Randomized, double-blind trial of preoperative
pregabalin versus placebo to improve quality of
recovery after breast cancer surgery

Fabio Vieira Toledo; Jose Fernando Amaral Meletti; Luiza Mansur Cerioni Silva; Nathalia Maria Medeiros Serra; Maria Nathalia Prado Simoes Mendonça; Paulo Henrique Carvalho Guerra; Clóvis Antônio Lopes Pinto

doi:10.1016/j.bjane.2026.844749

Original Investigation

Randomized, double-blind trial of preoperative pregabalin versus placebo to improve quality of recovery after breast cancer surgery

Ensaio randomizado, duplo-cego, de pregabalina pré-operatória versus placebo para melhora da qualidade de recuperação após cirurgia de câncer de mama

Fabio Vieira Toledo, Jose Fernando Amaral Meletti, Luiza Mansur Cerioni Silva, Nathalia Maria Medeiros Serra, Maria Nathalia Prado Simoes Mendonça, Paulo Henrique Carvalho Guerra, Clóvis Antônio Lopes Pinto

http://dx.doi.org/10.1016/j.bjane.2026.844749 Braz J Anesthesiol, vol.76, n3, 844749, 2026

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Abstract

Introduction

Surgery remains one of the most important treatments for breast cancer. In this context, the quality of postoperative recovery has become a key concern. Adequate control of acute pain is essential to optimize patient comfort and recovery. Pregabalin may contribute to this goal by preventing central sensitization and reducing perioperative anxiety.

Objectives

To evaluate the effect of perioperative pregabalin versus placebo on postoperative recovery quality in patients undergoing breast cancer surgery.

Method

In this randomized controlled trial, 92 patients received either pregabalin (150 mg orally, 1 hour before surgery) or a matching placebo, both prepared in identical capsules. The primary outcome was the QoR-15 score measured preoperatively, and at 24 and 48 hours postoperatively. The 24- and 48-hour assessments were conducted via telephone. The QoR-15 is a validated instrument that assesses the quality of recovery, with total scores ranging from 0 (very poor recovery) to 150 (excellent recovery). Secondary outcomes included opioid consumption, pain scores, incidence of nausea and vomiting, and lengths of stay in the Post-Anesthesia Care Unit (PACU) and hospital. An exploratory analysis of longitudinal changes in QoR-15 scores within each group was also performed. Analyses were performed per protocol.

Results

Eighty-four patients completed the study. There were no differences in overall QoR-15 score between the groups at any of the three assessment time points (preoperative, 24h, and 48h). In the exploratory longitudinal within-group analysis, better maintenance of recovery quality was observed in the pregabalin group compared with baseline, with medians (IQR) of 138 (122.3–145), 132.5 (125.8–135.3), and 134 (131.5–136) [p = 0.006 between 24h and 48h]. In the placebo group, the medians (IQR) were 140 (128–145.3), 129 (126–134.3), and 134 (126.8–136.3) [p = 0.002 between pre and 24h; p = 0.026 between pre and 48h].

Conclusion

Although exploratory analysis showed a trend toward improvement within the pregabalin group, there was no significant difference in QoR-15 scores between groups.

Keywords

Anesthesia and analgesia; Anesthesia recovery periods; Mastectomy; Postoperative pain; Pregabalin

Resumo

Introdução

A cirurgia permanece como um dos tratamentos mais importantes para o câncer de mama. Nesse contexto, a qualidade da recuperação pós-operatória tornou-se uma preocupação central. O controle adequado da dor aguda é essencial para otimizar o conforto e a recuperação dos pacientes. A pregabalina pode contribuir para esse objetivo ao prevenir a sensibilização central e reduzir a ansiedade perioperatória.

Objetivos

Avaliar o efeito da pregabalina perioperatória versus placebo na qualidade de recuperação pós-operatória em pacientes submetidos à cirurgia de câncer de mama.

Métodos

Neste ensaio clínico randomizado, 92 pacientes receberam pregabalina (150 mg por via oral, 1 hora antes da cirurgia) ou placebo correspondente, ambos preparados em cápsulas idênticas. O desfecho primário foi o escore QoR-15 medido no pré-operatório e em 24 e 48 horas após a cirurgia. As avaliações de 24 e 48 horas foram realizadas por telefone. O QoR-15 é um instrumento validado que avalia a qualidade de recuperação, com pontuação total variando de 0 (recuperação muito ruim) a 150 (recuperação excelente). Desfechos secundários incluíram consumo de opioides, escores de dor, incidência de náuseas e vômitos e tempo de permanência na Sala de Recuperação Pós-Anestésica (SRPA) e no hospital. Também foi realizada uma análise exploratória das mudanças longitudinais nos escores de QoR-15 dentro de cada grupo. As análises foram realizadas por protocolo.

Resultados

Oitenta e quatro pacientes completaram o estudo. Não houve diferenças no escore global de QoR-15 entre os grupos em nenhum dos três momentos de avaliação (pré-operatório, 24h e 48h). Na análise exploratória longitudinal intra-grupo, observou-se melhor manutenção da qualidade de recuperação no grupo pregabalina em relação ao basal, com medianas (IIQ) de 138 (122,3–145), 132,5 (125,8–135,3) e 134 (131,5–136) (p = 0,006 entre 24h e 48h). No grupo placebo, as medianas (IIQ) foram 140 (128–145,3), 129 (126–134,3) e 134 (126,8–136,3) (p = 0,002 entre pré e 24h; p = 0,026 entre pré e 48h).

Conclusão

Embora a análise exploratória tenha mostrado tendência de melhora dentro do grupo pregabalina, não houve diferença significativa entre os grupos nos escores de QoR-15.

Palavras-chave

Anestesia e analgesia; Período de recuperação anestésica; Mastectomia; Dor pós-operatória; Pregabalina

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Submitted date:
07/28/2025

Accepted date:
03/19/2026