Thrombophlebitis, diazepam

Diazepam, a long-acting benzodiazepine can be used either intravenously (risk of thrombophlebitis) or intramuscularly or rectally (both of the last two routes are associated with slow absorption). 

Diazepam may be used in status epilepticus where it is administered intravenously. However, there is a risk of thrombophlebitis. Diazepam has a long half-life and it is rapidly absorbed into the brain. 

Hypotension follows the intravenous injection of benzodiazepines, but is usually mild and transient (SED-11, 92) (56), except in neonates who are particularly sensitive to this effect (57). Local reactions to injected diazepam are quite common and can progress to compartment syndrome (SEDA-17, 44). In one study (58), two-thirds of the patients had some problem, and most eventually progressed to thrombophlebitis. Flunitrazepam is similar to diazepam in this regard... 

Midazolam, being water-soluble, might be expected to produce fewer problems in five separate studies there were no cases of thrombophlebitis, and in two others the incidence was 8-10%, less than with diazepam but similar to thiopental and saline (61). 

In several cases the special nature of a formulation will preclude dilution by an aqueous infusion fluid. Injectable products containing phenytoin, digoxin and diazepam may come into this category if they are formulated in a nonaqueous but water-miscible solvent (such as an alcohol-water mixture) or as a solubilised (e.g. micellar) preparation. Addition of the formulation to water may result in precipitation of the dmg, depending on the final concentration of the dmg and solvent. It has been suggested that precipitation of the relatively insoluble diazepam may account for the high (3.5%) incidence of thrombophlebitis which occurs when diazepam is given intravenously. 

Diazepam (Diazemuls) Reduced thrombophlebitis improved LD.I0 (mice) 4,71,72... 

J. Sarubin. Verinindene Thrombophlebitis-Hautigkeu nach i.v. Gabc von Diazepam in neuem Losungsmitiel (Sojabtthnendl-Emulsion). Fortsehr. Med,. 100 2135-21.16. 1982... 

Propylene glycol and 20 % Cremophor EL have been compared as vehicles for diazepam [170] in view of the number of reports of thrombophlebitis associated with intravenous diazepam. The Cremophor vehicle caused significantly less postinjection thrombophlebitis possibly because it prevents the precipitation of the drug substance at the site of injection by its solubilizing effect. Ease of injection... 

Table 7.16(a) Frequency (%) of thrombophlebitis after i.v. diazepam dissolved in propylene ycol or Cremophor EL... 

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