through increasing levels of cyclic GMP (cGMP). This results in smooth muscle relaxation, vasodilatation of penile arteries, increased blood flow and penile erection. This effect is regulated by phosphodiesterase type 5 (PDE-5) which degrades cGMP.

•SCA patients have elevated free hemoglobin concentrations compared to normal volunteers as a result of hemolysis. This will result in increase in NO scavenging with subsequent prevention of vasodilation.

•Other associated risk factors for priapism include Lactate dehydrogenase (LDH), bilirubin and reticulocyte count which are elevated in patients with SCA and priapism.

•Chronic scavenging of NO results in a decreased expression of downstream regulatory molecules including PDE5 that normally degrades cGMP, the second messenger in NO signaling.

•The combination of chronically decreased PDE5 and normal cGMP generation following nerve stimulation may result in an unregulated, prolonged erection.

•In patients with SCA, there is:

–Reduction in NO bioavailability

–A significant down regulation of PDE-5

–Uncontrolled cGMP activity.

–Elevated levels of adenosine in the penis may also contribute to the pathogenesis of priapism but this has not been well established.

•Risk factors for priapism in SCA patients include:

–Prolonged sexual activity

–Fever

–Dehydration

–Exposure to alcohol

–The use of marijuana

–The use of cocaine, psychotropic drugs, and testosterone

•In priapism these new concepts have specific implications, as the physiologic mechanisms of erection are specifically controlled by nitric oxide.

•Notably, priapism is more frequent in the severe forms of SCD, with an association to pulmonary hypertension (up to five times more common than in other SCD patients) and strokes.

•Episodes of priapism are also linked to a rise in serum markers of hemolysis, such as increase of reticulocytes, indirect bilirubin, and lactate dehydrogenase (LDH).

23.9.5 Clinical Features

•Priapism may occur at any age. The mean age of onset is 12–15 years but has been reported in children.

•70–90 % of affected patients report their first episode prior to 20 years of age.

•The exact prevalence of priapism is not known but it has been estimated to range from 6 to 45 %.

•Priapism has been reported in various hemoglobinopathies. Commonly it is seen in sickle cell anemia (homozygous sickle cell) but has been reported in patients with hemoglobin SC disease, sickle cell beta thalassemia and rarely in those with sickle cell trait.

•Priapism may occur as an isolated episode or as part of generalized SCA vasoocclusive crisis.

•Priapism may occur also during sleep or following an active sexual intercourse.

•These patients usually present with an erect painful penis and on palpation, the penis is hard in consistency while the glans penis is soft.

•Many of these patients are not aware of this as a complication of SCA and this leads to delay in seeking medical advice.

•The mean duration of symptoms was reported to range from 6 to 70 h (mean 22 h). Some of these patients may resort to sexual intercourse in an attempt to relieve the pain.

•Stuttering priapism:

–An episode of priapism lasting more than a few minutes but less than 3 h.

–Stuttering priapism typically occur in clusters, approximately two to three times per week for several weeks.

–About 60 % of those who develop stuttering priapism will develop an attack of acute priapism in the future.

•The majority of patients with SCD report intermittent episodes preceding an acute episode.

•This emphasizes the need to investigate stuttering episodes in sickle cell outpatients, in order to actively prevent acute episodes and educate the patients.

•The most common precipitants of priapism are sexual activity (including masturbation), dehydration, fever and exposition to a cold environment.

23.9.6 Treatment

•Priapism is a serious complication of SCD.

•There are no definitive guidelines available for the treatment of SCD-related priapism.

•Although conservative management has commonly been advocated, most experts advocate emergent surgical decompression when conservative management fails.

•Patients with SCD should be educated regarding the need to seek prompt specialized treatment for any episode of priapism that lasts longer than 2 h.

•Numerous therapeutic options have been attempted, including blood transfusion, exchange blood transfusion, diethylstilbestrol, gonadotropin-releasing hormone analogues, various adrenergic agonists, and hydroxyurea.

•Few agents have actually been examined in a controlled clinical trial, making it difficult for practitioners to treat this complication.

•The parents of children with SCD should be educated about priapism and how to treat it initially.

•Some educated and willing parents could also be taught how to aspirate the cavernosa and then inject intracavernosal epinephrine or phenylephrine for prolonged episodes or for those not relieved with oral pseudoephedrine.

•It is recommended that treatment should be conservative initially.

•The patient is encouraged to drink extra fluids, urinate, exercise, and take oral analgesics. These simple measures have occasionally been sufficient enough to produce detumescence.

•If the episode of priapism persists beyond 2 h, the patient should report to the emergency department.

–The patient is assessed clinically

–The patient should be started on intravenous fluids at 1.5 their maintenance requirements.

–The patient should be given analgesics to relive the discomfort and pain.

–Anxiolytics, such as lorazepam, midazolam, or hydroxyzine pamoate, and supplemental oxygen may also be given if needed.

•If priapism persists beyond 4 h, intracaverno-

sal blood aspiration and instillation of an α-agonist should be performed under local or

regional anesthesia and repeated as needed.

•Alpha-agonists act as vasoconstrictors and are thought to induce contraction of the smooth muscle of the penile arteries of the corpora cavernosa, forcing blood out of the corpora cavernosa and into the venous system.

•Beta-agonists, on the other hand, act as vasodilators by blocking β-receptors, resulting in

smooth muscle relaxation of the vasculature. This allows oxygenated arterial blood to enter the cavernosa, washing out stagnant, already damaged sickle cells.

•Various adrenergic agonists have been used in the treatment of priapism, including:

–Pure α-agonists (e.g., metaraminol)

–Mixed α- and β-agonists (e.g., etilefrine, phenylephrine, and epinephrine)

–Pure β-agonists (e.g., terbutaline)

–Etilefrine is the ideal α-agonist to use

–Phenylephrine (preferable, since it is more selective) or epinephrine can be used also.

–Metaraminol is associated with side effects including transient but severe hypertension.

•The procedure consist of intracavernosal aspiration followed by irrigation with 10 mL of a 1:1,000,000 solution of epinephrine. Aspiration continued until detumescence occurred. If detumescence lasts for at least 30 min, the patient is discharged from the emergency department.

•Others use intracavernosal aspiration and irrigation with diluted epinephrine (20 mL of a solution of 1 mL 1:1,000 epinephrine in 1 L of 0.9 % sodium chloride) are performed.

–Irrigation and aspiration are performed until sustained detumescence was achieved or a maximum of 200 mL of solution was used, after which an emergency shunt is performed.

–If irrigation was successful, the patient is observed for 24 h and then discharged home.

•The procedure of aspiration and irrigation (Figs. 23.9, 23.10, 23.11, 23.12, and 23.13):

–Apply local anesthetic blockade

–A 21-gauge needle is used for children.

Fig. 23.11 Clinical photograph showing a child with sickle cell disease and priapism being treated with aspiration and irrigation

–Puncture one of the corpora cavernosa, usually via the glans

–In the majority of cases it is not necessary to puncture the two corpora cavernosa.

–Blood should be collected for gas analysis and confirmation of the diagnosis.

–Thereafter the corpora cavernosa are drained.

–Irrigation and drainage of the full extension of the corpora is more efficient.

–The volume of blood removed in the aspiration:

•This should be limited to a maximum of 7.5 mL/kg (10 % of the blood volume in children >1 year of age), because of the risk of provoking hypovolemia or shock.

–Alpha-adrenergic agonists (etilefrine, phenylephrine, epinephrine, metaraminol) are then injected.

–Injection of adrenergic agents is known to be associated with complications including:

•Infection

•Hematomas

•Urethral injury

•Fibrosis at the injection site

•Rarely, penile necrosis.

–The proposed dosages are:

•10 ml of adrenaline 1:1,000,000

– The overall success rate is 87 %

– A 100 % success was reported in those <24 h duration of priapism

– In 20 % of cases it was necessary to repeat the injection.

•Other authors propose diluting 1 mL of adrenaline 1:1,000 solution in 1 L of