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Meta-Analysis
. 2016 May 23;2016(5):CD007126.
doi: 10.1002/14651858.CD007126.pub3.

Single dose intravenous paracetamol or intravenous propacetamol for postoperative pain

Ewan D McNicol  1 , McKenzie C Ferguson, Simon Haroutounian, Daniel B Carr, Roman Schumann
Affiliations
Meta-Analysis

Single dose intravenous paracetamol or intravenous propacetamol for postoperative pain

Ewan D McNicol et al. Cochrane Database Syst Rev. .

Abstract

Background: This is an updated version of the original Cochrane review published in Issue 10, 2011. Paracetamol (acetaminophen) is the most commonly prescribed analgesic for the treatment of acute pain. It may be administered orally, rectally, or intravenously. The efficacy and safety of intravenous (IV) formulations of paracetamol, IV paracetamol, and IV propacetamol (a prodrug that is metabolized to paracetamol), compared with placebo and other analgesics, is unclear.

Objectives: To assess the efficacy and safety of IV formulations of paracetamol for the treatment of postoperative pain in both adults and children.

Search methods: We ran the search for the previous review in May 2010. For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 1), MEDLINE (May 2010 to 16 February 2016), EMBASE (May 2010 to 16 February 2016), LILACS (2010 to 2016), a clinical trials registry, and reference lists of reviews for randomized controlled trials (RCTs) in any language and we retrieved articles.

Selection criteria: Randomized, double-blind, placebo- or active-controlled single dose clinical trials of IV paracetamol or IV propacetamol for acute postoperative pain in adults or children.

Data collection and analysis: Two review authors independently extracted data, which included demographic variables, type of surgery, interventions, efficacy, and adverse events. We contacted study authors for additional information. We graded each included study for methodological quality by assessing risk of bias and employed the GRADE approach to assess the overall quality of the evidence.

Main results: We included 75 studies (36 from the original review and 39 from our updated review) enrolling a total of 7200 participants.Among primary outcomes, 36% of participants receiving IV paracetamol/propacetamol experienced at least 50% pain relief over four hours compared with 16% of those receiving placebo (number needed to treat to benefit (NNT) = 5; 95% confidence interval (CI) 3.7 to 5.6, high quality evidence). The proportion of participants in IV paracetamol/propacetamol groups experiencing at least 50% pain relief diminished over six hours, as reflected in a higher NNT of 6 (4.6 to 7.1, moderate quality evidence). Mean pain intensity at four hours was similar when comparing IV paracetamol and placebo, but was seven points lower on a 0 to 100 visual analog scale (0 = no pain, 100 = worst pain imaginable, 95% CI -9 to -6, low quality evidence) in those receiving paracetamol at six hours.For secondary outcomes, participants receiving IV paracetamol/propacetamol required 26% less opioid over four hours and 16% less over six hours (moderate quality evidence) than those receiving placebo. However, this did not translate to a clinically meaningful reduction in opioid-induced adverse events.Meta-analysis of efficacy comparisons between IV paracetamol/propacetamol and active comparators (e.g., opioids or nonsteroidal anti-inflammatory drugs) were either not statistically significant, not clinically significant, or both.Adverse events occurred at similar rates with IV paracetamol or IV propacetamol and placebo. However, pain on infusion occurred more frequently in those receiving IV propacetamol versus placebo (23% versus 1%). Meta-analysis did not demonstrate clinically meaningful differences between IV paracetamol/propacetamol and active comparators for any adverse event.

Authors' conclusions: Since the last version of this review, we have found 39 new studies providing additional information. Most included studies evaluated adults only. We reanalyzed the data but the results did not substantially alter any of our previously published conclusions. This review provides high quality evidence that a single dose of either IV paracetamol or IV propacetamol provides around four hours of effective analgesia for about 36% of patients with acute postoperative pain. Low to very low quality evidence demonstrates that both formulations are associated with few adverse events, although patients receiving IV propacetamol have a higher incidence of pain on infusion than both placebo and IV paracetamol.

PubMed Disclaimer

Conflict of interest statement

EM: none known.

MF: none known. Prior to initial planning and conception of this review update, the institution at which MF is employed received payment for fee‐for‐service activities from Mallinckrodt Pharmaceuticals, which produces paracetamol/acetaminophen.

SH: none known.

DC: none known.

RS: none known.

Figures

1
1
2016 Study flow diagram.
2
2
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
4
4
Forest plot of comparison: 1 Number of participants with > 50% pain relief over 4 hours, outcome: 1.1 Propacetamol or paracetamol versus placebo.
5
5
Forest plot of comparison: 2 Number of participants with > 50% pain relief over 6 hours, outcome: 2.1 Propacetamol or paracetamol versus placebo.
6
6
Forest plot of comparison: 15 Pain on infusion, outcome: 15.3 Propacetamol versus paracetamol.
1.1
1.1. Analysis
Comparison 1 Number of participants with > 50% pain relief over 4 hours, Outcome 1 Paracetamol or propacetamol vs placebo.
1.2
1.2. Analysis
Comparison 1 Number of participants with > 50% pain relief over 4 hours, Outcome 2 Paracetamol or propacetamol vs NSAIDs.
1.3
1.3. Analysis
Comparison 1 Number of participants with > 50% pain relief over 4 hours, Outcome 3 Propacetamol vs opioids.
1.4
1.4. Analysis
Comparison 1 Number of participants with > 50% pain relief over 4 hours, Outcome 4 Paracetamol vs propacetamol.
2.1
2.1. Analysis
Comparison 2 Number of participants with > 50% pain relief over 6 hours, Outcome 1 Paracetamol or propacetamol vs placebo.
2.2
2.2. Analysis
Comparison 2 Number of participants with > 50% pain relief over 6 hours, Outcome 2 Paracetamol or propacetamol vs NSAIDs.
2.3
2.3. Analysis
Comparison 2 Number of participants with > 50% pain relief over 6 hours, Outcome 3 Propacetamol vs opioids.
2.4
2.4. Analysis
Comparison 2 Number of participants with > 50% pain relief over 6 hours, Outcome 4 Paracetamol vs propacetamol.
3.1
3.1. Analysis
Comparison 3 Pain intensity at 4 h, Outcome 1 Paracetamol vs placebo.
3.2
3.2. Analysis
Comparison 3 Pain intensity at 4 h, Outcome 2 Paracetamol vs NSAIDs.
3.4
3.4. Analysis
Comparison 3 Pain intensity at 4 h, Outcome 4 Paracetamol vs ketamine.
4.1
4.1. Analysis
Comparison 4 Pain intensity at 6 h, Outcome 1 Paracetamol vs placebo.
4.2
4.2. Analysis
Comparison 4 Pain intensity at 6 h, Outcome 2 Paracetamol vs NSAIDs.
4.3
4.3. Analysis
Comparison 4 Pain intensity at 6 h, Outcome 3 Paracetamol vs opioids.
4.4
4.4. Analysis
Comparison 4 Pain intensity at 6 h, Outcome 4 Paracetamol vs ketamine.
5.1
5.1. Analysis
Comparison 5 Number of participants requiring rescue medication, Outcome 1 Paracetamol or propacetamol vs placebo.
5.2
5.2. Analysis
Comparison 5 Number of participants requiring rescue medication, Outcome 2 Paracetamol or propacetamol vs NSAIDs.
5.3
5.3. Analysis
Comparison 5 Number of participants requiring rescue medication, Outcome 3 Propacetamol vs opioids.
5.4
5.4. Analysis
Comparison 5 Number of participants requiring rescue medication, Outcome 4 Paracetamol vs propacetamol.
6.1
6.1. Analysis
Comparison 6 Time to rescue medication (minutes), Outcome 1 Paracetamol or propacetamol vs placebo.
6.2
6.2. Analysis
Comparison 6 Time to rescue medication (minutes), Outcome 2 Paracetamol vs NSAIDs.
7.1
7.1. Analysis
Comparison 7 Opioid consumption (IV morphine equivalents) over 4 hours, Outcome 1 Paracetamol or propacetamol vs placebo.
7.2
7.2. Analysis
Comparison 7 Opioid consumption (IV morphine equivalents) over 4 hours, Outcome 2 Paracetamol or propacetamol vs NSAIDs.
7.3
7.3. Analysis
Comparison 7 Opioid consumption (IV morphine equivalents) over 4 hours, Outcome 3 Propacetamol vs opioids.
8.1
8.1. Analysis
Comparison 8 Opioid consumption (IV morphine equivalents) over 6 hours, Outcome 1 Paracetamol or propacetamol vs placebo.
8.2
8.2. Analysis
Comparison 8 Opioid consumption (IV morphine equivalents) over 6 hours, Outcome 2 Paracetamol or propacetamol vs NSAIDs.
8.3
8.3. Analysis
Comparison 8 Opioid consumption (IV morphine equivalents) over 6 hours, Outcome 3 Propacetamol vs opioids.
8.4
8.4. Analysis
Comparison 8 Opioid consumption (IV morphine equivalents) over 6 hours, Outcome 4 Paracetamol vs propacetamol.
9.1
9.1. Analysis
Comparison 9 Global evaluation rated as good/satisfied or excellent/very satisfied, Outcome 1 Paracetamol or propacetamol vs placebo.
9.2
9.2. Analysis
Comparison 9 Global evaluation rated as good/satisfied or excellent/very satisfied, Outcome 2 Paracetamol or propacetamol vs NSAIDs.
9.3
9.3. Analysis
Comparison 9 Global evaluation rated as good/satisfied or excellent/very satisfied, Outcome 3 Propacetamol vs opioids.
9.4
9.4. Analysis
Comparison 9 Global evaluation rated as good/satisfied or excellent/very satisfied, Outcome 4 Paracetamol vs propacetamol.
10.1
10.1. Analysis
Comparison 10 Global evaluation using a numerical rating scale (0 to 10), Outcome 1 Paracetamol or propacetamol vs placebo.
10.2
10.2. Analysis
Comparison 10 Global evaluation using a numerical rating scale (0 to 10), Outcome 2 Paracetamol vs NSAIDs.
10.3
10.3. Analysis
Comparison 10 Global evaluation using a numerical rating scale (0 to 10), Outcome 3 Propacetamol vs opioids.
11.1
11.1. Analysis
Comparison 11 Number of participants with adverse events, Outcome 1 Paracetamol or propacetamol vs placebo.
11.2
11.2. Analysis
Comparison 11 Number of participants with adverse events, Outcome 2 Paracetamol or propacetamol vs NSAIDs.
11.3
11.3. Analysis
Comparison 11 Number of participants with adverse events, Outcome 3 Propacetamol vs opioids.
12.1
12.1. Analysis
Comparison 12 Number of participants with serious adverse events, Outcome 1 Paracetamol or propacetamol vs placebo.
12.2
12.2. Analysis
Comparison 12 Number of participants with serious adverse events, Outcome 2 Paracetamol or propacetamol vs NSAIDs.
12.3
12.3. Analysis
Comparison 12 Number of participants with serious adverse events, Outcome 3 Paracetamol or propacetamol vs opioids.
13.1
13.1. Analysis
Comparison 13 Number of participants withdrawing due to adverse events, Outcome 1 Paracetamol or propacetamol vs placebo.
13.2
13.2. Analysis
Comparison 13 Number of participants withdrawing due to adverse events, Outcome 2 Paracetamol or propacetamol vs NSAIDs.
13.3
13.3. Analysis
Comparison 13 Number of participants withdrawing due to adverse events, Outcome 3 Paracetamol or propacetamol vs opioids.
13.4
13.4. Analysis
Comparison 13 Number of participants withdrawing due to adverse events, Outcome 4 Paracetamol vs ketamine.
14.1
14.1. Analysis
Comparison 14 Number of participants withdrawing due to lack of efficacy, Outcome 1 Paracetamol or propacetamol vs placebo.
14.2
14.2. Analysis
Comparison 14 Number of participants withdrawing due to lack of efficacy, Outcome 2 Paracetamol or propacetamol vs NSAIDs.
14.3
14.3. Analysis
Comparison 14 Number of participants withdrawing due to lack of efficacy, Outcome 3 Paracetamol or propacetamol vs opioids.
14.4
14.4. Analysis
Comparison 14 Number of participants withdrawing due to lack of efficacy, Outcome 4 Paracetamol vs ketamine.
15.1
15.1. Analysis
Comparison 15 Number of participants with pain on infusion, Outcome 1 Paracetamol vs placebo.
15.2
15.2. Analysis
Comparison 15 Number of participants with pain on infusion, Outcome 2 Propacetamol vs placebo.
15.3
15.3. Analysis
Comparison 15 Number of participants with pain on infusion, Outcome 3 Propacetamol vs paracetamol.
16.1
16.1. Analysis
Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 1 Nausea.
16.2
16.2. Analysis
Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 2 Vomiting.
16.3
16.3. Analysis
Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 3 Nausea/vomiting.
16.4
16.4. Analysis
Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 4 Pruritus.
16.5
16.5. Analysis
Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 5 Respiratory depression.
16.6
16.6. Analysis
Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 6 Sedation.
16.7
16.7. Analysis
Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 7 Urinary retention.
16.8
16.8. Analysis
Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 8 Allergy/skin rash/local reaction.
17.1
17.1. Analysis
Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 1 Nausea.
17.2
17.2. Analysis
Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 2 Vomiting.
17.3
17.3. Analysis
Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 3 Nausea/vomiting.
17.4
17.4. Analysis
Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 4 Pruritus.
17.5
17.5. Analysis
Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 5 Respiratory depression.
17.6
17.6. Analysis
Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 6 Sedation.
17.7
17.7. Analysis
Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 7 Urinary retention.
17.8
17.8. Analysis
Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 8 Allergy/skin rash/local reaction.
18.1
18.1. Analysis
Comparison 18 Individual adverse events: paracetamol or propacetamol vs opioids, Outcome 1 Nausea.
18.2
18.2. Analysis
Comparison 18 Individual adverse events: paracetamol or propacetamol vs opioids, Outcome 2 Vomiting.
18.3
18.3. Analysis
Comparison 18 Individual adverse events: paracetamol or propacetamol vs opioids, Outcome 3 Nausea/vomiting.
18.4
18.4. Analysis
Comparison 18 Individual adverse events: paracetamol or propacetamol vs opioids, Outcome 4 Pruritus.
18.5
18.5. Analysis
Comparison 18 Individual adverse events: paracetamol or propacetamol vs opioids, Outcome 5 Respiratory depression.
18.6
18.6. Analysis
Comparison 18 Individual adverse events: paracetamol or propacetamol vs opioids, Outcome 6 Sedation.
19.1
19.1. Analysis
Comparison 19 Individual adverse events: paracetamol vs ketamine, Outcome 1 Nausea.
19.2
19.2. Analysis
Comparison 19 Individual adverse events: paracetamol vs ketamine, Outcome 2 Vomiting.
19.3
19.3. Analysis
Comparison 19 Individual adverse events: paracetamol vs ketamine, Outcome 3 Sedation.
See this image and copyright information in PMC

Update of

Comment in

References

References to studies included in this review

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    1. Lahtinen P, Kokki H, Hendolin H, Hakala T, Hynynen M. Propacetamol as adjunctive treatment for postoperative pain after cardiac surgery. Anesthesia & Analgesia 2002;95:813‐9. [12351250] - PubMed
Landwehr 2005 {published data only}
    1. Landwehr S, Kiencke P, Giesecke T, Eggert D, Thumann G, Kampe S. A comparison between IV paracetamol and IV metamizol for postoperative analgesia after retinal surgery. Current Medical Research and Opinion 2005;21:1569‐75. [PUBMED: 16238896] - PubMed
Lee 2010 {published data only}
    1. Lee SY, Lee WH, Lee EH, Han KC, Ko YK. The effects of paracetamol, ketorolac, and paracetamol plus morphine on pain control after thyroidectomy. Korean Journal of Pain 2010;23:124‐30. - PMC - PubMed
Leykin 2008 {published data only}
    1. Leykin Y, Casati A, Rapotec A, Dalsasso M, Barzan L, Fanelli G, et al. Comparison of parecoxib and proparacetamol in endoscopic nasal surgery patients. Yonsei Medical Journal 2008;49:383‐8. - PMC - PubMed
Ma 2003 {published data only}
    1. Ma EL, Wang XR, Jiang ZM, Cui Y, Wang R, Liu J. A randomized, double blind, and controlled clinical trial of the non‐addictive propacetamol in postoperative analgesia. Zhongguo Yi Xue Ke Xue Yuan Xue Bao [Acta Acadamiae Medicinae Sinicae] 2003;25:329‐32. [PUBMED: 12905750 ] - PubMed
Maghsoudi 2014 {published data only}
    1. Maghsoudi R, Etemadian M, Lotfi SMT, Movasagi G, Amjadi M. Opioid sparing effects of intravenous paracetamol after PCNL: a randomized double blinded clinical trial. Journal of Endourology 2012;26:A354. - PubMed
    1. Maghsoudi R, Tabatabai M, Radfar MH, Movasagi G, Etemadian M, Shati M, et al. Opioid‐sparing effect of intravenous paracetamol after percutaneous nephrolithotomy: a double‐blind randomized controlled trial. Journal of Endourology 2014;28:23‐7. - PubMed
Marty 2005 {published data only}
    1. Marty J, Benhamou D, Chassard D, Empairaire N, Roche A, Mayaud A, et al. Effects of single‐dose injectable paracetamol versus propacetamol in pain management after minor gynecologic surgery: a multicenter, randomized, double‐blind, active‐controlled, two‐parallel‐group study. Current Therapeutic Research 2005;66:294‐306. - PMC - PubMed
Mimoz 2001 {published data only}
    1. Mimoz O, Incagnoli P, Gillon MC, Kuhlman L, Mirand A, Soilleux H, et al. Analgesic efficacy and safety of nefopam vs. propacetamol following hepatic resection. Anaesthesia 2001;51:520‐5. - PubMed
Mitra 2012 {published data only}
    1. Mitra S, Khandelwal P, Sehgal A. Diclofenac‐tramadol vs. diclofenac‐acetaminophen combinations for pain relief after caesarean section. Acta Anaesthesiologica Scandinavica 2012;56:706‐11. - PubMed
Moller 2005a {published data only}
    1. Moller PL, Juhl GI, Payen‐Champenois C, Skoglund LA. Intravenous acetaminophen (paracetamol): comparable analgesic efficacy, but better local safety than its prodrug, propacetamol, for postoperative pain after third molar surgery. Anesthesia & Analgesia 2005;101:90‐6. - PubMed
Moller 2005b {published data only}
    1. Moller PL, Sindet‐Pedersen S, Petersen CT, Juhl GI, Dillenschneider A, Skoglund LA. Onset of acetaminophen analgesia: comparison of oral and intravenous routes after third molar surgery. British Journal of Anaesthesia 2005;94:642‐8. - PubMed
Mowafi 2012 {published data only}
    1. Mowafi HA, Elmakarim EA, Ismail S, Al‐Mahdy M, El‐Saflan AE, Elsaid AS. Intravenous lornoxicam is more effective than paracetamol as a supplemental analgesic after lower abdominal surgery: a randomized controlled trial. World Journal of Surgery 2012;36:2039‐44. - PubMed
Ohnesorge 2009 {published data only}
    1. Ohnesorge H, Bein B, Hanss R, Francksen H, Mayer L, Scholz J, et al. Paracetamol versus metamizol in the treatment of postoperative pain after breast surgery: a randomized, controlled trial. European Journal of Anaesthesiology 2009;26:648‐53. - PubMed
Omar 2011 {published data only}
    1. Omar AAA, Al Issa KA. Intravenous paracetamol (Perfalgan) for analgesia after cesarean section: a double‐blind randomized controlled study. Rawal Medical Journal 2011;36:1‐12.
Oncul 2011 {published data only}
    1. Oncul AM, Cimen E, Kucukyavuz Z, Cambazoglu M. Postoperative analgesia in orthognathic surgery patients: diclofenac sodium or paracetamol?. British Journal of Oral & Maxillofacial Surgery 2011;49:138‐41. - PubMed
Oreskovic 2014 {published data only}
    1. Oreskovic Z, Bicanic G, Hrabac P, Tripkovic B, Delimar D. Treatment of postoperative pain after total hip arthroplasty: comparison between metamizol and paracetamol as adjunctive to opioid analgesics ‐ Prospective, double‐blind, randomised study. Archives of Orthopaedic & Trauma Surgery 2014;134:631‐6. - PubMed
Paech 2014 {published data only}
    1. Paech MJ, McDonnell NJ, Sinha A, Baber C, Nathan EA. A randomised controlled trial of parecoxib, celecoxib and paracetamol as adjuncts to patient‐controlled epidural analgesia after caesarean delivery. Anaesthesia & Intensive Care 2014;42:15‐22. - PubMed
Peduto 1998 {published data only}
    1. Peduto VA, Ballabio M, Stefanini S. Efficacy of propacetamol in the treatment of postoperative pain. Morphine‐sparing effect in orthopedic surgery. Italian Collaborative Group on Propacetamol. Acta Anaesthesiologica Scandinavica 1998;42:293‐8. [PUBMED: 9542555] - PubMed
Salonen 2009 {published data only}
    1. Salonen A, Silvola J, Kokki H. Does 1 or 2 g paracetamol added to ketoprofen enhance analgesia in adult tonsillectomy patients?. Acta Anaesthesiologica Scandinavica 2009;53:1200‐6. - PubMed
Sanyal 2014 {published data only}
    1. Sanyal P, Pal A, Biswas J, Mukhopadhyay P, Dasgupta S, Das SH. Choice of non‐opioid analgesics for postoperative analgesia in patients undergoing lower abdominal gynecological surgeries. BJOG: An International Journal of Obstetrics and Gynaecology 2014;121:189.
Shimia 2014 {published data only}
    1. Shimia M, Parish M, Abedini N. The effect of intravenous paracetamol on postoperative pain after lumbar discectomy. Asian Spine Journal 2014;8:400‐4. - PMC - PubMed
Siddik 2001 {published data only}
    1. Siddik SM, Aouad MT, Jalbout MI, Rizk LB, Kamar GH, Baraka AS. Diclofenac and/or propacetamol for postoperative pain management after cesarean delivery in patients receiving patient controlled analgesia morphine. Regional Anesthesia and Pain Medicine 2001;26:310‐5. - PubMed
Sinatra 2005 {published data only}
    1. Sinatra RS, Jahr JS, Reynolds L, Groudine SB, Royal MA, Breitmeyer JB, et al. Intravenous acetaminophen for pain after major orthopedic surgery: an expanded analysis. Pain Practice 2012;12:357‐65. - PubMed
    1. Sinatra RS, Jahr JS, Reynolds LW, Viscusi ER, Groudine SB, Payen‐Champenois C. Efficacy and safety of single and repeated administration of 1 gram intravenous acetaminophen injection (paracetamol) for pain management after major orthopedic surgery. Anesthesiology 2005;102:822‐31. [PUBMED: 15791113] - PubMed
Tiippana 2008 {published data only}
    1. Tiippana E, Bachmann M, Kalso E, Pere P. Effect of paracetamol and coxib with or without dexamethasone after laparoscopic cholecystectomy. Acta Anaesthesiologica Scandinavica 2008;52:673‐80. - PubMed
Togrul 2011 {published data only}
    1. Togrul T, Baysal Yildirim Z, Cengiz M, Cigdem A, San I, Kar M. Comparison of intravenous paracetamol and tramadol for postoperative analgesia in patients with septo‐rhinoplasty. Anestezi Dergisi 2011;19:213‐6.
Tunali 2013 {published data only}
    1. Tunali Y, Akcil EF, Dilmen OK, Tutuncu AC, Koksal GM, Akbas S, et al. Efficacy of intravenous paracetamol and dexketoprofen on postoperative pain and morphine consumption after a lumbar disk surgery. Journal of Neurosurgical Anesthesiology 2013;25:143‐7. - PubMed
Tuncel 2012 {published data only}
    1. Tuncel A, Balci M, Postaci A, Aslan Y, Koseoglu E, Sacan O, et al. Comparison of intraoperative local levobupivacaine infiltraton anaesthesia, intravenous paracetamol and lornoxicam treatments for postoperative pain management in patients underwent transperitoneal laparoscopic renal and adrenal surgery. Journal of Endourology 2012;26:A287.
Unal 2013 {published data only}
    1. Unal C, Cakan T, Baltaci B, Basar H. Comparison of analgesic efficacy of intravenous paracetamol and intravenous dexketoprofen trometamol in multimodal analgesia after hysterectomy. Journal of Research in Medical Sciences 2013;18:897‐903. - PMC - PubMed
Van Aken 2004 {published data only}
    1. Aken H, Thys L, Veekman L, Buerkle H. Assessing analgesia in single and repeated administrations of propacetamol for postoperative pain: comparison with morphine after dental surgery. Anesthesia & Analgesia 2004;98:159‐65. [PUBMED: 14693612] - PubMed
Varrassi 1999 {published data only}
    1. Varrassi G, Marinangeli F, Agro F, Aloe L, Cillis P, Nicola A, et al. A double‐blinded evaluation of propacetamol versus ketorolac in combination with patient‐controlled analgesia morphine: analgesic efficacy and tolerability after gynecologic surgery. Anesthesia & Analgesia 1999;88:611‐6. [PUBMED: 10072016] - PubMed
Vuilleumier 1998 {published data only}
    1. Vuilleumier PA, Buclin T, Biollaz J. Comparison of propacetamol and morphine in postoperative analgesia. Schweizerische Medizinische Wochenschrift 1998;14:259‐63. [9540151] - PubMed
Wininger 2010 {published data only}
    1. Wininger SJ, Miller H, Minkowitz HS, Royal MA, Ang RY, Breitmeyer JB, et al. A randomized, double‐blind, placebo‐controlled, multicenter, repeat‐dose study of two intravenous acetaminophen dosing regimens for the treatment of pain after abdominal laparoscopic surgery. Clinical Therapeutics 2010;32:2348‐69. - PubMed
Zhou 2001 {published data only}
    1. Zhou TJ, Tang J, White PF. Propacetamol versus ketorolac for treatment of acute postoperative pain after total hip or knee replacement. Anesthesia & Analgesia 2001;92:1569‐75. [PUBMED: 11375848] - PubMed

References to studies excluded from this review

Alhashemi 2006 {published data only}
    1. Alhashemi JA, Daghistani MF. Effects of intraoperative I.V. acetaminophen vs I.M. meperidine on post‐tonsillectomy pain in children. British Journal of Anaesthesia 2006;96:790‐5. [PUBMED: 16613928] - PubMed
Alhashemi 2007 {published data only}
    1. Alhashemi JA, Daghistani MF. Effect of intraoperative intravenous acetaminophen vs. intramuscular meperidine on pain and discharge time after paediatric dental restoration. European Journal of Anaesthesiology 2007;24:128‐33. [PUBMED: 16895621] - PubMed
Alimian 2014 {published data only}
    1. Alimian M, Pournajafian A, Kholdebarin, Ghodraty M, Rokhtabnak F, Yazdkhasti P. Analgesic effects of paracetamol and morphine after elective laparotomy surgeries. Anesthesiology & Pain Medicine 2014;4:e12912. - PMC - PubMed
Anand 2013 {published data only}
    1. Anand A, Sprenker CJ, Karlnoski R, Norman J, Miladinovic B, Wilburn B, et al. Intravenous acetaminophen vs. ketorolac for postoperative analgesia after ambulatory parathyroidectomy. Scandinavian Journal of Pain 2013;4:249‐53. - PubMed
Ang 1990 {published data only}
    1. Ang ET, Goldfarb G, Boccard E. Analgesic efficacy of propacetamol hydrochlorate 2 g versus pentazocine 30 mg after orthopedic surgery. European Journal of Pain 1990;11:137‐42.
Ashrafnejad 2012 {published data only}
    1. Ashrafnejad B, Hassani V. Comparison between analgesic effect of morphine and propacetamol after orthopedic surgeries. Pain Practice 2012;12:123.
Aydogan 2008 {published data only}
    1. Aydogan H, Dogru K, Erdem S, Bicer C, Aksu R, Boyaci A. The effect of IV paracetamol on the hemodynamic indices, liver functions and the postoperative analgesia in the patients underwent major orthopaedic surgery. Erciyes Tip Dergisi [Erciyes Medical Journal] 2008;30:71‐7.
Caliskan 2013 {published data only}
    1. Caliskan E, Sener M, Kocum A, Ozyilkan NB, Ezer SS, Aribogan A. The efficacy of intravenous paracetamol versus dipyrone for postoperative analgesia after day‐case lower abdominal surgery in children with spinal anesthesia: a prospective randomized double‐blind placebo‐controlled study. BMC Anesthesiology 2013;13:1‐8. - PMC - PubMed
Candiotti 2010 {published data only}
    1. Candiotti KA, Bergese SD, Viscusi ER, Singla SK, Royal MA, Singla NK. Safety of multiple‐dose intravenous acetaminophen in adult inpatients. Pain Medicine 2010;11:1841‐8. - PubMed
Cok 2011 {published data only}
    1. Cok OY, Eker HE, Pelit A, Canturk S, Akin S, Aribogan A, et al. The effect of paracetamol on postoperative nausea and vomiting during the first 24 h after strabismus surgery: a prospective, randomised, double‐blind study. European Journal of Anaesthesiology 2011;28:836‐41. - PubMed
Dowling 2014 {published data only}
    1. Dowling O, Campese C, Macchio F, Aronsohn J, Gold J, Bosshart D, et al. Effect of single dose IV acetaminophen on postoperative/postdischarge nausea and vomiting, pain, and patient satisfaction in outpatients undergoing laparoscopic cholecystectomy. Anesthesia and Analgesia 2014;118:S29.
Elseify 2011 {published data only}
    1. Elseify ZA, El‐Khattab SO, Khattab AM, Atta EM, Aijoub LF. Combined parecoxib and I.V. paracetamol provides additional analgesic effect with better postoperative satisfaction in patients undergoing anterior cruciate ligament reconstruction. Saudi Journal of Anaesthesia 2011;5:45‐9. - PMC - PubMed
Fijalkowska 2006 {published data only}
    1. Fijalkowska A, Trela‐Stachurska K, Rechberger T. Efficacy of intravenous paracetamol for early postoperative analgesia after gynaecological surgery. Anaesthesiology Intensive Therapy 2006;38:66‐8.
Fourcade 2005 {published data only}
    1. Fourcade O, Sanchez P, Kern D, Mazoit JX, Minville V, Samii K. Propacetamol and ketoprofen after thyroidectomy. European Journal of Anaesthesiology 2005;22:373‐7. [PUBMED: 15918387] - PubMed
Garcia 1999 {published data only}
    1. Garcia F, Rodriguez‐Huertas F, Gutierrez M, Bustos A, Sariego M, Garcia‐ Baquero A. Preoperative propacetamol and postoperative pain after laparoscopic surgery for tubal blockage. Revista de la Sociedad Espanola del Dolor 1999;6:83‐7.
Gehling 2010 {published data only}
    1. Gehling M, Arndt C, Eberhart LHJ, Koch T, Kruger T, Wulf H. Postoperative analgesia with parecoxib, acetaminophen, and the combination of both: a randomized, double‐blind, placebo‐controlled trial in patients undergoing thyroid surgery. British Journal of Anaesthesia 2010;104:761‐7. - PubMed
Ghaffaripour 2012 {published data only}
    1. Ghaffaripour JS, Mahmoudi H, Lahsaee S, Jaafari H, Kazemi AP, Mirshamsi M. Comparison of propacetamol and morphine in postoperative pain relief after orthopedic surgery. Pain Practice 2012;12:129.
Gousheh 2013 {published data only}
    1. Gousheh SM, Nesioonpour S, Javaher Foroosh F, Akhondzadeh R, Sahafi SA, Alizadeh Z. Intravenous paracetamol for postoperative analgesia in laparoscopic cholecystectomy. Anesthesiology & Pain Medicine 2013;3:214‐8. - PMC - PubMed
Granry 1997 {published data only}
    1. Granry JC, Rod B, Monrigal JP, Merckx J, Berniere J, Jean N, et al. The analgesic efficacy of an injectable prodrug of acetaminophen in children after orthopaedic surgery. Paediatric Anaesthesia 1997;7:445‐9. [PUBMED: 9365969] - PubMed
Grundmann 2006 {published data only}
    1. Grundmann U, Wornle C, Biedler A, Kreuer S, Wrobel M, Wilhelm W. The efficacy of the non‐opioid analgesics parecoxib, paracetamol and metamizol for postoperative pain relief after lumbar microdiscectomy. Anesthesia & Analgesia 2006;103:217‐22. [PUBMED: 16790656] - PubMed
Hernandez Palazon 2001 {published data only}
    1. Hernandez‐Palazon J, Tortosa JA, Martinez‐Lage JF, Perez‐Flores D. Intravenous administration of propacetamol reduces morphine consumption after spinal fusion surgery. Anesthesia & Analgesia 2001;92:1473‐6. [PUBMED: 11375828] - PubMed
Irct2012062410102N {published data only}
    1. IRCT2012062410102N1. A comparison of analgesic effect of intravenous acetaminophen (Apotel) versus oxycodone tablet and oral acetaminophen codeine in rhinoplasty and septoplasty surgery. irct.ir/searchresult.php?keyword=A%20comparison%20of%20analgesic%20effec... (accessed 24 March 2015).
Ko 2010 {published data only}
    1. Ko MJ, Lee JH, Cheong SH, Shin CM, Kim YJ, Choe YK, et al. Comparison of the effects of acetaminophen to ketorolac when added to lidocaine for intravenous regional anesthesia. Korean Journal of Anesthesiology 2010;58:357‐61. - PMC - PubMed
Kocum 2013 {published data only}
    1. Kocum AI, Sener M, Caliskan E, Bozdogan N, Micozkadioglu D, Yilmaz I, et al. Intravenous paracetamol and dipyrone for postoperative analgesia after day‐case tonsillectomy in children: a prospective, randomized, double blind, placebo controlled study. Revista Brasileira de Otorrinolaringologia 2013;79:89‐94. - PMC - PubMed
Memis 2010 {published data only}
    1. Memis D, Inal MT, Kavalci G, Sezer A, Sut N. Intravenous paracetamol reduced the use of opioids, extubation time, and opioid‐related adverse effects after major surgery in intensive care unit. Journal of Critical Care 2010;25:458‐62. - PubMed
Murat 2005 {published data only}
    1. Murat I, Baujard C, Foussat C, Guyot E, Petel H, Rod B, et al. Tolerance and analgesic efficacy of a new i.v. paracetamol solution in children after inguinal hernia repair. Paediatric Anaesthesia 2005;15:663‐70. - PubMed
NCT01691690 {published data only}
    1. NCT01691690. Analgesic effect of single dose intravenous acetaminophen in pediatric patients undergoing tonsillectomy. clinicaltrials.gov/ct2/show/NCT01691690 (accessed 24 March 2015).
NCT01721486 {published data only}
    1. NCT01721486. Efficacy of iv vs oral administration of acetaminophen for pain control following tonsillectomy with or without adenoidectomy. clinicaltrials.gov/ct2/show/NCT01721486 (accessed 24 March 2015).
Nikoda 2006 {published data only}
    1. Nikoda VV, Makarova VV, Maiachkin RB, Bondarenko AV. Clinical aspects of analgesia with intravenous paracetamol in the early postoperative period. Anesteziologiia i Reanimatologiia 2006;6:54‐8. - PubMed
Olonisakin 2012 {published data only}
    1. Olonisakin RP, Amanor‐Boadu SD, Akinyemi AO. Morphine‐sparing effect of intravenous paracetamol for post operative pain management following gynaecological surgery. African Journal of Medicine & Medical Sciences 2012;31:429‐36. - PubMed
Pernia 2000 {published data only}
    1. Pernia A, Torres LM, Calderon E. Management of postoperative pain through intravenous patient controlled analgesia (iv PCA) versus propacetamol and metamizol. Revista de la Sociedad Espanola del Dolor 2000;7:354‐60.
Rashwan 2013 {published data only}
    1. Rashwan D, Fathy El‐Rahmawy G. Multimodal analgesia after upper limb orthopedic surgeries: patient controlled intravenous low dose tramadol analgesia with or without intravenous acetaminophen ‐ a comparative study. Egyptian Journal of Anaesthesia 2013;29:231‐4.
Silvanto 2007 {published data only}
    1. Silvanto M, Munsterhjelm E, Savolainen S, Tiainen P, Niemi T, Ylikorkala O, et al. Effect of 3 g of intravenous paracetamol on post‐operative analgesia, platelet function and liver enzymes in patients undergoing tonsillectomy under local anaesthesia. Acta Anaesthesiologica Scandinavica 2007;51:1147‐54. [PUBMED: 17711562] - PubMed
Topal 2009 {published data only}
    1. Topal A, Erol A, Tuncer, S, Tavlan A, Kilicaslan A, Otelcioglu S. The effect of intravenous paracetamol on postoperative analgesia and morphine consumption. Anestezi Dergisi 2009;17:29‐32.
Toygar 2008 {published data only}
    1. Toygar P, Akkaya T, Ozkan D, Ozel O, Uslu E, Gumus H. Does iv paracetamol have preemptive analgesic effect on lumber disc surgeries?. Agri Dergisi 2008;20:14‐9. - PubMed
Turner 2014 {published data only}
    1. Turner L. The impact of IV acetaminophen on postoperative pain in women undergoing pelvic organ prolapse repair: a double‐blind randomized placebo controlled trial. https://clinicaltrials.gov/show/NCT02155738 2014.
Uvarov 2008 {published data only}
    1. Uvarov DN, Orlov MM, Levin AV, Sokolov AV, Nedashkovskii EV. Role of paracetamol in a balanced postoperative analgesia scheme after thoracotomy. Anesteziologiia i Reanimatologiia 2008;4:46‐9. - PubMed
Uzun 2010 {published data only}
    1. Uzun S, Aycan IO, Erden IA, Sahin A, Aypar U. The addition of metamizole to morphine and paracetamol improves early postoperative analgesia and patient satisfaction after lumbar disc surgery. Turkish Neurosurgery 2010;20:341‐7. - PubMed
Verchere 2002 {published data only}
    1. Verchere E, Grenier B, Mesli A, Siao D, Sesay M, Maurette P. Postoperative pain management after supratentorial craniotomy. Journal of Neurosurgical Anesthesiology 2002;14:96‐101. [PUBMED: 11907388] - PubMed
Zeidan 2014 {published data only}
    1. Zeidan A, Mazoit JX, Ali Abdullah M, Maaliki H, Ghattas T, Saifan A. Median effective dose (ED50) of paracetamol and morphine for postoperative pain: a study of interaction. British Journal of Anaesthesia 2014;112:118‐23. - PubMed
Ziolkowski 2008 {published data only}
    1. Ziolkowski R, Srebrzynski A, Kaczka K, Butwicka A, Kuzdak K, Pomorski L. Assessment of postoperative analgesia using intravenous paracetamol during first day following thyroid surgery for goiter. Clinical and Experimental Medical Letters 2008;49:41‐6.

References to studies awaiting assessment

Atashkhoyi 2014 {published data only}
    1. Atashkhoyi S, Rasouli S, Fardiazar Z, Ghojazadeh M, Marandi PH. Preventive analgesia with intravenous paracetamol for post‐cesarean section pain control. International Journal of Women's Health and Reproduction Sciences 2014;2:131‐7.
Dawoodi 2014 {published data only}
    1. Dawoodi I, Khety Z. Comparative efficacy and safety study of analgesic effect of fentanyl I.V. and paracetamol I.V. in postoperative patients in multidisciplinary hospital. Research Journal of Pharmaceutical, Biological and Chemical Sciences 2014;5:664‐8.
Jabalameli 2014 {published data only}
    1. Jabalameli M, Goudarzi L. Preventive effects of intravenous paracetamol in post‐partum pain of elective cesarean delivery with spinal anesthesia. Journal of Isfahan Medical School 2014;32:1227‐37.
Majumdar 2014 {published data only}
    1. Majumdar S, Das A, Kundu R, Mukherjee D, Hazra B, Mitra T. Intravenous paracetamol infusion: superior pain management and earlier discharge from hospital in patients undergoing palliative head‐neck cancer surgery. Perspectives in Clinical Research 2014;5:172‐7. - PMC - PubMed
Pekmezci 2014 {published data only}
    1. Pekmezci A, Cesur M, Aksoy M, Ince I, Aksoy AN. The effect of ilioinguinal‐iliohypogastric block with or without intravenous paracetamol for pain relief after caesarean delivery. Acta Medica Mediterranea 2014;30:1183‐8.
Rasheed 2007 {published data only}
    1. Borodiciene J, Gudaityte J, Gerulyte I, Macas A, Suskeviciene I. Randomized controlled study of the acetaminophen effectiveness after adenotonsillectomy or tonsillectomy in children. European Journal of Anaesthesiology 2014;31:173.
    1. Dabir S, Parsa T, Abbasinazari M, Parviz Y. Comparison of a single dose of intravenous paracetamol with single dose of rectal indomethacin for pain management after open septorhinoplasty surgery. La Prensa Medica 2016;102:1.
    1. Rasheed A, Aqil M, Haq A, Usman SK. Comparative study of tramadol & propacetamol for postoperative pain management in patients undergoing nasal surgeries. Medical Forum Monthly 2007;18:21‐5.
Ritchie 2015 {published data only}
    1. Ritchie R, Sloan PA, Reddy A, Chau D, Lukens MF, Nimma S. Intraoperative acetaminophen for pediatric post‐tonsillectomy pain relief: a comparison of 2 surgical techniques. Anesthesia and Analgesia 2015;120:S225.
Singla 2015 {published data only}
    1. Singla NK, Hale ME, Davis JC, Bekker A, Gimbel J, Jahr J, et al. IV acetaminophen: Efficacy of a single dose for postoperative pain after hip arthroplasty: subset data analysis of 2 unpublished randomized clinical trials. American Journal of Therapeutics 2015;22:2‐10. - PubMed

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