Original article 247
Intraoperative administration of dexmedetomidine reduces the analgesic requirements for children undergoing hypospadius surgery Khaled R. Al-Zaben, Ibraheem Y. Qudaisat, Subhi M. Al-Ghanem, Islam M. Massad, Mahmoud M. Al-Mustafa, Abdelkarim S. Al-Oweidi, Sami A. Abu-Halaweh, Hamdi M. Abu-Ali and Mohammad M. Saleem Background The present study was designed to assess whether an intraoperative administration of dexmedetomidine would decrease the intraoperative and postoperative analgesic requirements for paediatric patients undergoing hypospadius surgery. Methods Forty-eight children (American Society of Anesthesiologists-1) aged 1–12 years undergoing hypospadius repair under general anaesthesia were randomly assigned into dexmedetomidine or placebo groups, D and P, respectively. Group D received a loading dose of dexmedetomidine 1 mg kg1 after induction of anaesthesia, followed by a continuous infusion at a rate of 0.7 mg kg1 h1. Group P received a volume-matched 0.9% saline. Both groups received fentanyl for intraoperative analgesia and intravenous morphine and oral paracetamol for postoperative analgesia. For both groups, heart rate, blood pressure and fentanyl requirements were recorded intraoperatively. During their stay for 2 h in the recovery room, heart rate, blood pressure, pain scores, behaviour scores and total morphine requirements were recorded. After discharge
Introduction Hypospadius repair in children is a painful procedure that may require more than one modality of pain control, including caudal anaesthesia, administration of narcotic drugs and nonsteroidal antiinflammatory drugs with its potential complications and disadvantages.1–4 Dexmedetomidine is an a-2-adrenergic receptor agonist that exhibits a a-2 : a-1 selectivity ratio of 1600 : 1.5 It has sedative and analgesic effects, it reduces the opioid requirements during the perioperative period in adults6,7 and its effect is not associated with respiratory depression.8 Dexmedetomidine has been used in paediatric patients for sedation during mechanical ventilation9 and after adenotonsillectomy and superficial lower abdominal and genital surgery to reduce the postoperative agitation.10,11 It has been used also for sedation for diagnostic imaging12 and for premedication to decrease anxiety.13 From the Department of Anaesthesia (KRA-Z, IYQ, SMA-G, IMM, MMA-M, ASA-O, SAA-H) and Department of General Surgery, Faculty of Medicine, University of Jordan, Amman (HMA-A, MMS), Jordan. Correspondence to Dr Khaled R. Al-Zaben, Department of Anaesthesia, Faculty of Medicine, University of Jordan, Amman, Jordan E-mail:
[email protected] 0265-0215 ß 2010 Copyright European Society of Anaesthesiology
from postanaesthesia care unit, paracetamol requirements over 24 h were also recorded. Results Intraoperatively, the dexmedetomidine-treated group had significantly fewer fentanyl requirements, slower heart rate and lower mean arterial blood pressure (P < 0.001). In the postanaesthesia care unit, this group also consumed significantly less morphine, had lower pain scores, lower behaviour score in the immediate postoperative period, lower heart rates and mean arterial blood pressures when compared with the placebo group (P < 0.001). Group D consumed significantly less paracetamol than group P in the ward over 24 h. Conclusion Intravenous administration of dexmedetomidine intraoperatively during hypospadius repair in children reduces intraoperative and postoperative analgesic requirements and lowers heart rate and blood pressure. Eur J Anaesthesiol 2010;27:247–252 Keywords: dexmedetomidine, hypospadius, paediatric, pain Received 9 September 2009 Revised 28 October 2009 Accepted 6 November 2009
The intravenous use of a-2-agonists for postoperative analgesia had been demonstrated for clonidine with equivalent efficacy to the caudal route in children undergoing hypospadius surgical repair.14 As dexmedetomidine possesses analgesic properties and is well tolerated when used intravenously, the intravenous use of dexmedetomidine might prove useful for reduction of intraoperative and postoperative analgesic requirements in paediatric patients. The aim of this study was to test the hypothesis that intraoperative intravenous administration of dexmedetomidine will reduce the perioperative analgesic requirements in paediatric patients undergoing hypospadius repair surgery under sevoflurane general anaesthesia.
Methods The present study was carried out at Jordan University Hospital, Amman, Jordan, in the period from June 2008 to February 2009. After obtaining the approval of the ethics committee, an informed consent was taken from the parents of 48 American Society of Anesthesiologists-1 (ASA-1) children, aged 1–12 years planned for hypospadius surgical repair under general anaesthesia. Exclusion DOI:10.1097/EJA.0b013e32833522bf
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248 Al-Zaben et al.
criteria included history of allergy to dexmedetomidine, children with renal or hepatic dysfunction or cardiac disease and children with behavioural disturbances or mental retardation. If preoperative sedative or analgesic premedication was needed, the patient was excluded from the study. A computer-generated randomization table was used to assign each patient to either the placebo group (group P, n ¼ 24) or the dexmedetomidine group (group D, n ¼ 24). A 50-ml syringe containing dexmedetomidine (Precedex; Hospira, Lake Forest, Illinois, USA), 1 mg ml1 in normal saline (group D), or normal saline (group P) was prepared shortly before anaesthesia by an anaesthesiologist who was not involved in anaesthetic management of the patients. In the operating room, monitors for heart rate (HR), blood pressure (BP), pulse oximetry, end-tidal CO2 and a paediatric bispectral index probe (Cardiocap II; Datex Ohmeda, Helsinki, Finland) were applied to each patient. After induction of anaesthesia with sevoflurane and 50% nitrous oxide in oxygen, a gauge 22 intravenous catheter was sited and infusion of normal saline 5–10 ml kg1 h1 was commenced. Fentanyl 2 mg kg1 was given intravenously and endotracheal intubation was facilitated by the administration of atracurium 0.5 mg kg1. Anaesthesia was maintained with 2% sevoflurane in 60% nitrous oxide and 40% oxygen. Each patient in both groups received an initial loading dose of 1 ml kg1 from the supplied solution over 10 min followed by an infusion of 0.7 ml kg1 h1 from the same solution until the end of surgery. In each case, the analgesic aim was to keep the HR and mean BP within 80–120% of their baseline values. An intraoperative elevation in BP or HR of more than 20% of their baseline was considered as inadequate analgesia and was treated with intravenous fentanyl 1 mg kg1 boluses; sevoflurane concentration was adjusted to maintain a bispectral index score between 40 and 60. Intraoperative decrease in BP or HR of more than 20% from the preoperative value was defined as hypotension or bradycardia, respectively, and was treated by fluid boluses, atropine or ephedrine as necessary. Monitoring data were collected before starting the study infusion and then every 10 min thereafter until the end of surgery. In each case, the total amount of additional fentanyl administered during the operation and the required end-tidal sevoflurane concentration were recorded. At the end of the procedure, sevoflurane and the infusion medications were discontinued, the trachea was extubated and time to tracheal extubation was recorded. Patients were then sent to the postanaesthesia care unit (PACU), where they were monitored and received oxygen delivered by a face mask for 2 h.
During their stay in the PACU, patients’ pain scores were monitored on admission and at 10, 20, 30, 60 and 120 min postoperatively using an objective pain score (OPS), which uses five criteria: localization of pain, movement, crying, agitation and posture.15 Each criterion given a score between 0 and 2 with 2 being the worst, giving a total score between 0 and 10; a postoperative pain score equal or more than 4 was managed by the administration of 100 mg kg1 boluses of morphine up to 300 mg kg1. Also, patients’ behaviour scores were recorded at the same time intervals using a scale described by Watcha et al.16 where: 0 ¼ child is asleep, 1 ¼ calm, 2 ¼ crying but can be consoled, 3 ¼ crying and cannot be consoled and 4 ¼ agitated and thrashing around. The time to first analgesic dose, the total amount of morphine consumption, HR, mean BP and SpO2 were recorded. The patients’ data were recorded by a qualified nurse who was blinded with respect to patient’s group allocation and purpose of the study. Children were discharged from the PACU when they were calm, had no complaints of pain or vomiting, had stable vital signs and spent at least 2 h since admission. Postoperative pain in the ward was managed by a qualified nurse with oral paracetamol 15 mg kg1 when patient is in pain with a minimum of 4 h between doses and with a maximum daily dose of 90 mg kg1. The number of doses given to each patient in both groups over 24 h was recorded.
Statistical analysis Statistical analysis was done using Statgraphics centurion XV (Statpoint; Herdon, Virginia, USA). Data were expressed as either mean and standard deviation or numbers and percentages. The demographic data of patients were studied for each of the two groups. Continuous covariates (HR, BP, pain score) were compared using the t-test, whereas for the categorical covariate (behavioural score), the comparison was studied using x2 test with the P value reported at the 95% confidence interval. The level of significance used was P equal to 0.05. To calculate the sample size, a power analysis (a ¼ 0.05 and b ¼ 0.85) showed that 23 patients per study group are adequate to detect 30% reduction in morphine, fentanyl and paracetamol requirements relative to the placebo group.6
Results Forty-eight patients were enrolled in the study. All patients completed the study without any subsequent exclusion. There were no significant differences (P > 0.05) between thetwogroups regarding age, weight, oxygensaturationand duration of surgery (Table 1). The mean of additional intraoperative fentanyl administered in group D was significantly lower than that in group P (0.46 0.78 vs. 1.79 1.1 mg kg1, respectively, P < 0.001).
European Journal of Anaesthesiology 2010, Vol 27 No 3
Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
Dexmedetomidine reduces analgesics in hypospadius surgery 249
Table 1
Demographic data
Variable Age (years) Weight (kg) Duration of surgery (min) SpO2%a a
Dexmedetomidine group (N ¼ 24) (mean SD)
Placebo group (N ¼ 24) (mean SD)
P value (t-test)
4.3 3.9 16.79 8.6 60.6 20.8 98% 2%
4.1 3.3 16.46 7.2 52.3 19.8 98% 2%
>0.05 >0.05 >0.05 >0.05
SpO2 ¼ peripheral oxygen saturation. P < 0.05 is considered significant.
Table 2
Perioperative data
Variable
Dexmedetomidine group (N ¼ 24)
Placebo group (N ¼ 24)
0.46 0.78 0.033 0.06 7 20.1 9.26 1.46 0.88 10.33 2.26 1.456 0.204
1.79 1.1 0.2125 0.09 22 5.67 4.26 2.25 0.74 6.04 1.73 2 0.1
Additional fentanyl in OR (mg kg1); mean SD Morphine in PACU (mg kg1); mean SD Number of patients needing morphine in PACU Time to first analgesia (min); mean SD Number of paracetamol doses in the ward over 24 h; mean SD Time to extubation (min); mean SD End-tidal sevoflurane (vol.%); mean SD
P value
