Efficacy and safety of perioperative parecoxib for acute postoperative pain treatment in children: a meta-analysis

Abstract

Perioperative parecoxib administration reduces postoperative pain, opioid consumption, and adverse events in adult patients. However, the efficacy and safety of parecoxib in children remain unclear. This meta-analysis included related published studies to address this concern. Eight databases in the literature until February 2015 were systematically explored to identify randomized controlled trials (RCTs) comparing perioperative parecoxib administration and placebo/standard treatments for acute postoperative pain in children. Primary outcomes were postoperative pain scores and adverse events. The Face, Legs, Activity, Crying, Consolability scale was used to score pain in children younger than 6 years, whereas the Visual Analog Scale was used in children older than 6 years. Secondary outcomes were sedation scores (measured using the Ramsay scale), agitation scores (measured using the Sedation-Agitation Scale), and opioid consumption. The methodological quality of RCTs was independently assessed in accordance with the “Risk of bias” of Cochrane Collaboration. Data were analyzed using Review Manager 5.2. Twelve RCTs involving 994 patients met the inclusion criteria. Compared with children who received placebo treatment, those who received parecoxib demonstrated lower early (2 h) and later (12 h) postoperative pain scores; lower incidence rates of postoperative nausea, vomiting, and agitation; higher early (1 h) postoperative sedation scores; and lower agitation scores. Similarly, children who received parecoxib had lower early (2 h) and later (12 h) postoperative pain scores, lower incidence rates of postoperative nausea and vomiting, and lower early (1 h) postoperative sedation scores compared with those who received standard treatments; however, these children showed no significant difference in agitation scores. Unfortunately, data on the effect of parecoxib on opioid consumption were insufficient. Overall, these results suggested that perioperative parecoxib administration was associated with less acute postoperative pain and fewer adverse events compared with placebo or standard treatments. Parecoxib administration also resulted in less emergence agitation compared with placebo treatment and less excessive sedation concern compared with standard treatments. However, the long-term effects, effects on opioid consumption, and patient satisfaction of parecoxib administration warrant further investigation.

Keywords

NSAID / cyclooxygenase 2 inhibitor / child / pain, postoperative / opioid / placebo

1 Introduction

Pediatric postoperative pain management is important [1] because the memory of pain during childhood exacerbates present and future pain experiences [2]. However, the majority of children still suffer from significant postoperative pain, especially acute pain, caused by inadequate pain assessments or treatments [3].

Multimodal pain therapy has been recently developed for pediatric acute pain treatment; this therapy involves the administration of non-opioid analgesics, opioids, and co-analgesics, such as lidocaine, dexamethasone, or ketamine, as well as regional anesthesia (especially ultrasound guidance nerve block) [4]. Among these drugs, opioids are the most frequently used to treat pain in children, but the use of these compounds has raised issues on side effects, particularly respiratory depression, and adverse events; however, data supporting the occurrence of side effects and adverse events aside from iatrogenic overdose or drug errors are rare [5,6]. Consequently, non-opioids such as NSAIDs have been used as adjuvants to opioids. NSAIDs may reduce postoperative pain, opioid consumption, and the incidence of postoperative nausea and vomiting in the perioperative period [7]. However, the use of nonselective NSAIDs remains controversial because of their tendency to increase bleeding [8].

Cyclooxygenase-2 (COX-2)-selective agents have attracted attention as an effective and safe treatment for acute postoperative pain in children [9]. However, rofecoxib is a COX-2-selective agent whose administration has been restricted because of reportedly increasing the risk of cardiovascular events [10]. Celecoxib, also a COX-2-selective agent, is rarely applied in children [9] and only available in oral formulation.

Parecoxib, the first parenteral COX-2-selective agent, has advantages over the aforementioned NSAIDs or placebo in adult patients [11]. This agent can be intravenously or intramuscularly administered, which is advantageous for patients who experience postoperative nausea and vomiting or inability to swallow [12]. Parecoxib used in conjunction with opioids reduces opioid consumption and increases patient satisfaction [13]. In addition, parecoxib does not influence platelet aggregation [14], and rarely causes gastrointestinal ulceration [15], not to mention the few serious adverse effects, such as acute renal failure, Stevens-Johnson syndrome, or hypersensitivity reactions [15]. Although parecoxib is not yet licensed for use in children [12], the pharmacokinetic profile of parecoxib in children has recently been studied [12], and some random controlled trials (RCTs) [16−31] in China have used this compound. Therefore, a meta-analysis of related published studies was performed to assess the effects of perioperative parecoxib administration on acute postoperative pain, opioid consumption, and adverse events. Meta-analysis is a statistical technique widely recognized as the best in the aggregation and quantification of therapeutic effects from multiple studies.

2 Methods

This meta-analysis was performed in accordance with the guidelines of the Cochrane Handbook for Systematic Reviews Intervention [32], the Quality of Reporting of Meta-analysis Statement [33], and the recommendations of the preferred reporting items for systematic reviews and meta-analyses statement [34].

2.1 Search sources and strategy

RCTs were searched from four English literature databases (PubMed, Ovid Medline, Ovid Embase, and Cochrane Library) and four Chinese literature databases (Chinese BioMedical Literature, Chinese National Knowledge Infrastructure, VIP, and Wanfang). The following queries were used, “parecoxib, parecoxib sodium, dynastat, or selective cyclooxygenase-2 inhibitor” and “child, neonate, newborn, infant, preschool children, or adolescent.” References found in the selected articles (including reviews and meta-analyses) were also manually searched. Publication languages were not restricted. As of this writing, the most recent publication date was February 2015. Titles and abstracts of potential relevant trials were read by two reviewers to exclude irrelevant investigations, whereas inclusion and exclusion criteria were established a priori.

2.2 Inclusion and exclusion criteria

Inclusion criteria were as follows: (1) studies described as RCTs; (2) children (younger than 18 years) who underwent selective operation with general anesthesia; (3) perioperative application of parecoxib sodium (dose: 0.5 mg/kg, 1.0 mg/kg, and 20 mg or 40 mg in bolus intravenously); (4) control groups accepted placebo or standard treatments (opioids or tramadol); and (5) studies that reported at least one of following outcomes: (i) primary outcomes: pain scores and adverse events: nausea and vomiting, pruritus, uroschesis, agitation, etc.; (ii) secondary outcomes: sedation scores, agitation scores, and opioid consumption.

Exclusion criteria were as follows: (1) ketamine intravenous anesthesia; (2) treatment groups included adult population; and (3) duplicate publications.

2.3 Data extraction and assessment of study quality

Data from trials that met the inclusion criteria were extracted by two reviewers. Authors were contacted for missing data when necessary. The following information was extracted from each study: author; publication year; sample size; and patient ASA state, age, surgery type, parecoxib administration, and placebo or standard analgesics administration. Outcomes were pain scores, adverse events (nausea and vomiting, pruritus, uroschesis, and agitation), sedation scores, agitation scores, and opioid consumption (either doses or percentage of patients receiving treatments). The two reviewers rechecked the article together when conflicting results were found, and a third reviewer was consulted when the two reviewers could not reach an agreement.

2.4 Quality assessment of the RCTs

The quality of the included RCTs was assessed by two reviewers in accordance with the standard “Risk of bias” table in Cochrane Handbook 5.1.0 [32]. The table includes the following items: (1) appropriateness of randomized sequence generation; (2) concealment of allocation sequence; (3) blindness of participants and personnel to the study; (4) appropriateness of outcome assessment blinding; (5) description of incomplete outcome data; (6) absence of selective outcome reporting; and (7) inexistence of other biases. Three options were available for each item, namely, “Yes” for a low risk of bias, “No” for a high risk of bias, and “Unclear” if otherwise.

2.5 Statistical analysis

Data were analyzed using Review Manager software (RevMan 5.2; The Cochrane Collaboration, Oxford, UK). The mean difference (MD) and 95% confidence interval (CI) were calculated for continuous variables. Correspondingly, the odds ratio (OR) and 95% CI were calculated using the Mantel-Haenszel method for dichotomous data. Heterogeneity was assessed by I² statistic. In accordance with Cochrane review guidelines [32], a fixed-effects model was used when I²<50% and P>0.01; otherwise, a random-effects model was selected. Clinical and methodological heterogeneities were ruled out when heterogeneity was significant (I²>75%). Subgroup analysis on the basis of parecoxib dose was subsequently performed. The results were expressed as MD or OR [95% CI], P value, and I². A funnel plot for each outcome was not prepared because of the limited number of studies (<10) [35].

3 Results

3.1 Description of included and excluded studies

A total of 119 publications were deemed relevant to the search terms. Fifty studies remained after adjusting for duplicates. Of these 50 studies, 21 were removed after reviewing the titles and abstracts because they did not meet the inclusion criteria. Full texts of the remaining 29 articles were further examined, and 13 articles were excluded because of the inclusion of adult patients. Four other RCTs were discarded because they did not fulfill the inclusion criteria. In the first study [16], propofol or sevoflurane was not administered as the general anesthesia. The second one [17] used dezocine mixed with parecoxib, not parecoxib alone, in the experimental group. In the third study [18], the dose of parecoxib was 0.8 mg/kg, which did not fulfill the inclusion criteria. The last study was excluded because it was published twice [19,21]. Finally, 12 articles [20−31] involving 994 patients (treatment group, 475 patients; control group, 519 patients) were included in this meta-analysis. The flow chart for the selection of RCTs is shown in Fig. 1. The characteristics of the included trials are listed in Table 1.

3.2 Assessment of the study quality

The quality of the included RCTs was relatively low (Fig. 2). One RCT had a high risk of bias with randomization [20]. Furthermore, none of the authors referred to allocation concealment [20–31]. Two trials blinded the observers [21,22], whereas the other 10 trials did not mention a blinding of outcome assessments [20,23–31]. Moreover, one trial had a high risk for selective reporting because some outcomes that were mentioned in the Methods section were missing [21].

3.3 Parecoxib administration versus placebo treatment

3.3.1 Pain

Four trials [21,23,27,28] reported pain scores at 2 h and two trials [25,28] at 12 h after surgery. The Face, Legs, Activity, Crying, Consolability (FLACC) scale [21,23,28] was used to assess postoperative pain in patients younger than 6 years, whereas the Visual Analog Scale (VAS) [21,27,28] was used in those older than 6 years. The Bieri Faces Pain Scale was used in one trial [25]. The total score of these three scales ranged from 0 to 10, which represented the pain state from no pain to the strongest pain. Parecoxib administration was associated with less pain both at 2 h (MD= −1.92 [−3.05,−0.80], P<0.00001, I² = 98%) (Fig. 3a) and 12 h (MD= −2.05 [−2.35,−1.76], P = 0.15, I² = 51%) (Fig. 4a) after surgery compared with placebo treatment.

3.3.2 Adverse events

Four trials [21,23,27,28] reported postoperative nausea and vomiting, and pruritus. Two trials [23,27] indicated uroschesis, and two trials [20,24] reported agitation. Parecoxib administration was associated with lower incidence rates of postoperative nausea and vomiting (OR= 0.38 [0.16, 0.87], P = 0.51, I² = 0%) (Fig. 5a), and agitation (OR= 0.04 [0.02, 0.09], P = 0.33, I² = 0%) (Fig. 5d). No significant differences in the incidence of pruritus (OR= 0.61 [0.26, 1.39], P = 0.32, I² = 15%) (Fig. 5b) and uroschesis (OR= 1.00 [0.14, 7.40], P = 1.00, I² = 0%) were found between parecoxib and placebo treatments (Fig. 5c).

3.3.3 Sedation

Four trials [21,23,25,30] reported sedation scores at 1 h and two trials [25,30] at 12 h after surgery. The Ramsay scale was used to evaluate postoperative sedation in the included trials. Scores “1” to “6” represented the sedation state from anxiety to deep sleep. The results indicated that children in the parecoxib group had higher sedation scores at 1 h (MD= 0.81 [0.14, 1.48], P<0.00001, I² = 95%) but lower scores at 12 h after surgery (MD= −0.13 [−0.21,−0.05], P = 0.25, I² = 27%) compared with the placebo group.

3.3.4 Emergence agitation

Two trials [23,28] reported emergence agitation scores at 10 min after extubation. The Sedation-Agitation Scale (SAS) was used to assess emergence agitation. Scores “1” to “7” represented the agitation state from inability to wake up to dangerous agitation. Children in the parecoxib (1.0 mg/kg) group had lower agitation scores than those in the placebo group (MD= −1.37 [−1.54,−1.21], P = 0.28, I² = 14%).

3.3.5 Opioid consumption

Two trials investigated perioperative and postoperative fentanyl requirements. Qin et al. [21] showed that fentanyl consumption at 0.5−8 h after surgery was higher in the placebo and low-dose parecoxib (0.5 mg/kg) groups than in the high-dose parecoxib (1.0 and 1.5 mg/kg) groups. Li et al. [27] demonstrated that the perioperative and postoperative dosages of fentanyl were lower in the parecoxib group than in the placebo group. However, we could not pool these data because diverse units were used in the different trials.

3.4 Parecoxib administration versus standard treatments

Fentanyl and tramadol were considered standard treatments in this meta-analysis. Considering the limited included studies, we combined these treatments and compared them with parecoxib in the evaluation of pain, sedation, and emergence agitation. However, these two treatments were considered independently and compared with parecoxib in the examination of adverse events.

3.4.1 Pain

Four trials [23,27−29] reported pain scores at 2 h and four trials [25,26,28,29] at 12 h after surgery. The FLACC scale [23,26,28] was used to assess postoperative pain in patients younger than 6 years, whereas the VAS scale [27−29] was used in those older than 6 years. The Bieri Faces Pain Scale was used in one trial [25]. Parecoxib administration was associated with less pain at 2 h [MD= −0.32 [−0.42,−0.21], P = 0.36, I² = 6%) (Fig. 3b) and 12 h (MD= −0.36 [−0.71,−0.01], P<0.00001, I² = 95%) (Fig. 4b) after surgery compared with standard treatments.

3.4.2 Adverse events

Three trials [22,23,26] reported postoperative nausea and vomiting and two trials [23,26] reported pruritus when parecoxib administration was compared with fentanyl treatment. Five trials [25,27−29,31] reported postoperative nausea and vomiting and three trials [27,28,31] indicated pruritus when parecoxib administration was compared with tramadol treatment. Parecoxib administration reduced the incidence of postoperative nausea and vomiting (OR= 0.09 [0.03, 0.29], P = 0.35, I² = 4%) (Fig. 6a) compared with fentanyl treatment. No significant difference in the incidence of pruritus (OR= 1.00 [0.24, 4.18], P = 0.46, I² = 0%) was found between the two treatments (Fig. 6b). Compared with tramadol treatment, parecoxib administration reduced the incidence of postoperative nausea and vomiting (OR= 0.25 [0.11, 0.60], P = 0.61, I² = 0%) (Fig. 6c). No significant difference in the incidence of pruritus (OR= 1.00 [0.19, 5.19], P = 0.41, I² = 0%) was found between the two treatments (Fig. 6d).

3.4.3 Sedation

Three trials [23,25,26] reported sedation scores at 1 h and two trials [25,26] at 12 h after surgery. The Ramsay scale was used to evaluate postoperative sedation in these trials. The total score ranged from 1 to 6. The results indicated that children in the parecoxib group had lower sedation scores at 1 h after surgery than those in the standard group (MD= −0.81[−1.21,−0.41], P = 0.003, I² = 83%). However, no significant difference at 12 h after surgery (MD= −0.14 [−0.32, 0.03], P = 0.24, I² = 26%).

3.4.4 Emergence agitation

Two trials [23,28] reported emergence agitation scores at 10 min after extubation. SAS was used to assess emergence agitation. Parecoxib administration did not significantly reduce emergence agitation compared with standard treatments (MD= −0.08 [−0.21, 0.05], P = 0.85, I² = 0%).

3.4.5 Opioid consumption

Two trials investigated perioperative and postoperative fentanyl requirements. Li et al. [27] demonstrated that the perioperative and postoperative dosages of fentanyl are lower in the parecoxib group than in the tramadol group. Subramaniam et al. [22] indicated that fewer patients received postoperative rescue analgesic in the parecoxib group (1/30) than in the fentanyl group (12/30). Unfortunately, we also could not pool these data because of the diversity in the units used in the different studies.

4 Discussion

Parecoxib is a commonly used component of multimodal analgesia in adults. This compound is as effective or more effective than the older NSAIDs and more effective than placebo in adult patients [11]. However, the effectiveness of parecoxib in children is less well defined because of the very few related published studies. Despite the insufficient evidence, pediatricians worldwide, particularly those in China, are currently investigating the efficacy and safety of parecoxib administration in children [16−31].

This meta-analysis of published trials determined whether or not differences in postoperative pain, adverse effects, sedation, agitation, and opioid consumption exist between patients who received perioperative parecoxib administration and placebo/standard treatments.

Importantly, parecoxib administration was associated with less postoperative pain in the early (2 h) and later (12 h) postoperative periods compared with placebo or standard treatments. These results should be interpreted with caution because of data heterogeneity; nevertheless, the data conform to the study of the pharmacokinetic profile of parecoxib in children [12]. This study showed that parenteral parecoxib administration (1.0 mg/kg with 40 mg maximum) results in free valdecoxib (active metabolite of parecoxib) concentration above the IC₅₀ of COX-2, which continues at least 12 h. The analgesic effects of parecoxib depend on its capacity to downregulate the peripheral and central expression levels of COX-2. In the periphery, parecoxib can effectively decrease the synthesis of prostaglandin to exert anti-inflammatory and analgesic effects. In the central nervous system, this drug can restrain pain hypersensitivity to produce preemptive analgesic effects [23]. The pooled data on postoperative pain did not show homogeneity possibly because of three reasons. First, all of the included trials were of relatively low quality, and high risks of bias on randomization, allocation concealment, and blinding were found in some trials. Second, the participants were 1 to 12 years old; thus, the pharmacokinetic properties may vary. Last, different tools, such as VAS, FLACC, and Bieri Faces Pain Scale, were used to assess postoperative pain.

Conversely, homogeneous pooled data showed that parecoxib effectively decreased postoperative nausea, vomiting, and agitation but barely influenced pruritus and uroschesis. NSAIDs combined with opioids not only exert analgesic effects [36] but also reduce opioid requirements. Opioid consumption in adults can be reduced by as much as 20%−50% [37]. Consequently, the incidence of opioid-related adverse effects is decreased [37]. Although pooled data for opioid consumption in children are limited in this study because of the diverse units used in different trials, three trials [21,22,27] reported reduced opioid consumption after parecoxib administration compared with placebo or standard treatments. In addition, the included trials demonstrated that none of the children had respiratory depression [21,23–25,27–31], headache [25,30], fever [25], hypotension [30], arrhythmia [24,28,31], or dysfunction of blood coagulation [24,31]. These results suggest that perioperative parecoxib is a safe option for pediatric postoperative pain treatment.

Patients in the parecoxib group also exhibited higher postoperative sedation scores than those in the placebo group but lower scores than those in the standard group at 1 h after surgery. Patients in the parecoxib group showed lower sedation scores than those in the placebo group. However, no significant difference was found between the parecoxib and standard groups at 12 h after surgery. Thus, parecoxib administration displays stronger sedative effects compared with placebo treatment. In addition, parecoxib unlikely results in excessive sedation; therefore, administration of this compound demands less monitoring requirements compared with standard treatments.

Parecoxib administration was associated with less postoperative emergence agitation compared with placebo treatment. Although the efficacy of parecoxib on acute postoperative pain from this study is disputable because of data heterogeneity, the low incidence of emergence agitation conversely supports the effective analgesia of parecoxib.

Several limitations reduce the explanatory power of our results. First, available data on scores for postoperative pain, sedation, and agitation were not homogeneous at some time points. The pooled effect should be interpreted cautiously because of the significant heterogeneity of these results. In addition, the number of studies and participants were rather small; hence, the power of the analysis may be insufficient, and a serious risk of random error is probable [38]. Third, available trials had relatively high risks of bias, and most of the participants were Chinese. Finally, several pooled analyses (e.g., opioid consumption) were not possible because of insufficient available data. Therefore, additional large and high-quality RCTs are required for further study.

5 Conclusions

Perioperative parecoxib administration was associated with less acute postoperative pain and adverse events compared with placebo or standard treatments. Moreover, parecoxib administration demonstrated less emergence agitation compared with placebo treatment and less excessive sedation concern compared with standard treatments. However, actual clinical conditions and doctors’ experience should be considered when these results are used to guide clinical practice. Further high-quality RCTs should be performed to clarify the exact efficacy of parecoxib for postoperative pain. The long-term effects, effect on opioid consumption, and patient satisfaction of parecoxib administration should also be examined comprehensively.

References

[1] Astuto M, Rosano G, Rizzo G, Disma N, Di Cataldo A. Methodologies for the treatment of acute and chronic nononcologic pain in children. Minerva Anestesiol 2007; 73(9): 459–465

[2] Dahmani S, Michelet D, Abback PS, Wood C, Brasher C, Nivoche Y, Mantz J. Ketamine for perioperative pain management in children: a meta-analysis of published studies. Paediatr Anaesth 2011; 21(6): 636–652

[3] Russell P, von Ungern-Sternberg BS, Schug SA. Perioperative analgesia in pediatric surgery. Curr Opin Anaesthesiol 2013; 26(4): 420–427

[4] Schultz-Machata AM, Weiss M, Becke K. What’s new in pediatric acute pain therapy? Curr Opin Anaesthesiol 2014; 27(3): 316–322

[5] Morton NS, Errera A. APA national audit of pediatric opioid infusions. Paediatr Anaesth 2010; 20(2): 119–125

[6] Niesters M, Overdyk F, Smith T, Aarts L, Dahan A. Opioid-induced respiratory depression in paediatrics: a review of case reports. Br J Anaesth 2013; 110(2): 175–182

[7] Michelet D, Andreu-Gallien J, Bensalah T, Hilly J, Wood C, Nivoche Y, Mantz J, Dahmani S. A meta-analysis of the use of nonsteroidal antiinflammatory drugs for pediatric postoperative pain. Anesth Analg 2012; 114(2): 393–406

[8] Lewis SR, Nicholson A, Cardwell ME, Siviter G, Smith AF. Nonsteroidal anti-inflammatory drugs and perioperative bleeding in paediatric tonsillectomy. Cochrane Database Syst Rev 2013; 7: CD003591

[9] Hilário MOE, Terreri MT, Len CA. Nonsteroidal anti-inflammatory drugs: cyclooxygenase 2 inhibitors. J Pediatr (Rio J) 2006; 82(8 Suppl): S206–S212

[10] Jüni P, Nartey L, Reichenbach S, Sterchi R, Dieppe PA, Egger M. Risk of cardiovascular events and rofecoxib: cumulative meta-analysis. Lancet 2004; 364(9450): 2021–2029

[11] Lloyd R, Derry S, Moore RA, McQuay HJ. Intravenous or intramuscular parecoxib for acute postoperative pain in adults. Cochrane Database Syst Rev 2009; (2): CD004771

[12] Hullett B, Salman S, O’Halloran SJ, Peirce D, Davies K, Ilett KF. Development of a population pharmacokinetic model for parecoxib and its active metabolite valdecoxib after parenteral parecoxib administration in children. Anesthesiology 2012; 116(5): 1124–1133

[13] Langford RM, Joshi GP, Gan TJ, Mattera MS, Chen WH, Revicki DA, Chen C, Zlateva G. Reduction in opioid-related adverse events and improvement in function with parecoxib followed by valdecoxib treatment after non-cardiac surgery: a randomized, double-blind, placebo-controlled, parallel-group trial. Clin Drug Investig 2009; 29(9): 577–590

[14] Graff J, Arabmotlagh M, Cheung R, Geisslinger G, Harder S. Effects of parecoxib and dipyrone on platelet aggregation in patients undergoing meniscectomy: a double-blind, randomized, parallel-group study. Clin Ther 2007; 29(3): 438–447

[15] Anonymous . Dynastat; MIMS abbreviated prescribing information. E-MIMS Ver 5.01.0100 2010; MultiMedia Australia Pty Limited, St Leonards, Australia

[16] Ding X, Chen X. The influence of parecoxib on hemodynamics and emergence agitation after ketamine anesthesia in children. Jiangsu Med J (Jiangsu Yi Yao) 2012; 38(24): 3023–3024 (in Chinese)

[17] He ZW. Parecoxib combined with dezocine for prevention emergence agitation after combined anesthesia with remifentanil and sevoflurane in children. Mod Hosp (Xian Dai Yi Yuan) 2014; 14(5): 40–42 (in Chinese)

[18] Wang RM, Chai XQ, Chen KZ. The preemptive analgesia of dezocine in combination with parecoxib in children undergoing tonsillectomy. Anhui Med J (Anhui Yi Xue) 2014; 35(11): 1483–1485 (in Chinese)

[19] Qin PS. The combination of parecoxib single IV injection with fentanyl PCA and for limbs operation in children. Wenzhou: Wenzhou Medical College, 2010 (in Chinese)

[20] Lv H, Li J, Chen HR, Liu YQ, Xie LB, Cai QF, Li L. Effect of preemptive analgesia with Parecoxib sodium in children undergoing adenoidectomy. Chin J Clinicians (Zhonghua Lin Chuang Yi Shi Za Zhi) (Electronic Edition) 2012; 6(12): 3422–3423 (in Chinese)

[21] Qin PS, Cai MY, Li J, Wang JG, Lian QQ. A clinical observation of single intravenous injection of parecoxib combined with fentanyl for postoperative pain management in children. Chin J. Chin J Clin Pharmacol Ther (Zhongguo Lin Chuang Yao Li Xue Yu Zhi Liao Xue) 2011; 16(9): 1021–1025 (in Chinese)

[22] Subramaniam R, Joshi C, Sharma A, Prasad CN. Analgesic efficacy of single-dose parecoxib for corneal suturing in children. Eur J Anaesthesiol 2007; 24(5): 464–465

[23] Miao YL, Shi WZ, Guo WZ, Zhong J, Fang WW, Liu J, Wang ZJ, Liu G. Effect of preemptive analgesia with Parecoxib sodium in children undergoing endoscopic adenoidectomy and tonsillectomy of snoring disease. Clin J Med Offic (Lin Chuang Jun Yi Za Zhi) 2012; 40(2): 300–302 (in Chinese)

[24] Li K, Pan JZ. Parecoxib prevents restlessness during waking- up from sevoflurane anesthesia in children. Mod Hosp (Xian Dai Yi Yuan) 2011; 11(2): 30–31(in Chinese)

[25] Sun CL, Zhao XT, Li XZ. Different drugs’ effects on restlessness and pain after tonsillectomy in children. Theory Pract Med (Yi Xue Li Lun Yu Shi Jian) 2014; 27(9): 1127–1129(in Chinese)

[26] Ma XG, Yan XT. The clinical observation of parecoxib in preemptive analgesia in the control of adenoid and tonsil surgery. J Hubei Univ Natly: Med Ed (Hubei Min Zu Xue Yuan Xue Bao: Yi Xue Ban) 2013; 30(3): 53–55(in Chinese)

[27] Li XZ, Li W, Xia Q. Clinical study of preemptive analgesia with parecoxib sodium in children undergoing upper limb orthopedic surgery. West China Med J (Huaxi Yi Xue) 2011; 26(8): 1189–1191 (in Chinese)

[28] Zhang YZ, Li Q, Liu QX. The use of parecoxib and tramadol in preemptive analgesia in laparoscopic hernia repair in children. J Clin Pediatr Surg (Lin Chuang Xiao Er Wai Ke Za Zhi) 2014; 13(3): 250–252 (in Chinese)

[29] Ye WL, Jiang WN. Comparation of the efficacy of parecoxib and tramadol for corneal suturing in children. Strait Pharm J (Hai Xia Yao Xue) 2013; 25(7): 164–165 (in Chinese)

[30] Fan WJ, Wu N, Niu L. The clinical observation of parecoxib in preemptive analgesia in hypospadias operation in children. Chin J Clin Res (Zhongguo Lin Chuang Yan Jiu) 2013; 26(12): 1358–1359 (in Chinese)

[31] Yuan YX, Li WB, Gao RY, Dong YJ. Parecoxib combined with tramadol for prevention emergence agitation after general anesthesia in children. J Qiqihar Med Coll (Qiqihar Yi Xue Yuan Xue Bao) 2010; 31(11): 1729–1730 (in Chinese)

[32] Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions version 5.1.0. The Cochrane Collaboration, 2011 [2011-03].

[33] Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, Stroup DF. Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting of Meta-analyses. Lancet 1999; 354(9193): 1896–1900

[34] Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 2009; 339: b2700

[35] Sterne JA, Sutton AJ, Ioannidis JP, Terrin N, Jones DR, Lau J, Carpenter J, Rücker G, Harbord RM, Schmid CH, Tetzlaff J, Deeks JJ, Peters J, Macaskill P, Schwarzer G, Duval S, Altman DG, Moher D, Higgins JP. Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ 2011; 343: d4002

[36] Desjardins PJ, Grossman EH, Kuss ME, Talwalker S, Dhadda S, Baum D, Hubbard RC. The injectable cyclooxygenase-2-specific inhibitor parecoxib sodium has analgesic efficacy when administered preoperatively. Anesth Analg 2001; 93(3): 721–727

[37] Maund E, McDaid C, Rice S, Wright K, Jenkins B, Woolacott N. Paracetamol and selective and non-selective non-steroidal anti-inflammatory drugs for the reduction in morphine-related side-effects after major surgery: a systematic review. Br J Anaesth 2011; 106(3): 292–297

[38] Wetterslev J, Thorlund K, Brok J, Gluud C. Trial sequential analysis may establish when firm evidence is reached in cumulative meta-analysis. J Clin Epidemiol 2008; 61(1): 64–75

RIGHTS & PERMISSIONS

Higher Education Press and Springer-Verlag Berlin Heidelberg