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Effects of dexmedetomidine infusion on laryngeal mask airway removal and postoperative recovery in children anaesthetised with sevoflurane.

SUMMARY

We investigated the effects of dexmedetomidine infusion on the end-tidal concentration of sevoflurane required for smooth removal of the laryngeal mask airway (LMA) and on the incidence of respiratory complications during postoperative recovery in paediatric patients anaesthetised with sevoflurane. Eighty-seven patients (ASA 1 or 2, aged 3-7 years) were randomly allocated to receive saline (Group C), 0.5 [micro]g/kg dexmedetomidine (Group [D.sub.l]), or 1 [micro]g/kg dexmedetomidine (Group [D.sub.2]) after LMA insertion. A predetermined end-tidal sevoflurane concentration for each patient was determined using the Dixon's up-and-down method (starting at 2.2% and step was 0.2%). The LMA was removed after the predetermined concentration had been maintained stable for five minutes. Sevoflurane minimum alveolar concentration for smooth LMA removal and postoperative recovery were assessed. The end-tidal concentration of sevoflurane required for smooth LMA removal in 50% of children ([MAC.sub.LMA-RM]) in Group [D.sub.2] (0.84 [+ or -] 0.15%) was significantly lower than in Group [D.sub.l] (1.39 [+ or -] 0.20%; P=0.003), the latter being significantly lower than in Group C (1.73 [+ or -] 0.14%; P <0.001). The incidence of breath-holding was significantly lower in Group [D.sub.2] (3%) than in Group C (27%; P=0.009), but comparable between Groups [D.sub.1] (17%) and C (P=0.385). The incidence of severe coughing was significantly lower in Groups [D.sub.1] (14%) and [D.sub.2] (6%) as compared to Group C (39%; P=0.005), but comparable between Groups [D.sub.1] and [D.sub.2] (P=0.323). In conclusion, dexmedetomidine infusion produced a dose-dependent decrease in the end-tidal concentration of sevoflurane required for smooth LMA removal in children and was associated less agitation in the post-anaesthetic care unit.

Key Words: dexmedetomidine, laryngeal mask airway, sevoflurane, children

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The laryngeal mask airway (LMA) is frequently used in elective paediatric anaesthesia for peripheral, short duration surgical procedures. Anaesthetists have been debating the optimal timing for removal of the LMA (i.e. whether it has to be performed while patients are deeply anaesthetised or awake). As it reduces the incidence of coughing, biting, laryngospasm, excess salivation and hypoxaemia in children (1,2), paediatric anaesthetists often prefer to remove the LMA while the patient is still anaesthetised. Some researchers have quantified the requirement of sevoflurane for safe LMA removal in paediatric patients. The reported minimum alveolar concentration (MAC) of sevoflurane for smooth LMA removal in anaesthetised children was 1.84% (3), which could be reduced to 1.47% if a concurrent regional technique was used (e.g. caudal anaesthesia) (4). However, these requirements were much higher than the awakening sevoflurane concentration, which was 0.78% in children (5), and there were still time intervals between LMA removal and return to responsiveness. In addition, detailed descriptions of patients' recovery after LMA removal, such as the incidence of respiratory events or emergence agitation, were not reported in these studies.

Dexmedetomidine is a potent [alpha]2-adrenoceptor agonist, which has known sedative, analgesic and anxiolytic effects and no clinically apparent respiratory depression after intravenous administration (6). It has been reported that dexmedetomidine can diminish airway and circulatory responses during extubation in children (7,8). Co-administered with propofol, dexmedetomidine can provide successful LMA insertion in paediatric patients and preserve ventilatory functions (9). It has also been repeatedly demonstrated that dexmedetomidine can decrease emergence agitation in children after sevoflurane-based general anaesthesia (8,10,11). Therefore, it could be expected that dexmedetomidine could reduce the sevoflurane requirement for smooth LMA removal in children. We conducted this prospective, randomised, double-blind study to determine the effects of two different doses of dexmedetomidine infusion on the end-tidal concentration of sevoflurane required for smooth LMA removal and on postoperative recovery measures such as incidence of respiratory complications in paediatric patients anaesthetised with sevoflurane.

METHODS

Subject selection and randomisation

This study was approved by the ethics committee of Children's Hospital of Fudan University (ethics approval number 2010-025) and written informed consent was obtained from the parents. We studied 87 patients, ASA physical status 1 or 2, aged 3-7 years. All children were undergoing elective minor surface surgery for about one hour under general anaesthesia. Exclusion criteria included gastroesophageal reflux, abnormal airway, asthma, a history of upper respiratory tract infection in the preceding two weeks, or neurological or heart disease.

Using computer-generated numbers (SPSS 13.0), patients were randomly allocated to one of three groups. Group C received saline, Group [D.sub.1] received dexmedetomidine 0.5 [micro]g/kg and Group [D.sub.2] received dexmedetomidine 1 [micro]g/kg. All treatments in each group were diluted to 10 ml with 0.9% saline and were labelled 'study drug', which were prepared by an independent anaesthesia nurse before anaesthesia induction.

Study procedure

Patients were not given any premedication and fasted for six hours before surgery. All patients were connected to routine monitoring after they arrived at the operating theatre. The pulse oximeter, electrocardiogram and non-invasive arterial pressure were continuously measured during the whole study.

After preoxygenation (100% oxygen 6 1/minute) with a mask for three minutes, anaesthesia was induced with 8% sevoflurane in oxygen via a semiclosed anaesthetic circuit (Drager Fabius GS) without any opioids or muscle relaxants. One minute after loss of the eyelash reflex, 24-gauge intravenous access was established and a lactated Ringer's solution infusion was started (5 ml/kg/hour). An LMA was inserted when jaw relaxation was adequate (no response to jaw lift). The LMA was selected as: size 2 for 10-20 kg, size 2.5 for 20-30 kg and size 3 for 30-50 kg. Using an infusion pump, the prepared 'study drug' (saline, 0.5 [micro]g/kg dexmedetomidine or 1 [micro]g/kg dexmedetomidine) was administrated after LMA insertion. The infusion process continued for ten minutes.

Anaesthesia was maintained with sevoflurane in oxygen (1 1/minute) and air (1 1/minute). The sevoflurane concentration was adjusted between 2-3%, in response to the haemodynamics of each patient. The inspired/end-tidal sevoflurane concentrations and carbon dioxide were measured continuously using a Datex Capnomac airway gas monitor (Datex-Ohmeda, Helsinki, Finland) precalibrated with a standard gas mixture. The accuracy of end-tidal measurements was maximised by confirming return of the end-tidal carbon dioxide trace to zero and a good waveform with a plateau. The sampling tube was attached to the L-connecter between the LMA and anaesthetic circuit. Spontaneous ventilation was maintained during the operation. If the patients became apnoeic, or the end-tidal carbon dioxide partial pressure increased over 45 mmHg (6.0 kPa), ventilation was gently assisted manually, targeting an end-tidal carbon dioxide partial pressure at between 34 mmHg (4.5 kPa) and 45 mmHg (6.0 kPa). According to the site and area of the surgery, each patient was given a regional or local anaesthetic block using 0.3-0.5% ropivacaine before surgery started. No opioids were used during the operation.

After the surgery had been completed, the fresh gas flow was set at 6 l/minute and the inhaled sevoflurane concentration was adjusted to make the end-tidal sevoflurane concentration reach a predetermined value. The LMA was removed with the cuff inflated after the ratio of predetermined end-tidal to inspiratory concentration was maintained at 0.95-1.00 for five minutes (stable status). The jaw was slightly lifted after LMA removal and a facemask was applied with the patient spontaneously breathing 100% oxygen. Oropharyngeal secretions were gently suctioned before the end-tidal sevoflurane concentration had been adjusted. If the LMA could not be removed because of severe body movement or teeth clenching, sevoflurane or propofol were used to deepen the anaesthesia in order to facilitate LMA removal.

Measurement of the end-tidal concentration of sevoflurane required for smooth LMA removal

According to the Dixon's up-and-down method (12), the target end-tidal concentration of sevoflurane used for each patient was determined by the response of the previously tested patient. The initial concentration in each group was set as 2.2%, which was chosen based on the result in a previous study that LMA removal under 2.2% sevoflurane was successful (3).

The definition of smooth LMA removal was absence of the development of coughing, teeth clenching or gross purposeful muscle movements during or within one minute after LMA removal, development of breath-holding, laryngospasm, or desaturation to Sp[O.sub.2] <90% during or immediately after LMA removal. If LMA removal was not smooth, the end-tidal concentration of sevoflurane given to the next patient was increased by 0.2%. Conversely, if LMA removal was smooth, the predetermined end-tidal concentration of sevoflurane for the next patient was decreased by the same amount. An anaesthetist and a nurse who were unaware of the dose of dexmedetomidine and the end-tidal concentration of sevoflurane used in each patient assessed the conditions of LMA removal.

Children were included until seven independent pairs (i.e. non-smooth to smooth LMA removal) of consecutive subjects were obtained in each group. The end-tidal concentration of sevoflurane required for smooth LMA removal in 50% of children (defined as [MAC.sub.LMA-RM]) was determined in each group by calculating the mean of the midpoint concentration of all independent pairs of patients who manifested a crossover from a negative response to a positive one (i.e. non-smooth to smooth LMA removal).

Assessment of incidence of respiratory complications in recovery after LMA removal

Patients were kept in the post-anaesthesia care unit until they attained an Aldrete score (13) (including activity, respiration, circulation, consciousness and oxygen saturation) of 9 or more and were free from nausea and vomiting. The postoperative recovery, including the incidence of respiratory complications and emergence agitation after LMA removal, was continually assessed by an anaesthetist blinded to the treatment group. This anaesthetist repeatedly called the patient's name and tapped the patient's shoulders every minute until the patient opened his or her eyes. The emergence time (from LMA removal to eyes opening on command) and the recovery time (from LMA removal to when the recovery score reached a 9 or 10) were recorded.

Incidence of untoward airway events after LMA removal such as laryngospasm, breath-holding (for 20 seconds or more), severe coughing or strain (severe cough was defined as four or more coughs and Sp[O.sub.2] <95%) and excess salivation (salivation requiring suction) were recorded by the same blinded observer. Behaviour during postoperative period was rated on a 1-5-point scale: l=sleeping, 2=awake and calm, 3=irritable and crying, 4=inconsolable crying, 5=severe restlessness, disorientation and thrashing around (14). Scores >3 were considered to indicate agitation. The agitation scores were recorded by the blinded observer. If an agitated patient could not be calmed, propofol 1.0 mg/kg was provided.

Patients who had pain (complaining of pain or trying to remove the surgical dressing) were given fentanyl 1 [micro]g/kg intravenously and this was recorded by the blinded observer.

Data analysis

The statistical package SPSS 13.0 for Windows was used to perform the statistical analysis. Data are presented as mean [+ or -] standard deviation or numbers (percentage). Student's t-test, one-way analysis of variance and chi-square test were used for statistical analysis. Paired comparisons were corrected with Bonferroni's test. Differences at P <0.05 were considered to be statistically significant.

RESULTS

Eighty-seven patients were enrolled in this study. Patient demographics and surgical data were similar in the three groups (P >0.05; Table 1).

Individual responses to LMA removal in each group are shown in Figure 1. The [MAC.sub.LMA-RM] of sevoflurane in Group [D.sub.2] (0.84 [+ or -] 0.15%) was significantly lower than in Group [D.sub.1] (1.39 [+ or -] 0.20%; P=0.003), the latter being significantly lower than in Group C (1.73 [+ or -] 0.14%; P <0.001). The corresponding decreases in [MAC.sub.LMA-RM] of sevoflurane in response to dexmedetomidine administration are shown in Figure 2.

No patient suffered laryngospasm, bronchospasm or hypoxaemia (Sp[O.sub.2] <90%). The incidence of breath holding was significantly lower in Group [D.sub.2] (3%) than in Group C (27%; P=0.009), but comparable between Groups [D.sub.1] (17%) and C (P=0.385). The incidence of severe coughing was significantly lower in Groups [D.sub.1] (14%) and [D.sub.2] (6%) as compared to Group C (39%; P=0.005), but comparable between Groups [D.sub.1] and [D.sub.2] (P=0.323). The incidence of excess salivation was comparable among the three groups (P=0.754).

The emergence time was significantly prolonged in Group [D.sub.2] (8 [+ or -] 3 minutes) and in Group C (8 [+ or -] 3 minutes) as compared to Group [D.sub.1] (6 [+ or -] 2 minutes; P=0.014), but comparable between Groups [D.sub.2] and C (P=0.203). The recovery time was significantly prolonged in Group [D.sub.2] (16 [+ or -] 6 minutes) and in Group C (15 [+ or -] 6 minutes) as compared to Group [D.sub.1] (12 [+ or -] 5 minutes; P=0.010), but comparable between Groups [D.sub.2] and C (P=0.467).

The incidence of emergence agitation was significantly lower in Groups [D.sub.1] (17%) and [D.sub.2] (6%) as compared to Group C (42%; P=0.003), but comparable between Groups [D.sub.1] and [D.sub.2] (P=0.179). The incidence of pain was comparable among the three groups (P=0.719). The mean arterial blood pressure and heart rate of patients are shown in Figure 3.

Significant haemodynamic effects were observed at a higher dose of 1 [micro]g/kg dexmedetomidine. However, the deviation did not exceed 20% of the values before the dexmedetomidine infusion.

DISCUSSION

In this prospective, randomised, double-blind study, the administration of dexmedetomidine 0.5 and 1 [micro]g/kg significantly reduced the end-tidal concentration of sevoflurane required for smooth LMA removal in 50% of children ([MAC.sub.LMA_RM]) from 1.73-1.39% and 0.84%, respectively. The incidence of respiratory complications and agitation after sevoflurane anaesthesia were reduced in dexmedetomidine groups without a prolongation in recovery time. This is the first study to examine the dose-related effects of dexmedetomidine infusion on the sevoflurane requirement for smooth LMA removal, and on the upper airway complications in recovery after LMA removal in children.

Dexmedetomidine has the effects of sedation, analgesia and anxiolysis. It has been reported that dexmedetomidine can reduce the analgesic requirements of postsurgical ventilated intensive care unit patients (15-17), and is a useful adjunct for awake (18) and fibreoptic nasotracheal (19) intubation, and could provide smooth extubation (8) in children after general anaesthesia. In our study, the [MAC.sub.LMA-RM] of sevoflurane was reduced by 20 and 51% with the administration of 0.5 and 1 [micro]g/kg dexmedetomidine, respectively. The reduction may be attributed to better tolerance of the LMA provided by dexmedetomidine and the diminished airway responses to laryngeal stimulation during LMA removal (7,8). The [MAC.sub.LMA-RM] of sevoflurane without dexmedetomidine calculated in this study is 1.73%, which is slightly less than the result reported previously (1.84%) (3). This difference might be attributable to the use of regional or local anaesthetic blocks, which may decrease the sevoflurane requirement because of the analgesic effect and the systemic absorption of local anaesthetics.

LMA removal in the anaesthetised state carries the disadvantage of active pharyngeal reflexes remaining suppressed, resulting in a delayed return of airway reflexes, which potentially leaves the patient's airway unprotected. Therefore, when an LMA is removed in the anaesthetised state, it is important to apply the least amount of anaesthesia possible without untoward effects. In our study, the LMA could be removed at a lower concentration of sevoflurane with the administration of dexmedetomidine. The higher the dexmedetomidine doses administered, the lower the concentration of sevoflurane required for achieving smooth LMA removal. As a result, it was expected that the incidence of airway complications should be reduced in the dexmedetomidine groups. According to our observations, the incidences of severe coughing were significantly reduced from 39% in Group C, to 14% in Group [D.sub.1], and 6% in Group [D.sub.2]. The incidence of breath holding in Group [D.sub.2] was only 3%, while it was 27 and 17% in Groups C and [D.sub.1], respectively. The reduction can be explained by the following points: as a result of the use of dexmedetomidine, the required sevoflurane concentration was less when the LMA was removed, which may reduce the amount of sevoflurance requiring clearance from the patient's body. So we speculated that the time interval between LMA removal and the return of normal airway reflexes may be shorter in the dexmedeto-midine groups and the occurrence of airway complications could be reduced. On the other hand, dexmedetomidine has not been associated with clinically apparent respiratory depression after intravenous administration (6). It may be the sedative, analgesic and anxiolytic properties of its own that caused the reduction in airway events during emergence. So there may be two factors--the difference in dexmedetomidine doses and the difference in sevoflurane concentrations--causing the difference in the presence or absence of airway complications among three groups. However, it was dexmedetomidine that resulted in the reduction of sevoflurane requirement for LMA removal. Without dexmedetomidine, it would be more difficult to have smooth removal of the LMA with such low concentrations of sevoflurane (0.84% sevoflurane with 1 [micro]g/kg dexmedetomidine). Similarly, we could attribute the reduction of the incidence of airway complications to the dexmedetomidine infusion. For clinical anaesthetists, it would be much safer to remove the LMA at a lower concentration of sevoflurane, if this was associated with less airway problems.

In this study, the administration of dexmedetomidine significantly decreased the incidence of agitation after sevoflurane anaesthesia in the postoperative recovery period. Postoperative pain is thought to be one of the major causes of emergence agitation. In our study, regional or local anaesthetic block was used for analgesia, and the incidences of pain among the three groups were similar. To a great extent, this confounding factor should have been eliminated. Though it has a sedative effect, the use of dexmedetomidine did not prolong the recovery time in the post-anaesthesia care unit. Instead, 0.5 [micro]g/kg dexmedetomidine significantly reduced the emergence time and recovery time. This may be related to the reduction in sevoflurane concentration with dexmedetomidine infusion.

Some limitations need to be considered for the present study. First, most surgical procedures in our study were less than one hour. The anaesthesia technique we used was general anaesthesia combined with regional or local anaesthetic block, and no opioids were used during the operation. The results might be different if a regional block cannot be used or the analgesic effect is not adequate, or opioids have to be used. Second, it has been reported that 2 [micro]g/kg or even larger doses of dexmedetomidine were safe and effective for paediatric magnetic resonance imaging procedures (20-22). However, patients who received 2 [micro]g/kg dexmedetomidine in our pilot study were sleepy and unresponsive for a long time after surgery. Therefore, we decided to use lower doses in our study. Other doses of dexmedetomidine might be assessed in future studies. Third, according to our research protocol, dexmedetomidine was administrated using an infusion pump (after LMA insertion), and the period for infusion was ten minutes. It is not known if there might be an advantage in giving a smaller dose just prior to extubation to allow smooth LMA removal. This could be evaluated in further studies.

In conclusion, dexmedetomidine infusion produced a dose-dependent decrease in the end-tidal concentration of sevoflurane required for smooth LMA removal in children and was associated with less agitation in the post-anaesthesia care unit.

Caption: Figure 1: Consecutive end-tidal sevoflurane concentrations and response to laryngeal mask airway removal of each patient in the three groups. A solid shape indicates a 'non-smooth' laryngeal mask airway removal and a hollow one indicates smooth laryngeal mask air, ray removal (see text definition of smooth removal).

Caption: Figure 2: The administration of dexmedetomidine produced a dose-dependent decrease in the [MAC.sub.LMA-RM] of sevoflurane required for laryngeal mask airway removal in children. * P <0.05 compared with [MAC.sub.LMA-RM] using saline. ([dagger]) P <0.05 compared with [MAC.sub.LMA-RM] using 0.5 [micro]g/kg dexmedetomidine. [MAC.sub.LMA-RM] is represented by an open box. The horizontal bars represent standard deviation. [MAC.sub.LMA-RM] = end-tidal concentration of sevoflurane required for smooth LMA removal in 5(V)/of children.

Caption: Figure 3: Changes in heart rate and mean arterial blood pressure. * P <0.05 compared with values before administration of dexmedetomidine/saline. ([dagger]) P <0.05 compared with values before laryngeal mask airway removal. Measurement points: [T.sub.0] = just before administration of dexmedetomidine/saline, [T.sub.1] = one minute after administration of dexmedetomidine/saline, [T.sub.2] = five minutes after administration of dexmedetomidine/saline, [T.sub.3] = just after the end of administration of dexmedetomidine/saline, [T.sub.4] = just before laryngeal mask airway removal, [T.sub.5] = one minute after laryngeal mask airway removal. HR = heart rate, MAP = mean arterial pressure.

ACKNOWLEDGEMENTS

The authors thank the staff of anaesthesia nurses and surgeons at the Children's Hospital of Fudan University, without whose help and co-operation this study would not have been possible.

REFERENCES

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L. HE *, X. WANG ([dagger]), S. ZHENG ([double dagger])), Y. SHI ([section])

Department of Anesthesiology, Children's Hospital of Fudan University, Shanghai, China

* MD, Attending Anesthesiologist.

([dagger]) MD, Assistant Professor.

([double dagger]) MD, Professor.

([section]) MD, Attending Anesthesiologist.

Address for correspondence: Dr S. Zheng, Department of Surgery, Children's Hospital of Fudan University, Shanghai 201102, China. Email: sarahiyiyi@hotmail.com

Table 1
Patients' demographic and surgical data

                                 Group C             Group [D.sub.1]
                                 (n=26)              (n=29)

Age, years                       4.8 [+ or -] 1.6    4.6 [+ or -] 1.5
Weight, kg                       16 [+ or -] 6       18 [+ or -] 7
Gender, male/female              14/12               16/13
ASA physical status, 1/2         24/2                27/2
Duration of anaesthesia, min     51 [+ or -] 18      45 [+ or -] 16
Duration of surgery, min         29 [+ or -] 13      26 [+ or -] 11
Type of surgery
  Inguinal hernia repair         10                  12
  Orchiopexy                     6                   7
  Excision of skin tumour        3                   3
  Reconstruction of              5                   6
    polydactyly
  Central venous catheter        2                   1
    insertion
Time from end of                 33 [+ or -] 14      32 [+ or -] 12
  dexmedetomidine/saline
  infusion to LMA removal, min

                                 Group [D.sub.2]     P
                                 (n=32)

Age, years                       4.7 [+ or -] 1.8    0.813
Weight, kg                       17 [+ or -] 6       0.497
Gender, male/female              15/16               0.856
ASA physical status, 1/2         28/3                0.921
Duration of anaesthesia, min     49 [+ or -] 15      0.326
Duration of surgery, min         27 [+ or -] 12      0.578
Type of surgery                                      0.976
  Inguinal hernia repair         14
  Orchiopexy                     5
  Excision of skin tumour        5
  Reconstruction of              5
    polydactyly
  Central venous catheter        3
    insertion
Time from end of                 34 [+ or -] 13      0.725
  dexmedetomidine/saline
  infusion to LMA removal, min

Values are mean [+ or -] standard devation or numbers. ASA = American
Society of Anesthesiologists, LMA = laryngeal mask airway.
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Title Annotation:Original Papers
Author:He, L.; Wang, X.; Zheng, S.; Shi, Y.
Publication:Anaesthesia and Intensive Care
Article Type:Report
Geographic Code:9CHIN
Date:May 1, 2013
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