Techniques to increase lumbar puncture success in newborn babies: the NeoCLEAR RCT.

Background: Lumbar puncture is an essential tool for diagnosing meningitis. Neonatal lumbar puncture, although frequently performed, has low success rates (50-60%). Standard technique includes lying infants on their side and removing the stylet 'late', that is, after the needle is thought to have entered the cerebrospinal fluid. Modifications to this technique include holding infants in the sitting position and removing the stylet 'early', that is, following transection of the skin. To the best of our knowledge, modified techniques have not previously been tested in adequately powered trials. Objectives: The aim of the Neonatal Champagne Lumbar punctures Every time - An RCT (NeoCLEAR) trial was to compare two modifications to standard lumbar puncture technique, that is, use of the lying position rather than the sitting position and of 'early' rather than 'late' stylet removal, in terms of success rates and short-term clinical, resource and safety outcomes. Methods: This was a multicentre 2 × 2 factorial pragmatic non-blinded randomised controlled trial. Infants requiring lumbar puncture (with a working weight ≥ 1000 g and corrected gestational age from 27+0 to 44+0 weeks), and whose parents provided written consent, were randomised by web-based allocation to lumbar puncture (1) in the sitting or lying position and (2) with early or late stylet removal. The trial was powered to detect a 10% absolute risk difference in the primary outcome, that is, the percentage of infants with a successful lumbar puncture (cerebrospinal fluid containing < 10,000 red cells/mm3). The primary outcome was analysed by modified intention to treat. Results: Of 1082 infants randomised (sitting with early stylet removal, n = 275; sitting with late stylet removal, n = 271; lying with early stylet removal, n = 274; lying with late stylet removal, n = 262), 1076 were followed up until discharge. Most infants were term born (950/1076, 88.3%) and were aged < 3 days (936/1076, 87.0%) with a working weight > 2.5 kg (971/1076, 90.2%). Baseline characteristics were balanced across groups. In terms of the primary outcome, the sitting position was significantly more successful than lying [346/543 (63.7%) vs. 307/533 (57.6%), adjusted risk ratio 1.10 (95% confidence interval 1.01 to 1.21); p = 0.029; number needed to treat = 16 (95% confidence interval 9 to 134)]. There was no significant difference in the primary outcome between early stylet removal and late stylet removal [338/545 (62.0%) vs. 315/531 (59.3%), adjusted risk ratio 1.04 (95% confidence interval 0.94 to 1.15); p = 0.447]. Resource consumption was similar in all groups, and all techniques were well tolerated and safe. Limitations: This trial predominantly recruited term-born infants who were < 3 days old, with working weights > 2.5 kg. The impact of practitioners' seniority and previous experience of different lumbar puncture techniques was not investigated. Limited data on resource use were captured, and parent/practitioner preferences were not assessed. Conclusion: Lumbar puncture success rate was higher with infants in the sitting position but was not affected by timing of stylet removal. Lumbar puncture is a safe, well-tolerated and simple technique without additional cost, and is easily learned and applied. The results support a paradigm shift towards sitting technique as the standard position for neonatal lumbar puncture, especially for term-born infants during the first 3 days of life. Future work: The superiority of the sitting lumbar puncture technique should be tested in larger populations of premature infants, in those aged > 3 days and outside neonatal care settings. The effect of operators' previous practice and the impact on family experience also require further investigation, alongside in-depth analyses of healthcare resource utilisation. Future studies should also investigate other factors affecting lumbar puncture success, including further modifications to standard technique. Trial registration: This trial is registered as ISRCTN14040914 and as Integrated Research Application System registration 223737. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 15/188/106) and is published in full in Health Technology Assessment; Vol. 27, No. 33. See the NIHR Funding and Awards website for further award information.

Newborn babies are more susceptible to getting meningitis, and this can be fatal or have lifelong complications. A lumbar puncture is an essential test for diagnosing meningitis. Lumbar puncture involves taking a small amount of spinal fluid from the lower back using a needle. Analysing the fluid confirms or excludes meningitis, allowing the right treatment to be given. Lumbar punctures are commonly performed in newborns, but are technically difficult. In 50­60% of lumbar punctures in newborns, either no fluid is obtained or the sample is mixed with blood, making analysis less reliable. No-one knows which is the best technique, and so practice varies. The baby can be held lying on their side or sat up, and the 'stylet', which is a thin piece of metal that sits inside (and aids insertion of) the needle, can be removed either soon after passing through the skin (i.e. 'early stylet removal') or once the tip is thought to have reached the spinal fluid (i.e. 'late stylet removal'). We wanted to find the best technique for lumbar puncture in newborns. Therefore, we compared sitting with lying position, and 'early' with 'late' stylet removal. We carried out a large trial in newborn care and maternity wards in 21 UK hospitals. With parental consent, we recruited 1082 full-term and premature babies who needed a lumbar puncture. Our results demonstrated that the sitting position was more successful than lying position, but the timing of stylet removal did not affect success. In summary, the sitting position is an inexpensive, safe, well-tolerated and easily learned way to improve lumbar puncture success rates in newborns. Our results strongly support using this technique in newborn babies worldwide.

ONCE DAILY GENTAMICIN DOSE BANDING IN NEWBORNS WITH SIGNS OF EARLY ONSET OF NEONATAL SEPSIS (EONS), BASED ON INITIAL BIRTH WEIGHT AND GESTATIONAL AGE.

AIM: Prospective assessment of safety of dose banding of once daily gentamicin in newborns with signs of EONS in their first days of life. METHOD: All neonates admitted on the level-3 neonatal unit, with at least three consecutive once daily gentamicin doses, started no later than 48 hrs after birth were included. The dose was based on initial birth weight and not adjusted to daily changes of the bodyweight(W). A gentamicin trough level of 2 mg/L was permitted. Neonates with hypoxic ischaemic encephalopathy at birth were not started on a gentamicin regimen. Data was taken from a database system registered as a service evaluation.Of more than 1200 admitted neonates eighty nine (60 boys, 29 girls; born between Feb 2014 and Jul 2015) received at least three consecutive gentamicin doses for EONS soon after birth (within first 24 hrs: 96.6%), while the majority of antibiotic courses started with a gentamicin regimen were stopped within 36 hrs. 23 (25.8%) neonates with a gestational age (GA) of less than 30 weeks started on 5 mg/kg 48-hourly. Neonates 30 weeks and older started on weight based dosing range: Up to 3 kg: 48 (53.9%) neonates on 5 mg/kg 24 hourly. Between 3-3.5 kg: 13 (14.6%) at fixed 15 mg 24 hourly; between 3.5-4 kg: 5 (5.6%) neonates at fixed 17.5 mg 24 hourly. The first trough level (95.5%) was taken before the third dose. Daily weight (W) was recorded. Routine blood samples was recorded including creatinine, C-reactive protein and a routine sample was sent for investigation of bacterial growth. RESULTS: The first trough level for neonates up to 30 weeks on 48 hourly regimen (GA-mean 27, range 24-29; W-mean 0.96 kg, range 0.54-1.4 kg; W-change 3.9%) was for all less than 2 mg/L (mean 0.66 mg/L, range 0.2-1.3). For neonates 30 weeks and older, up to 3 kg: (GA-mean 34, range 30-41; W-mean 2.16 kg, range 1.09-2.86 kg; W-change 2.9%) on 24 hourly regimen the level was for 37(82%) up 2 mg/L (mean 1.6 mg/L, range 0.2-2; for 3 cases no level; eight cases 2 up to 3 mg/L of which 3 results cannot be explained with change of a disease status). Neonates between 3-3.5 kg: (GA-mean 38, range 33-42; W-mean 3.3 kg, range 3-3.48 kg; W-change 0.96%) on 24 hourly regimen: all except for one less than 2 mg/L (mean 1.3 mg/L, range 0.4-2; one at 2.7 with hyperinsulinaemia). Between 3.5-4 kg: (GA-mean 39, range 36-41; W-mean 3.78 kg, range 3.6-3.9 kg; W-change 1.3%) on 24 hourly regimen: all less than 2 mg/L (mean 1.1 mg/L, range 0.4-1.7). None of the samples for 73(82%) neonates sent for bacterial investigation showed bacterial growth over 5 days. CONCLUSION: Dose banding for gentamicin in EONS is a promising safe option for dosing neonates. There needs to be a revision and re-evaluation in context of the disease profile of the population of a newborn unit as indicated by results for dosing neonates 30 weeks and older but less than 3 kg.