Clinical trial NCT05919732
Conditions: Inguinal Hernia
Sponsor: Nemours Children's Clinic
Start date: 2016-03-08; Completion date: 2018-03-08
Enrollment: 20 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
It is well established that preterm inguinal hernias discovered in the NICU pose a significant surgical risk due to the associated co-morbid conditions that accompany these patients. Currently, the standard of care in the United States is general anesthesia. There have been studies that have established that elective outpatient repair of inguinal hernias found in the NICU can be safely performed. Patients that are ready for discharge from the NICU will have inguinal hernia repair prior to leaving. Inguinal hernia repair will also be done on those premature infants that are seen in the Nemours surgical clinic. Spinal anesthesia is currently the most common anesthetic procedure used in the surgical treatment of preterm inguinal hernias after general anesthesia. Caudal catheter technique has been proven to safely provide post-operative care of premature infants. The caudal catheter technique involves placement of a small catheter under ultrasound guidance into the caudal epidural canal to allow re-dosing of local anesthetic during the case and has been shown to be safe and effective management in neonates (Somri M, 2007).

Detailed description:
This is a prospective, blinded, randomized controlled trial evaluating the effectiveness of awake caudal catheter infusion versus single dose caudal injection and general anesthesia in the surgical management of preterm infant inguinal hernia repair. Spinal anesthesia has been advocated for but highly rejected in the pediatric surgical community due to its high failure rate, which can be up to 28%. Spinal anesthesia is a form of regional anesthesia involving injection of a local anesthetic into the subarachnoid space, via a fine needle, in a single injection. The failure rate has to do with the time constraint of spinal anesthesia, which is approximately 1 hour. It is difficult to perform a bilateral inguinal hernia in that time duration, necessitating a return trip to the operating room for the contralateral side or intubation midway through the surgical case. An alternative to spinal anesthesia that results in an ability to sustain regional anesthetic effect for a longer duration is the caudal catheter infusion. We hypothesize that awake caudal catheter infusion will allow for the following benefits (1) greater than 2 hour anesthetic time via re-dosing which will allow for the completion of the planned surgical procedure (2) exhibit a negligible failure rate (3) minimize post-operative complications that have been associated with general anesthesia in the preterm neonate.

Arms: arm 1: Awake continuous caudal infusion. arm 2: General anesthesia and single-dose caudal injection
Interventions: intervention 1: Bupivacaine, Dexmedetomidine, Caffeine, Tylenol intervention 2: Propofol, rocuronium, caffeine, Tylenol, bupivacaine
Intervention descriptions: intervention 1: bupivacaine .3% + 1: 200,000 epinephrine (dose 3mg/kg). Dexmedetomidine 0.5mcg/kg, Caffeine 15mg/kg, rectal Tylenol 30mg/kg intervention 2: propofol 3mg/kg and rocuronium 0.6mg/kg. Caffeine 15mg/kg and rectal Tylenol 30mg/kg.

single shot caudal with bupivacaine 0.25% + 1:200,000 epinephrine (total dose 2.5mg/kg)

Protocol documents:
Prot_SAP_000.pdf: 
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1. Title of Project: 
Awake caudal catheter infusion versus general anesthesia and single-dose caudal injection for 
preterm NICU patients undergoing inguinal herniorrhaphy. 
 
2. Principal Investigator: Kanika A. Bowen, MD, MMS, Nemours Pediatric Surgery 
Co-Investigator(s): Robert Bryskin, MD, Nemours Anesthesiology and Jim Kirk, DO. 
University of Florida Neonatology 
 
3. Abstract: 
This is a prospective, blinded, randomized controlled trial evaluating the effectiveness of awake 
caudal catheter infusion versus single dose caudal injection and general anesthesia in the surgical 
management of preterm infant inguinal hernia repair.  Currently, the standard of care in the 
United States is general anesthesia.  Spinal anesthesia has been advocated for but highly rejected 
in the pediatric surgical community due to its high failure rate which can be up to 28%.  Spinal 
anesthesia is a form of regional anesthesia involving injection of a local anesthetic into the 
subarachnoid space, via a fine needle, in a single injection. The failure rate has to do with the 
time constraint of spinal anesthesia which is approximately 1 hour.  It is difficult to perform a 
bilateral inguinal hernia in that time duration, necessitating a return trip to the operating room for 
the contralateral side or intubation midway through the surgical case. We hypothesize that awake 
caudal catheter infusion will allow for the following benefits (1) greater than 2 hour anesthetic 
time via redosing which will allow for the completion of the planned surgical procedure (2) 
exhibit a negligible failure rate (3) minimize post-operative complications that have been 
associated with general anesthesia in the preterm neonate. 
 
4. Background: 
It is well established that preterm inguinal hernias discovered in the NICU pose a significant 
surgical risk due to the associated co-morbid conditions that accompany these patients.  There 
have been studies that have established that elective outpatient repair of inguinal hernias found in 
the NICU can be safely performed. However, due to the low associated risk of incarceration and 
subsequent bowel loss many institutions are reluctant to treat this way and practice is widely 
variable (Sulkowski JP, 2015). The most common practice in NICUs across the country is to wait 
until the patient is ready for discharge from the NICU and to perform inguinal hernia repair prior 
to discharge (Crankson SJ, 2015). This allows for the patient to undergo significant growth in the 
NICU without increasing the risk of incarceration.  Currently and historically this operation is 
performed under general anesthesia, which requires the preterm neonate to be intubated during 
the procedure and depending on their respiratory status, sometimes afterward.  A recent review of 
current practices in regards to inguinal hernia repair in the United States demonstrated that 70% 
of repairs are performed with general anesthesia (Wiener ES, 1996). Due to the known risk of 
apnea and bradycardia in the preterm infant, alternatives to general anesthesia for inguinal hernia 
repair has been hotly debated in the surgical, anesthetic, and neonatology literature. General 
anesthesia with single-shot caudal injection is an established practice with demonstrated safety. A 
study utilized this technique where 91 out of 126 patients safely underwent general anesthesia and 
caudal injection (Murphy, 2008). Recent studies suggest that low gestational and 
postconceptional age, low birth weight, anemia, and complicated past medical history affect 
respiratory complication rates, particularly apnea in formerly premature infants undergoing 
elective inguinal hernia repair (Ozdemir T, 2013). Spinal anesthesia is currently the most 
common anesthetic procedure used in the surgical treatment of preterm inguinal hernias after 
general anesthesia, although spinal anesthesia is not currently in wide surgical practice due to its 
high failure rate that is up to 28% in some studies (López T, 2012). Spinal anesthesia in the 
preterm infant has been found to decrease apneic events as well as decrease post-operative 
prolonged mechanical ventilation, although the latter is disputed in the literature (G, 2003) 


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(Craven PD, 2003). A significant portion of this failure is due to the short duration of anesthetic 
time, which is less than 1 hour depending upon patient weight. Therefore, it is hard to make a 
surgical argument for its preferential use.  An alternative to spinal anesthesia that results in an 
ability to sustain regional anesthetic effect for a longer duration is the caudal catheter infusion. 
Caudal anesthesia is hailed as the single most important regional anesthesia technique in children 
(M, 2015). Compared with neuraxial techniques in adults, it can be easily learned and reproduced 
(Schuepfer G, 2000).  The caudal catheter technique has been previously reported in multiple 
publications and textbooks to safely provide post-operative neuraxial analgesia in pre-term/low-
weight/neonatal patients.  Caudal catheter technique involves placement of a small catheter under 
ultrasound guidance into the caudal epidural canal to allow re-dosing of local anesthetic during 
the case and has been shown to be safe and effective management in neonates (Somri M, 2007). 
Ultrasound guidance has been demonstrated to be fundamental for the performance of successful 
posterior approaches in pediatric patients (Kirchmair L, 2004). Ultrasound guided placement of 
caudal anesthesia is also successfully used in patients with difficult anatomy (Schwartz D, 2008). 
The use of peri-operative analgesic blocks has also been shown to result in quicker awakening 
and a more comfortable postoperative course (Conroy JM, 1993). Current literature has showed 
caudal anesthesia with a failure rate of less than 5% which is significantly less than spinal 
anesthesia (Geze S, 2011) (Marhofer P, 2015) (Wong SY, 2004) (Hosseini Jahromi SA, 2012). 
Currently, there is only one published article that has used single-injection caudal injection in the 
management of preterm NICU inguinal hernias (Geze S, 2011).  There were no reported adverse 
events and no failures in a sample of 15 neonates. 
 
If the results of the study support the hypothesis, this contribution could be significant and impact 
clinical practice and the standard of care by allowing surgeons to safely perform the operation in 
an adequate time period. In addition, it could decrease preterm neonatal post-operative 
complications, which are significant.  In general, pediatric surgeons are leaders in surgical 
innovation which has been shown in the rapid advancement of laparoscopic techniques and 
minimally invasive procedures.  Once it is established that the completion rate with awake caudal 
catheter technique in preterm infant hernias is high without increasing morbidity and mortality, 
there should not be a significant argument against its use.  It has already been established that 
regional anesthesia has a significant benefit to the preterm infant (Tobias JD, 1992). As a 
prospective, randomized trial it also is attempting to reach the gold standard in clinical research as 
opposed to a retrospective trial.  This research project is a study that other investigators could 
continue to build upon for its other possible indications. Awake caudal catheter technique is 
useful analgesia in procedures that occur below the level of the umbilicus.  In other high-risk 
pediatric patients, this technique has the potential to be used in lower extremity surgical 
procedures as well as urologic procedures (Londergan TA, 1994). Caudal catheter placement is 
performed by a significant number of anesthesiologists, but the reinforcement of its benefits by 
this paper has the potential to increase its application and awareness among the community.  The 
neonatologists’ community as well as the NICU patients would benefit from solid evidence that 
the use of regional anesthesia can be effectively used as an alternative to general anesthesia in 
some surgical instances. Therefore, our study has the ability to change clinical practice in three 
distinct fields of medicine. 
 
5. Specific Aims: 
An elective operative procedure on preterm neonatal patients has long been debated among 
pediatric surgeons, neonatologists, and anesthesiologists.  Anesthesia in this particular group of 
patients pose a significant risk due to their associated medical conditions which can be multiple 
and quite varied.  The most common risk factor for these neonates undergoing general anesthesia 
is their inherent bronchopulmonary dysplasia which ranges from mild to severe.  It is well 


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established that general anesthesia in preterm infants can cause apnea and bradycardia (Welborn 
LG, 1994).  Recent literature has shown the effectiveness of spinal anesthesia for preterm NICU 
inguinal hernias in the prevention of apnea and bradycardia immediately post-operatively 
(Rukewe A, 2010).  Spinal anesthesia has significant drawbacks, resulting in failure to gain wide 
acceptance in the pediatric surgery community.  Depending on the size of a pediatric patient, 
spinal anesthesia may not last one hour and can therefore lead to a failure rate of up to 28% 
(López T, 2012). That is a significant factor for pediatric surgeons who can complete a bilateral 
inguinal hernia repair with general anesthesia virtually 100% of the time. Caudal catheter infusion 
allows for greater than two hours of operating time for the pediatric surgeon without the use of 
general anesthesia. That would be an adequate amount of time to perform a preterm neonatal 
bilateral inguinal hernia. 
 
Our long-term goal is to establish if there is a significant medical benefit to preterm infants by 
measuring their time to return to baseline respiratory function and by monitoring occurrences of 
apnea and bradycardia post-operatively after hernia repair. Our overall objective is to establish if 
awake caudal catheter infusion in NICU inguinal hernia repair is a safe and effective alternative 
to general anesthesia and single-shot caudal injection.  Our central hypothesis is that NICU 
inguinal hernia repair can be completed with a close to 0% failure rate and that the avoidance of 
general anesthesia and therefore intubation in these patients will result in a faster return to 
baseline respiratory function and fewer instances of bradycardia and desaturations. We plan to 
test our central hypothesis and thereby accomplish our overall objective for this project by 
pursuing the following two specific aims: 
 
1. To investigate if caudal catheter infusion in preterm infants during inguinal hernia repair has 
a low failure rate which allows for completion of the operation without the use of general 
anesthesia. 
• 
We hypothesize that awake caudal catheter infusion in preterm infants will result in a less 
than 96% failure rate.   
 
2. 
To determine if a significant medical benefit can be demonstrated between the use of 
awake caudal catheter technique versus single-dose caudal injection and general 
anesthesia in regards to respiratory status, bradycardia, and apnea post-operatively. 
• 
We hypothesize that awake caudal catheter technique when compared with single-dose 
caudal injection and general anesthesia will be of greater benefit to preterm infants via 
the following primary quantifiable measures:  reduction in the time to return of baseline 
respiratory function, reduction in the number of apneic episodes (defined as cessation of 
breathing by a premature infant that lasts for more than 20 seconds and/or is accompanied 
by hypoxia or bradycardia), and a reduction in bradycardic events (heart rate <90).  
• 
We hypothesize that secondary measures will be of greater benefit to preterm infants as 
well with decreased days to hospital discharge, decreased number of post-operative 
narcotic use days, decreased mechanical ventilation days, and decreased time to full oral 
feeds. 
 
Such results are expected to advance the field of pediatric anesthesiology and pediatric surgery 
which will impact clinical practice by changing the peri-operative management of high risk NICU 
patients. 
 


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6. Research Plan: 
Inclusion and Exclusion Criteria 
Patients included in the study are preterm infants in the NICU less than 50 weeks post gestational 
age born at less than 37 weeks gestational age.  Patients will be within 1 week of meeting NICU 
discharge criteria with or without supplemental oxygen prior to surgical scheduling for inguinal 
hernia repair. Males and females will be included in this study, but there is a known higher 
incidence of male inguinal hernias in the literature, approximately 6:1. 
 
Patients undergoing other invasive procedures including but not limited to gastrostomy tube 
placement, tracheostomy, and/or laser eye treatments will be excluded.  Any patient with a 
medical condition that would prevent a regional anesthetic from being performed (i.e. bleeding 
diathesis, vertebral anomalies, spinal cord injury prior to surgery) and any contradictions to the 
prescribed medications in the protocol will be excluded. 
 
This will be a prospective, blinded, randomized controlled clinical trial.  When the NICU staff 
and surgeon decide that inguinal hernia repair is warranted, a research representative will 
approach the family for research consent. Dr. Bryskin and Dr. Felema will provide the anesthesia 
for both groups and will obtain anesthesia consent on the day of surgery. The general anesthesia 
and single-shot caudal group will be induced with intravenous (IV) propofol 3mg/kg and 
rocuronium 0.6mg/kg and intubated. Caffeine 15mg/kg and rectal Tylenol 30mg/kg will then be 
given for apnea prevention and pain control. Caudal will be performed under ultrasound guidance 
with bupivacaine 0.25% + 1:200,000 epinephrine (total dose 2.5mg/kg) prior to start of the 
surgery.  At the conclusion of the operation, neuromuscular blockade will be reversed with 
neostigmine and glycopyrrolate. The patient will be extubated once criteria are met. If the patient 
is unable to extubate within 20-30 minutes, they will be transferred to the NICU intubated with 
assisted ventilation.  The general anesthesia group will not receive narcotics for pain management 
intra-operatively due to the increased risk of apnea and bradycardia.  Since the study is attempting 
to answer whether the act of exposure to general anesthesia changes the likelihood of apnea and 
bradycardia, we need to maintain the same approach to pain management in both groups. No 
Precedex will be given in the general anesthesia group.  Pain management in the NICU will be 
the following: mild to moderate pain based on a FLACC scale will receive rectal or oral Tylenol, 
while moderate-severe pain will receive IV morphine 0.05mg/kg.   
 
In the caudal infusion group, Precedex 0.5 mg/kg IV will be administered for sedation over 10 
minutes and maintained with an infusion of 0.7 mg/kg/h.  Under ultrasound guidance a 20 gauge 
angio-catheter will be placed into the caudal space and secured to the skin with a tegaderm. A low 
volume extension catheter will be connected to the angio-catheter and bupivacaine .3% + 1: 
200,000 epinephrine (dose 3mg/kg) will be administered via the catheter. An additional dose of 
1mg/kg will be administered at 1 hour post initial dosing time to extend the duration of the 
caudal. Intravenous caffeine and rectal Tylenol will be administered for apnea prevention and 
additional pain control. If patient agitation is noted during the operation, an additional bolus of 
Precedex 0.5 mg/kg will be administered. If agitation persists, pain, and/or respiratory distress are 
noted during the operation, general anesthesia will be induced with propofol 3 mg/kg and 
rocuronium 0.6 mg/kg followed by endotracheal intubation.  The angio-catheter will be removed 
at the end of the surgical procedure. Pain management in the NICU will be the following: mild to 
moderate pain based on a FLACC scale will receive rectal or oral Tylenol, while moderate-severe 
pain will receive IV morphine 0.05mg/kg. 
 


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Blinding of the study will occur on the day of surgery by the anesthesiologists.  Prior to a patient 
arrival to operating room, the anesthesiologist will randomly draw an envelope from a folder that 
will allocate group assignment (this precludes bias while discussing patient care with parents and 
getting consent). It is etimated that we will need approximately 20 patients in each group.  10 
evelopes at a time will be placed in the folder, 5 will be in the awake caudal catheter group and 5 
will be in the general anesthesia and single-dose caudal group.  This will keep the numbers equal 
when going forward with the study. 
Intra-operatively, neither the anesthesiologist nor the surgeon will be blinded since they are 
present from the induction of anesthesia until the conclusion of the operation for patient safety. 
The pre-operative, intra-operative, and post-operative care by the NICU will be blinded. All 
patients will have had a caudal procedure (single vs. catheter) and extubation will be attempted in 
all patients prior to NICU transport.  If extubation cannot be accomplished within 30 minutes 
following completion of the operation, the patient will be transported to the NICU intubated.  
Since post-operatively the same medical personnel cannot be used in every case, a protocol sheet 
will be placed at patient’s bedside as a reference material.  This is also a way to provide 
continuing education about the study and who should be contacted if there is a concern that 
escalation in narcotics use is indicated. 
 
Blinding of the NICU staff will be maintained since in an extubated patient, there will be no way 
to determine allocation based on the caudal wounds. In the intubated patient it will not be clear 
whether the patient started out intubated or was intubated because of a caudal failure.  Since the 
intra-operative anesthesia approach will be standardized, there will be no additional information 
that the NICU staff will require.  The anesthesia record will be placed in a sealed envelope in the 
chart prior to departure from the OR. The NICU staff will be able to unseal the envelope in the 
event that rescue patient management is needed or if it is felt to influence management. In 
addition, personal contact information for the two anesthesiologists involved in the study will be 
provided to the staff in the event there would be an urgent question requiring clarification. The 
envelope label will also instruct medical records personnel to open the envelope and make 
contents part of the patient’s medic record upon hospital discharge.  A letter will be sent to 
parents upon discharge specifying their child's group assignment. 
 
A research specialist and two other surgeons will have completed CITI courses and be available 
to give informed consent to parents for the study.  Baptist IRB will be submitted for approval 
after acceptance by the CRRC. Cases are normally scheduled 3-7 days ahead of time so the 
research specialist should have sufficient time to perform the consent process.  In the event that 
the research specialist is unavailable, another trained surgeon will be accessible.  Although we 
will try to prevent selection bias in the NICU, there is bound to be times when parents will opt out 
of the randomization process and will elect to have either general anesthesia and single-shot 
caudal or caudal catheter infusion.  Those patients will still be consented for use of their data in 
the study. At the time of manuscript preparation, those patients will be identified as refusing 
randomization.    
 
Inguinal hernia repair will be performed by one of five pediatric surgeons employed by Nemours 
Children’s Clinic in the same standard fashion.  Key components of the operation include groin 
incision and a high ligation of the hernia sac, which is the standard of care in the United States. 
Laparoscopic inguinal hernia repair will not be performed in these patients for three reasons: 
Firstly, so that there is standardization among surgeons performing the operation and secondly for 
statistical analysis. Thirdly, there is only one surgeon that performs this operation routinely. 
Caudal catheter placement and infusion will be performed and monitored by Dr. Bryskin and Dr. 
Felema who are employed by Nemours Children’s Clinic in the Department of Pediatric 


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Anesthesiology.  Having a limited number of anesthesiologists performing the standardized intra-
operative approach will also allow for excellent quality control of the study. 
 
Statistical Analysis  
Currently, there are no published articles in the literature to help generate a level of data which 
can be used to determine the power analysis. We would want a power of 80% and a significance 
level of 0.05 for the study and after the first 10 patients are enrolled we can calculate a reliable 
sample size.  Based on previous studies conducted in a prospective, randomized fashion we 
approximate approximately 20 patients in each arm though this is only speculation until the first 
ten patients are enrolled (Oghazian MB, 2015) (Rakhshani A, 2015) (Mathur NB, 2015). A 
review from 1/1/2014 – 12/31/14 of NICU patients undergoing inguinal hernia repair at Wolfson 
was performed and totaled 21. We estimate approximately 80% study inclusion and 20% 
exclusion.  Jobayer Hossain, a Nemours statistician will perform all statistical analysis of the 
study and has indicated the following will be used in the analysis. Demographic and baseline data 
will be summarized by treatment groups, namely general anesthesia and caudal catheter groups. 
Quantitative variables will be summarized by mean/SE or median/interquartile range (IQ), 
whichever appropriate. Categorical variables will be summarized by frequencies and percentages. 
A chi-square or Fisher exact analysis will be used to compare the general anesthesia group and 
the caudal catheter infusion group in the primary outcome, which is time to return to baseline 
respiratory function.  A Cox hazard model ratio will compare the hazard risk between the two 
groups and a log rank test will calculate the median time to return to baseline function. In 
addition, a Cox proportional hazards model will be used to compare the risk of failure between 
two groups. A poisson regression analysis will compare the number of bradycardic events, apneic 
events, catheter complications, and number of post-operative narcotic use days between the 
general anesthesia group and the caudal catheter infusion group. A logistic regression model will 
be used to compare the proportion of successful surgical completion between two groups. We 
estimate the study will run two years for adequate patient accrual. Data will be input by the 
research nurse and sent for analysis to the statistician for periodic review every three months. 
Primary outcomes that will be analyzed in the statistical analysis are: time to return of baseline 
respiratory function, successful surgical completion, catheter complications, number of apneic 
episodes (defined as cessation of breathing by a premature infant that lasts for more than 20 
seconds and/or is accompanied by hypoxia or bradycardia), and bradycardic events (heart rate 
<90). Secondary outcomes are: days to hospital discharge, number of post-operative narcotic use 
days, operative time, mechanical ventilation days, and time to full oral feeds. 
 
7. Possible Discomforts and Risks: 
Adverse events associated with caudal catheter placement or single-shot caudal placement are 
very low.  This procedure is routinely done in neonatal surgery.  The most common 
complications are infection which in a large study is less than .03% and failure of adequate pain 
control which is less than 5%. 
 
If, for some reason, the catheters do not work, your child will be intubated and general anesthesia 
will be given. The patients in the general anesthesia and single-dose caudal injection will only 
receive an injection after they are intubated and not placement of a catheter. 
 
8. Possible Benefits: 
We believe that this technique for pain management in preterm infants will improve post-
operative complications that are common to the NICU which include decreased respiratory rate 
and low heart rate. 
 


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9. Conflict of Interest 
No conflict of interest exists with the PI or investigators.