Outcome following anaesthesia in infancy in the Nordic countries: Subgroup analysis of the NECTARINE study.

INTRODUCTION: The neonate and children audit of anaesthesia practice in Europe (NECTARINE) prospective observational study reported an incidence of 35.2% of critical events requiring intervention during 6542 anaesthetics in 5609 infants up to 60 weeks postmenstrual age (PMA) from 165 centres in 31 European countries. METHODS: Sub-analysis of the cohort from the Nordic countries (8% of the entire cohort) was conducted. Secondary aims were to describe the Nordic countries' anaesthetic practices and compare morbidity and mortality with the overall European cohort. RESULTS: Eleven Nordic centres recruited 447 infants (66% males, 37.3% born preterm and 45% had congenital anomalies) undergoing anaesthesia for 530 surgical or non-surgical procedures at 25-60 weeks PMA. Perioperative critical events triggered interventions in 228/530 (43%) cases. Hypotension (12.6%) or hypoxaemia (11.7%) were more common in younger patients and those with co-morbidities. Hypo/hypercapnia occurred in 1.5%/4.7% of cases. More than two attempts for intubation were required in 13 (2.9%) infants (max three attempts). Distribution of ASA-Physical Status Scores was similar to the total European cohort (40% was ASA > 2). A total of 236/530 (44.5%) patients were admitted to the postoperative intensive care unit. Thirty-day morbidity (complications in 87/447 = 19.5%) and mortality (8/447, 1.8%) did not differ from the overall European cohort. Hospital re-admissions were significant up to 90 days (98/447 = 21.9%). CONCLUSIONS: In Nordic countries, anaesthesia in young infant children is resource-demanding, and perioperative critical events and co-morbidities are common. Thirty-day morbidity and mortality data in the Nordic countries did not differ from the overall European cohort.

Neonates undergoing pyloric stenosis repair are at increased risk of difficult airway management: secondary analysis of the NEonate and Children audiT of Anaesthesia pRactice IN Europe.

BACKGROUND: Hypertrophic pyloric stenosis in otherwise healthy neonates frequently requires urgent surgical procedure but anaesthesia care may result in respiratory complications, such as hypoxaemia, pulmonary aspiration of gastric contents, and postoperative apnoea. The primary aim was to study whether or not the incidence of difficult airway management and of hypoxaemia in neonates undergoing pyloric stenosis repair was higher than that in neonates undergoing other surgeries. METHODS: Data on neonates and infants undergoing anaesthesia and surgery for pyloric stenosis were extracted from the NEonate and Children audiT of Anesthesia pRactice In Europe (NECTARINE) database, for secondary analysis. RESULTS: We identified 310 infants who had anaesthesia for surgery for pyloric stenosis. Difficult airway management (more than two attempts at laryngoscopy) was higher in children with pyloric stenosis when compared with the entire NECTARINE cohort (7.9% [95% confidence interval {CI}, 5.22-11.53] vs 4.4% [95% CI, 1.99-6.58]; relative risk [RR]=1.81 [95% CI, 1.21-2.69]; P=0.004), whereas transient hypoxaemia with oxygen saturation <90% was comparable between the two cohorts. Postoperative complications occurred in 16 children (5.6%) within the 30-day follow-up. No mortality was reported at 30 and 90 days. CONCLUSIONS: Children undergoing surgery for pyloric stenosis had a higher incidence of difficult intubation compared with the entire NECTARINE cohort. CLINICAL TRIAL REGISTRATION: NCT02350348.

Emergence agitation in paediatric day case surgery: A randomised, single-blinded study comparing narcotrend and heart rate variability with standard monitoring.

BACKGROUND: Postoperative emergence agitation remains a significant challenge in paediatric anaesthesia. Although short-lived, it may cause harm to the patient and negative experiences for all. Differentiating agitation, delirium and pain is difficult. Electroencephalography allows precise titration of anaesthetic depth, and heart rate variability monitoring permits immediate intervention regarding nociception and pain. We examined if one of these measures could be used to reduce postoperative agitation in an unselected paediatric day surgical population. OBJECTIVE: The primary outcome was postoperative agitation with a Richmond Agitation-Sedation Scale greater than 0. Secondary outcomes were: length of stay, postoperative nausea and vomiting, fentanyl and propofol consumption, pain scores and use of postoperative analgesics. DESIGN: A randomised, single-blinded study constituting children aged 1 to 6 years, undergoing minor general day surgical procedures. SETTING: Paediatric day surgical department 29th March 2019 to 12th June 2020. PATIENTS: Ninety-eight children (ASA 1 or 2) were enrolled, and 93 children were included in the final analysis. INTERVENTIONS: Children received standard monitoring (n=31), standard monitoring plus either Narcotrend (n=31), or Anaesthesia Nociception Index monitoring (n=31). Sevoflurane or fentanyl was titrated immediately according to monitor thresholds. RESULTS: Kaplan-Meier analysis yielded a statistically significant difference between the groups (P = 0.016) with the lowest agitation levels in the Anaesthesia Nociception Index group, intermediate levels in the control group and the highest agitation levels in the Narcotrend monitored group. Intergroup pairwise comparison however, showed no difference. The Anaesthesia Nocioception Index group received slightly more fentanyl (P = 0.277). The control group patients had the highest pain scores despite receiving more caudal blocks and the Narcotrend group had more sevoflurane adjustments. Other secondary outcomes were comparable. CONCLUSION: Children in the Anaesthesia Nociception Index group were the least agitated with the highest fentanyl doses, without increasing the length of stay in the PACU or postoperative nausea and vomiting. CLINICAL REGISTRATION: The study was registered in REDCap online trial database 1/11/2018 trial registration nr. OP720. https://open.rsyd.dk/OpenProjects/openProject.jsp?openNo=720&lang=da.

[Preoperative risk assessment of patients with congenital heart disease in non-cardiac surgery].

Over the last decades, remarkable advances in survival in patients with congenital heart disease (CHD) have been reported. Currently, 90% of infants born with CHD can expect to reach adulthood. Moderate and severe CHD is associated with increased perioperative mortality. To ensure optimal management of CHD patients undergoing non-cardiac surgery, preoperative risk assessment is pivotal, along with a multidisciplinary approach and collaboration across hospitals. The objective of this review is to provide a simple model to identify CHD patients at risk prior to non-cardiac surgery.

Morbidity and mortality after anaesthesia in early life: results of the European prospective multicentre observational study, neonate and children audit of anaesthesia practice in Europe (NECTARINE).

BACKGROUND: Neonates and infants requiring anaesthesia are at risk of physiological instability and complications, but triggers for peri-anaesthetic interventions and associations with subsequent outcome are unknown. METHODS: This prospective, observational study recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. The primary aim was to identify thresholds of pre-determined physiological variables that triggered a medical intervention. The secondary aims were to evaluate morbidities, mortality at 30 and 90 days, or both, and associations with critical events. RESULTS: Infants (n=5609) born at mean (standard deviation [sd]) 36.2 (4.4) weeks postmenstrual age (35.7% preterm) underwent 6542 procedures within 63 (48) days of birth. Critical event(s) requiring intervention occurred in 35.2% of cases, mainly hypotension (>30% decrease in blood pressure) or reduced oxygenation (SpO2 <85%). Postmenstrual age influenced the incidence and thresholds for intervention. Risk of critical events was increased by prior neonatal medical conditions, congenital anomalies, or both (relative risk [RR]=1.16; 95% confidence interval [CI], 1.04-1.28) and in those requiring preoperative intensive support (RR=1.27; 95% CI, 1.15-1.41). Additional complications occurred in 16.3% of patients by 30 days, and overall 90-day mortality was 3.2% (95% CI, 2.7-3.7%). Co-occurrence of intraoperative hypotension, hypoxaemia, and anaemia was associated with increased risk of morbidity (RR=3.56; 95% CI, 1.64-7.71) and mortality (RR=19.80; 95% CI, 5.87-66.7). CONCLUSIONS: Variability in physiological thresholds that triggered an intervention, and the impact of poor tissue oxygenation on patient's outcome, highlight the need for more standardised perioperative management guidelines for neonates and infants. CLINICAL TRIAL REGISTRATION: NCT02350348.

The Use of Tablet Computers to Reduce Preoperative Anxiety in Children Before Anesthesia: A Randomized Controlled Study.

PURPOSE: Children undergoing surgery and general anesthesia often experience preoperative anxiety (POA) with related negative short-, medium- and long-term consequences. Anxiolytic premedication has negative side effects, and nonpharmacologic interventions are often resource demanding and not always readily available in a busy clinical setting. The use of an age-appropriate game on a tablet computer may reduce POA, postoperative pain, and occurrence of emergence delirium (ED). DESIGN: Children aged 3 to 6 years scheduled to undergo elective minor surgery were randomly assigned to play a game on a tablet computer while in the holding area before anesthesia (n = 30) or prepared as per departmental standard only (n = 30). METHODS: POA, ED, and levels of pain were assessed by the modified Yale Preoperative Anxiety Scale, Pediatric Anesthesia Emergence Delirium, and Face, Legs, Activity, Cry, Consolability scale, respectively. FINDINGS: A total of 60 children were randomized to either the intervention group or the control group. Gender, bodyweight, duration of anesthesia and surgery, and fentanyl dosages were comparable between the two groups. Tablet-gaming children tended to be less anxious than control subjects at the time of anesthesia induction (modified Yale Preoperative Anxiety Scale, 55.7 vs 65.8; 95% confidence interval, -0.63 to 20.8; P = .066). There was no difference in occurrence of ED or pain 20 minutes after arrival in the postanesthesia care unit. CONCLUSIONS: Although not statistically significant, the use of an age-appropriate tablet computer game may reduce the level of anxiety at the anesthetic induction in 3 to 6 years old children undergoing elective day-case surgery. However, the occurrence of ED and levels of pain appeared unaffected. Standardization of nonpharmacologic interventions to reduce perioperative anxiety and pain is required.

Apolipoprotein E ε4 and cognitive function after surgery in middle-aged and elderly Danish twins.

BACKGROUND: Transient cognitive impairment is common in adult patients of all ages following anaesthesia and surgery. Apolipoprotein E (APOE) ε4 carriers may have a larger deterioration in short-term cognitive function after major surgery compared with APOE ε4 noncarriers. OBJECTIVES: The aim was to examine the effect of APOE ε4 on the association between exposure to surgery and anaesthesia, and subsequent cognitive functioning. A more pronounced deterioration in cognitive function in APOE ε4 carriers was hypothesised. DESIGN: An observational cross-sectional and a 6 to 10 years longitudinal twin cohort design. SETTING: Survey and register study of 2936 Danish twins aged 45 to 92 years. MAIN OUTCOME MEASURES: Cognitive function was assessed using five age-sensitive cognitive tests. In the cross-sectional study, we compared twins exposed to surgery with a reference group (unexposed). Linear regression models were used adjusting for sex and age and stratified by APOE ε4 carrier status. In the longitudinal cognitive follow-up study 1671 twins participated. Intrapair analyses were also performed using 70 same-sexed twin pairs concordant for APOE ε4 carrier status, but discordant for major surgery. RESULTS: APOE ε4 carriers had lower cognitive scores compared with noncarriers, and this was statistically significant in elderly twins 70+ years of age (mean difference, -0.67; 95% CI, -1.14 to -0.17). There was no significant impact on cognitive function after surgery according to APOE ε4 carrier status in the cross-sectional study. Similarly, there was no APOE ε4 modification in the longitudinal study. Also, in the intrapair analyses no evidence was found of lower cognitive score after major surgery compared with the nonexposed cotwins among APOE ε4 carriers. CONCLUSION: No evidence was found of more pronounced long-term deterioration in cognitive function after surgery among APOE ε4 carriers, but elderly APOE ε4 carriers in general performed worse on the cognitive tests than noncarriers.

Anesthesia and the developing brain: A way forward for laboratory and clinical research.

All commonly used general anesthetics have been shown to cause neurotoxicity in animal models, including nonhuman primates. Opinion, however, remains divided over how cumulative evidence from preclinical and human studies in this field should be interpreted and its translation to current practices in pediatric anesthesia and surgery. A group of international experts in laboratory and clinical sciences recently convened in Genoa, Italy, to evaluate the current state of both laboratory and clinical research and discuss future directions for basic, translational, and clinical studies in this field. This paper describes those discussions and conclusions. A central goal identified was the importance of continuing to pursue laboratory research efforts to better understand the biological pathways underlying anesthesia neurotoxicity. The distinction between basic and translational experimental designs in this field was highlighted, and it was acknowledged that it will be important for future animal research to try to causally link structural changes with long-term cognitive abnormalities. While inherent limitations will continue to affect the ability of even large observational cohorts to determine if anesthesia impacts neurodevelopment or behavioral outcomes, the importance of conducting further large well-designed cohort studies was also emphasized. Adequately powered cohorts could clarify which populations are at increased risk, provide information on environmental and healthcare-related risk modifiers, and guide future interventional trials. If anesthetics cause structural or functional adverse neurological effects in young children, alternative or mitigating strategies need to be considered. While protective or mitigating strategies have been repeatedly studied in animals, there are currently no human data to support alternative anesthetic strategies in clinical practice. Lastly, it was noted that there is still considerable debate over the clinical relevance of anesthesia neurotoxicity, and the need to evaluate the impact of other aspects of perioperative care on neurodevelopment must also be considered.

Long-term neurocognitive outcomes following surgery and anaesthesia in early life.

PURPOSE OF REVIEW: Repeated controversial and alarming statements of the potential dangers of anaesthetic agents on neurological outcomes in children continue to be issued based primarily on preclinical studies. This review assesses the current evidence of laboratory and clinical data and identifies areas of concerns. RECENT FINDINGS: Published animal and laboratory data consistently indicate that prolonged and excessive use of anaesthetic agents can lead to morphological changes and neurocognitive impairment in animals without a clear cut-off age or a superiority of one technique over another. Retrospective human studies and prospective clinical trials indicate that short exposures to anaesthesia and surgery are safe and have no effect on long-term neurological outcomes. Small and consistent continuing improvements in the perioperative period (aggregation of marginal gains) will impact on long-term neurological morbidity in humans. SUMMARY: It is biologically plausible that anaesthetic agents may induce structural changes during mammalian brain development and beyond. However, in the absence of alternatives the impact of the choice of anaesthetic drugs on long-term neurocognitive outcomes is almost certainly to be of limited relevance in humans. The underlying disease processes, surgical intervention, and trauma as well as other known perioperative factors more significantly affect these outcomes.

Oral Clefts and Academic Performance in Adolescence: The Impact of Anesthesia-Related Neurotoxicity, Timing of Surgery, and Type of Oral Clefts.

OBJECTIVE: Early life exposure to anesthesia and surgery is suspected to associate with cognitive impairment later in life. We compared academic achievement among adolescents with cleft lip only (CL), cleft palate only (CP), and cleft lip and cleft palate (CLP) with a noncleft control group to investigate whether outcome depends on timing and number of operations during childhood and/or type of oral cleft. DESIGN: Nationwide register-based follow-up study. SETTING: Danish birth cohort 1986 to 1990. PARTICIPANTS: Five hundred fifty-eight children with isolated CL (n = 171), CLP (n = 222), or CP (n = 195), of which 509 children had been exposed to anesthesia and one or more cleft operation(s), and a 5% sample of the birth cohort (n = 14,677). MAIN OUTCOME MEASURE(S): Test score in the Danish standardized ninth-grade exam and proportion of nonattainment, defined as "results for ninth-grade exam unavailable." Data adjusted for sex, birth weight, parental age, and parental level of education. RESULTS: Compared to controls, children with CL achieved higher scores (mean difference 0.12, 95% CI -0.05; 0.29) and children with CLP presented with lower scores (mean difference -0.06, 95% CI -0.21; 0.09), albeit both statistically insignificant. Children with CP achieved significantly lower scores, mean difference -0.20 (95% CI -0.38; -0.03). Odds ratios for nonattainment at final exam were: CL 0.79 (95% CI 0.46; 1.35), CLP 1.07 (95% CI 0.71; 1.61), CP 2.59 (95% CI 1.78; 3.76). CONCLUSIONS: Oral cleft type rather than number and timing of anesthesia and operations associate to poorer academic performance. Although a potential neurotoxic effect due to anesthetic agents is not reflected in the data, it cannot be completely excluded.

Cognitive Functioning after Surgery in Middle-aged and Elderly Danish Twins.

BACKGROUND: Postoperative cognitive dysfunction is common, but it remains unclear whether there are long-term adverse cognitive effects of surgery combined with anesthesia. The authors examined the association between exposure to surgery and level of cognitive functioning in a sample of 8,503 middle-aged and elderly twins. METHODS: Results from five cognitive tests were compared in twins exposed to surgery, classified as major, minor, hip and knee replacement, or other, with those of a reference group without surgery using linear regression adjusted for sex and age. Genetic and shared environmental confounding was addressed in intrapair analyses of 87 monozygotic and 124 dizygotic same-sexed twin pairs in whom one had a history of major surgery and the other did not. RESULTS: Statistically significantly lower composite cognitive score was found in twins with at least one major surgery compared with the reference group (mean difference, -0.27; 95% CI, -0.48 to -0.06), corresponding to one tenth of an SD, that is, a negligible effect size. In the intrapair analysis, the surgery-exposed co-twin had the lower cognitive score in 49% (95% CI, 42 to 56%) of the pairs. None of the other groups differed from the reference group except the knee and hip replacement group that tended to have higher cognitive scores (mean difference, 0.35; 95% CI, -0.18 to 0.87). CONCLUSIONS: A history of major surgery was associated with a negligibly lower level of cognitive functioning. The supplementary analyses suggest that preoperative cognitive functioning and underlying diseases were more important for cognitive functioning in mid- and late life than surgery and anesthesia.

Perioperative use of cerebral and renal near-infrared spectroscopy in neonates: a 24-h observational study.

BACKGROUND: Neonates undergoing surgery and intensive care still carry a significant morbidity and mortality often related to hypoxic/ischemic events; some of which may go undetected by conventional monitoring. Near-infrared spectroscopy (NIRS) is a noninvasive, continuous method of measuring regional tissue oxygen saturation, and may be used to supplement conventional monitoring to improve neonatal perioperative care. However, high costs and lack of evidence regarding improved outcomes have minimized wider perinatal use of NIRS. The aim of this study was to investigate the applicability of NIRS in neonates and premature infants undergoing noncardiac surgeries. METHOD: Neonates were monitored with both cerebral and renal NIRS for 24 h after induction of anesthesia and compared with systemic blood pressure (BP), peripheral oxygen saturation (SpO2 ), and heart rate (HR). RESULTS: A total of 23 368 min of data were collected from 21 neonates. NIRS reported cerebral/renal hypoxia 2.8 (±8.3)%/19.3 (±25.4)% of the time intraoperatively and 9.6 (±17.0)%/9.9 (±18.9)% of the time postoperatively. A moderate positive correlation was found between SpO2 and NIRS (φcerebral = 0.371, φrenal = 0.542). BP showed a weaker positive correlation (φcerebral = 0.231, φrenal = 0.246), and HR no correlation (φcerebral = -0.083, φrenal = -0.029). NIRS reported hypoxia two to three times more frequently than SpO2 , and SpO2 readings were 10-15 s delayed compared to NIRS. Furthermore, NIRS appeared effective at detecting postoperative apnea. CONCLUSION: Near-infrared spectroscopy is an easily applicable technique that appears effective at detecting hypoxic events and postoperative apneas in neonates. The high incidences of regional hypoxia reported by NIRS in this study imply that there is a need for a more specific regional cerebral and renal monitoring. Despite some practical and economical limitations, NIRS may be considered a useful supplement to perinatal perioperative intensive care.

Sedative medications outside the operating room and the pharmacology of sedatives.

PURPOSE OF REVIEW: There is a growing medical demand for suitable sedatives and analgesics to support the ongoing progress in diagnostic procedures and imaging techniques. This review provides an update of the pharmacology of the most commonly used drugs used for these procedures and shortly mention new drugs on the horizon. RECENT FINDINGS: There are many drugs available for procedural sedation; however, they all have drawbacks and shortcomings. Multiple adverse effects are associated with the use of these agents, hence monitoring is essential, and emergency equipment should be readily available. Newer drugs are on the horizon (e.g., remimazolam, fospropofol, and etomidate analogues) with a theoretical more predictable onset and offset; whether these will revolutionize the sedational practice sedation remains unknown. SUMMARY: Clinicians should be aware of the pharmacokinetic/pharmacodynamic differences of all agents in order to select appropriate medications for specific procedures and patients.

The effects of epinephrine and dobutamine on skin flap viability in rats: a randomized double-blind placebo-controlled study.

BACKGROUND: Intraoperative reduction in arterial pressure may cause hypoperfusion of skin flaps, which may increase the risk of flap failure. There is no international consensus regarding the use of vasoactive or inotropic agents to restore or maintain flap perfusion. The purpose of this study was to evaluate the effects of the intraoperative administration of epinephrine and dobutamine on axial-pattern skin flap survival in rats. METHODS: Fifty-four Sprague Dawley rats were randomized into three groups (n = 18). A tubed axial-pattern skin flap was performed. Animals were randomized to receive an intraperitoneal injection of epinephrine 0.1 mg/kg, dobutamine 0.3 mg/kg, or saline (0.5 ml). The rats were euthanized after 7 days and the viable area of the flap was compared between the groups using a digital imaging and computer software. RESULTS: Seven rats/flaps were excluded from the study due to autocannibalism (n = 3), postoperative tracheal obstruction (n = 2), anesthesia-induced respiratory arrest (n = 1), and abnormal behavior requiring euthanization (n = 1). The mean flap survival was 46% ± 9% in the saline group (n = 17), 41% ± 9% in the epinephrine group (n = 14) (p = 0.088 compared to the saline group), and 54% ± 9% in the dobutamine group (n = 16) (p = 0.02 compared to the saline group and p = 0.001 compared to the epinephrine group). CONCLUSIONS: Intraoperative intraperitoneal injection of dobutamine improves skin flap survival in rats, whereas intraperitoneal epinephrine tends to decrease skin flap survival.

Anesthesia-related neurotoxicity and the developing animal brain is not a significant problem in children.

A multitude of animal studies have shown that virtually all general anesthetics used in clinical practice possibly during a vulnerable period of brain development (i.e., brain growth spurt, peak of synaptogenesis) may lead to neurodegeneration (particularly apoptosis) and abnormal synaptic development with functional deficits in learning and behavior later in life. Initial studies were mainly performed in immature rodent pups, but more recent studies have included nonhumans primates (rhesus monkeys). Given the number of neonates, infants, and young children anesthetized annually worldwide, these findings could have significant public health implications. So far, relatively few human (cohort) studies focusing on this topic have been published with inconsistent results. While some studies have indicated an association between exposure to anesthesia and surgery, other studies have indicated no such association. Prospective studies are underway, but the result will not be available for several years. This paper reviews some of the preclinical background behind anesthesia-related neurotoxicity but focuses mainly on the human studies so far. It is concluded that although disturbing, the animal data lack verification in humans. Fortunately, the humans studies performed so far have been unable to confirm these animal data. A single brief anesthetic seems safe in infants. Multiple anesthetic and surgical exposures on the other hand are different. But there may be other reasons for this than merely the anesthetics. Currently, there is no need to change current anesthetic clinical practice or to postpone or cancel truly urgent surgeries in young children.

Neurosurgical conditions and procedures in infancy are associated with mortality and academic performances in adolescence: a nationwide cohort study.

BACKGROUND: Few human cohort studies on anesthesia-related neurotoxicity and the developing brain have focused on and compared specific surgeries and conditions. These studies cannot disentangle the effects of anesthesia from those of the surgery and underlying conditions. This study aimed at assessing the impact of specific neurosurgical conditions and procedures in infancy on mortality and academic achievements in adolescence. METHODS: A nationwide unselected register-based follow-up study of the Danish birth cohorts 1986-1990 compared academic performances of all children having undergone neurosurgeries as infants with a randomly selected, age-matched 5% sample of the same cohorts. The two groups were compared regarding mortality prior to June 1st, 2006, average test scores at ninth grade, and finally the proportion of children not attaining test scores. RESULTS: The exposure group comprised 228 and the control group 14 698 individuals. Hydrocephalus (n = 130), craniotomy (n = 43), and myelomeningocele/encephalocele children (n = 55) had a higher mortality (18.5.0%, 18.6%, and 7.3%, respectively) vs controls (1.3%; P < 0.00001, P < 0.00001, and P = 0.0052, respectively). Average test scores were significantly lower than controls in hydrocephalus and craniotomy (P = 0.0043 and P = 0.0077) but not myelomeningocele/encephalocele children (P = 0.2785); the proportion of available test scores were significantly lower in all three groups (40.8%, 60.0%, and 67.3%, respectively) vs 86.8% in controls (P < 0.00001, P = 0.000077, and P = 0.000064). CONCLUSION: Neurosurgery in infancy was associated with high mortality and significantly impaired academic achievements in adolescence. When studying anesthesia-related neurotoxicity and the developing brain, focus on specific surgeries/conditions is important. Pooling of major/minor conditions and major/minor surgeries should be avoided.

[Potential neurotoxicity of general anaesthetics to the developing brain]. / Generelle anæstetikas potentielle neurotoksicitet for den immature hjerne.

Animal studies (including non-human primates) have shown that most general anaesthetics cause enhanced neuroapoptosis with subsequent long-term neurocognitive deficits later in life. Some human cohort studies have indicated an association between anaesthesia/surgery and adverse neurocognitive outcome whereas other studies have not. Overall, the data do not justify any change in paediatric anaesthetic clinical practice. Naturally, the risks and benefits of a procedure should always be carefully considered before exposing a child to general anaesthesia.