Priapism

To be updated with 2021 AUA/SMSNA Guidelines on Priapism

• Guideline search up to February 2021

Definition

• Priapism: a persistent penile erection that continues > 4 hours beyond, or is unrelated to, sexual stimulation★
• Typically, only the corpora cavernosa are affected.

Classification (3)

1. Ischemic
2. Non-ischemic
3. Recurrent non-ischemic (stuttering)

Ischemic priapism (veno-occlusive, low-flow)

• Majority of cases
• Characterized by little or no cavernous blood flow
• Associated with (features that distinguish this from non-ischemic priapism)
  1. Pain
  2. Fully rigid and tender corpora cavernosa
  3. Abnormal blood gas (i.e., hypoxic, hypercarbic, acidotic)
• Requires prompt evaluation and may require emergency management
  • Natural history of untreated acute ischemic priapism includes days to weeks of painful erections followed by permanent loss of erectile function
  • Duration of ischemic priapism is associated with the risk of future erectile dysfunction
    • In sickle cell disease patients in whom priapism was reversed, spontaneous erections (with or without use of sildenafil) were reported in:
      • 100% when priapism was reversed by 12 hours
      • 78% when reversed by 12-24 hours
      • 44% when reversed by 24-36 hours
      • 0% when reversed ≥36 hours
      • Bennett, Nelson, and John Mulhall. "Sickle cell disease status and outcomes of African-American men presenting with priapism." The journal of sexual medicine 5.5 (2008): 1244-1250.
    • A more recent study that the cutoff for irreversible restoration of erectile tissue is 48 hours[1]
    • Interventions beyond 48-72 hours of onset may relieve erection and pain but have little benefit in preserving potency

Non-ischemic priapism (arterial, high-flow)

• Relatively rare
• May last hours to weeks and is frequently recurrent
• Pathogenesis:
  • Likely results from unregulated control of arterial inflow and cavernous smooth muscle tone
  • Usually involves perineal or penile trauma resulting in laceration of the cavernous artery (or one of its branches within the corpora) and unregulated cavernous arterial inflow. The arteriolacunar fistula is typically unilateral.
    • Most common cause is a straddle injury to the crura
      • Other mechanisms of traumatic arterial laceration include coital trauma, kicks to the penis or perineum, pelvic fractures, birth canal trauma to the male newborn, needle lacerations, iatrogenic needle injury, complications of penile diagnostics, vascular erosions complicating metastatic infiltration of the corpora, and after iatrogenic trauma from coldknife urethrotomy, corporoplasty, and penile revascularization procedures
        • Sustained partial erection may develop 24 hours after perineal or penile blunt trauma
        • After either aggressive medical management of ischemic priapism or surgical shunting, priapism may rapidly recur with conversion from ischemic (low-flow) to non-ischemic (high-flow)
  • Other causes include Fabry disease and sickle cell anemia
• Associated with (features that distinguish this from ischemic priapism)
  1. Lack of pain (beyond pain from potential acute traumatic etiology)
  2. Tumescent but less rigid corpora cavernosa
     • Erection is partial and bendable because there is no restriction of venous outflow,
     • Patients do report additional engorgement with sexual stimulation, with return to partial erection after climax
  3. Normal penile blood gas (features that distinguish this from non-ischemic priapism)
• Once properly diagnosed, does not require emergent intervention

Recurrent ischemic priapism

• Definition: Recurrent ischemic episodes, with or without meeting the 4-hour time criteria for priapism
  • Unwanted painful erections occur repeatedly with intervening periods of detumescence
  • Both acute ischemic priapism and non-ischemic priapism may recur over time
• Commonly known as "stuttering" priapism
• Commonly associated with sickle cell disease
  • Priapism in children and adolescents is most commonly related to sickle cell disease
    • The sickle cell genetic mutation is the result of a single amino acid substitution in the beta-globin subunit of hemoglobin S.
    • Clinical features seen in homozygous sickle cell disease: chronic hemolysis, vascular occlusion, tissue ischemia, and end-organ damage.
    • Sickle cell trait can be a predisposing factor to ischemic priapism.
  • Pathogenesis is related to hemolysis and reduced nitric oxide
• Management focuses on treatment of acute episodes and prevention of future events.

Pathogenesis

Risk factors (8)

1. Medications (9):
   1. α-blockers (prazosin, terazosin, doxazosin, tamsulosin)
   2. Anti-anxiety agents (hydroxyzine)
   3. Anti-depressants and antipsychotics (trazodone, bupropion, fluoxetine, sertraline, lithium, clozapine, risperidone, olanzapine, chlorpromazine, thioridazine, phenothiazines)
   4. Anti-coagulants (heparin, warfarin)
   5. Antihypertensives (hydralazine, guanethidine, propranolol)
   6. Attention-deficit/hyperactivity disorder agents (methylphenidates (concerta, daytrana, focalin, metadate, methylin, quillivant, ritalin), atomoxetine (strattera))
   7. Recreational drugs (alcohol, cocaine (intranasal and topical), marijuana)
   8. Hormones (gonadotropin-releasing hormone, testosterone)
   9. Vasoactive erectile agents (papaverine, phentolamine, prostaglandin E1, oral phosphodiesterase type 5 (PDE5) inhibitors, combination intracavernous therapy)
      • Most case reports describing priapism after use of a PDE5 inhibitor reveal histories of increased risk of priapism: sickle cell disease, spinal cord injury, use of a PDE5 inhibitor recreationally, use of a PDE5 inhibitor in combination with intracavernosal injections, history of penile trauma, use of psychotropic medications, or use of recreational drugs; risk is even lower for daily dosing PDE5 inhibitor
2. Genitourinary conditions (straddle injury, coital injury, pelvic trauma, kick to penis or perineum, arteriovenous or arteriocavernous bypass surgery, urinary retention)
3. Thrombotic disease states (asplenia, erythropoietin use, hemodialysis with heparin use, and cessation of warfarin)
4. Hematologic dyscrasias (sickle cell disease, thalassemia, granulocytic leukemia, myeloid leukemia, lymphocytic leukemia, multiple myeloma, hemoglobin Olmsted variant, fat emboli associated with hyperalimentation, hemodialysis, glucose-6-phosphate dehydrogenase deficiency)
5. Infectious (toxin-mediated) causes (scorpion sting, spider bite, rabies, malaria)
6. Metabolic conditions (amyloidosis, Fabry disease, gout)
7. Cancer (metastatic or regional infiltration) (prostate, urethra, testis, bladder, rectum, lung, kidney)
8. Neurogenic conditions (syphilis, spinal cord injury, autonomic neuropathy, lumbar disk herniation, spinal stenosis, cerebral vascular accident, brain tumor, spinal anesthesia, cauda equina syndrome)

Molecular basis of ischemic and stuttering priapism

• Direct result of NO imbalance resulting in aberrant molecular signaling, PDE5 activity downregulation, adenosine overproduction, and reductions in Rho-kinase activity, translating into enhanced corporal smooth muscle relaxation and inhibition of vasoconstriction in the penis
• Excessive adenosine accumulation in the penis, coupled with increased A(2B)R signaling, contributes to priapism in two independent lines of mutant mice.

Diagnosis and Evaluation

UrologySchool.com Summary

• Recommended
  • History and Physical Exam
  • Labs (2)
    1. Corporal blood gas
    2. CBC
• Optional
  • Labs (2)
    • Hemoglobin electrophoresis
    • Screening for psychoactive drugs and urine toxicology
  • Imaging
    • Penile duplex Doppler ultrasonography
      • When the diagnosis of acute ischemic versus non-ischemic priapism is indeterminate

History and Physical Exam

• In the majority of cases, the differentiation of acute ischemic priapism versus NIP may be made using only the history and physical exam. 
  • In cases where the subtype is indeterminate, additional testing may be warranted.

History

• Signs and Symptoms
  • Sexual history
    • Duration of erection, presence of pain
    • Baseline erectile function
• Risk factors
  • Medical history
    • Personal or family history of sickle cell disease, hemoglobinopathies, hypercoagulable states
    • Pelvic, genital, or perineal trauma, especially a perineal straddle injury
    • Previous episodes of priapism and method of treatment
  • Medications that might have precipitated the episode
    • Use of any erectogenic therapies (both prescription and nutritional supplements)
    • Use of recreational drugs

Physical Exam

• Genitalia
  • The corpora cavernosa are typically affected while the corpus spongiosum and the glans penis are not
  • In ischemic priapism, the corpora cavernosa are often fully rigid and tender
  • In non-ischemic priapism, the corporal cavernosa will be tumescent, partially erect, but not completely rigid. The penis is also unlikely to be tender
• Abdominal, pelvic, and perineum
  • May reveal evidence of trauma or malignancy.

Laboratory

• Corporal blood gas by aspiration
  • Should be obtained in the emergency evaluation of priapism★
  • Most common diagnostic methods of distinguishing acute ischemic priapism from NIP when the diagnosis cannot be made by history alone
  • Blood aspirated from the corpus cavernosum in patients with acute ischemic priapism is hypoxic (dark red), while corporal blood in NIP patients is normally oxygenated (bright red)

Source	PO2 (mm Hg)	PCO2 (mm Hg)	pH
Normal arterial blood (room air)	>90	<40	7.40
Normal mixed venous blood (room air)	40	50	7.35
Ischemic priapism (first corporal aspirate)	<30	>60	<7.25

• CBC
  • May identify elevated white blood cell counts, potentially identifying cases where priapism is due to underlying malignancy (e.g., leukemia). 
  • Among men with sickle cell disease, acute ischemic priapism is associated with lower hemoglobin and elevated lactate dehydrogenase, bilirubin, aspartate aminotransferase, reticulocyte count, white blood cells, and platelet counts.
  • Platelet and eosinophil counts may also be elevated in men with acute ischemic priapism.
  • While these laboratory values may contribute to the identification of underlying cause, they often will not be used to guide treatment of the acute presentation
• Hemoglobin electrophoresis
  • May be appropriate in select clinical scenarios and based on underlying clinical suspicion (e.g., patient race)
    • In most cases, most men with SCD have been diagnosed previously. 
      • The yield of identifying men with previously undiagnosed SCD among a cohort of men presenting with priapism is not well established. 
    • Electrophoresis and other sickle cell testing should be reserved for select clinical scenarios.
• Urine and serum toxicology panels
  • A thorough medication and social history may provide enough information for the examining practitioner to determine the underlying cause of the priapism presentation without collection of these studies.
    • Testing for potential substances may have a high rate of false negativity, particularly with synthetic and otherwise altered versions of common illicit substances
    • patient history alone may provide much of this information without needing to perform additional testing

Imaging

Color Doppler US

• Should not be incorporated into the acute evaluation and management of priapism in the emergency department by non-urologist specialists★
  • Not the primary way to diagnose priapism
• May be utilized in less clearly delineated cases to differentiate between acute ischemic priapism and non-ischemic priapism★
• Findings
  • Acute ischemic priapism
    • Bilateral absence of flow through the cavernosal arteries
    • Peak systolic flows <50 cm/sec
    • Mean velocity <6.5 cm/sec
    • Diastolic reversal (i.e., negative end diastolic velocities)
  • Non-ischemic priapism
    • Peak systolic velocities of >50 cm/sec.
    • In the non-acute setting, may identify anatomical abnormalities, such as a cavernous artery fistula or pseudoaneurysm in patients who already have been diagnosed with non-ischemic priapism. These abnormalities may occur following a straddle injury or direct scrotal trauma and are, therefore, most often found in the perineal portions of the corpora cavernosa.

Pelvic MRI

• Likely does not have a role in the initial diagnostic and treatment phase of priapism★
• Can be used to demonstrate:
  1. A well-established arteriolar-sinusoidal fistula
  2. Presence and extent of tissue thrombus
  3. Corporal smooth muscle infarction
  4. Corporal malignancy or metastasis

Penile arteriography

• Too invasive as a diagnostic procedure to differentiate ischemic from nonischemic priapism

Management

Ischemic priapism

Patient Counselling

• Natural history of untreated acute ischemic priapism is possible permanent loss of erectile function and corporal fibrosis leading to penile shortening
  • ED is the most significant complication in patients with prolonged acute ischemic priapism.
• All patients with persistent acute ischemic priapism should be counseled that there is the chance of erectile dysfunction
  • If acute ischemic priapism event >36 hours, likelihood of erectile function recovery is low.
  • In a patient with acute ischemic priapism >36 hours, surgical interventions, such as distal shunting, with or without tunneling, may be required to achieve detumescence; as it is unlikely the acute ischemic event will resolve with ICI therapy of phenylephrine and aspiration.
    • As the duration of the priapism increases, patients may be refractory to first-line treatments, such as ICI of phenylephrine and aspiration, with or without irrigation.

Non-surgical management

• Conservative therapies (i.e., observation, oral medications, cold compresses, exercise) are not recommended in the management of acute ischemic priapism
  • Minimal corporal blood flow in priapism limits of oral agents
  • Cold compresses should never be used in persons with SCD to avoid provoking vasoconstriction and intravascular sickling
• First-line: intracavernosal phenylephrine and corporal aspiration, with or without irrigation★
  • Clinicians treating acute ischemic priapism may elect to proceed with alpha adrenergics, or aspiration and saline irrigation, or a combination of both therapies based on their clinical judgment★
    • ICI with phenylephrine should begin as rapidly as possible following diagnosis★
      • These statements are taken near verbatim from AUA guidelines, but are conflicting
      • Intracavernosal treatments should not be delayed due to other systemic therapies (e.g., hydration, exchange transfusion), but may be administered concomitantly in most cases.★
      • Surgical shunting should not be performed until both alpha adrenergics and aspiration and saline irrigation have been attempted
      • Even in cases where preserved erectile function is unlikely, clinicians may elect to perform combined treatments to improve penile pain, if present. 
      • Intracavernosal therapies may be deferred when ED is anticipated, and expedited placement of a penile prosthesis is planned.
    • If priapism >36 hours, proceed with surgical procedures, without prolonged attempts at phenylephrine and aspiration/irrigation
      • The response to phenylephrine decreases with increased duration of priapism
        • Corpus cavernosum specimens from patients with prolonged priapism show no contractions to high-dose phenylephrine.
  • Intracavernosal α-adrenergic injection
    • α-agonists (phenylephrine, etilefrine, ephedrine, epinephrine, norepinephrine, metaraminol) cause cavernous smooth muscle contraction of the cavernous artery and arterioles, and therefore are vasoconstricrsto
      • Phenylephrine
        • α-agonist of choice
          • Use in this context is off-label
        • Relatively selective α1-adrenergic receptor agonist with minimal β-mediated ionotropic and chronotropic cardiac effects
        • Technique★
          • The optimal regimen for phenylephrine dosing, frequency, and method of administration has not been clearly defined
            • Phenylephrine diluted in 1mL of normal saline to a concentration of 100-500 mcg doses (optimally premixed by pharmacy to minimize risks of miscalculation/overdose)
            • Doses administered ≥5 minutes apart
            • Administered intracavernosally (not subcutaneously)
            • Administered laterally (3 or 9 o’clock position) near the base of the penile shaft
            • Small needles may be used (e.g., 27G)
            • May be continued for up to 1 hour
              • If the erection persists despite repeated attempts with injections and aspiration/irrigation > 1 hour, proceed with more definitive therapy (i.e., shunting procedure).
            • In cases where the combination of phenylephrine and aspiration/irrigation are performed, aspiration should precede phenylephrine administration to permit fresh, oxygenated blood to fill the corpora and potentially improve the yield of phenylephrine administration
              • The penis is aspirated between successive injections by tightly pinching the shaft at the penoscrotal junction, just below the site of needle insertion
            • No recommendations can be made about maximum safe dosage.
              • Although there is no upper limit to the number of injections which may be performed, injections should be stopped if blood pressure changes are detected.
                • Hypertensive stroke has been reported as a complication of cumulative administration of 2 mg [20mL if 100 μg/mL; 10ml if 200 μg/mL]
      • Potential side effects of intracavernous sympathomimetics:
        1. Hypertension (most common)
        2. Reflex bradycardia (most common)
        3. Tachycardia
        4. Irregular cardiac rhythms
        5. Headache
        6. Dizziness
      • Patients receiving intracavernosal injections with phenylephrine should be monitored for blood pressure and heart rate★
        • Blood pressure and heart rate monitoring seems especially prudent in patients with a history of cardiovascular disease, hypertension, prior stroke, and those using medications such as monoamine oxidase inhibitors (MAOIs).
      • Use in patients on Monoamine Oxidate Inhibitors (MAOIs) (e.g. isocarboxazid, phenelzine, selegiline, tranylcypromine)
        • No reports of toxicity when used for priapism in males using MAOI
        • Potentiation of phenylephrine effects by prior administration of MAOI is most significant with use of oral phenylephrine, which is dissimilar from intracavernosal administration.
        • Gradual dose escalation may be reasonable when treating priapism in men using these medications.
    • Corporal aspiration, with or without irrigation
      • Corporal aspiration refers to the intracavernosal placement of a needle followed by withdrawal of corporal blood. Irrigation indicates subsequent instillation of fluid (typically saline) into the corpora.
        • These two procedures are often combined to remove clotted, deoxygenated blood and restore arterial flow and smooth muscle and endothelial function. They may be performed alone or combined with instillations of phenylephrine.
          • So studies have compared aspiration and irrigation with saline to alpha adrenergic injections alone
          • In comparing outcomes data between combination therapy of aspiration, irrigation, and intracavernosal alpha adrenergics to alpha adrenergics alone, results appear to suggest greater resolution rates with combination therapy.
      • Aspiration will immediately soften the erection and relieve pain; aspiration alone may relieve priapism in 36% of cases
      • Aspiration should be repeated until no more dark blood is coming out from the corpora and fresh bright red blood is obtained
      • Technique★
        • Steps for aspiration/irrigation with phenylephrine administration:
          1. Perform a penile block with local numbing medication (if not previously performed).
          2. Place a 16-18 gauge butterfly needle in the 3 or 9 o’clock position (to avoid the dorsal neurovascular bundle) on the penis near the base.
          3. Connect the butterfly needle to a 30-60 cc Luer Lock syringe.
          4. Alternate between aspiration of blood clots and instillation of saline (chilled if available and if the patient does not have sickle cell disease) until some degree of detumescence can be achieved.
          5. Instill phenylephrine.
          6. Allow 3-5 minutes of time to pass.
          7. Repeat steps 4-6 until detumescence is achieved or until the decision has been made to proceed with surgical shunting.
          8. If temporary detumescence is achieved with aspiration followed by a rapid refilling of blood despite multiple attempts of phenylephrine instillation, consideration may be given to placement of a firm penile wrap at the time of aspiration to maintain detumescence.

Surgical management (Shunting)

• Principle of shunt procedure is to reestablish corporal inflow by relieving venous outflow obstruction; this requires creation of a fistula between the corpora cavernosa and the glans penis, corpora cavernosa and corpus spongiousum, or corpora cavernosa and dorsal or saphenous veins.
• In patients with a distal corporoglanular shunt should be performed
  • A surgical shunt should not be considered as first-line therapy.
• Indications (2):
  1. Persistent acute ischemic priapism after intracavernosal phenylephrine and aspiration, with or without irrigation★
  2. Injections of sympathomimetics has resulted in a significant cardiovascular side effect
  3. Malignant or poorly controlled hypertension
  5. Consider for ischemic priapism events ≤72 hours
     • In priapism lasting > 72 hours, consideration should be given to foregoing a shunt
• Approach: distal vs. proximal
  • Distal (6)
    • Percutaneous (3) (through distal glans towards corpus cavernosum) WET
      1. Winter: large-bore needle or angiocatheter (least effective)
      2. Ebbehoj: straight incision with No. 11 blade
      3. T shunt: No. 10 blade is rotated 90° after insertion
         • After Ebbehoj or T shunt, the glans is sutured closed with absorbable suture. Discharge home if the penis remains flaccid for 15 minutes. If erection returns or persists, a second T shunt is recommended on the opposite side of the meatus.
    • Open (3): ACT
      1. Al -Ghorab: excision of a 5-mm circular cone segment of the distal tunica albuginea
      2. Combined distal shunt and corporal tunneling maneuver
      3. Tunnelling: modification of the Al-Ghorab; after excising the circular core of distal tunica albuginea, a 7/8 Hegar dilator is inserted down each corporal body through the tunica window
         • Addition of tunneling may afford slightly higher rates of successful detumescence
    • The optimal type of distal corporoglanular shunt has not been defined★
      • Use of tunneling is associated with greater degradation of post-procedure erectile function compared to distal shunting alone★
  • Proximal (2)
    • Options (open)
      1. Proximal corpus cavernosum to spongiosum shunt (Quackles); require a trans-scrotal or transperineal approach
      2. Proximal corpus cavernosum to saphenous vein shunt (Grayhack) - a wedge of tunica albuginea is removed and the vein is anastomosed end to side of corpora cavernosa.
      3. Proximal corpus cavernosum to deep dorsal vein shunt (Barry)
  • Distal shunts are preferred over proximal
    • There is inadequate evidence to quantify the benefit of performing a proximal shunt (of any kind) in a patient with persistent acute ischemic priapism after distal shunting.★
      • Proximal shunting represents a historical procedure and has largely been replaced by distal shunts with tunneling procedures★
      • Proximal shunts are technically more difficult to perform, likely no surgeons who have extensive experience★
        • Should not be considered a mandatory procedure for men who have been confirmed to have failed distal shunting★
  • Percutaneous distal shunting is less invasive than open distal shunting and can be performed with local anesthetic in the emergency department.
  • Open shunting procedures, especially those that require passage of dilators into the corpora cavernosa, will require general anesthesia and an operating room
• Complications of shunting (6):
  1. Penile edema
  2. Hematoma
  3. Infection
  4. Urethral fistula
  5. Penile necrosis
  6. Pulmonary embolism
• Methods to prevent shunt obstruction and subsequent failure (3):
  1. Avoid compressive penile dressings
  2. Consider anticoagulation
  3. Patient should periodically squeeze and release the distal penis to “milk” the shunt maintaining patency
• Resolution of acute ischemic priapism
  • Characterized by the penis returning to a flaccid, nonpainful state, with restoration of penile blood flow.
    • Oftentimes, persistent penile edema, ecchymosis, and partial erections occur and mimic unresolved priapism. This often relates to the duration of priapism and may also signify segmental regions of cavernosal ischemia/necrosis.
  • After shunting, follow-up with the patient regarding erectile function and any subsequent ED therapies
• Priapism refractory to shunting
  • A vascular study (such as a PDUS) or cavernosal blood gas should be performed prior to performing additional interventions (repeat distal or proceeding to proximal shunting). ★
    • Goal is to assess penile hemodynamic characteristics and extent of necrosis/fibrosis to differentiate persistent acute ischemic priapism from reactive hyperemia or conversion to non-ischemic priapism and inform secondary treatment decisions
      • Penile corporal blood gas can help with decision making about proceeding to additional surgical procedures including placement of an immediate penile prosthesis.
      • Penile duplex ultrasound
        • Can be used to
          • Differentiate between acute ischemic and non-ischemic priapism
          • Determine shunt patency by showing restoration of cavernosal arterial inflow in a patient who has undergone a distal shunt
        • Use is limited by
          • Number of specialists who can currently perform the procedure
          • Equipment might not be readily available
    • Further surgical decisions should not be based only on exam
    • Evaluating the status of a patient with refractory priapism is particularly important in the event that a patient is referred from another institution and/or the clinician is seeing a patient who had been previously treated elsewhere and a complete patient history may not be available.

Early implantation (within 2 weeks) of penile prosthesis

• May be considered in a patient with untreated acute ischemic priapism greater than 36 hours or in those who are refractory to shunting, with or without tunneling. ★
  • Alternatively, these men may be managed with conservative therapies such as pain control and outpatient follow-up and bypass more invasive procedures (e.g., surgical shunting).
  • It is important to note that before considering conservative management or penile prosthesis placement in men with a priapism >36 hours, the timeline should be sufficiently confirmed.
    • Patient histories relating to an exact timeline may often be unreliable, particularly in cases of concomitant substance use, episodes of intermittent detumescence, recurrent priapism (e.g., SCD), or partial (not fully rigid) erections. In these settings, clinical judgment is required to identify the true timeline for onset of ischemia (i.e., onset of severe, persistent penile pain). 
    • If the timeline is in question, clinicians should preferentially attempt to decompress the priapism, particularly in younger men or those with high baseline erectile function.
• Advantages to prostheses placed in the setting of acute ischemic priapism (5):★
  1. Detumescence
  2. Relief of pain
  3. Preservation of penile length
  4. Return to sexual activity
  5. Overall satisfaction
• Disadvantage to immediate implantation (1):
  1. Significantly higher rates of complications (infection, urethral injury, device migration, device erosion, and revision surgeries) when inserted in the acute managment of ischemic priapism compared to elective insertion in a patient with erectile dysfunction
     1. Infection rates < 10%★

Sickle cell disease induced ischemic priapism

• Classically, treatment of SCD-induced ischemic priapism involved analgesics, hydration, oxygen, bicarbonate, and exchange transfusion. Unfortunately, acute neurologic complications may follow exchange transfusions. Hematologists have begun to question the emphasis on intravenous hydration, sodium bicarbonate for alkalinization, and exchange transfusion as first line therapy for SCD-associated priapism; hematologic consultation should be obtained in the management of priapism but hematologic therapy alone is not effective management of SCD priapism
• Initial treatment of low-flow priapism resulting from sickle cell disease is conservative, with hydration, oxygenation, alkalization, analgesia, and exchange transfusion aimed at reducing HbS concentration (from Chapter 146)
• Evacuation of blood and irrigation of the corpora cavernosa along with intracavernous injections of α-adrenergic sympathomimetic agents, such as phenylephrine or epinephrine solution, can be a concurrent therapy (from Chapter 146)

Stuttering priapism

• Drug therapy is typically initiated at bedtime
• Options (5):
  1. Pseudoephedrine, an oral α-adrenergic agonist, promotes muscle contraction within the erectile tissue
  2. If pseudoephedrine is unsuccessful, other agents can be used, including an oral β agonist
  3. Recently, preliminary findings have suggested that the use of continuous, long-term oral PDE5 inhibitor therapy may prevent recurrent priapism based on the hypothesis that PDE5 dysregulation may be involved in priapism
  4. GnRH agonists or anti-androgens (e.g. bicalutamide)
     • Can be used to suppress the androgenic effects on penile erection.
     • Chronic administration may affect libido or fertility, cause gynecomastia, cause hot flushes, promote osteoporosis, increase the risks of cardiovascular disease, and worsen sexual function
       • May be used in adults but should not be used in patients who have not achieved full sexual maturation and adult stature.
  5. Intracavernous α-adrenergic agent
     • May avert a full-blown episode of ischemic priapism when administered at home for prolonged morning erections
     • Intracavernosal injection of phenylephrine (by the adult patient or parent) should be considered as an adjunct to daily systemic therapies in patients with stuttering priapism

Non-ischemic priapism

• Cavernous aspiration has only a diagnostic role in nonischemic priapism.
  • Repeated aspirations, injection, and irrigation with intracavernous sympathomimetics have no role in the treatment of nonischemic priapism.
• First-line: observation
  • Non-ischemic priapism is not an emergency; initial observation is recommended
  • Spontaneous resolution or response to conservative therapy has been reported in up to 62% of cases
    • No comparative studies of intervention vs. conservative management in non-ischemic priapism
  • Conservative measures include ice applied to the perineum and site-specific compression
• Second-line: embolization with interventional angiography
  • Patients demanding immediate relief can be offered selective arterial embolization
    • Although ultimately successful, embolization of non-ischemic priapism may require retreatment; a single treatment of embolization carries a recurrence rate of 30%.
    • Normal post-embolization erectile function has been reported in 75-86% of patients. Bilateral arterial embolization significantly increased the risk of ED.
• Surgery
  • In cases of longstanding arterial priapism in which a pseudocapsule around the fistula has developed, surgical ligation has been reported to be successful. The surgical approach is transcorporal.
  • Formation of a pseudocapsule may take weeks to months after trauma. Corporal exploration before the formation of a pseudocapsule may result in ligation of the cavernous artery rather than selective ligation of the fistula.
  • Currently this intervention is reserved for patients:
    1. Who do not wish to pursue expectant management and are poor candidates/refuse angioembolization
    2. In places where technology is not available
    3. In whom angioembolization has failed

Questions

1. What is the definition of priapism? What are the subtypes?
2. What proportion of patients will recover erectile function for priapism reversed within a) 12 hours b) 12-24 hours c) 24-36 hours d) >36 hours
3. After what duration of priapism is shunting no longer recommended?
4. List risk factors for priapism.
5. Which medications are associated with risk of priapism?
6. What are the initial investigations in a patient with suspected priapism?
7. What is the expected PO2, PCO2, and pH of normal arterial gas vs. mixed venous gas vs. corporal aspirate from ischemic priapism?
8. What is the maximum dose of phenylephrine that should be administered?
9. What are potential adverse effects related to phenylephrine injection?
10. List and briefly describe the different shunting procedures
11. What are potential complications of shunting?
12. What are potential advantages to immediate implantation of prosthesis in the management of priapism?
13. What medication can be used for prophylaxis in stuttering priapism? What are other options?

Answers

1. What is the definition of priapism? What are the subtypes?
   • Definition: a full or partial erection that continues > 4 hours beyond sexual stimulation and orgasm or is unrelated to sexual stimulation
   • Subtypes: ischemic, stuttering, non-ischemic
2. What proportion of patients will recover erectile function for priapism reversed within a) 12 hours b) 12-24 hours c) 24-36 hours d) >36 hours
   1. 100%
   2. ≈80%
   3. ≈45%
   4. 0%
3. After what duration of priapism is shunting no longer recommended?
   • >72 hours
4. List risk factors for priapism.
5. Which medications are associated with risk of priapism?
6. What are the initial investigations in a patient with suspected priapism?
   • H+P, CBC, coagulation profile, blood gas, +/- urine toxicology screen, +/- sickle cell preparation and electrophoresis
7. What is the expected PO2, PCO2, and pH of normal arterial gas vs. mixed venous gas vs. corporal aspirate from ischemic priapism?
   • Normal arterial blood gas: PO2 > 90, PCO2 <40, pH 7.4
   • Mixed venous gas: PO2 40, PCO2 50, pH 7.35
   • Ischemic priapism: PO2 < 30, PCO2 >60, pH < 7.25
8. What is the maximum dose of phenylephrine that should be administered?
   • 2mg
9. What are potential adverse effects related to phenylephrine injection?
   1. Headache
   2. Dizziness
   3. Hypertension
   4. Reflex bradycardia
   5. Tachycardia
   6. Irregular cardiac rhythms
10. List and briefly describe the different shunting procedures
    • Distal
      • Percutaneous
        1. Winter
        2. Ebbehoj
        3. T-shunt
      • Open
        1. Al-Ghorab
        2. Corporal snake
        3. Combined T-shunt and Corporal Snake
    • Proximal
      1. Cavernosum-spongiosum
      2. Cavernosum-saphenous/deep dorsal vein
11. What are potential complications of shunting?
    • Penile edema, hematoma, infection, urethral fistula, penile necrosis, and pulmonary embolism
12. What are potential advantages to immediate implantation of prosthesis in the management of priapism?
    1. Corporal fibrosis not yet established
    2. Penile length may be preserved
13. What medications can be used for prophylaxis in stuttering priapism?
    1. Phenylephrine
    2. Oral beta agonist
    3. PDE5 inhibitor
    4. GnRH or antiandrogens
    5. Intracavernosal alpha-agonist

References

• Wein AJ, Kavoussi LR, Partin AW, Peters CA (eds): CAMPBELL-WALSH UROLOGY, ed 11. Philadelphia, Elsevier, 2015, vol 1, chap 58
• Bivalacqua, Trinity J., et al. "Acute ischemic priapism: an AUA/SMSNA guideline." Journal of Urology 206.5 (2021): 1114-1121.