J.Moideen Abdul Kadhar

DEFINITION

Priapism is a full or partial erection that continues more than 4 hours beyond sexual stimulation and orgasm or is unrelated to sexual stimulation

HISTORICAL PERSPECTIVES

The term priapism has its origin in reference to the Greek god Priapus, who was worshipped as a god of fertility and protector of horticulture.

Priapus is memorialized in sculptures for his giant phallus.

HISTORICAL PERSPECTIVESThe frst recorded account of priapism in

English medical literature appears in the Lancet and is attributed to Tripe(1845).

Historically the most commonly cited observation on this condition in North American literature is Frank Hinman (Sr)’s landmark article describing the natural history of priapism (Hinman, 1914).

He first described “acute transitory attacks of priapism” as opposed to persistence or rapid recurrence of a single episode.

Physiology of Erection

The dorsal artery is responsible for engorgement of the glans during erection.

The bulbourethral artery supplies the bulb and corpus spongiosum.

The cavernous artery effects tumescence of the corpus cavernosum

The tiny venules leading from the peripheral sinusoids form the subtunical venous plexus before exiting as the emissary veins.

Skin and Subcutaneous Tissue.

Multiple superfcial veins run subcutaneously and unite near the root of the penis to form a single (or paired) superfcial dorsal vein, which in turn drains into the saphenous veins.

Occasionally, the superfcial dorsal vein may also drain a portion of the corpora cavernosa.

Pendulous Penis. The emissary veins

from the corpus cavernosum and spongiosum drain dorsally to the deep dorsal, laterally to the circumfex, and ventrally to the periurethral veins.

The deep dorsal vein, which is the main venous drainage of the glans penis and distal two thirds of the corpora cavernosa.

Usually a single vein, but sometimes more than one deep dorsal vein, runs upwards behind the symphysis pubis to join the periprostatic venous plexus.

There are also small venous channels accompanying the paired dorsal artery.

These become enlarged after the deep dorsal vein is ligated and may be the cause of recurrent leakage in venogenic ED

Infrapubic Penis.

Emissary veins draining the proximal corpora cavernosa join to form cavernous and crural veins.

These join the periurethral veins from the urethral bulb to form the internal pudendal veins.

The veins of the three systems communicate variably with each other.

Indeed, variations in the number, distribution, and termination of these venous systems are common

Mechanism of erectionNeuroendocrine signals from the brain,

created by audiovisual or tactile stimuli, activate the autonomic nuclei of the spinal erection centre .

Signals are relayed via the cavernosal nerve to the erectile tissue of the copora cavernosa, activating the veno-occlusive mechanism .

This triggers increased arterial blood flow into sinusoidal spaces (secondary to arterial and arteriolar dilatation), relaxation of cavernosal smooth muscle, and opening of the vascular space.

Mechanism of erectionThe result is expansion of the sinusoidal spaces

against the tunica albuginea, which compresses the subtunical venous plexuses, decreasing venous outflow.

Maximal stretching of the tunica albuginea acts to compress the emissary veins which lie within its inner circular and outer longitudinal layers, reducing venous flow even further.

Rising intracavernosal pressure and contraction of the ischiocavernosus muscles produces a rigid erection.

Following orgasm and ejaculation, vasoconstriction (due to increased sympathetic activity, endothelin, PGF2, and breakdown of cGMP) produces detumescence

Definitions Ischemic priapism (low-flow) is a persistent erection

marked by rigidity of the corpora cavernosa, with little or no cavernous arterial infow.

● Nonischemic priapism (arterial, high-flow) is a persistent erection caused by unregulated cavernous arterial infow.The corpora are tumescent but not rigid, and the erection is not painful.

Stuttering priapism describes a pattern of recurrence. The term has traditionally described recurrent prolonged and painful erections in men with SCD.

Ischemic Priapism(Veno-Occlusive, Low-Flow)

It is a persistent erection marked by rigidity of the corpora cavernosa and little or no cavernous arterial inflow.

In ischemic priapism there are time dependent changes in the corporal metabolic environment with progressive hypoxia, hypercarbia, and acidosis.

The patient typically complains of penile pain after 6 to 8 hours, and the examination reveals a rigid erection.

The condition is analogous to a muscle compartment syndrome, with initial occlusion of venous outfow and subsequent cessation of arterial infows.

Etiopathogenesis of Ischemic

It is the most common form of priapism and also the most serious and dangerous because of the acute ischemia of the corpora cavernosa.

The seriousness is directly related to severity of the obstruction and the duration of the blockage of the drainage of the corpora cavernosa.

It is associated with a decrease in venous outflow and vascular stasis, which in turn cause tissue hypoxia, anoxia, and acidosis. It must be considered as a urological emergency.

Cavernous hypoxia and acidosis begin after 4 hours and increase to peak levels in 24 hours.

Po 2 and pH of the trapped blood decrease to the levels of anoxia and acidosis in this time frame.

Penile pain occurs with significant tissue hypoxia. Hypoxia and acidosis lead to loss of contractility of the

cavernous smooth muscle, impairing the venous stasis. Histological changes start with edema of the cavernous

tissue, then anoxia and necrosis of the cavernous smooth muscle cells, leading to irreversible fibrosis and may be replaced by collagen, which will result in ED.

Transforming Growth Factor (TGF)-beta may also play a major role in the final process.

CausesSince the first report of priapism, which was

published in 1824 by Callaway , there have been several causes that relate to low-flow priapism:

Hematological disorders, Genitourinary leisons Drugs, Metastatic lesions, Neurological, Idiopathic.

Drugs: Drug use would account for most of the incidents of priapism cases.

a-Adrenergic Receptor AntagonistsPrazosin, terazosin, doxazosin, tamsulosin

Antianxiety AgentsHydroxyzine

AnticoagulantsHeparin, warfarin

AntihypertensivesHydralazine, guanethidine, propanolol

Drugs (Recreational)Alcohol, cocaine (intranasal and topical), crack cocaine, marijuana

Antidepressants and AntipsychoticsTrazodone, bupropion, fluoxetine, sertraline, lithium, clozapine, resperidone, olazapine, chlorpromazine, thoridazine, phenothaizines.

Vasoactive Erectile AgentsPapaverine, phentolamine, prostaglandin E 1 , oral phosphodiesterase type 5 inhibitors, combination intracavernous therapy.

GenitourinaryStraddle injury, coital injury, pelvic trauma, kick to penis/perineum,arteriovenous or arteriocavernous bypass surgery, urinary retention

Hematologic DyscrasiasSickle cell disease, thalassemia, granulocytic leukemia, myeloid leukemia, lymphocytic leukemia, multiple myeloma,hemodialysis, glucose 6-phosphate dehydrogenase deficiency

HormonesGonadotropin-releasing hormone, testosterone

Infectious (Toxin Mediated)Scorpion sting, spider bite, rabies, malaria

Brazilian banana spider,” Phoneutria nigriventer,the venom contains a neurotoxin that has calcium channel blocking properties, inhibits glutamate release, and inhibits calcium reuptake and glutamate reuptake.

Bites can cause intense pain, loss of muscle control—paralysis, breathing problems—asphyxiation, and priapism

Phoneutria nigriventer - "armed spider"

Priapism caused by Phoneutria bite

MetabolicAmyloidosis, Fabry disease, gout

Neoplastic (Metastatic or Regional Infiltration)Prostate, urethra, testis, bladder, rectal, lung, kidney

NeurogenicSyphilis, spinal cord injury, cauda equina compression, autonomic neuropathy, lumbar disk herniation, spinal stenosis, cerebral vascular accident, brain tumor, spinal anesthesia, cauda equina syndrome

Sickle Cell DiseaseSCD priapism has traditionally been ascribed to

stagnation of blood within the sinusoids of the corpora cavernosa during physiologic erection, secondary to obstruction of venous outflow by sickled erythrocytes

Hemolysis releases hemoglobin into the plasma. Free Hbg reacts with nitric oxide (NO) to produce

methemoglobin and nitrate.This is a scavenging reaction; the vasodilator NO

is oxidized to inert nitrate.Sickled erythrocytes release arginase-I into blood

plasma, which converts L-arginine into ornithine, effectively removing substrate for NO synthesis.

Oxidant radicals further reduce NO bioavailability. The combined effects of NO scavenging and arginine catabolism result in a state of NO resistance and insufficiency termed hemolysis-associated endothelial dysfunction

Hemolysis and reduced nitric oxide are responsible for the pathogenesis of leg ulcers, priapism, and stroke in SCD patients.

ASPEN syndrome (priapism, exchange transfusion,and neurologic events) describes cerebral vascular accidents in SCD patients who have received exchange transfusions

Iatrogenic Priapism: Intracavernous Injections

Erectogenic drugs particularly when administered intracavernously may result with low-flow priapism.

Most common of these drugs are papaverine, prostaglandin E1 (PGE1), phentolamine, and moxisylate.

In most of these cases, priapism result from an over dosage of these drugs.

The incidence of priapism is less with PGE1 or combinations than papaverine alone.

This may be explained by the presence of some enzymes that metabolize PGE1 in the penile tissue.

Phosphodiesterase Type 5 InhibitorsFew case reports have documented priapism

following a PDE type 5 inhibitor therapy. The majority of cases reports detailing

priapism following a PDE type 5 inhibitor reveal histories of men with increased risk for priapism: SCD, spinal cord injury, men who used PDE5 inhibitor recreationally, men who used PDE5 inhibitor in combination with intracavernous injection, men with history of penile trauma, men on psychotropic medications, and men abusing narcotics.

Etiology of StutteringPriapism

Stuttering (intermittent) priapism describes a pattern of recurrent priapism.

The term has traditionally been used to describe recurrent unwanted and painful erections in men with SCD.

Patients typically awaken with an erection that persists up to 4 hours and becomes progressively painful secondary to ischemia.

SCD patients may experience stuttering priapism from childhood.

Patients with stuttering priapism will experience repeated painful intermittent attacks up to several hours before remission.

MOLECULAR BASIS OF PRIAPISMIn the penis the vascular endothelium is a source

of vaso-relaxing factors such as NO and adenosine, as well as vaso-constrictor factors such as RhoA/Rho-kinase.

Recent evidence suggests that in states of priapism there may be aberrant NO and adenosine signaling, thus identifying a potential role for NO/cGMP, as well as adenosine and RhoA/Rho-kinase signaling in the pathophysiology of ischemic priapism

Dysregulation of the PDE-5 and Rho-kinase enzymes may also be contributory to the etiology of priapism in the sickle cell population

.

Pathophysiology of NonischemicPerineal/penile traumaSickle cell diseaseIatrogenicGenitourinary disorderPsychotropicsMetastatic tumorFabry’s diseaseHFP has been described following iatrogenic

injury: cold-knife urethrotomy, Nesbitt corporoplasty, and deep dorsal vein arterialization

Pathophysiology of NonischemicThe initial results in injury to the arterial

wall that necroses completely over time.Increased arterial pressure during a natural

erection causes the weakened arterial wall to rupture and present as priapism at a time remote from the original injury.

This type of priapism results from an arteriolacunar fistula wherein the ruptured artery opens directly into the lacunar spaces of the cavernosal tissue,bypassing the helicine arteries..

The high flow results in shear stress of the adjacent areas.

This causes increased smooth muscle relaxation and trabecular dilatation through release of nitric oxide and activation of cGMP.

Unlike the situation in low-flow priapism, there is no transformation of the trabecular smooth muscles into fibroblasts even after prolonged periods, and therefore these patients are unlikely to develop ED as a direct consequence of the priapism

Because the tissue is well oxygenated, there is the lack of ischemia and necrosis and so patients rarely complain of pain.

The trauma tends to cause uncontrolled inflow into the cavernosal sinusoids and bypass the control that the helicine arteries provide and results in priapism.

Branches of the cavernosal artery have been identified as the most frequent vessels injured in nonischemic priapism.

PATHOLOGYPenile tissue necrosis and progressive

fibrosis are the end-stage manifestations of ischemic priapism, hampering the physical reactivity of the erectile tissue and its elasticity needed for physiologic blood engorgement.

After 12 hours, Trabecular interstitial edema develops;

After 24 hours, the sinusoidal endothelium is denuded and thrombocytes adhere to the exposed basement membrane; and

After 48 hours, thrombi form in the sinusoidal spaces and smooth muscle cells undergo necrosis or become transformed to fibroblast-like cells

Irreversible effects resulted most consistently from the combination of hypoxia, acidosis, and glucopenia at a time interval of 4 hours

Pathologic changes also occur in the penis when ischemic priapism is relieved. In this event, as a result of reperfusion injury, the cavernosal tissue sustains damage from oxidative stress.

HistoryDuration of erectionPresence of painPrevious episodes of priapism and method of

treatmentBaseline erectile functionUse of any erectogenic therapies (both

prescription and nutritional supplements)Medications and recreational drugsSickle cell disease, hemoglobinopathies,

hypercoagulable statesTrauma to the pelvis, perineum, or penis

Physical examinationIt reveals the rigidity of the penis, which will help in the

differential diagnosis of low-flow and high-flow priapism.Low-flow priapism causes rigid erections in the corpora

cavernosa but a normal corpus spongiosum keeping the glans penis soft.

Tenderness, severe pain (especially after four hours),and loss of elasticity of the penis also helps to identify low-flow priapism.

Although malignancies rarely cause priapism, examination of the abdomen, testicles, perineum, rectum, and prostate may help identify a cancer primary.

Malignant infiltration of the penis causes indurated nodules within or replacing corporal tissue.

Diagnosis and classification of the cause of priapism may often be made by history and physical examination alone.

Aspiration of penile cavernosal blood may act as both a diagnostic and therapeutic maneuver.

Laboratory and Radiologic EvaluationThe laboratory evaluation of patients with priapism

should include a complete blood count (CBC) with special attention to the white blood count (WBC), white blood cell differential and platelet count.

Acute infections or hematologic abnormalities that can cause priapism, such as sickled red blood cells, leukemia and platelet abnormalities, may be suggested or identified by the CBC.

The reticulocyte count is often elevated in men with sickle cell anemia. Hemoglobin electrophoresis identifies the presence of sickle cell disease or trait as well as other hemoglobinopathies.

Blood gas testing and color duplex ultrasonography are currently the most reliable diagnostic methods of distinguishing ischemic from nonischemic priapism .

Blood aspirated from the corpus cavernosum in patients with ischemic priapism is hypoxic and therefore dark, crankcase oil” appearance while blood from the corpus cavernosum in patients with nonischemic priapism is normally oxygenated and therefore bright red.

In ischemic priapism, corporal blood analysis usually reveals an acidotic and hypoxic blood content (pH <7.25,PO 2 <30, PCO 2 >60).

Blood gas values that are similar to arterial levels (pH >7.3, PO 2 >50, PCO 2 <40) suggest nonischemic priapism.

Normal flaccid penis cavernous blood gas levels are approximately equal to those in normal mixed venous blood.

UltrasonographyColor duplex

ultrasonography should be performed in the lithotomy or frogleg position, scanning in the perineum first and then along the entire shaft of the penis.

As an alternative to cavernosal blood gas sampling to differentiate ischemic from nonischemic priapism.

.

ischemic priapism ---- no blood flow in the cavernosal arteries,

nonischemic priapism ----- normal to high blood flow velocities in the cavernosal arteries.

As a screening test for anatomical abnormalities, such as a cavernous artery fistula or pseudoaneurysm, in men who already have the diagnosis of nonischemic priapism.

Penile arteriography may be used as an adjunctive study to identify the presence and site of a cavernous artery fistula (ruptured helicine artery).

Since color duplex ultrasonography has largely supplanted arteriography for the diagnosis of cavernous artery fistulae, arteriography is usually only performed as part of an embolization procedure

MRIThree possible roles in the assessment of priapism

1. imaging of a well-established arteriolar-sinusoidal fistula

2. to demonstrate the presence and extent of tissue thrombus and corporal smooth muscle infarction.

3. imaging of corporal metastasis mimicking priapism

Management of low-flow priapism

Therapeutic goals in the management of priapism are to alleviate pain and fear, abort the erection, maintain detumescenceand prevent long-term complications, particularly ED.

These goals are achieved through attempts at reducing the arterial inflow and increasing the outflow from the corpora.

Management of ischemic priapism must proceed in a stepwise fashion depending upon the degree of response to each intervention.

Conservative????Conservative measures for the erection

include ice compresses and ejaculation.Pain management may be achieved through

either local penile or systemic analgesia.This could include dorsal nerve block, penile block.

Medical managementPrimary medical management involves corporeal

aspiration to remove the collected blood and achieve detumescence, and instillation of an alpha-adrenergic agonist drug to induce smooth muscle contraction and maintain the detumescence.

Aspiration can be performed using a 21- or 22-gauge butterfly needle inserted into the corpora.

A pure alpha-adrenergic stimulant such as phenylephrine is diluted to a concentration of about 0.5mg/ml and 0.5 – 1ml of this solution is administered repeatedly at intervals of 5 – 7 minutes for up to 1 hour through the butterfly needle to achieve detumescence

Alternative drugs are epinephrine (10 – 20 μg per dose)and ephedrine (50 – 100mg per dose).

Resolution rates following the use of these agents is higher (43 – 81 % ) than with aspiration or irrigation alone (24 – 36 % )

Oral agents have been used, such as pseudoephedrine and terbutaline, a beta-2 adrenergic antagonist.

As such, systemic oral agents are not recommended in the treatment of acute ischemic priapism episodes.

Surgical Treatment of Ischemic Priapism

If conservative measures are unsuccessful, then a surgical approach may be necessary.

The goal of surgical treatment is to allow blood to flow in and out of the penis freely to prevent ischemia and fibrosis of the penis.

The principles of most of the priapism surgeries involve creation of a fistula between the engorged corpus cavernosum and the glans, corpus spongiosum, and dorsal or saphenous veins.

Patients should be counseled that erectile function outcomes decline significantly when IP has lasted longer than 24 hours and that complete ED is anticipated if IP persists for longer than 36 hours.

Shunt procedures are subdivided on the basis of anatomic location on the penis.

A distal cavernoglanular shunt should be the first choice of shunting procedures.

Shunts….Percutaneous distal shunts—Ebbehoj (1974),

Winter (1976),or T-shunt (Brant, 2009)Open distal shunt—Al-Ghorab (Hanafy, 1976;

Borrelli, 1983) or Corporal Snake (Burnett, 2009)

Open proximal shunt—Quackles (1964) or Sacher (1972)

Saphenous vein—Grayhack (1964) Deep dorsal vein shunt—Barry (1976)

Winter shuntA distal cavernoglanular

shunt procedure is depicted by the transglanular placement of a large-bore needle or angiocatheter in the distal glans and corpus cavernosum.

A core of tunica albuginea separating the glans and the corpus cavernosumis removed with the needle, thus creating a fistula

Ebbehoj shuntA glans-cavernosal

shunt is made with a No. 11 blade.

Intracavernosal pressure is monitored.

After skin closure, maintenance of pressure at 40 mmHg or less for 10 min or more is indicative of an adequate shunt

T-shaped shuntT-shaped glans-

cavernosal shunt using a No.10 scalpel.

The blade is inserted into each corpus cavernosum from the glans, turned 90 degrees laterally and then pulled out to create a T-shaped shunt

Open-Al GhorabAn open corporoglanular shunt is indicated if

percutaneous shunting fails to reestablish cavernous blood inflow.

The Al-Ghorab shunt requires the excision of circular cone segments of the distal tunica albuginea (5 × 5 mm).

The incision is traditionally made transversely on the dorsal aspect of the glans approximately 1 cm distal to the coronal sulcus.

Dissection is carried down to the bulging corporal bodies

When detumescence occurs, the skin is sutured closed with chromic suture.

It is important to avoid obliterating the spongy tissue layer of the glans penis with the closure stitches .

Proximal shuntsIf distal shunting fails, then proximal shunting is

recommended.Proximal shunting establishes a communication

between the corpora cavernosa and spongiosa at the base of the penis.

We must be aware of the unique anatomic relationship between the corpus spongiosum and urethra.

Shunting may also be accomplished with vein grafting to the corpora cavernosa.

Venous shunts have increased the risk of thromboembolism

Quackels Cavernoso-Spongiosal Shunt

The shunt is created in the perineum between the urethralbulb and crura. If placed too distal, it will not be effective and will carry a higher risk of urethral injury

Barry Cavernoso-Dorsal Vein Shunt

The superficial or deep dorsal vein is anastomosed to the tunica albuginea.

Once again an ellipse of tunica tissue is excised that is proportionate to the size of the dorsal vein.

Grayhack Cavernoso-Saphenous Shunt

The saphenous vein is mobilized by dividing and ligating the tributaries.

The saphenous vein is spatulated and anastomosed to the tunica

Immediate Implantationof Penile Prosthesis

The natural history of untreated ischemic priapism or priapism refractory to interventions is severe fibrosis, penile length loss, and complete ED.

Penile prosthesis in the acute management of ischemic priapism when the patient has failed sympathomimetic intracavenous therapies and shunting.

The advantages of early penile implantation in the acute management of ischemic priapism are preservation of penile length and technically easier implant insertion.

Treatment of Nonischemic Priapism

Agents used are microcoils, polyvinyl alcohol, N-butylcyanoacrylate, gel-foam, and autologous blood clot .

Permanent materials pose a greater theoretic risk of erectile dysfunction; many authors recommend use ofautologous blood clot and absorbable gels

The success rates with selective pudendal artery catherterization followed by embolization are quite high (89% to 100%), regardless of the embolization material used

SURGICAL MANAGEMENTIt is reserved for patients who do not wish to

pursue expectant management or who are poor candidates for angio-embolization.

It is also reserved for patients who refuse the procedure; for patients in places where technology is not available; and for patients whose angio-embolization failed

The surgical approach is transcorporal. Intraoperative Doppler ultrasound guidance

is recommended.

Open surgery is performed through exploratory corporotomy to identify the pseudocapsule under ultrasound guidance followed by microsurgical closure of the ruptured artery

Recurrent (Stuttering) PriapismIf sickle cell disease is responsible, then

hematological management is necessary for the treatment.

Hydration, analgesics, oxygenation, and bicarbonate and blood transfusion (if necessary) may be appropriate treatment of recurrent priapism due to sickle cell disease.

The goal of hydration with intravenous fluid is to inhibit sickling by decreasing tonicity and improving circulation.

The goal of the management of recurrent (stuttering) priapism is prevention of future episodes, while management of each episode should follow the specific treatment recommendations for ischemic priapism.

Oral alpha adrenergic medications (e.g., etilefrine 0.5 mg/kg/day) ,self-intracavernosal injection of an alpha adrenergic agent such as 500 mg phenylephrine every 5 min until detumescence.

If the patient has no concerns regarding sexual function and the priapism episodes continue, then an antiandrogen or gonadotropin-releasing hormone agonist may be used

These agents suppress nocturnal penile erection and can prevent recurrent episodes of priapism.

Oral baclofen, an antispasticity medication,has also recently been shown to treat recurrent priapism.

Sildenafil has been noted to relieve recurrent episodes of priapism in patients with sickle cell disease.

It is believed that selective vasodilation of the corporal blood vessels prevents sickling of red cells in the corporal bodies

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