Benefits and harm of paracetamol and ibuprofen in combination for postoperative pain

preplanned subgroup analyses of the multicenter randomized PANSAID trial

Kasper H Thybo, Daniel Hägi-Pedersen, Jørn Wetterslev, Jørgen B Dahl, Janus C Jakobsen, Niels Anker Pedersen, Karina Jakobsen, Hans Henrik Bülow, Louise Ibsen, Søren Overgaard, Ole Mathiesen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

BACKGROUND: The 'Paracetamol and Ibuprofen in Combination' (PANSAID) trial showed that combining paracetamol and ibuprofen resulted in lower opioid consumption than each drug alone and we did not findan increase in risk of harm when using ibuprofen versus paracetamol. The aim of this subgroup analysis was to investigate differences in benefits and harms of the interventions in different subgroups. We hypothesized the intervention effects would differ in subgroups with different risk of pain or adverse events.

METHODS: In these preplanned subgroup analyses of the PANSAID trial population, we assessed subgroup heterogeneity in intervention effects between 1) subgroups (sex, age, use of analgesics, American Society of Anesthesiologists score, and type of anesthesia) and morphine consumption, and 2) subgroups (sex, age, use of non-steroidal anti-inflammatory drugs, and American Society of Anesthesiologists score) and serious adverse events.

RESULTS: Test of interaction between age and the pairwise comparison between paracetamol 1 g versus paracetamol 0.5 g + ibuprofen 200 mg (P=0.009) suggested lower morphine consumption in patients>65 years. However, post hoc analyses of related outcomes showed no interaction for this pairwise comparison. All other tests of interaction regarding both benefit and harm were not statistically significant.

CONCLUSION: These preplanned subgroup analyses did not suggest that patients in the investigated subgroups benefitteddifferently from a basic non-opioid analgesic regimen consisting of paracetamol and ibuprofen. Further, there was no evidence of subgroup heterogeneity regarding harm and use of ibuprofen. Because of reduced statistical power in subgroup analyses we cannot exclude clinically relevant subgroup heterogeneity.

OriginalsprogEngelsk
TidsskriftActa Anaesthesiologica Scandinavica
ISSN0001-5172
DOI
StatusE-pub ahead of print - 24. okt. 2019

Fingeraftryk

Ibuprofen
Acetaminophen
Morphine
Pharmaceutical Preparations
Population

Citer dette

@article{0c18848b24564f1cb99217890bbf4279,
title = "Benefits and harm of paracetamol and ibuprofen in combination for postoperative pain: preplanned subgroup analyses of the multicenter randomized PANSAID trial",
abstract = "BACKGROUND: The 'Paracetamol and Ibuprofen in Combination' (PANSAID) trial showed that combining paracetamol and ibuprofen resulted in lower opioid consumption than each drug alone and we did not findan increase in risk of harm when using ibuprofen versus paracetamol. The aim of this subgroup analysis was to investigate differences in benefits and harms of the interventions in different subgroups. We hypothesized the intervention effects would differ in subgroups with different risk of pain or adverse events.METHODS: In these preplanned subgroup analyses of the PANSAID trial population, we assessed subgroup heterogeneity in intervention effects between 1) subgroups (sex, age, use of analgesics, American Society of Anesthesiologists score, and type of anesthesia) and morphine consumption, and 2) subgroups (sex, age, use of non-steroidal anti-inflammatory drugs, and American Society of Anesthesiologists score) and serious adverse events.RESULTS: Test of interaction between age and the pairwise comparison between paracetamol 1 g versus paracetamol 0.5 g + ibuprofen 200 mg (P=0.009) suggested lower morphine consumption in patients>65 years. However, post hoc analyses of related outcomes showed no interaction for this pairwise comparison. All other tests of interaction regarding both benefit and harm were not statistically significant.CONCLUSION: These preplanned subgroup analyses did not suggest that patients in the investigated subgroups benefitteddifferently from a basic non-opioid analgesic regimen consisting of paracetamol and ibuprofen. Further, there was no evidence of subgroup heterogeneity regarding harm and use of ibuprofen. Because of reduced statistical power in subgroup analyses we cannot exclude clinically relevant subgroup heterogeneity.",
author = "Thybo, {Kasper H} and Daniel H{\"a}gi-Pedersen and J{\o}rn Wetterslev and Dahl, {J{\o}rgen B} and Jakobsen, {Janus C} and Pedersen, {Niels Anker} and Karina Jakobsen and B{\"u}low, {Hans Henrik} and Louise Ibsen and S{\o}ren Overgaard and Ole Mathiesen",
note = "{\circledC} 2019 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.",
year = "2019",
month = "10",
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doi = "10.1111/aas.13496",
language = "English",
journal = "Acta Anaesthesiologica Scandinavica",
issn = "0001-5172",
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Benefits and harm of paracetamol and ibuprofen in combination for postoperative pain : preplanned subgroup analyses of the multicenter randomized PANSAID trial. / Thybo, Kasper H; Hägi-Pedersen, Daniel; Wetterslev, Jørn; Dahl, Jørgen B; Jakobsen, Janus C; Pedersen, Niels Anker; Jakobsen, Karina; Bülow, Hans Henrik; Ibsen, Louise; Overgaard, Søren; Mathiesen, Ole.

I: Acta Anaesthesiologica Scandinavica, 24.10.2019.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Benefits and harm of paracetamol and ibuprofen in combination for postoperative pain

T2 - preplanned subgroup analyses of the multicenter randomized PANSAID trial

AU - Thybo, Kasper H

AU - Hägi-Pedersen, Daniel

AU - Wetterslev, Jørn

AU - Dahl, Jørgen B

AU - Jakobsen, Janus C

AU - Pedersen, Niels Anker

AU - Jakobsen, Karina

AU - Bülow, Hans Henrik

AU - Ibsen, Louise

AU - Overgaard, Søren

AU - Mathiesen, Ole

N1 - © 2019 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

PY - 2019/10/24

Y1 - 2019/10/24

N2 - BACKGROUND: The 'Paracetamol and Ibuprofen in Combination' (PANSAID) trial showed that combining paracetamol and ibuprofen resulted in lower opioid consumption than each drug alone and we did not findan increase in risk of harm when using ibuprofen versus paracetamol. The aim of this subgroup analysis was to investigate differences in benefits and harms of the interventions in different subgroups. We hypothesized the intervention effects would differ in subgroups with different risk of pain or adverse events.METHODS: In these preplanned subgroup analyses of the PANSAID trial population, we assessed subgroup heterogeneity in intervention effects between 1) subgroups (sex, age, use of analgesics, American Society of Anesthesiologists score, and type of anesthesia) and morphine consumption, and 2) subgroups (sex, age, use of non-steroidal anti-inflammatory drugs, and American Society of Anesthesiologists score) and serious adverse events.RESULTS: Test of interaction between age and the pairwise comparison between paracetamol 1 g versus paracetamol 0.5 g + ibuprofen 200 mg (P=0.009) suggested lower morphine consumption in patients>65 years. However, post hoc analyses of related outcomes showed no interaction for this pairwise comparison. All other tests of interaction regarding both benefit and harm were not statistically significant.CONCLUSION: These preplanned subgroup analyses did not suggest that patients in the investigated subgroups benefitteddifferently from a basic non-opioid analgesic regimen consisting of paracetamol and ibuprofen. Further, there was no evidence of subgroup heterogeneity regarding harm and use of ibuprofen. Because of reduced statistical power in subgroup analyses we cannot exclude clinically relevant subgroup heterogeneity.

AB - BACKGROUND: The 'Paracetamol and Ibuprofen in Combination' (PANSAID) trial showed that combining paracetamol and ibuprofen resulted in lower opioid consumption than each drug alone and we did not findan increase in risk of harm when using ibuprofen versus paracetamol. The aim of this subgroup analysis was to investigate differences in benefits and harms of the interventions in different subgroups. We hypothesized the intervention effects would differ in subgroups with different risk of pain or adverse events.METHODS: In these preplanned subgroup analyses of the PANSAID trial population, we assessed subgroup heterogeneity in intervention effects between 1) subgroups (sex, age, use of analgesics, American Society of Anesthesiologists score, and type of anesthesia) and morphine consumption, and 2) subgroups (sex, age, use of non-steroidal anti-inflammatory drugs, and American Society of Anesthesiologists score) and serious adverse events.RESULTS: Test of interaction between age and the pairwise comparison between paracetamol 1 g versus paracetamol 0.5 g + ibuprofen 200 mg (P=0.009) suggested lower morphine consumption in patients>65 years. However, post hoc analyses of related outcomes showed no interaction for this pairwise comparison. All other tests of interaction regarding both benefit and harm were not statistically significant.CONCLUSION: These preplanned subgroup analyses did not suggest that patients in the investigated subgroups benefitteddifferently from a basic non-opioid analgesic regimen consisting of paracetamol and ibuprofen. Further, there was no evidence of subgroup heterogeneity regarding harm and use of ibuprofen. Because of reduced statistical power in subgroup analyses we cannot exclude clinically relevant subgroup heterogeneity.

U2 - 10.1111/aas.13496

DO - 10.1111/aas.13496

M3 - Journal article

JO - Acta Anaesthesiologica Scandinavica

JF - Acta Anaesthesiologica Scandinavica

SN - 0001-5172

ER -