Systematic review of the neurocognitive outcomes used in studies of paediatric anaesthesia neurotoxicity.

BACKGROUND: Neurotoxicity of anaesthetics in developing brain cells is well documented in preclinical studies, yet results are conflicting in humans. The use of many and different outcome measures in human studies may contribute to this disagreement. METHODS: We conducted a systematic review to identify all measures used to assess long-term neurocognitive outcomes following general anaesthesia (GA) and surgery in children. The quality of studies was assessed according to the Newcastle-Ottawa Scale (NOS) for observational studies. PubMed/MEDLINE, EMBASE, Cinahl, Web of Science, and the Cochrane Library were searched for studies investigating neurocognitive outcome after GA in children <18 yr. RESULTS: Sixty-seven studies were identified from 19 countries during 1990-2017. Most assessments were performed within cognition, sensory-motor development, academic achievement or neuropsychological diagnosis. Few studies assessed other outcomes (magnetic resonance imaging, serum-biomarkers, mortality, neurological examination, measurement of head circumference, impairment of vision). Rating according to the NOS rewarded a mean of six stars out of nine. Some concerns prevail regarding potential inter-rater variability because of equivocal description of rating criteria. Specific features such as stability over lifetime and inter-relations of outcomes (e.g. prediction of subsequent development or diagnosis of neuropsychological conditions) are discussed. The importance of validity and reliability of the various test instruments are described. The studies vary immensely in important characteristics. CONCLUSIONS: Future observational studies should be more consistent in the choice of study population, age at exposure, follow-up, indication for and type of surgery, and outcomes. Assessment of sensory-motor development seems feasible in young children (age <4 yr), and intelligence/cognition in older children.

Short report: Self-compassion and satisfaction with life in Danish adolescents with Developmental Language Disorder (DLD): `We are all in the same boat´.

BACKGROUND: Adolescents with Developmental Language Disorder (DLD) are at risk of emotional health problems and low self-esteem. However, little is known about their self-compassion (SC) and satisfaction with life (SWL). The present study compared self-compassion and satisfaction with life reported by Danish adolescents with DLD compared to typically developing (TD) peers, and whether severity of language difficulty is associated with SC and SWL. METHODS: Results were obtained from 10 Danish adolescents with DLD compared with 14 age-matched TD adolescents and 132 TD peers, aged 15 years. RESULTS: For SC and SWL results showed that adolescents with DLD reported more positive feelings compared to the TD adolescents. Interestingly for SC, the negative, but not the positive, domain differentiated the two groups, as adolescents with DLD reported less symptoms on self-judgment, isolation and overidentification. SC and SWL was strongly correlated with language abilities for the DLD group, but not for the TD group. CONCLUSIONS: Results from our pilot study showed that Danish adolescents with DLD reported being less harsh on themselves. Language abilities were associated with self-compassion for the DLD, but not for the TD group. Whether these group differences are due to environmental factors such as the specific Danish school setting of the DLD group or internal factors are discussed and requires further research.

School performance in cholesteatoma-operated children in Denmark: a nationwide population-based register-study.

Conclusion Cholesteatoma in childhood had no long-term effect on school performance for the majority who completed lower secondary school. Aim To investigate whether individuals operated on for cholesteatoma in childhood have impaired school performance in adolescence. Methods All children born in Denmark between 1986-1991 with cholesteatoma surgery performed before the age of 15 years were included (cholestetaoma group). A control group consisting of a 5% random sample of all children born in Denmark during the same period was used for comparison. Final marks (average, mathematics, Danish, and English) achieved upon completion of lower secondary school (9th grade; age 15 or 16 years) were compared between groups. Results A total of 549 individuals met the inclusion criteria for the cholesteatoma group and 15 106 for the control group. High parental education and female sex were strongly associated with high 9th grade marks. The cholesteatoma group did equally as well as the control group in all outcome-measures except from in English (1st foreign language), where children with ≥2 cholesteatoma surgeries scored 0.26 marks lower (95% confidence interval = 0.03-0.48). In the cholesteatoma group, though, the odds ratio for not attaining a 9th grade exam was 1.33 (95% confidence interval = 1.03-1.72%) when compared with the control group.

Changes in lymphocyte subpopulations and adhesion/activation molecules following endotoxemia and major surgery.

Major surgery as well as endotoxin-induced sepsis is accompanied by lymphocytopenia in peripheral blood. The purpose of this study was to investigate the redistribution of lymphocyte subpopulations and adhesion/activation molecules on lymphocytes. Twenty-four rats were included in the investigation. Eight rats received an intraperitoneal injection of E. coli endotoxin (2 mg kg-1), eight rats had a sham operation performed while eight rats received isotonic saline and served as a control group. Blood samples were obtained by making an incision in the tail before and 2 and 5 h after surgery or administration of endotoxin or saline. After isolation of lymphocytes by gradient centrifugation, flow-cytometric immunophenotyping was performed using CD2, CD3, CD4, CD8, CD11/CD18, CD20, CD44 and MHC II monoclonal antibodies. Endotoxemia and surgery were both accompanied by increased serum cortisol, lymphocytopenia, and a decrease in CD2, CD3 and CD4 lymphocytes. Only endotoxemia was followed by a decrease in CD8, CD11/CD18 and CD44 lymphocytes in peripheral blood. Our results show that several of the changes in lymphocyte subpopulations following surgery and sepsis are associated with increased serum cortisol. Sepsis is, in addition, accompanied by an upregulation of adhesion receptors.

Age-related postoperative morphine requirements in children following major surgery--an assessment using patient-controlled analgesia (PCA).

To investigate if small children require less morphine for postoperative analgesia than do older children and adolescents we analysed the morphine consumption pattern of 28 consecutive children on intravenous patient-controlled analgesia (PCA) following major surgery. The median age-specific morphine requirements between 2 comparable groups of children aged 4-8 years and 9-15 years were compared. We used the Pharmacia-Deltec pump in all children and the same settings: a bolus dose of 25 microgram/kg, an 8 minutes lockout interval and no background infusion. In addition, all children received paracetamol as a supplemently to the morphine. In this study children aged 4-8 years had significantly higher total postoperative morphine requirements compared to children aged 9-15 years, i.e. 11.6 microgram/kg/hour and 7.5 microgram/kg/hour respectively (p = 0.037). Hence, we conclude that children of this age group may have a higher total postoperative morphine requirement following major surgery than older children and adolescents.

[Aorto-esophageal fistula originating from a peptic ulcer in Barrett's esophagus]. / Aortoøsofageal fistel udgået fra et peptisk ulcus i Barrett's esophagus.

A case of an aorto-esophageal fistula originating from a peptic ulcer in a Barrett's esophagus and which ran a fatal course is presented.

[Patient-controlled analgesia in children]. / Patientkontrolleret smertebehandling af børn.

In order to introduce intravenous patient-controlled analgesia (PCA) in children in the Department of Anaesthesiology and Intensive Care, Odense University Hospital, we evaluated the technique in 13 children following major orthopaedic or abdominal surgery. The pump (Pharmacia-Deltec, CADD-PCA) was loaded with 1 mg/ml morphine in a 50 milliliters cassette. A bolus dose of 25 micrograms/kg and a lock-out interval of eight minutes were the initial settings. The morphine dose used, pain scores and side effects were currently recorded. Ages ranged from 4-15 years (mean 10.5 years) and the method was used for a mean of 89 hours (range 57-144 hours) postoperatively. Morphine requirements averaged 9.5 microgram/kg/hour (range 5.4-15.6 microgram/kg/hour). Pain control was good and side effects were few and of minor nature. PCA is an effective and safe means of providing good quality analgesia in children.

[Postoperative pain relief in children]. / Postoperativ smertebehandling af børn.

Postoperative pain management in children has been subject to increasing interest during the last decade, but is still insufficient. A survey is presented concerning postoperative pain management in children. The value of monitoring the pain as well as the opioid side effects in children is stressed, and such methods are presented. Acute Pain Service is mentioned and the most important pharmacological aspects regarding non-steroidal anti-inflammatory drugs, paracetamol, opioids and local anaesthetics are discussed. The management of postoperative pain in neonates is reviewed separately. It is concluded that the present insufficient management of postoperative pain in children is not due to the lack of methods and techniques, but rather to lack of sufficient utilization and comprehension of the possibilities. Moreover, pain management in children should be individualised. It is also necessary to be more aware of side effects of the pharmacological treatment.

[Severe bronchospasm in a 1-year old child treated with halothane]. / Svaer bronkospasme hos et-årigt barn behandlet med halotan.

A case of severe bronchospasm in a one-year old mechanically ventilated girl which in spite of maximal conventional bronchodilatory treatment only responded to halothane inhalation is presented. The benefits and limitations of this therapy are discussed.

[Persistent pulmonary hypertension in newborn infants]. / Persisterende pulmonal hypertension hos nyfødte.

On the basis of a review of the literature, a survey is presented concerning persistent pulmonary hypertension of the newborn. In this article the authors focus on the pathophysiology, diagnostic criteria and treatment, including mechanical ventilation, pharmacological vasodilation and extracorporal membrane oxygenation. Particular emphasis is placed on the treatment of the condition with inhaled nitric oxide. Nitric oxide is a selective pulmonary vasodilator and able to improve ventilation/ perfusion mismatching in cases where there is an affection of the pulmonary parenchyma. Data from randomized trials with close long-term follow-up is necessary before routine nitrogen oxide treatment can be recommended.

[Bronchodilating inhalation anesthetics in bronchial asthma and status asthmaticus]. / Bronkodilaterende inhalationsanaestetika ved asthma bronchiale og status asthmaticus.

On the basis of a review of the literature, a survey is presented concerning the use of halogenated inhalational anaesthetics (halothane, enflurane, isoflurane) in anaesthesia of asthmatic patients and in intensive care units in the treatment of status asthmaticus refractory to maximal standard therapy. Particular emphasis is placed on the bronchospasmolytic, cardiovascular and organotoxic effect of the anaesthetics. It is concluded that halogenated inhalational anaesthetics are established as bronchospasmolytics, and that their use in bronchospastic disease should be individualized to the patient and his other specific disease process.

[Sedation and analgesia in ventilator-treated children]. / Sedering og analgesi til børn i respirator.

Ventilator-treated children often require sedation in order to facilitate the ventilation. Sedatives alone or in combination with analgesics are commonly used for this purpose. In some cases, however, the addition of a neuromuscular blocking agent (NMB) may be necessary. In this article a survey is presented regarding both pharmacological and non-pharmacological means of improving the ventilator treatment in ventilated children. The most commonly employed sedatives, opioids and NMB's are discussed. The authors stress that whichever drug is used, it should be administered to the children guided by its effects rather than by a rigid scheme. In that respect monitoring of the treatment is important.