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 Previous Article | Table of Contents | Next Article 
Blood, Vol. 95 No. 1 (January 1), 2000:
pp. 78-82
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Outpatient penile aspiration and epinephrine irrigation for young
patients with sickle cell anemia and prolonged priapism
Elpis Mantadakis,
David H. Ewalt,
Joe Don Cavender,
Zora R. Rogers, and
George R. Buchanan
From the Division of Hematology-Oncology, Department of Pediatrics
and Department of Urology, The University of Texas Southwestern Medical
Center at Dallas and Children's Medical Center, Dallas, Texas.
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Abstract |
The optimal management of prolonged priapism for patients with
sickle cell anemia (SCA) has not been established. We prospectively studied in an outpatient setting the efficacy and safety of a procedure
that employs aspiration of blood from the corpora cavernosa and
irrigation with a dilute epinephrine solution under local anesthesia to
relieve priapism in young patients with SCA. If hydration and
analgesics failed to produce detumescence or if priapism had lasted
>4 hours, the protocol was activated in the emergency room or clinic.
Fifteen patients with homozygous SCA (Hb SS) were treated on 39 occasions; 10 patients were treated once, 1 patient twice, 2 patients 3 times, 1 patient 6 times, and 1 patient 15 times. Median age of
patients at first treatment was 14.3 years (range, 3.9-18.3 years). The
procedure was successful in producing immediate detumescence on 37 of
39 occasions (95% efficacy, 95% confidence intervals
(CI): 81%-99%). No serious immediate or long-term side effects were
observed. None of the patients who demonstrated detumescence required
hospitalization. The 2 patients whose priapism persisted after
aspiration and irrigation presented with episodes lasting >24 hours.
All evaluable patients whose priapism resolved after aspiration and
irrigation self-reported normal erectile function at a median of 40 months (range, 3-58 months) after the last procedure. Thus, aspiration
of the corpora cavernosa followed by irrigation with dilute epinephrine
is effective in producing immediate and sustained detumescence and
should be the initial therapy employed for patients with SCA and
prolonged priapism. (Blood, 2000; 95:78-82)
© 2000 by The American Society of Hematology.
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Introduction |
Priapism is a sustained, unwanted, and painful erection
usually unrelated to sexual activity.1 The prevalence of
severe priapism in patients with sickle cell anemia (SCA), based upon review of hospital admissions, is 2% to 5%.2 However, we
recently estimated that the prevalence of priapism may be as high as
89%3 in young males (by the age of 20 years) with
homozygous SCA (Hb SS) or hemoglobin S- 0 thalassemia.
Retrospective studies of adults with SCA indicate that 30% to 45%
have experienced priapism on 1 or more occasions.4,5
Prolonged priapism is a urologic emergency requiring urgent
intervention to avoid irreversible ischemic penile injury, corporal fibrosis, and impotence.6 Numerous therapeutic
interventions, including hydration, analgesics, simple erythrocyte
transfusion, exchange transfusion, vasodilators, and
hormones,7 have been used for the treatment of priapism
associated with SCA. However, none of them is predictably effective in
relieving priapism, and many may delay efforts or procedures that
potentially allow reperfusion of the corpora cavernosa. In addition,
some interventions have been associated with serious side
effects,8,9 and most if not all of these interventions
require hospitalization.
Alpha adrenergic agents have been shown to be effective in the
treatment of priapism resulting from intrapenile injections of
vasoactive drugs (such as papaverine, phentolamine, or prostaglandin E1), which are used for the treatment of impotence.10,11
Thus, we prospectively studied whether aspiration of blood from the corpora cavernosa and intrapenile irrigation with epinephrine, a potent
 -agonist, is effective in terminating prolonged episodes of priapism
in patients with SCA as well. Preliminary results with the use of this
procedure from our center have been previously described.12
Our overall and long-term experience with this therapeutic approach is
described below.
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Materials and methods |
Management protocol
In January 1993 we established a prospective management protocol for
the outpatient management of prolonged episodes of priapism. Patients
with SCA who experienced priapism were advised to drink extra fluids,
use oral analgesics, exercise gently, and attempt to urinate soon after
development of the complication. When these measures failed or if an
episode lasted longer than 2 hours, the patients were advised to seek
medical attention at the emergency room of the Children's Medical
Center of Dallas. When intravenous hydration and parenteral morphine
failed to induce detumescence within 1 to 2 additional hours, the
protocol was applied. Our goal was to perform the procedure within 2 hours of presentation to the emergency room and <4-6 hours from the
beginning of the episode.
Procedure
After induction of conscious sedation with intravenous midazolam
and/or morphine, the lateral side of the penis was thoroughly swabbed
with povidone iodine. A 1% lidocaine solution (1/2 mL) was infiltrated
under the skin and more deeply into the tunica albuginea. A 23-gauge
needle was then inserted perpendicularly into the corpus cavernosum
(ie, unilateral insertion), and as much blood as possible was aspirated
into a dry 10-mL syringe through a 3-way stopcock. Another 10-mL
syringe containing a 1:1 000 000 solution of epinephrine (ie, 1 mL of
1:1000 epinephrine diluted in 1 L normal saline) was then attached to
the 3-way stopcock, and the corpora cavernosa were irrigated with the
epinephrine solution. If needed, additional blood was aspirated until
detumescence occurred. After withdrawal of the needle, firm pressure
was applied by the urologist for 5 minutes (timed by the clock) to
prevent hematoma formation, and the patient was discharged home if
there was continued and/or sustained detumescence 30 minutes following the procedure.
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Results |
Between January 1993 and November 1998, 39 aspiration and irrigation
procedures were performed on 15 patients (Table
1). All patients had homozygous SCA and all
except 2 patients (Nos. 6 and 7) were known to us to have
previously experienced brief and self-limited episodes of priapism. Ten
patients were treated once according to the protocol, 1 patient twice,
2 patients 3 times, 1 patient 6 times, and 1 patient 15 times.
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Table 1.
Initial results in 15 patients with SCA who underwent
penile aspiration and epinephrine irrigation for prolonged priapism
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The median age of patients at first treatment was 13.7 years (range,
3.9-18.3 years). Two patients (Nos. 7 and 11) were <6 years of age.
Although patients were advised to seek prompt medical attention, the
procedure was performed after prolonged episodes of priapism (lasting 6 to 28 hours) on 12 occasions. Five patients (Nos. 1, 4, 5, 8, and 15)
who had multiple (2 to 15) procedures always presented to the emergency
room sooner after the second (or later) episode compared to the initial event.
The procedure was successful in producing detumescence within <1
minute on 37 of the 39 occasions (95% efficacy, 95% CI:
81%-99%).13 Ten of 15 patients (67%) required only 1 aspiration and irrigation treatment, and all 7 patients with adequate
follow-up (Nos. 3, 6, 9, 11, 12, 13, and 14) had no recurrences of
severe priapism at a median follow-up of 39 months (range, 12-58 months).
The only immediate complication that occurred was formation of a small
intrapenile hematoma on 2 occasions (Nos. 12 and 14). None of the
patients whose priapism resolved required hospitalization. A 6-year-old
boy (No. 14) whose priapism persisted after aspiration and irrigation
did not present to the emergency room until 28 hours after his first
episode of priapism. He underwent an emergency cavernosal-glanular
shunt without response. His priapism finally resolved slowly following
a simple red blood cell transfusion, 7 days of hydration, and
parenteral analgesics. The second patient who failed to demonstrate
detumescence, a 16-year-old boy (No. 4), also presented after an
episode of priapism lasting 28 hours. He developed severe acute chest
syndrome shortly after presentation and was admitted to the intensive
care unit, where he underwent an automated exchange transfusion
(Hb S of 30.6% at the end of the exchange). His priapism
resolved within 48 hours. Notably, 18 months later, following another
priapism episode of 6 hours duration, the patient demonstrated
immediate detumescence in response to the aspiration and irrigation performed.
The patient who required aspiration and irrigation on 15 occasions (No.
1) returned to the emergency room 6 times within 72 hours with
recurrent priapism requiring repeated aspiration and irrigation.
After the patient was started on monthly intramuscular leuprolide therapy, he did not experience any priapism recurrences and
therefore did not require further aspiration and irrigation procedures.
No recurrences were seen within 72 hours following this last procedure
(patient No. 1) and the remaining 33 procedures performed in the other
14 patients.
As of February 1999, 1 patient (No. 10) died from a cause unrelated to
SCA (drowning), and 2 patients (Nos. 2 and 7) did not return to
follow-up. The remaining 12 patients continue to be followed by us
(Table 2). All 11 of the boys who underwent
successful aspiration and irrigation, as well as patient No. 4, self-report normal erectile function. Direct questioning was done in
person or by telephone at a median follow-up of 40 months (range, 3-58 months) after the last procedure. The 6-year-old boy (patient No. 14)
who underwent emergency shunting has residual penile fibrosis, which
was evident on physical examination performed 40 months after the
procedure.
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Table 2.
Long-term follow-up of patients with SCA who underwent
penile aspiration and epinephrine irrigation for prolonged priapism
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To attempt to prevent further recurrences of priapism, 7 patients who
required aspiration and irrigation on 1 (Nos. 3, 9, 11, 12, 13, and 14)
or more (No. 8) occasions take as-needed or scheduled oral
pseudoephedrine at bedtime. Review of medical records and
self-reporting by patients and their families suggest that oral
pseudoephedrine decreases recurrences of both stuttering (ie, brief and
self-limited) and major (ie, lasting >2 hours) priapism.
Two patients who required multiple aspiration and irrigation procedures
(Nos. 1 and 5) and 1 patient (No. 12) who had a prolonged episode of
priapism have received monthly intramuscular injections of leuprolide
without further recurrences of severe priapism.
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Discussion |
Priapism is a painful and disabling vaso-occlusive complication of
SCA.1-7 Despite the high prevalence of priapism and its potentially devastating consequence, ie, impotence,14,15
neither the natural history of priaspism nor its optimal therapy have been established. In addition, patients with SCA frequently do not
associate priapism with their underlying disease and may delay seeking
medical attention. For example, we recently ascertained that only 7%
of boys diagnosed with SCA but without a known history of priapism knew
what priapism was and were aware that it is a complication of
SCA.3
Two clinical patterns of priapism have been described. Severe episodes
lasting more than 2 to 3 hours often require medical intervention for
pain control and to prevent ischemic injury to the penis. Shorter
episodes, so called stuttering spells, last from a few minutes to 2 hours and resolve spontaneously, but they may recur and or be followed
by prolonged events.3 Although involvement of the corpus
spongiosum and glans penis has been described in 1 series of adults
with SCA and priapism (tricorporal priapism), the vast majority of
cases in children, adolescents, and young adults are bicorporal, as was
the case in our series.16
The underlying mechanism of priapism is the obstruction of venous
drainage of the penis.17,18 After abnormally long
erections, blood trapped in the corpora cavernosa becomes deoxygenated,
resulting in local acidosis and further sludging of sickled
erythrocytes. This leads to increased intracavernous pressure. When the
latter exceeds the mean arterial pressure for prolonged periods of
time, the penis becomes ischemic,17,18 possibly resulting
in corporal fibrosis and impotence. Priapism often has its onset in the
early morning hours during periods of rapid-eye-movement sleep. This time is normally associated with erections and the relative nocturnal acidosis and dehydration favor sickling of erythrocytes.7
Many interventions have been used to treat priapism in children and
adults with SCA. Nonsurgical measures include oral or intravenous
hydration, alkalinization to ameliorate acidosis, analgesics, and
frequent urination.7 Although all of these maneuvers
have been credited with terminating episodes of priapism, they have not
been carefully studied and are less likely to succeed after prolonged episodes.
Vasoactive agents, given either orally and by injection, have commonly
been used to treat priapism. For example, terbutaline, a
2-agonist, has been shown to be effective in the
management of intraoperative penile tumescence and of pharmacologically
induced priapism,19-21 but it has not been formally studied
in patients with SCA. A single case report describes the successful use
of hydralazine, a vasodilator, in a patient with SCA and
priapism.22
Rifkind and coworkers23 first reported on the successful
use of exchange transfusion in a 26-year old man with homozygous SCA
who presented with a 3-day history of priapism. Although a small case
series of patients successfully treated with this approach has been
published,24 exchange transfusion is not universally successful, and automated exchange transfusion may not be available. In
addition, the procedure has been associated with the onset of severe
neurologic complications known as ASPEN syndrome (association of SCA,
priapism, exchange transfusion, and neurological
events).8,9 Although simple red cell transfusion therapy
has been employed to treat priapism, the efficacy of this strategy (ie,
immediate detumescence) has been unpredictable.25,26 In
addition, the risks of ASPEN syndrome described above apply to simple
erythrocyte transfusions as well.8,9
Surgical management of priapism with a variety of shunt
procedures, usually between the corpora cavernosa and glans
penis27-30 or saphenous vein,31 has
been successful in relieving severe and refractory priapism, with the
objective of maintaining potency. But shunt procedures are limited by a
high failure rate and frequent complications, such as skin sloughing,
chordae, cellulitis, and urethral fistulas.32 Thus, most
urologists limit surgical shunts for priapism in those patients with
SCA whose priapism persists after less invasive measures.
Interventions that have been used to prevent priapism include hormones
and red cell transfusions. Hormonal interventions decrease the
production of testosterone (eg, gonadotropin-releasing hormone analogues) or its action (eg, estrogens). Published experience includes
1 small randomized clinical trial using stilboestrol33 and
1 case report and a single case series describing the successful use of
gonadotropin-releasing hormone analogues.34,35
Sayer and Parsons36 were the first to report the successful
use of intracorporeal epinephrine in a 34-year old man with paranoid
schizophrenia and priapism. Molina and coworkers37 subsequently described the successful use of intrapenile injections of
a dilute 1:1 000 000 epinephrine solution for the treatment of
priapism in 18 patients. Although 6 patients had SCA, no specific details were provided, and long-term follow-up was
lacking.37 In that report, all aspiration and irrigation
procedures were successful when the duration of priapism was <35
hours, while only 1 of 3 procedures was successful after longer
episodes of priapism.37 Dittrich and
coworkers11 have also described the use of intracavernous
injections of phenylephrine in 36 patients with pharmacologically
induced erections or priapism due to anesthesia, but none of their
patients had SCA.
This report is, to the best of our knowledge, the first to date to
demonstrate the safety and efficacy of this approach in an outpatient
population of young patients with SCA. Among 15 consecutive and
unselected patients with homozygous SCA treated on 39 occasions, the
procedure was 95% effective in producing immediate detumescence, with
no serious complications. Most patients (10 of 15 or 67%) required
only 1 aspiration and irrigation procedure, and 7 patients (Nos. 3, 6, 9, 11, 12, 13, and 14) had no further recurrences at a median follow-up
of 39 months. None of the successfully treated patients required
hospitalization, and immediate pain relief accompanied the
treatment-induced detumescence in each case. All successfully treated
patients with adequate follow-up maintain normal erectile function.
Both patients whose priapism continued despite aspiration and
irrigation were first presented to us following priapism episodes
lasting more than 24 hours. Thus, although the number of patients who
failed to demonstrate detumescence is small (n = 2), success of
penile aspiration and irrigation with dilute epinephrine appears to be
less in patients with extremely prolonged episodes of priapism.
Evidence-based guidelines for the prevention of recurrent priapism in
patients with SCA do not exist, since none of the reported therapeutic
interventions have been compared in a randomized fashion. We often
prescribe 30 mg of oral pseudoephedrine at bedtime for SCA patients who
required aspiration and irrigation for priapism. This agent appears to
be successful in causing detumescence in patients with
pharmacologically induced priapism, and most episodes of priapism occur
at night.11 Although oral pseudoephedrine appears to
decrease the number of recurrent episodes of priapism, this observation
has not been studied in a controlled fashion. For patients who fail to
respond to oral pseudoephedrine or who require multiple aspiration and
irrigation procedures, we have successfully employed injections of
leuprolide, a gonadotropin-releasing hormone analogue that suppresses
the hypothalamic-testicular axis and the production of testosterone.
35
Our study has several limitations. First, since both aspiration of
blood and irrigation of the corpora cavernosa with epinephrine were
employed, it is unclear which of the 2 contributed most to the observed
outcome. While simple aspiration of blood from the corpora cavernosa
under spinal anesthesia was successful in producing rapid detumescence
in a small patient series,38 our initial experience
suggested that mere aspiration usually led to refill of the corpora
cavernosa and recurrent priapism until epinephrine was instilled. Thus,
we elected to use both aspiration of blood and irrigation of the
corpora cavernosa with epinephrine. Second, the long-term follow-up of
some patients, especially older adolescents who were transitioned to
adult SCA care, was not optimal, and 2 patients discontinued follow-up.
Third, a single successfully treated patient (No. 1) represents 38% of
our overall experience (15 of 39 aspiration and irrigation procedures),
thus possibly overestimating the efficacy of the procedure. However,
even if we estimate the efficacy of penile aspiration and irrigation by patient rather than by event, it remains highly effective, with 13 of
15 patients (87%) exhibiting immediate detumescence. Finally, potency
at last follow-up was determined by self-reporting alone. Thus, the
ultimate potency of young men with SCA who required aspiration and
irrigation for priapism during childhood remains to be determined.
In conclusion, aspiration of blood from the corpora cavernosa followed
by irrigation with a dilute 1:1 000 000 epinephrine solution is
effective in inducing detumescence in young patients with SCA and
prolonged episodes of priapism. This simple, safe, and readily
available (following urologic consultation) intervention does not
require hospitalization or regional or general anesthesia. Moreover, it
is 95% effective. Multicenter, randomized, placebo-controlled trials
are needed to better define the role of oral -adrenergic agonists
and other strategies in preventing recurrences of severe episodes of
priapism in both children and adults with SCA.
| |
Acknowledgments |
We are indebted to Patricia Ellisor for expert secretarial assistance
and Juanita Dale, RN, PhD, and Bonita Williams, MSN, PNP, for help with
data collection.
| |
Footnotes |
Submitted June 8, 1999; accepted August 31, 1999.
Reprints: George R. Buchanan, University of
Texas Southwestern Medical Center, Department of Pediatrics, 5323 Harry Hines Boulevard, Dallas, TX 75235-9063; e-mail:
gbuch2{at}mednet.swmed.edu.
The publication costs of this
article were defrayed in part by
page charge payment. Therefore,
and solely to indicate this fact,
this article is hereby marked
"advertisement"
in accordance with 18 U.S.C.
section 1734.
| |
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G. B. Segel, M. G. Hirsh, and S. A. Feig
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F. Labat, A. M. Dubousset, C. Baujard, A. P. Wasier, D. Benhamou, and G. Cucchiaro
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A D Gbadoe, Y Atakouma, K Kusiaku, and J K Assimadi
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Top
Abstract
Introduction