Pediatric Anesthesia ISSN 1155-5645
ORIGINAL ARTICLE
Comparison of caudal bupivacaine alone with bupivacaine plus two doses of dexmedetomidine for postoperative analgesia in pediatric patients undergoing infra-umbilical surgery: a randomized controlled double-blinded study Khaled R. Al-Zaben1, Ibraheem Y. Qudaisat1, Sami A. Abu-Halaweh1, Subhi M. Al-Ghanem1, Mahmoud M. Al-Mustafa1, Aboud N. Alja’bari1 & Hashem M. Al-Momani2 1 Department of Anesthesia, Faculty of medicine, University of Jordan, Amman, Jordan 2 Department of Surgery, Faculty of medicine, University of Jordan, Amman, Jordan
What is already known
• Caudally co-administered dexmedetomidine prolongs the postoperative analgesic effects of local anaesthesthetics. Data about the effects of different doses of dexmedetomidine are still insufficient.
What this article adds
• A 1 lgkg 1 lgkg
1
dose of caudal dexmedetomidine achieved comparable prolongation of postoperative analgesia to 2 with shorter duration of postoperative sedation and a lower incidence of other side effects.
Keywords dexmedetomidine; caudal block; bupivacaine; children; postoperative analgesia; surgery Correspondence Khaled R. Al-Zaben, Department of Anesthesia and Intensive Care, University of Jordan Hospital, Queen Rania street, Amman 11942, Jordan Email: [email protected] Section Editor: Per-Arne Lonnqvist Accepted 10 April 2015 doi:10.1111/pan.12686
© 2015 John Wiley & Sons Ltd Pediatric Anesthesia 25 (2015) 883–890
Summary Background: Data are still insufficient about the effects of different concentrations of caudal dexmedetomidine when used to prolong postoperative analgesia in children. The aim of this study was to assess the analgesic efficacy and side effects of two doses of caudal dexmedetomidine (1 and 2 lgkg 1) co-administered with bupivacaine in terms of postoperative pain scores and requirement of postoperative analgesia over 24 h in children undergoing infra-umbilical surgery. Methods: Ninety-one children, aged 1–6 years, undergoing infra-umbilical surgery were included and randomly allocated into three groups of caudal block. Group B received 0.25% bupivacaine 2 mgkg 1 (0.8 mlkg 1). Groups BD1 and BD2 received dexmedetomidine 1 and 2 lgkg 1, respectively along with bupivacaine 2 mgkg 1 in a total volume of 0.8 mlkg 1. Anesthesia was induced and maintained with sevoflurane in 100% oxygen. Hemodynamic and other routine intraoperative monitoring was carried out in addition to endtidal sevoflurane concentration. Time to spontaneous eye opening and postoperative pain and sedation scores were recorded in addition to time to first analgesia, paracetamol analgesic requirements, and any side effects during the first 24 postoperative hours. Results: Time to first analgesia requirement was significantly longer in BD1 and BD2 groups compared to B group with mean values (95% CI) of 809 min (652–965), 880 (733–1026), and 396 (343–448), respectively, P < 0.001. Postoperative paracetamol analgesic requirements over 24 h were higher in group B compared to BD1 and BD2 groups (Mean (95% CI): 3.2 (2.9–3.5) doses, 1.9 (1.5–2.3), and 1.6 (1.3–1.9), respectively), P < 0.001. The dexmedetomidine groups had significantly higher postoperative sedation 883
Adjuvant caudal dexmedetomidine in children
K.R. Al-Zaben et al.
scores compared to plain bupivacaine group that were dose dependent and for longer time in BD2 group. Two patients in BD2 group developed bradycardia and hypotension, and one developed urine retention compared to none in other groups. Conclusion: A 1 lgkg 1 dose of caudal dexmedetomidine achieved comparable prolongation of postoperative analgesia to 2 lgkg 1 dose, with shorter duration of postoperative sedation and lower incidence of other side effects.
Introduction Caudal analgesia is the commonest regional block performed in pediatric anesthesia. Various adjuvant drugs are effective in prolonging the duration of caudal analgesia when co-administered with the local anesthetic (1). Dexmedetomidine is a highly selective a-2 agonist with sedative and analgesic properties (2,3). Recent studies suggest that the co-administration of dexmedetomidine with caudal local anesthetics could prolong postoperative analgesia and sedation in children. The recent metaanalysis study by Tong et al. (1) summarized the reported results of those studies and highlighted the benefits of dexmedetomidine in this regard. However, in their meta-analysis, Tong et al. concluded that the data of the effects of different concentrations of dexmedetomidine were still insufficient and called for further studies to explore this issue. The primary aim of our study was to assess the analgesic efficacy of two doses of caudal dexmedetomidine (1 and 2 lgkg 1) co-administered with bupivacaine. Outcomes of interest were time to first requirement of analgesia, number of paracetamol doses required, and average pain scores over 24 h postoperatively. Methods This prospective, randomized, double-blinded study was conducted at University of Jordan Hospital, Amman, Jordan in the period between January and August, 2014. The study was approved by the hospital’s local ethics (IRB) committee (IRB-L/2014/36), and written informed parental consent was obtained for each enrolled patient according to the World Medical Association Declaration of Helsinki. Ninety-one children (ASA I, age: 1–6 years) scheduled for lower abdominal and perineal surgery under general anesthesia were randomly assigned into three groups using a computer-generated randomization list, Figure 1. Study exclusion criteria included a history of developmental delay or mental retardation, known or suspected coagulopathy or recent use of anticoagulant/antiplatelet drugs, known allergy to any of the study drugs, and any signs of infection or congenital abnormalities at the site of the 884
proposed caudal block. If preoperative sedative or analgesic premedication was needed, the patient was excluded from the study. The study drugs were prepared by an anesthetist, who was not involved in the study, in syringes that were only labeled with drug’s serial number. The drugs were handed to the anesthetist in charge who was blinded to the identity of the drug. All healthcare personnel providing direct patient care, parents, or guardians were blinded to the caudal medications administered. In the operating room, routine monitors were applied and baseline readings were taken. In addition, a bispectral index (BIS) probe (Cardiocap II, Datex Ohmeda, Helsinki, Finland) was attached to each patient and conscious reference readings were taken. After inhalational induction of anesthesia using sevoflurane, a laryngeal mask airway of appropriate size was inserted. Anesthesia was maintained with sevoflurane in oxygen and air. A caudal block was then performed with the patients in the lateral decubitus position using a 23-G short-beveled needle under sterile conditions. All blocks were carried out by the primary investigator. Group B (n = 30) received a caudal injection of plain bupivacaine 0.25% at a dose of 2 mgkg 1 (0.8 mlkg 1), and Group BD1 (n = 31) received the same dose of bupivacaine mixed with preservative-free dexmedetomidine 1 lgkg 1 (PrecedexÒ; Hospira, Lake Forest, Illinois, USA). Group BD2 (n = 30) received the same dose of bupivacaine mixed with dexmedetomidine 2 lgkg 1. To standardize the volume of injected drugs in groups BD1 and BD2 at 0.8 mlkg 1, bupivacaine dose was prepared from 0.5% vials and after adding the dexmedetomidine dose, the total volume was brought up to 0.8 mlkg 1 by adding normal saline. Surgical intervention was started 15 min after the caudal injection. Continuous monitoring included patient’s heart rate (HR), ECG, endtidal carbon dioxide, peripheral arterial oxygen saturation (SpO2), and BIS score. Non-invasive blood pressure readings were taken every 5 min. Measurements from all monitors were recorded before induction of anesthesia and then every 5 min until end of surgery. Readings at 10 min were used for comparisons. We defined failure of caudal block (insufficient analgesia) as intraoperative increase in mean blood © 2015 John Wiley & Sons Ltd Pediatric Anesthesia 25 (2015) 883–890
K.R. Al-Zaben et al.
Adjuvant caudal dexmedetomidine in children
Figure 1 CONSORT flow diagram of patient recruitment.
pressure (MBP) or HR by more than 20% and treated it with fentanyl 1 lgkg 1. An intraoperative decrease of blood pressure (BP) or HR by ≥20% from the preoperative value was defined as hypotension or bradycardia, respectively, and treatment was planned with intravenous fluid bolus, ephedrine, or atropine, as necessary. Sevoflurane concentration was adjusted to maintain BIS between 40 and 60, and the required concentration was recorded every 10 min. Lactated Ringer’s solution at a rate of 6 mlkg 1h 1 was used for intraoperative fluid maintenance. At the end of surgery, sevoflurane was discontinued and laryngeal mask was removed while patients were still sleeping. Patients were then taken asleep to the postanesthesia care unit (PACU) and allowed to spontaneously wake up (spontaneous eye opening). Observation in the PACU was carried out for a minimum period of 120 min. In PACU, patients’ HR and SpO2 were continuously monitored and BP measurements were recorded every 10 min. An experienced nurse, unaware of the given caudal analgesic treatment, recorded postoperative pain and sedation scores. Postoperative pain was assessed using a validated modified objective pain score (4), which uses five criteria: localization of pain, movement, crying, agitation, and posture. Each criterion is given a score between 0 and 2 with two being the worst, giving a total score between 0 and 10. Assessment of sedation was performed by using an objective score based on eye opening (0: eyes open spontaneously, 1: eyes open in © 2015 John Wiley & Sons Ltd Pediatric Anesthesia 25 (2015) 883–890
response to verbal stimulation, 2: eyes open in response to physical stimulation) (5,6). Time for awakening was recorded as the period from discontinuation of sevoflurane to spontaneous eye opening. After transfer of patients to the ward, pain scores were documented at 4, 8, 12, and 24 h postoperatively. If the objective pain score was ≥4, syrup paracetamol 15 mgkg 1 was administered. The duration of analgesia was defined as the time from caudal injection to the time at which pain score was 4 or more and was recorded in addition to the total consumption of paracetamol in the first 24 h. Side effects of drugs used (e.g., urine retention, lower limb weakness, and emesis) were also recorded. All the assessments of the variables studied were recorded by a ward nurse observers unaware of the mixture used for caudal blocks. Outcomes of interest were postoperative pain scores, time to first requirement of analgesia, and the number of postoperative required doses of analgesia over 24 h. Other measures included: intraoperative sevoflurane requirement to achieve the required BIS value, time for recovery from anesthesia, sedation score, duration of motor block, and side effects including bradycardia, hypotension, nausea, vomiting, and urinary retention. Statistical analysis Statistical analyses were carried out using IBM STATISTICS 19.0 statistical package for WINDOWS, (SPSS Inc., 885
K.R. Al-Zaben et al.
Adjuvant caudal dexmedetomidine in children
Chicago, IL, USA). Patients’ demographics were summarized using descriptive statistics as frequencies for categorical variables and median (range) for continuous variables. Data were compared using analysis of variance for continuous variables, Kruskal–Wallis test for ordinal, and chi-square test for categorical ones. Posthoc analyses were carried out as appropriate. Time to first analgesic administration and duration of postoperative sedation were also analyzed by the Kaplan–Meier survival analysis and log-rank test. The sample size was calculated to detect a 65% reduction in the analgesic requirement during the first 24 h from 75% in the bupivacaine group with a = 0.05 and b = 0.80. Statistical significance was defined at a P value of
ORIGINAL ARTICLE
Comparison of caudal bupivacaine alone with bupivacaine plus two doses of dexmedetomidine for postoperative analgesia in pediatric patients undergoing infra-umbilical surgery: a randomized controlled double-blinded study Khaled R. Al-Zaben1, Ibraheem Y. Qudaisat1, Sami A. Abu-Halaweh1, Subhi M. Al-Ghanem1, Mahmoud M. Al-Mustafa1, Aboud N. Alja’bari1 & Hashem M. Al-Momani2 1 Department of Anesthesia, Faculty of medicine, University of Jordan, Amman, Jordan 2 Department of Surgery, Faculty of medicine, University of Jordan, Amman, Jordan
What is already known
• Caudally co-administered dexmedetomidine prolongs the postoperative analgesic effects of local anaesthesthetics. Data about the effects of different doses of dexmedetomidine are still insufficient.
What this article adds
• A 1 lgkg 1 lgkg
1
dose of caudal dexmedetomidine achieved comparable prolongation of postoperative analgesia to 2 with shorter duration of postoperative sedation and a lower incidence of other side effects.
Keywords dexmedetomidine; caudal block; bupivacaine; children; postoperative analgesia; surgery Correspondence Khaled R. Al-Zaben, Department of Anesthesia and Intensive Care, University of Jordan Hospital, Queen Rania street, Amman 11942, Jordan Email: [email protected] Section Editor: Per-Arne Lonnqvist Accepted 10 April 2015 doi:10.1111/pan.12686
© 2015 John Wiley & Sons Ltd Pediatric Anesthesia 25 (2015) 883–890
Summary Background: Data are still insufficient about the effects of different concentrations of caudal dexmedetomidine when used to prolong postoperative analgesia in children. The aim of this study was to assess the analgesic efficacy and side effects of two doses of caudal dexmedetomidine (1 and 2 lgkg 1) co-administered with bupivacaine in terms of postoperative pain scores and requirement of postoperative analgesia over 24 h in children undergoing infra-umbilical surgery. Methods: Ninety-one children, aged 1–6 years, undergoing infra-umbilical surgery were included and randomly allocated into three groups of caudal block. Group B received 0.25% bupivacaine 2 mgkg 1 (0.8 mlkg 1). Groups BD1 and BD2 received dexmedetomidine 1 and 2 lgkg 1, respectively along with bupivacaine 2 mgkg 1 in a total volume of 0.8 mlkg 1. Anesthesia was induced and maintained with sevoflurane in 100% oxygen. Hemodynamic and other routine intraoperative monitoring was carried out in addition to endtidal sevoflurane concentration. Time to spontaneous eye opening and postoperative pain and sedation scores were recorded in addition to time to first analgesia, paracetamol analgesic requirements, and any side effects during the first 24 postoperative hours. Results: Time to first analgesia requirement was significantly longer in BD1 and BD2 groups compared to B group with mean values (95% CI) of 809 min (652–965), 880 (733–1026), and 396 (343–448), respectively, P < 0.001. Postoperative paracetamol analgesic requirements over 24 h were higher in group B compared to BD1 and BD2 groups (Mean (95% CI): 3.2 (2.9–3.5) doses, 1.9 (1.5–2.3), and 1.6 (1.3–1.9), respectively), P < 0.001. The dexmedetomidine groups had significantly higher postoperative sedation 883
Adjuvant caudal dexmedetomidine in children
K.R. Al-Zaben et al.
scores compared to plain bupivacaine group that were dose dependent and for longer time in BD2 group. Two patients in BD2 group developed bradycardia and hypotension, and one developed urine retention compared to none in other groups. Conclusion: A 1 lgkg 1 dose of caudal dexmedetomidine achieved comparable prolongation of postoperative analgesia to 2 lgkg 1 dose, with shorter duration of postoperative sedation and lower incidence of other side effects.
Introduction Caudal analgesia is the commonest regional block performed in pediatric anesthesia. Various adjuvant drugs are effective in prolonging the duration of caudal analgesia when co-administered with the local anesthetic (1). Dexmedetomidine is a highly selective a-2 agonist with sedative and analgesic properties (2,3). Recent studies suggest that the co-administration of dexmedetomidine with caudal local anesthetics could prolong postoperative analgesia and sedation in children. The recent metaanalysis study by Tong et al. (1) summarized the reported results of those studies and highlighted the benefits of dexmedetomidine in this regard. However, in their meta-analysis, Tong et al. concluded that the data of the effects of different concentrations of dexmedetomidine were still insufficient and called for further studies to explore this issue. The primary aim of our study was to assess the analgesic efficacy of two doses of caudal dexmedetomidine (1 and 2 lgkg 1) co-administered with bupivacaine. Outcomes of interest were time to first requirement of analgesia, number of paracetamol doses required, and average pain scores over 24 h postoperatively. Methods This prospective, randomized, double-blinded study was conducted at University of Jordan Hospital, Amman, Jordan in the period between January and August, 2014. The study was approved by the hospital’s local ethics (IRB) committee (IRB-L/2014/36), and written informed parental consent was obtained for each enrolled patient according to the World Medical Association Declaration of Helsinki. Ninety-one children (ASA I, age: 1–6 years) scheduled for lower abdominal and perineal surgery under general anesthesia were randomly assigned into three groups using a computer-generated randomization list, Figure 1. Study exclusion criteria included a history of developmental delay or mental retardation, known or suspected coagulopathy or recent use of anticoagulant/antiplatelet drugs, known allergy to any of the study drugs, and any signs of infection or congenital abnormalities at the site of the 884
proposed caudal block. If preoperative sedative or analgesic premedication was needed, the patient was excluded from the study. The study drugs were prepared by an anesthetist, who was not involved in the study, in syringes that were only labeled with drug’s serial number. The drugs were handed to the anesthetist in charge who was blinded to the identity of the drug. All healthcare personnel providing direct patient care, parents, or guardians were blinded to the caudal medications administered. In the operating room, routine monitors were applied and baseline readings were taken. In addition, a bispectral index (BIS) probe (Cardiocap II, Datex Ohmeda, Helsinki, Finland) was attached to each patient and conscious reference readings were taken. After inhalational induction of anesthesia using sevoflurane, a laryngeal mask airway of appropriate size was inserted. Anesthesia was maintained with sevoflurane in oxygen and air. A caudal block was then performed with the patients in the lateral decubitus position using a 23-G short-beveled needle under sterile conditions. All blocks were carried out by the primary investigator. Group B (n = 30) received a caudal injection of plain bupivacaine 0.25% at a dose of 2 mgkg 1 (0.8 mlkg 1), and Group BD1 (n = 31) received the same dose of bupivacaine mixed with preservative-free dexmedetomidine 1 lgkg 1 (PrecedexÒ; Hospira, Lake Forest, Illinois, USA). Group BD2 (n = 30) received the same dose of bupivacaine mixed with dexmedetomidine 2 lgkg 1. To standardize the volume of injected drugs in groups BD1 and BD2 at 0.8 mlkg 1, bupivacaine dose was prepared from 0.5% vials and after adding the dexmedetomidine dose, the total volume was brought up to 0.8 mlkg 1 by adding normal saline. Surgical intervention was started 15 min after the caudal injection. Continuous monitoring included patient’s heart rate (HR), ECG, endtidal carbon dioxide, peripheral arterial oxygen saturation (SpO2), and BIS score. Non-invasive blood pressure readings were taken every 5 min. Measurements from all monitors were recorded before induction of anesthesia and then every 5 min until end of surgery. Readings at 10 min were used for comparisons. We defined failure of caudal block (insufficient analgesia) as intraoperative increase in mean blood © 2015 John Wiley & Sons Ltd Pediatric Anesthesia 25 (2015) 883–890
K.R. Al-Zaben et al.
Adjuvant caudal dexmedetomidine in children
Figure 1 CONSORT flow diagram of patient recruitment.
pressure (MBP) or HR by more than 20% and treated it with fentanyl 1 lgkg 1. An intraoperative decrease of blood pressure (BP) or HR by ≥20% from the preoperative value was defined as hypotension or bradycardia, respectively, and treatment was planned with intravenous fluid bolus, ephedrine, or atropine, as necessary. Sevoflurane concentration was adjusted to maintain BIS between 40 and 60, and the required concentration was recorded every 10 min. Lactated Ringer’s solution at a rate of 6 mlkg 1h 1 was used for intraoperative fluid maintenance. At the end of surgery, sevoflurane was discontinued and laryngeal mask was removed while patients were still sleeping. Patients were then taken asleep to the postanesthesia care unit (PACU) and allowed to spontaneously wake up (spontaneous eye opening). Observation in the PACU was carried out for a minimum period of 120 min. In PACU, patients’ HR and SpO2 were continuously monitored and BP measurements were recorded every 10 min. An experienced nurse, unaware of the given caudal analgesic treatment, recorded postoperative pain and sedation scores. Postoperative pain was assessed using a validated modified objective pain score (4), which uses five criteria: localization of pain, movement, crying, agitation, and posture. Each criterion is given a score between 0 and 2 with two being the worst, giving a total score between 0 and 10. Assessment of sedation was performed by using an objective score based on eye opening (0: eyes open spontaneously, 1: eyes open in © 2015 John Wiley & Sons Ltd Pediatric Anesthesia 25 (2015) 883–890
response to verbal stimulation, 2: eyes open in response to physical stimulation) (5,6). Time for awakening was recorded as the period from discontinuation of sevoflurane to spontaneous eye opening. After transfer of patients to the ward, pain scores were documented at 4, 8, 12, and 24 h postoperatively. If the objective pain score was ≥4, syrup paracetamol 15 mgkg 1 was administered. The duration of analgesia was defined as the time from caudal injection to the time at which pain score was 4 or more and was recorded in addition to the total consumption of paracetamol in the first 24 h. Side effects of drugs used (e.g., urine retention, lower limb weakness, and emesis) were also recorded. All the assessments of the variables studied were recorded by a ward nurse observers unaware of the mixture used for caudal blocks. Outcomes of interest were postoperative pain scores, time to first requirement of analgesia, and the number of postoperative required doses of analgesia over 24 h. Other measures included: intraoperative sevoflurane requirement to achieve the required BIS value, time for recovery from anesthesia, sedation score, duration of motor block, and side effects including bradycardia, hypotension, nausea, vomiting, and urinary retention. Statistical analysis Statistical analyses were carried out using IBM STATISTICS 19.0 statistical package for WINDOWS, (SPSS Inc., 885
K.R. Al-Zaben et al.
Adjuvant caudal dexmedetomidine in children
Chicago, IL, USA). Patients’ demographics were summarized using descriptive statistics as frequencies for categorical variables and median (range) for continuous variables. Data were compared using analysis of variance for continuous variables, Kruskal–Wallis test for ordinal, and chi-square test for categorical ones. Posthoc analyses were carried out as appropriate. Time to first analgesic administration and duration of postoperative sedation were also analyzed by the Kaplan–Meier survival analysis and log-rank test. The sample size was calculated to detect a 65% reduction in the analgesic requirement during the first 24 h from 75% in the bupivacaine group with a = 0.05 and b = 0.80. Statistical significance was defined at a P value of
