Background
Chloral hydrate has been the drug of choice for uncooperative infants and children requiring sedation for echocardiography. Recently, the commercially available liquid formulation was discontinued by the manufacturer, and the only oral form of chloral hydrate available was made using reconstituted crystals. The aim of this study was to compare sedation efficacy before and after this change in chloral hydrate formulas.
Methods
Consecutive patients presenting for echocardiography sedation during the transition from the manufacturer-derived old formulation to the locally reconstituted new formulation were retrospectively reviewed for time to onset of level 3 sedation, duration of level ≤3 sedation, requirement for additional sedative medications, sedation failure, ability to complete the echocardiographic examination, and adverse events related to the sedatives.
Results
The cohort included 124 patients (63 old, 61 new). Although the mean age at sedation was younger for the new group, the weight and average dose of chloral hydrate used were not significantly different. There were no adverse events in either group. Time to onset of sedation was the same between the two formulations, but the duration of sedation was significantly shorter for the new group (42.4 ± 24.5 vs 55.3 ± 26.2 min, P = .01). In addition, the need for secondary sedating agents because of inadequate sedation and sedation failure were significantly greater using the new compared with the old formulation.
Conclusions
Chloral hydrate reformulation using reconstituted crystals results in a shorter duration of sedation, more frequent requirement for a secondary sedative agent, more frequent sedation failure, and occasional inability to complete the echocardiographic examination compared with the manufacturer’s formulation.
Highlights
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Two forms of chloral hydrate for pediatric echocardiography sedation were compared.
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The pharmacy-derived version was less effective than the manufacturer-derived version.
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The pharmacy-derived version had more use of secondary agents and sedation failure.
Transthoracic echocardiography, although the mainstay of diagnosis and surveillance for pediatric patients with heart disease, can be difficult to perform in infants and toddlers because of lack of cooperation and anxiety. Use of sedation in this age group improves image quality and reduces diagnostic errors, particularly in those with more complex disease. Chloral hydrate has been the medication of choice for many pediatric echocardiography laboratories because of its low cost, oral availability (100 mg/mL solution), and safety profile. However, chloral hydrate is no longer produced in the United States, and no clearly superior alternative has emerged without intravenous access and an anesthesiologist present. The pharmacy at the Children’s Hospital of Wisconsin has been preparing an oral formulation of chloral hydrate from reconstituted crystals (50 mg/mL) since December 2013 as a replacement for the commercially available drug. We sought to compare efficacy of the pharmacy-reconstituted (new) formulation with the manufacturer-derived (old) formulation for their ability to provide adequate sedation to perform a complete echocardiographic examination in an otherwise uncooperative patient.
Methods
Consecutive patients presenting to the echocardiography sedation laboratory before and after the transition, occurring in December 2013, were retrospectively reviewed in compliance with institutional review board requirements for a quality improvement initiative. Because this was a quality improvement initiative, no patients were excluded. Data were collected on patient characteristics and sedation parameters. Chloral hydrate dosing is done by the individual physician supervising the echocardiography laboratory on the day of sedation, with recommended guidelines as follows: infants <3 months of age, 50 mg/kg; infants 3 to 9 months of age, 75 mg/kg; and infants and children >9 months of age, 100 mg/kg up to a maximum dose of 1,000 mg.
These guidelines were available as part of the ordering algorithm in the electronic medical record and were used by all staff members during the entire study duration. Sedation score was assessed during direct nurse monitoring on the basis of the Ramsay sedation scale as part of an institutional sedation protocol ( Table 1 ). Sedation failure was defined as failure to reach level 3 sedation on the Ramsay sedation scale. Adverse events were considered any complication requiring intervention, excluding additional sedation, or admission. Descriptive data are presented as number with percentage of total, mean ± SD, or median with range. Patients receiving the old formulation were compared with those receiving the new formulation by Fisher exact test or Wilcoxon rank sum test. The primary outcome of interest was sedation failure. Other outcomes of interest were time to onset of level 3 sedation, duration of level ≤3 sedation, requirement for additional sedative medications, ability to complete the echocardiographic examination, and adverse events related to the sedatives. Analyses were performed using Stata/IC version 13 (StataCorp LP, College Station, TX), with P values < .05 considered to indicate statistical significance.
| Score | Sedation level | Description |
|---|---|---|
| 6 | None | Agitated, anxious, or in pain above baseline |
| 5 | Minimal | Spontaneously awake without stimulus; may exhibit anxiolysis |
| 4 | Drowsy but easily arouses to consciousness to light tactile or verbal/tactile stimulus | |
| 3 | Moderate | Arouses to consciousness with moderate tactile or loud verbal stimulus |
| 2 | Deep | Arouses slowly to consciousness with sustained painful tactile stimulus |
| 1 | Arouses, but not consciousness, with painful stimulus | |
| 0 | Unresponsive to painful stimulus |
Results
During the 4-month period, 124 patients underwent sedation in the echocardiography sedation laboratory at the Children’s Hospital of Wisconsin. The median age was 7 months (range: 2 weeks to 30 months), with a median weight of 6.8 kg (range: 2.6–13.2 kg). The old formulation was used in 63 patients and the new formulation in 61 patients. Comparison between the old and new groups can be seen in Table 2 . There were no adverse events in either group, including those receiving secondary sedative agents. Although the mean age at sedation was younger for the new group, the weight and average dose of chloral hydrate used were not significantly different between groups. The mean times of onset to sedation between the old and new groups (23 ± 10.8 vs 24.4 ± 9.9 min, P = .22) were similar, but the duration of sedation was significantly shorter for the new group (42.4 ± 24.5 vs 55.3 ± 26.2 min, P = .01). Although time to onset of adequate sedation was similar between groups, Figure 1 demonstrates a shift with the new formulation toward later onset. Figure 2 demonstrates the shift toward shorter duration of level 3 sedation with the new formulation. The need for secondary sedating agents (midazolam 0.2–0.3 mg/kg intranasal) because of inadequate sedation and sedation failure were significantly greater using the new compared with the old formulation.
| Variable | Old formulation ( n = 63) | New formulation ( n = 61) | P |
|---|---|---|---|
| Age (mo) | 10.3 ± 7.7 | 7.1 ± 5.4 | .04 |
| Weight (kg) | 7.5 ± 2.7 | 6.7 ± 2.2 | .16 |
| Chloral hydrate dose (mg/kg) | 75.9 ± 12.3 | 74.6 ± 16.7 | .71 |
| Time to onset of sedation (min) | 23 ± 10.8 | 24.4 ± 9.9 | .22 |
| Duration of sedation (min) | 55.3 ± 26.2 | 42.4 ± 24.5 | .01 |
| Sedation >60 min | 23 (36.5%) | 13 (21.3%) | .08 |
| Secondary agent required | 0 (0%) | 5 (8.2%) | .03 |
| Sedation failure | 0 (0%) | 8 (13.1%) | .003 |
| Incomplete echocardiographic examination | 0 (0%) | 2 (3.3%) | .24 |
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