Britta S. von Ungern-Sternberg

Long-term Differences in Language and Cognitive Function After Childhood Exposure to Anesthesia

BACKGROUND: Over the past decade, the safety of anesthetic agents in children has been questioned after the discovery that immature animals exposed to anesthesia display apoptotic neurodegeneration and long-term cognitive deficiencies. We examined the association between exposure to anesthesia in children under age 3 and outcomes in language, cognitive function, motor skills, and behavior at age 10. METHODS: We performed an analysis of the Western Australian Pregnancy Cohort (Raine) Study, which includes 2868 children born from 1989 to 1992. Of 2608 children assessed, 321 were exposed to anesthesia before age 3, and 2287 were unexposed. RESULTS: On average, exposed children had lower scores than their unexposed peers in receptive and expressive language (Clinical Evaluation of Language Fundamentals: Receptive [CELF-R] and Expressive [CELF-E]) and cognition (Colored Progressive Matrices [CPM]). After adjustment for demographic characteristics, exposure to anesthesia was associated with increased risk of disability in language (CELF-R: adjusted risk ratio [aRR], 1.87; 95% confidence interval [CI], 1.20–2.93, CELF-E: aRR, 1.72; 95% CI, 1.12–2.64), and cognition (CPM: aRR, 1.69; 95% CI, 1.13–2.53). An increased aRR for disability in language and cognition persisted even with a single exposure to anesthesia (CELF-R aRR, 2.41; 95% CI, 1.40–4.17, and CPM aRR, 1.73; 95% CI, 1.04–2.88). CONCLUSIONS: Our results indicate that the association between anesthesia and neuropsychological outcome may be confined to specific domains. Children in our cohort exposed to anesthesia before age 3 had a higher relative risk of language and abstract reasoning deficits at age 10 than unexposed children.

Bronchiectasis in Infants and Preschool Children Diagnosed with Cystic Fibrosis after Newborn Screening

OBJECTIVES To determine the prevalence of bronchiectasis in young children with cystic fibrosis (CF) diagnosed after newborn screening (NBS) and the relationship of bronchiectasis to pulmonary inflammation and infection. STUDY DESIGN Children were diagnosed with CF after NBS. Computed tomography and bronchoalveolar lavage were performed with anesthesia (n = 96). Scans were analyzed for the presence and extent of abnormalities. RESULTS The prevalence of bronchiectasis was 22% and increased with age (P = .001). Factors associated with bronchiectasis included absolute neutrophil count (P = .03), neutrophil elastase concentration (P = .001), and Pseudomonas aeruginosa infection (P = .03). CONCLUSIONS Pulmonary abnormalities are common in infants and young children with CF and relate to neutrophilic inflammation and infection with P. aeruginosa. Current models of care for infants with CF fail to prevent respiratory sequelae. Bronchiectasis is a clinically relevant endpoint that could be used for intervention trials that commence soon after CF is diagnosed after NBS.

Risk assessment for respiratory complications in paediatric anaesthesia: A prospective cohort study

BACKGROUND Perioperative respiratory adverse events in children are one of the major causes of morbidity and mortality during paediatric anaesthesia. We aimed to identify associations between family history, anaesthesia management, and occurrence of perioperative respiratory adverse events. METHODS We prospectively included all children who had general anaesthesia for surgical or medical interventions, elective or urgent procedures at Princess Margaret Hospital for Children, Perth, Australia, from Feb 1, 2007, to Jan 31, 2008. On the day of surgery, anaesthetists in charge of paediatric patients completed an adapted version of the International Study Group for Asthma and Allergies in Childhood questionnaire. We collected data on family medical history of asthma, atopy, allergy, upper respiratory tract infection, and passive smoking. Anaesthesia management and all perioperative respiratory adverse events were recorded. FINDINGS 9297 questionnaires were available for analysis. A positive respiratory history (nocturnal dry cough, wheezing during exercise, wheezing more than three times in the past 12 months, or a history of present or past eczema) was associated with an increased risk for bronchospasm (relative risk [RR] 8.46, 95% CI 6.18-11.59; p<0.0001), laryngospasm (4.13, 3.37-5.08; p<0.0001), and perioperative cough, desaturation, or airway obstruction (3.05, 2.76-3.37; p<0.0001). Upper respiratory tract infection was associated with an increased risk for perioperative respiratory adverse events only when symptoms were present (RR 2.05, 95% CI 1.82-2.31; p<0.0001) or less than 2 weeks before the procedure (2.34, 2.07-2.66; p<0.0001), whereas symptoms of upper respiratory tract infection 2-4 weeks before the procedure significantly lowered the incidence of perioperative respiratory adverse events (0.66, 0.53-0.81; p<0.0001). A history of at least two family members having asthma, atopy, or smoking increased the risk for perioperative respiratory adverse events (all p<0.0001). Risk was lower with intravenous induction compared with inhalational induction (all p<0.0001), inhalational compared with intravenous maintenance of anaesthesia (all p<0.0001), airway management by a specialist paediatric anaesthetist compared with a registrar (all p<0.0001), and use of face mask compared with tracheal intubation (all p<0.0001). INTERPRETATION Children at high risk for perioperative respiratory adverse events could be systematically identified at the preanaesthetic assessment and thus can benefit from a specifically targeted anaesthesia management. FUNDING Department of Anaesthesia, Princess Margaret Hospital for Children, Swiss Foundation for Grants in Biology and Medicine, and the Voluntary Academic Society Basel.

Comparative analysis of outcome measures used in examining neurodevelopmental effects of early childhood anesthesia exposure

Introduction:Immature animals exposed to anesthesia display apoptotic neurodegeneration and neurobehavioral deficits. The safety of anesthetic agents in children has been evaluated using a variety of neurodevelopmental outcome measures with varied results. Methods:The authors used data from the Western Australian Pregnancy Cohort (Raine) Study to examine the association between exposure to anesthesia in children younger than 3 yr of age and three types of outcomes at age of 10 yr: neuropsychological testing, International Classification of Diseases, 9th Revision, Clinical Modification–coded clinical disorders, and academic achievement. The authors’ primary analysis was restricted to children with data for all outcomes and covariates from the total cohort of 2,868 children born from 1989 to 1992. The authors used a modified multivariable Poisson regression model to determine the adjusted association of anesthesia exposure with outcomes. Results:Of 781 children studied, 112 had anesthesia exposure. The incidence of deficit ranged from 5.1 to 7.8% in neuropsychological tests, 14.6 to 29.5% in International Classification of Diseases, 9th Revision, Clinical Modification–coded outcomes, and 4.2 to 11.8% in academic achievement tests. Compared with unexposed peers, exposed children had an increased risk of deficit in neuropsychological language assessments (Clinical Evaluation of Language Fundamentals Total Score: adjusted risk ratio, 2.47; 95% CI, 1.41 to 4.33, Clinical Evaluation of Language Fundamentals Receptive Language Score: adjusted risk ratio, 2.23; 95% CI, 1.19 to 4.18, and Clinical Evaluation of Language Fundamentals Expressive Language Score: adjusted risk ratio, 2.00; 95% CI, 1.08 to 3.68) and International Classification of Diseases, 9th Revision, Clinical Modification–coded language and cognitive disorders (adjusted risk ratio, 1.57; 95% CI, 1.18 to 2.10), but not academic achievement scores. Conclusions:When assessing cognition in children with early exposure to anesthesia, the results may depend on the outcome measure used. Neuropsychological and International Classification of Diseases, 9th Revision, Clinical Modification–coded clinical outcomes showed an increased risk of deficit in exposed children compared with that in unexposed children, whereas academic achievement scores did not. This may explain some of the variation in the literature and underscores the importance of the outcome measures when interpreting studies of cognitive function.

Laryngeal Mask Airway Is Associated with an Increased Incidence of Adverse Respiratory Events in Children with Recent Upper Respiratory Tract Infections

Background:The laryngeal mask airway (LMA) has been advocated as an alternative technique to tracheal intubation for airway management of children with recent upper respiratory tract infections (URIs). The authors determined the occurrence of adverse respiratory events and identified the associated risk factors to assess the safety of LMA in children. Methods:During a period of 5 months, parents of children scheduled to undergo general anesthesia with an LMA were asked to fill out a questionnaire regarding their child’s medical history and potential symptoms of URI. In addition, all episodes of adverse respiratory events in the perioperative period (laryngospasm, bronchospasm, coughing, airway obstruction, and oxygen desaturation) as well as details of anesthesia management were recorded. Results:Among the 831 children included in the study, 27% presented with a history of a recent URI within the last 2 weeks before anesthesia. The presence of a recent URI doubled the incidence of laryngospasm (odds ratio, 2.6; 95% confidence interval, 1.3–5.0), coughing (odds ratio, 2.7; 95% confidence interval, 1.7–4.3), and oxygen desaturation (odds ratio, 1.9; 95% confidence interval, 1.2–2.8). This incidence was even higher in young children; in those undergoing ear, nose, and throat surgery; and when there were multiple attempts to insert the LMA. Conclusion:An LMA used in children with recent URIs was associated with a higher incidence of laryngospasm, cough, and oxygen desaturation compared with healthy children. However, the overall incidence of adverse respiratory events was low, suggesting that if anesthesiologists allow at least a 2-week interval after a URI, they can safely proceed with anesthesia using an LMA.

Respiratory Reflex Responses of the Larynx Differ between Sevoflurane and Propofol in Pediatric Patients

Background:The effects of anesthetics on airway protective reflexes have not been extensively characterized in children. The aim of this study was to compare the laryngeal reflex responses in children anesthetized with either sevoflurane or propofol under two levels of hypnosis using the Bispectral Index score (BIS). The authors hypothesized that the incidence of apnea with laryngospasm evoked by laryngeal stimulation would not differ between sevoflurane and propofol when used in equipotent doses and that laryngeal responsiveness would be diminished with increased levels of hypnosis. Methods:Seventy children, aged 2–6 yr, scheduled to undergo elective surgery were randomly allocated to undergo propofol or sevoflurane anesthesia while breathing spontaneously through a laryngeal mask airway. Anesthesia was titrated to achieve the assigned level of hypnosis (BIS 40 ± 5 or BIS 60 ± 5) in random order. Laryngeal and respiratory responses were elicited by spraying distilled water on the laryngeal mucosa, and a blinded reviewer assessed evoked responses. Results:Apnea with laryngospasm occurred more often during anesthesia with sevoflurane compared with propofol independent of the level of hypnosis: episodes lasting longer than 5 s, 34% versus 19% at BIS 40 and 34% versus 16% at BIS 60; episodes lasting longer than 10 s, 26% versus 10% at BIS 40 and 26% versus 6% at BIS 60 (group differences P < 0.04 and P < 0.01, respectively). In contrast, cough and expiration reflex occurred significantly more frequently in children anesthetized with propofol. Conclusion:Laryngeal and respiratory reflex responses in children aged 2–6 yr were different between sevoflurane and propofol independent of the levels of hypnosis examined in this study.

Impact of laryngeal mask airway cuff pressures on the incidence of sore throat in children

Background:  Hyperinflation of laryngeal mask airway cuffs can cause harm to the upper airway mainly by exerting high pressures on pharyngeal and laryngeal structures thus impairing mucosal perfusion. Although cuff manometers can be used to guide the monitoring of cuff pressures, their use is not routine in many institutions. In a prospective audit, we assessed the incidence of sore throat following day‐case‐surgery in relation to the intracuff pressure within the laryngeal mask airway.

Decrease of functional residual capacity and ventilation homogeneity after neuromuscular blockade in anesthetized young infants and preschool children

Background: Based on age-dependent differences in pulmonary mechanics, the effect of neuromuscular blockade may differ in infants compared with older children. The aim of this study was to determine the impact of neuromuscular blockade and its reversal by positive end-expiratory pressure (PEEP) on functional residual capacity (FRC) and ventilation distribution in young infants and preschool children. Methods: The authors studied 14 infants (aged 0–6 months) and 25 preschool children (aged 2–6 yr). FRC and lung clearance index were calculated. Measurements were taken (1) after intubation, (2) during neuromuscular blockade, and (3) during neuromuscular blockade plus application of PEEP (3 cm H2O). Results: Functional residual capacity (mean ± SD) decreased from 21.3 ± 4.7 ml/kg to 12.2 ± 4.8 ml/kg (P < 0.001) during neuromuscular blockade in infants and from 25.6 ± 5.9 ml/kg to 23.0 ± 5.3 ml/kg (P < 0.001) in preschool children. With the application of PEEP, FRC increased to 22.3 ± 5.9 ml/kg (P = 0.4829, compared with baseline) in infants and 28.2 ± 5.8 ml/kg (P < 0.001) in children. The lung clearance index increased after neuromuscular blockade, whereas baseline values were regained after the application of PEEP. The changes induced by neuromuscular blockade were significantly greater in infants compared with preschool children (P < 0.001). Conclusions: Although the use of neuromuscular blockade decreased FRC and ventilation distribution substantially in both groups, the changes were more pronounced in young infants. With PEEP, FRC increased and ventilation homogeneity was restored. These results provide a rationale to use PEEP in anesthetized, paralyzed infants and children.

Lower cuff pressures improve the seal of pediatric laryngeal mask airways.

Background:  Hyperinflation of laryngeal mask airway (LMA) cuffs may be harmful because of the exertion of high pressures on pharyngeal and laryngeal structures. Although cuff manometers may be used to monitor cuff pressure, their use is not routine in many institutions and clinical endpoints are used instead. Furthermore, it is common clinical practice to add air to the cuff in the presence of an air leak to obtain a better seal.

Apnea after Awake Regional and General Anesthesia in Infants: The General Anesthesia Compared to Spinal Anesthesia Study-Comparing Apnea and Neurodevelopmental Outcomes, a Randomized Controlled Trial

Background:Postoperative apnea is a complication in young infants. Awake regional anesthesia (RA) may reduce the risk; however, the evidence is weak. The General Anesthesia compared to Spinal anesthesia study is a randomized, controlled trial designed to assess the influence of general anesthesia (GA) on neurodevelopment. A secondary aim is to compare rates of apnea after anesthesia. Methods:Infants aged 60 weeks or younger, postmenstrual age scheduled for inguinal herniorrhaphy, were randomized to RA or GA. Exclusion criteria included risk factors for adverse neurodevelopmental outcome and infants born less than 26 weeks gestation. The primary outcome of this analysis was any observed apnea up to 12 h postoperatively. Apnea assessment was unblinded. Results:Three hundred sixty-three patients were assigned to RA and 359 to GA. Overall, the incidence of apnea (0 to 12 h) was similar between arms (3% in RA and 4% in GA arms; odds ratio [OR], 0.63; 95% CI, 0.31 to 1.30, P = 0.2133); however, the incidence of early apnea (0 to 30 min) was lower in the RA arm (1 vs. 3%; OR, 0.20; 95% CI, 0.05 to 0.91; P = 0.0367). The incidence of late apnea (30 min to 12 h) was 2% in both RA and GA arms (OR, 1.17; 95% CI, 0.41 to 3.33; P = 0.7688). The strongest predictor of apnea was prematurity (OR, 21.87; 95% CI, 4.38 to 109.24), and 96% of infants with apnea were premature. Conclusions:RA in infants undergoing inguinal herniorrhaphy reduces apnea in the early postoperative period. Cardiorespiratory monitoring should be used for all ex-premature infants.