OBJECTIVES: To evaluate the evidence for the effectiveness of clonidine, when given as a premedication, in reducing postoperative pain in children less than 18 years of age. We also sought evidence of any clinically significant side effects.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 12, 2012), Ovid MEDLINE (1966 to 21 December 2012) and Ovid EMBASE (1982 to 21 December 2012), as well as reference lists of other relevant articles and online trial registers.
SELECTION CRITERIA: We included all randomized (or quasi-randomized), controlled trials comparing clonidine premedication to placebo, a higher dose of clonidine, or another agent when used for surgical or other invasive procedures in children under the age of 18 years and where pain or a surrogate (principally the need for supplementary analgesia) was reported.
DATA COLLECTION AND ANALYSIS: Two authors independently performed the database search, decided on the inclusion eligibility of publications, ascertained study quality and extracted data. They then resolved any differences between their results by discussion. The data were entered into RevMan 5 for analyses and presentation. Sensitivity analyses were performed, as appropriate, to exclude studies with a high risk of bias.
MAIN RESULTS: We identified 11 trials investigating a total of 742 children in treatment arms relevant to our study question. Risks of bias in the studies were mainly low or unclear, but two studies had aspects of their methodology that had a high risk of bias. Overall, the quality of the evidence from pooled studies was low or had unclear risk of bias. Four trials compared clonidine with a placebo or no treatment, six trials compared clonidine with midazolam, and one trial compared clonidine with fentanyl. There was substantial methodological heterogeneity between trials; the dose and route of clonidine administration varied as did the patient populations, the types of surgery and the outcomes measured. It was therefore difficult to combine the outcomes of some trials for meta-analysis.When clonidine was compared to placebo, pooling studies of low or unclear risk of bias, the need for additional analgesia was reduced when clonidine premedication was given orally at 4 µg/kg (risk ratio (RR) 0.24, 95% confidence interval (CI) 0.11 to 0.51). Only one small trial (15 patients per arm) compared clonidine to midazolam for the same outcome; this also found a reduction in the need for additional postoperative analgesia (RR 0.25, 95% CI 0.09 to 0.71) when clonidine premedication was given orally at 2 or 4 µg/kg compared to oral midazolam at 0.5 mg/kg. A trial comparing oral clonidine at 4 µg/kg with intravenous fentanyl at 3 µg/kg found no statistically significant difference in the need for rescue analgesia (RR 0.89, 95% CI 0.56 to 1.42). When clonidine 4 µg/kg was compared to clonidine 2 µg/kg, there was a statistically significant difference in the number of patients requiring additional analgesia, in favour of the higher dose, as reported by a single, higher-quality trial (RR 0.38, 95% CI 0.23 to 0.65).The effect of clonidine on pain scores was hard to interpret due to differences in study methodology, the doses and route of drug administration, and the pain scale used. However, when given at a dose of 4 µg/kg, clonidine may have reduced analgesia requirements after surgery. There were no significant side effects of clonidine that were reported such as severe hypotension, bradycardia, or excessive sedation requiring intervention. However, several studies used atropine prophylactically with the aim of preventing such adverse effects.
AUTHORS' CONCLUSIONS: There were only 11 relevant trials studying 742 children having surgery where premedication with clonidine was compared to placebo or other drug treatment. Despite heterogeneity between trials, clonidine premedication in an adequate dosage (4 µg/kg) was likely to have a beneficial effect on postoperative pain in children. Side effects were minimal, but some of the studies used atropine prophylactically with the intention of preventing bradycardia and hypotension. Further research is required to determine under what conditions clonidine premedication is most effective in providing postoperative pain relief in children.
METHODS: Patients (n = 94) scheduled for gynaecological laparotomy received i.v. fentanyl infusion (3 μg/kg/h) after induction of general anaesthesia. Post-operative fentanyl requirements were quantified by using a patient-controlled analgesia and the number of i.v. fentanyl rescue analgesia required were recorded. Pain control was assessed using visual analogue scores (VAS) and fentanyl's adverse effects were documented. CYP3A4*4, CYP3A4*5 and CYP3A4*18 alleles of cytochrome P450 3A4 were identified by polymerase chain reaction-restriction fragment length polymorphism. Differences in fentanyl requirements, VAS scores and adverse effects among the various genotypes were compared.
RESULTS AND DISCUSSION: No CYP3A4*4 and CYP3A4*5 alleles were detected. Eighty-nine patients (94·7%) were wild-type, five (5·3%) were heterozygous and none was homozygous. No significant difference was demonstrated between the genotype groups in terms of fentanyl consumption, pain control and adverse effects.
WHAT IS NEW AND CONCLUSION: CYP3A4*4 and CYP3A4*5 are rare in the Malaysian Malay population. Genetic polymorphism of CYP3A4*18 may not play an important role in influencing postoperative fentanyl requirements.
Materials and Methods: Data of five strong opioids consumption (morphine, oxycodone, fentanyl, pethidine, and methadone) between 2005 and 2014 from Malaysia, Singapore, Indonesia, Thailand, and Vietnam were extracted from the Pain and Policy Studies Group. Defined daily doses per 1000 inhabitants per day (DDD/1000 inhabitants/day) was used for calculating the annual amount of opioid use.
Results: The total consumption of five strong opioids was increased in all five Southeast Asian countries during a 10-year study period. Malaysia was recorded with the largest increase of the opioid consumption (993.18%), followed by Indonesia (530.34%), Vietnam (170.17%), Singapore (116.16%), and Thailand (104.66%). Malaysia also had the highest total strong opioid consumption (11.2 DDD/1000 inhabitants/day), primarily for methadone. Among the opioids used for pain management, fentanyl was primarily used in Malaysia and Singapore but the greatest increase in these two countries was for oxycodone. Fentanyl was also primarily used in Indonesia while morphine was predominantly used in Thailand and Vietnam.
Conclusion: Growing trends of strong opioids consumption in all five Southeast Asian countries demonstrated in this study may indicate improved access to opioid analgesics in these countries. Given the increasing trends, it is important to ensure that the utilization of opioids is according to the guideline to prevent the negative consequences of opioids particularly when used in chronic non-cancer pain.
DESIGN: Randomized Control Trial. Adult Muslim patients who had undergone a laparoscopic cholecystectomy through the Day Surgery Unit were randomly selected using computer-generated sequence into two groups, interventional and control groups.
METHODS: The control group listened to the natural environment and received Fentanyl for pain relief, and the interventional group listened to the Qur'an recitation and received Fentanyl for pain relief. A total of 112 (79.4%) participants completed the study. The level of the pain and anxiety was measured using the Wong-Baker Faces pain scale and Spielberger State-Trait Anxiety Inventory, respectively. Statistical analysis was conducted using SAS version 9.3 (Statistical Analysis System, SAS Institute Inc, Cary, North Carolina).
FINDINGS: This study compared the effects of Qur'an audio therapy on patients' anxiety levels, opioid consumption, pain, and LOS in the PACU. The findings showed that by listening to chosen verses from the Qur'an in the recovery period post-anaesthesia, anxiety scores were significantly reduced (P = .0001), opiate use was reduced (P = .0081), and overall PACU LOS was also reduced (P = .0083).
CONCLUSIONS: Adding the use of listening to the Qur'an as a complementary therapy is a simple and cost-effective measure to reduce the need for narcotics in the PACU, and reduce the overall PACU length of stay. This intervention benefits the patient, the PACU, and reduces health care organization costs.
Methods: Thirty-two patients undergoing elective AH were randomised into Group ITM (ITM 0.2 mg + 2.5 mL 0.5% bupivacaine) (n = 16) and Group EB (0.25% bupivacaine bolus + continuous infusion of 0.1% bupivacaine-fentanyl 2 μg/mL) (n = 16).The procedure was performed before induction, and all patients subsequently received standard general anaesthesia. Both groups were provided patient-controlled analgaesia morphine (PCAM) as a backup. Visual analogue scale (VAS) scores, total morphine consumption, hospital stay duration, early mobilisation time and first PCAM demand time were recorded.
Results: The median VAS score was lower for ITM than for EB after the 1st hour [1.0 (IqR 1.0) versus 3.0 (IqR 3.0), P < 0.001], 8th hour [1.0 (IqR 1.0) versus 2.0 (IqR 1.0), P = 0.018] and 16th hour [1.0 (IqR1.0) versus (1.0 (IqR 1.0), P = 0.006]. The mean VAS score at the 4th hour was also lower for ITM [1.8 (SD 1.2) versus 2.9 (SD 1.4), P = 0.027]. Total morphine consumption [11.3 (SD 6.6) versus 16.5 (SD 4.8) mg, P = 0.016] and early mobilisation time [2.1 (SD 0.3) versus 2.6 (SD 0.9) days, P = 0.025] were also less for ITM. No significant differences were noted for other assessments.
Conclusions: The VAS score was better for ITM than for EB at earlier hours after surgery. However, in terms of acceptable analgaesia (VAS ≤ 3), both techniques were comparable over 24 hours.