Section 4 Plastic and Reconstructive Problems

HANDL I NG BOTUL I NUM TOX I NS

temperature, and no microbial growth was noted. The same results were found in eight vials of this product kept refrigerated for 15 days after reconstitution. 52

number of individuals were resistant to the toxin, so higher dilutions are no longer recommended.

Hankins and colleagues evaluated 46 patients with glabellar wrinkles injected with different concentrations of onabotulinumtoxinA ranging from 10 and 100 U/mL for up to 21 weeks. They found no differences in effect or duration of treatment, but larger volumes were associated with greater discomfort. 72 Le Louarn 41 described his dilution technique, in which large volumes of saline mixed with epineph- rine were added (2 or 3 times the initial volume) to abobotulinumtoxinA and onabotulinumtoxinA. This diluted toxin was used to treat areas of the face where a higher spread, in his opinion, would be beneficial, such as the frontalis, platysma, and orbicularis oculi muscles. In a study with 10 volunteers, 73 Hsu and colleagues injected the forehead with 5 U of onabotulinumtox- inA diluted to 20 (5mL) or 100 U/mL (1mL). They found that higher-volume injections resulted in greater diffusion and a larger affected area and sug- gested that muscle contraction influences the pattern of toxin spread. Carruthers and colleagues studied the effect of dif- ferent dilutions of onabotulinumtoxinA in the treatment of glabellar rhytides. They followed 80 patients treated with dilutions of 10, 20, 33.3, or 100 U/mL in the glabella (20/group) for 48 weeks. There were no statistical differences in treatment success or adverse effect reports, although six cases of eyebrow ptosis were F all in the higher-dilution group. 74 Another trial enrolled 20 patients treated for lateral orbital rhytides observed for 90 days. Two different dilutions of onabotulinumtoxinA were used (20 and 100 U/mL); no statistically significant differences were detected in response or adverse effects, even though the lower-dilution group showed a slightly better response. 75

Dilution Issues

There is considerable discussion about the effect of dilution of BoNTs on clinical effect, duration, or diffusion. The package insert for onabotulinumtox- inA and incobotulinumtoxinA recommends dilution of 100 U in 1 to 8mL of saline (12.5–100 U/mL). 15,19 For abobotulinumtoxinA, 300 U can be diluted in 0.6 to 2.5mL (120–500 U/mL). 16 Rimabotulinum- toxinB can be diluted as much as 6 times using normal saline, but a more-concentrated solution cannot be generated. 43,51,61,62 Many authors believe that higher dilutions could be associated with greater risk of diffusion to unwanted sites, 12,63–68 unsatisfactory results, or shorter dura- tion, but this is not unanimous in the literature. To better understand the effect of dilution on diffu- sion, side effects, and treatment success, studies were reviewed according to indication. Expert consensus panels for cosmetic indications recommend dilutions between 1 and 3mL of saline for onabotulinumtoxinA 22 and between 1.5 and 2.5mL for abobotulinumtoxinA. 32,69 In 1996, a group reported the use of large volumes os low dose BoNTA 70 , with dilutions of 5 and 10 mL of onabotulinumtoxin A. Two years later, Fulton 71 compared injections to one side of the face with dilutions of 10mL with those of 15 and 20mL/vial in 10 individuals. He noted that the 10- and 15-mL dilutions were efficacious but had shorter duration. Frequent retreatments were needed to maintain long-term results. He also reported that a great Facial Muscles Cosmetic Indications

DERMATOLOG I C SURGERY