Priapismo en la drepanocitosis. Diagnóstico y opciones terapéuticas / Priapism in sickle cell disease. Diagnosis and therapeutics options

El priapismo es una complicación de la anemia drepanocítica y se define como una erección prolongada, dolorosa y persistente del pene de más de 4 horas de duración sin estimulación sexual asociada. El 95 por ciento de las crisis de priapismo en estos pacientes es de tipo isquémico o de bajo flujo y constituyen una emergencia médica que, de no diagnosticarse y tratarse adecuadamente, provoca necrosis del tejido y disfunción eréctil. En este trabajo se revisan el diagnóstico y las opciones terapéuticas actuales y futuras de esta grave complicación(AU)

Priapism is a common complication of sickle cell disease and it is characterized by a prolonged, painful and persistent erection of the penis lasting more than 4 hours without associated sexual stimulation. The 95 percent of priapism crisis in these patients is ischemic type and represents a medical emergency that can provoke erectile tissue necrosis and erectile dysfunction if not treated properly. In this paper we reviewed the diagnosisand the current and perspectives therapeutic options of this severe complication(AU)

Daily use of phosphodiesterase type 5 inhibitors as prevention for recurrent priapism / Prevenção do priapismo recorrente com a utilização diária de inibidores da fosfodiesterase tipo 5

Summary Objective: The pathogenesis of recurrent priapism is currently being investigated based on the regulation of the phosphodiesterase 5 (PDE5) enzyme. We explored the daily use of PDE5 inhibitors to treat and prevent priapism recurrences. Method: We administered PDE5 inhibitors using a long-term therapeutic regimen in seven men with recurrent priapism, with a mean age of 29.2 years (range 21 to 35 years). Six men (85.7%) had idiopathic priapism recurrences and one man (24.3%) had sickle cell disease-associated priapism recurrences. Tadalafil 5 mg was administered daily. The mean follow-up was 6.6 months (range 3 to 12 months). Results: Daily long-term oral PDE5 inhibitor therapy alleviated priapism recurrences in all patients. Five (71.4%) had no episodes of priapism and two (28.6%) referred decrease in their episodes of priapism. All patients referred improvement in erectile function. Conclusion: These findings suggest the hypothesis that PDE5 dysregulation exerts a pathogenic role for both sickle cell disease-associated priapism and for idiopathic priapism, and that it offers a molecular target for the therapeutic management of priapism. These preliminary observations suggest that continuous long-term oral PDE5 inhibitor therapy may treat and prevent recurrent priapism.

Resumo Objetivo: Uma das teorias propostas para explicar a etiologia do priapismo recorrente está baseada no mecanismo de regulação da fosfodiesterase tipo 5. Estudamos o uso diário dos inibidores de fosfodiesterase tipo 5 no tratamento e na prevenção do priapismo recorrente. Método: Sete homens com diagnóstico de priapismo recorrente, com idade média de 29,5 anos (21 a 35 anos), utilizaram inibidor de fosfodiesterase tipo 5 em dose diária (tadalafila 5 mg/dia) por período prolongado. Seis homens (85,7%) apresentavam priapismo recorrente de etiologia idiopática, e um homem (24,3%), de etiologia associada à anemia falciforme. O seguimento médio foi de 6,6 meses (3 a 12 meses). Resultados: Todos os pacientes se beneficiaram com a utilização de inibidores de fosfodiesterase tipo 5. Cinco (71,4%) não apresentaram nenhum episódio de priapismo e dois (28,6%) relataram diminuição dos episódios. Todos os pacientes relataram melhora da função erétil. Conclusão: Estes achados sugerem que a hipótese do mecanismo de regulação da fosfodiesterase tipo 5 exerce papel importante na patogenia do priapismo recorrente. O uso contínuo e diário de inibidores da fosfodiesterase tipo 5 pode ser uma opção no tratamento do priapismo recorrente.

The possible protective effects of dipyridamole on ischemic reperfusion injury of priapism

ABSTRACT Purpose To investigate the protective effects against ischemia reperfusion injury of dipyridamole in a model of induced priapism in rats. Materials and Methods Twenty-four male Sprague-Dawley rats were divided into four groups, control, P/R, P/R+DMSO and P/R+D. 3ml blood specimens were collected from vena cava inferior in order to determine serum MDA, IMA, TAS, TOS and OSI values, and penile tissue was taken for histopathological examination in control group. Priapism was induced in P/R group. After 1h, priapism was concluded and 30 min reperfusion was performed. In P/R+DMSO group 1ml/kg DMSO was administered intraperitoneally 30 min before reperfusion, while in P/R+D group 10mg/kg dipyridamole was administered intraperitoneally 30 min before reperfusion. Blood and penis specimens were collected after the end of 30 min reperfusion period. Sinusoidal area (µm2), tears in tunica albuginea and injury parameters in sinusoidal endothelium of penis were investigated. Results Histopathological examination revealed no significant changes in term of sinusoidal area. A decrease in tears was observed in P/R+D group compared to P/R group (p<0.05). Endothelial injury decreased in P/R+D group compared to P/R group (p>0.05). There were no significant differences in MDA and IMA values between groups. A significant increase in TOS and OSI values was observed in P/R+D group compared to P/R group. A significant decrease in TAS levels was observed in P/R+D group compared to the P/R group. Conclusions The administration of dipyridamole before reperfusion in ischemic priapism model has a potential protective effect against histopathological injury of the penis.

Protective effect of curcumin on priapism and ischemia-reperfusion injury in rats.

OBJECTIVE: We aimed to identify the oxidative stress effects of the ischemic priapism on cavernosal tissues and to assess the biochemical and histopathological effects of curcumin in rats. MATERIALS AND METHODS: 26 adult male Sprague Dawley rats were randomly divided into three groups. Group 1 (Control, n = 8): only penectomy was performed and 3 ml blood samples were obtained from the vena cava inferior (VCI). Group 2 (ischemia-reperfusion group; n= 8): penectomy was performed after 1 hour ischemic priapism + 30 min reperfusion and 3 ml blood samples were obtained from the VCI. Group III (IR + CURC group, n = 10): 200 mg/kg/day curcumin per orally before surgery for 7 days + penectomy after 1 hour ischemic priapism + 30 min reperfusion and 3 ml blood samples from the VCI. Total oxidant status (TAS), total antioxidant status (TAS) and paraoxonase (PON1) levels were measured. Tissue samples were investigated and scored histopathologically in terms of bleeding, edema and necrosis. RESULTS: TOS levels were higher (p = 0.002), and TAS levels were lower (p = 0.001) in the IR group compared to the control group. As a result of curcumin treatment, TAS levels were increased (p = 0.003), and TOS levels were decreased (p = 0.004) in the IR + CURC group compared to the IR group. In the treatment group (IR + CURC) TAS and TOS levels were similar to levels in the control group. PON1 levels were increased with ischemia-reperfusion (p = 0.21) and decreased with curcumin treatment (p = 0.53), however these changes were not statistically significant. There was no significant difference in the effects of curcumin on histopathological changes. CONCLUSIONS: This study showed that curcumin has preventive effects on oxidative stress parameters against ischemia-reperfusion injury.

Prophylactic phenylephrine for iatrogenic priapism: a pilot study with Peyronie's patients.

PURPOSE: Although penile duplex Doppler ultrasonography (PDDU) is a common and integral procedure in a Peyronie's disease workup, the intracavernosal injection of vasoactive agents can carry a serious risk of priapism. Risk factors include young age, good baseline erectile function, and no coronary artery disease. In addition, patients with Peyronie's disease undergoing PDDU in an outpatient setting are at increased risk given the inability to predict optimal dosing. The present study was conducted to provide support for a standard protocol of early administration of phenylephrine in patients with a sustained erection after diagnostic intracavernosal injection of vasoactive agents to prevent the deleterious effects of iatrogenic priapism. MATERIALS AND METHODS: This was a retrospective review of Peyronie's disease patients who received phenylephrine reversal after intracavernosal alprostadil (prostaglandin E1) administration to look at the priapism rate. Safety was determined on the basis of adverse events reported by subjects and efficacy was determined on the basis of the rate of priapism following intervention. RESULTS: Patients with Peyronie's disease only had better hemodynamic values on PDDU than did patients with Peyronie's disease and erectile dysfunction. All of the patients receiving prophylactic phenylephrine had complete detumescence of erections without adverse events, including no priapism cases. CONCLUSIONS: The reversal of erections with phenylephrine after intracavernosal injections of alprostadil to prevent iatrogenic priapism can be effective without increased adverse effects.

[Strategies for the treatment and prevention of priapism in children].

Priapism is defined as abnormal persisting penile erection beyond or unrelated to sexual stimulation. It is rare in children and the appropriate management consensus is lacking. We have reviewed the literature on the treatment and prevention of priapism in children in the last 5 years. The following advances were reported: (1) compression or thrombin injection guided by ultrasound in nonischemic priapism prior to selective angioembolization; (2) anti-androgen therapy is the key for the prevention of nonischemic priapism occurring and reoccurring after angioembolization; (3) etiological interventions are enough to resolve some priapism in children; (4) T tunnel may be applied to the distal shunt failed cases in children. Combined with the new progress in treatment of priapism in children, we have designed the algorithm of priapism management and the algorithm of stuttering priapism prevention. The two algorithms will be helpful for clinicians dealing with the clinical challenges in children's priapism management.

Priapism in sickle cell disease.

Priapism, an unwanted painful erection of the penis, is a little discussed but common complication of sickle cell disease. What is known about the prevalence of priapism, efficacy of management approaches, and outcome is drawn primarily from retrospective and single-center reports. Priapism occurs in two patterns: prolonged and stuttering (ie, recurrent brief episodes that resolve spontaneously). If priapism persists for 4 hours or more without detumescence, the patient is at risk for irreversible ischemic penile injury, which may terminate in fibrosis and impotence. Large multicenter studies examining the epidemiology and current treatments and well-organized trials of novel therapies are urgently needed for patients who have sickle cell disease and priapism.

The role of red blood cell exchange transfusion in the treatment and prevention of complications of sickle cell disease.

Patients with sickle cell disease have abnormal red blood cells (RBCs). This can cause chronic hemolytic anemia and vaso-occlusion leading to tissue hypoxemia and organ dysfunction. RBC exchange transfusion can, without increasing the whole-blood viscosity, quickly replace abnormal erythrocytes with normal and raise the hematocrit resulting in improved delivery of oxygen to hypoxic tissues. Unfortunately, transfusion can also be associated with complications. This paper reviews the role of transfusion, both simple and exchange, in the treatment and prevention of sickle-related complications. The benefits of exchange versus simple transfusion and transfusion versus alternative therapies are discussed.

[Ambulatory treatment and prevention of priapism using alpha-agonists. Apropos of 172 cases]. / Traitement ambulatoire et prévention du priapisme par médications alpha-agonistes. A propos de 172 cas.

From 1985 to 1995, 172 patients (149 on self intracavernous injection of vasoactive drugs, 16 with Sickle cell disease, 6 surgical patients under heparin therapy, and 1 after oral administration of trazodone), having experienced one or several episodes of priapism, lasting from 3 h to 8 days have been treated or submitted to self medication with alpha-agonist agents (eprephrine, phenylephrine or etilefrine) with an eventual drainage of the corporae. All episodes have disappeared and sexual function was preserved. A conservative treatment of priapism has been designed using corporal drainage and intracavernous etilefrine for acute priapism; as well as preventive treatment for those of the patients exposed to Sickle cell disease to avoid surgery and its frequent fribrotic sequelae, leading to impotence in 50% of the cases.

Priapism.

Priapism in adult patients with sickle cell disease is a devastating complication for which there is no consensus regarding management. Innumerable attempts at pharmacologic and surgical intervention have been employed. Distinction between infarctive low-flow priapism with hypoxia and acidosis and normal-flow priapism without acidosis can be obtained using currently available imaging techniques. Cavernosonography and radionuclide scanning to assess penile hemodynamics are useful in determining whether priapism is of the low-flow type. Advances in our understanding of the physiology of erection have prompted a more physiologic approach to the assessment and management of priapism. Based on this technology, it would be possible to develop a prospective multiinstitutional study, thereby providing sufficient numbers of patients to better evaluate therapy. After the episode of priapism has abated and detumescence has occurred, we recommend that the patient be given the option of beginning a trial of hydroxyurea or another antisickling agent.

[Diagnostic and therapeutic applications of intracavernous injection of vasoactive drugs in impotence. Defense for the use of facilitating drugs. Part I--Pharmacology, classification and complications of active drugs]. / Applications diagnostiques et thérapeutiques des injections intracaverneuses (IC) de drogues vasoactives dans l'impuissance. Plaidoyer pour l'utilisation des drogues facilitatrices. Partie I--Pharmacologie, classification et complications des drogues actives.

The article discusses drugs which promote erection when injected via the intracavernous (IC) route during consultation. The diagnostic and therapeutic applications in the treatment of impotence are discussed also. 25% of impotent patients noted an improvement after this treatment while 50% of patients suffering from impotence of psychological origin noted an improvement. Auto-injection is also discussed. IC treatment now seems justified in most cases which have not responded to traditional therapeutic approaches and this includes cases of psychological origin. Vasoactive drugs can be described as being inducers (use of these drugs induces a rigid erection, even in the presence of the doctor), facilitating drugs (which produce a rigid erection only if sexual stimulation is present also) and inhibitors (which stop the erection). The former group (which has papaverine as leader) produces a significant number of side effects, not least of these being priapism; there is a risk of lasting iatrogenic impotence which is not negligible. These risks are reduced considerably when one uses facilitating drugs which, although less powerful, suffice in treating a large proportion of cases of impotence. Papaverine can not be replaced as a diagnostic drug but facilitating drugs should be used first in therapy and inducers should be used only if these facilitating drugs have failed.