Factors affecting diazepam availability from intravenous admixture solutions

Arruda, Walter Oleschko; Brito Filho, Dilermando; Rosa, Solange L. C.; Fontoura, Paulo S. G.; Cardoso, Moema De Araújo

doi:10.1590/S0004-282X1989000300007

Abstracts

The authors studied the availability of parenteral solutions of diazepam in glass bottles or polyethylene (PE) containers during infusion through polyvinyl chloride (PVC) administration sets. Diazepam solutions in concentration of 10O0mg/5OOml in 0.9% sodium chloride (NS) and 5% glucose (G5W) injection were infused at a flow rate of 30ml/h, and samples were taken from the bottle and at the end of the administration set, till 12 hours of infusion. The samples were tested in triplicate using ultraviolet spectrophotometry. The greatest loss of diazepam was observed in all solutions at 30 minutes of infusion (63.5% G5W glass, 60.5% NS glass, 55% G5W PE and 58% NS PE from the original concentration of 200 ug/ml). The diazepam concentrations in the containers did not significantly changed. The loss of diazepam from solutions infused through PVC administration sets should be kept in mind in severe clinical situations as status epilepticus, tetanus and eclampsia.

Foram estudadas as variações de concentração do diazepam diluído em diferentes solventes e frascos, para emprego endovenoso contínuo. Foram feitas soluções em soro fisiológico (NS) e soro glicosado a 5% (G5W), frascos de vidro ou de polietileno (PE), volume total de 500ml, concentração inicial de diazepam de 200 ug/ml. Cada frasco foi conectado a equipo de polivinilcloreto (PVC) e as soluções foram infundidas a razão de 30 ml/h. Amostras coletadas dos frascos e dos equipos até 12 horas de infusão foram testadas em triplicata, por espectrofotometria ultravioleta. O maior decréscimo da concentração de diazepam ocorreu em todos os frascos aos 30 minutos de infusão, com concentrações 63,5% (G5W vidro), 55% (G5W PE), 60,5% (NS vidro) e 58% (NS PE) da concentração inicial. As concentrações nos frascos de vidro e PE permaneceram constantes. A diminuição das concentrações de diazepam deve-se à adsorção do diazepam aos equipos de PVC e essa perda deve ser levada em conta durante seu emprego em situações clinicas graves como status epilepticus, tétano e eclâmpsia.

Factors affecting diazepam availability from intravenous admixture solutions

Fatores que influenciam a infusão endovenosa continua de diazepam

Walter Oleschko Arruda^I; Dilermando Brito Filho^II; Solange L. C. Rosa^III; Paulo S. G. Fontoura^III; Moema De Araújo Cardoso^IV

^IIntensive Care Unit, Hospital de Clínicas, Universidade Federal do Paraná, and Laboratory of Toxicology, Instituto Médico Legal do Paraná: M.D., Neurologist, recipient of the National Research Council (CNPq) grant

^IIIntensive Care Unit, Hospital de Clínicas, Universidade Federal do Paraná, and Laboratory of Toxicology, Instituto Médico Legal do Paraná:M.D., Chief of Laboratory

^IIIIntensive Care Unit, Hospital de Clínicas, Universidade Federal do Paraná, and Laboratory of Toxicology, Instituto Médico Legal do Paraná: B.A.

^IVIntensive Care Unit, Hospital de Clínicas, Universidade Federal do Paraná, and Laboratory of Toxicology, Instituto Médico Legal do Paraná: M.D.

SUMMARY

The authors studied the availability of parenteral solutions of diazepam in glass bottles or polyethylene (PE) containers during infusion through polyvinyl chloride (PVC) administration sets. Diazepam solutions in concentration of 10O0mg/5OOml in 0.9% sodium chloride (NS) and 5% glucose (G5W) injection were infused at a flow rate of 30ml/h, and samples were taken from the bottle and at the end of the administration set, till 12 hours of infusion. The samples were tested in triplicate using ultraviolet spectrophotometry. The greatest loss of diazepam was observed in all solutions at 30 minutes of infusion (63.5% G5W glass, 60.5% NS glass, 55% G5W PE and 58% NS PE from the original concentration of 200 ug/ml). The diazepam concentrations in the containers did not significantly changed. The loss of diazepam from solutions infused through PVC administration sets should be kept in mind in severe clinical situations as status epilepticus, tetanus and eclampsia.

RESUMO

Foram estudadas as variações de concentração do diazepam diluído em diferentes solventes e frascos, para emprego endovenoso contínuo. Foram feitas soluções em soro fisiológico (NS) e soro glicosado a 5% (G5W), frascos de vidro ou de polietileno (PE), volume total de 500ml, concentração inicial de diazepam de 200 ug/ml. Cada frasco foi conectado a equipo de polivinilcloreto (PVC) e as soluções foram infundidas a razão de 30 ml/h. Amostras coletadas dos frascos e dos equipos até 12 horas de infusão foram testadas em triplicata, por espectrofotometria ultravioleta. O maior decréscimo da concentração de diazepam ocorreu em todos os frascos aos 30 minutos de infusão, com concentrações 63,5% (G5W vidro), 55% (G5W PE), 60,5% (NS vidro) e 58% (NS PE) da concentração inicial. As concentrações nos frascos de vidro e PE permaneceram constantes. A diminuição das concentrações de diazepam deve-se à adsorção do diazepam aos equipos de PVC e essa perda deve ser levada em conta durante seu emprego em situações clinicas graves como status epilepticus, tétano e eclâmpsia.

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Acknowledgements - Maria Lúcia Nossar Simões de Dalgo, Diretora Científica, Laboratórios B. Braun S.A., kindly give information concerning the chemical nature of B. Braun products as well as available literature. Diazepam (VALIUM) injections were kindly supplied by Dr. Coriolano Miranda, Gerente do Departamento Médico, Laboratório Roche. We wish to thank Prof. Murilo G. Bittencourt and Prof. Paulo R. Cruz Marquetti for their support.

Rua Gonçalves Dias, 713 - 80240 Curitiba PR - Brasil.

1. Arruda WO - Estado de mal epiléptico. Folha Médica 94: 357. 1987.
2. Baskett TF, Bradford CR - Active management of severe pre-eclampsia. Can Med Assoc J 109: 1209, 1973.
3. Clausa RM - Trataiuento de Tétano Grave. Dissertação de Mestrado. Universidade Federal do Paraná, Curitiba, 1981.
4. Cloyd JC, Vezeau C, Miller KW - Availability of diazepam from plastic containers. Am J Hosp Pharm 37: 492, 1980.
5. Dundee JW, Haslett WHK - The benzodiazepines: a review of their actions and uses relative to anaesthetic practice. Br J Anaesth 42: 217, 1970.
6. Hancock EG, Black CD - Effect of a polyethylene-lined administration set on the availability of diazepam injection. Am J Hosp Pharm 42: 335, 1985.
7. Kowaluk EA, Roberts MS, Blackburn HD, Polack AE - Interactions between drugs and polyvinyl chloride infusion bags. Am J Hosp Pharm 38: 1308, 1981.
8. Kowaluk EA, Roberts MS, Polack AE - Interactions between drugs and intravenous delivery systems. Am J Hosp Pharm 39: 460, 1982.
9. Kowaluk EA, Roberts MS, Polack AE - Factors affecting the availability of diazepam stored in plastic bags and administered through intravenous sets. Am J Hosp Pharm 40:417, 1983.
10. Lin S-Y - Pluronic surfactants affecting diazepam solubility, compatibility and adsorption from i.v. admixture solutions. J Parent Sci Technol 41: 83, 1987.
11. MacKichan J, Duffner PK, Cohen ME - Adsorption of diazepam to plastic tubing. N Engl J Med 301: 332, 1979.
12. Mason NA, Cline S, Hyneck ML, Berardi RR, No NFH, Flynn GL - I actors affecting diazepam infusion: solubility, administration-set composition and flow-rate. Am J Hosp Pharm 38: 1449, 1981.
13. Parker WA, Morris ME, Shearer CA - Incompatibility of diazepam injection in plastic intravenous bags. Am J Hosp Pharm 36: 505, 1979.
14. Parker WA, MacCara ME - Compatibility of diazepam with intravenous fluid containers and administration sets. Am J Hosp Pharm 37: 496, 1980.
15. Yliruusi JK, Sothmann AG, Laine RH, Rajasilta RA, Kristoffersson ER - Sorptive loss of diazepam and nitroglycerin from solutions to three types of containers. Am J Hosp Pharm 39: 1018, 1982.
16. Yliruusi JK, Uotila JA, Kristoffersson ER - Effect of flow rate and type of i.v. container on adsorption of diazepam to i.v. administration systems. Am J Hsop Pharm 43: 2795, 1986.

Publication Dates

Publication in this collection
06 June 2011
Date of issue
Sept 1989

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Arruda WO - Estado de mal epiléptico. Folha Médica 94: 357. 1987.

[2] 2. Baskett TF, Bradford CR - Active management of severe pre-eclampsia. Can Med Assoc J 109: 1209, 1973.

[3] 3. Clausa RM - Trataiuento de Tétano Grave. Dissertação de Mestrado. Universidade Federal do Paraná, Curitiba, 1981.

[4] 4. Cloyd JC, Vezeau C, Miller KW - Availability of diazepam from plastic containers. Am J Hosp Pharm 37: 492, 1980.

[5] 5. Dundee JW, Haslett WHK - The benzodiazepines: a review of their actions and uses relative to anaesthetic practice. Br J Anaesth 42: 217, 1970.

[6] 6. Hancock EG, Black CD - Effect of a polyethylene-lined administration set on the availability of diazepam injection. Am J Hosp Pharm 42: 335, 1985.

[7] 7. Kowaluk EA, Roberts MS, Blackburn HD, Polack AE - Interactions between drugs and polyvinyl chloride infusion bags. Am J Hosp Pharm 38: 1308, 1981.

[8] 8. Kowaluk EA, Roberts MS, Polack AE - Interactions between drugs and intravenous delivery systems. Am J Hosp Pharm 39: 460, 1982.

[9] 9. Kowaluk EA, Roberts MS, Polack AE - Factors affecting the availability of diazepam stored in plastic bags and administered through intravenous sets. Am J Hosp Pharm 40:417, 1983.

[10] 10. Lin S-Y - Pluronic surfactants affecting diazepam solubility, compatibility and adsorption from i.v. admixture solutions. J Parent Sci Technol 41: 83, 1987.

[11] 11. MacKichan J, Duffner PK, Cohen ME - Adsorption of diazepam to plastic tubing. N Engl J Med 301: 332, 1979.

[12] 12. Mason NA, Cline S, Hyneck ML, Berardi RR, No NFH, Flynn GL - I actors affecting diazepam infusion: solubility, administration-set composition and flow-rate. Am J Hosp Pharm 38: 1449, 1981.

[13] 13. Parker WA, Morris ME, Shearer CA - Incompatibility of diazepam injection in plastic intravenous bags. Am J Hosp Pharm 36: 505, 1979.

[14] 14. Parker WA, MacCara ME - Compatibility of diazepam with intravenous fluid containers and administration sets. Am J Hosp Pharm 37: 496, 1980.

[15] 15. Yliruusi JK, Sothmann AG, Laine RH, Rajasilta RA, Kristoffersson ER - Sorptive loss of diazepam and nitroglycerin from solutions to three types of containers. Am J Hosp Pharm 39: 1018, 1982.

[16] 16. Yliruusi JK, Uotila JA, Kristoffersson ER - Effect of flow rate and type of i.v. container on adsorption of diazepam to i.v. administration systems. Am J Hsop Pharm 43: 2795, 1986.