Department of Anaesthesiology and Reanimation, Medical Faculty, Inonu University, Malatya, Turkey
* Corresponding author: akoroglu{at}inonu.edu.tr
Accepted for publication February 8, 2005.
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Abstract |
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Methods. Eighty children aged between 1 and 7 yr were randomly allocated to receive sedation with either dexmedetomidine (group D, n=40) or midazolam (group M, n=40). The loading dose of the study drugs was administered for 10 min (dexmedetomidine 1 µg kg1 or midazolam 0.2 mg kg1) followed by continuous infusion (dexmedetomidine 0.5 µg kg1 h1 or midazolam 6 µg kg1 min1). Inadequate sedation was defined as difficulty in completing the procedure because of the child's movement during MRI. The children who were inadequately sedated were given a single dose of rescue midazolam and/or propofol intravenously. Mean arterial pressure (MAP), heart rate (HR), peripheral oxygen saturation () and ventilatory frequency (VF) were monitored and recorded during the study.
Results. The quality of MRI was significantly better and the rate of adequate sedation was higher in group D than in group M (P<0.001). In group D, the requirement for rescue drugs was lower and the onset of sedation time was shorter than in group M (P<0.001). MAP, HR and VF decreased from baseline during sedation in both groups (P<0.001).
Conclusions. Dexmedetomidine provided adequate sedation in most of the children aged 17 yr without haemodynamic or respiratory effects during MRI procedures.
Keywords: brain, magnetic resonance imaging ; sedation, paediatrics ; sedative, dexmedetomidine
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Introduction |
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There has been debate over the appropriate drugs and dosage regimens for MRI sedation in children.1 Dexmedetomidine is a potent highly selective 2-adrenoreceptor agonist with a distribution half-life of approximately 8 min and a terminal half-life of 3.5 h.4 5 Dexmedetomidine, as a sedative agent, can provide easily controllable analgesia and sedation without respiratory depression57 and has been widely used in the intensive care unit (ICU) for sedation and postoperative analgesia.8 9 Its use for sedation in children in situations outside the operating theatre or ICU has not been studied, other than in a few case reports.1012
In this preliminary study, the aim was to improve sedation and develop a regimen based on dexmedetomidine, and to evaluate the sedative, haemodynamic and respiratory effects of dexmedetomidine compared with midazolam in children undergoing MRI examination.
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Methods |
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The sedation level was measured every 10 min using the Ramsay sedation scale13 by evaluating response to sound, verbal commands or tactile stimulation by anaesthetist 1. The Ramsay scale assigns a score of 16 based on the clinical assessment of the level of sedation (1=anxious, agitated, restless; 2=awake, but cooperative, tranquil, orientated; 3=responds to verbal commands only). Scores 46 apply to sleeping patients and are graded according to the response to loud noise or a glabellar tap (4=brisk response; 5=sluggish response; 6=no response). The children were taken into the MRI room after a Ramsay score of 6 and haemodynamic and respiratory stability were achieved. If a Ramsay score of 6 was not achieved after infusion of the study drug for 25 min, the infusion rate was increased by anaesthetist 2 to 0.7 µg kg1 h1 in group D and 8.4 µg kg1 min1 in group M for 5 min. If a Ramsay score of 6 was not achieved after 25+5 min of study drug infusion or inadequate sedation occurred during MRI examination, a single rescue dose of midazolam 0.05 mg kg1 i.v. was given. If this was not sufficient, propofol 0.5 mg kg1 i.v. was administered 3 min after the rescue dose of midazolam. Inadequate sedation was defined as difficulty in completing the procedure because of movement during MRI examination.
Mean arterial pressure (MAP), heart rate (HR), peripheral oxygen saturation () and ventilatory frequency (VF) were monitored continuously by anaesthetist 1 and recorded at 5-min intervals during the study period. Spontaneous respiration was maintained in all children. If
fell below 93% for 30 s, oxygen was given via a facemask.
The quality of the MRI examination was evaluated by a radiologist using a three-point scale (1=no motion; 2=minor movement; 3=major movement necessitating another scan). At the end of the MRI, drug infusion was discontinued and the children were transferred to the recovery room.
The onset of sedation time was defined as the time from starting drug infusion to achieving a Ramsay score of 6. Recovery time was the time between discontinuation of drug infusion and reaching a Ramsay score of 2. Discharge time was the time between discontinuation of drug infusion and discharge of the child from the unit. Discharge criteria were the return of vital signs and level of consciousness to baseline, and the ability to maintain a patent airway.
Statistical analyses were made using SPSS® 10.0 (SPSS Inc., Chicago, IL, USA). Analysis of variance for repeated measures was performed on haemodynamic and respiratory parameters, with compensation for post hoc comparisons using the Bonferroni correction. Intergroup statistical analyses were performed using the t-test, and non-parametric data were analysed using the 2-test. Statistical significance was assumed at P<0.05. Results are presented as mean (SD) or their 95% confidence interval (CI). Because of the lack of a primary outcome, the power of the study was calculated based on the onset of sedation time. Setting a significance level of P=0.05, it was calculated that a group size of 40 patients allowed detection of a difference between groups with a power of 100%.
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Results |
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VF was decreased significantly from baseline in both groups during sedation (P<0.001) but was not significantly different between groups before or during sedation. Mean VF in groups D and M was 27 (3.6) bpm and 28 (5.2) bpm, respectively, before sedation, and 25 (3.2) bpm and 24 (4.8) bpm, respectively, during sedation. The maximum decreases in VF during sedation in groups D and M were 8% and 14%, respectively. did not fall below 93% in any children in group D during the study, but VF<93% was observed in three children in group M (P>0.05) before MRI examination. These three children had been given rescue propofol because of a Ramsay score <6 before MRI examination. In these children, the decrease in
was easily treated with oxygen supplementation via a facemask.
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Discussion |
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Previous studies indicate that infusion of dexmedetomidine 0.10.7 µg kg1 h1 provides effective sedation.7 11 12 15 16 A sedation score between 2 and 4 was obtained with 0.5 µg kg1 loading and 0.250.5 µg kg1 h1 infusion dose of dexmedetomidine.10 In our study, a dexmedetomidine loading dose of 1 µg kg1 and infusion of 0.50.7 µg kg1 h1was used. Effective sedation with midazolam has been reported with loading doses of 0.20.5 mg kg1 and infusion of 18 µg kg1 min1 in children.17 18 These doses are similar to our midazolam doses. Midazolam, as a sole sedative agent, has been associated with a higher incidence of failed sedation during MRI procedures, which is consistent with our results.3 It is known that midazolam has a quick onset of action and a short recovery room stay when it is administered intravenously over 25 min.17 However, in our study the midazolam loading dose was administered over 10 min to parallel that of the dexmedetomidine. The rate of administration of the midazolam loading dose may explain the low rate of adequate sedation rate. There were also more distressed patients before sedation in group M. Adequate sedation was obtained with dexmedetomidine in most of the children and the others were effectively sedated with rescue midazolam.
Arian and colleagues19 reported a sedation induction time of 25 min and a recovery time of 34 min with dexmedetomidine in adults. The onset of sedation time and the recovery time was shorter in our study. This could be explained by the fact that the subjects were children and that the duration of infusion was shorter.
Although the most important disadvantage of dexmedetomidine is adverse haemodynamic effects, there are conflicting reports on these.5 6 9 15 20 21 Hypotension and bradycardia have been reported, particularly with high-bolus dosing regimens, in patients with pre-existing cardiac problems and a loading dose infusion given over <10 min.4 9 22 Midazolam is said to have more haemodynamic stability,17 but in our study MAP and HR decreased significantly after both drugs. These decreases could be because of high baseline values which, in turn, could have occurred because the children were not premedicated. On the other hand, the decreases in MAP and HR were <20% from baseline and were considered to be clinically insignificant.
Respiratory events make up a large proportion (5.5%) of the complications of the sedation in children.3 Some authors have reported that dexmedetomidine had no respiratory effects,7 23 but others have described respiratory complications with large and rapid loading doses.4 21 24 A loading dose of dexmedetomidine given over 2 min caused irregular respiration, apnoea, slight hypoxaemia and hypercapnia.20 Respiratory depression and apnoea were not observed in any of the children who received dexmedetomidine during our study. The desaturation observed in three children who received midazolam may have been caused by rescue propofol.
Propofol, chloral hydrate, and midazolam have been used as sedative agents for children,1 18 and a complication rate of 20% in sedation performed for diagnostic procedures in children has been reported.3 Chloral hydrate may cause desaturation and may be associated with restlessness and prolonged imbalance.3 18 Propofol can cause respiratory depression, loss of protective airway reflexes and bradycardia in appropriate doses.25 26 Midazolam may cause paradoxical excitation and agitation with higher doses.18 In our study, no complications were seen in any child who received dexmedetomidine.
In conclusion, dexmedetomidine provided adequate sedation at 1 µg kg1 loading and 0.50.7 µg kg1 h1 infusion doses in most of the children (aged between 17 yr) without affecting haemodynamics and respiration. Thus dexmedetomidine may be a suitable agent for MRI sedation in children.
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References |
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