Assessment of infant position and timing of stylet removal to improve lumbar puncture success in neonates (NeoCLEAR): an open-label, 2 × 2 factorial, randomised, controlled trial

Abstract

Newborn infants are the highest-risk age group for bacterial meningitis. Lumbar punctures are therefore frequently performed in neonates, but success rates are low (50-60%). In Neonatal Champagne Lumbar punctures Every time-A Randomised Controlled Trial (NeoCLEAR), we sought to optimise infant lumbar puncture by evaluating two modifications to traditional technique: sitting position versus lying down and early stylet removal (stylet removal after transecting the subcutaneous tissue) versus late stylet removal. NeoCLEAR was an open-label, 2 × 2 factorial, randomised, controlled trial, conducted in 21 UK neonatal and maternity units. Infants requiring lumbar puncture at 27+0 to 44+0 weeks corrected gestational age and weighing 1000 g or more were randomly assigned (1:1:1:1) to sitting position and early stylet removal, sitting position and late stylet removal, lying position and early stylet removal, or lying position and late stylet removal using a 24/7, web-based, secure, central randomisation system. Block randomisation was stratified within site by corrected gestational age (27+0 to 31+6 weeks, 32+0 to 36+6 weeks, 37+0 to 40+6 weeks, or 41+0 to 44+0 weeks), using variable block sizes of four and eight with equal frequency. Laboratory staff were masked to allocation. The primary outcome was successful first lumbar puncture, defined as obtaining a cerebrospinal fluid sample with a red blood cell count of less than 10 000 cells per μL. The primary and secondary (including safety) outcomes were analysed by the groups to which infants were assigned regardless of deviation from the protocol or allocation received, but with exclusion of infants who were withdrawn before data collection or who did not undergo lumbar puncture (modified intention-to-treat analysis). This study is registered with ISRCTN, ISRCTN14040914. Between Aug 3, 2018, and Aug 31, 2020, 1082 infants were randomly assigned to sitting (n=546) or lying (n=536), and early (n=549) or late (n=533) stylet removal. 1076 infants were followed-up until discharge and included in the modified intention-to-treat analysis. 961 (89%) infants were term, and 936 (87%) were younger than 3 days. Successful first lumbar puncture was more frequently observed in sitting than in lying position (346 [63·7%] of 543 vs 307 [57·6%] of 533; adjusted risk ratio 1·10 [95% CI 1·01 to 1·21], p=0·029; number needed to treat=16). Timing of stylet removal had no discernible effect on the primary outcome (338 [62·0%] of 545 infants in the early stylet removal group and 315 [59·3%] of 531 in the late stylet removal group had a successful first lumbar puncture; adjusted risk ratio 1·04 [95% CI 0·94-1·15], p=0·45). Sitting was associated with fewer desaturations than was lying (median lowest oxygen saturations during first lumbar puncture 93% [IQR 89-96] vs 90% [85-94]; median difference 3·0% [2·1-3·9], p<0·0001). One infant from the sitting plus late stylet removal group developed a scrotal haematoma 2 days after lumbar puncture, which was deemed to be possibly related to lumbar puncture. NeoCLEAR is the largest trial investigating paediatric lumbar puncture so far. Success rates were improved when sitting rather than lying. Sitting lumbar puncture is safe, cost neutral, and well tolerated. We predominantly recruited term neonates younger than 3 days; other populations warrant further study. Neonatal lumbar puncture is commonly performed worldwide; these results therefore strongly support the widespread adoption of sitting technique for neonatal lumbar puncture. UK National Institute for Health and Care Research.