Brazilian Journal of Anesthesiology
https://bjan-sba.org/article/doi/10.1016/j.bjane.2020.10.002
Brazilian Journal of Anesthesiology
Clinical Research

Effect of pre-administered flurbiprofen axetil on the EC50 of propofol during anesthesia in unstimulated patients: a randomized clinical trial

Efeito da pré-administração de flurbiprofeno axetil na CE50 do propofol durante anestesia em pacientes não estimulados: estudo clínico randomizado

Jing Ma, Mian Peng, Fei Wang, Lei Chen, Zong-Ze Zhang, Yan-Lin Wang

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Abstract

Background and objectives
Preoperative use of flurbiprofen axetil (FA) is extensively adopted to modulate the effects of analgesia. However, the relationship between FA and sedation agents remains unclear. In this study, we aimed to investigate the effects of different doses of FA on the median Effective Concentration (EC50) of propofol.

Methods
Ninety-six patients (ASA I or II, aged 18–65 years) were randomly assigned into one of four groups in a 1:1:1:1 ratio. Group A (control group) received 10 mL of Intralipid, and groups B, C and D received 0.5 mg.kg-1, 0.75 mg.kg-1 and 1 mg.kg-1 of FA, respectively, 10 minutes before induction. The depth of anesthesia was measured by the Bispectral Index (BIS). The “up-and-down” method was used to calculate the EC50 of propofol. During the equilibration period, if BIS ≤ 50 (or BIS > 50), the next patient would receive a 0.5 μg.mL-1-lower (or-higher) propofol Target-Controlled Infusion (TCI) concentration. The hemodynamic data were recorded at baseline, 10 minutes after FA administration, after induction, after intubation and 15 minutes after intubation.

Results The EC50 of propofol was lower in Group C (2.32 μg.mL-1, 95% Confidence Interval [95% CI] 1.85–2.75) and D (2.39 μg.mL-1, 95% CI 1.91–2.67) than in Group A (2.96 μg.mL-1, 95% CI 2.55–3.33) (p = 0.023, p = 0.048, respectively). There were no significant differences in the EC50 between Group B (2.53 μg.mL-1, 95% CI 2.33–2.71) and Group A (p ˃ 0.05). There were no significant differences in Heart Rate (HR) among groups A, B and C. The HR was significantly lower in Group D than in Group A after intubation (66 ± 6 vs. 80 ± 10 bpm, p < 0.01) and 15 minutes after intubation (61 ± 4 vs. 70 ± 8 bpm, p < 0.01). There were no significant differences among the four groups in Mean Arterial Pressure (MAP) at any time point. The MAP of the four groups was significantly lower after induction, after intubation, and 15 minutes after intubation than at baseline (p < 0.05).

Conclusion
High-dose FA (0.75 mg.kg-1 or 1 mg.kg-1) reduces the EC50 of propofol, and 1 mg.kg-1 FA reduces the HR for adequate anesthesia in unstimulated patients. Although this result should be investigated in cases of surgical stimulation, we suggest that FA pre-administration may reduce the propofol requirement when the depth of anesthesia is measured by BIS.

Keywords

Flurbiprofen axetil;  NSAIDs;  Median effective concentration;  Propofol

Resumo

Justificativa e objetivos
A administração pré-operatória de Flurbiprofeno Axetil (FA) é amplamente usada para a modulação da analgesia. No entanto, a relação entre FA e fármacos sedativos permanece obscura. Neste estudo, nosso objetivo foi investigar os efeitos de diferentes doses de FA na Concentração Efetiva mediana (CE50) do propofol.

Métodos
Noventa e seis pacientes (ASA I ou II, com idades de 18–65 anos) foram alocados aleatoriamente em quatro grupos na proporção de 1:1:1:1. Dez minutos antes da indução, o Grupo A (grupo controle) recebeu 10 mL de Intralipid, enquanto os grupos B, C e D receberam FA na dose de 0,5 mg.kg-1; 0,75 mg.kg-1 e 1 mg.kg-1, respectivamente. A profundidade da anestesia foi medida pelo Índice Bispectral (BIS). O método up-and-down foi usado para calcular a CE50 do propofol. Durante o período de equilíbrio, se o valor do BIS fosse ≤ 50 ou BIS > 50, o próximo paciente tinha a infusão de propofol ajustada para uma concentração alvo-controlada 0,5 μg.mL-1 inferior ou superior, respectivamente. Os dados hemodinâmicos foram registrados no início do estudo, 10 minutos após a administração de FA, após a indução, após a intubação e 15 minutos após a intubação.

Resultados
A CE50 do propofol foi menor no Grupo C (2,32 μg.mL-1, Intervalo de Confiança de 95% [95% IC] 1,85–2,75) e D (2,39 μg.mL-1, 95% IC 1,91–2,67) do que no Grupo A (2,96 μg.mL-1; 95% IC 2,55–3,33) (p = 0,023, p = 0,048, respectivamente). Não houve diferenças significantes na CE50 entre o Grupo B (2,53 μg.mL-1, 95% IC 2,33–2,71) e o Grupo A (p > 0,05). Não houve diferenças significantes na Frequência Cardíaca (FC) entre os grupos A, B e C. A FC foi significantemente menor no grupo D do que no grupo A após a intubação (66 ± 6 vs. 80 ± 10 bpm, p < 0,01) e 15 minutos após a intubação (61 ± 4 vs. 70 ± 8 bpm, p < 0,01). Não houve diferenças significantes entre os quatro grupos na Pressão Arterial Média (PAM) em qualquer momento. A PAM dos quatro grupos foi significantemente menor após a indução, após a intubação e 15 minutos após a intubação do que na linha de base (p < 0,05).

Conclusão
FA em altas doses (0,75 mg.kg-1 ou 1 mg.kg-1) reduz a CE50 do propofol, e 1 mg.kg-1 de FA reduz a FC durante níveis adequados de anestesia em pacientes não estimulados. Embora esse resultado deva ser investigado na presença de estimulação cirúrgica, sugerimos que a pré-administração de FA pode reduzir a necessidade de propofol durante anestesia cuja profundidade seja monitorada pelo BIS.

Palavras-chave

Flurbiprofeno axetil;  AINE;  Concentração efetiva mediana;  Propofol

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