increasing pain is usually associated with multiple extractions. For inclusion in the cohort, it was a prerequisite that 6 or more extractions were to be performed. Ninety-two percent of patients had received no previous dental surgery. Sufficient pain was therefore present to demonstrate the analgesic properties of the drug combinations used. Although measuring pain and pain relief can be difficult in the pediatric patient, the pain assessment methods used have all been validated. The Oucher facial pain scale is validated for use in children, as is a visual scale that children readily understand. Seventy-two percent of children in the S/M group (vs 52% in the K/M group) were responders. The Oucher facial pain scale showed the S/M group to experience less pain than those in the K/M group. Even though the S/M group showed improved clinical analgesia, this was not statistically significant (P > .05). The analgesia provided was effective and reliable for pain due to multiple dental extractions. Using the modified Hannalah objective pain scale (Table 5 and Figure 5) as a behavioral-cardiovascular checklist, no significant differences were found between the 2 groups at the various time intervals measured postoperatively (P = .05). As the children had received no local anesthesia, no significant differences reflected on the combination of drugs that were used. Your life is worth living. Cheap cialis professional online

Intranasal pharmacokinetic studies in volunteers are reported for fentanyl, alfentanil, sufentanil, butorphanol, oxycodone, and buprenorphine. Mean times for achieving maximum serum concentrations vary from 5 to 50 minutes, while mean figures for bioavailability vary from 46 to 71%. Fentanyl, pethidine (meperidine), and butorphanol have been studied for postoperative pain. Mean onset times vary from 12 to 22 minutes and times to peak effect from 24 to 60 minutes. There is considerable interindividual variation in pharmacokinetics and clinical outcome. This may partly be due to lack of optimization of nasal formulations. Patient-controlled intranasal opioid analgesia may be an effective alternative to intravenous patient-controlled analgesia. Adverse effects are mainly those related to the opioids themselves rather than being due to nasal administration. Fewer patients with intranasal patient-controlled analgesia suffer opioid adverse effects, such as episodes of vomiting, when compared with intravenous patient-controlled analgesia.

The use of oral midazolam as a premedicant in pediatric dentistry preceded the use of the intranasal route and still needs to be compared with it. Using intranasal midazolam in healthy volunteers, the mean (± SD) peak plasma concentration of midazolam of 71 (±25) ng/mL is reached after 14 (±5) minutes. Mean bioavailability following intranasal administration is 0.83 ± 0.19. It has an elimination half-life of 4 hours. Intranasal midazolam (0.3 mgAg, 0.4 mgAg, 0.5 mgAg) has been used in conscious sedation of young pediatric dental patients. There is a rapid onset of sedation, with the maximal effect occurring between 8 and 15 minutes. This sedation lasts for 25-40 minutes. All 3 doses of intranasal midazolam are effective in modifying the behavior of the uncooperative-child patient to accept dental treatment. Another recent study showed that, for premedication in young children, intranasal midazolam (0.3 mgAg) achieves maximum sedation and anxiolysis at 20 minutes. Patient mask acceptance is good in the majority of children (more than 75%). It does, however, cause significant nasal irritation. Most parents are satisfied with its use for premedication. viagra professional online

In children, intranasal administration of low doses of ketamine produce plasma concentrations associated with analgesia. Intranasal ketamine permits pleasant and rapid separation of children from their parents, cooperative acceptance of monitoring and of mask inhalation induction, and does not cause prolonged postanesthetic recovery or delayed discharge home. The bioavailability of the nasal spray is approximately 45%. The area under the curve (0 to 6 hours) of its metabolite, norketamine, is low (approximately 100 ng/mL) in both enantiomers. Most reports demonstrate no or mild psychotomimetic effects when ketamine is dosed at su-banesthetic doses. This is further reduced by the use of the S-enantiomer of ketamine.

This study directly compared a combination of sufentanil/midazolam with intranasal ketamine/midazolam to determine which drug combination is preferable for sedation and postoperative pain relief in preschool children. This is, to our knowledge, the first time that a randomized double-blind study has been used in this way. This study demonstrated the safety and efficacy of both methods. Key features were the ease of administration, combined with rapid onset of action. Both groups were equally sedated. A smooth mask induction of anesthesia was experienced in the majority of children. Effective postoperative analgesia for multiple dental extractions was provided. However, these techniques may potentially still induce deep sedation and should not be attempted by operators unskilled in advanced anesthesia techniques.
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The study of the intranasal route is still in its infancy. But the intranasal administration of drugs for sedation and analgesia has some promising features, especially in preschool children with fear of separation from parents and unfamiliar surroundings. Improvements of nasal sprayer devices and formulations may improve clinical outcome. Further adequately designed clinical studies are needed.


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Blog invites submissions of review articles, reports on clinical techniques, case reports, conference summaries, and articles of opinion pertinent to the control of pain and anxiety in dentistry.

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