Priapismo em crianças: revisão de fisiopatologia e tratamento
- SourceAvailable from: nih.gov[Show abstract] [Hide abstract]
ABSTRACT: Intracavernous injections of etilefrine were effective in seven children with acute sickle cell priapism, and stuttering priapism resolved in five children after one to seven months of oral etilefrine. Compared with our previous reports in adults, etilefrine appears to be more effective in childhood.Archives of Disease in Childhood 08/2001; 85(1):52-3. · 3.05 Impact Factor
- Mayo Clinic Proceedings 02/2005; 80(1):111-4. · 5.79 Impact Factor
Objective: Priapism may cause serious sequelae concerning the future sex life of the patient, as it can determine
impotence, erectile dysfunction or psychogenic sexual aversion. It is a common symptom of sickle cell disease in children
and adolescents. There are few good quality evidence manuscripts about the problem in current medical literature.
Sources: Literature review on the databases MEDLINE and LILACS covering the period from 1966 to 2008.
Summary of the findings: The basis for the treatment of low flow priapism includes treating sickle cell disease and
the usage of intracavernous adrenergic agents as necessary. Surgery is indicated in a minority of cases. The treatment
of pediatric cases demands dose adjustments, adequate drug choice and sedoanalgesia to cover procedures involving
pain or trauma.
Conclusions: A new physiopathologic theory concerning sickle cell disease, which questions the traditional vascular
blockage mechanisms by deformed red cells and proposes that endothelial inflammatory activation is the main cause
of clinical problems, allows to propose new therapeutic maneuvers to solve sickle cell priapism. The absence of good
quality evidence to treat sickle cell priapism suggests the necessity to conduct good prospective multicenter protocols
to investigate the condition.
J Pediatr (Rio J). 2009;85(3):194-200: Priapism, sickle cell disease, children.
Priapism in children:
review of pathophysiology and treatment
Lisieux Eyer de Jesus,1 Samuel Dekermacher2
Jornal de Pediatria
Priapism can present in childhood and adolescence,
commonly to emergency services, and data about the disease
and its therapy are rare in literature, especially concerning
pediatric cases. The purpose of this manuscript is to review
and to systematize the procedures used to treat children
with priapism. We reviewed all the pertinent literature in
Portuguese, Spanish, French and English using the databases
MEDLINE and LILACS from 1966 to June 2008 using the
keywords priapism and/or sickle cell disease (SCD), limiting
ages from 0 to 18 years old.
Priapism in childhood commonly presents as a common
symptom of SCD especially after puberty, mainly as low flow
or as a complication of penile trauma (normally high flow,
non-ischemic episodes). This phenotypic manifestation of
SCD can cause persistent impotence, erectile dysfunction
and behavioral problems in the sexual realm, as affected
individuals fear the induction of an episode of painful erection
in the course of normal sexual activity, which is the most
common cause of priapism episodes after puberty.1
SCD is genetically determined by a mutation in the
β-globin chain of hemoglobin. The erythrocytes contain
a deviant form of hemoglobin, hemoglobin S, whose
biochemical characteristics cause functional problems.
SCD can exhibit various manifestations (called pathologic
phenotypes), which include pulmonary hypertension,
cerebral vascular accidents, lower extremity ulcerations,
osteonecrosis, painful crises, and priapism among
other less common clinical problems. Priapism in sickle
cell patients has been classically attributed to vaso-
occlusion episodes, secondary to the deformation of
red blood cells containing hemoglobin S by hypoxemia
and acidosis in the corpora cavernosa (CC) (caused by
vasoconstriction, hypovolemia or stasis in the CC during
physiologic erection), causing microvascular obstruction,
in a vicious cycle: red cell deformation causes vascular
obstruction and secondary ischemia, which promotes
new red cell deformation (vicious cycle theory, accepted
since the 1940s).2
Jornal de Pediatria - Vol. 85, No. 3, 2009 195
Priapism in children - de Jesus LE & Dekermacher S
Experimental studies and clinical experience have
raised doubts about this model since the 1940s, when
it was demonstrated experimentally that SCD patients
intentionally exposed to hypoxemic conditions did not
present problems.3-5 It is known that patients with SCD and
chronic persistent hypoxemia (for example, cyanotic heart
diseases) can survive and that orthopedic surgeries of the
extremities can be performed using tourniquets without
any problems in these patients. Anatomic vascular lesions
have been demonstrated in various organic territories in
SCD, by autopsy or arteriography, suggesting that vascular
problems in these patients may not depend on episodes of
gelation of abnormal hemoglobin (causing deformation of
red blood cells). In the neurologic and chronic pulmonary
lesions of sickle cell patients it has been demonstrated that
the pathophysiology includes vascular remodeling before
the onset of symptoms.6,7
A new model of the pathophysiology of SCD has been
proposed from the 1970s and 1980s, based on the mediating
function of the vascular endothelium in the microcirculation
(inflammatory theory). SCD is characterized by hemolysis,
whose intensity varies across individuals and at different
moments in a patient’s life. The instability of the hemoglobin
S molecule leads to the exposure of the highly oxidative group
heme and causes degradation of the cellular membrane,
releasing hemoglobin and arginase into the extracellular
environment, in a process that is possibly more intense the
less effective the reticuloendothelial system is to remove
abnormal circulating cells (it is common for sickle cell patients
to be functionally asplenic after preschool age, in a process
called autosplenectomy). Free hemoglobin oxidizes into
methemoglobin, liberating heme groups and ferrous ions.
Freed arginase in the extracellular environment consumes
L-arginine, a substrate for the endothelial synthesis of nitric
oxide. Nitric oxide is directly consumed in the oxidation of
hemoglobin to methemoglobin and in the neutralization
of heme groups and ferrous ions. The oxidative lesion,
direct consumption and deficit of nitric oxide synthesis
cause endothelial activation, release of inflammatory and
thrombogenic factors and a tendency to vasoconstriction.
Permanent vascular injuries occur over the long term,
perhaps fostered by chronic tissue hypoxemia and the
synthesis of vasoproliferative substances.8 Secondary or
simultaneous sinusoidal blockage by deformed red blood cells
in the microcirculation and worsening of the local process
of hemolysis may occur (the vicious cycle theory associates
here as a corollary of the process) (Figure 1).9,10
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.8,11 Episodes
of priapism are also linked to a rise in serum markers
Figure 1 - Mechanisms of microcirculatory lesions in sickle cell
disease: hemolysis, endothelial activation, hemoglo-
bin gelation with sickling, microthrombosis, decline in
production and excess consumption of nitric oxide
of hemolysis, such as increase of reticulocytes, indirect
bilirubin, and lactate dehydrogenase (LDH).8,12,13
Normal erection is induced by the parasympathetic
autonomic nervous system. Neural mediators determine
the release of nitric oxide in the CC, provoking a local
increase of cyclic metabolites (cGMP) by the activation of
guanylate-cyclase. cGMP then incites the cellular efflux of
calcium and the relaxation of smooth muscle of efferent
(helicine) arteries and of the CC itself, increasing afferent
blood flow. The draining venules, anatomically located
between the CC, are passively compressed by the turgid
and rigid corpora and blood accumulates. At the end of the
process, generally signaled by ejaculation and orgasm, the
sympathetic nervous system determines the vasoconstriction
of the efferent arteries of the CC, reducing the blood inflow.
Venous drainage mechanisms them predominate and
detumescence results. Nitric oxide is the main physiologic
mediator of erection, by the mechanisms described, but
other accessory biochemical processes are also likely to
play an important role.
The description of erection – dependent on the release
and local control of nitric oxide – and the contemporary ideas
regarding endothelial activation and relative microvascular
loss of nitric oxide in SCD suggest a relationship between
the disease, chronic erectile problems and priapism. Chronic
deficiency of nitric oxide provides a negative feedback on
phosphodiesterase in the CC. It has been postulated that this
enzyme deficiency leads to uncontrolled erection episodes
(priapism), caused by increases in cGMP by nitric oxide-
independent mediators. Simultaneously the mechanisms
of normal erection are hampered, in an apparent paradox.
Based on this idea, the pharmacological inhibition of
196 Jornal de Pediatria - Vol. 85, No. 3, 2009
Priapism in children - de Jesus LE & Dekermacher S
phosphodiesterase could make possible a rebalance at a
new level of function (Figure 2).8
Definitions and epidemiology
Priapism is defined as a non-physiologic persistent
erection that is either not provoked by sexual stimulus or
persists after ejaculation and orgasm. It normally involves
the CC and spares the spongiosum (tricorporal priapism is
uncommon and has poor prognosis). The problem was first
reported in SCD patients in 1934 in its most frequent form
of recurrent self-limited short episodes (stuttering episodes
in the English literature). Acute episodes are defined as
painful erection and/or persisting more than 4-6 hours.
Approximately 2/3 of patients presenting with an acute
attack of priapism relate previous intermittent episodes.
A classification of priapism episodes as high or low flow
has evolved during the 1980s,14 and became essential to
suggest causality and to determine prognosis and treatment.
High flow episodes are characterized by an increase of
arterial supply to the CC: venous drainage remains normal.
Their prognosis is better, they usually do not have to be
addressed as emergencies and secondary impotence is rare
(< 20%). In children high flow priapism is typically caused
by post-traumatic arteriocavernosal fistula (from penile,
perineal or pelvic trauma), and is generally manifested
several days after the trauma. It can also be caused by
intracavernosal injections of vasoactive agents, scorpion
or snake bites, substance abuse (mainly cocaine, which
can cause high or low output priapism), some therapeutic
drugs (especially psychiatric medications with autonomic
nervous system effects), infectious diseases or tumors.
Figure 2 - Mechanisms determinant of erection: relations between
nitric oxide and phosphodiesterase
On low flow priapism there is a loss of vascular regulation.
Venous drainage is impaired, presumably as a consequence
of vascular blockage by deformed red blood cells. The
situation may be further complicated as the fixed resistance
maintained by the adventitia of the CC causes a compartment
syndrome. This is an emergency and should be resolved
within 6 hours of the onset of the episode to minimize the
sequelae. In addition to SCD, other hematologic diseases with
hypercoagulability or hyperviscosity (principally leukemias)
and several drugs can cause low flow priapism.
SCD priapism may occasionally be of high output
type, arising from a defect in the regulation of vascular
tone in the CC, but it is estimated that more than 80% of
sickle cell episodes are low flow (although the specialized
literature seldom proves that, clinical presentation of acute
pain suggests this is the case). On the other hand, it is
known that conversion between the two forms of priapism
is possible (cases of impotence after episodes of high flow
perhaps might be due to conversion to low flow), especially
in prolonged episodes, possibly by modifications in the
regulation of afferent vascular tone.
Considering the high taxes of miscegenation of the
black population of African origin (up to 40% of those
carrying SCD genotype) to other ethnic groups in Brazil,
the prevalence of sickle cell anemia in our country is very
high. Textbooks suggest that the frequency of priapism in
children with SCD varies between 2 and 6%.15 Incidence
statistics are adversely affected by a serious selection
bias: only children seen in hospitals for acute episodes,
specialty clinics and tertiary referral centers tend to be
More than 1/4 of priapism episodes in urologic practice
are caused by SCD. In children nearly all cases of priapism
are secondary to sickle cell anemia or trauma. At least 1/3
of male adults with SCD present this symptom at some
point, usually beginning in school age (the mean age for
the onset of manifestations is 11 years), but it is rare
to present this symptom for the first time after the third
decade of life.1 Nearly 1/4 present during the prepubertal
period.1,16 Nocturnal episodes are more frequent.17 Priapism
varies in frequency across the different ethnic groups with
SCD. An absolute majority relates intermittent episodes
preceding an acute episode, which 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 are sexual
activity (including masturbation), dehydration, fever and
exposition to a cold environment.
The physical examination detects an erection restricted
to the CC. The spongiosum and the glans remain flaccid,
except for the rare cases of tricorporal priapism. Because
Jornal de Pediatria - Vol. 85, No. 3, 2009 197
Priapism in children - de Jesus LE & Dekermacher S
of the lack of involvement of the periurethral spongiosum,
there are normally no micturating problems.
In high flow cases the erection is less rigid and the
penis is pink and pulsatile. There can be signs of trauma
(hematomas, bruises). It may be possible to resolve the
erection compressing the arteriovenous fistula feeder vessel,
but the erection will recur immediately after the compression
is withdrawn. In low flow cases the penis is rigid, extremely
painful and seems ischemic: it does not pulse, is pale or
grayish and cold. These manifestations are more evident
after the episode has evolved for at least 4 hours.
To investigate a patient presenting with ischemic priapism
the following laboratory studies should be ordered:
- Complete blood count and coagulation profile (to evaluate
the degree of anemia, to detect signs of other hemato-
logic diseases and to investigate a possible triggering
- A search for sickle cells in a blood sample (if there is
no prior diagnosis of SCD);
- Hemoglobin electrophoresis;
- Urinalysis and urine culture;
- An arterial blood gas analysis should be obtained if there
is any suspicion of hypoxemia or systemic acidosis.
The distinction between high and low flow priapism
can be established by the analysis of blood aspirated
from the CC. In low flow cases blood will be dark, acidotic
(pH < 7), hypoxemic (pO2 < 40 mmHg) and hypercarbic
(pCO2 > 70 mmHg). In high flow cases it will be bright
red (arterial), alkalotic (pH > 7), with normal oxygenation
(pO2 > 60 mmHg) and low pCO2 (< 70 mmHg).18
Use of scintigraphy has been proposed to differentiate
low (decreased uptake, “cold” CC) from high flow cases,
but the limited availability of the test, its low specificity and
sensitivity and the lack of a comparative or gold standard has
limited its use. There are no studies comparing cavernosal
blood analysis to cavernosal scintigraphy in sickle cell
priapism. Unfortunately, the few published studies tend to
view sickle cell priapism as low flow by definition.15
Doppler ultrasound is more useful for high flow cases,
to identify an arteriovenous fistula supplying the erection.
Cavernosography is rarely used, because blood analysis is
adequate and less aggressive. Arteriography of the internal
pudendal artery has some limited use in high flow cases
in which there is an intention to treat by embolization or
surgery (where it is important to locate the fistula that will
be addressed by the surgeon or radiologist).
The prognosis for erectile function in sickle cell patients
is poor.19 Most authors report that between 1/4 to 1/2 of
patients become impotent after prolonged episodes of
priapism. The prognosis may be better for prepubertal
children.20 We could find no explanations for this
phenomenon. Perhaps the absence of androgenic activity
could explain the relative protection of prepubertal patients.
The frequently suggested association between impotence
and surgical treatment (1/4 to 1/2 of operated cases) should
be questioned. There is a strong selection bias, as surgery
has been systematically reserved for the most serious and
advanced cases, not responsive to other interventions
and low and high flow episodes are not systematically
qualified in published reports. The use of different surgical
techniques also makes it difficult to compare data from
Acute cases have a much poorer prognosis than cases
of intermittent priapism. In addition to impotence, erectile
dysfunction and aversion to sexual activity (as the patient
fears to induce episodes of priapism) are common. Cerebral
vascular accidents are more frequent close to an episode
of acute priapism. The ASPEN syndrome (association of
sickle cell disease, priapism, exchange transfusion and
neurological events), describes strokes in SCD patients
who have undergone exchange transfusions.12,13
For high flow priapism treatment is elective. Compression
and ice packs while waiting for the spontaneous resolution
of small fistulas (up to 6 weeks, according to most authors),
embolization or surgery are the common suggestions.
In cases of low flow priapism, the latency between
effective treatment and the beginning of an episode
determines the prognosis for erectile function. There are
serious difficulties in evaluating treatments for sickle cell
priapism, because of the nearly complete absence of good
quality evidence in the literature (only one study was
considered to be of adequate quality for analysis among
all studies examined in a recent Cochrane Collaboration
Men with SCD should be alerted regarding the need
to seek prompt specialized treatment for any episode of
priapism that lasts longer than 2 hours. Eighty-six percent
of SCD patients do not spontaneously report complaints
regarding intermittent priapism during regular consultations
because of cultural factors, absence of perception of the
phenomenon as abnormal (especially in children and
adolescents), shame or a lack of understanding of the
relationship of the phenomenon to SCD. The physician
must actively inquire about priapism in the anamnesis of
any SCD patient.
Ischemia can be demonstrated by cavernosal blood
analysis 4 to 6 hours into an episode. After 12 hours
interstitial edema begins. In 48 hours it is possible
to detect necrosis of smooth muscle and invasion by
fibroblasts. Later biopsies of the CC demonstrate fibrosis.
This sequence suggests that histological lesions are already
198 Jornal de Pediatria - Vol. 85, No. 3, 2009
Priapism in children - de Jesus LE & Dekermacher S
present after the 12th hour into the episode; thus, ideally,
intervention should be able to end the episode before
this time period.22
Even before seeking care, the patient should be instructed
to drink plenty of liquids, urinate, take a warm bath, use
analgesics and undertake physical activity. Some cases will
resolve spontaneously. If the episode does not resolve in
2 hours, it is critical that the patients seek medical care
(or, according to a protocol that we consider inappropriate
for pediatric patients, it is possible to self-administer an
injection of an α-adrenergic - see below). All patients should
receive routine treatment for the complications of SCD:
generous venous hydration (approximately twice normal
requirements), oxygen, systemic alkalinization, analgesia
and/or sedation. Some authors propose, without scientific
basis, use of cold enemas. The intense discomfort and the
risk of hypothermia (which is greater in pediatric patients)
advise against this treatment. The use of ice packs on the
penis (standardized in the cases of high flow priapism) is
debatable in low flow cases, because presumably it would
diminish the blood supply and increase ischemia, although
it has analgesic effects and possibly limit cellular damage
due to ischemia (cryoprotection). Despite its traditional use
there is no available scientific evidence.
Exchange transfusions have been questioned for three
- Absence of good quality scientific evidence of its ef-
- Consideration of new ideas regarding the pathophysiology
of SCD, progressing from red blood cell deformity and
mechanical circulatory blockade to primary endothelial
activation and vascular decompensation23;
- Risks associated with transfusion, considering the classic
hazards of infectious diseases transmission, immuno-
logic risks and ASPEN syndrome (possible induction of
a stroke in sickle cell patients transfused for treatment
of an episode of priapism),11 in addition to the logistical
difficulties for obtaining blood for emergency exchange
Next on treatment of any low flow priapism episode the
CC can be aspirated and irrigated. The procedure is performed
under local anesthesia in adults, but sedation in pediatric
patients is advised, considering the low cooperation of
children with a painful therapeutic procedure that consumes
a relatively long time and the potential for worsening in
SCD patients submitted to stress. Anesthesia for SCD has
specific risks and requires special care. Rigorous asepsis
should be followed: the most frequent complications of the
procedure are infectious. Antibiotic prophylaxis is advised,
using first-generation cephalosporins as the first choice.
After local anesthetic blockade, one of the CC is
punctured, usually via the glans (in the majority of
cases it is not necessary to access the two CC, which
communicate): irrigation and drainage of the full extension
of the corpora is more efficient using the most distal
access available. A 21-gauge needle is typically used for
children. For adolescents and adults, a 19-gauge needle
can be used. First of all, blood should be collected for gas
analysis and confirmation of the diagnosis. Thereafter the
CC are drained. The volume removed in the aspiration
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 – generally non-selective (etilefrine,
phenylephrine, epinephrine, metaraminol) – are then
injected. The exact pharmacologic action of these drugs
to solve an episode of priapism is debatable: they may
induce a constriction of afferent arteries, increasing venous
return (α effect), dilatation of vascular smooth muscle
(β effect) or have other actions over the local vessels,
ignored at the present time.17 Besides the risk of infection,
the injection of adrenergic agents can be complicated by
hematomas, urethral lesions, and fibrosis at the injection
site. There are case reports of penile necrosis, only in
adults and after prolonged episodes, one of them after
a secondary necrotizing infection.24 Systemic effects are
extremely rare. The proposed dosages are:
- Adrenaline 1:1,000,000: dose 10 mL (87% success
rate overall, 100% success in cases whose evolution
was < 24 hours). In 20% of cases it was necessary to
repeat the injection.25 Other authors propose diluting
1 mL of adrenaline 1:1,000 solution in 1 L of saline and
injecting 20 mL in repeated boluses, until a maximum
of 10 injections (200 mL).26
- Etilefrine: Gbadoe et al. propose use of 5-10 mg per
intracavernosal injection, without dilution. The authors
report resolution in five of six episodes (lasting 4-28
hours). In a maximum follow-up of 4 years, no cases
of impotence were related. Other authors suggest this
same protocol for home management of priapism epi-
sodes, by self-administered injections.27
Also recommended for the control of acute episodes,
as second choices:
- Intracavernosal injection of methylene blue. Postulated
action: capture (scavenging) of oxygen-free radicals
and/or inhibition of guanylate cyclase. Experience was
with a few cases in adult patients (injection of 50 mg),
none with SCD.28,29 Local infectious complications (CC
abscess) and penile discoloration have been reported.
- Phosphodiesterase inhibitors: a deficiency of phospho-
diesterase has been demonstrated experimentally in
priapism, possibly related to defects in the regulation
of erection (phosphodiesterase downregulation; see
above). Some clinical experience was published in acute
cases of SCD priapism in adults, with a single oral dose
of 50 mg, resolving the episode within 90 min in all
- Ketamine injections (0.5-1 mg/kg): the mechanism
of action is not understood, but may be dependent on
Jornal de Pediatria - Vol. 85, No. 3, 2009 199
Priapism in children - de Jesus LE & Dekermacher S
the modulation of the autonomic nervous system and
penile vascular tone. There are some published clinical
reports in adults and children, which have been highly
- Hydralazine: only one case has been published, in a 16
year-old patient. The authors suggest that the vasodila-
tory action of the drug resolved the symptoms.33
- Calcium-channel blockers, possibly by directly modulat-
ing the mechanisms of erection. Few cases were reported,
restricted to adults. There are various other published
studies describing priapism secondary to use of these
- Anticoagulants: their use is based on the inhibition of
local thrombogenic mechanisms. Doses and effects are
poorly defined in the literature, which advocates direct
use in the CC.35
- Corticosteroids, possibly acting as anti-inflammatory
effect and by controlling the release of mediators from
the activated endothelium.
- Continuous epidural anesthesia, possibly modifying the
activity of the autonomic nervous system.36
- Inhaled nitric oxide.37
- Surgery: most authors would indicate surgery only in
low flow priapism episodes, after 12 hours, if conven-
tional medical treatment and injection of the CC with
adrenergics could not solve the problem. This can be
performed by a distal cavernosa-spongiosum shunt
(Winter shunt, which creates a cavernosa-spongiosum
shunt by puncturing the glans with a Tru-Cut needle and
Al-Ghorab shunt, which proposes to suture the distal
extremity of the CC to the spongiosum into the glans)
or a proximal shunt (Grayhack shunt: laterolateral
spongiosum to proximal penile CC suture) or by caver-
nosa-venous diversion (to the saphenous vein or to the
dorsal vein of the penis). In an extensive review of the
literature, Khoriaty et al. reported normal potency in
62% patients (n = 65) treated with saphenous-cavern-
ous shunts (74% in patients < 40 years of age, 73% of
unilateral vs. 55% of bilateral shunts), but described
serious complications (pulmonary embolism and penile
necrosis). Of 32 cases of spongiosum-cavernous anas-
tomoses, 63% preserved potency (70% of the patients
younger than 40 years). The complications reported
were limited to urethral fistulas.38
Prophylaxis of recurrence of acute episodes or of
occurrence of acute episodes in patients with recurrent
self-limited priapism (considered as prodromes for acute
episodes) has the following therapeutic proposals:
Oral administration of α-adrenergics: 0.5 mg/kg etilefrine
at night or divided into two daily doses (maximum of
30 mg/d), associated with intracavernosal self-injec-
tion in cases of acute episodes lasting more than 1
- Terbutaline: only one group published a clinical report
about use of this drug.40
- Therapy with hydroxyurea, with the aim of inducing the
synthesis of fetal hemoglobin, modifying the mecha-
nisms of endothelial activation and resulting in general
improvement of SCD. Given the side effects and risks,
this approach has been reserved for serious cases.
Despite this, the association of priapism and stroke in
SCD patients and the serious impact on the sexual life
of young patients have prompted use of the drug in
those cases, although it remains controversial among
- Use of anti-androgenic hormonal manipulation, us-
ing gonadotrophin inhibitors (goserelin, leuprolide) or
finasteride to reduce androgen levels to those attained
by castration. This treatment, although efficacious, is
fraught with side effects usually unacceptable to patients
(loss of libido and erectile function). In pediatric patients
iatrogenic persistent alteration of the still immature
hypothalamus-pituitary-gonadal axis is theoretically
possible. This treatment is costly. There is no sufficient
evidence in the literature regarding its efficacy and
safety. In the case of finasteride, there is no significant
activity of androgens in pre-pubertal children that would
justify usage of the drug. Those drugs are second- or
third-line treatment options.17
- Estrogens/diethylestilbestrol: mechanism of action un-
known. It is believed to be anti-androgen or to change the
function of affected red blood cells. All available studies
have treated adult patients (none refers to children).
In a prospective placebo-controlled study of excellent
technical quality the drug is extremely effective, but
its use is limited by the recurrence of symptoms 6 to
8 weeks after discontinuation of the medication and
because of the side effects (loss of libido and erectile
function, gynecomastia, testicular atrophy). It should
be considered a last resort medication, not appropriate
for use in pre-pubescent patients.17
- Phosphodiesterase inhibitors: a single published article
addressed only the successful prophylactic use in four
adult patients (three with SCD) who had frequent recur-
rences and no response to other forms of therapy.43
- Ketoconazole, for its mild anti-androgen effect.44,45 All
cases reported in the literature are short-term post-
operative use after penile surgery in patients without
hematologic disease, and there are some theoretical
worries with respect to the induction of resistance with
the prolonged use of an antifungal drug.
The placement of a penile prosthesis should be considered
in adulthood, so that patients with erectile dysfunction as a
consequence of prior crises can become sexually active.
The clinical and surgical management in cases of priapism
involving patients with SCD is full of controversies: in
fact, there is no clinical evidence of great quality available
at the moment. A change in the understanding of the
pathophysiology of the disease can dramatically alter the
therapeutic proposals in the near future. Well-designed
200 Jornal de Pediatria - Vol. 85, No. 3, 2009
Priapism in children - de Jesus LE & Dekermacher S
Lisieux Eyer de Jesus
Rua Presidente Domiciano 52/801
CEP 24210-270 - Niterói, RJ - Brazil
Tel.: +55 (21) 2622.3843, +55 (21) 9985.9737
1. Adeyoju AB, Olujohungbe AB, Morris J, Yardumian A, Bareford D,
Akenova A, et al. Priapism in sickle-cell disease; incidence, risk
factors and complications – an international multicenter study.
BJU Int. 2002;90:898-902.
2. Ham TH, Castle WB. Relationship of increased hypotonic fragility
and of erythrostasis to the mechanism of hemolysis in certain
anemias. Trans Assoc Am Physicians. 1940;55:127-32.
3. Klinefelter HF. The heart in sickle cell anemia. Am J Med Sci.
4. Henderson AB, Thornell HE. Observations on the effect of lowered
oxygen tension on sicklemia and sickle cell anemia among military
flying personnel. J Lab Clin Med. 1946;31:769-76.
5. Sproule BJ, Halden RE, Miller WF. A study of the cardiopulmonary
alterations in patients with sickle-cell disease and its variants. J
Clin Invest. 1958;37:486-95.
6. Stockman JA, Nigro MA, Mishkin MM, Oski FA. Occlusion of
large cerebral vessels in sickle cell anemia. N Engl J Med.
7. Powars D, Weidman JA, Odom-Maryon T, Niland JC, Johnson C.
Sickle cell chronic lung disease: prior morbidity and the risk of
pulmonary failure. Medicine (Baltimore). 1988;67:66-76.
8. Kato GJ, Gladwin MT, Steinberg MH. Deconstructing sickle cell
disease: reappraisal of the role of hemolysis in the development
of clinical subphenotypes. Blood Rev. 2007;21:37-47.
9. Firth PG. Anaesthesia for peculiar cells – a century of sickle cell
disease. Br J Anaesth. 2005;95:287-99.
10. Firth PG, Head CA. Sickle cell disease and anesthesia.
11. Siegel JF, Rich MA, Brock WA. Association of sickle cell disease,
priapism, exchange transfusion and neurological events: ASPEN
syndrome. J Urol. 1993;150:1480-2.
12. Nolan VG, Wyszynski DF, Farrer LA, Steinberg MH.
Hemolysis-associated priapism in sickle-cell disease. Blood.
13. Merritt AL, Haiman C, Henderson SO. Myth: blood transfusion
is effective for sickle cell anemia-associated priapism. CJEM.
14. Hauri D, Spycher M, Bruhlman W. Erection and priapism: a new
physiological concept. Urol Int. 1983;38:138-45.
15. Miller ST, Rao SP, Dunn EK, Glassberg KI. Priapism in children
with sickle cell disease. J Urol. 1995;154:844-7.
16. Liu J, Al-Hothari MA, Mahboob FA. Non surgical treatment of
recurrent or stuttering priapism in sickle cell children. Saudi Med
17. Maples BI, Hagemann TM. Treatment of priapism in pediatric
patients with sickle cell disease. Am J Health Syst Pharm.
18. Van der Horst C, Stuebinger H, Seif C, Melchior D, Martinez-
Portillo FJ, Juenemann KP. Priapism: etiology, pathophysiology
and management. Int Braz J Urol. 2003;29:391-400.
19. El-Banasawy MS, Dawood A, Farouk A. Low flow priapism: risk
factors for erectile dysfunction. BJU Int. 2002;89:285-90.
20. Chacrabarty A, Upadhyay J, Dhabuwala CB, Sarnaik S,
Perlmutter AD, Connor JP. Priapism associated with sickle cell
hemoglobinopathy in children: long-term effects on potency. J
21. Chinegwundoh F, Anie KA. Treatments for priapism in boys and men
with sickle cell disease Cochrane Database Syst Rev. 2004;(4):
22. Pflueger A, Blackwell KA, Sampson SM. 38-year-old man with
priapism and a history of paranoid schizophrenia. Mayo Clin Proc.
23. Burnett AL. Pathophysiology of priapism: dysregulatory erection
physiology thesis. J Urol. 2003;170:26-34.
24. Montoya Martinez G, Otero Garcia JM, Lopez Samano V, Gonzalez
Martinez J, Serrano Brambilla E. Penile necrosis: a review of 18
cases at the Hospital de Especialidades Centro Medico Nacional
Siglo XXI. Arch Esp Urol. 2006;59:571-6.
25. Mantadakis E, Ewalt DH, Cavender JD, Rogers ZR Buchanam GR.
Outpatient penile aspiration and epinephrine irrigation for young
patients with sickle cell anemia and prolonged priapism. Blood.
26. Molina l, Bejany D, Lynne CM, Politano VA. Diluted
epinephrine solution for the treatment of priapism. J Urol.
27. Gbadoe AD, Atakouma Y, Kusiaku K, Assimadi JK. Management
of sickle cell priapism with etilefrine. Arch Dis Child.
28. Martínez Portillo F, Hoang-Boehm J, Weiss J, Alken P, Jünemann
K. Methylene blue as a successful treatment alternative for
pharmacologically induced priapism. Eur Urol. 2001;39:20-3.
29. Steers WB, Selby JB Jr. Use of methylene blue and selective
embolization of the pudendal artery for high flow priapism refractory
to medical and surgical treatments. J Urol. 1991;146:1361-3.
30. Bialecki ES, Bridges KR. Sildenafil relieves priapism in patients
with sickle cell disease. Am J Med. 2002;113:252.
31. Ravindran RS, Dryden GE, Somerville GM. Treatment of
priapism with ketamine and physostigmine. Anesth Analg.
32. Appadu B, Calder I. Ketamine does not always work in treatment
of priapism. Anaesthesia. 1991;46:426-7.
33. Baruchel S, Rees J, Bernstein ML, Goodyer P. Relief of sickle cell
priapism by hydralazine. Report of a case. Am J Pediatr Hematol
34. Russell JM, MacGregor RJ, Watson L. Prazosin and priapism. Med
J Aust. 1985;143:321.
35. Francis RB. Large-vessel occlusion in sickle cell disease:
pathogenesis, clinical consequences, and therapeutic implications.
Med Hypotheses. 1991;35:88-95.
36. McHardy P, McDonnell C, Lorenzo AJ, Salle JL, Campbell FA.
Management of priapism in a child with sickle cell anemia;
successful outcome using epidural analgesia. Can J Anaesth.
37. Burnett AL, Musicki B, Jin L Bivalacqua TJ. Nitric oxide/ redox-
based signaling as a therapeutic target for penile disorders. Expert
Opin Ther Targets. 2006;10:445-57.
38. Khoriaty N, Schick E. Surgery for priapism. J Urol (Paris).
39. Bachir D, Virag R, Lee K, Belloy M de Montalembert M, Denis L,
et al. Prevention and treatment of erectile disorders in sickle cell
disease. Rev Med Interne. 1997; 18 Suppl 1:46s-51s.
40. Ahmed I, Shaikh NA. Treatment of intermittent idiopathic priapism
with oral terbutaline. Br J Urol. 1997;80:341.
41. Okpala I. Investigational agents for sickle cell disease. Expert
Opin Investing Drugs. 2006;15:833-42.
42. Saad ST, Lajolo C, Gilli S, Marques Junior JF, Lima CS, Costa FF, et
al. Follow-up of sickle cell disease patients with priapism treated
by hydroxiurea. Am J Hematol. 2004;77:45-9.
43. Burnett AL, Bivalacqua TJ, Champion HC, Musicki B. Long-term
oral phosphodiesterase 5 inhibitor therapy alleviates recurrent
priapism. Urology. 2006;67:1043-8.
44. Stock JA, Kaplan GW. Ketoconazole for prevention of postoperative
penile erections. Urology. 1995;45:308-9.
45. Evans KC, Peterson AC, Ruiz HE, Costabile RA. Use of oral
ketoconazole to prevent post-operative erections following penile
surgery. Int J Impot Res. 2004;16:346-9.
prospective studies, preferably multicenter, given the
small samples available in individual services, are urgently
Considering the serious potential complications, it
is important to educate patients and physicians for the
importance of early detection of recurrent episodes of
priapism (stuttering), in order to prevent acute cases. The
careful classification of episodes into high and low flow
episodes using cavernosal blood analysis and prompt care
of acute cases of low flow priapism is essential to increase
the chances of less aggressive but effective treatment with
a lower incidence of permanent sequelae.