PSU Volume 64 No 01 JANUARY 2025
Palliative Care in Pediatric Surgery
Palliative care in pediatric surgery has developed considerably
over the past decade, shifting from a traditional focus on end-of-life
support to a broader integration that enhances the quality of life for
young patients facing complex and often life-limiting conditions. This
evolution acknowledges that palliative care (PPC) in pediatrics should
not be limited to terminal care but serve as an essential component
throughout the continuum of a child's surgical journey, including
symptom management, psychological support, and ethical decision-making.
Historically, PPC in pediatric surgery was underemphasized, partly due
to the misconception that palliative care equated to giving up hope for
a cure. This perception began to shift with the American Academy of
Pediatrics' 2000 guidelines, which emphasized adding life to a child's
years rather than simply prolonging life. Pediatric surgeons often
navigate challenging ethical considerations, balancing their commitment
to life-prolonging interventions with the realities of quality of life
in conditions that are not always curable. Surgeons are uniquely
positioned to assess whether a surgical intervention might alleviate
symptoms or enhance a child's comfort. However, this often requires
realistic and sensitive conversations with families who may feel
conflicted between pursuing aggressive interventions and protecting
their child from additional suffering.
In pediatric oncology, where palliative care has gained notable
integration, PPC aims to manage both the immediate symptoms related to
cancer and the lasting effects of treatment. Despite advancements in
survival rates, pediatric cancer remains a leading cause of mortality
beyond infancy. Many children with cancer endure significant symptom
burdens, including chronic pain, fatigue, and emotional distress, which
palliative care can effectively address. Studies have shown that even
as survival rates improve, a significant number of survivors face
debilitating long-term effects, such as organ dysfunction, cognitive
impairments, and secondary malignancies. These realities position PPC
not only as an end-of-life intervention but as a necessary part of the
child's cancer treatment, ensuring comfort and symptom relief
regardless of prognosis.
One of the critical roles that PPC plays in pediatric oncology is in
symptom management. For children with advanced cancer, surgical
palliative interventions often alleviate physical symptoms like bowel
obstruction, respiratory distress, and severe pain, all of which
significantly impact a child's quality of life. The literature
highlights cases where surgical palliative interventions have reduced
pain or prevented complications, such as respiratory support surgeries
or procedures to relieve severe gastrointestinal symptoms. These
interventions, often conducted in collaboration with palliative care
teams, are part of a multidisciplinary approach where PPC aids in
assessing risks, guiding parents through options, and helping set
realistic expectations about what surgery might or might not achieve.
In pediatric urology, the focus on PPC has emerged more recently.
Conditions such as congenital lower urinary tract obstruction,
neurogenic bladder dysfunction, and exstrophy-epispadias complex often
demand repeated surgeries, intensive hospital stays, and chronic
symptom management. Incorporating palliative care in pediatric urology
means addressing not only the physical symptoms but also the
psychosocial issues children and families face as a result of these
lifelong conditions. PPC provides critical support for children
undergoing complex urologic procedures, helping manage chronic pain and
providing resources for families to navigate the ongoing care that
often extends well into adolescence.
Moreover, prenatal palliative interventions have become a significant
component in maternal-fetal surgery. The availability of early
diagnostics has allowed physicians to identify severe congenital
conditions such as congenital diaphragmatic hernia (CDH) prenatally,
providing families with the option of maternal-fetal surgery. This
third option complicates traditional decision-making, which previously
offered only termination or post-birth interventions. Maternal-fetal
surgery exemplifies PPC's role in improving life outcomes through
early, targeted interventions. The palliative care team's involvement
in these cases is invaluable, guiding families through the
decision-making process by weighing potential benefits and risks while
considering quality-of-life outcomes for the child. PPC professionals
work alongside fetal surgeons, genetic counselors, and neonatologists,
providing a well-rounded approach that respects both the parents'
hopes, and the practical realities associated with these surgeries.
One of the most pressing issues in pediatric surgical palliative care
is timing. Surgeons and PPC physicians frequently differ in opinions on
when PPC should be introduced. PPC professionals advocate for early
involvement, ideally at diagnosis, to set the foundation for
comprehensive, long-term care that includes symptom management and
anticipatory guidance. In contrast, many surgeons only initiate PPC
consultations when the child's condition deteriorates, making curative
treatment unlikely. This discrepancy in timing, often attributed to
cultural differences between surgical and palliative care fields,
results in missed opportunities for early symptom control and
comprehensive family support. Studies reveal that some surgeons delay
PPC consultations out of concern that introducing palliative care too
early might discourage families or imply that treatment has been
exhausted.
Communication between PPC teams and pediatric surgeons is crucial for
achieving optimal care outcomes. Surveys highlight that PPC
professionals believe these discussions should occur much earlier in
the disease process to maximize the benefits of palliative
interventions. In many cases, families report that they wish they had
been introduced to palliative care earlier, as it would have helped
them manage their child's symptoms more effectively and provided
emotional support during difficult times. For pediatric surgeons,
initiating conversations about PPC can be challenging, particularly if
they feel it conflicts with families' expectations for life-saving
measures. Consequently, PPC training for surgeons has emerged as a key
area for improving collaboration and communication. In response,
residency programs and continuing medical education increasingly
include training modules focused on PPC to enhance understanding and
acceptance of palliative practices among surgeons.
Research further indicates the need for multidisciplinary approaches
that include PPC in pediatric surgical care. Integrating PPC
professionals as core team members in surgical planning can foster an
environment where families feel supported in their decisions, whether
they pursue aggressive interventions or prioritize comfort and quality
of life. Collaborative care allows each team member to contribute their
specialized expertise. PPC professionals offer insight into symptom
management and psychological support, while surgeons provide technical
assessments of what surgery might accomplish. Through this
collaboration, PPC ensures that surgical interventions align with
family goals and the child's best interests, even when curative options
are no longer viable.
Looking forward, the scope of PPC in pediatric surgery continues to
expand. Conditions such as neurodegenerative disorders, complex
congenital malformations, and progressive illnesses are increasingly
managed with an interdisciplinary approach that includes PPC from early
stages. Pediatric surgeons are recognizing the value of palliative
interventions, not only for terminally ill patients but also for
children with chronic, debilitating conditions. Additionally, as more
pediatric surgical specialists receive PPC training, there is a greater
opportunity for meaningful collaborations that can enhance the quality
of life for children undergoing intensive surgical care. The evidence
supports that PPC integration leads to more compassionate, well-rounded
care that respects both the child's dignity and the families experience.
In conclusion, the integration of palliative care into pediatric
surgery represents a transformative shift towards a patient-centered
model that prioritizes quality of life alongside medical treatment. By
focusing on early symptom management, ethical decision-making, and
supportive family care, PPC complements surgical interventions,
ensuring that young patients with complex medical needs receive
holistic, compassionate care. As PPC becomes more embedded in pediatric
surgery practices, it promises to further bridge the gap between
life-saving surgery and quality of life, offering families comfort,
guidance, and hope in the face of challenging medical journeys.
References:
1- Shelton J, Jackson GP: Palliative care and pediatric surgery. Surg Clin North Am. 91(2):419-28, 2011
2- Inserra A, Narciso A, Paolantonio G, Messina R, Crocoli A:
Palliative care and pediatric surgical oncology. Semin Pediatr Surg.
25(5):323-332, 2016
3- Spruit JL, Prince-Paul M. Palliative care services in pediatric oncology: Ann Palliat Med. 8(Suppl 1), 2019
4- Ott KC, Vente TM, Lautz TB, Waldman ED: Pediatric palliative care and surgery. Ann Palliat Med. 11(2):918-926, 2022
5- De Bie FR, Tate T, Antiel RM: Maternal-fetal surgery as part of
pediatric palliative care. Semin Fetal Neonatal Med. 28(3):101440, 2023
6- Ellis D, Mazzola E, Wolfe J, Kelleher C: Comparing Pediatric
Surgeons' and Palliative Care Pediatricians' Palliative Care Practices
and Perspectives in Pediatric Surgical Patients. J Pediatr Surg.
59(1):37-44, 2024
7- Li O, Lee R, Boss RD, Wang MH: Palliative Care for Pediatric Urology. J Pain Symptom Manage. 68(1), 2024
NPO Guidelines in Pediatric Surgery
The practice of "nil per os" (NPO), or nothing by mouth, for
children undergoing surgery has been a subject of intense scrutiny and
evolution over the years. Various studies and guidelines highlight the
balance between minimizing the risk of pulmonary aspiration during
anesthesia and reducing the adverse effects of prolonged fasting on
children?s metabolic and psychological well-being.
Historically, the NPO protocol has been rigid, often enforcing a
midnight fast for all patients scheduled for surgery. This practice,
aimed at preventing aspiration, has faced criticism for its negative
impact on children. Prolonged fasting can lead to dehydration,
hypoglycemia, and behavioral issues like irritability and anxiety.
Studies show that the current international guidelines allow more
flexibility, advocating for fasting durations of 2 hours for clear
liquids, 4 hours for breast milk, and 6 hours for solids. However,
these guidelines are frequently exceeded in practice due to scheduling
inefficiencies and miscommunication.
One of the major challenges identified is parental compliance with
fasting instructions. Research indicates that less than 10% of parents
fully adhere to the prescribed NPO times, with most either
under-fasting or over-fasting their children. The reasons for
non-compliance include inadequate understanding of instructions, fear
of surgical delays or cancellations, and the difficulty of denying food
or drinks to a distressed child. Miscommunication between healthcare
providers and parents further exacerbates the issue, as conflicting or
unclear instructions lead to confusion. Studies recommend clearer
communication strategies, such as providing separate written
instructions for solids and liquids and ensuring consistency in
messaging.
The metabolic implications of prolonged fasting are particularly
concerning for pediatric patients, as their smaller glycogen reserves
make them more susceptible to hypoglycemia. This metabolic stress not
only affects their energy levels but also impairs their ability to cope
with the stress of surgery, potentially delaying recovery. Research
highlights the benefits of shorter fasting periods, noting that
children allowed to consume clear liquids up to 2 hours before surgery
exhibit better hydration, reduced irritability, and lower gastric pH
levels without increasing the risk of aspiration.
Recent quality improvement initiatives have shown promise in addressing
the shortcomings of current NPO practices. For instance, allowing
children to drink clear liquids up to 1 hour before surgery has been
shown to significantly reduce fasting times and improve overall patient
comfort. Such liberalized fasting guidelines align with modern evidence
suggesting that aspiration risk does not increase with shorter fasting
durations. These changes have been endorsed by leading anesthesia
societies in Europe and Canada, emphasizing the importance of
minimizing disruption to normal physiological states preoperatively.
Despite these advancements, the implementation of more liberal NPO
guidelines faces resistance. Anesthesiologists and surgeons often
express concerns about flexibility in scheduling and the potential for
last-minute changes in surgery times. This conservatism results in a
default return to the midnight fasting rule in many institutions,
particularly for inpatients or cases with higher perceived aspiration
risks. To counter this, some hospitals have developed task forces to
standardize and enforce updated guidelines, incorporating strategies
like using arrival times instead of surgery times to calculate fasting
periods and encouraging the administration of clear liquids closer to
the surgery.
Compliance with updated NPO guidelines also varies significantly across
healthcare settings. Data show that prolonged fasting is more common in
settings with less robust quality improvement frameworks or where the
operational culture is resistant to change. For example, effective
fasting times for clear liquids can extend beyond seven hours, even
when shorter durations are recommended. Educational initiatives
targeting healthcare providers and parents are critical in bridging
this gap, ensuring both groups understand the rationale and safety of
revised fasting protocols.
The adverse effects of prolonged fasting extend beyond the
physiological to the psychological, with many children experiencing
heightened anxiety and behavioral challenges due to hunger and thirst.
These factors contribute to a less favorable surgical experience, both
for the patient and their family. Addressing these issues requires a
multifaceted approach, including better preoperative education,
consistent adherence to evidence-based guidelines, and ongoing
monitoring and adjustment of fasting practices based on patient
outcomes.
In conclusion, while significant strides have been made in revising and
liberalizing NPO guidelines for children, the practical application of
these recommendations remains inconsistent. Barriers such as
communication lapses, entrenched practices, and operational constraints
continue to impede progress. Moving forward, greater emphasis on
quality improvement initiatives, clearer communication strategies, and
more flexible approaches to fasting durations are essential to enhance
compliance and improve the overall surgical experience for pediatric
patients. These changes must be supported by ongoing research and a
willingness among healthcare providers to adopt evidence-based
practices, ensuring that children receive care that is both safe and
compassionate.
References:
1- Brunet-Wood K, Simons M, Evasiuk A, Mazurak V, Dicken B, Ridley D,
Larsen B: Surgical fasting guidelines in children: Are we putting them
into practice? J Pediatr Surg. 51(8):1298-302, 2016
2- Beazley B, Bulka CM, Landsman IS, Ehrenfeld JM: Demographic
Predictors of NPO Violations in Elective Pediatric Surgery. J
Perianesth Nurs. 31(1):36-40, 2016
3- Kafrouni H, Ojaimi RE: Preoperative Fasting Guidelines in Children:
Should They Be Revised? Case Rep Anesthesiol. 2018:8278603, 2018
4- Friedrich S, Meybohm P, Kranke P: Nulla Per Os (NPO) guidelines: time to revisit? Curr Opin Anaesthesiol. 33(6):740-745, 2020
5- Singla K, Bala I, Jain D, Bharti N, Samujh R: Parents' perception
and factors affecting compliance with preoperative fasting instructions
in children undergoing day care surgery: A prospective observational
study. Indian J Anaesth. 64(3):210-215, 2020
6- Schmidt AR, Fehr J, Man J, D'Souza G, Wang E, Claure R, Mendoza J:
Pre-operative fasting times for clear liquids at a tertiary children's
hospital; what can be improved? Anesth Pain Med (Seoul). 16(3):266-272,
2021
TLR4 in Necrotizing Enterocolitis
Toll-like receptor 4 (TLR4) plays a pivotal role in the
pathogenesis of necrotizing enterocolitis (NEC), a life-threatening
gastrointestinal disease in premature infants. NEC is associated with a
high mortality rate and severe long-term complications, including
short-bowel syndrome and neurodevelopmental impairment. The role of
TLR4 in NEC pathogenesis has been extensively studied, revealing its
involvement in immune activation, epithelial injury, and intestinal
ischemia. The following review synthesizes findings from six key
studies to provide a comprehensive understanding of the molecular
mechanisms underlying TLR4-mediated NEC and emerging therapeutic
approaches.
NEC is primarily a disease of premature infants, occurring in up to 10%
of those born with a birth weight under 1500 grams. Its pathogenesis is
multifactorial, involving intestinal immaturity, dysbiotic microbiota,
and exaggerated immune responses. TLR4, an innate immune receptor, has
been identified as a central mediator of these processes. It recognizes
lipopolysaccharides (LPS) on Gram-negative bacteria, triggering
proinflammatory signaling cascades that disrupt the intestinal
epithelial barrier. In premature infants, TLR4 expression is
significantly elevated compared to full-term counterparts, contributing
to increased susceptibility to NEC.
The role of TLR4 extends beyond its recognition of microbial pathogens.
Research has shown that TLR4 activation leads to apoptosis and
necroptosis of intestinal epithelial cells. These processes compromise
the integrity of the gut barrier, facilitating bacterial translocation
into the bloodstream and triggering systemic inflammation.
TLR4-mediated necroptosis, specifically, has been highlighted as a
distinct mechanism contributing to the rapid and severe tissue damage
characteristic of NEC. Studies in TLR4-knockout animal models have
confirmed the critical role of TLR4 in driving necroptosis, with these
models demonstrating reduced epithelial injury and inflammatory
responses.
Another critical mechanism by which TLR4 contributes to NEC is through
its effects on the mesenteric vasculature. Activation of TLR4 on
endothelial cells induces vasoconstriction and intestinal ischemia,
exacerbating tissue injury. In animal models, the inhibition of TLR4
signaling has been shown to restore mesenteric perfusion and mitigate
ischemic damage. This highlights the interconnected nature of
inflammatory and ischemic processes in NEC pathogenesis.
The interaction between TLR4 and the enteric nervous system has also
been implicated in NEC. Research has demonstrated that TLR4 activation
leads to the loss of enteric glial cells, which are essential for
maintaining intestinal motility and barrier integrity. The depletion of
these glial cells disrupts the anti-inflammatory feedback mechanisms of
the gut, further amplifying TLR4-mediated damage. The restoration of
enteric glial cell function has been proposed as a therapeutic
strategy, with promising results observed in preclinical models.
One of the most consistent clinical observations in NEC is the
protective effect of human breast milk. This protection is attributed
to specific components of breast milk, such as human milk
oligosaccharides (HMOs), which have been shown to inhibit TLR4
signaling. Studies focusing on HMOs, including 2?-fucosyllactose and
6?-sialyllactose, have demonstrated their ability to reduce
TLR4-mediated inflammation and apoptosis in experimental NEC models.
These oligosaccharides bind directly to TLR4, preventing its activation
by LPS and other microbial ligands. Formula-fed infants, lacking these
protective factors, exhibit higher rates of NEC, further underscoring
the importance of breast milk in prevention strategies.
The role of the microbiome in NEC is closely linked to TLR4 activity.
Premature infants with NEC exhibit a dysbiotic microbiota characterized
by reduced bacterial diversity and an overrepresentation of pathogenic
strains. This dysbiosis increases the availability of microbial ligands
that activate TLR4, perpetuating the inflammatory cycle. Probiotic
administration has emerged as a potential intervention, with several
studies demonstrating that probiotics can restore microbial balance,
reduce TLR4 activation, and protect against NEC. The exact mechanisms
by which probiotics exert these effects are under investigation, but
they likely involve competitive inhibition of pathogenic bacteria and
modulation of host immune responses.
Therapeutic approaches targeting TLR4 directly have shown promise in
preclinical studies. Small-molecule inhibitors of TLR4, such as
specific antagonists that block LPS binding, have been effective in
reducing NEC severity in animal models. These inhibitors work by
attenuating the proinflammatory signaling cascades initiated by TLR4
activation, thereby preserving the integrity of the intestinal barrier.
Additionally, strategies aimed at enhancing the expression of
protective molecules, such as brain-derived neurotrophic factor (BDNF),
have been explored. BDNF is reduced in NEC and plays a critical role in
modulating TLR4 activity and maintaining intestinal homeostasis.
Another innovative approach involves the use of anti-necroptotic
agents. Necrostatin-1, a specific inhibitor of necroptosis, has been
shown to reduce intestinal injury and inflammation in NEC models. This
therapy targets the downstream effects of TLR4 activation, preventing
the catastrophic cell death and barrier dysfunction associated with
necroptosis. Combined approaches that integrate TLR4 inhibition with
necroptosis suppression may offer synergistic benefits.
Despite these advances, translating preclinical findings into clinical
practice remains challenging. The heterogeneity of NEC, its
unpredictable onset, and the limitations of current diagnostic tools
complicate the development and implementation of targeted therapies.
The Bell staging system, commonly used to classify NEC severity, has
limitations in its ability to distinguish NEC from other neonatal
gastrointestinal conditions. Improved diagnostic criteria and
biomarkers are needed to identify at-risk infants and tailor
interventions effectively.
Future research should focus on elucidating the complex interplay
between TLR4 signaling, the microbiome, and host factors in NEC.
Advances in genomic and proteomic technologies offer opportunities to
identify novel targets and refine therapeutic strategies. Additionally,
the integration of precision medicine approaches, including the use of
individualized probiotic formulations and personalized nutrition plans,
holds promise for improving outcomes in NEC.
In conclusion, TLR4 is a central player in the pathogenesis of NEC,
orchestrating a cascade of inflammatory, ischemic, and apoptotic
processes that culminate in severe intestinal injury. Insights into the
molecular mechanisms of TLR4-mediated NEC have paved the way for
innovative therapeutic strategies, ranging from breast milk-derived
interventions to targeted molecular inhibitors. While significant
challenges remain, continued research into TLR4 and its role in NEC
holds the potential to transform the prevention and treatment of this
devastating disease, ultimately improving survival and quality of life
for premature infants.
References:
1- Hackam DJ, Sodhi CP: Toll-Like Receptor-Mediated Intestinal
Inflammatory Imbalance in the Pathogenesis of Necrotizing
Enterocolitis. Cell Mol Gastroenterol Hepatol. 6(2):229-238.e1, 2018
2- Mihi B, Good M: Impact of Toll-Like Receptor 4 Signaling in
Necrotizing Enterocolitis: The State of the Science. Clin Perinatol.
46(1):145-157, 2019
3- Sodhi CP, Wipf P, Yamaguchi Y, Fulton WB, Kovler M, Ni¤o DF,
Zhou Q, Banfield E, Werts AD, Ladd MR, Buck RH, Goehring KC, Prindle T
Jr, Wang S, Jia H, Lu P, Hackam DJ:. The human milk oligosaccharides
2'-fucosyllactose and 6'-sialyllactose protect against the development
of necrotizing enterocolitis by inhibiting toll-like receptor 4
signaling. Pediatr Res.89(1):91-101, 2021
4- Kovler ML, Gonzalez Salazar AJ, Fulton WB, Lu P, Yamaguchi Y, Zhou
Q, Sampah M, Ishiyama A, Prindle T Jr, Wang S, Jia H, Wipf P, Sodhi CP,
Hackam DJ: Toll-like receptor 4-mediated enteric glia loss is critical
for the development of necrotizing enterocolitis. Sci Transl Med.
13(612):eabg3459, 2021
5- Liu T, Zong H, Chen X, Li S, Liu Z, Cui X, Jia G, Shi Y: Toll-like
receptor 4-mediated necroptosis in the development of necrotizing
enterocolitis. Pediatr Res. 91(1):73-82, 2022
6- Duess JW, Sampah ME, Lopez CM, Tsuboi K, Scheese DJ, Sodhi CP,
Hackam DJ: Necrotizing enterocolitis, gut microbes, and sepsis. Gut
Microbes. 15(1):2221470, 2023
PSU Volume 64 No 02 FEBRUARY 2025
Uretero-Inguinal Hernia
Uretero-inguinal hernia (UIH) is an exceedingly rare condition,
characterized by the displacement of the ureter into the inguinal
canal. This phenomenon can be congenital or acquired and is often
associated with complex anatomical anomalies or predisposing factors.
It poses diagnostic and therapeutic challenges due to its unusual
presentation and the potential for severe complications if not
identified and managed appropriately.
UIH has two primary classifications: paraperitoneal and
extraperitoneal. Paraperitoneal UIH, which constitutes approximately
80% of cases, involves the ureter adhering to a hernial sac and being
pulled into the inguinal canal. This type is often linked to sliding
hernias and may involve other abdominal viscera. In contrast,
extraperitoneal UIH, accounting for the remaining 20%, occurs without a
hernial sac and is typically associated with congenital anomalies of
the ureteral and renal systems. This variety is believed to result from
abnormal embryological development, such as late separation of the
Wolffian duct or adherence of the ureter to genitoinguinal structures.
UIH predominantly affects males, possibly due to the developmental
descent of the Wolffian duct structures into the scrotum, creating a
pathway for ureteral involvement. In adults, risk factors include
advanced age, obesity, renal transplantation, and collagen disorders.
In children, the condition is exceptionally rare, with only a limited
number of documented cases.
Clinical manifestations of UIH are varied and depend on the extent of
ureteral involvement and the presence of secondary complications.
Patients may present with symptoms ranging from an asymptomatic
inguinal mass to signs of obstructive uropathy, such as flank pain,
hematuria, or hydronephrosis. In many cases, UIH is discovered
incidentally during surgical exploration for inguinal hernia repair.
Imaging modalities like ultrasound, computed tomography (CT), and
voiding cystourethrography (VCUG) play critical roles in preoperative
diagnosis, helping identify ureteral involvement and associated urinary
tract anomalies.
Management of UIH requires careful surgical intervention to prevent
iatrogenic injuries. The approach varies depending on the type and
severity of the hernia, as well as the patient?s overall condition. For
paraperitoneal UIH, high ligation of the hernial sac and repositioning
of the ureter are common strategies. For extraperitoneal cases,
interventions may include ureteral reimplantation or
ureteroneocystostomy, especially in the presence of significant
obstruction or stricture.
In pediatric cases, the rarity of UIH necessitates heightened clinical
awareness, particularly in the presence of congenital urological
anomalies. Early recognition and intervention are essential to avoid
complications like ureteral injury or progressive renal impairment.
Long-term follow-up with renal function tests and imaging is crucial to
monitor outcomes and prevent recurrence.
The literature highlights the importance of individualized care and the
role of multidisciplinary teams, including pediatric surgeons,
urologists, and radiologists, in managing this complex condition.
Advances in laparoscopic techniques have improved visualization and
allowed for more precise interventions, reducing morbidity, and
enhancing recovery.
UIH represents a fascinating interplay between congenital and acquired
factors, with implications for both surgical practice and urological
management. Continued documentation of cases and research into the
underlying mechanisms will be essential to refine diagnostic and
therapeutic strategies for this rare entity.
References:
1- Handu AT, Garge S, Peters NJ, Kanojia RP, Rao KL: Undiagnosed
ureteroinguinal hernia with solitary kidney in a child with ureteric
injury during herniotomy. J Pediatr Surg. 47(4):799-802, 2012
2- Lakshmi Narayanan P, C D N, Sekar V, Vadyala AR: Laparoscopic
approach to ureteroinguinal hernia. Int J Surg Case Rep. 77:161-164,
2020
3- Turner A, Subramanian P. Ureteroinguinal Hernia: A Rare General Surgery Phenomenon. Cureus. 13(12):e20586, 2021
4- Cianci MC, Tocchioni F, Mantovani A, Ghionzoli M, Morini F:
Unexpected Pediatric Uretero-Inguinal Hernia: Case-Report and
Literature Review. Urology. 2023 Jun;176:178-182, 2023
5- Delgado-Miguel C, Mu¤oz-Serrano AJ, Aguado P, Fuentes E,
D¡ez R: Ureteroinguinal Herniation with Consecutive Ureteral
Stricture in a 2-Month-Old Infant: Case Report. European J Pediatr Surg
Rep. 12(1):e16-e19, 2024
6-Ger‡el G: A surprise during hernia surgery: inguinoscrotal megaureter. Turk J Pediatr. 66(3):378-382, 2024
Antithrombotic Therapy
Antithrombotic therapy for children is a rapidly evolving area of
medical research and practice due to the increasing recognition and
diagnosis of thromboembolic events (TEs) in pediatric populations.
Unlike adults, children experience TEs primarily as a consequence of
severe illness or medical interventions, such as central venous
catheterization. This distinct etiology necessitates tailored
approaches to diagnosis, treatment, and prevention.
Pediatric TEs differ significantly from adult cases in terms of
epidemiology, pathophysiology, and therapeutic implications. While the
incidence of VTE in the general pediatric population remains low (0.07
to 0.14 per 10,000 children), hospitalized children face a much higher
risk up to 1000-fold greaterdue to the widespread use of central venous
access devices (CVADs) and other invasive procedures. Neonates and
adolescents constitute the most vulnerable groups, reflecting distinct
physiological and pathophysiological factors such as immature
coagulation systems and pubertal hormonal changes.
The pediatric coagulation system undergoes significant maturation
during the first year of life, which alters the pharmacodynamics and
pharmacokinetics of anticoagulant medications. For instance, younger
children often require higher weight-based doses of anticoagulants,
despite having lower levels of coagulation proteins. These differences
pose unique challenges in drug selection, dosing, and monitoring.
Historically, antithrombotic therapy in children has relied on
unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and
vitamin K antagonists (VKAs). However, recent advances have introduced
direct oral anticoagulants (DOACs) as a promising alternative due to
their consistent pharmacokinetics, ease of administration, and reduced
monitoring requirements. Clinical trials have demonstrated that DOACs,
such as rivaroxaban and dabigatran, are as effective as standard
anticoagulants while offering improved safety profiles.
The American Society of Hematology (ASH) 2018 guidelines emphasize the
use of anticoagulation in symptomatic VTE and stress the importance of
individualized therapy based on the patient's clinical status and risk
factors. For asymptomatic cases, the decision to treat remains
contentious, reflecting the low certainty of evidence regarding the
balance between risks and benefits. The recommendations also underline
the need for multidisciplinary care involving pediatric hematologists
to optimize treatment outcomes.
Updated guidance from the International Society on Thrombosis and
Haemostasis (ISTH) has refined outcome definitions for pediatric VTE
clinical trials, introducing parameters like patient-important bleeding
to standardize safety assessments. These developments aim to enhance
the comparability and applicability of trial results.
Despite significant progress, challenges remain. Many recommendations
for pediatric antithrombotic therapy are extrapolated from adult
studies due to the limited number of pediatric-specific trials. This
reliance underscores the need for robust, age-appropriate research to
address gaps in knowledge, particularly regarding long-term outcomes
and the management of chronic conditions such as post-thrombotic
syndrome.
Meta-analyses and network comparisons have further clarified the
efficacy and safety of various anticoagulants. For example, DOACs have
shown non-inferiority to traditional agents in preventing recurrent
TEs, with lower risks of major bleeding. However, concerns persist
about their use in specific pediatric subgroups, such as neonates and
critically ill children, highlighting the importance of cautious
implementation based on individual risk profiles.
Prophylactic anticoagulation remains a debated topic in pediatric care.
Although standard in adult practice, its routine use in children is not
widely endorsed due to the scarcity of high-quality evidence supporting
its benefits. Studies investigating the role of prophylaxis in
high-risk settings, such as CVAD-related thrombosis, have yielded mixed
results, further complicating clinical decision-making.
Emerging research continues to expand the therapeutic arsenal for
pediatric TEs. The advent of age-specific formulations of DOACs,
coupled with advances in imaging and biomarker technologies, holds
promise for improving diagnostic precision and treatment efficacy.
Moreover, ongoing trials are expected to address critical questions
about optimal dosing, duration of therapy, and long-term safety.
In conclusion, antithrombotic therapy in children has evolved
significantly, driven by a growing understanding of pediatric
hemostasis and advances in pharmacology. While traditional
anticoagulants remain the cornerstone of treatment, DOACs represent a
paradigm shift in managing pediatric TEs. Nevertheless, the field
requires continued investment in research and collaboration to refine
therapeutic strategies and ensure the best outcomes for young patients.
References:
1- Monagle P, Chan AKC, Goldenberg NA, Ichord RN, Journeycake JM,
Nowak-GŒttl U, Vesely SK: Antithrombotic therapy in
neonates and children: Antithrombotic Therapy and Prevention of
Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based
Clinical Practice Guidelines. Chest. 141(2 Suppl):e737S-e801S, 2012
2- Young G. Anticoagulation Therapies in Children: Pediatr Clin North Am. 64(6):1257-1269, 2017
3- Monagle P, Cuello CA, Augustine C, Bonduel M, Brand?o LR, Capman T,
Chan AKC, Hanson S, Male C, Meerpohl J, et al: American Society of
Hematology 2018 Guidelines for management of venous thromboembolism:
treatment of pediatric venous thromboembolism. Blood Adv.
2(22):3292-3316, 2018
4- Whitworth H, Amankwah EK, Betensky M, Castellucci LA, Cuker A,
Goldenberg NA, Male C, Rinzler E, Zia A, Raffini L: Updated guidance
for efficacy and safety outcomes for clinical trials in venous
thromboembolism in children: Communication from the ISTH SSC
Subcommittee on Pediatric and Neonatal Thrombosis and Hemostasis. J
Thromb Haemost. 21(6):1666-1673, 2023
5- Gao H, Chen M, Huang Y, Liu H, Lin Y, Chen M: Efficacy and safety of
antithrombotic therapy for preventing and treating pediatric
thromboembolic disease: A systematic review. Sci Rep. 14(1):13378, 2024
6- Manco-Johnson MJ, Annam A, Schardt : Anticoagulation in Pediatric Patients. Tech Vasc Interv Radiol. 27(2):100958, 2024
Adamkiewicz Artery in Pediatric Posterior Thoracic Tumors
Posterior thoracic tumors in pediatric patients, particularly those
of neurogenic origin such as neuroblastomas and ganglioneuromas, pose
unique surgical challenges due to their proximity to the Artery of
Adamkiewicz (AKA). This artery, the primary blood supply to the
anterior spinal cord, is often located between the T8 and L1 vertebral
levels and exhibits significant anatomical variability. Inadvertent
injury to the AKA during tumor resection can lead to catastrophic
outcomes, including anterior spinal cord ischemia, paraparesis, or
paraplegia. Consequently, accurate preoperative identification of the
AKA is critical to surgical planning and patient safety.
Recent advancements in imaging techniques, particularly spinal
angiography (SA) and Magnetic Resonance Angiography (MRA), have
revolutionized preoperative evaluation for pediatric patients with
posterior thoracic tumors. These modalities allow detailed mapping of
the spinal vasculature, enabling surgeons to plan resections that
minimize the risk of vascular injury. Studies have demonstrated that
incorporating these imaging techniques into preoperative protocols not
only improves surgical outcomes but also reduces the incidence of
neurologic complications.
One study involving 36 pediatric patients evaluated the utility of
preoperative spinal angiography. Among these patients, SA identified
the AKA in all cases, demonstrating its reliability in mapping vascular
anatomy. In four cases where the AKA was in close proximity to the
tumor, surgical plans were modified, with three patients undergoing
non-surgical management, such as radiation therapy, to mitigate risk.
Importantly, no complications arose from the SA procedure itself,
highlighting its safety and efficacy as a preoperative tool.
Another key finding from recent research is the significant reduction
in neurologic complications when SA is employed. A retrospective
analysis comparing outcomes before and after the routine use of SA in
pediatric posterior thoracic tumor resections revealed a marked
decrease in the incidence of postoperative spinal ischemia. Prior to
implementing routine SA, one patient in the study cohort developed
paraplegia following resection. Post-SA implementation, no such
complications were observed, underscoring the role of detailed
preoperative vascular mapping in enhancing patient safety.
In addition to spinal angiography, Magnetic Resonance Angiography (MRA)
has shown promise as a non-invasive alternative for visualizing the
AKA. A case report highlighted the successful use of MRA in a
14-month-old child with a thoracic neuroblastoma. The imaging
identified the precise location of the AKA, allowing the surgical team
to avoid critical vascular structures during resection. MRA's
non-invasive nature and ability to provide high-resolution images make
it particularly suitable for pediatric patients, where minimizing
procedural risks is paramount.
Despite these advancements, challenges remain in achieving consistent
and accurate preoperative identification of the AKA. The artery's
variability in origin, pathway, and laterality necessitates a tailored
approach for each patient. Moreover, the choice of imaging
modality—whether SA, MRA, or a combination—often depends on
institutional resources and expertise. While spinal angiography remains
the gold standard for AKA visualization, its invasive nature, and
associated risks, though minimal, must be carefully weighed against the
benefits in each case.
The integration of imaging findings into surgical decision-making has
profound implications for treatment strategies. In cases where the AKA
is identified in close proximity to the tumor, surgeons may opt for
partial resections, alternative surgical approaches, or adjunctive
therapies such as radiation. This tailored approach not only preserves
spinal cord function but also improves overall outcomes by reducing the
likelihood of tumor recurrence or residual disease.
Studies also emphasize the importance of interdisciplinary
collaboration in managing these complex cases. The involvement of
pediatric surgeons, interventional radiologists, and neuro-oncologists
ensures a comprehensive evaluation of risks and benefits, facilitating
informed decision-making. Multidisciplinary tumor boards play a pivotal
role in this process, integrating imaging findings with clinical and
pathological data to devise individualized treatment plans.
Further research is needed to refine imaging techniques and establish
standardized protocols for preoperative evaluation of the AKA. Emerging
technologies, such as advanced MRI sequences and 3D vascular mapping,
hold promise for enhancing the accuracy and accessibility of
preoperative imaging. Additionally, longitudinal studies assessing
long-term outcomes in patients undergoing surgery with preoperative AKA
identification will provide valuable insights into the efficacy of
these strategies.
In conclusion, the preoperative identification of the Adamkiewicz
Artery is a critical component of surgical planning for pediatric
posterior thoracic tumors. Techniques such as spinal angiography and
Magnetic Resonance Angiography enable precise vascular mapping,
significantly reducing the risk of spinal ischemia and associated
neurologic complications. By incorporating these modalities into
preoperative protocols and fostering interdisciplinary collaboration,
healthcare teams can optimize surgical outcomes and improve the quality
of life for pediatric patients with these challenging tumors. Continued
advancements in imaging technology and research will further enhance
the safety and efficacy of these interventions, paving the way for
improved standards of care in pediatric oncology.
References:
1- Boglino C, Martins AG, Ciprandi G, Sousinha M, Inserra A: Spinal
cord vascular injuries following surgery of advanced thoracic
neuroblastoma: an unusual catastrophic complication. Med Pediatr Oncol.
32(5):349-52, 1999
2- Nordin AB, Fallon SC, Jea A, Kim ES: The use of spinal angiography
in the management of posterior mediastinal tumors: case series and
review of the literature. J Pediatr Surg. 48(9):1871-7, 2013
3- Schmidt A, Hempel JM, Ellerkamp V, Warmann SW, Ernemann U, Fuchs J:
The Relevance of Preoperative Identification of the Adamkiewicz Artery
in Posterior Mediastinal Pediatric Tumors. Ann Surg Oncol.
29(1):493-499, 2022
4- Clark RA, Jacobson JC, Murphy JT: Preoperative spinal angiography
decreases risk of spinal ischemia in pediatric posterior thoracic tumor
resection. Pediatr Surg Int. 38(10):1427-1434, 2022
5- Almeida AI, Vasconcelos-Castro S, Sampaio L: Successful technical
note-Identification of the Adamkievicz artery with 1.5 Tesla MR
angiography in a 14-month-old child. Radiol Case Rep. 18(1):188-191,
2022
5- Zarfati A, Guérin F, Dioguardi Burgio M, Fuchs J, Sarnacki S,
Losty PD, Pio L: Preoperative Identification of Adamkiewicz Artery in
Pediatric Posterior Thoracic Tumors: Fact or Fiction? A Systematic
Review from the International Society of Pediatric Surgical Oncology
(IPSO). J Pediatr Surg. 59(12):161985, 2024
PSU Volume 64 No 03 MARCH 2025
NAVA
Neurally-Adjusted Ventilatory Assist (NAVA) is a novel mode of
mechanical ventilation that synchronizes ventilator support with the
patient?s respiratory efforts by monitoring the electrical activity of
the diaphragm (EAdi). Introduced over two decades ago, NAVA has
garnered attention for its potential to improve patient-ventilator
interaction, reduce ventilator-induced injuries, and enhance clinical
outcomes in various patient populations. This review delves into the
physiological principles, clinical applications, comparative
effectiveness, and challenges associated with NAVA.
Unlike conventional ventilation modes that rely on pneumatic signals
such as flow or pressure for triggering, NAVA uses EAdi to initiate and
terminate ventilator assistance. The diaphragm's electrical activity,
detected via a nasogastric tube equipped with specialized electrodes,
reflects the central respiratory drive. This signal provides a precise
and dynamic measure of respiratory effort, allowing ventilatory support
to be proportional to the patient?s needs throughout each breath. By
ensuring that the ventilator is in tune with the patient?s neural
respiratory cycle, NAVA minimizes asynchrony, a common issue in
traditional ventilation modes. Studies have consistently demonstrated
the ability of NAVA to optimize ventilator-patient interaction,
particularly in patients with complex respiratory mechanics, such as
those with low lung compliance or high airway resistance.
One of the key advantages of NAVA is its ability to enhance synchrony,
even in challenging conditions like acute respiratory distress syndrome
(ARDS) or chronic obstructive pulmonary disease (COPD). Conventional
modes such as pressure support ventilation (PSV) often struggle to
maintain synchrony, leading to asynchrony indices as high as 30% in
some populations. In contrast, studies comparing NAVA and PSV show
significantly lower asynchrony indices in NAVA, underscoring its
superiority in ensuring coordination between neural and mechanical
respiratory cycles. This improved synchrony has far-reaching
implications, including reduced work of breathing, better gas exchange,
and enhanced patient comfort.
NAVA also plays a crucial role in preserving diaphragm function. In
traditional ventilation, excessive assistance can suppress respiratory
drive, leading to ventilator-induced diaphragm dysfunction (VIDD). By
delivering proportional support, NAVA prevents over-assistance and
maintains adequate diaphragm activity, reducing the risk of atrophy.
This aspect of diaphragm-protective ventilation is particularly
important in patients requiring prolonged mechanical support.
Additionally, NAVA contributes to lung protection by minimizing
ventilator-induced lung injury (VILI). Conventional modes often deliver
fixed tidal volumes or pressures, which can result in barotrauma or
volutrauma in vulnerable patients. With NAVA, the ventilator
dynamically adjusts pressure in response to the patient's effort,
reducing the likelihood of excessive lung stress or strain. Studies in
animal models and human subjects confirm that NAVA helps distribute
ventilation more evenly across lung regions, thereby mitigating the
risk of localized overdistension.
The versatility of NAVA makes it applicable to diverse patient
populations, including adults with acute respiratory failure, pediatric
patients, and neonates. In adult intensive care units (ICUs), NAVA has
been shown to improve clinical outcomes such as duration of ventilation
and patient comfort. A narrative review highlighted that NAVA's
proportional support not only ensures adequate gas exchange but also
reduces the risk of apnea and asynchrony during noninvasive ventilation
(NIV). These benefits are particularly pronounced in patients with ARDS
or COPD exacerbations, where traditional modes often fall short.
In pediatric intensive care units (PICUs), NAVA is increasingly being
used as a weaning mode for invasively ventilated children. Systematic
reviews indicate that NAVA reduces the length of PICU stays and
sedation requirements compared to traditional modes. For example, a
cohort study involving children recovering from cardiac surgery
reported higher extubation success rates and shorter ventilation
durations with NAVA. Despite these promising findings, the evidence
base remains limited, necessitating further research to establish
standardized protocols and optimize outcomes.
The use of NAVA in neonates, particularly preterm infants, presents
unique challenges and opportunities. Neonates often require prolonged
respiratory support due to immature lungs and respiratory control
mechanisms. Traditional ventilation modes frequently fail to achieve
synchrony in this population due to their rapid respiratory rates and
small tidal volumes. NAVA, by directly responding to neural signals,
offers a solution to these issues. Studies have demonstrated that NAVA
reduces bronchopulmonary dysplasia (BPD) and improves extubation
success rates in preterm infants. However, technical difficulties in
acquiring reliable EAdi signals and the prevalence of apnea in this
population remain significant barriers to widespread adoption.
When compared to conventional ventilation modes, NAVA consistently
outperforms in terms of synchrony, patient comfort, and physiological
outcomes. Meta-analyses of studies comparing NAVA and PSV during
noninvasive ventilation reveal significantly lower asynchrony indices
and fewer ineffective efforts in the NAVA group. However, the data on
clinical outcomes such as mortality and length of ICU stay are less
conclusive. For instance, while some studies report shorter ventilation
durations and reduced sedation requirements with NAVA, others note no
significant differences in mortality rates or overall clinical
outcomes. These discrepancies highlight the need for larger,
multicenter randomized controlled trials (RCTs) to validate the
observed benefits and explore their impact on long-term outcomes.
Despite its advantages, NAVA is not without limitations. One of the
primary challenges is the reliance on a specialized nasogastric tube
for EAdi signal acquisition. This requirement can lead to discomfort
and may not be feasible in all patients. Additionally, the need for
trained personnel to manage NAVA settings and interpret EAdi signals
has hindered its widespread adoption. Cost considerations also play a
role, as NAVA-specific equipment and training represent a significant
investment for healthcare facilities.
In neonates, the frequent occurrence of apnea and insufficient
triggering of EAdi signals pose specific challenges. These issues
necessitate careful titration of NAVA settings and ongoing monitoring
to ensure effective ventilation. Furthermore, the limited availability
of robust clinical data in this population underscores the need for
targeted research.
The future of NAVA lies in expanding its clinical applications and
addressing existing limitations. Technological advancements aimed at
improving EAdi signal acquisition and patient comfort could enhance the
feasibility of NAVA in a broader range of patients. Research efforts
should focus on conducting large-scale RCTs to establish evidence-based
guidelines for NAVA use across different populations. Additionally,
exploring the integration of NAVA with other innovative ventilation
strategies could pave the way for personalized respiratory support
tailored to individual patient needs.
In conclusion, NAVA represents a significant advancement in mechanical
ventilation, offering improved synchrony, diaphragm preservation, and
lung protection compared to conventional modes. While challenges
remain, the growing body of evidence supporting its physiological and
clinical benefits makes NAVA a promising tool in the management of
respiratory failure. Continued research and innovation are essential to
fully realize its potential and optimize outcomes for patients across
the age spectrum.
References:
1- Navalesi P, Longhini F: Neurally adjusted ventilatory assist. Curr Opin Crit Care. 21(1):58-64, 2015
2- Sugunan P, Hosheh O, Garcia Cusco M, Mildner R: Neurally-Adjusted
Ventilatory Assist (NAVA) versus Pneumatically Synchronized Ventilation
Modes in Children Admitted to PICU. J Clin Med. 10(15):3393, 2021
3- Umbrello M, Antonucci E, Muttini S: Neurally Adjusted Ventilatory
Assist in Acute Respiratory Failure-A Narrative Review. J Clin Med.
11(7):1863, 2022
4- Weiyun T, Linli S, Liuzhao C: Neurally-Adjusted Ventilatory Assist
Versus Pressure Support Ventilation During Noninvasive Ventilation.
Respir Care. 67(7):879-888, 2022
5- Fang SJ, Chen CC, Liao DL, Chung MY: Neurally adjusted ventilatory
assist in infants: A review article. Pediatr Neonatol. 64(1):5-11, 2023
6- Lefevere J, van Delft B, Decaluwe W, Derriks F, Cools F: Neurally
adjusted ventilatory assist in preterm infants: A systematic review and
meta-analysis. Pediatr Pulmonol. 59(7):1862-1870, 2024
Botulinum Toxin for Long Gap Esophageal Atresia
Long gap esophageal atresia (LGEA) is a rare but significant
congenital condition, occurring in approximately 1 in 3,000 to 4,500
live births. The defining characteristic of LGEA is the presence of a
substantial gap between the proximal and distal esophageal segments,
often making primary anastomosis unfeasible. Traditional management
approaches include delayed primary repair, organ interpositions, or
esophageal replacement procedures, but these are frequently associated
with high morbidity, prolonged hospital stays, and suboptimal
functional outcomes. In recent years, the use of botulinum toxin (BTX),
a neurotoxin derived from Clostridium botulinum, has emerged as a
potential adjunct in managing LGEA by facilitating tissue elongation
and reducing complications.
The mechanism of action of botulinum toxin lies in its ability to block
the release of acetylcholine at neuromuscular junctions. This
inhibition results in muscle relaxation, which can be exploited to
reduce tissue tension in the esophagus. Initial experimental studies in
animal models have demonstrated the efficacy of BTX in elongating
esophageal tissue, with mechanical stress that often precludes
successful primary anastomosis in LGEA.
Botulinum toxin (BTX) is applied intramurally to the esophageal
musculature through precise injections, typically performed under
direct visualization during surgery or using endoscopic techniques for
minimally invasive delivery. The toxin is injected into multiple points
along the esophageal wall, often at a dose of 2 units/kg per site,
targeting both proximal and distal esophageal segments. Timing is
crucial, with injections planned to allow BTX's peak effect, occurring
around two weeks post-administration, to coincide with critical phases
of elongation or repair. This method ensures localized muscle
relaxation, enhancing tissue compliance and facilitating esophageal
elongation while minimizing systemic effects.
Building upon these findings, further research explored the utility of
BTX in a clinical context. In one randomized controlled trial, pig
models with simulated esophageal atresia were treated with BTX prior to
surgical interventions. The results demonstrated not only improved
esophageal elongation but also a reduction in stricture formation and
leakage rates post-anastomosis. The significant reductions in muscle
tension observed in pig models. One study conducted in 2013 evaluated
the intramural injection of BTX in piglets, showing that treated
esophageal segments exhibited an 18% greater elongation under tension
compared to controls. This finding underscored the potential of BTX to
reduce the histological analysis further revealed that BTX-treated
tissues exhibited more organized muscle regeneration and less collagen
deposition at anastomotic sites, suggesting enhanced healing. These
outcomes align with the hypothesis that BTX's muscle-relaxing and
anti-fibrotic properties can mitigate some of the mechanical and
biological challenges associated with esophageal repair.
The integration of BTX into surgical protocols for LGEA has also been
studied in conjunction with advanced techniques such as the Foker
process. This method, which relies on applying continuous tension to
stimulate esophageal growth, is a cornerstone of modern LGEA
management. However, its implementation is often limited by the
prolonged sedation and immobility required for traction. A 2024 study
investigating BTX-enhanced Foker procedures demonstrated that the
addition of BTX significantly reduced the duration of traction, from an
average of 16.6 days in traditional Foker processes to 12.1 days in
BTX-enhanced protocols. This reduction not only minimizes the risks
associated with prolonged sedation but also expedites recovery,
highlighting the practical benefits of incorporating BTX into clinical
practice.
Despite these promising results, challenges remain in translating BTX
therapy from experimental and early clinical studies to routine use.
One key consideration is the optimal timing of BTX administration. The
toxin's peak effect typically occurs two weeks post-injection,
suggesting that precise scheduling is crucial for maximizing its
benefits during surgical planning. Additionally, concerns about
potential side effects, such as transient dysphagia or gastroesophageal
reflux due to temporary reductions in esophageal motility, warrant
careful monitoring and further research.
The anti-fibrotic effects of BTX are another area of interest. By
reducing smooth muscle spasms and the mechanical stress that
contributes to scar formation, BTX may lower the incidence of
refractory strictures—a common and debilitating complication of
esophageal surgery. However, clinical data on long-term outcomes in
human subjects remain sparse, and larger cohort studies with extended
follow-up are necessary to confirm these findings.
Another intriguing application of BTX lies in its potential to enhance
minimally invasive surgical techniques for LGEA. Thoracoscopic
approaches, which are gaining popularity due to their reduced morbidity
compared to open surgery, could benefit from the muscle-relaxing
properties of BTX. Early studies suggest that BTX injections can
facilitate the mobilization of esophageal segments, making minimally
invasive procedures more feasible even in complex cases of LGEA.
The future of BTX in LGEA treatment appears promising, with ongoing
research exploring new frontiers. For instance, the combination of BTX
with regenerative medicine techniques, such as tissue engineering and
stem cell therapies, could revolutionize the field. By creating
bioengineered esophageal tissues pre-treated with BTX, it may be
possible to further optimize surgical outcomes and reduce reliance on
traditional, high-risk procedures.
In conclusion, botulinum toxin represents a novel and versatile tool in
the management of long gap esophageal atresia. Its ability to reduce
tissue tension, enhance elongation, and improve anastomotic healing
positions it as a valuable adjunct in addressing the challenges of this
complex condition. While further clinical studies are needed to refine
its applications and establish standardized protocols, the integration
of BTX into LGEA management has the potential to significantly improve
outcomes for affected infants and their families. With ongoing
advancements in both surgical techniques and pharmacological
interventions, the role of BTX is likely to expand, offering new hope
in the treatment of this challenging congenital anomaly.
References:
1- Ellebæk M, Qvist N, Rasmussen L: Secondary anastomosis after
preoperative botulinum type A toxin injection in a case with long gap
oesophageal atresia. Eur J Pediatr Surg. 23(4):325-6, 2013
2- Larsen HF, Jensen TS, Rasmussen L, Ellebæk M, Qvist N:
Intramural injection with botulinum toxin significantly elongates the
pig esophagus. J Pediatr Surg. 48(10):2032-5, 2013
3- Dibbern CB, Rose M, Ellebæk MB, Qvist N: The Effect of
Intramural Botulinum Toxin Injections on the Elongation of the Piglet
Oesophagus Is Time Dependent. Eur J Pediatr Surg. 27(1):56-60, 2017
4- Pike AH, Zvara P, Antulov MR, et al: Intramural Injection of
Botulinum Toxin A in Surgical Treatment of a Long Gap Esophageal
Atresia-Rat Model. Eur J Pediatr Surg. 30(6):517-523, 2020
5- Svensson E, Zvara P, Qvist N, et al: The Effect of Botulinum Toxin
Type A Injections on Stricture Formation, Leakage Rates, Esophageal
Elongation, and Anastomotic Healing Following Primary Anastomosis in a
Long- and Short-Gap Esophageal Atresia Model - A Protocol for a
Randomized, Controlled, Blinded Trial in Pigs. Int J Surg Protoc.
25(1):171-177, 2021
6- Izadi S, Koo DC, Shieh HF, et al: Botulinum Toxin Enhanced Foker
Process for Long Gap Esophageal Atresia. J Pediatr Surg. 59(12):161628,
2024
Newborn Infant Parasympathetic Evaluation Monitor
The Newborn Infant Parasympathetic Evaluation (NIPE) monitor
represents a significant advancement in neonatal and pediatric care,
offering a non-invasive means of assessing pain and discomfort in
infants under two years of age. The device, developed to measure
parasympathetic activity through heart rate variability (HRV), provides
an objective pain index, ranging from 0 to 100. This technology
addresses longstanding limitations of traditional pain assessment
methods, which have relied heavily on subjective observations and
behavioral scales, such as the Premature Infant Pain Profile Revised
(PIPP-R) and the Face, Legs, Activity, Cry, Consolability (FLACC) scale.
Traditional behavioral scales have several drawbacks, including high
interobserver variability, time-intensive scoring, and limited
applicability in deeply sedated or anesthetized patients. The NIPE
monitor overcomes these issues by continuously analyzing high-frequency
HRV to evaluate parasympathetic tone. A decrease in the NIPE score
indicates heightened pain or stress, while an increase suggests
improved comfort. The monitor generates instantaneous (NIPEi) and mean
(NIPEm) indices, allowing real-time and averaged pain assessments,
respectively.
Several studies have explored the utility of the NIPE monitor across
various clinical settings, including acute pain during procedural
interventions, intraoperative nociception, and postoperative pain
management. However, the results have been mixed, highlighting both the
potential and the limitations of this technology.
The NIPE monitor has been evaluated for its ability to detect acute
procedural pain in preterm and term neonates. A 2020 study by Gendras
et al. examined its effectiveness during routine painful and stressful
procedures in preterm infants. While the NIPE index demonstrated high
sensitivity and negative predictive value for predicting severe pain
during skin-breaking procedures, no significant correlation was found
between NIPE and PIPP-R scores during routine painful interventions.
This raised concerns about its ability to fully capture acute pain
responses, especially in less invasive procedures.
Other studies have similarly reported mixed findings. For instance, the
monitor successfully detected significant decreases in NIPE scores
during painful interventions, but its correlation with traditional pain
scales like the Neonatal Acute Pain (DAN) scale was inconsistent. These
discrepancies may stem from differences in patient demographics,
procedural types, and study methodologies.
Intraoperative pain assessment is another area where the NIPE monitor
shows promise. Traditional methods of evaluating nociception during
surgery, such as observing changes in heart rate and blood pressure,
are empirical and prone to variability. The NIPE monitor offers an
objective alternative by continuously measuring parasympathetic
activity. A 2024 systematic review highlighted the monitor's ability to
detect nociceptive events like skin incisions and intubations during
surgery, as well as insufficient analgesia. It also demonstrated high
sensitivity and specificity for identifying pain.
However, the device's utility may be limited by the complexity of
intraoperative pain management. For example, a study comparing open and
laparoscopic inguinal hernia repairs found significant differences in
NIPE scores, with laparoscopic procedures associated with greater pain
despite similar analgesic regimens. This finding underscores the
importance of contextual factors, such as the type of surgical
intervention and the adequacy of regional anesthesia.
Postoperative pain assessment has also been explored using the NIPE
monitor. A 2023 prospective study demonstrated a weak but statistically
significant correlation between intraoperative NIPE indices and
postoperative FLACC scores. This association was strongest immediately
after surgery but diminished over time, likely due to the
administration of postoperative analgesia. The findings suggest that
while the NIPE monitor can predict early postoperative pain, its
utility may decrease as external factors, such as analgesic
interventions, modify the pain response.
Another study compared pain outcomes in infants undergoing open versus
laparoscopic hernia repairs. Postoperative NIPE scores were
significantly lower in the laparoscopic group, reflecting higher pain
levels. These results highlighted the monitor's ability to objectively
differentiate pain levels between surgical approaches, providing
valuable insights for tailoring postoperative care.
Beyond pain assessment, the NIPE monitor has been used to evaluate
comfort and stress levels in neonates. Studies have shown increased
NIPE scores during interventions promoting comfort, such as
skin-to-skin contact and facilitated tucking. However, these findings
are not universal, with some studies reporting no significant changes
during specific comfort measures. The variability in results
underscores the need for further research to clarify the monitor's role
in non-pain-related assessments.
While the NIPE monitor offers several advantages, its adoption in
clinical practice faces challenges. One major limitation is its
inconsistent correlation with traditional pain scales, which remain the
gold standard for pain assessment. The reliance on HRV as a sole
indicator of pain may overlook other physiological and behavioral
components of the pain response.
Another issue is the heterogeneity of study populations and
methodologies. Variations in gestational age, clinical settings, and
procedural types make it difficult to generalize findings. Furthermore,
the monitor's accuracy in detecting subtle changes in parasympathetic
activity may be influenced by confounding factors such as medication
use, underlying medical conditions, and environmental stressors.
Finally, the NIPE monitor's primary focus on parasympathetic activity
may limit its applicability in conditions were sympathetic responses
dominate. For instance, pain responses involving significant
sympathetic activation may not be adequately captured, reducing the
monitor's overall sensitivity.
Despite these challenges, the NIPE monitor holds promise as a valuable
tool for neonatal and pediatric pain assessment. To fully realize its
potential, further research is needed to address existing limitations.
Large-scale, multicenter studies with standardized protocols are
essential for validating its accuracy and reliability. Additionally,
integrating the NIPE monitor with other pain assessment methods, such
as behavioral scales and biochemical markers, could enhance its
clinical utility.
Advances in technology may also improve the monitor's performance. For
example, refining the HRV algorithm to account for individual
variability and incorporating machine learning techniques could
increase its sensitivity and specificity. Expanding its use to other
clinical settings, such as the evaluation of chronic pain and stress,
could further broaden its applications.
The Newborn Infant Parasympathetic Evaluation monitor represents a
significant step forward in the objective assessment of pain and
discomfort in neonates and infants. While its utility has been
demonstrated in various clinical settings, including procedural pain,
surgery, and postoperative care, inconsistencies in findings highlight
the need for further research. With continued refinement and
validation, the NIPE monitor has the potential to revolutionize pain
management and improve outcomes for this vulnerable population.
References:
1- Gendras J, Lavenant P, Sicard-Cras I, Consigny M, Misery L, Anand
KJS, Sizun J, Roué JM: The newborn infant parasympathetic
evaluation index for acute procedural pain assessment in preterm
infants. Pediatr Res. 89(7):1840-1847, 2021
2- Recher M, Boukhris MR, Jeanne M, Storme L, Leteurtre S, Sabourdin N,
De Jonckheere J: The newborn infant parasympathetic evaluation in
pediatric and neonatology: a literature review. J Clin Monit Comput.
35(5):959-966, 2021
3- Ivanic S, Tong LS, Laird A, Malhotra A, Nataraja RM, Lang C, Pacilli
M: The Newborn Infant Parasympathetic Evaluation (NIPE™) monitor
predicts post-operative pain in children undergoing day-procedures: A
prospective observational study. J Pediatr Surg. 58(4):684-688, 2023
4- Manzar S: Does the Newborn Infant Parasympathetic Evaluation Monitor
Predict Post-Operative Pain? J Pediatr Surg. 58(9):1852, 2023
5- Sakthivel M, Su V, Nataraja RM, Pacilli M: Newborn and Infant
Parasympathetic Evaluation (NIPE™) Monitor for Assessing Pain
During Surgery and Interventional Procedures: A Systematic Review. J
Pediatr Surg. 59(4):672-677, 2024
6- Sakthivel M, Bapna T, Ivanic S, Lang C, Nataraja RM, Pacilli M: An
Objective Evaluation of Intraoperative and Postoperative Pain in
Infants Undergoing Open Inguinal Herniotomy and Laparoscopic Inguinal
Hernia Repair Using the Newborn Infant Parasympathetic Evaluation
(NIPE™) Monitor. J Pediatr Surg. 60(2):161651, 2025