Brazilian Journal of Anesthesiology
https://bjan-sba.org/article/doi/10.1590/S0034-70942010000500004
Brazilian Journal of Anesthesiology
Scientific Article

Caracterização anestésica da nanoemulsão não lipídica de propofol

Anesthetic profile of a non-lipid propofol nanoemulsion

Roberto Takashi Sudo; Laura Bonfá; Margarete Manhães Trachez; Roberto Debom; Marisa D. R Rizzi; Gisele Zapata-Sudo

http://dx.doi.org/10.1590/S0034-70942010000500004 Braz J Anesthesiol, vol.60, n5, p.475-483, 2010
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Resumo

JUSTIFICATIVA E OBJETIVOS: Uso clínico de formulação lipídica de propofol causa dor durante injeção, reação alérgica e crescimento microbiano. Propofol tem sido reformulado em diferentes apresentações não lipídicas para reduzir os efeitos adversos, mas essas mudanças podem modificar sua farmacocinética e farmacodinâmica. Neste trabalho, investigamos a farmacologia e a toxicologia do propofol lipídico (CLP) e da nanoemulsão não lipídica (NLP). MÉTODO: CLP and NLP foram infundidos na veia jugular de ratos sob medida da pressão arterial (PA), frequência cardíaca (FC) e frequência respiratória (FR). Ambas as formulações (1%) foram infundidas (40 µL.min-1) durante 1 hora. Doses hipnóticas e anestésicas, assim como recuperações, foram determinadas. A dor induzida pelo veículo do CLP e NLP foi comparada por meio da contagem do número de contorções abdominais ("writhing test") após injeção intraperitonial (i.p.) em camundongos. Ácido acético (0,6%) foi usado como controle positivo. RESULTADOS: As doses hipnóticas e anestésicas com 1% CLP (6,0 ± 1,3 e 17,8 ± 2,6 mg.kg-1, respectivamente) e 1% NLP (5,4 ± 1,0 e 16,0 ± 1,4 mg.kg-1, respectivamente) não foram significativamente diferentes. A recuperação da hipnose e da anestesia foi mais rápida com NLP do que com CLP. As alterações de FC, PA e FR causadas pelo NLP não foram significativamente diferentes das do CLP. Ácido acético e veículo do CLP provocaram 46,0 ± 2,0 e 12,5 ± 0,6 contorções em 20 min após injeção i.p., respectivamente. Observou-se ausência de contorções abdominais com veículo de NLP. Nenhuma resposta inflamatória abdominal foi notada com a injeção i.p. de ambos os veículos de propofol. CONCLUSÕES: O NLP pode representar melhor alternativa do que o CLP para anestesia venosa com menores efeitos adversos

Palavras-chave

ANESTÉSICO, Venoso, ANIMAIS

Abstract

BACKGROUND AND OBJECTIVES: The clinical use of a lipid propofol formulation causes pain during injection, allergic reactions, and bacterial growth. Propofol has been reformulated in different non-lipid presentations to reduce the incidence of adverse effects, but those changes can modify its pharmacokinetics and pharmacodynamics. In the present study, we investigate the pharmacology and toxicology of lipid propofol (CLP) and the non-lipid nanoemulsion (NLP). METHODS: Conventional lipid formulation of propofol and NLP were infused in the jugular veins of rats and blood pressure (BP), heart rate (HR), and respiratory rate (RR) were measured. Both formulations (1%) were infused (40 µL.min-1) over 1 hour. Hypnotic and anesthetic doses as well as recoveries were determined. The pain induced by the CLP and NLP vehicles was compared by counting the number of abdominal contortions ("writhing test") after the intraperitoneal (i.p.) injection in mice. Acetic acid (0.6%) was used as positive control. RESULTS: Hypnotic and anesthetic doses of 1% CLP (6.0 ± 1.3 and 17.8 ± 2.6 mg.kg-1, respectively) and 1% NLP (5.4 ± 1.0 and 16.0 ± 1.4 mg.kg-1, respectively) were not significantly different. Recovery from hypnosis and anesthesia was faster with NLP than with CLP. Changes in HR, BP, and RR caused by NLP were not significantly different from those caused by CLP. Acetic acid and the vehicle of CLP caused 46.0 ± 2.0 and 12.5 ± 0.6 abdominal contortions 20 min after i.p. injection, respectively. The absence of abdominal contractions was observed with the vehicle of NLP. Abdominal inflammatory response was not observed after the i.p. injection of both propofol vehicles. CONCLUSIONS: Non-lipid formulation of propofol can be a better alternative to CPL for intravenous anesthesia with fewer adverse effects

Keywords

ANESTHESICS, Intravenous, ANIMALS

References

Glen JB. Animal studies of the anesthetic activity of ICI 35-868. Br J Anaesth. 1980;52:731-742.

Rolly G, Versichelen L, Zubair NA. Use of ICI 35868 as an anesthetic induction agent. Acta Anaesth Belg. 1980;31:241-247.

Shao X, Li H, White PF. Bisulfite-containing propofol: is it a costeffective alternative to Diprivan for induction of anesthesia?. Anesth Analg. 2000;91:871-875.

Kay B, Rolly G. ICI35868: The effect of a change of formulation on the incidence of pain after intravenous injection. Acta Anesthesiol Belg. 1997;28:317-322.

Jones C. Fundamentals of emulsions. Am J Anesth. 2000;27(^sSuppl):12-15.

Egan TD. Target-controlled drug delivery: progress toward an intravenous "vaporizer" and automated anesthetic administration. Anesthesiology. 2003;99:1214-1219.

Sabsovich I, Rehman Z, Yunen J. Propofol infusion syndrome: a case of increasing morbidity with traumatic brain injury. Am J Crit Care. 2007;16:82-85.

Dubey PK, Kumar A. Pain on injection of lipid-free Propofol and Propofol emulsion containing medium-chain triglyceride: a comparative study. Anesth Analg. 2005;101:1060-1062.

Baker MT, Naguib M. Propofol: the challenges of formulation. Anesthesiology. 2005;103:860-876.

Abad-Santos F, Galvez-Mugica MA, Santos MA. Pharmacokinetics and pharmacodynamics of a single bolus of propofol 2% in healthy volunteers. J Clin Pharmacol. 2003;43:397-405.

Ando R, Watanabe C. Characteristics of propofol-evoked vascular pain in anaesthetized rats. Br J Anaesth. 2005;95:384-392.

Hart B. Diprivan: a change of formulation. Eur J Anesthesiol. 2000;17:71-73.

Rau J, Roizen MF, Michael F, Doenicke AW, O'Connor M, Strohschneider U. Propofol in a emulsion of long- and medium-chain triglycerides: the effect on pain. Anesth Analg. 2001;93:382-384.

Doenicke AW, Roizen MF, Rau J. Pharmacokinetics and pharmacodynamics of propofol in a new solvent. Anesth Analg. 1997;85:1399-1403.

Paul M, Dueck M, Kampe S. Pharmacological characteristics and side effects of a new galenic formulation of propofol witout soyabean oil. Anaesthesia. 2003;58:1056-1062.

Banaszczyk MG, Carlo AT, Milan V. Propofol phosphate, a waterdrug soluble propofol prodrug: in vivo evaluation. . .

Cooke A, Anderson A, Buchanan K. Water-soluble propofol analogues with intravenous anaesthetic activity. Bioorg Med Chem Lett. 2001;11:927-930.

Trapani A, Laquintana V, Lopedota A. Evaluation of new propofol aqueous solution for intravenous anesthesia. Int J Pharm. 2004;278:91-98.

Bielen SJ, Lysco GS, Cough WB. The effect of a cyclodextrin vehicle on the cardiovascular profile of propofol in rats. Anesth Analg. 1996;82:920-924.

Trapani G, Latrofa A, Franco M. Inclusion complexation of propofol with 2-hydroxypropyl-beta-cyclodextrin: physicochemical, nuclear magnetic resonance spectroscopic studies, and anesthetic properties in rat. J Pharm Sci. 1998;87:514-518.

Huang YW, Buerkle H, Lee TH. Effect of pretreatment with ketorolac on propofol injection pain. Acta Anaesthesiol Scand. 2002;46:1021-1024.

Iwama H, Nakane M, Ohmori S. Nafamostat mesilate, a kalicrein inhibitor, prevents pain on injection with propofol. Br J Anesth. 1998;81:963-964.

Ohmizo H, Obara S, Iwana H. Mechanism of injection pain with long and long-medium chain triglyceride emulsive propofol. Can J Anaesth. 2005;52:595-599.

Fujii Y, Nakayama M. A lidocaine/metoclopramide combination decreases pain on injection of propofol. Can J Anesth. 2005;52:474-477.

Doenick AW, Roizen MF, Rotzen MF. Reducing pain during propofol injection: the role of solvent. Anesth Analg. 1996;82:472-474.

Martinez V, Coutinho SV, Thakur S. Differential effects of chemical colonic irritation on behavioral pain response to intraperitoneal acetic acid in mice. Pain. 1999;81:179-186.

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