Authors' objectives: 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. 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. The neonatal period carries the highest risk of bacterial meningitis (≈ 1 per 4000–5000 births), which is associated with significant mortality (≈ 10%) and morbidity (20–50%). Meningitis is diagnosed by analysis of cerebrospinal fluid (CSF), obtained via lumbar puncture (LP). LPs are frequently performed in newborns because of the non-specific clinical features of neonatal meningitis. However, LP success rates in newborns are much lower (50–60%) than in older children (78–87%). Unsuccessful LPs include those with heavily blood-stained CSF or LPs that fail to obtain CSF at all. Treatment for suspected or confirmed neonatal meningitis involves intravenous antibiotics, typically for 14–21 days. Unsuccessful LPs lead to repeated attempts, whereas LPs with equivocal or uninterpretable CSF results often prompt cautious treatment with extended courses of antibiotics. Prolonged antibiotic use is associated with a range of complications, including induced antimicrobial resistance. Consequently, interventions to improve neonatal LP success rates should allow more accurate diagnosis of meningitis, which will help reduce unnecessary courses of antibiotic therapy and extended hospitalisation, and will save healthcare resources. There have been few modifications to the original LP technique. Thus far, the sitting position, as employed for older patients, and ‘early stylet removal’ (ESR) have been suggested. ESR promises advantages because, in neonates, a ‘loss of resistance’ on entering the CSF is often indistinguishable and a needle advanced too far can cause venous puncture and a blood-stained tap, impairing CSF interpretation. We conducted the Neonatal Champagne Lumbar punctures Every time – An RCT (NeoCLEAR) trial to determine the optimal LP technique in neonates in terms of the effect of infant position (sitting vs. lying) and timing of stylet removal [ESR vs. late stylet removal (LSR)] on success [i.e. a CSF red blood cell (RBC) count of < 10,000/mm3] of first LP.

Authors' results and conclusions: 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. 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. From August 2018 to August 2020, 1082 participants from 21 centres in the UK were randomised in a 2 × 2 factorial design, resulting in two principal comparisons: (1) sitting position (n = 546) compared with lying position (n = 536) and (2) ESR (n = 549) compared with LSR (n = 533). A total of 1079 infants had a ‘first’ LP, and 166 (15.4%) infants had a second LP (each of these LP ‘procedures’ involved one or more ‘attempts’). Nine infants were withdrawn during the trial, but in the case of only one of these participants was consent withdrawn before data collection for the primary outcome. Three infants did not receive a LP, and in the case of a further two infants the consent form was missing. Overall, six infants were excluded, leaving 1076 infants for the final (modified intention-to-treat) analysis: (1) sitting position (n = 543) compared with lying position (n = 533) and (2) ESR (n = 545) compared with LSR (n = 531). All infants were followed up until discharge. Baseline characteristics were similar for the two groups in both comparisons, as recorded at trial entry and at time of first LP. The majority of infants were born at term, were < 3 days old and were not receiving respiratory support. Raised C-reactive protein was the most common indication for LP. First comparison: sitting position compared with lying position The primary outcome – a successful first LP – was achieved in 346 of 543 (63.7%) infants in the sitting arm and 307 of 533 (57.6%) infants in the lying arm [aRR 1.10 (95% CI 1.01 to 1.21); p = 0.03; adjusted absolute risk difference 6.1% (95% CI 0.7% to 11.4%), adjusted number needed to treat (NNT) 16 (95% CI 9 to 134)]. Infants allocated to the sitting position were less likely than infants allocated to the lying position to exhibit moderate or severe struggling at the time of needle insertion [169/541 (31.2%) vs. 202/527 (38.4%), aRR 0.82 (95% CI 0.71 to 0.94); p = 0.006]. Other secondary outcomes did not reach statistical significance, but predominantly favoured the sitting position. Based on microscopy of CSF extracted from the first and second LPs (and any culture/polymerase chain reaction results), infants who were sitting were more likely to be ‘negative’ for meningitis than infants who were lying [396/537 (73.7%) vs. 359/521 (68.9%)], and a result of ‘uninterpretable CSF’ (i.e. no sample obtained or CSF not possible to analyse, usually due to a heavily blood contaminated or clotted sample) was more likely to be recorded for infants who were lying than for infants who were sitting [139/521 (26.7%) vs. 114/537 (21.2%)]. Median duration of antibiotic treatment and length of stay were not significantly different in the sitting and lying arms {median 5 [interquartile range (IQR) 4–6] days in each arm, for both duration of antibiotic treatment and length of stay}. Four (0.3%) of 1241 first or second LPs, 1 in ESR and 1 in LSR arms, respectively, were abandoned because of cardiovascular deterioration. Lowest oxygen saturation (SpO2) during the first LP averaged 93% (IQR 89–96%) in the sitting arm and 90% (IQR 85–94%) in the lying arm (adjusted Med D 3.0%, 95% CI 2.1% to 3.9%; p < 0.001). Three of 1075 (0.3%) infants required increased respiratory support within 1 hour of their first LP (sitting arm, n = 1; lying arm, n = 2; not significantly different). The proportion of infants whose lowest SpO2 fell below 80% during the first LP (analysed post hoc) was 6.6% (35 of 532) in the sitting arm and 14.2% (72 of 508) in the lying LP arm, and this pattern was consistent in preterm and term-born babies. In 47 of 543 (8.7%) first LPs in infants allocated to the sitting position, at least one attempt involved switching to the lying position [compared with 4/533 (0.8%) infants allocated to the lying allocation, who were switched to sitting]. Of the 47 LPs where there was at least one attempt in which the allocated technique was not adhered to, the decision to change position was mostly made on the second (22/247) or third (24/257) attempt. The decision to change position was usually made by a clinical (45/47). Similarly, for the second LP, the sitting allocation was less often followed [for at least one attempt in 16/76 (22.5%) of infants allocated to sitting vs. 6/90 (7.0%) of infants allocated to lying]. There were no obvious differences in baseline infant characteristics between LPs that were carried out in the allocated position and those that were not. In prespecified subgroup analyses, the effect of position on the proportion of infants with a successful first LP was consistent across working weight and CGA at trial entry, but a difference in effect was observed between infants enrolled within 3 days of life (n = 836, RR 1.14, 95% CI 1.04 to 1.25) and those enrolled after 3 days (n = 140, RR 0.9, 95% CI 0.78 to 1.05; p = 0.001).

Authors' 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. 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. Trial design and oversight The NeoCLEAR trial was a 2 × 2 factorial open-label multicentre randomised controlled trial (RCT), with an internal pilot. The study protocol was published previously. The NeoCLEAR trial was co-ordinated by the National Perinatal Epidemiology Unit – Clinical Trials Unit. The University of Oxford (Oxford, UK) sponsored the trial. Trial oversight was conducted by the Trial Steering Committee and an independent Data Monitoring Committee. The funder [i.e. the National Institute for Health and Care Research (NIHR)] did not have a role in study design, conduct, data collection, analysis or interpretation. Ethics approval was obtained.

Project Status: Completed

URL for project: https://www.journalslibrary.nihr.ac.uk/programmes/hta/15/188/106

Year Published: 2023

URL for published report: https://www.journalslibrary.nihr.ac.uk/hta/THJY0671

URL for additional information: English

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: England, United Kingdom

DOI: 10.3310/THJY0671

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk