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Meta-Analysis
. 2021 Jun 14;6(6):CD012978.
doi: 10.1002/14651858.CD012978.pub2.

Pre-emptive and preventive NSAIDs for postoperative pain in adults undergoing all types of surgery

Brett Doleman  1 , Jo Leonardi-Bee  2 , Thomas P Heinink  3 , Hannah Boyd-Carson  4 , Laura Carrick  5 , Rahil Mandalia  6 , Jon N Lund  7 , John P Williams  1
Affiliations
Meta-Analysis

Pre-emptive and preventive NSAIDs for postoperative pain in adults undergoing all types of surgery

Brett Doleman et al. Cochrane Database Syst Rev. .

Abstract

Background: Postoperative pain is a common consequence of surgery and can have many negative perioperative effects. It has been suggested that the administration of analgesia before a painful stimulus may improve pain control. We defined pre-emptive nonsteroidal anti-inflammatories (NSAIDs) as those given before surgery but not continued afterwards and preventive NSAIDs as those given before surgery and continued afterwards. These were compared to a control group given the NSAIDs after surgery instead of before surgery.

Objectives: To assess the efficacy of preventive and pre-emptive NSAIDs for reducing postoperative pain in adults undergoing all types of surgery.

Search methods: We searched the following electronic databases: CENTRAL, MEDLINE, Embase, AMED and CINAHL (up to June 2020). In addition, we searched for unpublished studies in three clinical trial databases, conference proceedings, grey literature databases, and reference lists of retrieved articles. We did not apply any restrictions on language or date of publication.

Selection criteria: We included parallel-group randomized controlled trials (RCTs) only. We included adult participants undergoing any type of surgery. We defined pre-emptive NSAIDs as those given before surgery but not continued afterwards and preventive NSAIDs as those given before surgery and continued afterwards. These were compared to a control group given the NSAIDs after surgery instead of before surgery. We included studies that gave the medication by any route but not given on the skin.

Data collection and analysis: We used the standard methods expected by Cochrane, as well as a novel publication bias test developed by our research group. We used GRADE to assess the certainty of the evidence for each outcome. Outcomes included acute postoperative pain (minimal clinically important difference (MCID): 1.5 on a 0-10 scale), adverse events of NSAIDs, nausea and vomiting, 24-hour morphine consumption (MCID: 10 mg reduction), time to analgesic request (MCID: one hour), pruritus, sedation, patient satisfaction, chronic pain and time to first bowel movement (MCID: 12 hours).

Main results: We included 71 RCTs. Seven studies are awaiting classification. We included 45 studies that evaluated pre-emptive NSAIDs and 26 studies that evaluated preventive NSAIDs. We considered only four studies to be at low risk of bias for most domains. The operations and NSAIDs used varied, although most studies were conducted in abdominal, orthopaedic and dental surgery. Most studies were conducted in secondary care and in low-risk participants. Common exclusions were participants on analgesic medications prior to surgery and those with chronic pain. Pre-emptive NSAIDs compared to post-incision NSAIDs For pre-emptive NSAIDs, there is probably a decrease in early acute postoperative pain (MD -0.69, 95% CI -0.97 to -0.41; studies = 36; participants = 2032; I2 = 96%; moderate-certainty evidence). None of the included studies that reported on acute postoperative pain reported adverse events as an outcome. There may be little or no difference between the groups in short-term (RR 1.00, 95% CI 0.34 to 2.94; studies = 2; participants = 100; I2 = 0%; low-certainty evidence) or long-term nausea and vomiting (RR 0.85, 95% CI 0.52 to 1.38; studies = 5; participants = 228; I2 = 29%; low-certainty evidence). There may be a reduction in late acute postoperative pain (MD -0.22, 95% CI -0.44 to 0.00; studies = 28; participants = 1645; I2 = 97%; low-certainty evidence). There may be a reduction in 24-hour morphine consumption with pre-emptive NSAIDs (MD -5.62 mg, 95% CI -9.00 mg to -2.24 mg; studies = 16; participants = 854; I2 = 99%; low-certainty evidence) and an increase in the time to analgesic request (MD 17.04 minutes, 95% CI 3.77 minutes to 30.31 minutes; studies = 18; participants = 975; I2 = 95%; low-certainty evidence). There may be little or no difference in opioid adverse events such as pruritus (RR 0.40, 95% CI 0.09 to 1.76; studies = 4; participants = 254; I2 = 0%; low-certainty evidence) or sedation (RR 0.51, 95% CI 0.16 to 1.68; studies = 4; participants = 281; I2 = 0%; low-certainty evidence), although the number of included studies for these outcomes was small. No study reported patient satisfaction, chronic pain or time to first bowel movement for pre-emptive NSAIDs. Preventive NSAIDs compared to post-incision NSAIDs For preventive NSAIDs, there may be little or no difference in early acute postoperative pain (MD -0.14, 95% CI -0.39 to 0.12; studies = 18; participants = 1140; I2 = 75%; low-certainty evidence). One study reported adverse events from NSAIDs (reoperation for bleeding) although the events were low which did not allow any meaningful conclusions to be drawn (RR 1.95; 95% CI 0.18 to 20.68). There may be little or no difference in rates of short-term (RR 1.26, 95% CI 0.49 to 3.30; studies = 1; participants = 76; low-certainty evidence) or long-term (RR 0.85, 95% CI 0.52 to 1.38; studies = 5; participants = 456; I2 = 29%; low-certainty evidence) nausea and vomiting. There may be a reduction in late acute postoperative pain (MD -0.33, 95% CI -0.59 to -0.07; studies = 21; participants = 1441; I2 = 81%; low-certainty evidence). There is probably a reduction in 24-hour morphine consumption (MD -1.93 mg, 95% CI -3.55 mg to -0.32 mg; studies = 16; participants = 1323; I2 = 49%; moderate-certainty evidence). It is uncertain if there is any difference in time to analgesic request (MD 8.51 minutes, 95% CI -31.24 minutes to 48.27 minutes; studies = 8; participants = 410; I2 = 98%; very low-certainty evidence). As with pre-emptive NSAIDs, there may be little or no difference in other opioid adverse events such as pruritus (RR 0.56, 95% CI 0.09 to 3.35; studies = 3; participants = 211; I2 = 0%; low-certainty evidence) and sedation (RR 0.84, 95% CI 0.44 to 1.63; studies = 5; participants = 497; I2 = 0%; low-certainty evidence). There is probably little or no difference in patient satisfaction (MD -0.42; 95% CI -1.09 to 0.25; studies = 1; participants = 72; moderate-certainty evidence). No study reported on chronic pain. There is probably little or no difference in time to first bowel movement (MD 0.00; 95% CI -15.99 to 15.99; studies = 1; participants = 76; moderate-certainty evidence).

Authors' conclusions: There was some evidence that pre-emptive and preventive NSAIDs reduce both pain and morphine consumption, although this was not universal for all pain and morphine consumption outcomes. Any differences found were not clinically significant, although we cannot exclude this in more painful operations. Moreover, without any evidence of reductions in opioid adverse effects, the clinical significance of these results is questionable although few studies reported these outcomes. Only one study reported clinically significant adverse events from NSAIDs administered before surgery and, therefore, we have very few data to assess the safety of either pre-emptive or preventive NSAIDs. Therefore, future research should aim to adhere to the highest methodology and be adequately powered to assess serious adverse events of NSAIDs and reductions in opioid adverse events.

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Conflict of interest statement

Brett Doleman: has received a grant from Association of Anaesthetists of Great Britain and Ireland (AAGBI) for a randomized controlled trial of pre‐emptive paracetamol (ongoing) and has previously undertaken a meta‐analysis of pre‐emptive paracetamol (Doleman 2015b).

John P Williams: has received a grant from AAGBI for a randomized controlled trial of pre‐emptive paracetamol (ongoing) and has previously undertaken a meta‐analysis of pre‐emptive paracetamol (Doleman 2015b).

Jon Lund: has received a grant from AAGBI for a randomized controlled trial of pre‐emptive paracetamol (ongoing) and has previously undertaken a meta‐analysis of pre‐emptive paracetamol (Doleman 2015b).

Jo Leonardi‐Bee: no declarations of interest in relation to this review

Thomas Heinink: no declarations of interest

Hannah Boyd‐Carson: no declarations of interest

Laura Carrick: no declarations of interest

Rahil Mandalia: no declarations of interest

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
4
4
Funnel plot with mean difference on the X‐axis and inverse sample size on the Y‐axis for pre‐emptive early acute postoperative pain
5
5
Subgroup analysis for pre‐emptive early postoperative pain (NSAID versus COX‐2 inhibitor)
6
6
Subgroup analysis for pre‐emptive early postoperative pain (baseline pain level). Subgroups are 1 (mild), 2 (moderate) and 3 (severe)
7
7
Funnel plot with mean difference on the X‐axis and inverse sample size on the Y‐axis for pre‐emptive late acute postoperative pain
8
8
Subgroup analysis for pre‐emptive late postoperative pain (NSAID versus COX‐2 inhibitor)
9
9
Subgroup analysis for pre‐emptive late postoperative pain (baseline pain). Subgroups are 1 (mild) and 2 (moderate)
10
10
Funnel plot with mean difference on the X‐axis and inverse sample size on the Y‐axis for pre‐emptive 24‐hour morphine consumption
11
11
Subgroup analysis for pre‐emptive 24‐hour morphine consumption (NSAID versus COX‐2)
12
12
Subgroup analysis for pre‐emptive 24‐hour morphine consumption (baseline consumption). Subgroups are 1 (low), 2 (medium) and 3 (high)
13
13
Funnel plot with mean difference on the X‐axis and inverse sample size on the Y‐axis for pre‐emptive time to analgesic request
14
14
Subgroup analysis for pre‐emptive pruritus (NSAID versus COX‐2). Effect estimate presented as log risk ratio
15
15
Subgroup analysis for pre‐emptive sedation (NSAID versus COX‐2). Effect estimate is log risk ratio
16
16
Funnel plot with mean difference on the X‐axis and inverse sample size on the Y‐axis for preventive early acute postoperative pain
17
17
Subgroup analysis for preventive early postoperative pain (NSAID versus COX‐2)
18
18
Subgroup analysis for preventive early postoperative pain (baseline pain). Subgroups are 1 (mild), 2 (moderate) and 3 (severe)
19
19
Subgroup analysis for preventive late nausea and vomiting (NSAID versus COX‐2)
20
20
Funnel plot with mean difference on the X‐axis and inverse sample size on the Y‐axis for preventive late acute postoperative pain
21
21
Subgroup analysis for preventive late postoperative pain (NSAID versus COX‐2)
22
22
Subgroup analysis for preventive late postoperative pain (baseline pain). Subgroups are 1 (mild) and 2 (moderate)
23
23
Funnel plot with mean difference on the X‐axis and inverse sample size on the Y‐axis for preventive 24‐hour morphine consumption
24
24
Subgroup analysis for preventive 24‐hour morphine consumption (NSAID versus COX‐2)
25
25
Subgroup analysis for 24‐hour morphine consumption (baseline morphine consumption). Subgroups are 1 (low) and 2 (medium)
26
26
Subgroup analysis for preventive time to analgesic request (NSAID versus COX‐2)
27
27
Subgroup analysis for preventive sedation (NSAID versus COX‐2). Effect estimate is log risk ratio
1.1
1.1. Analysis
Comparison 1: Pre‐emptive NSAIDS/COX‐2 inhibitors versus post‐incision NSAIDS/COX‐2 inhibitors, Outcome 1: Early acute postoperative pain (within 6 hours postoperatively)
1.2
1.2. Analysis
Comparison 1: Pre‐emptive NSAIDS/COX‐2 inhibitors versus post‐incision NSAIDS/COX‐2 inhibitors, Outcome 2: Nausea and vomiting (short‐term)
1.3
1.3. Analysis
Comparison 1: Pre‐emptive NSAIDS/COX‐2 inhibitors versus post‐incision NSAIDS/COX‐2 inhibitors, Outcome 3: Nausea and vomiting (long‐term)
1.4
1.4. Analysis
Comparison 1: Pre‐emptive NSAIDS/COX‐2 inhibitors versus post‐incision NSAIDS/COX‐2 inhibitors, Outcome 4: Late acute postoperative pain (24‐48 hours postoperatively)
1.5
1.5. Analysis
Comparison 1: Pre‐emptive NSAIDS/COX‐2 inhibitors versus post‐incision NSAIDS/COX‐2 inhibitors, Outcome 5: 24‐hour morphine consumption (mg)
1.6
1.6. Analysis
Comparison 1: Pre‐emptive NSAIDS/COX‐2 inhibitors versus post‐incision NSAIDS/COX‐2 inhibitors, Outcome 6: Time to first analgesic request (minutes)
1.7
1.7. Analysis
Comparison 1: Pre‐emptive NSAIDS/COX‐2 inhibitors versus post‐incision NSAIDS/COX‐2 inhibitors, Outcome 7: Pruritus (long‐term)
1.8
1.8. Analysis
Comparison 1: Pre‐emptive NSAIDS/COX‐2 inhibitors versus post‐incision NSAIDS/COX‐2 inhibitors, Outcome 8: Sedation (long‐term)
2.1
2.1. Analysis
Comparison 2: Preventive NSAIDS/COX‐2 inhibitors versus post‐incision NSAIDS/COX‐2 inhibitors, Outcome 1: Early acute postoperative pain (within 6 hours postoperatively)
2.2
2.2. Analysis
Comparison 2: Preventive NSAIDS/COX‐2 inhibitors versus post‐incision NSAIDS/COX‐2 inhibitors, Outcome 2: Re‐operation for bleeding
2.3
2.3. Analysis
Comparison 2: Preventive NSAIDS/COX‐2 inhibitors versus post‐incision NSAIDS/COX‐2 inhibitors, Outcome 3: Nausea and vomiting (short‐term)
2.4
2.4. Analysis
Comparison 2: Preventive NSAIDS/COX‐2 inhibitors versus post‐incision NSAIDS/COX‐2 inhibitors, Outcome 4: Nausea and vomiting (long‐term)
2.5
2.5. Analysis
Comparison 2: Preventive NSAIDS/COX‐2 inhibitors versus post‐incision NSAIDS/COX‐2 inhibitors, Outcome 5: Late acute postoperative pain (24‐48 hours postoperatively)
2.6
2.6. Analysis
Comparison 2: Preventive NSAIDS/COX‐2 inhibitors versus post‐incision NSAIDS/COX‐2 inhibitors, Outcome 6: 24‐hour morphine consumption (mg)
2.7
2.7. Analysis
Comparison 2: Preventive NSAIDS/COX‐2 inhibitors versus post‐incision NSAIDS/COX‐2 inhibitors, Outcome 7: Time to first analgesic request (minutes)
2.8
2.8. Analysis
Comparison 2: Preventive NSAIDS/COX‐2 inhibitors versus post‐incision NSAIDS/COX‐2 inhibitors, Outcome 8: Pruritus (long‐term)
2.9
2.9. Analysis
Comparison 2: Preventive NSAIDS/COX‐2 inhibitors versus post‐incision NSAIDS/COX‐2 inhibitors, Outcome 9: Sedation (long‐term)
2.10
2.10. Analysis
Comparison 2: Preventive NSAIDS/COX‐2 inhibitors versus post‐incision NSAIDS/COX‐2 inhibitors, Outcome 10: Patient satisfaction
2.11
2.11. Analysis
Comparison 2: Preventive NSAIDS/COX‐2 inhibitors versus post‐incision NSAIDS/COX‐2 inhibitors, Outcome 11: Time to bowel movement (hours)
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Peduto 1995 {published data only}
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Priya 2002 {published data only}
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Riest 2006 {published data only}
    1. Riest G, Peters J, Weiss M, Pospiech J, Hoffmann O, Neuhauser M, et al. Does perioperative administration of rofecoxib improve analgesia after spine, breast and orthopaedic surgery? European Journal of Anaesthesiology 2006;23(3):219-26. [PMID: ] - PubMed
Riest 2008 {published data only}
    1. Riest G, Peters J, Weiss M, Dreyer S, Klassen PD, Stegen B, et al. Preventive effects of perioperative parecoxib on post-discectomy pain. British Journal of Anaesthesia 2008;100(2):256-62. [PMID: ] - PubMed
Rogers 1995 {published data only}
    1. Rogers JEG, Fleming BG, Macintosh KC, Johnston B, Morgan-Hughes JO. Effect of timing of ketorolac administration on patient-controlled opioid use. British Journal of Anaesthesia 1995;75(1):15-8. [PMID: ] - PubMed
Salonen 2001 {published data only}
    1. Salonen A, Kokki H, Tuovinen K. IV ketoprofen for analgesia after tonsillectomy: comparison of pre- and post-operative administration. British Journal of Anaesthesia 2001;86(3):377-81. [PMID: ] - PubMed
Sandin 1993 {published data only}
    1. Sandin R, Sternlo JE, Stam H, Brodd B, Bjorkman R. Diclofenac for pain relief after arthroscopy: a comparison of early and delayed treatment. Acta Anaesthesiologica Scandinavica 1993;37(8):747-50. [PMID: ] - PubMed
Shuying 2014 {published data only}
    1. Shuying L, Xiao W, Peng L, Tao Z, Ziying L, Liang Z. Preoperative intravenous parecoxib reduces length of stay on ambulatory laparoscopic cholecystectomy. International Journal Of Surgery 2014;12(5):464-8. [PMID: ] - PubMed
Sun 2008 {published data only}
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Trampitsch 2003 {published data only}
    1. Trampitsch E, Pipam W, Moertl M, Sadjak A, Dorn C, Sittl R, et al. Preemptive randomized, double-blind study with lornoxicam in gynecological surgery. Der Schmerz 2003;17(1):4-10. [PMID: ] - PubMed
Vanlersberghe 1996 {published data only}
    1. Vanlersberghe C, Lauwers MH, Camu F. Preoperative ketorolac administration has no preemptive analgesic effect for minor orthopaedic surgery. Acta Anaesthesiologica Scandinavica 1996;40(8 Pt 1):948-52. [PMID: ] - PubMed
Vijayendra 1998 {published data only}
    1. Vijayendra HS, Bhardwaj N, Bala I, Chari P. Pre-emptive analgesic effect of intravenous ketorolac tromethamine in patients undergoing orthopaedic surgery. Journal of Anaesthesiology Clinical Pharmacology 1998;14:125-7.
Vogol 1992 {published data only}
    1. Vogel RI, Desjardins PJ, Major KV. Comparison of presurgical and immediate postsurgical ibuprofen on postoperative periodontal pain. Journal of Periodontology 1992;63(11):914-8. [PMID: ] - PubMed
Wang 2010 {published data only}
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Wnek 2004 {published data only}
    1. Wnek W, Zajaczkowska R, Wordliczek J, Dobrogowski J, Korbut R. Influence of pre-operative ketoprofen administration (preemptive analgesia) on analgesic requirement and the level of prostaglandins in the early postoperative period. Polish Journal of Pharmacology 2004;56:547-52. [PMID: ] - PubMed
Yagar 2011 {published data only}
    1. Yağar S, Turan SK, Ayık İ, Güçlü ÇY, Koç M, Kantaroğlu S, et al. Comparative study of pre-emptive and postoperative IV tenoxicam in laparoscopic cholecystectomy. Journal of the Turkish Anaesthesiology & Intensive Care Society 2011;39:19-24.
Yamashita 2006 {published data only}
    1. Yamashita K, Fukusaki M, Ando Y, Fujinaga A, Tanabe T. Preoperative administration of intravenous flurbiprofen axetil reduces postoperative pain for spinal fusion surgery. Journal of Anesthesia 2006;20(2):92-5. [PMID: ] - PubMed
Yan 2004 {published data only}
    1. Yan XB, Wang MA, Ouyang W, Wang XW, Shui Y. Timing of lornoxicam administration in relation to its postoperative analgesic effects. Chinese Journal of Clinical Rehabilitation 2004;8(11):2180-1.
Young 2006 {published data only}
    1. Young AN, Taylor RW, Buschang PH, Taylor SE, Linnebur SA. Evaluation of preemptive valdecoxib therapy on initial archwire placement discomfort in adults. Angle Orthodontist 2006;76(2):251-9. [PMID: ] - PubMed
Yuan 2019 {published data only}
    1. Yuan Y, Cui D, Zhang Y. Preemptive meloxicam achieves a better effect on postoperative pain control and similar tolerance compared with postoperative meloxicam in patients receiving arthroscopic knee surgery. Inflammopharmacology 2019;27(6):1091-1100. [PMID: ] - PubMed
Yuswono 2014 {published data only}
    1. Yuswono AR, Maskoen TT, Fuadi I. Comparison of pre-operative and post-operative intravenous 40 mg parecoxib NA in gynecologic laparatomy surgery post-operative pain management. Jurnal Anestesi Perioperatif 2014;2:169-73.
Zhang 2011 {published data only}
    1. Zhang Z, Zhao H, Wang C, Han F, Wang G. Lack of preemptive analgesia by intravenous flurbiprofen in thyroid gland surgery: a randomized, double-blind and placebo-controlled clinical trial. International Journal of Medical Sciences 2011;8(5):433-8. [PMID: ] - PMC - PubMed
Zhang 2017 {published data only}
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Zhou 2017 {published data only (unpublished sought but not used)}
    1. Zhou F, Du Y, Huang W, Shan J, Xu G. The efficacy and safety of early initiation of preoperative analgesia with celecoxib in patients underwent arthroscopic knee surgery. Medicine 2017;96(42):e8234. [PMID: ] - PMC - PubMed
Zhou 2019 {published data only}
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References to studies excluded from this review

Bridgman 1996 {published data only}
    1. Bridgman JB, Gillgrass TG, Zacharias M. The absence of any pre-emptive analgesic effect for non-steroidal anti-inflammatory drugs. British Journal of Oral and Maxillofacial Surgery 1996;34(5):428-31. [PMID: ] - PubMed
Castiglione 1997 {published data only}
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Hill 1987 {published data only}
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Hou 2019 {published data only}
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Jung 2003 {published data only}
    1. Jung YS, Kim MK, Park HS, Lee EW, Kang JW. A study on efficacy of preemptive analgesia: a comparison on efficacy of preoperative and postoperative analgesic administration. Journal of the Korean Dental Society of Anesthesiology 2003;3:10-8. [DOI: 10.17245/jkdsa.2003.3.1.10] - DOI
Jung 2005 {published data only}
    1. Jung YS, Kim MK, Um YJ, Park HS, Lee EW. The effects on postoperative oral surgery pain by varying NSAID administration times: comparison on effect of preemptive analgesia. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology 2005;100(5):559-63. [PMID: ] - PubMed
Lau 2009 {published data only}
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Liu 1997 {published data only}
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Liu 2018 {published data only}
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Nelson 1993 {published data only}
    1. Nelson WE, Henderson RC, Almekinders LC, DeMasi RA, Taft TN. An evaluation of pre- and postoperative nonsteroidal antiinflammatory drugs in patients undergoing knee arthroscopy. A prospective, randomized, double-blinded study. American Journal of Sports Medicine 1993;21:510-6. [PMID: ] - PubMed
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Ramirez 2009 {published data only}
    1. Ramírez V, Petuel N. Preventive Analgesia with Ketorolac in Patients Subject to Obstruction of Bilateral Tubes with Local Anaesthesia and Sedation [Thesis]. 2009.
Rosaeg 2001 {published data only}
    1. Rosaeg OP, Krepski B, Cicutti N, Dennehy KC, Lui AC, Johnson DH. Effect of preemptive multimodal analgesia for arthroscopic knee ligament repair. Regional Anesthesia and Pain Medicine 2001;26(2):125-30. [PMID: ] - PubMed
Sai 2001 {published data only}
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Settecase 2002 {published data only}
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Turaga 2008 {published data only}
    1. Turaga K, Wright A, Lee R, Dias WP, Destache C, Christian R, et al. A randomized trial of the peri-operative use of COX-2 inhibitors in Lichtenstein herniorrhaphy. Hernia 2008;12(5):515-9. [PMID: ] - PubMed
Wuolijoki 1987 {published data only}
    1. Wuolijoki E, Oikarinen VJ, Ylipaavalniemi P, Hampf G, Tolvanen M. Effective postoperative pain control by preoperative injection of diclofenac. European Journal of Clinical Pharmacology 1987;32(3):249-52. [PMID: ] - PubMed
Zhu 2020 {published data only}
    1. Zhu X. Efficacy of preemptive analgesia versus postoperative analgesia of celecoxib on postoperative pain, patients' global assessment and hip function recovery in femoroacetabular impingement patients underwent hip arthroscopy surgery. Inflammopharmacology 2020;28(1):131-7. [PMID: ] - PMC - PubMed
Zor 2014 {published data only}
    1. Zor ZF, Cetiner S, Isik B. Efficacy of preemptive lornoxicam on postoperative analgesia after surgical removal of mandibular third molars. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology 2014;117(1):27-31. [PMID: ] - PubMed

References to studies awaiting assessment

Aoki 2002 {published data only}
    1. Aoki H, Satomoto M, Yamada S, Adachi Y, Higuchi H, Umeda E, et al. The effectiveness of perioperative intravenous flurbiprofen in minor ear, neck and nose surgery. Masui - Japanese Journal of Anesthesiology 2002;51(8):857-61. [PMID: ] - PubMed
Bai 1998 {published data only (unpublished sought but not used)}
    1. Bai SJ, Nam SH, Lee YW, Nam YT, Kim WJ. The effects of preemptive intravenous ketorolac for total hip replacement patients. Korean Journal of Anesthesiology 1998;35:511-7. [DOI: ]
Beg 2001 {published data only}
    1. Beg AK, Runi FM, Iqbal KM, Ahmed S. Comparison of intravenous ketorolac tromethamine and intravenous pethedine hydrochloride in patients undergoing abdominal hysterectomy: an analysis of pre-emptive analgesic effect. Bangladesh Journal of Obstetrics and Gynecology 2001;16:22-6.
Belzarena 1994 {published data only}
    1. Belzarena SD. Prevention of postoperative pain after abdominal dermolipectomy with intravenous tenoxicam. Revista Brasileira de Anestesiologia 1994;44:103-7.
De Oliveira 1999 {published data only}
    1. De Oliveira JCC, Fenner Lyra Junior H, De Oliveira Filho GR, Dos Santos JM, Felicio F. Comparison between preoperative and postoperative tenoxican in hemorrhoidectomies. Revista Brasileira de Anestesiologia 1999;49:169-72.
Jia 2011 {published data only (unpublished sought but not used)}
    1. Jia DL, Han B, Wang J, Zhang LP, Guo XY. Application of parecoxib for postoperative analgesia in arthroscopic surgery of the knee. Chinese Journal of New Drugs 2011;20:440-3.
Nicholson 2014 {published data only}
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References to other published versions of this review

Doleman 2018b
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