Intravenous cannula for percutaneous rescue needle gastrostomy in a neonate with tracheoesophageal fistula-A case report.

Tracheoesophageal fistula offers concrete difficulties for anesthesiologists, which comprise associated congenital anomalies and more importantly the problems concerning ventilation and oxygenation. Among all the types of tracheoesophageal fistula, ventilatory problems are frequently encountered with type C fistula. Effective ventilation can be a challenge in such cases where the endotracheal tube invariably ventilates the fistula causing stomach inflation and respiratory compromise. Thorough knowledge and experience are of utmost importance when it comes to the successful airway management and better survival of neonates undergoing tracheoesophageal fistula repair. We report a case of a 3-day-old neonate, diagnosed with type C tracheoesophageal fistula and esophageal atresia posted for thoracoscopic repair. We want to highlight our experience of percutaneous needle gastrostomy done using an intravenous cannula, as a rescue measure for stomach decompression, to manage life-threatening hypoxia.

Randomized controlled trial of low vs high oxygen during neonatal anesthesia: Oxygenation, feasibility, and oxidative stress.

BACKGROUND: To reduce risk for intermittent hypoxia a high fraction of inspired oxygen is routinely used during anesthesia induction. This differs from the cautious dosing of oxygen during neonatal resuscitation and intensive care and may result in significant hyperoxia. AIM: In a randomized controlled trial, we evaluated oxygenation during general anesthesia with a low (23%) vs a high (80% during induction and recovery, and 40% during maintenance) fraction of inspired oxygen, in newborn infants undergoing surgery. METHOD: Thirty-five newborn infants with postconceptional age of 35-44 weeks were included (17 infants in low and 18 in high oxygen group). Oxygenation was monitored by transcutaneous partial pressure of oxygen, pulse oximetry, and cerebral oxygenation. Predefined SpO2 safety targets dictated when to increase inspired oxygen. RESULTS: At start of anesthesia, oxygenation was similar in both groups. Throughout anesthesia, the high oxygen group displayed significant hyperoxia with higher (difference-20.3 kPa, 95% confidence interval (CI)-28.4 to 12.2, p < .001) transcutaneous partial pressure of oxygen values than the low oxygen group. While SpO2 in the low oxygen group was lower (difference - 5.8%, 95% CI -9.3 to -2.4, p < .001) during anesthesia, none of the infants spent enough time below SpO2 safety targets to mandate supplemental oxygen, and cerebral oxygenation was within the normal range and not statistically different between the groups. Analysis of the oxidative stress biomarker urinary F2 -Isoprostane revealed no differences between the low and high oxygen group. CONCLUSION: We conclude that in healthy newborn infants, use of low oxygen during general anesthesia was feasible, while the prevailing practice of using high levels of inspired oxygen resulted in significant hyperoxia. The trade-off between careful dosing of oxygen and risks of hypo- and hyperoxia in neonatal anesthesia should be further examined.

Do We Have Viable Protective Strategies against Anesthesia-Induced Developmental Neurotoxicity?

Since its invention, general anesthesia has been an indispensable component of modern surgery. While traditionally considered safe and beneficial in many pathological settings, hundreds of preclinical studies in various animal species have raised concerns about the detrimental and long-lasting consequences that general anesthetics may cause to the developing brain. Clinical evidence of anesthetic neurotoxicity in humans continues to mount as we continue to contemplate how to move forward. Notwithstanding the alarming evidence, millions of children are being anesthetized each year, setting the stage for substantial healthcare burdens in the future. Hence, furthering our knowledge of the molecular underpinnings of anesthesia-induced developmental neurotoxicity is crucially important and should enable us to develop protective strategies so that currently available general anesthetics could be safely used during critical stages of brain development. In this mini-review, we provide a summary of select strategies with primary focus on the mechanisms of neuroprotection and potential for clinical applicability. First, we summarize a diverse group of chemicals with the emphasis on intracellular targets and signal-transduction pathways. We then discuss epigenetic and transgenerational effects of general anesthetics and potential remedies, and also anesthesia-sparing or anesthesia-delaying approaches. Finally, we present evidence of a novel class of anesthetics with a distinct mechanism of action and a promising safety profile.

Tracheoesophageal fistula in the developing world: are we ready for thoracoscopic repair?

PURPOSE: Tracheoesophageal fistula (TEF) is a bellwether for a country's ability to care for sick newborns. We aim to review the existing literature from low- and middle-income countries in regard to management of those newborns and the possible approaches to improve their outcomes. METHODS: A review of the existing English literature was conducted with the aim of assessing challenges faced by providers in LMIC in terms of diagnostic, preoperative, operative and post-operative care for TEF patients. We also review the limited literature for performing thoracoscopic repair in the developing world context and suggest methods for introduction of advanced thoracoscopic procedures including techniques for providing anesthesia to these challenging babies. RESULTS: While outcomes related to technique from LMIC are comparable to the developed world, rates of secondary complications like sepsis and pneumonia are higher. In many areas, repairs are conducted in a staged fashion with minimal utilization of thoracoscopic approach. The paucity of resources creates strain on intraoperative and post-operative management. CONCLUSION: Clearly, not all developing world contexts are ready to attempt thoracoscopic repair but we outline suggestions for assessing the existing capabilities and a stepwise gradual implementation of advanced thoracoscopy when appropriate.

Remifentanil: applications in neonates.

Remifentanil is a synthetic opioid derivative that was introduced into clinical practice in the United States in 1996. The unique modification of its chemical structure to include a methyl-ester ring allows its hydrolysis by non-specific plasma and tissue esterases. This molecular configuration results in its rapid metabolism thereby providing a rapid onset, easy titration by continuous infusion, and a short context-sensitive half-life with rapid elimination. These principles are stable and consistent across all age groups regardless of the infusion characteristics. Owing to these pharmacokinetic characteristics, it is an effective agent in the neonatal population allowing the provision of intense analgesia and anesthesia with a rapid recovery profile in various clinical scenarios. Here, we review the pharmacokinetics of remifentanil in neonates, discuss its clinical applications including intraoperative administration for anesthetic care, unique applications for procedural sedation including endotracheal intubation, and its potential use for sedation in the Intensive Care Unit setting during mechanical ventilation.

Perioperative care of infants with pyloric stenosis.

Pyloric stenosis (PS) is one of the most common surgical conditions affecting neonates and young infants. The definitive treatment for PS is surgical pyloromyotomy, either open or laparoscopic. However, surgical intervention should never be considered urgent or emergent. More importantly, emergent medical intervention may be required to correct intravascular volume depletion and electrolyte disturbances. Given advancements in surgical and perioperative care, morbidity and mortality from PS should be limited. However, either may occur related to poor preoperative resuscitation, anesthetic management difficulties, or postoperative complications. The following manuscript reviews the current evidence-based medicine regarding the perioperative care of infants with PS with focus on the preoperative assessment and correction of metabolic abnormalities, intraoperative care including airway management (particularly debate related to rapid sequence intubation), maintenance anesthetic techniques, and techniques for postoperative pain management. Additionally, reports of applications of regional anesthesia for either postoperative pain control or as an alternative to general anesthesia are discussed. Management recommendations are provided whenever possible.

Sevoflurane exposure during the neonatal period induces long-term memory impairment but not autism-like behaviors.

OBJECTIVE: To examine whether neonatal exposure to sevoflurane induces autism-like behaviors in mice. BACKGROUND: There are continuing reports regarding the potential negative effects of anesthesia on the developing brain. Recently, several studies suggest that neurotoxicity caused by anesthesia may lead to neurodevelopmental impairments. However, unlike reports focusing on learning and memory, there are only a few animal studies focusing on neurodevelopmental disorders after general anesthesia. Therefore, we have focused on autism, a representative neurodevelopmental disorder. METHODS: Neonatal mice (P6-7) were exposed to a titrated dose of sevoflurane for 6 h. Apoptosis was evaluated by assessing the expression level of cleaved (activated) caspase-3. Autism-like behaviors, general activity, anxiety level, and long-term memory were evaluated with multiple behavioral assays. RESULTS: Western blotting confirmed that neonatal exposure to sevoflurane increased the expression level of activated caspase-3, indicative of apoptosis. Mice exposed to sevoflurane also showed impaired long-term memory in fear tests. However, sevoflurane-exposed mice did not exhibit autism-like features in all of the following assays: social interaction (three-chamber test, caged social interaction), social communication (ultrasonic vocalization test), or repetitive behavior (self-grooming test, digging). There were also no differences in general activity (open field test, home cage activity) and anxiety (open field test, light-dark box) after sevoflurane exposure. CONCLUSIONS: Our results confirm previous studies that neonatal sevoflurane exposure causes neurodegeneration and long-term memory impairment in mice. However, sevoflurane did not induce autism-like features. Our study suggests that mice are more vulnerable to long-term memory deficits than autism-like behaviors after exposure to sevoflurane.

[Neonatal cleft lip repair: perioperative safety and surgical outcomes]. / Chirurgie néonatale des fentes labiales : sécurité anesthésique et résultats chirurgicaux.

INTRODUCTION: There is no international consensus on timing for surgical repair of cleft lip and palate. We argue that neonatal timing for repair of the lip deformity allows a better integration of the baby in his family and is of major support for the parents. Recent studies tend to challenge this neonatal practice. PATIENTS AND METHODS: We want to study retrospectively the perioperative safety and the surgical outcomes of this procedure over the past 20 years in a series of 42 non-selected babies who had labial repair during the first four weeks of their life. All of them have been operated by the same senior surgeon. RESULTS: Median operative time is 45 minutes for unilateral cleft and 70 minutes in case of bilateral malformation. Oral feeding is initiated at the end of the operative day. Children's hospital stay is four days. The results show no anaesthetic complication. Four children had secondary lip correction. CONCLUSION: The risk of anaesthetic and surgical interventions limited to the lip before the age of 28 days is very low in a medical care environment specialized in neonatal surgery and postoperative care. The over all complication rate is very low.

Fetal and Neonatal Anesthesia.

Anesthesia for fetal and neonatal surgery requires subspecialized knowledge and expertise. Attention to important anatomic, physiologic, and metabolic differences seen in pregnancy and at birth are essential for the optimal care of these patients. Thorough preoperative evaluations tailored intraoperative strategies and careful postoperative management are critical when devising the anesthetic approach for each of these cases.

Neurotoxic Impact of Individual Anesthetic Agents on the Developing Brain.

Concerns about the safety of anesthetic agents in children arose after animal studies revealed disruptions in neurodevelopment after exposure to commonly used anesthetic drugs. These animal studies revealed that volatile inhalational agents, propofol, ketamine, and thiopental may have detrimental effects on neurodevelopment and cognitive function, but dexmedetomidine and xenon have been shown to have neuroprotective properties. The neurocognitive effects of benzodiazepines have not been extensively studied, so their effects on neurodevelopment are undetermined. However, experimental animal models may not truly represent the pathophysiological processes in children. Multiple landmark studies, including the MASK, PANDA, and GAS studies have provided reassurance that brief exposure to anesthesia is not associated with adverse neurocognitive outcomes in infants and children, regardless of the type of anesthetic agent used.

Anesthetic Management of a Neonate with Coarctation of the Aorta and Duct-Dependent Circulation Posted for Tracheoesophageal Fistula Repair.

Coarctation of the aorta (CoA) is a congenital heart disease found in a newborn with an incidence of 6%. It presents a significant clinical challenge in neonates posted for major surgeries like tracheoesophageal fistula (TEF) repair. We report the case of anesthetic management of a 2-day-old infant with CoA and duct-dependent circulation posted for TEF repair. We describe how physiology affects its perioperative management and the role of maintaining balance in peripheral vascular resistance and systemic vascular resistance to maintain ductal flow.

Roles of Testosterone and Estradiol in Mediation of Acute Neuroendocrine and Electroencephalographic Effects of Sevoflurane During the Sensitive Period in Rats.

Testosterone (T), predominantly acting through its derivative 17ß-estradiol (E2), regulates the brain's sexual differentiation in rodents during the perinatal sensitive period, which mirrors the window of vulnerability to the adverse effects of general anesthetics. The mechanisms of anesthesia's adverse effects are poorly understood. We investigated whether sevoflurane alters T and E2 levels and whether they contribute to sevoflurane's acute adverse effects in postnatal day 5 Sprague-Dawley rats. The rats underwent electroencephalography recordings for 2 h of baseline activity or for 1 h before and another hour during 2.1% sevoflurane exposure, followed by collection of trunk blood and brain tissue. Pharmacological agents, including the GABA type A receptor inhibitor bicuculline and the aromatase inhibitor formestane, were administered 30 min before sevoflurane anesthesia. Sevoflurane increased serum T levels in males only. All other effects of sevoflurane were similar in both sexes, including increases in serum levels of E2, hypothalamic mRNA levels of aromatase, estrogen receptor α (Erα) [not estrogen receptor ß (Erß)], Na+-K+-Cl- cotransporter (Nkcc1)/K+-Cl- cotransporter (Kcc2) mRNA ratio, electroencephalography-detectable seizures, and stress-like corticosterone secretion. Bicuculline and formestane alleviated these effects, except the T level increases. The ERα antagonist MPP, but not the ERß antagonist PHTPP, reduced electroencephalography-detectable seizures and normalized the Nkcc1/Kcc2 mRNA ratio. Collectively, sevoflurane exacerbates levels of T in males and E2 in both sexes during the period of their organizational effects in rodents. Sevoflurane acts through GABAAR-mediated, systemic T-independent elevation of E2 to cause electroencephalography-detectable seizures, stress-like corticosterone secretion, and changes in the expression of genes critical for brain development.

Postoperative Analgesia in Neonates and Infants Using Epidural Chloroprocaine and Clonidine.

INTRODUCTION: In neonates and infants, epidural analgesia has gained popularity as a means of providing postoperative analgesia, limiting opioid-related adverse effects and improving the postoperative course. In addition to a local anesthetic agent, adjunctive agents may be added to further augment analgesia. Clonidine is an α2-adrenergic agonist that is frequently added to single-shot caudal analgesia, but there are limited data regarding its use in a continuous epidural infusion, especially in patients ≤12 months of age. METHODS: We retrospectively reviewed the hospital records of neonates and infants who received postoperative epidural infusions with 2-chloroprocaine, and clonidine was identified over a 4-year period. RESULTS: The study cohort included 52 neonates and infants ranging in age from 0 to 12 months and in weight from 2.1 to 10.1 kilograms. The catheters were dosed with either 1.5% 2-chloroprocaine (n=47) or 3% 2-chloroprocaine (n=5) with clonidine (median concentration 0.2 µg/mL) infused at a median rate of 0.72 mL/kg/hour. Pain scores were uniformly ≤3 at all evaluation points during the first 72 postoperative hours with a limited need for supplemental systemic opioids. No serious adverse effects were noted. CONCLUSION: With the recognized limitations of a retrospective study, these preliminary data demonstrate the safety of adding clonidine to an epidural infusion of 2-chloroprocaine in neonates and infants less than 12 months of age. Future studies are needed to determine its analgesic efficacy compared to 2-chloroprocaine alone and the optimal clonidine concentration for postoperative epidural infusions.

Neonatal exposure to sevoflurane expands the window of vulnerability to adverse effects of subsequent exposure to sevoflurane and alters hippocampal morphology via decitabine-sensitive mechanisms.

BACKGROUND: Deficiencies in neurocognitive function have been found in late childhood or adolescence in patients who had prolonged and/or repeated early-life general anesthesia. Animal studies suggest that anesthetic-induced impairment in the neuron-specific K+-2Cl- (Kcc2) Cl- exporter expression, which regulates developmental maturation of GABA type A receptor (GABAAR) signaling from excitatory to inhibitory, may play a mediating role. We tested whether the DNA methyltransferase (DNMT) inhibitor decitabine ameliorates the anesthetic's adverse effects. METHODS: Sprague-Dawley male rats were injected with vehicle or decitabine 30 min before 2.1 % sevoflurane exposure for 5 h on postnatal day 5 (P5). On P19, P20, or P21, electroencephalography-detectable seizures were measured during 1 h of sevoflurane exposure, followed by collection of the trunk blood and brain tissue samples. Other rats were evaluated for changes in hippocampal CA1 dendrite morphology and gene expressions on ≥ P120. RESULTS: Rats in the vehicle plus sevoflurane group responded to sevoflurane exposure on P19, P20 or P21 with electroencephalography-detectable seizures and stress-like corticosterone secretion and had altered hippocampal dendrite morphology in adulthood. These rats had expressions of Kcc2 and Dnmt genes downregulated and upregulated, respectively, in the P19 - P21 cortex and hypothalamus and the ≥ P120 hippocampus. All measured parameters in the sevoflurane-exposed rats that were pretreated with decitabine were not different from those in the control group. CONCLUSIONS: Neonatal exposure to sevoflurane sensitizes rats to adverse effects of repeated exposure to the anesthetic. The anesthetic-caused changes in the decitabine-sensitive mechanisms may play a mediating role in the developmental effects of early-life anesthesia.

Anesthesia for Major Surgery in the Neonate.

Perioperative risk of morbidity and mortality for neonates is significantly higher than that for older children and adults. At particular risk are neonates born prematurely, neonates with major or severe congenital heart disease, and neonates with pulmonary hypertension. Presently no consensus exists regarding the safest anesthetic regimen for neonates. Regional anesthesia appears to be safe, but does not reduce the overall risk of postoperative apnea. Former preterm infants require postoperative observation for apnea. The anesthesiologist caring for the neonate for major surgery should be knowledgeable of the unique physiology of the neonate and maintain the highest level of vigilance throughout.

Anesthesia Neurotoxicity in the Developing Brain: Basic Studies Relevant for Neonatal or Perinatal Medicine.

Diagnostic and invasive procedures in premature infants may require general anesthesia. General anesthetics interfere with the development of the immature animal brain. Accelerated apoptosis, disturbed synaptogenesis, and cytoarchitecture are among the mechanisms suspected to underlie this phenomenon. The implications for humans are unknown. This article presents current suspected mechanisms of anesthesia-induced neurotoxicity and elaborates on the difficulties in translating results from animal research to human. Ethical considerations limit the conduct of such experiments in human neonates, but the use of animal models is still considered feasible. Vulnerable periods in brain development need further identification as do neurotoxic and neuroprotective interventions.

Monitoring Cerebral and Renal Oxygenation Status during Neonatal Digestive Surgeries Using Near Infrared Spectroscopy.

BACKGROUND: Depending on the initial pathology, hypovolemia, intra-abdominal hypertension, and sepsis are often encountered in neonatal digestive surgery. Accurate newborn monitoring during and after surgery is essential to adapt resuscitation protocols. Near infrared spectroscopy (NIRS) is non-invasive and can detect hypoperfusion which indicates a low circulatory blood flow, regardless of the cause. OBJECTIVE: Evaluating changes in cerebral and renal regional oxygen saturation during neonatal digestive surgeries, conducted according to normal practices, with commonly used monitoring parameters. Analyzing retrospectively the inter-relationships between NIRS values and mean arterial pressure (MAP) values as well as pre-ductal SpO2. METHODS: Prospective, descriptive, monocentric study. All neonates referred for surgery were included. NIRS allows the measurement of cerebral and renal oxygenation fluctuations, as well as calculating difference in intraoperative and postoperative values. RESULTS: Nineteen patients were included. Cerebral regional oxygen saturation (C rSO2) values were stable while renal regional oxygen saturation (R rSO2) values tended to decrease with time during surgery. Indeed, 72% of rSO2 decline episodes occurred after the first 30 min of surgery, without any significant statistical differences for the next 90 min of surgery. After surgery, the lowest average C and R rSO2 values were evidenced during the first 6 h, with 60% of C rSO2 and R rSO2 anomalies occurring in that time frame. There was no significant statistical difference observed in the following 18 h. There was a significant correlation between R rSO2 and SpO2 values (p < 0.01), but not with C rSO2 values. There was no correlation with the MAP either for the C rSO2 values or R rSO2 ones. CONCLUSION: NIRS is a promising non-invasive bedside tool to monitor cerebral and tissue perfusion, analyzing tissue microcirculation. NIRS has its interest to guide neonatal digestive surgeries (bowel manipulation, viscera reduction) and may represent an early warning for identifying patients requiring resuscitation during or after these surgeries.

Acetaminophen for analgesia following pyloromyotomy: does the route of administration make a difference?

BACKGROUND: During the perioperative care of infants with hypertrophic pyloric stenosis, an opioid-sparing technique is often advocated due to concerns such as postoperative hypoventilation and apnea. Although the rectal administration of acetaminophen is commonly employed, an intravenous (IV) preparation is also currently available, but only limited data are available regarding IV acetaminophen use for infants undergoing pyloromyotomy. The objective of the current study was to compare the efficacy of IV and rectal acetaminophen for postoperative analgesia in infants undergoing laparoscopic pyloromyotomy. METHODS: A retrospective review of the use of IV and rectal acetaminophen in infants undergoing laparoscopic pyloromyotomy was performed. The efficacy was assessed by evaluating the perioperative need for supplemental analgesic agents, postoperative pain scores, tracheal extubation time, time in the postanesthesia care unit, time to oral feeding, and time to hospital discharge. RESULTS: The study cohort included 68 patients, of whom 34 patients received IV acetaminophen and 34 received rectal acetaminophen. All patients also received local infiltration of the surgical site with 0.25% bupivacaine. No intraoperative opioids were administered. There was no difference between the two groups with regard to postoperative pain scores, need for supplemental analgesic agents, time in the postanesthesia care unit, or time in the hospital. There was no difference in the number of children who tolerated oral feeds on the day of surgery or in postoperative complications. CONCLUSION: Our preliminary data suggest that there is no clinical difference or advantage with the use of IV versus rectal acetaminophen in infants undergoing laparoscopic pyloromyotomy.

Neonatal pain management.

The past 2-3 decades have seen dramatic changes in the approach to pain management in the neonate. These practices started with refuting previously held misconceptions regarding nociception in preterm infants. Although neonates were initially thought to have limited response to painful stimuli, it was demonstrated that the developmental immaturity of the central nervous system makes the neonate more likely to feel pain. It was further demonstrated that untreated pain can have long-lasting physiologic and neurodevelopmental consequences. These concerns have resulted in a significant emphasis on improving and optimizing the techniques of analgesia for neonates and infants. The following article will review techniques for pain assessment, prevention, and treatment in this population with a specific focus on acute pain related to medical and surgical conditions.