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Cochrane Database of Systematic Reviews

Infiltración con bupivacaína liposomal en el sitio quirúrgico para el tratamiento del dolor posoperatorio

Información

DOI:
https://doi.org/10.1002/14651858.CD011419.pub2Copiar DOI
Base de datos:
  1. Cochrane Database of Systematic Reviews
Versión publicada:
  1. 01 febrero 2017see what's new
Tipo:
  1. Intervention
Etapa:
  1. Review
Grupo Editorial Cochrane:

  1. Grupo Cochrane de Dolor y cuidados paliativos

Copyright:
  1. Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Autores

  • Thomas W Hamilton

    Correspondencia a: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, UK

    [email protected]

    [email protected]

  • Vassilis Athanassoglou

    Nuffield Department of Anaesthetics, Oxford University Hospitals NHS Foundation Trust, Oxford, UK

  • Stephen Mellon

    Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, UK

  • Louise H H Strickland

    Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, UK

  • Marialena Trivella

    Centre for Statistics in Medicine, University of Oxford, Oxford, UK

  • David Murray

    Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, UK

  • Hemant G Pandit

    Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, UK

Contributions of authors

Thomas Hamilton wrote the protocol with input from Vassilis Athanassoglou. Statistical and methodological advice were provided by Marialena Trivella. The search strategy was designed by Joanne Abbott with input from Thomas Hamilton. Other authors provided general advice on the protocol. Future updates of this review will be performed by Thomas Hamilton.

Sources of support

Internal sources

  • No sources of support supplied

External sources

  • National Institute for Health Research, UK, Other.

    TWH is supported by the NIHR Biomedical Research Centre, based at Oxford University Hospitals Foundation Trust, Oxford

Declarations of interest

  • TWH is an orthopaedic registrar and manages patients with peri‐operative and postoperative pain. TWH receives funding from the National Institute for Health Research (NIHR).

  • VA: none known; VA is a consultant anaesthetist and manages patients with peri‐operative and postoperative pain.

  • SM none known.

  • LHS: none known; LHS is a nurse and surgical assistant and manages patients with perioperative and post‐operative pain.

  • MT: none known.

  • DM is a consultant orthopaedic surgeon and manages patients with perioperative and postoperative pain. DM receives funding from Zimmer Biomet (1998 to present) who manufacture orthopaedic implants, including knee replacements.

  • HGP is a consultant orthopaedic surgeon and manages patients with peri‐operative and postoperative pain. HGP receives funding from Zimmer Biomet (2015 to present) who manufacture orthopaedic implants, including knee replacements.

Acknowledgements

The authors wish to thank Joanne Abbott, Information Specialist, for her assistance with developing the search strategy.

TWH Funding Acknowledgement: supported by the NIHR Biomedical Research Centre, based at Oxford University Hospitals Foundation Trust, Oxford. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

CRG Funding Acknowledgement: the National Institute for Health Research (NIHR) is the largest single funder of the Cochrane PaPaS Group. Disclaimer: the views and opinions expressed therein are those of the authors and do not necessarily reflect those of the NIHR, NHS or the Department of Health.

Version history

Published

Title

Stage

Authors

Version

2017 Feb 01

Liposomal bupivacaine infiltration at the surgical site for the management of postoperative pain

Review

Thomas W Hamilton, Vassilis Athanassoglou, Stephen Mellon, Louise H H Strickland, Marialena Trivella, David Murray, Hemant G Pandit

https://doi.org/10.1002/14651858.CD011419.pub2

2014 Dec 05

Liposomal bupivacaine infiltration at the surgical site for the management of postoperative pain

Protocol

Thomas W Hamilton, Vassilis Athanassoglou, Stephen Mellon, Marialena Trivella, David Murray, Hemant G Pandit

https://doi.org/10.1002/14651858.CD011419

Differences between protocol and review

In line with current Cochrane guidance, we have added selective outcome reporting and blinding of participants and personnel (performance bias) to the 'Risk of bias' assessment and also completed a GRADE assessment for all included studies. These were not included in the protocol but have been included in this review and will be included in subsequent updates. In our protocol we stated we would assess for adverse events as both a primary and secondary outcome. To avoid duplication we have assessed the incidence of serious adverse events including the incidence of cardiac events and incidence of wound complications as a primary outcome, and incidence of adverse events as a secondary outcome.

Notes

We updated the searches in full in October 2019, and while we did identify some potentially relevant studies, none were likely to change the conclusions. Therefore, this review has now been stabilised following discussion with the authors and editors. The review will be re‐assessed for updating in 2022. If appropriate, we will update the review before this date if new evidence likely to change the conclusions is published, or if standards change substantially which necessitate major revisions.

Keywords

MeSH

Medical Subject Headings (MeSH) Keywords

Medical Subject Headings Check Words

Humans;

PICO

Population
Intervention
Comparison
Outcome

El uso y la enseñanza del modelo PICO están muy extendidos en el ámbito de la atención sanitaria basada en la evidencia para formular preguntas y estrategias de búsqueda y para caracterizar estudios o metanálisis clínicos. PICO son las siglas en inglés de cuatro posibles componentes de una pregunta de investigación: paciente, población o problema; intervención; comparación; desenlace (outcome).

Para saber más sobre el uso del modelo PICO, puede consultar el Manual Cochrane.

Study flow diagram
Figuras y tablas -
Figure 1

Study flow diagram

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Risk of bias summary: review authors' judgements about each risk of bias item for each included study
Figuras y tablas -
Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study

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Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
Figuras y tablas -
Figure 3

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies

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Forest plot of comparison: 1 Liposomal bupivacaine vs control, outcome: 1.1 Cumulative pain score 0 to 72 hours
Figuras y tablas -
Figure 4

Forest plot of comparison: 1 Liposomal bupivacaine vs control, outcome: 1.1 Cumulative pain score 0 to 72 hours

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Table of results for included simultaneous parallel‐arm trials
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Figure 5

Table of results for included simultaneous parallel‐arm trials

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Forest plot of comparison: 1 Liposomal bupivacaine vs control, outcome: 1.2 Participants not requiring postoperative opioids
Figuras y tablas -
Figure 6

Forest plot of comparison: 1 Liposomal bupivacaine vs control, outcome: 1.2 Participants not requiring postoperative opioids

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Illustrative example of an adaptive‐design trial. The decision to escalate, or de‐escalate a dose is conditional on the failure of the previous dose on the efficacy, or safety, or cost‐effectiveness of the intervention, introducing bias in any pooled analysis. The randomisation ratio is altered with each escalation/de‐escalation while the control group population is typically reported cumulatively for all dose levels
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Figure 7

Illustrative example of an adaptive‐design trial. The decision to escalate, or de‐escalate a dose is conditional on the failure of the previous dose on the efficacy, or safety, or cost‐effectiveness of the intervention, introducing bias in any pooled analysis. The randomisation ratio is altered with each escalation/de‐escalation while the control group population is typically reported cumulatively for all dose levels

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Table of results for adaptive‐design trials
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Figure 8

Table of results for adaptive‐design trials

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Comparison 1 Liposomal bupivacaine vs control, Outcome 1 Cumulative pain score 0 to 72 hours.
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Analysis 1.1

Comparison 1 Liposomal bupivacaine vs control, Outcome 1 Cumulative pain score 0 to 72 hours.

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Comparison 1 Liposomal bupivacaine vs control, Outcome 2 Participants not requiring postoperative opioids.
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Analysis 1.2

Comparison 1 Liposomal bupivacaine vs control, Outcome 2 Participants not requiring postoperative opioids.

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Summary of findings for the main comparison. Summary of findings: liposomal bupivacaine vs placebo

Liposomal bupivacaine infiltration at the surgical site compared with placebo for the management of postoperative pain

Patient or population: aged 18 years and older undergoing elective surgery at any surgical site

Settings: inpatient

Intervention: surgical site infiltration of liposomal bupivacaine

Comparison: surgical site infiltration of placebo

Outcomes

Impact

Number of participants
(number of studies)

Quality of the evidence
(GRADE)

Cumulative pain score from the end of operation (0 hours) to 72 hours (NRS 0 to 10)

A reduction in cumulative pain score associated with the use of liposomal bupivacaine was reported in one study.

The mean cumulative pain score from the end of operation to 72 hours (NRS 0 to 10) in the placebo control group was 202.5 points with the mean cumulative pain score from the end of operation to 72 hours in the liposomal bupivacaine intervention group being 60.7 points lower (90.4 lower to 31.1 lower).

189 participants

(1 study)

⊕⊝⊝⊝
very lowa

Serious adverse events

No reported drug‐related serious adverse events, no study withdrawals due to drug‐related adverse events

382 participants

(2 studies)

⊕⊕⊝⊝
lowb

Mean pain score at 12, 24, 48, 72 and 96 hours following surgery (NRS 0 to 10)

No data reported

No studies

Time to first postoperative opioid dose over initial 72 hours

A longer time to first postoperative opioid dose associated with the use of liposomal bupivacaine was reported in two studies. In the placebo control group the time to first postoperative opioid was 4.3 and 1.2 hours compared to 7.2 and 14.3 hours in the liposomal bupivacaine groups respectively. The distribution of data was not reported.

382 participants

(2 studies)

⊕⊕⊝⊝
lowc

Total postoperative opioid consumption over first 72 hours

A reduction in total postoperative opioid consumption over first 72 hours associated with the use of liposomal bupivacaine was reported in one study. In the placebo control group the mean cumulative parenteral morphine equivalent dose over the first 72 hours was 29.1 mg and was 6.8 mg lower (12.8 mg lower to 0.9 mg lower) in the liposomal bupivacaine intervention group.

189 participants

(1 study)

⊕⊝⊝⊝
very lowd

Percentage of participants not requiring postoperative opioids over initial 72 hours

One study reported a higher proportion of participants not requiring postoperative opioids over initial 72 hours associated with the use of liposomal bupivacaine (RR 0.82; 95% CI 0.72 to 0.94), and one study found no difference (RR 0.99; 95% CI 0.95 to 1.03).

382 participants

(2 studies)

⊕⊝⊝⊝
very lowe

Incidence of adverse events within 30 days of surgery

The incidence of cardiac events and wound complications within 30 days of surgery were not reported in any study

Adverse events within 30 days of surgery were reported in all studies with nausea, constipation and vomiting being the most common.

382 participants

(2 studies)

⊕⊕⊝⊝
lowf

CI: confidence interval; NRS: numeric rating scale; RR: risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: We are moderately confident in the effect estimate; the true effect is likely to be close the estimate of effect, but there is a possibility that it is substantially different.
Low quality: Our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.
Very low quality: We have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

aWe downgraded the quality of this evidence due to the sparseness of data (‐1), indirectness (‐1) and risk of bias (‐1) due to the unclear risk of bias due to the sample size (50‐199).
bWe downgraded the quality of this evidence one level due to the sparseness of data and a further level due the high risk of bias due to Golf 2011 being subject to a risk of performance bias as well as the unclear risk of bias due to the sample size (50‐199) of the two studies.
cWe downgraded the quality of this evidence one level due to the sparseness of data and a further level due to Golf 2011 being subject to a high risk of performance bias (as well as the unclear risk of bias due to the sample size (50‐199) of the two studies). No meta‐analysis was carried out because time to first postoperative opioid dose follows a skewed distribution and hence meta‐analysis isn't recommended. Additionally there was expected heterogeneity due population characteristics (bunionectomy vs haemorrhoidectomy).
dWe downgraded the quality of this evidence due to the sparseness of data (‐1), indirectness (‐1) and risk of bias (‐1) due to the unclear risk of bias due to the sample size (50‐199).
eWe downgraded the quality of this evidence one level due to the to the sparseness of data, one level due to inconsistency, and a further level due to Golf 2011 being subject to a high risk of performance bias as well as the unclear risk of bias due to the sample size (50‐199) of the two studies.
fWe downgraded the quality of this evidence one level due to the sparseness of data and a further level due the high risk of bias due to Golf 2011 being subject to a risk of performance bias as well as the unclear risk of bias due to the sample size (50‐199) of the two studies.

Figuras y tablas -
Summary of findings for the main comparison. Summary of findings: liposomal bupivacaine vs placebo
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Summary of findings 2. Summary of findings: liposomal bupivacaine vs bupivacaine hydrochloride

Liposomal bupivacaine infiltration at the surgical site compared with bupivacaine hydrochloride for the management of postoperative pain

Patient or population: aged 18 years and older undergoing elective surgery at any surgical site

Settings: inpatient

Intervention: surgical site infiltration of liposomal bupivacaine

Comparison: surgical site infiltration of bupivacaine hydrochloride

Outcomes

Impact

Number of participants
(number of studies)

Quality of the evidence
(GRADE)

Cumulative pain score from the end of operation (0 hours) to 72 hours (NRS 0 to 10)

No difference in cumulative pain score was reported in two studies.

In one study the mean cumulative pain score from the end of operation to 72 hours (NRS 0 to 10) in the active control group was 335.0 points and 24.0 points higher (5.7 lower to 53.7 higher) in the liposomal bupivacaine intervention group. In the other study the mean cumulative pain score from the end of operation to 72 hours (NRS 0 to 10) in the active control group was 468.2 points and 26.7 points lower (91.3 lower to 37.9 higher) in the liposomal bupivacaine intervention group. Data were not pooled as differences in outcomes were expected due to differences in surgical interventions between studies.

379 participants

(2 studies)

⊕⊝⊝⊝
very lowa

Serious adverse events

No reported drug‐related serious adverse events, no study withdrawals due to drug‐related adverse events

583 participants

(3 studies)

⊕⊕⊕⊝
moderateb

Mean pain score at 12, 24, 48, 72 and 96 hours following surgery (NRS 0 to 10)

A reduction in mean pain score at 12 hours, but not 24, 48 or 72 hours, associated with the use of liposomal bupivacaine was reported in one study. Mean pain score at these time points were not reported in other studies.

In the study that reported mean pain score (NRS 0 to 10) at 12 hours in the active control group it was 6.9 points and 1.3 points lower (2.4 lower to 0.2 lower) in the liposomal bupivacaine intervention group at this time point.

134 participants

(1 study)

⊕⊝⊝⊝
very lowc

Time to first postoperative opioid dose over initial 72 hours

No data reported

No studies

Total postoperative opioid consumption over first 72 hours

No difference in cumulative parenteral morphine equivalent dose over first 72 hours was reported in one study though no estimate of variance was provided and as such estimates of effect could not be calculated.

134 participants

(1 study)

⊕⊝⊝⊝
very lowd

Percentage of participants not requiring postoperative opioids over initial 72 hours

No difference in the percentage of participants not requiring postoperative opioids over initial 72 hours was reported in one study (RR 0.95; 95% CI 0.86 to 1.05).

134 participants

(1 study)

⊕⊝⊝⊝
very lowe

Incidence of adverse events within 30 days of surgery

The incidence of cardiac events and wound complications within 30 days of surgery were not reported in any study

Adverse events within 30 days of surgery were reported in all studies with nausea, constipation and vomiting being the most common.

583 participants

(3 studies)

⊕⊕⊕⊝
moderatef

CI: confidence interval; NRS: numeric rating scale; RR: risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: We are moderately confident in the effect estimate; the true effect is likely to be close the estimate of effect, but there is a possibility that it is substantially different.
Low quality: Our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.
Very low quality: We have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

aWe downgraded the quality of this evidence one level due to the sparseness of data, a further level because Smoot 2012 was subject to a high risk of bias due to the risk of performance bias and attrition bias due to early termination of the study (as well as the unclear risk of bias due to the sample size (50‐199)), and a further level due to inconsistency. We did not pool of results as we predicted that participant characteristics, as well as nature of postoperative pain, would be different following breast augmentation and knee replacement. As such we expected there to be heterogeneity of the results due to population characteristics, not due to intervention characteristics.
bWe downgraded the quality of this evidence one level due the high risk of bias due to Smoot 2012 being subject to a risk of performance and attrition bias due to early termination of the study (as well as the unclear risk of bias due to the sample size (50‐199)).
cWe downgraded the quality of this evidence one level due to the sparseness of data, and a further level because Smoot 2012 was subject to a high risk of bias due to the risk of performance bias and attrition bias due to early termination of the study (as well as the unclear risk of bias due to the sample size (50‐199)), and by a further level due to indirectness due to the limitations in interpreting data from a single study.
dWe downgraded the quality of this evidence one level due to the sparseness of data, a further level because Smoot 2012 was subject to a high risk of bias due to the risk of performance bias and attrition bias due to early termination of the study (as well as the unclear risk of bias due to the sample size (50‐199)) and by a further level due to indirectness due to the limitations in interpreting data from a single study.
eWe downgraded the quality of this evidence one level due to the sparseness of data, and a further level because Smoot 2012 was subject to a high risk of bias due to the risk of performance bias and attrition bias due to early termination of the study (as well as the unclear risk of bias due to the sample size (50‐199)), and by a further level due to indirectness due to the limitations in interpreting data from a single study.
fWe downgraded the quality of this evidence one level due the high risk of bias due to Smoot 2012 being subject to a risk of performance and attrition bias due to early termination of the study (as well as the unclear risk of bias due to the sample size (50‐199)).

Figuras y tablas -
Summary of findings 2. Summary of findings: liposomal bupivacaine vs bupivacaine hydrochloride
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Comparison 1. Liposomal bupivacaine vs control

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Cumulative pain score 0 to 72 hours Show forest plot

3

Mean Difference (IV, Random, 95% CI)

Totals not selected

1.1 vs placebo

1

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

1.2 vs bupivacaine hydrocholoride

2

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

2 Participants not requiring postoperative opioids Show forest plot

3

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

2.1 vs placebo

2

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2.2 vs bupivacaine hydrochloride

1

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Figuras y tablas -
Comparison 1. Liposomal bupivacaine vs control
Ir a la tabla de la revisión