Conscious sedation has been defined as a technique in which the use of a drug or drugs produces a state of depression of the central nervous system enabling treatment to be administered, but during which verbal contact with the patient is maintained throughout the period of sedation [12]. During conscious sedation, no interventions are required to maintain a patent airway, spontaneous ventilation is adequate, and cardiovascular function is usually maintained [1314]. The drugs and techniques used to provide conscious sedation for dental treatment should carry a margin of safety sufficiently wide to render loss of consciousness unlikely [15].

Conscious sedation is used as an adjunct to behavior management techniques for treating child patients in the dental setting. It avoids the major risks associated with GA and aims for behavior improvement, apprehension and anxiety reduction, and an increase in amnesia [1]. In a Cochrane systematic review addressing conscious sedation in anxious pediatric dental patients, the authors were not able to draw a conclusion regarding the most effective drug or method of sedation for anxious children [16]. However, the use of midazolam is a possible option for conscious sedation in pediatric dentistry. Children required to undergo conscious sedation with midazolam should be carefully selected. American Society of Anesthesiologists (ASA) class I or class II patients may be candidates for conscious sedation as outpatients. However, ASA class III and IV patients must undergo conscious sedation in hospital settings along with consultation with their medical doctor [1213].

As mentioned above, various routes of administration can be considered for the use of midazolam in conscious sedation. The oral route of administration is the most widely used in children. It is easy to administer and has decreased the risks for allergic reaction. However, when taken orally, the onset and duration of action of midazolam is prolonged, gastric absorption is unpredictable, and a stable sedative level is attained 30 min following drug intake [171819]. The bioavailability of midazolam is decreased when it passes the portal circulation to reach systemic circulation. Therefore, a higher oral dosage (0.3–0.5 mg/kg up to 12 mg maximum) is required [9]. The oral route of administration is useful in needle-phobic young children who cannot cope with dental treatment, as well as patients with learning difficulties or other medical conditions. However, oral intake of the drug is completely dependent on the compliance of the child patient and determination of the appropriate dosage is difficult because some of the solution may be spat out [9]; moreover, no oral preparation (i.e., liquid form) is available. Therefore, the IV solution is mixed with juice to mask the strong, bitter taste and improve acceptability in child patients. For optimal sedation, the drug should be administered 10–20 min before commencement of dental treatment. One study compared cola (PepsiCo, Harrison, NY, USA), 10% sodium citrate, pomegranate juice, and grapefruit juice as mixtures with midazolam for oral intake, and concluded that drug ingestion was simpler and sedation was more effective when midazolam was added to sodium citrate because it reduced gastric pH, which facilitated better absorption of the drug [20]. Another study investigating the use of oral midazolam for sedation of child patients reported that the technique was well tolerated by children and accepted by parents [21]. Oral midazolam sedation has been reported to be safe and effective, although some patients became agitated during or after treatment [21].

Wilson et al. [22] performed a randomized, controlled cross-over trial to investigate the effectiveness of 0.5 mg/kg oral midazolam sedation for orthodontic extraction of permanent teeth. They concluded that oral sedation using midazolam was safe and acceptable in patients 10–16 years of age. In another study, involving 5–10-year-old children, oral midazolam was compared with nitrous oxide inhalation sedation. Oral sedation proved to be safe and effective but was not the method of choice for all patients [23]. This may have been due to the unpleasant taste of the oral solution or the emergence of paradoxical reactions. Transmucosal, intranasal route of administration is another effective method in child patients. The sedative effect is observed within 5 min of administration of 0.1–0.2 mg/kg midazolam intranasally or transmucosal (sublingual). Preparations used via the nasal route are made to order and administered using a metered nasal spray. Studies have demonstrated the rapid onset (5–10 min) of intranasal midazolam sedation, as well as the short recovery time following administration [17181924]. Intranasal midazolam is rapidly absorbed from the nasal mucosa into the circulation and the peak effect occurs sooner compared with the oral route. Therefore, the nasal route could be a better option in children. Despite rapid onset and ease of administration, large volumes of the solution can cause coughing, sneezing, and expulsion of the drug [9]. The use of intranasal midazolam is associated with nasal irritation and unacceptability in children with nasal discharge [25] and could lead to occasional respiratory depression [26]. Karl et al. [27] compared intranasal and sublingual routes of administration of midazolam in child patients 6 months to 10 years of age. Their results revealed that sublingual administration of midazolam was as effective as the intranasal route. However, the sublingual route was better accepted by child patients. The compliance of the 6-month-old patients with sublingual lozenges was not clearly addressed in this study. The IV route is one of the most common routes of administration of midazolam. The general advantages of IV midazolam sedation include rapid onset (3–4 min) with adequate patient cooperation, ability to titrate the dose, and good amnesia of the procedure [28]. In pediatric dentistry, however, it may only serve as a possible option in anxious adolescents [28]. The fact that cannulation must be performed may make it a less favorable route of administration in very young children. The recommended dosage for IV midazolam in children is 0.25–1.5 µg/kg/min. The drug must be administered slowly so that its effects are assessed and overdosage is avoided [4]. Robb et al. [28] reported 18 cases of conscious sedation with IV midazolam in children 11–15 years of age. No loss of consciousness or fall in oxygen saturation levels was observed, which suggested the safe use of this drug for conscious sedation. The intramuscular (IM) route of administration has not been extensively studied in pediatric patients. In children, however, the disadvantages of this technique outweigh its advantages. A stable level of sedation is attained 30 min following drug administration [171819] and administering IM injection to a child patient is unpleasant and most probably not acceptable. Rectal administration of midazolam has been demonstrated to be effective and safe for sedating child patients, with an onset of action as short as 5 min [2930]. However, interruption of absorption by defecation and lack of patient and parent acceptance are major disadvantages of rectally administered midazolam [24]. Patient sedation using midazolam via any of the above-mentioned routes of administration should be monitored for vital signs, including respiration and blood pressure, especially when midazolam is administered via the oral or IV route [2242930]. Using pulse oximetry throughout sedation is mandatory in case of any complication. Oxygen saturation levels < 90% should be investigated and the cause corrected.

Induction of GA may be challenging in a highly anxious or a pre-cooperative patient, as well those with a medically compromising condition or learning difficulty. Various medications have been advocated to ease child-separation anxiety from parents and to mitigate anxiety during different phases of the perioperative period. The ideal premedication agent for children should have an acceptable and atraumatic route of administration, a rapid and reliable onset, minimal side effects, and rapid elimination [31]. It has been reported that midazolam fulfills these criteria and, therefore, can be used as a premedication in child patients undergoing dental treatment under GA [63233]. Wilton et al. [34] first described the use of intranasal midazolam as premedication for GA. In a prospective randomized double-blind clinical trial, Weber et al. [35] used the intranasal route of administration for midazolam and concluded that it was an appropriate premedication in preschool children.

A placebo-controlled trial investigated the reaction time and psycho-motor coordination of children undergoing GA before discharge and at 48 h when premedicated with 0.2 mg/kg buccal mucosa injection of midazolam to a maximum dose of 10 mg [36]. Premedication with midazolam requires a low dose (0.2 mg/kg) for anxiolysis; however, for oral sedation, a higher dose (0.5 mg/kg) is required for anxiolysis as well as sedation. A total of 179 children participated in this study, each receiving buccal midazolam or placebo before induction of GA. Results revealed that reaction time was significantly slower and psychomotor coordination was also significantly impaired in the midazolam group. Midazolam was also associated with anterograde amnesia before discharge and at 48 h [36]. This indicates that impairment of children's cognitive function and amnesia lasting for up to 48 h post-GA should be expected when midazolam is used for premedication.

A more recent study, however, demonstrated that 0.2 mg/kg buccal midazolam reduced anxiety in most patients but did not have an effect on psychological morbidity, induction behavior, and subsequent dental attendance [37]. Kain et al. [38] reported that children premedicated with oral midazolam exhibited less negative behavioral changes during the first postoperative week compared to those in the placebo group. It has been suggested that high levels of trait anxiety could be a contraindication to the use of oral midazolam as a premedication for GA. In addition, the use of midazolam before GA for a child with low state baseline anxiety is deemed unnecessary [39]. Regarding recovery and discharge times, Viitanen et al. [40] reported that the use of oral midazolam as premedication for propofol-induced GA in 1–3-year-old children delayed early recovery but did not affect discharge time. The authors also concluded that oral midazolam did not improve the quality of recovery. A literature review of available randomized controlled trials investigating midazolam oral premedication studied the effects of midazolam on separation anxiety, induction anxiety, emergence agitation, recovery times, long-term outcomes, and dose and timing of the drug. The authors concluded that premedication with oral midazolam reduced anxiety in children at separation from parents and anesthesia induction. However, there appeared to be no evidence supporting the moderation of emergence agitation, and awakening times were slightly delayed, although no serious side effects were reported [41]. Finally, midazolam could be used as an emergency drug in the dental setting.