Intravenous access in distressed children : effects of midazolam and nitrous oxide on success rate, hormone and metabolic stress responses

Background and Aims: Intravenous (IV) access has demonstrated high levels of pain and distress in children. A stress full IV access should be avoided, primarily by the children, but also for the parents and staff. When testing children with suspected endocrine and metabolic disorders there is a substantial risk that a stressful IV access influences the hormone releases and metabolic response. The aims of this thesis were to facilitate painful procedures and IV access in children at a paediatric outpatient clinic. To study the feasibility, effects and stress response of Nitrous Oxide (N2O) compared to Midazolam and EMLA alone in children with endocrine disorders and obesity. Material and Methods: Children with anxiety or previous difficulties establishing IV access were included (n=140). 50 children were openly randomised to EMLA (n=25) or EMLA+ N2O (n=25). 90 children (60 obese and 30 growth retarded) were double blinded randomised to; midazolam, 0.3mg/kg, max 15 mg, (n=30), 50% N2O (n=30), and to 10% N2O (n=30). A subgroup of 20 anxious children undergoing repeatedly painful procedures was also included. These children underwent two procedures with EMLA and EMLA+N2O, the order of priority being randomised. Measurments: Number of attempts; defined both as the number required to succeed in setting up double IV lines, and as a successful IV line procedure with 2 attempts for two iv lines vs >2 attempts, IV access time; defined as time from start of setting up the IV lines until two IV lines were established. Recovery time; defined as the time from establishment of the IV lines until regained alertness. Total procedure time; defined as IV access time plus recovery time. Evaluations; children’s, parents’ and nurses’ satisfaction of the IV line procedure, Pain; evaluated by the child. Sedation levels; assessed using the Observer’s Assessment of Alertness/Sedation Score. Blood samples were obtained during 30 minutes at four time points after achieving venous access and, if possible, after 24 hours. 1; 0−1 min, 2; 5−6 min, 3; 14−15 min, and 4; 29−30 min. Analyses were compared between treatments and treatments over time. 60 children (40 obese and 20 growth retarded), served as controls. Results: Comparing all study children together with IV access problems, a significant difference in number of attempts between the treatments groups were seen (P<0.001) with differences between midazolam compared with 50% N2O and EMLA compared with midazoalm, 10%, 50% N2O. The percentage of successfully IV line procedures were 70% using 50% N2O. The children’s evaluations were significantly more positive for 50% N2O during IV access and painful procedures. 50% N2O was more efficient measured as total procedure time (P<0.001) and especially in obese children an unfavourable long procedure time was observed after midazolam. Significantly lower cortisol levels were detected when midazolam was used compared to both 50% and 10% N2O and to unstressed controls. Glucose levels among growth retarded children increased from 0 to 30 min, whereas the opposite was found in obese children regardless of treatment. The growth hormone levels decreased with time in the midazolam group compared to 50% and 10% N2O, where the effect of time was reversed. Conclusion: 50% N2O in combination with EMLA, was in all aspects superior to midazolam for facilitation of IV access for distressed children. The IV access procedure was more efficient, with a shorter total procedure time and an increased number of successful IV lines. Midazolam should only be used exceptionally in obese children due to the long recovery time. Treatment with N2O and midazolam influence the results of hormone analyses in the form of different levels and trends in glucose and stress hormones

A randomized controlled trial comparing intensive non-surgical treatment with bariatric surgery in adolescents aged 13-16 years (AMOS2): Rationale, study design, and patient recruitment.

BACKGROUND: Previous non-randomized studies show similar outcomes in adolescents and adults after bariatric surgery. We describe the study protocol, recruitment, and selected baseline data of patients in a randomized multi-center study, the Adolescent Morbid Obesity Surgery 2 (AMOS2). METHODS: Three clinics in Sweden collaborated in designing the study and recruitment of patients from August 1, 2014 to June 30, 2017. Patients were selected among adolescents 13-16 years of age attending third-level obesity care for at least one year. Patients were randomized 1:1 to bariatric surgery (predominantly Roux-en-Y gastric bypass) or intensive non-surgical treatment starting with an eight-week low-calorie-diet. RESULTS: Fifty adolescents (37 girls) were randomized, 25 (19 girls) to bariatric surgery. Mean age was 15.7 years (range 13.3-16.9), weight 122.6 kg (range 95-183.3), Body Mass Index (BMI) 42.6 kg/m2 (range 35.7-54.9) and BMI-SDS 3.45 (range 2.9-4.1). One patient had type 2 diabetes mellitus, and 12/45 (27%) had elevated liver enzymes. There were no significant differences between the groups. For the 39 eligible patients who were offered but declined inclusion, BMI was not different from included patients. However, patients who declined were younger, 15.2 years (p = 0.021). A sex difference was also noted with more of eligible girls, 37/53 (69.8%), than boys, 13/36 (36.1%), wanting to participate in the study (p = 0.002). CONCLUSIONS: This clinical trial, randomizing adolescents with severe obesity to bariatric surgery or intensive non-surgical treatment, aims at informing about whether it is beneficial to undergo bariatric surgery in early adolescence. It will also enlighten the outcome of comprehensive non-surgical treatment. The study was registered at www.clinicalTrials.gov number NCT02378259

Development of sleep patterns in children with obese and normal-weight parents

Aim To study the sleep development and sleep characteristics in children at different obesity risks, based on parental weight, and also to explore their weekday–weekend sleep variations and associated family factors. Methods A total of 145 children participating in a longitudinal obesity prevention project were included, of which 37 had normal‐weight parents (low obesity risk), and 108 had overweight/obese parents (high obesity risk). Sleep diaries at ages 1 and 2 years were used to study sleep development in children at different obesity risks. Objectively assessed sleep using an accelerometer at 2 years of age was used to analyse weekday–weekend sleep variations. Results There was no difference in sleep development from age 1 to age 2 among children at different obesity risks, but more children in the high‐risk group had prolonged sleep onset latency and low sleep efficiency. At 2 years of age, children in the high‐risk group had more weekday–weekend variation in sleep offset (mean difference 18 min, 95% confidence interval (CI) 4–33 min), midpoint of sleep (mean difference 14 min, 95% CI 3–25 min) and nap onset (mean difference 42 min, 95% CI 10–74 min) than children in the low‐risk group, after adjusting for other family factors. However, no difference could be detected between groups in weekday–weekend variation in sleep duration. Conclusions Unfavourable sleep characteristics, as well as more variation in sleep schedules, have been observed in children at high obesity risk. While the differences were relatively small, they may reflect the unfavourable sleep hygiene in families at high obesity risk

Laparoscopic Roux-en-Y gastric bypass in adolescents with morbid obesity-Surgical aspects and clinical outcome.

In this paper, we address surgical aspects on bariatric surgery in adolescents from a nationwide Swedish study. Laparoscopic gastric bypass surgery was performed for 81 adolescents with morbid obesity (13-18 years), while 81 adolescents with obesity-matched by age, sex, and BMI received conventional care. Another comparison group was adults undergoing gastric bypass at the same institution during the same time period. This report addresses the 2-year clinical outcome and five-year surgical adverse event rate. Body weight decreased from 133kg (SD = 22) at inclusion to 92kg (SD = 17) after 1 year and was 89 (SD = 18) after 2 years (p < 0·001) representing a 32% (-35 to -30) weight loss after 2 years, corresponding to 76% (-81 to -71) excess weight loss. Weight loss was similar in the adult gastric bypass patients (-31%) while weight gain (+3%) was seen in the conventionally treated obese adolescents. Significant improvement in cardiovascular and metabolic risk factors and inflammation was seen after surgery. The treatment was generally well tolerated and quality of life improved significantly. The surgical adverse events included cholecystectomies (10%) and operations for internal hernia (9%) but no postoperative mortality. Adolescents undergoing laparoscopic gastric bypass surgery achieve similar weight loss to adults. Improvements in risk factors and quality of life were substantial. There were surgical complications similar to the adult group, which may be preventable

Oral intake of mesoporous silica is safe and well tolerated in male humans.

BackgroundPrecisely engineered mesoporous silica has been shown to induce weight loss in mice, but whether it is safe to use in humans have not investigated.ObjectiveThe aim was to determine whether oral dosing, up to 9 grams/day, of precisely engineered mesoporous silica as a food additive can be used safely in male humans.DesignThis single blinded safety study consisted of two study arms including 10 males each (18-35 years). One arm consisted of participants with normal weight and one with obesity. After a placebo run-in period, all subjects were given porous silica three times daily, with increasing dose up to 9 grams/day (Phase 1). Subjects with obesity continued the study with highest dose for additional 10 weeks (Phase 2).ResultsAll participants completed Phase 1 and 90% completed Phase 2, with approximately 1% missed doses. Participants reported no abdominal discomfort, and changes in bowel habits were minor and inconsistent. The side effects observed were mild and tolerable, biomarkers did not give any safety concern, and no severe adverse events occurred.ConclusionMesoporous silica intake of up to 9 grams/day can be consumed by males without any major adverse events or safety concerns