Intracavernosal Injections (ICI) Utilizing Penile Medications
An intracavernosal (or intracavernous) injection is an injection into the base of the penis. This is often used to administer medications including alprostadil (prostaglandin E1 (PGE1)), Bimix (a combination of papaverine and phentolamine), and Trimix (a combination of papaverine, phentolamine and PGE1), to treat erectile dysfunction in adult men. This treatment can generate an erection in patients with SCI by direct cavernosal vasorelaxation, therefore bypassing the neurotransmission signals (release of nitric oxide from the nerve endings) requisite to initiate erection. Self‐administration is an issue for the subset of SCI patients with poor hand function (Ibrahim et al. 2016).
Discussion
The technique of penile intracavernosal injection (ICI) of vasoactive medications, such as papaverine, phentolamine and PGE1 alone or in combination, has been used to treat ED in men with SCI for over 20 years. Despite this, there is only one RCT study (Renganathan et al. 1997) in this area, comparing administration of intracavernosal papaverine with transdermal nitroglycerin. Patients who received ICI of papaverine were statistically more likely to have a complete response (erection) than those patients who received nitroglycerine (93% vs 61%).
Results from other non-RCTs support greater efficacy of ICI medications than PDE5i with a meta-analysis of 11 non-comparative case-series reports showing a random effects pooled estimate of 90% success rate (95% CI from 83-97%) achieving a satisfactory erection with intracavernosal injections (DeForge et al. 2006). Moemen et al. (2008) found a similar success rate of satisfactory erection with ICI but this was also comparable to the success rate of PDE5i found in the same subjects. Subjects also noted however that erections were firmer on ICI than PDE5i. It is clear that there is a dose response to the efficacy of ICI, with combination therapy introduced for synergistic effect as well as for possible economic reasons. Yildiz et al. (2011) reported that the efficacies of ICI of papaverine were similar to orally administered sildenafil citrate at all neurological lesion levels and severity in paraplegic men within the first year after SCI. In general, lower ICI doses were required in neurogenic patients, but the combination of SCI with co-morbidity such as diabetes or hypertension decreased the efficacy of injections (Sidi et al. 1987; Zaslau et al. 1999).
Complication rates with ICI have been reported to range from 15-32% (Lloyd & Richards 1989; Dietzen & Lloyd 1992; Renganathan et al. 1997; Moemen et al. 2008), with the caveat that accumulated clinical experience and choice of vasoactive medication/s with judicious adjustment of dosage reduce the risks substantially. The most common side effects of ICI are transient, such as pain and swelling at the injection site. The more serious side effect of priapism (or prolonged erection) has typically been reported with use of papaverine and can be treated with aspiration of blood from corpora with injection of an alpha-adrenergic medication (Sidi et al. 1987; Bodner et al. 1992). A reported long-term complication of ICI is fibrosis (scarring of the tunica albuginia), the risk of which can be reduced by lowering frequency of injections and minimising medication dose. Hirsch et al. (1994) noted evidence of sub-clinical corporal fibrosis in 2 out of 27 patients using ICI PGE1 with monitoring by quarterly penile ultrasound scans over 18 months.
Several small case series studies using intracavernosal injection of PGE1 (Hirsch et al. 1994; Tang et al. 1995) or PGE1 in combination with papaverine (Zaslau et al. 1999) have confirmed safety and efficacy in over 50 men with SCI without incidence of priapism. Soler et al. (2009) reported controversial results where some patients developed priapism after PGE1 administration, but it was easily treated by orally administered midodrine. Tang reported full functional erections with ICI PGE1 lasting an average duration of 59 minutes (range 30-120 mins) in 14 out of 15 men with 8 of them (7 with incomplete T4-L5 lesions and 1 with a complete L1 lesion) able to ejaculate. Prior to the availability of PDE5i, ICI had a high acceptance rate (70-86%) in the SCI population (Sidi et al. 1987; Earle et al. 1992; Watanabe et al. 1996), although longer term discontinuation has been reported in approximately 30-40%. Intracavernosal injection is also an option to consider in patients taking nitrate medications, where there are concerns about drug interactions with PDE5i.
Conclusion
There is level 2 evidence (from 1 low quality RCT: Renganathan et al. 1997) that supports the use of ICI as treatment for erectile dysfunction in men with SCI.
