Neonatal Anesthesia Research Articles

Pre-clinical and clinical trials for anesthesia in neonates: gaps and future directions.

Literature examining possible deleterious effects of anesthesia exposure on the developing brain has increased substantially over the past 30years. Initial concerning findings in animal models, both rodents and non-human primates, prompted increasingly thorough examinations in humans, including randomized controlled trials. This review will provide a concise overview of what we know about anesthesia and the developing brain: the background in animal studies, the most robust results we have in humans, and the work yet to be done. This is particularly relevant to a pediatric radiology audience because we have the unique opportunity to modify anesthesia exposure during imaging through innovation.

Neonatal anesthesia with remimazolam Reduces the expression of synaptic proteins and increases depressive behavior in adult mice

The demand for pediatric anesthesia has risen in decades, raising concerns about the neurotoxic potential of anesthetics like remimazolam, which may impact neurodevelopment and later cognitive function. This study utilized a neonatal mouse model to assess remimazolam’s neurodevelopmental effects. Results indicate that remimazolam-exposed mice displayed cognitive impairment and depressive behaviors in adulthood. Acute reductions in synaptic protein expression post-anesthesia were observed, along with long-term decreases in hippocampal choline acetyltransferase levels, reduced dendritic spine density in the CA1 region, and microglial proliferation. Collectively, these findings suggest that remimazolam can induce neurotoxicity and neuroinflammation, leading to synaptic dysfunction and associated cognitive and behavioral deficits.

High-Dose Remifentanil Anesthesia With Minimal Sedation in Neonates: A Single-Center Retrospective Study.

Introduction Remifentanil is an opioid with rapid onset and elimination. Theoretically, reducing sedation using high-dose remifentanil may contribute to early emergence and prevention of postanesthetic complications related to residual anesthesia. However, there have been few reports of high-dose remifentanil anesthesia in neonatal surgery. This study aims to describe the techniques of high-dose remifentanil anesthesia in neonates and their safety outcomes. Methods This is a single-center, retrospective observational study from January 2016 to February 2022. Medical records from neonatal surgical procedures performed using high-dose remifentanil anesthesia were reviewed. "High dose" was defined as 0.5 mcg/kg/min or more. Patient profiles, anesthetic drugs used, and intra- and post-operative adverse events, including cardiopulmonary complications, were abstracted. Results There were 15 neonatal abdominal operations performed under high-dose (>0.5 mcg/kg/min) remifentanil anesthesia during the study period. The average remifentanil infusion rate was 1.9 (0.68-3.1) mcg/kg/min. Hypotension occurred in two patients (13%). Bradycardia was not observed in any patients. The mean time for tracheal extubation was 16 minutes. Five patients (33%) received naloxone administration before extubation, and two patients (13%) experienced hypoxemia immediately after extubation. No patient had cardiorespiratory complications after leaving the operating room. Conclusions High-dose remifentanil can be used without impairing hemodynamic stability in neonatal surgery, although there is concern about respiratory depression. Further research is needed on its potential impact on long-term outcomes.

Safety in Neonatal Anesthesia, a Major Concern

Safety in Neonatal Anesthesia, a Major Concern

Assessing the Safety and Efficacy of Spinal Anesthesia in Preterm and Term Neonates: A Multicenter Experience

Background: Worldwide, the incidence of premature birth is increasing with its attending congenital anomalies, so complex surgical interventions to manage these congenital anomalies or complications are usually performed at early days of life. Neonates are vulnerable to apnea, and congenital cardiopulmonary problems and they have higher morbidity and mortality compared to older children and adults etc. In the preterm neonate, the risk of bronchopulmonary dysplasia and apnoea make their management complex and this is further compounded by their smaller size. Objective of study: The aim of the study was to determine the safety and efficacy of spinal anesthesia among neonates. Methodology: The study is a prospective study conducted in three tertiary health Institutions in northeast Nigeria. It includes all neonates scheduled for surgery amenable under SA. Sociodemographic variables, Haemodynamic variables, duration of surgery, and complications observed were all recorded. Results: Spinal anaesthesia SA was done in 230 patients, 90% of the patients were term, and only 10% were preterm. The majority were male with a mean weight of 3002 ± 660 grams and a mean age of 14.51±7.28 days. SA was successful in 93% of the patients in the first attempt. Heart rate, mean arterial pressure and oxygen saturation remained stable all through the duration of surgery. About 6% of the patients were converted to General Anaesthesia GA on account of prolonged surgery. The highest level of sympathetic block was recorded at the level of T4 while the lowest was at T6. Herniotomy was the most common surgery performed. The surgery lasted an average of 72 ± 28 minutes. No complication was recorded. Conclusion: Spinal anaesthesia provides a safe and reliable option for neonates who may require surgery early in life to improve their chances of survival. It serves as an alternative to GA with enhanced haemodynamic stability in this fragile population.

Regional anesthesia in neonates with cleft lip and palate: Retrospective study

BackgroundOrofacial clefts are the most common congenital abnormalities. Cleft lip reconstruction is performed mostly in 3 months of life including the neonatal period. The consumption of opioids during anesthesia is one of the monitored parameters of anesthesia safety. We investigated the effect of using an infraorbital nerve block for reducing opioid consumption during cleft lip surgery in neonates. Patients/methodsOverall, 100 patients who underwent primary cleft lip surgery in neonatal age between 2018 and 2021 were included in the study. The primary outcome was to compare opioid requirements during cleft lip surgery with and without using regional anesthesia. Secondary outcomes included a first oral intake from surgery between neonates with and without regional anesthesia and complications rate of infraorbital nerve block. ResultsData from 100 patients (46 patients with and 64 without regional anesthesia) were retrospectively analyzed and classified into two groups according to whether regional anesthesia during neonatal cleft lip surgery had been performed or not. The use of infraorbital block was found to be positively correlated with lower doses of opioids used during the general anesthesia for the surgery (mean 0.48 μg/kg vs 0.29 μg/kg, p < 0.05). The postoperative course was evaluated based on the interval from surgery to first oral intake which was statistically insignificant shorter (p = 0.16) in the group of patients using regional anesthesia. No complications were recorded in the group of patients with regional anesthesia. ConclusionsRegional anesthesia is associated with reduced opioid consumption during anesthesia thereby increasing the safety of anesthesia in neonates. Clinicaltrials.gov identifierNCT06067854https://clinicaltrials.gov/study/NCT06067854?cond=NCT06067854&rank=1.

Outcomes after surgery for children in Africa (ASOS-Paeds): a 14-day prospective observational cohort study

Safe anaesthesia and surgery are a public health imperative. There are few data describing outcomes for children undergoing anaesthesia and surgery in Africa. We aimed to get robust epidemiological data to describe patient care and outcomes for children undergoing anaesthesia and surgery in hospitals in Africa. This study was a 14-day, international, prospective, observational cohort study of children (aged <18 years) undergoing surgery in Africa. We recruited as many hospitals as possible across all levels of care (first, second, and third) providing surgical treatment. Each hospital recruited all eligible children for a 14-day period commencing on the date chosen by each participating hospital within the study recruitment period from Jan 15 to Dec 23, 2022. Data were collected prospectively for consecutive patients on paper case record forms. The primary outcome was in-hospital postoperative complications within 30 days of surgery and the secondary outcome was in-hospital mortality within 30 days after surgery. We also collected hospital-level data describing equipment, facilities, and protocols available. This study is registered with ClinicalTrials.gov, NCT05061407. We recruited 8625 children from 249 hospitals in 31 African countries. The mean age was 6·1 (SD 4·9) years, with 5675 (66·0%) of 8600 children being male. Most children (6110 [71·2%] of 8579 patients) were from category 1 of the American Society of Anesthesiologists Physical Status score undergoing elective surgery (5325 [61·9%] of 8604 patients). Postoperative complications occurred in 1532 (18·0%) of 8515 children, predominated by infections (971 [11·4%] of 8538 children). Deaths occurred in 199 (2·3%) of 8596 patients, 169 (84·9%) of 199 patients following emergency surgeries. Deaths following postoperative complications occurred in 166 (10·8%) of 1530 complications. Operating rooms were reported as safe for anaesthesia and surgery for neonates (121 [54·3%] of 223 hospitals), infants (147 [65·9%] of 223 hospitals), and children younger than 6 years (188 [84·3%] of 223 hospitals). Outcomes following anaesthesia and surgery for children in Africa are poor, with complication rates up to four-fold higher (18% vs 4·4-14%) and mortality rates 11-fold higher than high-income countries in a crude, unadjusted comparison (23·15 deaths vs 2·18 deaths per 1000 children). To improve surgical outcomes for children in Africa, we need health system strengthening, provision of safe environments for anaesthesia and surgery, and strategies to address the high rate of failure to rescue. Jan Pretorius Research Fund of the South African Society of Anaesthesiologists and Association of Anesthesiologists of Uganda.

Ethics in Neonatal Anesthesia – A Tender Perioperative Care

Medical ethics, a set of norms and values applied to the behavior of medical care personnel, has been evolving along with the scientific and technical development in the field of neonatology, surgery, and anesthesia. Regarding the anesthetic management of a neonate, an anesthesiologist is always in an ethical dilemma. On one side, anesthesia is a necessity for surgery, and on the other hand, knowing that these interventions may have untoward or adverse effects. Autonomy, nonmaleficence, beneficence, and justice are the four basic principles of medical ethics, which are used in harmony with each other without any order of succession and along with virtues of compassion, integrity, honesty, truthfulness, and fairness provides an ethical decision-making framework for a tender perioperative care. Professionalism in the operating room and anesthesiologist – surgeon relationship is an integral part of the ethical concerns in neonatal anesthesia.

Filar cyst on lumbar sonography prior to neonatal spinal anaesthesia

Filar cyst on lumbar sonography prior to neonatal spinal anaesthesia

Successful Awake Caudal Anesthesia for Incarcerated Inguinal Hernia Repair in an Ex-Premature Baby at 8 Weeks of Age.

Introduction: Caudal anesthesia is a standard procedure in pediatric anesthesia because of its excellent safety and success rate. Usually, it is administered after general anesthesia, but in selected neonatal populations, awake caudal anesthesia is a method of choice.&#x0D; Prematurely born, low birth weight neonates are more prone to complications from general anesthesia than term neonates, even after simple surgery. Among these complications, post-operative apnea is the most common.&#x0D; Caudal epidural anesthesia in awake neonates is a recognized technique that enables the avoidance of general anesthesia and the complications associated with it. In skilled hands, it is also theoretically easier to perform consistent caudal anesthesia than an awake subarachnoid block. In our case, we report a successful awake caudal anesthesia in an ex-premature baby in the emergency setting for incarcerated inguinal hernia repair.&#x0D; To our knowledge, this case report on this topic has yet to be published in Armenia.&#x0D; Conclusion: Neuraxial (spinal, epidural, caudal) awake anesthesia is the method of choice for lower abdominal surgery in preterm infants. Both spinal and caudal anesthesia are effective methods; awake caudal anesthesia is a method of choice because of the success rate and lower analgesic requirements in the post-operative period.&#x0D; &#x0D;

Acute Effects of Hypothermia and Inhalant Anesthesia on Ultrasonic Vocalizations and Neuroendocrine Markers in Neonatal Rats.

Neonatal rodents undergo anesthesia for numerous procedures and for euthanasia by anesthetic overdose. However, data regarding whether neonatal anesthesia is humane are limited. Hypothermia (cryoanesthesia) is the most commonly used anesthetic protocol for neonatal rats 10 d of age or younger. However, hypothermia has recently been restricted in several countries due to perceived painful effects, including pain on rewarming. Minimizing the potential pain and distress of neonates in research is imperative, although very challenging. Traditional validated and nonvalidated behavioral and physiologic outcome measures used for adult rats undergoing anesthesia are unsuitable for evaluating neonates. Therefore, we investigated the effects of several anesthetic methods on neonatal rats by using the innovative objective approaches of noninvasive ultrasonic vocalizations and more invasive neuroendocrine responses (i. e., serum corticosterone, norepinephrine, glucose). Our results show that hypothermia leads to heightened acute distress in neonatal rats as indicated by prolonged recovery times, increased duration of vocalizations, and elevated corticosterone levels, as compared with neonates undergoing inhalational anesthesia. We demonstrate that inhalational anesthesia is preferable to cryoanesthesia for neonatal rats, and researchers using hypothermia anesthesia should consider using inhalational anesthesia as an alternative method.

Regional Anesthesia for Neonates.

Pain management in neonates and infants has many unique and important facets, particularly in former preterm infants. Untreated pain and surgical stress in neonates are associated with myriad negative sequelae, including deleterious inflammatory, autonomic, hormonal, metabolic, and neurologic effects. Meanwhile, opioid side effects are also very impactful and affect multiple systems and pathways, particularly in the neonatal and infant population. Regional anesthesia presents a unique opportunity to provide highly effective analgesia; prevent deleterious signaling cascade pathways within the endocrine, immune, and nervous systems from occurring; and create conditions to facilitate reduced reliance on opioids and other analgesics. In some cases, clinicians can completely avoid general anesthesia and systemic anesthetics. This review will discuss some of the unique aspects of pain management in neonates and infants and provide an overview of the different regional anesthetic options available, namely, spinal anesthesia, epidural anesthesia, and peripheral nerve blocks.

Effect of neuromuscular block on surgical conditions during laparoscopic surgery in neonates and small infants: A randomised controlled trial.

Neuromuscular block (NMB) is routinely used in paediatric and adult anaesthesia to facilitate endotracheal intubation and optimise surgical conditions. However, there are limited data regarding NMB and optimising the conditions for laparoscopic surgery in neonates and small infants. The goal of this study was to determine the effect of NMB on the conditions for laparoscopic surgery in neonates and small infants. A randomised controlled trial. Single-centre Children's Hospital, conducted from November 2021 to December 2022. One hundred and two ASA I-II neonates and small infants aged up to 60 weeks postmenstrual age who were scheduled to undergo an elective laparoscopic Ladd's procedure were included in the study. Patients were randomised into three groups: no NMB group, shallow NMB group and moderate NMB group. Each group was given different doses of rocuronium to achieve the target depth of NMB. The primary outcome was the quality of the surgical conditions evaluated with the Leiden-Surgical Rating Scale (L-SRS) by a blinded surgeon. Secondary outcomes included tracheal intubating conditions and adverse events. The percentage of L-SRS scores of 4 or 5 was similar among the three groups at all the assessment times (P > 0.05 for each time interval). The distribution of L-SRS scores was also similar among the three groups. There were no significant differences in operating condition scores between the groups at any time interval (P > 0.05 for each time interval). The incidence of adverse events during anaesthesia induction was significantly higher in the no NMB group (51.4%) than in the other two groups (13.6% and 14.7%) (adjusted P = 0.012 and adjusted P = 0.003). In particular, clinically unacceptable intubation conditions occurred in 12 patients (34.3%) in the no NMB group, significantly more than in the shallow NMB group (6.1%, adjusted P = 0.012) and moderate NMB group (2.9%, adjusted P = 0.003). There was no statistically significant difference in the incidence of adverse events in the PACU among the three groups (P = 0.103). The depth of NMB was not associated with superior surgical conditions during laparoscopic surgery, but it was associated with a reduction in adverse events during induction and maintenance of anaesthesia in neonates and small infants. Registered at www.chictr.org.cn (ChiCTR2100052296).

Propofol and thiopental for intravenous induction in neonates: study protocol for a dose-finding trial.

Propofol and thiopental are commonly used induction agents in neonatal anesthesia. Even though both hypnotics have been used off-label for many years, pharmacological knowledge regarding these agents is scarce in neonates. The significant variability in neonates' body composition, organ function, and maturation makes pharmacological studies highly relevant albeit challenging. As a result, there is currently limited data about the anesthetic induction dose of thiopental and propofol in neonates. In addition, a knowledge gap exists concerning the pharmacodynamics of induction doses. To determine the median effective anesthetic induction dose of propofol and thiopental in neonatal patients of different gestational and postnatal ages and evaluate the pharmacodynamics of the anesthesia induction doses on the neonatal systemic and cerebral hemodynamics. This is a single-center, prospective, open-label, interventional, dose-finding study, including neonatal patients from birth up to 28 postnatal days undergoing general anesthesia for surgical or diagnostic procedures. The patients will be stratified according to their gestational and postnatal age and allocated to one of the two trial arms: anesthesia induction with propofol or anesthesia induction with thiopental. We will use Dixon's up-and-down method to estimate the median effective anesthesia induction dose of both agents in neonates of different gestational and postnatal ages. In addition, we will study the relationship between anesthesia induction doses and changes in systemic and cerebral hemodynamics. Alterations in the systemic and cerebral regional hemodynamics secondary to anesthesia induction may be harmful in neonates, especially premature and critically ill newborns, due to their immature organ systems, reduced physiological reserves, and impaired cerebral autoregulation. Perfusion homeostasis is considered one of the significant and modifiable determinants of anesthesia-related neurocognitive outcomes. Therefore, dose-finding and safety pharmacological studies of the anesthetic induction agents in neonates are urgently needed and acknowledged as a high priority by the European Medicine Agency. Estimating adequate induction doses to ensure optimal depth of anesthesia while avoiding systemic and cerebral hemodynamic disturbances will help ensure safe anesthesia and potentially improve anesthesia-related outcomes in this group of patients. This article is protected by copyright. All rights reserved.

Morbidity and mortality after anesthesia in early life in Italy. A subgroup analysis of the NECTARINE Trial.

Recent literature on neonatal anesthesia focuses on the importance of keeping physiology within the ranges of normality to improve the long-term neurological outcome. The Neonate and Children audit of Anesthesia pRactice IN Europe (NECTARINE) showed a derangement of one or more than one physiological parameters during anesthesia needing a medical intervention in 35.2% of 6592 anesthesia procedure performed in infants up to 60 weeks postmenstrual age. Subanalysis of the Italian NECTARINE cohort providing a snapshot of anesthesia management, incidence of clinical events requiring intervention during anesthesia, and morbidity and mortality at 30 and 90 days. Secondary aim was to compare outcomes between Italy and Europe. Twenty-three Italian centers recruited 501 patients (63% male, 37% female) undergoing 611 procedures (441 surgical and 170 non-surgical) with a mean gestational age at birth of 38 weeks. Events requiring a medical intervention during anesthesia occurred in 177 cases (28.9%), lower than those reported in Europe (35.3%). The majority of events concerned episodes of cardiovascular instability, most commonly due to hypotension. The incidence of mortality at 30 days was 2.7%, consistent with the European incidence. Anesthetizing neonates is challenging. It is crucial that neonatal anesthesia practice is performed in specialized centers to maximize the potential positive outcome. We recommend a certification of quality for Institutions providing care for very young patients.

Prolonged Anesthesia Induction to Delivery Time Did Not Influence Plasma Remifentanil Concentration in Neonates.

Remifentanil, in combination with etomidate and sevoflurane, is commonly used in clinics for general anesthesia induction in cesarean section (CS). This study aimed to evaluate the correlation between the induction to delivery (I-D) time and neonatal plasma drug concentration and anesthesia, as well as its effects on neonates. Fifty-two parturients in whom general anesthesia was induced for CS were divided into group A (I-D<8 min) and group B (I-D≥8 min). Maternal arterial (MA), umbilical venous (UV), and umbilical arterial (UA) blood samples were collected at delivery to analyze the remifentanil and etomidate concentrations using liquid chromatography-tandem mass spectrometry. There were no statistically significant differences between the two groups in terms of plasma concentrations of remifentanil in the MA, UA, and UV blood (P > 0.05). The plasma concentration of etomidate in MA and UV was higher in group A than that in group B (P<0.05), whereas the UA/UV ratio of etomidate was higher in group B than that in group A (P<0.05). The Spearman rank correlation test showed no correlation between the I-D time and plasma remifentanil concentration in the MA, UA, and UV plasma (P>0.05). The concentrations of etomidate in the MA and UV were negatively correlated with the I-D time (P < 0.05). Prolonged I-D time did not significantly influence the maternal or neonatal plasma concentration of remifentanil. It is safe to administer remifentanil target-controlled infusion in combination with etomidate and sevoflurane for general anesthesia induction during CS.

SHANK2 protein contributes to sevoflurane-induced developmental neurotoxicity and cognitive dysfunction in C57BL/6 male mice

PurposeRepeated exposures to sevoflurane could induce epigenetic modifications in specific brain regions and cognitive impairments in the immature mice. Conflicting findings make neurobehavioral manifestations intricate and potential mechanisms elusive. Influence of neonatal anesthesia with sevoflurane on the expression of synaptic scaffold proteins and neuronal activity remains to be determined.MethodsC57BL/6 male and female mice in breeding ages were used to produce next generation. The offspring male mice were randomly scheduled to receive 3.0% sevoflurane plus 60% oxygen for 2 h daily at postnatal day (P) 6–8. Three-chambered social paradigm was used to test social affiliation and social memory. Morris water maze was used to test learning and memory. Whole genome bisulfite sequencing (WGBS), differentially methylated regions (DMRs) and KEGG enrichment analysis were performed to screen target gene in sequence context of CG. RT-PCR and immunoblotting analysis were used to assess expression of the Shank gene family, as well as DNA methylases.ResultsThe male mice undergoing sevoflurane anesthesia at P6-8 showed diminished preference for novel conspecific and prolonged escape latency and decreased platform-crossing times. The sevoflurane-exposed mice showed reduced mRNA and protein levels of the Shank2 gene. KEGG analysis disclosed the role of DNA hypermethylation of Shank2 gene in the pathway of glutamatergic synapse. In addition, sevoflurane anesthesia reduced mRNA and protein levels of the TET3 enzyme.ConclusionRepeated exposures to sevoflurane in neonatal period could impair social recognition memory and spatial reference memory in the male mice. Reduction of hippocampal SHANK2 protein could contribute to sevoflurane-induced neurotoxicity in the immature mice. Reduction of the TET3 enzyme should be responsible for DNA hypermethylation-related silencing of the Shank2 gene.Graphical

Social determinants for health and neonatal anesthesia in Colombia

The social determinants of health are the social characteristics in which people's lives and work develop, giving them the capacity to act in specific contexts and are responsible for the health conditions of individuals and populations.&#x0D; Recent World Bank data show that Colombia has made modest progress in terms of social equity. These data reveal that neonatal mortality in remote areas of the country is similar to that found in Sub-Saharan Africa. In these regions, there is no access to specialized neonatal health services. As for anesthesia services, this age group has the highest mortality and perioperative complication rates related to prematurity, the quality of health services and, especially, the expertise of the anesthesiologist.&#x0D; In Colombia, efforts to implement formal university programs for sub-specialization in pediatric anesthesiology have not received governmental support. Meanwhile, the Colombian Society of Anesthesiology, through its Committee of Pediatric Anesthesiology, has created ongoing education opportunities, which, although important, are insufficient to meet the needs of the country.&#x0D; For this reason, a State policy is required, aimed at meeting its social debt and that considers the specialized training of human resources as a pillar for the promotion of equity in health, so that the surgical neonate does not have to travel in the procurement of services, but rather have the State bring those services to them.

The Comparison between Spinal Anesthesia Bupivacaine and Sevoflurane Anesthesia for Cesarean Section on Apgar Score

The use of the anesthetic technique for cesarean section is still debatable because of the side effects caused by anesthesia for mothers and neonates. The succeed to determine anesthetic technique can be seen from the outcome of the final condition of the mother and the neonates. The assessment of the succeed to determine anesthetic technique in neonates has been using the Apgar score by assessing the clinical status of the newborn in the first and fifth minutes. This research is aimed to understand the comparison between Apgar scores in cesarean section using general anesthesia sevoflurane and spinal anesthesia bupivacaine. This research is analytical retrospective with a cross-sectional study approach, using a total sample of 40 patients who performed cesarean section from August to November 2021, the samples were taken by consecutive sampling. The data was taken from the medical records of the Melinda Mother and Child Hospital, Bandung. The results of this research showed that there was no significant difference in the APGAR Score first minute between general anesthesia and spinal anesthesia (p=0,054) in the fifth minute (p=0,708). There was no effect on APGAR scores in the general anesthesia sevoflurane group and spinal anesthesia bupivacaine group, and both anesthetic groups had a good effect on neonates

Endoplasmic Reticulum Stress-Activated Neuronal and Microglial Autophagy Contributes to Postoperative Cognitive Dysfunction in Neonatal rats.

Surgery and anesthesia in neonates may lead to cognitive impairment or abnormal behaviors. It has been shown that autophagy plays a critical role in neuropsychiatric disorders, while the role of autophagy in postoperative cognitive impairment in neonates is not known. Here, we determined this role and the involvement of endoplasmic reticulum (ER) stress in regulating brain cell autophagy after surgery. Seven-day old neonatal rats (P7) had right common carotid artery exposure under anesthesia with 3% sevoflurane for 2h. Learning and memory were tested using Barnes maze (BM) and fear conditioning (FC) on P31-42 and P42-44, respectively. In another experiment, rat brains were harvested for biochemical studies. The ratio of microtubule-associated protein 1 light chain 3 (LC3) BII/I was increased and sequestosome 1 (P62/SQSTM1) levels were decreased in the brain 24h after surgery and anesthesia in neonatal rats. Immunofluorescent staining of LC3B was co-localized with a neuronal or a microglial marker but was not co-localized with a marker for astrocytes in rats with surgery. These rats had a poorer performance in the BM and FC tests than control rats when they were adolescent. Pretreatment with an autophagy inhibitor, 3-methyladenine, attenuated the poor performance. Surgery and anesthesia increased the expression of 78kDa glucose-regulated protein (BIP/GRP78), an indicator of ER stress, 6h after surgery and anesthesia. The ER stress activator tunicamycin and inhibitor tauroursodeoxycholic acid increased the markers for autophagy in control rats and decreased the autophagy markers in rats with surgery, respectively. Our results suggest that surgery in neonatal rats induces ER stress that then activates neuronal and microglial autophagy, which contributes to learning and memory impairment later in life.