Anaesthesia 2014, 69, 240–244

doi:10.1111/anae.12533

Original Article Intranasal dexmedetomidine following failed chloral hydrate sedation in children B. L. Li,1 V. M. Yuen,2 X. R. Song,3 J. Ye,4 J. Ni,5 J. X. Huang6 and M. G. Irwin7 1 Resident, 3 Head and Professor, 5 Consultant, 6 Attending, Department of Anaesthesiology, Guangzhou Women and Children’s Medical Centre of Guangzhou Medical University, Guangzhou, China 2 Consultant, Department of Anaesthesiology, University of Hong Kong Shenzhen Hospital, Shenzhen, China 4 Associate Consultant, Department of Anaesthesiology, Southern Hospital, Southern Medical University, Guangzhou, China 7 Head and Professor, Department of Anaesthesiology, University of Hong Kong, Hong Kong

Summary Chloral hydrate is the most commonly used sedative for paediatric diagnostic procedures in China with a success rate of around 80%. Intranasal dexmedetomidine is used for rescue sedation in our centre. This prospective investigation evaluated 213 children aged one month to 10 years who were not adequately sedated following administration of chloral hydrate. Children were randomly assigned to receive rescue intranasal dexmedetomidine at 1 lg.kg 1 (group 1), 1.5 lg.kg 1 (group 2) or 2 lg.kg 1 (group 3). The sedation level was assessed every 10 min using a modified observer’s assessment of alertness/sedation scale. Successful rescue sedation in groups 1, 2 and 3 were 56 (83.6%), 66 (89.2%) and 51 (96.2%), respectively. Increasing the rescue dose was associated with an increased success rate with an odds ratio of 4.12 (95% CI 1.13–14.98), p = 0.032. We conclude that intranasal dexmedetomidine is effective for sedation in children who do not respond to chloral hydrate. .................................................................................................................................................................

Correspondence to: V. M. Yuen Email: [email protected] Accepted: 2 November 2013

Introduction Deep sedation is often required for children undergoing diagnostic procedures, including computer tomographic (CT) imaging studies, auditory brainstem responses and visual evoked potential measurements. Chloral hydrate is one of the most commonly used sedatives for diagnostic procedures in children at our institution. It has a pungent odour with a bitter caustic taste and causes a high incidence of nausea and vomiting. Nevertheless, it is associated with a high success rate in children undergoing CT scanning and auditory brainstem responses. An initial dose of 40 mg.kg 1 for 240

children over six months of age was shown to be successful in 77% of children undergoing auditory brainstem responses [1]. An initial dose of 72 mg.kg 1 was successful in 89% of patients undergoing CT scanning and a mean total dose of 78 mg.kg 1 increased this success to 98% in one study [2]. Using doses of 80–100 mg.kg 1, success rates were reported to be 93% for scanning [3]. Dexmedetomidine is a highly selective a2-adrenergic receptor agonist with sedative and mild analgesic effects. Sedation with dexmedetomidine is associated with minimal respiratory depression [4, 5] and it has © 2014 The Association of Anaesthetists of Great Britain and Ireland

Li et al. | Intranasal dexmedetomidine sedation

been increasingly used in paediatric non-invasive diagnostic procedures [6–14]. There is no unpleasant sensation when given intranasally and it is generally well tolerated [15]. When intranasal dexmedetomidine 1 and 2 lg.kg 1 was investigated as a pre-operative sedative, approximately 53% and 66% of children, respectively, were satisfactorily sedated at the time of anaesthetic induction [16–18]. In a retrospective study, intravenous dexmedetomidine was used successfully as a rescue sedative in children who failed to be sedated using chloral hydrate and/or midazolam for magnetic resonance imaging (MRI) [19]. The aim of this study was to evaluate the sedative effect of different doses of intranasal dexmedetomidine in patients who were not adequately sedated following administration of chloral hydrate.

Methods This prospective, randomised study was approved by the local Institutional Review Board. Children of ASA physical status 1–2 and aged between one month and 13 years initially received 50 mg.kg 1 oral choral hydrate sedation for CT scanning, auditory brainstem responses or visual evoked potentials. We enrolled children who had failed chloral hydrate sedation, i.e. there was no evidence of sedation 30 min following administration. Informed written and verbal consent was obtained from the parent or carer of each patient. Using a computer-generated random number table, children were assigned to receive 1, 1.5 or 2 lg.kg 1 intranasal dexmedetomidine. Undiluted preservative-free dexmedetomidine (Ai Bei Ningâ; Jiang Su Heng Rui Medicine Co. Ltd, Jiangsu Province, China) was prepared in a concentration of 100 lg.ml 1 and drawn up into a 1-ml tuberculin syringe. Half the volume of medication was dripped into each nostril whilst the child was lying supine and the child was encouraged to remain in this position for 2 min to maximise drug absorption. Monitoring consisted of non-invasive blood pressure, pulse oximetry, heart rate and respiratory rate. Sedation status was assessed using the modified observer’s assessment of alertness/sedation scale (MOAA/S; Table 1) and was recorded before, and every 10 min after, administration. Vital signs were recorded every 15 min after completion of the procedure until the child was awake and ready to © 2014 The Association of Anaesthetists of Great Britain and Ireland

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Table 1 Modified observer’s assessment of alertness/ sedation scale. 6 5 4 3 2 1 0

Appears alert and awake, responds readily to name spoken in normal tone Appears asleep, but responds readily to name spoken in normal tone Lethargic response to name spoken in normal tone Responds only after name is called loudly or repeatedly Responds only after mild prodding or shaking Does not respond to mild prodding or shaking Does not respond to a noxious stimulus

be discharged. Children were discharged when they attained an Aldrete score of 9 or above. Successful sedation was defined as an MOAA/S of between 0 and 3. Sedation onset time was defined as the time from drug administration to the onset of satisfactory sedation. Children were classified as awake if the MOAA/S was between 4 and 6. Recovery time was defined as the time from intranasal drug administration until the time that the child awoke. Hypotension or bradycardia was defined as a reduction in systolic pressure or heart rate, respectively, of more than 20% from baseline. Hypertension or tachycardia was defined as an increase in systolic pressure or heart rate, respectively, of more than 20% from baseline. Significant oxygen desaturation was defined as < 90%. Patients’ characteristics were analysed by one-way ANOVA or chi-squared tests as appropriate. The proportion of patients successfully sedated in each group was analysed by logistic regression. Sedation onset time and time to recovery were compared between groups using the Kruskal–Wallis test. Statistical analysis was performed using SPSS for Windows version 20.0 (SPSS Inc., Chicago, IL, USA). A p value of < 0.05 was considered statistically significant.

Results The failure rate of chloral hydrate sedation was 23.1%. Of the 215 patients eligible for inclusion in the study, two parents or legal guardians refused to participate. Of the 213 patients included in the study, 18 (9.3%) had vomited following chloral hydrate administration and nine (4.1%) patients had refused the oral medication. There were 71, 75 and 67 patients in groups 1, 2 and 3, respectively. Nineteen 241

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Li et al. | Intranasal dexmedetomidine sedation

Oral chloral hydrate (n = 930)

Failed chloral hydrate (n = 215)

Recruited and randomised (n = 213)

Group 1 Allocated to dexmedetomidine

Group 2 Allocated to dexmedetomidine

1 µg.kg–1 (n = 71)

1.5 µg.kg–1 (n = 75)

Withdrawal (n = 4) 

Withdrawal (n = 14)

Withdrawal (n = 1)

Patients did not return to sedation centre after



Patient did not return to



Patients did not return to sedation centre after

sedation centre after

examination (n = 3) 

Group 3 Allocated to dexmedetomidine 2 µg.kg–1 (n = 67)

examination (n = 11)

examination 

Patient returned to the ward after examination (n = 1)

Patient returned to the ward after examination (n = 1)

Completed study (n = 67)

Completed study (n = 74)

Completed study (n = 53)

Figure 1 CONSORT flow diagram. Table 2 Baseline characteristics of the patients included in the study. Values are number or median (IQR [range]).

Male:female Age; months Body weight; kg

Group 1 (dexmedetomidine 1 lg.kg 1) (n = 67)

Group 2 (dexmedetomidine 1.5 lg.kg 1) (n = 74)

Group 3 (dexmedetomidine 2 lg.kg 1) (n = 53)

52:15 24 (12–45 [1–120]) 11 (8–15 [5–26])

53:21 24 (12–38 [1–84]) 11 (9–15 [3–22]

33:20 26 (6.5–42 [1–101]) 11 (8–24 [3–25])

patients did not complete the study because 15 patients did not return to the sedation centre after the procedure, two patients were transferred directly back to the ward and the parents of a further two patients refused to be included in the study after randomisation (Fig. 1). Baseline characteristics of the patients are shown in Table 2. Successful rescue sedation with intranasal dexmedetomidine occurred in 56 (83.6%), 66 (89.2%) and 51 (96.2%) patients in 242

groups 1, 2 and 3, respectively. By univariate logistic regression, a higher rescue dosage was associated with an increased success rate (p = 0.03) with an odds ratio of 4.12 (95% CI 1.13–14.98), that is, the estimated odds of success were increased by 4.12 for an increase in intranasal dexmedetomidine dose by 1 lg.kg 1. Using logistic regression, there was no statistically significant association between age and success rate (p = 0.105) with an odds ratio of 0.99 (95% © 2014 The Association of Anaesthetists of Great Britain and Ireland

Li et al. | Intranasal dexmedetomidine sedation

Anaesthesia 2014, 69, 240–244

Table 3 Sedation onset time and wake-up time for those children successfully sedated. Values are median (IQR [range]). Group 1 (dexmedetomidine 1 lg.kg 1) (n = 56) Sedation onset time; min Wake-up time; min

15 (10–25 [5–85]) 70 (45–90 [25–160])

Group 2 (dexmedetomidine 1.5 lg.kg 1) (n = 66) 20 (15–20 [5–50]) 65 (50–90 [20–180])

Group 3 (dexmedetomidine 2 lg.kg 1) (n = 51) 15 (15–25 [5–55]) 70 (55–95 [30–180])

p value NS NS

Sedation onset time was defined as the time to attain satisfactory sedation from the time of intranasal drug administration. Wakeup time was defined as the time taken for the child to wake from the time of intranasal drug administration.

CI 0.97–1.00). In those patients who were successfully sedated, there were no differences in sedation onset or recovery times among the three groups (Table 3). No patients had clinically significant haemodynamic or respiratory disturbance that required intervention.

Discussion We have demonstrated that intranasal dexmedetomidine in a dose of between 1 and 2 lg.kg 1 may be used successfully as rescue sedation for non-painful diagnostic procedures when oral chloral hydrate sedation has failed. The success rate ranged from 83.6% to 96.2%. Increasing the dose of intranasal dexmedetomidine resulted in an increased incidence of successful rescue sedation. Chloral hydrate is one of the most commonly used sedatives in our centre and in many centres in China, probably because of its long history, relatively safe clinical profile and low cost. However, it is unpleasant to taste and associated with a high incidence of nausea and vomiting. More importantly, the side-effects of chloral hydrate sedation following hospital discharge are significant and, possibly, under appreciated. Kao et al. [2] reported sleepiness for more than 4 h, unsteadiness, hyperactivity, poor appetite and vomiting. Normal activity had still not resumed in 54% of children 4 h following discharge. Malviya et al. [20] reported similar post-discharge side-effects and prolonged recovery. This may be explained by systemic effects of the active metabolite of chloral hydrate, trichloroethanol, which has a peak effect approximately 2.2 h following administration and a half-life of 9.7 h in children [21]. The most common rescue sedation in our centre is administration of repeat doses of chloral hydrate, but, due to its prolonged elimination half-life, repeated doses of chloral hydrate may be undesirable. In our © 2014 The Association of Anaesthetists of Great Britain and Ireland

experience, children often refuse to accept a further dose of chloral hydrate, probably due to its unpleasant taste, and intranasal dexmedetomidine may be an effective alternative in failed chloral hydrate sedation. A published case series showed that intravenous dexmedetomidine could be used successfully as a rescue sedative in failed chloral hydrate and/or midazolam sedation for MRI studies [19]. In this report, the loading dose of intravenous dexmedetomidine ranged from 0.30 to 1.41 lg.kg 1 and the maintenance infusion rate was between 0.48 and 0.69 lg.kg 1.h 1. This dosage regimen is much lower than the reported dose range when intravenous dexmedetomidine is used as the sole agent for sedation in CT [9] and MRI scanning [6]. Administration of intranasal dexmedetomidine does not require intravenous cannulation and is a convenient and feasible alternative rescue sedative in children who have failed oral chloral hydrate sedation for CT scanning, auditory brainstem responses, visual evoked potentials or other non-painful diagnostic procedures. Our study has several limitations. First, the observer was not blinded to treatment group allocation because the dose of dexmedetomidine could be determined by observing the volume of undiluted drug administered to children. However, undiluted drug was administered in order that the volume of drug was kept to a minimum. Secondly, there was no control group in this study. A supplementary dose of chloral hydrate is commonly used following failed sedation after an initial dose and it would be interesting to compare intranasal dexmedetomidine with a further dose of oral chloral hydrate for rescue medication after failed sedation. Lastly, there was a wide variation in the age range of children included in this study. Chil243

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dren of different ages have different sedation success rates with chloral hydrate [22, 23] and younger children may require relatively larger doses of dexmedetomidine compared with older children [24, 25]. More research is required to compare the relationship between dose and age when intranasal dexmedetomidine is used, both as primary and rescue sedation for non-painful procedures in children. In conclusion, intranasal dexmedetomidine in a dose of 2 lg.kg 1 appears safe and efficacious when administered following failed oral chloral hydrate sedation for non-painful diagnostic procedures in children.

Acknowledgements We gratefully acknowledge the assistance of Ms Jeff SF Man, Department of Anaesthesiology, University of Hong Kong, for statistical analysis.

Competing interests No competing interests and no external funding declared. MGI is an Editor of Anaesthesia and this manuscript has undergone an additional external review as a result.

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© 2014 The Association of Anaesthetists of Great Britain and Ireland

Intranasal dexmedetomidine following failed chloral hydrate sedation in children.

Chloral hydrate is the most commonly used sedative for paediatric diagnostic procedures in China with a success rate of around 80%. Intranasal dexmede...
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