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. ICIs cause direct cavernosal vasorelaxation, bypassing the neurotransmission (release of nitric oxide from the nerve endings) resulting in an erection. Self‐administration is a barrier for SCI patients with poor hand function (Ibrahim et al. 2016b).Strengths of the injections are dictated by the concentrations of the individual components, i.e., double strength Trimix for example, whose combinations are unique to each compounding pharmacy.
Discussion
The technique of penile intracavernosal injection (ICI) of vasoactive medications, such as papaverine, phentolamine, and prostaglandin E1 (PGE1) alone or in combination, has been used to treat ED in men with SCI for over 20 years. In general, lower ICI doses were required in SCI patients, but in combination with co-morbidities such as diabetes or hypertension, higher doses may be needed to overcome endothelial damage (Sidi et al. 1987). 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%. Participants found that erections with ICIs were firmer than PDE5i (Moemen et al. 2008). Tang et al. (1995) 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 participants having successful ejaculation.
Past meta-analyses have observed that ICIs have greater efficacy than PDE5i, showing a random effects pooled estimate of 90% success rate (95% CI from 83-97%) achieving a satisfactory erection (DeForge et al. 2006). Similarly, Moemen et al. (2008) compared sildenafil and ICI use on the same group of participants, ICIs had significantly greater efficacy and IIEF-EF scores (32.6) than sildenafil (27.5). There is a dose response to the efficacy of ICI, with combination therapy introduced for synergistic effect as well as for possible economic reasons. There is only one RCT study (Renaganathan 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%).
Complication rates with ICI have been reported to range from 15-32% (Lloyd & Richards 1989; Dietzen & Lloyd 1992; Renaganathan 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. 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 the safety and efficacy in over 50 men with SCI without incidence of priapism. However, priapism has been reported with use of papaverine; ischemic priapism is a urologic emergency and requires intervention to alleviate pain and prevent damage to erectile tissues (Ericson et al. 2021). Priapism can be treated with aspiration of blood from corpora with injection of an alpha-adrenergic medication (Ericson et al. 2021; Sidi et al. 1987; Bodner et al. 1992). Soler et al. (2009) found that some patients developed priapism (i.e., prolonged erections) after PGE1 administration, but it was easily treated by orally administered midodrine; all participants returned to a flaccid penile state within 30-45 minutes of after administration. 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. 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.
