Morton Rosenberg, D.M.D.

Abstract

We report our experience with the use of the FDA approved oral midazolam syrup for uncooperative pediatric dental patients. Our results confirm those of other investigators that oral midazolam is a safe, effective oral sedative with a success rate at least equal if not greater to chloral hydrate. Palatability, need for supplementation with nitrous oxide – oxygen, state of consciousness, incidence of crying and oxygen saturation were also documented.

Introduction

Chloral hydrate has long been the most popular oral sedative used in pediatric dentistry. The success rate measured by the ability to treat uncooperative pediatric patients for restorative dentistry has been reported to be between 40 – 85% depending upon dosage, combination with other oral sedatives, and the co-administration of nitrous oxide-oxygen. ^,,,

Besides the many disadvantages inherent in any oral premedication (Table 1), in vivo and in vitro animal studies have raised the concern of the potential carcinogenicity of chloral hydrate due to its genotoxic effects causing chromosome changes. In addition, chloral hydrate is a reactive metabolite of trichlorethylene, a known carcinogen, and is structurally similar to other carcinogenic intermediates. Despite these disturbing preliminary animal studies, chloral hydrate remains an essential and popular oral sedative across the spectrum of pediatric medical and dental specialties.

Table 1

Disadvantages of Pediatric Oral Sedation

- Patient and child non-compliance with instructions

• Dosages are generally empirical

• Impossible to titrate to clinical endpoints

• Erratic absorption dependent upon many drug absorption characteristics

• Lipid solubility

• pH of gastric mucosa

• Mucosal surface area

• Type of oral formulation and vehicle

• Effect of hepatic (“first pass”) metabolism

• Bioavailability

• Factors influencing gastric emptying time

  • Food presence

  • Anxiety

• Not useful for extremely apprehensive patients

• Duration of action may extend into postoperative period

 Chloral hydrate appears to be ineffective when given in low doses or when used for treatment of older, handicapped children.^,, The risks of using recommended doses of chloral hydrate are minimal and center upon tissue irritability and gastric upset, but can result in oversedation especially in children under the age of 2 or weighing less than 35 lbs. Vomiting following administration of chloral hydrate is often the only complication reported when using recommended doses. The action of chloral hydrate is similar to the action of alcohol in depressing the central nervous system and inducing sleep as opposed to benzodiazepine sedation which demonstrates more specific anti-anxiety effects. Despite these caveats and with an awareness of the other problems associated with all oral sedative agents, chloral hydrate remains an effective, albeit non-specific central nervous system depressant, for the uncooperative pediatric dental patient as most recently evidenced by the excellent study of Ibricevic and Al-Jame in the Dental News.²

The introduction of the benzodiazepines into clinical practice was revolutionary in providing health care providers with selective anti-anxiety agents combined with a great margin of safety as compared with barbiturates and other older central nervous system depressants. Benzodiazepines appear to exert their pharmacologic effects by their interaction with the receptor for the inhibitory neurotransmitter, gamma-amino butyric acid (GABA) in the central nervous system. Benzodiazepines all possess sedative, anxiolytic, amnesic and hypnotic properties in varying degrees . However, oral diazepam (Valiumâ ), the most popular oral benzodiazepine premedication, although providing excellent anxiety relief in adults has had mixed reviews for the pediatric patient. ¹¹

Midazolam hydrochloride (Versedâ ), a short-acting, water-soluble benzodiazepine, is rapidly absorbed intramuscularly, intravenously, nasally, rectally and via the gastrointestinal tract. Although not approved by the Federal Drug Administration (FDA), anesthesiologists have long popularized oral administration of midazolam as a safe and effective premedication prior to general anesthesia. Besides the medical legal ramifications of using a drug in a manner other than what appears on FDA-approved and mandated labeling, the parental form of midazolam was terribly bitter tasting and had to be admixed by the practitioner with a sweet vehicle to make it palatable. However, the recent FDA approval and availability of midazolam syrup as a cherry-flavored syrup with its potential for greater efficacy and safety than older drugs will further increase its popularity for pediatric sedation. We report our experience with oral midazolam in the treatment of the uncooperative, pediatric dental patient.

Methods

Seventy-five children ranging in age from 36 months to 7 years of age (mean age 5.1 years) were referred to the Tufts University School of Dental Medicine Pediatric Sedation Clinic due to inability to perform restorative dental procedures due to behavior issues. All patients were American Society of Anesthesiology Physical Status I and were fasting 6 hours prior to appointment. Patients were administered oral Versed â (midazolam HCL) syrup (.05 mg/kg) via oral dispenser by their parents. After administration, the children remained in the waiting room with observation by dental staff. The patients were brought into the operatory when the parents indicated that they felt their children would accept the dental environment. Parameters measured included palatability, success rate of treatment, incidence of crying, necessary supplementation of oral technique with nitrous oxide - oxygen, incidence of gastric upset, and oxygen saturation (Sp0₂) via a BCI International Monitor (Waukesha, Wisconsin, USA) and finger sensor.

Results

Palatability

Palatability was assessed by facial grimaces and struggling in response to taste. Seventy-seven per cent ( 58/75) of the children accepted the medication without severe grimacing or struggling. In thirteen percent (10/75) of the children, struggling and severe facial grimacing were encountered. Nine percent (7/75) either totally refused or would only accept small aliquots of the syrup despite parental and staff encouragement.

Supplementation with Nitrous Oxide – Oxygen Sedation

Twelve per cent (8/68) children were administered nitrous oxide –oxygen to increase the depth of sedation in order to accept local anesthesia and be amenable for dental treatment. Of this group, two children were still unable to be treated.

Ability to Achieve Local Anesthesia/Perform Procedure (Success Rate)

From the original cohort of 75 patients, the rate of successful treatment was 84 per cent (63/75). Failures included: 7 children who refused medication, 2 children who continued to be uncooperative after the addition of nitrous oxide – oxygen, 3 children who remained uncooperative to the point of even refusing placement of the nitrous oxide – oxygen nasal hood.

State of Consciousness

Crying

During injection of local anesthesia, the following table describes the data on the incidence of crying.

Oxygen Saturation

Oxygen saturation (Sp0₂) remained between 96 – 98% for all patients sedated with oral midazolam with and without nitrous oxide – oxygen supplementation.

Gastric Upset

There were no cases of gastric upset (nausea or vomiting) reported.

Discussion

With its rapid absorption from the gastrointestinal tract, oral midazolam became an extremely popular oral premedication for pediatric patients in the hospital setting although it was not available as an FDA approved oral preparation. The drug was used mainly to facilitate parental-child separation prior to the induction of anesthesia as well as provide sedation and amnesia. Although higher doses have been advocated, there appears to be an optimal balance between anxiolytic activity and side effect liability in doses of 0.25 mg to 0.50 mg/kg. maximum of 20 mg with the dose being individualized based upon patient age, (older children need less of the drug), degree of anxiety, and the level of sedation desired.^, Higher doses of to a midazolam (0.75 – 1.0 mg/kg) result in greater side effects especially regarding loss of balance and head control which could result in airway obstruction when compared with the .5mg/ kg recommended dose.¹⁵ “Fixed” oral doses of sedative drugs are a dangerous practice in pediatrics and should be avoided and whenever possible drugs should be administered as calculated by body weight or surface area.. Oral midazolam has been shown to reduce anxiety significantly when compared with oral diazepam and a placebo.

The palatability of oral midazolam syrup as demonstrated in our results confirm the fact that this drug is much better tolerated and accepted than chloral hydrate where facial grimacing and struggling have been reported in up to 50% of children receiving the drug. Our success rate and measurements of efficacy, crying, and state of consciousness compared favorably with results in studies evaluating chloral hydrate for sedation during pediatric dental procedures ^2,4,5,7,10, and confirm other studies advocating oral midazolam as an effective and safe sedative for children.^4,,,, It is important to note that although there was a small percentage of patients who were asleep during treatment (4.4%), all of them occurred with the co-administration of nitrous oxide –sedation. The potentiation of oral midazolam by nitrous oxide has been documented and can result in clinically significant airway obstruction especially in the presence of enlarged tonsils. Despite the fact that oxygen saturations remained in acceptable ranges for every case during this study, we advocate the use of pulse oximetry as a simple, non-invasive monitor whenever a central nervous system depressant is administered to a child.

Versed â Syrup is supplied in a bottle with a child-resistant bottle cap and press-in bottle adapter (PIBA). A graduated, oral dispenser easily inserts in the PIBA. Each mL of syrup contains 2 mg of midazolam.

Conclusion

Oral midazolam is a safe, effective sedative choice for uncooperative children for dental procedures. This margin of safety can only be maintained with the following caveats in place:

Our goal in treating pediatric patients has always been to provide access to care for all children especially those with behavioral issues. The introduction of oral midazolam provides dentistry with safe, effective method of sedating the uncooperative pediatric patient and avoiding the alternative of general anesthesia. This enthusiasm must be tempered, however, by a careful analysis of the risk/benefit ratio inherent in any pharmacologic intervention, and the realization that success and safety depends upon the training and adherence to basic safety standards by the dentist.

Tufts University School of Dental Medicine

Associate Professor of Anesthesia

Tufts University School of Medicine

Senior Anesthetist

New England Medical Center Hospitals, Inc.

Boston, MA

Lonnie H. Norris, D.M.D., M.P.H.

Professor of Oral and Maxillofacial Surgery

Dean, Tufts University School of Dental Medicine

Correspondence address:

Tufts University School of Dental Medicine

Department of Oral and Maxillofacial Surgery

1 Kneeland Street

Boston, MA 02111

e-mail:MRosenberg@Infonet.Tufts.edu