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

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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 find an increase in risk of harm when using ibuprofen vs paracetamol. The aim of this subgroup analysis was to investigate the differences in benefits and harms of the interventions in different subgroups. We hypothesized that the intervention effects would differ in subgroups with different risk of pain or adverse events. Methods: In these pre-planned subgroup analyses of the PANSAID trial population, we assessed subgroup heterogeneity in intervention effects between (a) subgroups (sex, age, use of analgesics, American Society of Anesthesiologists (ASA) score, and type of anesthesia) and morphine consumption, and (b) subgroups (sex, age, use of non-steroidal anti-inflammatory drugs (NSAIDs), and ASA score) and serious adverse events. Results: Test of interaction between age and the pairwise comparison between paracetamol 1 g vs paracetamol 0.5 g + ibuprofen 200 mg (P =.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 pre-planned subgroup analyses did not suggest that patients in the investigated subgroups benefitted differently 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.

Original languageEnglish
JournalActa Anaesthesiologica Scandinavica
Volume64
Issue number2
Pages (from-to)245-253
ISSN0001-5172
DOIs
Publication statusPublished - Feb 2020

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Ibuprofen
Acetaminophen
Morphine
Pharmaceutical Preparations
Population

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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. / Benefits and harm of paracetamol and ibuprofen in combination for postoperative pain : preplanned subgroup analyses of the multicenter randomized PANSAID trial. In: Acta Anaesthesiologica Scandinavica. 2020 ; Vol. 64, No. 2. pp. 245-253.
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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 find an increase in risk of harm when using ibuprofen vs paracetamol. The aim of this subgroup analysis was to investigate the differences in benefits and harms of the interventions in different subgroups. We hypothesized that the intervention effects would differ in subgroups with different risk of pain or adverse events. Methods: In these pre-planned subgroup analyses of the PANSAID trial population, we assessed subgroup heterogeneity in intervention effects between (a) subgroups (sex, age, use of analgesics, American Society of Anesthesiologists (ASA) score, and type of anesthesia) and morphine consumption, and (b) subgroups (sex, age, use of non-steroidal anti-inflammatory drugs (NSAIDs), and ASA score) and serious adverse events. Results: Test of interaction between age and the pairwise comparison between paracetamol 1 g vs paracetamol 0.5 g + ibuprofen 200 mg (P =.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 pre-planned subgroup analyses did not suggest that patients in the investigated subgroups benefitted differently 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",
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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.

In: Acta Anaesthesiologica Scandinavica, Vol. 64, No. 2, 02.2020, p. 245-253.

Research output: Contribution to journalJournal articleResearchpeer-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 - 2020/2

Y1 - 2020/2

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 find an increase in risk of harm when using ibuprofen vs paracetamol. The aim of this subgroup analysis was to investigate the differences in benefits and harms of the interventions in different subgroups. We hypothesized that the intervention effects would differ in subgroups with different risk of pain or adverse events. Methods: In these pre-planned subgroup analyses of the PANSAID trial population, we assessed subgroup heterogeneity in intervention effects between (a) subgroups (sex, age, use of analgesics, American Society of Anesthesiologists (ASA) score, and type of anesthesia) and morphine consumption, and (b) subgroups (sex, age, use of non-steroidal anti-inflammatory drugs (NSAIDs), and ASA score) and serious adverse events. Results: Test of interaction between age and the pairwise comparison between paracetamol 1 g vs paracetamol 0.5 g + ibuprofen 200 mg (P =.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 pre-planned subgroup analyses did not suggest that patients in the investigated subgroups benefitted differently 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 find an increase in risk of harm when using ibuprofen vs paracetamol. The aim of this subgroup analysis was to investigate the differences in benefits and harms of the interventions in different subgroups. We hypothesized that the intervention effects would differ in subgroups with different risk of pain or adverse events. Methods: In these pre-planned subgroup analyses of the PANSAID trial population, we assessed subgroup heterogeneity in intervention effects between (a) subgroups (sex, age, use of analgesics, American Society of Anesthesiologists (ASA) score, and type of anesthesia) and morphine consumption, and (b) subgroups (sex, age, use of non-steroidal anti-inflammatory drugs (NSAIDs), and ASA score) and serious adverse events. Results: Test of interaction between age and the pairwise comparison between paracetamol 1 g vs paracetamol 0.5 g + ibuprofen 200 mg (P =.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 pre-planned subgroup analyses did not suggest that patients in the investigated subgroups benefitted differently 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

C2 - 31648374

VL - 64

SP - 245

EP - 253

JO - Acta Anaesthesiologica Scandinavica

JF - Acta Anaesthesiologica Scandinavica

SN - 0001-5172

IS - 2

ER -