Priapism

Definition

• Priapism: a full or partial erection that continues > 4 hours beyond sexual stimulation and orgasm or is unrelated to sexual stimulation

Subtypes (3)

1. Ischemic
2. Stuttering
3. Non-ischemic

Ischemic priapism (veno-occlusive, low-flow)

• Majority of cases
• Associated with (features that distinguish this from non-ischemic priapism)
  1. Pain
  2. Rigid corpora cavernosa
  3. Abnormal blood gas
• Once properly diagnosed, requires emergent intervention
  • 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
    • A more recent study that the cutoff for irreversible restoration of erectile tissue is 48 hours
    • Interventions beyond 48-72 hours of onset may relieve erection and pain but have little benefit in preserving potency

Stuttering priapism (intermittent)

• Transient prolonged erections lasting < 2 hours
• Characterized by a pattern of recurrence
• 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
• Any patient who has experienced an episode of ischemic priapism is also at risk for stuttering priapism

Non-ischemic priapism (arterial, high-flow)

• Relatively rare
• Pathogenesis:
  • 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

Causes (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), crack cocaine, 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 (1)
    1. Corporal blood gas
• Optional
  • Labs
    • CBC
    • Hemoglobin electrophoresis
    • Screening for psychoactive drugs and urine toxicology
  • Imaging
    • Penile duplex Doppler ultrasonography

History and Physical Exam

History

• Duration of erection, presence of pain
• PMHx: sickle cell disease, hemoglobinopathies, hypercoagulable states, trauma to the pelvis, perineum, or penis
• Medications
• Use of any erectogenic therapies (both prescription and nutritional supplements)
• Use of recreational drugs
• Previous episodes of priapism and method of treatment
• Baseline erectile function

Physical Exam

• In ischemic priapism, the corporal bodies will be completely rigid; the glans penis and corpus spongiosum are not. The penis may be tender
• In non-ischemic priapism, the corporal bodies will be tumescent, partially erect, but not completely rigid. The penis is also unlikely to be tender

Laboratory

• CBC and coagulation profile (PT/INR)
  • Evaluates for anemia, infection, hematologic abnormalities, and ensures that the patient can safely tolerate surgical interventions, if needed
• Corporal blood gas by aspiration
  • Recommended in the emergency evaluation of priapism

Source	PO2 (mm Hg)	PCO2 (mm Hg)	pH
Normal aterial 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

• Urine and serum toxicology panels
  • Should be done if recreational narcotic or prescription psychoactive drugs are suspected from the history
• Sickle cell preparation and hemoglobin electrophoresis
  • Should be requested in African-Americans

Imaging

• Color Doppler US
  • Indications:
    1. History suggests penile or perineal trauma or if the corporal aspirate reveals well-oxygenated blood
    2. Full or partial erection after treatments for ischemic priapism.
    • • The differential diagnosis includes resolved ischemia with penile edema, persistent ischemia, and conversion to high-flow state
  • Should assess the ventral surface of the penis in a sagittal, para-urethral plane and perineum.
• Penile arteriography
  • Too invasive as a diagnostic procedure to differentiate ischemic from nonischemic priapism
• MRI
  • 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

Management

Ischemic priapism

Non-surgical management

• Oral agents are not recommended in the management of acute ischemic priapism
• Cavernosal aspiration
  • Initial treatment of ischemic priapism is corpora cavernosa decompression by aspiration
    • After performing a dorsal nerve and ring block, a single, large-bore, 19-gauge needle should be inserted at the penoscrotal junction at the 3 or 9 o’clock position to avoid piercing the dorsal neurovascular bundle
    • 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
  • If corporal aspiration is unsuccessful, irrigation with normal saline or injection of an α-adrenergic should follow
• 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 vasoconstrictors
    • Potential side effects of intracavernous sympathomimetics:
      1. Headache
      2. Dizziness
      3. Hypertension
      4. Reflex bradycardia
      5. Tachycardia
      6. Irregular cardiac rhythms
      • Serial monitoring of blood pressure and pulse should be performed during and immediately after intracavernosal injection of sympathomimetic drugs
    • Contraindications (1):
      • Use of monoamine oxidase inhibitor
    • Phenylephrine
      • α-agonist of choice
      • Relatively selective α1-adrenergic receptor agonist with minimal β-mediated ionotropic and chronotropic cardiac effects
      • Typically diluted in normal saline to a concentration of 100-200 μg/mL and administered intracavernously as a 1-mL injection every 3-5 minutes. The penis is aspirated between successive injections by tightly pinching the shaft at the penoscrotal junction, just below the site of needle insertion
      • Most common side effects are hypertension and reflex bradycardia
        • No recommendations can be made about maximum safe dosage. Hypertensive stroke has been reported as a complication of cumulative administration of 2 mg [20mL if 100 μg/mL; 10ml if 200 μg/mL]
      • 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.

Surgical management

• Indications (2):
  1. Failure of repeated penile aspirations and injections of sympathomimetics
  2. Injections of sympathomimetics has resulted in a significant cardiovascular side effect
• Early surgical intervention may be preferable in patients with:
  1. Malignant or poorly controlled hypertension
  2. Using monoamine oxidase inhibitor medications contraindicating α-adrenergic therapies
• 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.
  • Consider for ischemic priapism events ≤72 hours
    • In priapism lasting > 72 hours, consideration should be given to foregoing a shunt
  • Classified: distal vs. proximal
    • Distal (6)
      • Percutaneous (3) (through distal glans towards corpus cavernosum) WET
        1. Winter: large-bore needle or angiocatheter
        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): ACC
        1. Al -Ghorab: excision of a 5-mm circular cone segment of the distal tunica albuginea
        2. Corporal snake: 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
        3. Combined T shunt and corporal snake maneuver
    • Proximal (2) (open)
      1. Proximal corpus cavernosum to spongiosum shunt (Quackles); require a trans-scrotal or transperineal approach
      2. Proximal corpus cavernosum to saphenous vein or deep dorsal vein shunt - a wedge of tunica albuginea is removed and the vein is anastomosed end to side of corpora cavernosa.
    • Distal shunts are preferred over proximal because they are technically easier to perform
      • 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
      • Consider open distal shunting if percutaneous distal shunting fails. If distal shunting fails, then proximal shunting is recommended
    • When ischemic priapism has been present for > 36 hours, immediate placement of bilateral T shunts is recommended, with passage of 20-Fr dilators into the fistula tract and well into the corpora cavernosa down to the crus. This technique is more traumatic and will require general anesthesia
  • 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
  • After shunting, follow-up with the patient regarding erectile function and any subsequent ED therapies
• Immediate implantation of penile prosthesis
  • Some have suggested performing an immediate penile prosthesis procedure in the acute management of ischemic priapism >48 hours in patients in whom aspiration, irrigation, phenylephrine, and shunting have failed.
  • Advantages to immediate implantation (2):
    1. Corporal fibrosis not yet established
    2. Penile length may be preserved
  • 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

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