Successful Treatment With Enoxaparin of Glans Ischemia Due to

Successful Treatment With Enoxaparin of Glans
Ischemia Due to Local Anesthesia After Circumcision
abstract
The severe ischemia or necrosis of the glans penis is a rarely seen
complication after circumcision. We report the case of a 7-year-old
boy with severe glans penis ischemia occurring 24 hours after circumcision with local anesthesia (0.1% xylocaine containing ephedrine). His hemogram and levels of proteins C and S and fibrinogen
were normal, but the D-dimer level was higher than normal (2.57 mg/L;
normal level 0–0.5 mg/L). Normal blood flow was indicated on color
Doppler ultrasonography. The severe ischemia in the glans penis was
successfully treated with subcutaneous injection of enoxaparin (lowmolecular-weight heparin) for 5 days, and the appearance of the
glans was close to normal on the fifth day. The patient did not require
any surgical intervention and was discharged without sequelae. As
a result, we consider that ischemia of the glans penis may initially be
managed with enoxaparin, especially in cases in which the D-dimer
level is higher than normal. Pediatrics 2013;131:e608–e611
AUTHORS: Erkan Efe, MD,a Sefa Resim, MD,a Burak Besir
Bulut, MD,a Mustafa Eren, MD,b Mesut Garipardic, MD,c
Fuat Ozkan, MD,d and Keramettin Ugur Ozkan, MDe
Departments of aUrology, cPediatrics, dRadiology, and ePediatric
Surgery, Faculty of Medicine, Kahramanmaras Sutcu Imam
University, Kahramanmaras, Turkey; and bDepartment of Urology,
Kahramanmaras State Hospital, Kahramanmaras, Turkey
KEY WORDS
glans penis, ischemia, complication of circumcision, enoxaparin,
D-dimer
ABBREVIATIONS
DPNB—dorsal penile nerve block
LMWH—low-molecular-weight heparin
www.pediatrics.org/cgi/doi/10.1542/peds.2012-1400
doi:10.1542/peds.2012-1400
Accepted for publication Aug 17, 2012
Address correspondence to Sefa Resim, MD, Department of
Urology, Faculty of Medicine, Kahramanmaras Sutcu Imam
University, 46050 Kahramanmaras, Turkey. E-mail: sresim@yahoo.
com
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2013 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have
no financial relationships relevant to this article to disclose.
FUNDING: No external funding.
e608
EFE at al
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CASE REPORT
Circumcision is one of the oldest surgical procedures performed worldwide
and is probably the most frequently
performed elective surgical procedure
among Muslim and Jewish people. After
circumcision, the most common complications are meatal stenosis, hemorrhage, and infection. Other complications,
such as chordee, ulceration and necrosis of the glans, and amputation of
the glans penis, are rarely seen, but
the complications of concealed penis
and insufficient removal of the foreskin
are fairly common.1
Although circumcision is not technically
difficult, it is accompanied by a rate of
morbidity of 0.1% to 35% and can result
in complications ranging from inconsequential to tragic.1,2
Ischemia or necrosis of the glans penis
is an uncommon but important postoperative complication. Ischemic complications usually take place as a result
of a tight bandage applied to the circumcised area, trauma, inadvertent
administration of vasoconstrictive solutions, diabetes mellitus, circumcision,
or vasculitis.2,3 We describe the case
of a child with severe ischemia in
the glans penis after circumcision with
local anesthetic containing a vasoconstrictor, in whom enoxaparin (lowmolecular-weight heparin [LMWH])
was administered and a successful
response was obtained.
PATIENT PRESENTATION
A 7-year-old boy was referred to our
outpatient clinic with a painful swelling
and discoloration of the glans penis. The
patient had undergone circumcision
with use of local anesthesia (0.1%
xylocaine containing ephedrine) 1 day
before admission at the referring
hospital. His family said that cyanosis
and edema occurred on the glans penis
24 hours after the circumcision. Physical examination revealed black and
necrotic appearance of the glans penis
and edema on the dorsal penile skin.
The urethra, corpus spongiosum, and
both corpora cavernosa were flaccid
(Fig 1). Urine passage was normal.
Laboratory studies showed no signs of
sickle cell anemia or other hematologic
diseases. His hemogram and levels of
proteins C and S and fibrinogen were
normal but the D-dimer level was
higher than normal (2.57 mg/L; normal
0–0.5 mg/L). To assess the depth and
severity of the ischemic process,
grayscale and color Doppler sonographic examination of the circumcised penis was performed by using
a 7.5-MHz linear-array transducer
connected to an ultrasonograph (Aplio
XV, Toshiba, Tokyo, Japan). Both corpora spongiosa and cavernosa demonstrated normal tissue echogenicity.
Thickening and echogenicity of the
surface of the glans penis were more
pronounced than expected for simple
edema. Color Doppler examination
revealed the normal penile and glandular blood flow (Fig 2). Diagnosis of
superficial glans ischemia was suggested, and a conservative treatment
approach was chosen. On the first day,
enoxaparin 2000 anti–factor Xa IU was
injected subcutaneously in the abdomen. On the next 4 days, enoxaparin
anti–factor Xa 50 IU/kg was injected
subcutaneously as a single daily dose.
At 48 hours after the beginning of
enoxaparin treatment, the glans penis
changed from black to a brownish
color, and on the fifth day, the dark
color had vanished (Fig 3). At the end of
the fifth day, the D-dimer level was
normal and enoxaparin treatment was
stopped.
DISCUSSION
In children, severe ischemia or necrosis
of the glans penis is rare. It occurs
commonly as a result of circumcision,
trauma, or the administration of vasoconstrictive solutions during circumcision.3,4 The diagnosis is usually based
on the appearance of skin on the glans
PEDIATRICS Volume 131, Number 2, February 2013
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FIGURE 1
Appearance of the glans penis in a 7-year-old boy
when he presented to our clinic.
penis. Ischemia of the glans penis after
circumcision commonly results from
dorsal penile nerve block (DPNB) with
local anesthetics and inadequate surgical technique or devices.3,5 In the
presented case, although the precise
cause of severe glandular ischemia
was not known, it might have been
secondary to the DPNB. The American
Academy of Pediatrics recommends
that the analgesia consist of general
anesthesia with caudal blocks for
postoperative pain relief. Different analgesic applications exist for circumcision, including topically applied
lidocaine-prilocaine cream, DPNB, and
subcutaneous ring blockage.6 DPNB is
an effective analgesic technique and
is widely used during circumcision.
DPNB is, however, associated with some
complications such as ischemia or
necrosis of the glans penis.7 Because
the dorsal penile arteries are end
arteries, the use of vasoconstrictor
drug–containing anesthetics such as
epinephrine may cause glans penis ischemia or necrosis. Our patient had
undergone circumcision with the use
of local anesthesia supplied by DPNB
(0.1% xylocaine containing ephedrine).
His mother noticed a discoloration of
the glans penis in her son after 1 day.
When the boy was presented to our
outpatient clinic, his glans penis was
almost black (Figs 1 and 2). Ephedrine
is a sympathomimetic drug, and it
has a high potential for ischemia.
e609
FIGURE 2
Increased pulsatile inflow from the cavernosal artery toward the cavernous body on the left side in color
Doppler ultrasonography.
serves as a clinically useful marker for
exclusion of venous thromboembolism.8 Elevated plasma levels of Ddimer antigen gradually normalize in
patients receiving anticoagulant therapy
for acute venous thromboembolism.9
Our patient had penile vascular thrombosis, and his D-dimer level was high.
FIGURE 3
Normal appearance of the glans penis on the fifth
day of enoxaparin treatment.
Therefore, when circumcision is performed with use of local anesthesia via
DPNB, the use of local anesthetics
containing a vasoconstrictor is contraindicated.
We measured the patient’s D-dimer
level, which serves as a clinically useful marker for exclusion of thrombosis,
and it was higher than normal. The Ddimer antigen is generated as a result
of fibrin formation and fibrinolysis. The
enzymes that function to generate this
antigen are thrombin, factor XIIIa, and
plasmin. Fibrin molecules that contain
the D-dimer antigen are formed in
both intravascular and extravascular
spaces during hemostasis, thrombosis, and tissue repair. The D-dimer antigen is a specific marker of fibrin
clot formation and fibrinolysis, which
e610
The decreased perfusion and localized
ischemia may progress to tissue necrosis.9 The safety of the LMWH enoxaparin as an anticoagulant in newborns
and children has been demonstrated,10
and it is indicated for the primary
prophylaxis and treatment of thromboembolism. It is administered via
subcutaneous injection and requires
regular monitoring of anti–factor Xa
activity. We administered an LMWH
(enoxaparin) for treatment of this
condition. At the end of the fifth day, the
D-dimer level turned to a normal range.
As in the current case, the main goal of
the treatment is to provide sufficient
blood flow and oxygen to the ischemic
penis. Burke et al described ischemia
of the glans penis occurring 40
minutes after DPNB with 0.75% ropivacaine and was successfully treated
with an intravenous infusion of iloprost
(a prostaglandin I2 analog).3 Aslan et al
treated a child with penile glanular ischemia after circumcision with pentoxifylline.11 Sara and Lowry report 2
cases of gangrene of the skin of the
glans penis after circumcision.12 These
cases involved the use of general anesthesia and DPNB with bupivacaine
without epinephrine. Sara and Lowry
treated 1 case with heparin infusion,
which was continued over 4 days, as
a prophylactic measure to prevent the
possible extension of the postulated
thrombotic process. After several days,
they observed that the color of the
glans had returned to normal, and
their patient was discharged from the
hospital on the ninth postoperative day,
without any residual defect of skin. In
addition, Berens and Pontus reported
the use of a caudal block to treat penile
ischemia after circumcision with local
anesthesia containing epinephrine.7
They suggested that the caudal anesthesia antagonized the epinephrineinduced vasoconstriction. In the present case, the patient presented to our
outpatient clinic 1 day after circumcision. When we examined the boy, his
glans penis was almost black. Therefore, we accepted this to be a case of
delayed ischemia of the glans penis
and we did not consider the caudal
anesthesia as a treatment modality.
However, in the literature we have not
encountered any report demonstrating
successful treatment of a child with
penile glanular ischemia after circumcision with enoxaparin. In the
present case, the black color of the
glans penis transformed into a brownish color after enoxaparin treatment,
and after 5 days, the dark color had
disappeared (Fig 3). In conclusion, we
suggest that enoxaparin, as an LMWH,
should be considered as the treatment
of choice in ischemia of the glans penis
that develops secondary to the administration of vasoconstrictive solutions
during circumcision. In addition, when
the circumcision is performed with
local anesthesia via DPNB, the local
anesthesia should never contain a vasoconstrictor agent.
EFE at al
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CASE REPORT
REFERENCES
1. Puri P, Kumar J, Ramesh V. Circumcision.
Indian J Sex Transm Dis. 2010;31(2):69–74
2. Barnes S, Ben Chaim J, Kessler A. Postcircumcision necrosis of the glans penis:
gray-scale and color Doppler sonographic
findings. J Clin Ultrasound. 2007;35(2):105–
107
3. Burke D, Joypaul V, Thomson MF. Circumcision supplemented by dorsal penile nerve
block with 0.75% ropivacaine: a complication.
Reg Anesth Pain Med. 2000;25(4):424–427
4. Sheinfeld J, Cos LR, Erturk E, Cockett AT.
Penile tourniquet injury due to a coil of
hair. J Urol. 1985;133(6):1042–1043
5. Sterenberg N, Golan J, Ben-Hur N. Necrosis
of the glans penis following neonatal
6.
7.
8.
9.
circumcision. Plast Reconstr Surg. 1981;68
(2):237–239
American Academy of Pediatrics, Task
Force on Circumcision. Circumcision policy
statement. Pediatrics. 1999;103(3):686–693
Berens R, Pontus SP Jr. A complication
associated with dorsal penile nerve block.
Reg Anesth. 1990;15(6):309–310
Adam SS, Key NS, Greenberg CS. D-dimer
antigen: current concepts and future prospects. Blood. 2009;113(13):2878–2887
Schutgens RE, Esseboom EU, Snijder RJ,
et al. Low molecular weight heparin (dalteparin) is equally effective as unfractionated heparin in reducing coagulation
activity and perfusion abnormalities
PEDIATRICS Volume 131, Number 2, February 2013
Downloaded from by guest on October 12, 2016
during the early treatment of pulmonary
embolism. J Lab Clin Med. 2004;144(2):
100–107
10. Shama A, Patole SK, Whitehall JS. Low
molecular weight heparin for neonatal
thrombosis. J Paediatr Child Health. 2002;
38(6):615–617
11. Aslan A, Karagüzel G, Melikoglu M. Severe
ischemia of the glans penis following
circumcision: a successful treatment via
pentoxifylline. Int J Urol. 2005;12(7):705–
707
12. Sara CA, Lowry CJ. A complication of circumcision and dorsal nerve block of the
penis. Anaesth Intensive Care. 1985;13(1):
79–82
e611
Successful Treatment With Enoxaparin of Glans Ischemia Due to Local
Anesthesia After Circumcision
Erkan Efe, Sefa Resim, Burak Besir Bulut, Mustafa Eren, Mesut Garipardic, Fuat
Ozkan and Keramettin Ugur Ozkan
Pediatrics 2013;131;e608; originally published online January 14, 2013;
DOI: 10.1542/peds.2012-1400
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1948. PEDIATRICS is owned, published,
and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk
Grove Village, Illinois, 60007. Copyright © 2013 by the American Academy of Pediatrics. All
rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.
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Successful Treatment With Enoxaparin of Glans Ischemia Due to Local
Anesthesia After Circumcision
Erkan Efe, Sefa Resim, Burak Besir Bulut, Mustafa Eren, Mesut Garipardic, Fuat
Ozkan and Keramettin Ugur Ozkan
Pediatrics 2013;131;e608; originally published online January 14, 2013;
DOI: 10.1542/peds.2012-1400
The online version of this article, along with updated information and services, is
located on the World Wide Web at:
/content/131/2/e608.full.html
PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1948. PEDIATRICS is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2013 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.
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