Chloral Hydrate For Emergent Pediatric Procedural Sedation: A New Look at an Old Drug LOUIS S. BINDER, MD, LAWRENCE

A. LEAKE, MD

Chloral hydrate has been time honored for pediatric procedural sedation, but its efficacy in sedation for emergency department (ED) procedures is unreported. It is hypothesized that chloral hydrate is safe and effective for ED pediatric sedation. Ninety-five consecutive children ranging from l-10 years and requiring procedural intervention in a municipal teaching hospital ED were included in a nonrandomized controlled trial. Patients with respiratory depression, somnolence, allergy, multisystem trauma, head injury, or abdominal pain were excluded. Forty-two subjects received chloral hydrate 25 to 50 mg/kg orally at physician discretion, and 53 subjects served as controls. Cooperation with procedural completion was rated by the treating physician using the four-point sedation scoring system modified from Moody et al (1 = poor, 4 = excellent). The two groups’ sedation scores were compared by the Mann Whitney U test with significance at P less than .05. Age-related subgroups of children were similarly compared. The treatment group achieved sedation score of 2.88, whereas controls had sedation score of 2.75 (P = 0.63, p error 20% at 0.37 score difference). Subgroup analysis of children less than 6 years old (2.95 experimental versus 2.57 control) and less than 4 years old (3.00 experimental versus 2.32 control) reveals statistically significant differences (P < .OOOl and P = .Ol, respectively) in favor of higher sedation scores in the chloral hydrate group. Time to sedation was 42.7 minutes, time to recovery was 42.0 minutes, and no adverse drug effects were noted. It is concluded that pediatric sedation for ED procedures for children under 6 years of age can be enhanced safely by the use of chloral hydrate 26-50 mu/kg administered orally. (Am J Emerg Bled 1991;9:530534. Copyright 0 1991 by W.B. Saunders Company)

Control of anxiety and combative behavior are important objectives in the completion of pediatric procedures. Much has been written about the accomplishments of these goals in the execution of pediatric procedures outside of the emergency department (ED) tie, computed tomographic [CT] and magnetic resonance imaging scans, dressing changes, endoscopies). ‘-’ However. the control of anxiety and behavior in the ED have been largely unstudied, with a few recent exceptions.x.’ The emergency department in many ways is a uniquely difficult milieu in which to attempt pediatric sedation. Unlike procedural sedation for CT scanning, where little stimulation of the patient (painful or otherwise) occurs, ED sedation is usually undertaken for invasive procedures, which are often painful. At the moment of pain, heightened levels of anxiety are provoked, and controlling behavior becomes exceedFrom the Department of Emergency Medicine, Texas Tech University Health Sciences Center at El Paso, 4800 Alberta Ave, El Paso, TX 79905. Address reprint requests to Dr Binder, Department of Emergency Medicine, Texas Tech University Health Sciences Center at El Paso, 4800 Alberta Ave, El Paso, TX 79905. Key Words: Pediatric sedation, pediatric procedural sedation, conscious pediatric sedation. Copyright 0 1991 by W.B. Saunders Company 0735-6757/91/0906-0002$5.00/O 530

ingly difficult. Second, a recently fed child presenting for an unscheduled procedural intervention risks vomiting, and creates variable absorption with the use of oral medications. Third, the high patient volume, high patient-physician ratio, and hurried pace of the ED do not allow personnel the luxury of prolonged one to one contact and observation of sedated patients. The American Academy of Pediatrics (AAP) and the American Academy of Pediatric Dentistry (AAPD) have recently established clinical guidelines for level I (conscious sedation) and level 2 (deep) sedation calling for two to three personnel in constant attendance, intravenous access. electronic monitoring, and frequent noting of vital signs.‘O However, whereas these recommendations are closely followed in ambulatory surgery units and in the radiology suite,‘.““’ they impose a difficult standard for ED practitioners. A national survey revealed that a majority of pediatric EDs do not comply with AAPiAAPD standards. with the most common monitoring protocols consisting of intermittent taking of vital signs. intermittent visual monitoring by staff, and parental observation.” Chloral hydrate was developed by Liebig in 1832 and has been a time-honored agent for pediatric dental sedation.‘J.‘5 It is metabolized by hepatic alcohol dehydrogenase to its active compound trichloroethanol and is subsequently excreted in the urine.lh Sedative doses produce a mild somnolence, but no analgesic effect.“-” The drug produces sedation within 30 to 60 minutes with recovery by 90 minutes.lh with no significant depression of ventilation and carbon dioxide receptor response to hypercarbnia.” Drug dosing may be adopted to various levels of sedation. No other side effects are encountered, creating a wide margin of safety in its use.14.15 Drawbacks to its use include an unpalatable taste (which can be mixed with juice or soft drinks), and a variable degree of gastrointestinal absorption (due to varying food intake before ED visitation and drug-induced gastric irritation). “.I’ Both of these drawbacks may be addressed by rectal administration if necessary. With these characteristics, chloral hydrate may be suitable and safe for pediatric sedation in the ED milieu. We undertook a controlled clinical trial of chloral hydrate to determine its efficacy of sedation and control of patient resistance with pediatric patients requiring procedural intervention in our ED. MATERIALS AND METHODS

A prospective, observational, and controlled clinical trial was conducted at R. E. Thomason General Hospital, the city-county hospital for El Paso, Texas. The study was reviewed by the Investigational Review Board of Texas Tech University Health Sciences Center at El Paso. who agreed

BINDER AND LEAKE n CHLORAL

TABLE1.

Sedation

2 3 4

531

Scale Description

Score 1

Scoring

HYDRATE

of Behavior

Uncooperative, marked combativeness and resistance; procedure cannot be accomplished Uncooperative, mild to moderate resistance; procedure accomplished with difficulty Cooperative but restless; procedure accomplished with minimal difficulty Asleep or cooperative, no movement; procedure accomplished easily

with the study methodology, but who did not require formal approval of the observational study design. Between July I, 1989, and April 30, 1990, consecutive children ranging in age from 1 to 10 years presenting to the ED of R. E. Thomason Hospital and requiring procedural intervention were enrolled in the study. Patients with known allergy to chloral hydrate, respiratory depression, or somnolence upon arrival to the ED, or the presence of multisystern trauma, head injury, and abdominal pain or trauma were excluded. Children received either chloral hydrate 25 to 50 mg/kg orally or no medication prior to procedural intervention. Distribution of subjects between the two groups and selection of chloral hydrate dose was performed in a nonrandomized fashion at physician discretion, consistent with a prospective observational design. Parental consent was obtained prior to chloral hydrate administration. Cooperation with procedural completion was rated by the treating physician using a modified version of the sedation scoring system reported by Moody et al (Table l), and ratings were grounded in identifiable behavioral terms observable during procedural execution. The chloral hydrate preparation used was Noctec (E. R. Squibb, Princeton, NJ), 500 mg/5 mL in 5-mL-unit dose vials for oral or rectal use. A papoose board for necessary restraint and local infiltration with lidocaine 1% was used when needed for wound repair, abscess drainage, and foreign body removal. Sedated and unsedated patients were monitored in the ED via serial vital sign determinations, intermittent monitoring by ED staff, physician monitoring at the depths of sedation during the procedure, and continuous parental observation. Pulse oximetry was not available in our ED. Patients were discharged when awake and ambulatory. Data collected include age, sex, procedural indication, dose of chloral hydrate given, time to sedation, time to recovery, and sedation score. Time to sedation was defined as TABLE 2.

Patient

the interval from the time that chloral hydrate was given to the time that the child was noted to be somnolent and (in most cases) exhibited reduced resistance and combativeness to examination or manipulation by the treating physician. Procedural intervention was undertaken at this time. Time to recovery was defined as the interval from the time of procedural intervention to the time that the child was noted as ambulatory, or time of discharge (as gait evaluation was performed by ED staff or physician prior to discharge). The two groups (sedated and unsedated) were compared by x2 and Student’s t-test for demographic data, and by the Mann Whitney U test for sedation score data, with significance at P < .05. Age-related subgroups of children were similarly compared. A p error of 20% was calculated for all negative trials. RESULTS Ninety-five children were enrolled in the study. Forty-two patients received chloral hydrate and 53 patients served as controls. Table 2 shows the age, sex, and procedural indication. Significant differences were noted between the mean ages of the control and chloral hydrate groups, and between the two groups with the distribution of procedural indication. In comparison to the control group, the chloral hydrate group was significantly younger (3.0 versus 4.7 years) and had a significantly higher incidence of abscess drainage, foreign body removal, and “other” procedures as opposed to wound repair (67% versus 96% incidence of wound repair). Table 3 depicts the data on chloral hydrate dosages, sedation scores, time to sedation, and time to recovery. Chloral hydrate doses used ranged from 25 to 50 mg/kg, with an average of 39 mg/kg; two patients required 15 mg/kg repeat doses. Time to sedation average 42.7 minutes for the patients in whom this information was documented, and time to recovery was 42.0 minutes. There were no significant differences by Mann Whitney U test between the sedation scores of patients with and without chloral hydrate. Table 4 reveals the distribution of sedation scores for subgroups of children less than 6 years old and children less than 4 years old. In both subgroups, a significant difference in sedation scores in favor of higher scores in the chloral hydrate group was found. No vomiting or problems with oral administration were noted, no airway, respiratory, or cardiovascular complications were noted, and all sedated children recovered promptly (longest time to recovery was 60 minutes).

Characteristics Total (n = 95)

No Sedation (n = 53)

Chloral Hydrate (n = 42)

Age

3.996

4.734

3.017

Sex

68127 (72%/28%)

39/l 4 (74%/26%)

29/l 3 (690/o/31%)

Procedure Wound repair Abscess Foreign body Other

79 (83%)

51 (96%)

5 (5%) 8 (8%) 3 (3%)

1 (2%) 1 (2%) 0

28 (67%) 4 (10%) 7 (17%) 3 (7%)

Statistical Significance P = .007 Student’s t-test NS P = .0047 X2

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TABLE 3.

Chloral

Hydrate 25 30 35 40 45 50

Dosage (n = 42)

Data and Overall

mg/kg-5 mg/kg4 mg/kg-7 mglkg-6 mg/kg-5 mg/kg-15

Sedation

Score

1 (Cannot be accomplished) 2 (Accomplished with difficulty) 3 (Accomplished with minimal difficulty) 4 (accomplished easily) Average

score

Sedation Average

patients patients patients patients patients patients

Repeat dosage: (n = 2; both 15 mg/kg) Time to sedation = 42.7 minutes (n = 33) Time to recovery = 42.0 minutes (n = 32)

OF EMERGENCY

Scores 39.0 mg/kg

(20-60) (20-60)

Total (n = 95)

No Sedation (n = 53)

Chloral Hydrate (n = 42)

3

3

0

34

19

15

37

19

18

21

12

9

2.80

2.86 versus 2.75, P = .63 via Mann Whitney at 0.37 score difference. l

JOURNAL

2.75’

2.86*

U test; 6 error 20%

DISCUSSION There are methodologic limitations apparent in our study design. A randomized and blinded protocol with a standard protocol dosage of chloral hydrate would have made for more valid comparison of the effects of chloral hydrate versus control in pediatric sedation, and would likely have avoided the age and procedural biases observed. Second, pulse oximetry or continuous bedside monitoring, if possible, may have detected evidence of ventilation or airway problems not observed by our physicians and nurses with intermittent monitoring. Third, 50 mg/kg of chloral hydrate represents a modest dose for pediatric sedation. Higher doses of chloral hydrate than were used here (50 to 75 mglkg) have been advocated for pediatric sedation.‘,4,6,‘4+‘5 Doses in this range might have been sufftcient to achieve statistical significance in the overall study group without increase in adverse drug effects, based on these studies. The lower dosing guidelines were chosen to accentuate patient safety concerns (see below), given the unavailability of pulse oximetry and continuous physician monitoring (per AAP and AAPD guidelines). Lastly, rectal administration of chloral hydrate has been hypothesized to result in more consistent drug absorption.‘4.‘6 The different limitations elucidated above would each be expected to work against the achievement of higher sedation scores in the chloral hydrate group. Higher doses of chloral hydrate (50 to 75 mg/kg) and rectal administration would have resulted both in higher chloral hydrate absorption and a greater degree of procedural sedation. Additionally, it is apparent that the noted age and procedural indication biases reflected a trend by our physicians to select younger children

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(generally less cooperative) and children undergoing more painful procedures (abscess drainage) or exacting procedural intervention (otic or nasal foreign body removal) for sedation. Sedation tended to be withheld for older children and children undergoing wound repair, with the perception that sedation was not needed for procedural completion with these groups. These selection biases were reported by several of our ED physicians following the conclusion of data collection and analysis, and likely biased against the achievement of high sedation scores in the treatment group by shifting more of the difficult sedation problems to that group. It seems probable that if age bias, procedural bias, and chloral hydrate dosing administration were corrected, the improved sedation scores in the treatment group would have been even more pronounced. Thus, the observations that effective pediatric sedation for ED procedure can be enhanced, and procedural execution can be facilitated, for children under 6 years of age by the use of chloral hydrate 25 to 50 mg/kg orally appear to be valid. Within the everyday monitoring capabilities of most EDs for sedated patients, chloral hydrate exhibited no clinical difficulties in administration or adverse effects to patients when used in the ED milieu. No vomiting or respiratory or cardiovascular complications were observed, and all patients recovered safely and promptly following drug administration. This wide margin of clinical safety in oral administration appears very well suited to ED requirements. and the time to sedation and recovery appear favorable for ED use as well. Our only adverse observation was with several cases of minimal response to chloral hydrate in our treatment group, similar to previous reports, despite adequate oral dosing. 14.1h We hypothesize that gastric contents in these children interfered with absorption, and that rectal administration would likely have alleviated this problem. As discussed previously, it is clear that agents that may be effective and safe for pediatric procedural sedation in other milieus may not be well suited to ED use. By their nature, no sedative drug will provide proficient sedation without the possibility of patient obtundation or blocking of airway reflexes in some children. The manpower constraints and clinical volume of the ED require an emphasis on safety in the course of ED pediatric sedation, over and above sedation TABLE 4.

Sedation

Sedation Children n 1 2 3 4 Children n 1 2 3 4

Scores for Subgroups

Score

No Sedation

Chloral Hydrate

less than 6 years’ 37 3 14 16 4

38 0 12 16 10

19 2 10 6 1

30 0 10 10 10

less than 4 yearst

* 2.95 versus 2.57, P < 10m4 via Mann Whitney t 3.00 versus 2.32, P = ,014 via Mann Whitney

U test, U test.

BINDER AND LEAKE n CHLORAL

HYDRATE

efficacy (if necessary), if AAP and AAPD guidelines for pediatric sedation cannot be strictly followed. An “ideal” ED sedative would be administered orally or intramuscularly (would not require intravenous access); have a rapid onset, short duration, and rapid recovery; be potentially reversible; produce a predictable degree of sedation and behavioral control for a specified dose; and would not or would only negligibly affect ventilation and airway reflexes, with few (if any) reports of ventilatory impairment. No such sedative or anxiolytic agent exists, but these criteria are useful in evaluating potential agents for pediatric ED use. When viewed by these criteria, chloral hydrate exhibits a favorable profile of easy administration, reasonably rapid effectiveness and dissipation, has an excellent safety record for ventilatory preservation in multiple reports,‘-6*‘4.‘5.‘8 and exhibits a light to moderate and predictable level of sedation and behavioral control when a specified dose is given. The drug has been shown successful in thousands of patients for sedation of patients for nonpainful procedures (CT scanning)le6 with extremely infrequent reports of toxicity.3*‘9 Comparative studies to date have shown equal sedation, efficacy, and procedural completion rates for preanesthesia, CT scanning, and electroencephalogram (EEG) examination with meperidine/promethazine/chlorpromazine (DPT) regimens, meperidine and pentobarbital combinations, and midazolam.s.‘8 There is a perception among many emergency physicians that chloral hydrate provides anxiolysis suitable for preanesthesia and radiologic procedures, but that its sedative effects are too unpredictable and variable for either painful or urgent procedural sedation. This bias was reflected in the study by Hawk et a1,13 who reported only 2% of pediatric emergency physicians used the drug as first choice for pediatric sedation for suturing. While much of the literature on chloral hydrate does address its use for preanesthesia and CTlEEG sedation, other studies”,‘4-‘6 address its efficacy in sedation for painful medical and dental procedures. The majority of procedures conducted in this study were wound repairs, which would not be painful following initial administration of local anesthesia (given in all cases). Additionally, anxiolysis and control of combative behavior during painful procedures (over and above pain control) are appropriate clinical objectives which may justify the use of sedating medication. The premise of this investigation is that, similar to prior reports, chloral hydrate can be an effective and safe adjunct to the successful completion of painful pediatric procedure in the ED milieu, which was confirmed by our data. It is true that variability in clinical response may occur with gastrointestinal absorption of chloral hydrate in fed patients (similar to our observations), which is likely the source of this perception. Other studies have shown consistent, improved, and predictable sedation in children when the drug is administered rectally.‘4U’6 Recently, both midazolam* and ketamine’ have been investigated in pediatric ED use in the alleviation of anxiety and control of behavior during invasive procedures. Clinical efftcacy in procedural sedation and no respiratory depression was seen in the midazolam study of 55 patients, but larger series have reported respiratory depression and hypoxia,20‘22 and decreased efficacy for procedural (versus radiographic) sedation. I6 In an uncontrolled study, ketamine

533

showed a 97% efficacy in achieving satisfactory sedation for procedural intervention, but hypertonicity and random purposeless movements of the extremities with this agent may interfere with procedural undertaking. However, these side effects are apparently easy to control.9 With the availability of several recent studies on painful procedural sedation for pediatric ED patients documenting the efficacy and safety of several agents,8*9*‘3 it is clear that several agents may be potentially acceptable for ED use for pediatric sedation. Lack of standardized doses, rating scales, patient populations, and patient monitoring practices have made comparison of different sedation regimens difficult. For these reasons, randomized and blinded clinical trials with standardized dosages of midazolam, ketamine, and chloral hydrate, with adequate numbers of subjects to detect complications in the ED milieu, and with continuous bedside monitoring by staff and pulse oximetry should be undertaken. CONCLUSION In a prospective observational and controlled series of 95 patients, effective sedation for ED procedures for children under 6 years of age can be enhanced, and procedural execution can be facilitated, by the use of chloral hydrate 25 to 50 mg/kg orally. No adverse cardiovascular, respiratory, or gastrointestinal effects were noted (consistent with other reports), creating a wide margin of clinical safety that is helpful in a busy ED milieu. Many features of this drug appear favorable for ED use when compared with the characteristics of an “ideal” ED pediatric sedative. Randomized and blinded clinical trials with chloral hydrate, midazolam, and ketamine are needed to more accurately and comparatively determine the risks and benefits of these agents for pediatric procedural sedation in the ED milieu. REFERENCES 1. Gomez MR, Reese DR: Computerized tomography of the head in infants and children. Pediatr Clin North Am 1976;23:473498 2. McCullough DS, Kufta C, Axelbaum SP, et al: Computerized axial tomography in clinical pediatrics. Pediatrics 1977; 59:173-181 3. Mitchell AA, Lovik C, LaCouture P, et al: Risks to children from computed tomographic scan premeditation. JAMA 1982; 247:2385-2388 4. Sander JE, Lo W: Computed tomographic premeditation in children. JAMA 1983;249:2639 (letter) 5. Weir MR, Segapeli JH, Tremper LJ: Sedation for pediatric procedures. Milit Med 1986;151:181-184 6. Thompson JR, Schneider S, Ashwal S, et al: The choice of sedation for computed tomography in children: A prospective study. Radiology 1982;143:475-479 7. Keeter S, Benator RM, Weinberg SM, et al: Sedation in pediatric CT: A national survey of current practice. Radiology 1990;175:745-752 8. Hennes HM, Wagner V, Bonadio WA, et al: The effect of oral midazolam on anxiety of preschool children during laceration repair. Ann Emerg Med 1990;19:1006-1009 9. Green SM, Nakamura R, Johnson NS: Ketamine sedation for pediatric procedures. Part 1. A prospective study. Ann Emerg Med 1990;19:1024-1032 10. Guidelines for the elective use of conscious sedation, deep sedation, and general anesthesia in pediatric patients. Pediatrics 1985;76:317-321 11. Strain JD, Campbell JB, Harvey LA, et al: IV Nembutol:

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Safe sedation for children undergoing CT. AJR 1988;151:975979 12. Saint-Maurice C, Landais A, Delleur MM, et al: The use of midazolam in diagnostic and short surgical procedures in children. Acta Anaesthesiol Stand, 1990;34:39-41 (suppl 92) 13. Hawk W, Crockett RK, Ochsenschlager DW, et al: Conscious sedation of the pediatric patient for suturing: A survey. Pediatr Emerg Care 1990;6:84-88 14. Moody EH, Mourino AP, Campbell RL: The therapeutic effectiveness of nitrous oxide and chloral hydrate administered orally, rectally, and combined with hydroxyzine for pediatric dentistry. ASDC J Dent Child 1986;53:425-429 15. Moore PA, Mickey EA, Hargreaves JA, et al: Sedation in pediatric dentistry: A practical assessment procedure. J Am Dent Assoc 1984;109:564-569 16. Zeltzer LK, Jay SM, Fisher DM: The management of pain associated with pediatric procedures. Pediatr Clin North Am 1989;36:941-964

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17. Lees MH, Olsen GD. McGilliard KL, et al: Chloral hydrate and the carbon dioxide chemoreceptor response: A study of puppies and infants. Pediatrics 1982;70:447-450 18. Saarnivaara L, Lindgren L, Klemola UM: Comparison of chloral hydrate and midazolam by mouth as premedicants in children undergoing otolaryngological surgery. Br J Anaesth 1988;61:390-396 19. Granoff DM, McDaniel DB, Borkowf SP: Cardiorespiratory arrest following aspiration of chloral hydrate. Am J Dis Child 1971;122:170-171 20. Diament MJ, Stanley P: The use of midazolam for sedation of infants and children. AJR 1988;150:377-378 21. Versed: Another dangerous drug slips through the FDA’s sieve. The Public Citizen Health Research Group Health Letter, Washington, DC, vol 4, 1988, pp 1-4 22. Forster A, Gardaz JD, Suter PM, et al: Respiratory depression by midazolam and diazepam. Anesthesiology 1980;53:497505

Chloral hydrate for emergent pediatric procedural sedation: a new look at an old drug.

Chloral hydrate has been time honored for pediatric procedural sedation, but its efficacy in sedation for emergency department (ED) procedures is unre...
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