RISKS AND ADVERSE OUTCOMES

TOP ABSTRACT RISKS AND ADVERSE OUTCOMES DRUGS AND DRUG REGIMENS MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSIONS REFERENCES

 
Practitioners are aware that conscious sedation procedures carry risks from the potential side effects of the medications. For example, nausea and vomiting are not uncommon with sedation agents such as chloral hydrate, meperidine and nitrous oxide.^5–7 The most serious adverse outcome of pediatric conscious sedation is respiratory compromise and its related consequences.^8–14 Respiratory compromise can lead to hypoxemia and predispose children to a range of deleterious conditions.¹⁴

Morbidity and mortality from pediatric conscious sedation have been reported periodically.^15–18 Since the publication of Goodson and Moore’s¹⁹ 1983 article on sedation misadventures, the safety of sedation regimens for children has received considerable scrutiny. In 1985, the emergence of the Guidelines for the Elective Use of Conscious Sedation, Deep Sedation, and General Anesthesia in Pediatric Patients²⁰ elevated the professional standards for the safe provision of sedation of children. Professional discourse on the standards and their subsequent revisions by American Academy of Pediatrics in 1992²¹ and AAPD in 1993²² and in 1996²³ has led to increasing attention on the safety of conscious sedation of children, especially in a dental setting. Even so, conscious sedation for children still appears to carry significant potential for adverse outcomes. Wilson⁴ noted that of the 1,758 pediatric dentists who responded to his 1996 survey, 30 percent had experienced compromised airways in patients sedated with sedatives and nitrous oxide/oxygen analgesia, and 5 percent noted that they had activated emergency medical services secondary to sedation procedures.

Many drug regimens and routes of administration have been investigated and reported for conscious sedation of children in the dental setting.

	DRUGS AND DRUG REGIMENS

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Many drug regimens and routes of administration have been investigated and reported for conscious sedation of children in the dental setting. One regimen that has been the subject of several studies^10,12,24,25 is an oral elixir of chloral hydrate (50 milligrams per kilogram), meperidine (1.5 mg/kg) and hydroxyzine pamoate (25 mg). In this context, we will refer to this elixir as the ChMH regimen. Previous studies have reported success rates with this regimen ranging from 60 to 66 percent.^24,25

The rationale for ChMH. The rationale for the ChMH regimen is based on its potential for anxiolytic, analgesic and antiemetic effects. Chloral hydrate is a psychotropic agent with anxiolytic, sedative and hypnotic properties.^6,26 It has a wide margin of safety and has been studied extensively as a sedative drug for children. It is relatively easy to administer and is well-absorbed orally, requiring approximately 30 to 60 minutes to reach its peak effect.⁵ Chloral hydrate is the most common sedative agent used in conscious sedation for pediatric dental patients.^2,3

Meperidine is a narcotic analgesic with effects similar to, but less potent than, morphine.⁶ Its therapeutic actions include sedation and analgesia. Meperidine can cause respiratory depression, which can be potentiated by anxiolytic agents such as chloral hydrate. Oral meperidine has a rapid onset of 10 to 15 minutes; however, it requires one to two hours to reach its peak effect.²⁷

Hydroxyzine pamoate is an antihistamine and psychotropic agent that possesses antiemetic, anxiolytic, sedative and hypnotic properties. Oral hydroxyzine is absorbed rapidly with onset within 15 to 30 minutes.²⁸ It has a wide margin of safety and is a popular drug in pediatric conscious sedation.^2,3 Hydroxyzine commonly is used as a sole agent or in combination with chloral hydrate and meperidine.^26,28 When used as a combination drug with other central nervous system depressants, hydroxyzine can potentiate the central nervous system depression effect.^6,28 The antihistamine and antiemetic properties of hydroxyzine are used to overcome the histamine-releasing effect of meperidine, as well as the nausea and vomiting effects of both chloral hydrate and meperidine. The adverse effects of hydroxyzine are mild and transitory in nature.⁶

Nathan and West²⁴ reported better sedation outcomes by adding meperidine to chloral hydrate and hydroxyzine than with the same regimen without meperidine. Hasty and colleagues¹⁰ corroborated this finding and reported that meperidine did not increase the risk of experiencing complications, including respiratory compromise. They attributed the more favorable outcomes to the analgesic effects of meperidine that decreased the perception of pain from dental procedures and increased the sedative impact of the regimen.

In the Pediatric Sedation Clinic, or PSC, in the School of Dentistry at the University of North Carolina at Chapel Hill, ChMH has been used as one of several regimens for more than a decade. Supplemental 100 percent oxygen, or O₂, is added to ChMH based on the theoretical concept that 100 percent O₂ elevates the partial pressure of arterial oxygen, or PaO₂, in the sedated child, and this elevated PaO₂ provides an extra measure of safety during conscious sedation.¹²

To date, there have been no reports or studies of adverse events using the ChMH/O₂ sedative regimen. Therefore, the purpose of this article is to report adverse events and sedation outcomes from five years of experience using the ChMH/O₂ regimen of chloral hydrate (50 mg/kg), meperidine (1.5 mg/kg) and hydroxyzine pamoate (25 mg) with 100 percent O₂ supplementation.

	MATERIALS AND METHODS

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We reviewed patients’ dental and anesthesia records during the five years from July 1, 1992, through June 30, 1997. All sedations were performed in healthy children referred to PSC because of their inability to cooperate for needed dental care in the conventional dental setting. Before sedation, the children’s pediatricians or family physicians evaluated them to ensure that they had no contraindications for outpatient conscious sedation.

A variety of sedative regimens with and without inhalation agents were employed in the PSC. In this study, we are reporting only on those children who received ChMH/O₂ in all of their sedation visits. Our study focuses on ChMH/O₂ because of its popularity among general and pediatric dentists and because there has been no report of adverse effects with this regimen. Our data are limited to children 24 to 84 months of age because our case files contain few ChMH/O₂ cases for children younger than 24 months of age or older than 84 months of age.

Conscious sedation procedures. The PSC standard for conscious sedation protocol was followed for all cases included in this study. This protocol required dietary restrictions that permitted no milk or solid food up to eight hours and no clear liquid for up to four hours before oral drug administration in accordance with the AAPD’s Guidelines for the Elective Use of Pharmacologic Conscious Sedation and Deep Sedation in Pediatric Dental Patients.^22,23 On the day of sedation, the child was weighed, and the oral medications, or meds, were dispensed by weight in a small cup. The child was asked to drink the meds from the cup. If the child refused, the meds were administered by syringe with a parent’s assistance. The method of administration and approximation of lost meds (in milliliters) were documented in the patient’s record. After drug administration, the child waited in a quiet, dimly lit holding area. Parents were urged to cuddle the children and rock them in a rocking chair to encourage a quiet waiting time.

We defined and recorded waiting time as the interval between drug administration and the seating of the child in the dental chair. Based on the sedative and analgesic agents in the ChMH, the recommended waiting time is 45 minutes. If the child was not drowsy or sleeping after 45 minutes, the operator had the prerogative to wait longer.

The parent or the operator carried the child to the operatory, and all children were secured on an immobilizing board to control involuntary movements that might occur during the dental procedure. Monitoring probes were attached. A nasal cannula was placed, and supplemental 100 percent O₂ was administered continuously throughout the operation. The maximum dose of local anesthetic was limited strictly to 4.4 mg/kg for all patients.

Patients were monitored continuously using a pulse oximeter, a precordial stethoscope and visual observation. Capnography was adopted for routine use in the PSC in 1995; accordingly, end-tidal carbon dioxide, or ETCO₂, measures were recorded in the anesthesia record from that time forward. A resident or attending faculty member was appointed as a dedicated monitoring assistant for each sedation. The monitoring assistant communicated as needed to help the operator with airway positioning and to leave the primary provider/dental operator (also a resident or attending faculty member) free to concentrate on the dental procedures. The monitoring assistant used a written time-based anesthesia record to document physiological signs every five minutes. Pulse rate; respiratory rate, or RR; oxyhemoglobin saturation, or SpO₂; and ETCO₂ (starting in 1995) were recorded. The monitoring assistant also documented the details and timing of any unusual or adverse events that occurred during the procedure. The dental operator documented the treatment rendered at each visit and the sedation outcome.

As a part of the protocol, each parent was given written postoperative instructions that included a telephone number at which to call the primary provider to report and discuss any postoperative sequelae or concerns. All such concerns were recorded in the patients’ records.

Data collection. Based on a comprehensive review of all sedation cases performed during the five-year period, 111 children met the inclusion criteria, which resulted in 195 conscious sedation appointments. All of the children were 24 to 84 months of age and received only ChMH/O₂ for all sedation appointments. From these 111 children, we collected the following data from dental and anesthesia records: age, sex, weight, medical history, current medical conditions, total sedation visits, compliance in taking meds, waiting time, total milligrams of local anesthetic given, treatment duration, vital signs, SpO₂, ETCO₂ (starting in 1995), adverse events, treatment rendered, sedation outcomes and postoperative sequelae.

We defined true desaturation as a pulse oximeter reading of SpO₂ below 95 percent taken while the patient was quiet and still. We defined true apnea as no visual signs of breathing, no breath sounds audible via precordial stethoscope and a capnograph reading of zero for RR and ETCO₂ for 25 seconds.¹⁰ We defined prolonged sedation as one in which the child needed more than 30 minutes after the conclusion of dental treatment to recover and meet the discharge criteria recommended in AAPD’s guidelines²⁰; in brief, the child needed to be walking, talking and drinking to be dismissed.

We recorded a sedation outcome based on the operator’s judgment using a subjective classification, wherein satisfactory sedation was defined as completion of planned care without difficulty. Unsatisfactory sedation was defined as a completion of planned care with difficulty due to disruptive behavior or completion of less care than planned. Aborted sedation was defined as discontinuation of care resulting from disruptive behavior with concerns for patient or dental team safety.

We collected the completed treatment as relative based value units, or RBVU, wherein all types of dental work were converted to numeric scores to make valid comparisons of the treatment rendered across all sedation appointments. For example, the score of a one-surface amalgam restoration in a primary tooth was 1.0, the score of a two-surface amalgam was 1.5, and the score of a prefabricated stainless steel crown in a primary tooth was 4.0.

The relative based value system called Dental Relative Based Value Scale/Units^29,30 was developed in 1985 through surveys that collected input from practitioners valuing each dental procedure based on its time and difficulty. The data were received from thousands of dentists from all specialties and were analyzed for validity and normal distribution. Standard deviations and means were used to develop the scale. The relative value has been used as a way to value dental procedures across disciplines and specialties and is considered to be a reliable measure. It is used widely by health insurance organizations and Medicaid agencies to determine the value of procedures for reimbursement.³⁰

Data analyses. Descriptive statistics were employed to illustrate results in frequencies and percentages. Each sedation visit was analyzed independently. We used ² tests to assess statistical differences in categorical data, while we used Student t test and analysis of variance, or ANOVA, for continuous data. We used Bonferroni inequality tests to determine the difference between group studies when ² tests revealed significant difference and Scheffé tests if ANOVA showed statistical significance.

	RESULTS

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The study patients’ demographics are given in Table 1. There was no difference in sex distribution. Eighty-seven percent of the children (97/111) cooperated in drinking all their meds from a cup during 174 visits. Although parental and operator coaxing were sometimes needed, for only 13 percent of the children (14/111) in 21 sedation visits was it necessary to administer meds via syringe. The patients received all meds via the syringe in 10 of 21 visits, while the remainder lost some meds because of their refusal to swallow; for example, they expectorated at least some of the meds.

Among the patients who drank all their meds from a cup (174/195), 75 percent had satisfactory sedation appointments, while 25 percent had either unsatisfactory or aborted sedation appointments. Only 48 percent of the patients who refused to drink their meds had satisfactory appointments. Sedation outcomes were higher among those children who drank all meds from a cup, and this difference was statistically significant (P = .013).

The mean waiting time was statistically significantly different among S, U and A sedation outcome groups (61, 58 and 49 minutes, respectively, P = .012). Scheffé test revealed that the mean waiting time of the S group was significantly longer than that of the A group.

The mean treatment duration of S and U groups were 65 and 64 minutes, respectively, and this difference was not statistically significant. Likewise, the RBVU was 11 and 12 in groups S and U, respectively, a difference that was not statistically significant (P = .193). In summary, there were no significant differences in the duration of treatment and amount of treatment achieved between the U and S groups.

Adverse events were reported in six of the 195 visits, or 3 percent of the sedation appointments. Adverse events included postoperative vomiting, true desaturation, true apnea and prolonged sedation (Table 3). All of the patients who experienced adverse events had satisfactory sedation appointments.

	DISCUSSION

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Compliance with drinking meds. The oral route of administration is the most popular choice by pediatric dentists,^28,31 but few studies have investigated acceptance for oral meds in children. Haas and colleagues³² compared the acceptance of oral chloral hydrate with oral midazolam for children 3 to 10 years of age, finding no difference in acceptance when both meds were mixed with syrup and orange juice. The ChMH oral regimen is a well-tolerated mixture, and we found that 91 percent of the children drank all their meds from the cup at their first sedation visit and only four patients refused to do so at the second visit. This was not surprising, as most children are accustomed to drinking meds from a cup and the bitterness of chloral hydrate is masked by the sweet taste of hydroxyzine in the ChMH regimen.

Among the noncompliant children, nine girls refused to drink meds compared with five boys. Ten children refused to do so in their first sedation visits, though they had no previous experience with the taste of these meds. In general, our findings suggest that a child’s refusal to drink meds should signal a concern; we recorded a loss of 5 to 30 percent of the meds using a syringe, and the percentage of successful sedation was lower in this group.

Waiting time. The waiting time for a given oral regimen varies depending on pharmacodynamics of the drugs in the specific regimen. Drug onset is the time in which the effect of the drug can be detected. For sedatives, onset might induce sleep in a nonstressful situation. Because dental procedures usually consist of multiple stimulations that include mild to moderate painful stimuli, the waiting time should be calculated to coincide with onset of the drugs’ peak effect.

PSC’s protocol recommends a waiting time of approximately 45 minutes. Occasionally children will go through a paradoxical excitation stage, which can prolong waiting time significantly. When the child is not sleeping or drowsy, more waiting time usually is given. There are, however, many occasions when the child may fall asleep soon after administration of meds, and this presents a temptation to initiate treatment sooner than the 45 minutes’ waiting time. On the basis of our findings, a strong argument can be made for waiting a minimum of 45 minutes for the ChMH regimen to take effect, no matter how profoundly the child is sleeping before this critical time. In some situations, children will fall asleep soon after receiving ChMH meds because of the rapid onset of the meperidine and hydroxyzine; however, the peak effect of the ChMH regimen is most likely in the range of 60 to 90 minutes. Hasty and colleagues¹⁰ speculated that sedation outcome would be better if invasive stimuli, such as injection and rubber dam clamp placement, are timed to occur as nearly as possible to the time of peak effect of meperidine.

Our findings suggest that waiting time may be a critical variable for a successful sedation outcome. Accordingly, physicians should thoughtfully consider this factor and pay attention to the specific actions of their sedation drugs. Most reported sedation studies do not describe or manage the waiting time variable; we suggest that waiting time should be analyzed more carefully in future sedation studies.

Waiting a sufficient amount of time between anesthetic administration and treatment may be a critical variable for a successful sedation outcome.

Sedation outcomes. We acknowledge that our assessment of sedation outcomes was highly subjective. The standard of research methodology for assessment of child behavior in the dental setting should rely on video technology using valid and reliable behavior assessment scales.³³ We made no attempt to achieve this standard, and, thus, our sedation outcome results must be viewed as global and subjective. Nevertheless, our findings are consistent with other studies that have used the ChMH regimen with the same dosages for healthy children 24 to 48 months of age.

Nathan and West²⁴ used a dichotomous behavioral rating scale and reported successful sedation (defined as treatment achieved without restraint) for 60 percent of their cases in a ChMH study involving 135 children whose mean age was 34 months. They also found that the ChMH regimen was 45.6 percent more successful than the regimen that used chloral hydrate and hydroxyzine alone. Croswell and colleagues²⁵ reported a 66 percent success rate in 44 patients (mean age 39 months). Our findings are in the same general range, with a 72 percent success rate reported for 195 sedations (mean age 47 months).

Most previous sedation studies for preschool children have not addressed sex differences per se. One exception is a study by Needleman and colleagues¹¹ that reports 15.5 percent greater success for boys than for girls in a sample of 385 sedations in 336 patients (mean age 30 months). In our study, we found that boys were more complaint in taking meds. Although not statistically significant, we found a clear trend that male sedation outcomes were more successful. Boys also had fewer aborted sedation visits—only two aborted appointments compared with eight aborted appointments for girls. Future pediatric sedation studies should examine potential sex differences more closely.

We found no difference in age and weight among our group of patients with different sedation outcomes, a similar finding to that reported by Needleman and colleagues.¹¹ Our sample size, however, was too small to draw valid conclusions about age and weight as predictors of sedation outcomes.

Treatment outcomes. RBVUs represent unit values reflecting the time and effort to complete various dental procedures. We found these unit values to be useful in converting various types of dental procedures to a common denominator for comparison purposes. Although the system has not been used often in clinical research, it has been used widely for management and cost analysis purposes.³⁰

We found no significant differences in mean value of care delivered in the satisfactory vs. unsatisfactory groups; indeed, the results showed slightly more work completed for the unsatisfactory group. We point out again that our sedation outcome assessment was subjective and based not on the quantity of treatment completed, but on the difficulty of completing care in a given situation and the operator’s judgment. The most likely explanation for our finding is that operators made every effort possible to complete the care for those children who were the most challenging in an attempt to limit future sedation visits or avoid care under general anesthesia.

We found that 93 children had all their treatment completed while under conscious sedation. Of the remaining 18 patients, five whose sedations were aborted were referred to have the remaining treatment completed while under general anesthesia. For the other 13 patients, treatments were not completed during the study period because of failed appointments or family relocation.

Vomiting as an adverse event. Although nausea and vomiting are common adverse reactions for both chloral hydrate and meperidine,^5,6 we found only one such incident among the 195 sedations in this study. Hasty and colleagues¹⁰ reported no vomiting with ChMH/O₂ for the 20 sedations in their study. In contrast, Needleman and colleagues¹¹ reported 8.1 percent vomiting intraoperatively using chloral hydrate/hydroxyzine/nitrous oxide/O₂. Nausea and vomiting are not uncommon side effects of N₂O/O₂.⁷ While we attribute the low incidence of vomiting in this study to our rigid adherence to the preoperative patient dietary restrictions, the absence of N₂O/O₂ cannot be discounted.

Apnea as an adverse event. A well-controlled study by Rohlfing and colleagues¹² reported that the risk of experiencing apnea during conscious sedation was 39 percent, and the risk was equal in patients who received supplementary 100 percent O₂ and those who did not. The respiratory depressive effects of narcotics plus synergistic drug reactions with sedative agents can increase the respiratory depression effect of a drug regimen, a phenomenon exacerbated by local anesthetics.^19,25,34 We found only one episode of true apnea in this study, but this number probably is artificially low because a capnograph was not used in the first one-half of the study. Almost certainly we would have diagnosed more apneic episodes if a capnograph had been used in all cases.

Desaturation as an adverse event. There is compelling evidence that oxygen desaturation events occur during conscious sedation of pediatric patients; however, most desaturations are artifacts.³⁵ We defined true desaturation as a pulse oximeter reading of SpO₂ below 95 percent while the patient is quiet and still. We found only one episode of true desaturation in this study.

The benefit of O₂ supplementation during conscious sedation has been suggested in several studies.^{9,10,12,25,36} It is our routine practice to provide all children with supplementary 100 percent O₂ intraoperatively via nasal cannula. This technique is convenient, easy and inexpensive. Furthermore, this approach is well-tolerated by children and does not compromise the operator’s access in any way. We did not see desaturation after the one apneic episode reported here.

Prolonged sedation/slow recovery. Concern about the recovery period and discharge criteria were emphasized in AAPD’s guidelines.^20,22,23 The discharge protocol in our study was to dismiss children within 15 to 30 minutes after the conclusion of the dental procedures if cardiovascular and respiratory functions were within normal limits. We expected to see more slow recoveries because both meperidine and chloral hydrate have reasonably long half-lives and wear off gradually within several hours.^5,6 However, we found only three instances of prolonged sedation/slow recovery among 195 sedations. Furthermore, we had no documented circumstances of postoperative sedation–related sequelae after the patients were dismissed to return home.

	CONCLUSIONS

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We acknowledge that this study is retrospective in nature, and it involved multiple operators over a five-year period. The method of assessing patient cooperation was subjective. The study, however, involved a highly standardized sedation protocol, including a written record of anesthesia and close attention to detail in record-keeping and chart documentation. Under the conditions of this study:

– adverse events occurred in only 3 percent of the sedation appointments when a strict sedation protocol was adhered to;

– the ChMH/O₂ regimen yielded a 72 percent success rate, while 23 percent of the cases were unsuccessful, and 5 percent were aborted;

– compliance with taking oral medications and waiting time after medication intake were important factors in predicting sedation success.