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 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 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

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

BackgroundLumbar 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.ObjectivesThe 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.MethodsThis 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 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.LimitationsThis trial predominantly recruited term-born infants who were 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.ConclusionLumbar 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 workThe 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 registrationThis trial is registered as ISRCTN14040914 and as Integrated Research Application System registration 223737.FundingThis 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

Study protocol: NeoCLEAR: Neonatal Champagne Lumbar punctures Every time – An RCT: a multicentre, randomised controlled 2 × 2 factorial trial to investigate techniques to increase lumbar puncture success

Background: The neonatal period carries the highest risk of bacterial meningitis (~ 1 in 5000 births), bearing high mortality (~ 10%) and morbidity (20–50%) rates. Lumbar puncture (LP) remains essential to the diagnosis of meningitis. Though LP is a common procedure in neonates, success rates are lower (50–60%) than in other patient populations. None of the currently-practised neonatal LP techniques are supported by evidence from adequately-powered, randomised controlled trials (RCTs). NeoCLEAR aims to compare two modifications to the traditional technique which are free, accessible, and commonly practised: sitting (as opposed to lying) position, and ‘early’ (as opposed to ‘late’) stylet removal. Methods/design Written parental informed consent permitting, infants in neonatal/maternity wards, of 27⁺ ⁰ to 44⁺ ⁰ weeks corrected gestational age and weighing ≥1000 g, who require an LP, will be randomly allocated to sitting or lying position, and to early or late stylet removal. The co-primary objectives are to compare success rates (the proportion of infants with cerebrospinal fluid red cell count < 10,000/mm³ on first LP procedure) in 1020 infants between the two positions, and between the two methods of stylet removal. Secondary outcomes relate to LP procedures, complications, diagnoses of meningitis, duration of antibiotics and hospital stay. A modified intention-to-treat analysis will be conducted. Discussion Two modifications to the traditional LP technique (sitting vs lying position; and early vs late stylet removal) will be simultaneously investigated in an efficient and appropriately-powered 2 × 2 factorial RCT design. Analysis will identify the optimal techniques (in terms of obtaining easily-interpretable cerebrospinal fluid), as well as the impact on infants, parents and healthcare systems whilst providing robust safety data. Using a pragmatic RCT design, all practitioners will be trained in all LP techniques, but there will inevitably be variation between unit practice guidelines and other aspects of individual care. An improved LP technique would result in: • Fewer uninterpretable samples, repeated attempts and procedures • Reduced distress for infants and families • Decreased antibiotic use and risk of antibiotic resistance • Reduced healthcare costs due to fewer procedures, reduced length of stay, shorter antibiotic courses, and minimised antibiotic-associated complications Trial registration ISRCTN14040914. Date assigned: 26/06/2018.Medicine, Faculty ofOther UBCNon UBCPediatrics, Department ofReviewedFacult