Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02851290 |
| Other study ID # |
H-38540 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
July 2016 |
| Est. completion date |
May 19, 2023 |
Study information
| Verified date |
May 2023 |
| Source |
Baylor College of Medicine |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Hypospadias is one of the most common genitourinary (GU) malformations, seen in approximately
1 of 250 male live births. Common methods of local anesthesia administration for hypospadias
surgery include caudal and dorsal penile nerve blocks. While both methods are known to be
effective with minimal risk, the effect on post-operative complications is not
well-established. The purpose of this randomized controlled trial is to evaluate if caudal
versus dorsal penile nerve block results in higher rates of post-operative complications.
Description:
Hypospadias is a one of the most common genitourinary (GU) malformations, seen in
approximately 1 of 250 male live births, characterized by proximal location of the urethral
meatus, dorsal hooded foreskin with incomplete ventral fusion, and ventral curvature of the
penis. Hypospadias repair includes several standard steps including urethroplasty,
mobilization of adjacent flaps for urethroplasty coverage, rotation of penile skin flaps and
circumcision. In order for the surgeon to operate in a clean and relatively bloodless field,
tourniquets and local epinephrine injection have been used. In a rabbit hypospadias repair
model, the authors used both tourniquet and local epinephrine infiltration to maintain a
clear surgical field, and showed increased apoptotic urethral myocytes on TUNNEL assay and
collagen deposition in the epinephrine cohort. The study also showed structural changes in
the mitochondria on scanning electron microscopy in the epinephrine cohort. This is the only
hypospadias study demonstrating pathologic changes in the urethra after tourniquet or
epinephrine injection. While single stage hypospadias surgical techniques have standardized
significantly over the two decades, surgical complications can still occur in up to 28% of
patients. Complications include urethrocutaneous fistulas, meatal stenosis, glans dehiscence,
urethral strictures, and urethral diverticulum. Risk factors for hypospadias surgical
complications have been extensively published and include: proximal urethral location,
previous operation, glans width <14 mm, no urethroplasty coverage layers, surgeon learning
curve, and age <4 years old.
The majority of hypospadias surgical complications need to be revised surgically and this
results in significant financial and emotional burden for the family. The financial impact of
hypospadias visits, repairs, and reoperations on society is largely unknown. A single study
in 2000 noted that $16.6 million was spent on operative and outpatient hypospadias care and
17,000 total outpatient hypospadias visits were made that year. No recent studies are
available and the cost to the patient per surgery and per surgical complication repair is
also unknown. Multiple objective hypospadias surgical questionnaires have been developed to
characterize postoperative appearance of the skin, meatus, urinary stream, and presence of
fistula. These studies have only been validated by the same institution and data correlating
questionnaire scores to complications is sparse.
Penile sensation is derived primarily from the dorsal nerve of the penis. Ventrally there is
some innervation to the frenulum that is derived from the perineal nerve branches. The dorsal
nerve of the penis is a branch of the pudendal nerve which is supplied from sacral nerves.
Common methods for penile block, which are performed by the hypospadias surgeon, include
dorsal nerve penile block (DNPB) or penile ring block. The DNPB involves infiltration of
local anesthetic using a short beveled needle in the subpubic location at the 10 and 2
o'clock positions such that the dorsal nerve of the penis is blocked as it enters the base of
the penis. The penile ring block is performed by infiltration of local anesthetic in the
subcutaneous tissue at the base of the penis. One prospective study showed that DNPB was
significantly better than ring block. Success rates of DNPB have been noted to be anywhere
from 90-100% in children undergoing circumcision. Complications from DNPB are exceptionally
rare at <0.1% including hematoma and local tissue edema.
Caudal block is a commonly performed regional block by anesthesiologists for hypospadias
surgery. It involves blockade of the same nerve pathway described above, at a more proximal
location, by infiltration of the caudal epidural space through the sacral hiatus. The
procedure is performed usually in the lateral position. Anatomic landmarks are defined by an
equilateral triangle formed by the bilateral posterior superior iliac spines, and the sacral
hiatus. Initially a short beveled needle or small gauge angiocatheter is inserted into the
sacral hiatus at a 45 degree angle and then once a "pop" is heard, the angle is "dropped" to
0 degrees and the needle is advanced. Aspiration is performed and in the absence of
cerebrospinal fluid or blood, a local anesthetic is injected. Complications are exceptionally
rare at the rate of <0.003% and include local anesthetic toxicity, neurological injury or
infection and success rates of up to 96% have been reported.
Penile physiology and blood flow parameters after DNPB and caudal block are largely unknown.
Very few studies show the effects of distal organ perfusion after regional blockade. One
study looking at children undergoing caudal block for urologic procedures found that caudal
block using 1.5 ml/kg of 0.15% ropivicaine increased the dorsalis pedis arterial parameters:
increased peak velocity 24%, volume flow 76%, arterial diameter 20%. The authors proposed a
sympatholytic mechanism as the reason for these physiologic changes. Another randomized
controlled trial primarily looking at post-operative pain outcomes in hypospadias repair
patients also found increased penile volumes of 27% in the caudal block arm, with the
proposed mechanism also being sympatholytic. Finally, there have been case reports in which
the sympatholytic effects of caudal blocks are used to treat glans ischemia after
circumcision.
Penile analgesia after caudal block is approximately equal to that of DNPB. A meta-analysis
of the circumcision analgesia literature, analyzing over 700 patients showed analgesic
equivalence of caudal versus parenteral analgesia. Also in the meta-analysis, caudal block
was found to be equivalent to DNPB with increased motor blockade found in the caudal block
arm. One randomized controlled trial assessing analgesia requirements in children undergoing
hypospadias repair after caudal block and penile block found that penile block resulted in
superior pain control. However, another randomized controlled trial found that caudal block
resulted in superior pain control as compared to penile block. After either bock, there are
usually no significant alterations in mean arterial pressure.
Recently, the association between caudal block and hypospadias surgical complications has
been theorized and has drawn international interest amongst pediatric urologists and
anesthesiologists. A randomized controlled trial of 54 distal hypospadias repair patients,
half assigned to caudal block and half to penile block, showed that all urethrocutaneous
fistulas were seen in the caudal block arm. Even though the primary outcome was
post-operative pain control between the groups, the authors theorized that caudal blocks lead
to sympathetic blockade, penile engorgement, tissue edema, and increased hypospadias surgical
complications. A nested case control series comparing 45 fistulas and 90 controls showed no
association between fistulas and caudal block. The authors found fistula to be associated
with proximal urethral location, penile epinephrine injection, and longer operative times.
Unpublished data presented at the 2015 American Urologic Association in New Orleans by Routh
et al. showed that in a retrospective single surgeon series of 452 primary hypospadias repair
patients, half which had caudal block and half which had penile block, caudal blockade was
highly associated with hypospadias surgical complications even after adjusting for operative
time (OR 3.9 (1.3-12.1)); p= 0.0008. This is the only study to date that has been powered
appropriately to assess the association between caudal block and hypospadias complications.
Thus, there is clinical equipoise regarding the utilization of caudal block versus penile
block for post-operative pain control and also in minimizing surgical complications in
hypospadias repair.
