Lumbar puncture position in infants—a systematic review and meta-analysis

To analyze the optimal lumbar puncture position in infants. A systematic review and meta-analysis. Infants (age < 1 year). December 2022 in PubMed, Scopus, and Web of Science. Randomized controlled trials focusing on lumbar puncture positions were included. Other lumbar puncture position than standard lateral decubitus position. First puncture success and overall success rate. Secondary outcome was desaturation during puncture and procedure-related harms. Risk of bias 2.0 assessment was performed. Outcomes are reported as risk ratios (RR) with 95% confidence intervals (CI). We screened 225 abstracts, and six studies were included. Four studies compared sitting position, one study head elevated lateral position, and one study prone position to lateral position. Risk of bias was high in two studies. First puncture success rate in sitting position (RR 1.00, CI: 0.78–1.18; 2 studies) and overall success rate in sitting position were similar to lateral position (RR 0.97, CI: 0.87–1.17; 3 studies). First attempt success rate was higher in elevated lateral position (RR 1.48, CI: 1.14–1.92; 1 study) and in prone position (RR 1.09, CI: 1.00–1.17; 1 study). Conclusion: Sitting position seems to be equally effective in terms of first attempt and overall success in lumbar puncture than standard lateral position. Elevated lateral position and prone positions had better first attempt success than standard lateral position, but these were assessed only in one study each and thus further studies in these positions are needed. Trial registration: This review was registered in PROSPERO. ID: CRD42022382953. What is Known: • Success rate in lumbar puncture has been poor and first attempt success rate has varied between 50 to 80% in literature. • Optimal lumbar puncture positions for infants have been debated between sitting and lateral decubitus position mostly. What is New: • This is the first meta-analysis focused on lumbar puncture positions in infants, and it found that sitting position was equal to standard lateral position. • Prone position and head elevated lateral positions had higher first puncture success rates, but these were assessed both only in one study, which creates uncertainty to the finding.


Introduction
Lumbar puncture is among the most common invasive procedures in children.Especially neonates and infants have high need for lumbar punctures due to the highest rates of bacterial meningitis, as for example the infant bacterial meningitis rate in the UK has been reported to be 0.4 per 1000 births [1,2].The first attempt success rate of lumbar puncture is low and has varied between 50 and 80% in previous studies [3][4][5].The rates of traumatic lumbar puncture (classified as red blood cell count > 10,000/µl) are higher in neonates than in infants [6].
Optimal lumbar puncture position in infants and neonates has remained controversial.Few observational studies assessing the success rate between different positions have found that sitting position might have a higher success rate [7][8][9].However, there are also reports with lower success rates in sitting position [10].Other alternative positions have rarely been studied in infants.Furthermore, the optimal puncture position has been evaluated by ultrasound in terms of how the puncture space opens in sitting position compared to lateral position.In these studies, sitting position has seemed to offer the widest opening angle for lumbar puncture [11,12].However, the clinical first attempt success rate of ultrasound-marked puncture sites in randomized controlled trials has been relatively comparable to standard palpation method [3,13,14].A recent large randomized controlled trial (RCT) found that sitting position was associated with better success rate than standard lateral position [15].Thus, we wanted to update the current evidence on optimal lumbar puncture position in infants.
The aim of this systematic review with meta-analysis was to compare first attempt and overall puncture success rates between different lumbar puncture positions in infants.

Search process
We searched PubMed, Scopus, and Web of Science databases on December 4, 2022.The following search phrase was utilized: "lumbar puncture" AND position AND (infant OR neonate OR newborn OR child OR pediatric).Reference lists of the included studies were also hand searched, and relevant articles included, if found.Search results were then uploaded to Covidence software (Covidence systematic review software, Veritas Health Innovation, Melbourne, Australia, 2022) for screening.Two authors independently screened the abstracts and the full texts.In cases of disagreement, a mutual consensus was searched by discussion.

Inclusion and exclusion criteria
We included randomized controlled studies that compared any other lumbar puncture position to standard lateral decubitus position.We classified infants as children aged 0 to 364 days.We excluded all observational studies.We excluded studies with older children if data were not presented separately for infants.Furthermore, non-English studies and studies that did not present any original data were excluded.

Outcome measures
Our main outcome measures were the rate of first attempt success and overall puncture success rate.In all analyses, alternative lumbar puncture positions were compared to standard lateral decubitus position.A lumbar puncture attempt is classified as needle perforating the skin.The definition for a successful puncture was that the fluid was clear and that red blood cell count was less than 10,000/µl.First attempt success rate is defined as obtaining successful cerebrospinal fluid sample with first puncture.Overall puncture success rate is defined as obtaining successful cerebrospinal fluid sample regardless of the number of attempts.Secondary outcomes were the rates of desaturation during the lumbar puncture and puncture-related adverse events.

Data extraction
The following data were extracted by one author and verified by the other author from each included study to a predesigned Excel worksheet: authors, journal, country, setting, main outcome(s), secondary outcome(s), number of participants in each group, number of successful punctures, number or first attempt successful punctures, overall number of punctures, and adverse events.

Risk of bias
Risk of bias was assessed according to Cochrane risk of bias 2.0 tool [16].Risk of bias is presented for each individual study and as a summary plot per assessed domains.Figures were generated by robvis package [17].

Statistics
This review has been conducted according to the guidelines in the Cochrane handbook of systematic reviews [18].Studies were pooled together in meta-analysis.Randomeffects model was chosen due to expected heterogeneity between the studies.Risk ratios with 95% confidence intervals (CI) were calculated with Mantel-Haenszel test.Publication bias is analyzed for all analyses where at least five studies are included [19].Review Manager version 5.4.1 was used in all statistical analyses.
Evidence quality for all outcomes was assessed by the Grading of Recommendations, Assessment, Development and Evaluations [20].This study has been reported according to the preferred reporting items in systematic reviews and meta-analyses 2020 (PRISMA) guideline and the checklist is found in the supplementary materials [21].

Risk of bias
Risk of bias was assessed to be high in two studies; one had some concerns and three studies had low risk of bias (Fig. 2).Most biases arise from the randomization process and bias due to outcome measurement (Fig. 2, Table 3).

Adverse events
Adverse events were reported heterogeneously between the studies (Table 3).One study reported that median lowest saturations were lower in the standard lateral position than in the  sitting position [15] and another study reported longer durations of desaturation in lateral position [42].Another study reported similar saturations in both groups [41].Puncture-related adverse events were rare in all positions, as only one study reported a single case of puncture site hemorrhage (Table 3).

Discussion
We found in this systematic review low-and moderatequality evidence that sitting position is equally effective as standard lateral position in terms of overall success and first attempt success in lumbar punctures performed to infants aged less than 12 months.In addition, we found low-quality evidence that elevated lateral position and prone position had higher first attempt success rates than standard lateral position, but these positions were analyzed only by one study each.All positions seemed to have low rates of adverse events and desaturation during the punctures.We did not identify any previous meta-analysis on the positions during lumbar punctures in infants.Our search retrieved three non-randomized studies that were excluded from this meta-analysis.All of these three assessed sitting position in comparison to lateral position and found that the success rate in sitting position was higher than in the standard lateral position [7][8][9].The systematic review by Hart et al. stated that the different positions seemed to be equally effective and better quality evidence is needed.However, the authors did not pool the results or conduct any critical appraisal [43].The success rates in the included studies varied between 58.2 and 100%.This causes clear heterogeneity in the results.Three studies were conducted in neonatal intensive care units, and these had both the lowest and highest success rates [15,39,42].The original studies did not control for the experience of the lumbar puncture performer in their analyses.Furthermore, operation room lumbar punctures were conducted by anesthesiologists, who typically use routinely lumbar punctures in their daily job while conducting neuraxial anesthesia [40,41].In the three studies that were carried out in the neonatal units, the puncture was performed by a pediatrician.One of the studies was conducted in the emergency department, where the setting is completely different from an operating room or neonatal intensive care unit, and the punctures were performed by pediatricians, family medicine doctors, or emergency medicine doctors [38].
One possible confounder to the results could have been the type of analgesia or procedural sedation used.Two of the included studies did not comment on the pain relief or sedation used [38,42].Two studies used non-nutritive sucking, topical analgesic cream/gel, and sucrose gel as analgesic [15,39].One study used topical analgesic cream/gel and midazolam [40], and one study used topical analgesia with nitric oxide inhalation [41].Thus, all the included studies were conducted on awake patients, with typical non-medical and topical analgesic methods; this does not cause any notable issues to the pooling and synthesis of these studies.
Our main strength is that we did not have protocol deviations.Furthermore, we were able to perform a systematic synthesis of an important topic.Most limitations arise from the limited reporting of the original studies included in this review.Only three of the included studies were judged to have low risk of bias; thus, the reporting quality was limited.Due to the low number of included studies, we did not conduct sensitivity or publication bias analysis.Marshall et al. defined the success rate as first procedure and did not clearly specify the number of attempts, whereas Hanson et al. defined the first puncture success as first attempt success rate.Heterogeneity was a notable limiting factor as for example the study settings were differing (neonatal intensive care unit vs emergency department), and this likely increased the heterogeneity and decreases the validity of the results.Furthermore, the included studies had heterogenous reporting especially in adverse events.Therefore, we decided not to pool these together in meta-analysis.Due to these factors, the evidence quality remained either very low or low mostly.Continuous research effort is needed to improve the success rates in lumbar punctures in infants.Further studies are needed to confirm the findings of all modified positions in relation to standard lateral positions before clear recommendations on the optimal position can be given.Ultrasound was believed to be a promising tool for help in lumbar punctures, but the success rates in randomized controlled trials have not been superior to standard methods in infants [44].There are some reports on the use of bioimpedance needles that are able to detect the cerebrospinal fluid and could thus guide more precisely the optimal depth of the puncture.However, bioimpedance needles have yet not been assessed in randomized trials nor in infants [45].

Conclusion
We found low-to moderate-quality evidence that sitting position seems to be equally effective in terms of first attempt and overall success in lumbar puncture than standard lateral position.Elevated lateral position and prone positions had better first attempt success than standard lateral position, but these were assessed only in one study each and the evidence quality was low.Further studies on optimal lumbar puncture position are needed before concluding which should be the preferred position.
Authors' contributions All authors contributed to the study conception and design.Material preparation, data collection, and analysis were performed by IK and MR.The first draft of the manuscript was written by IK, and all authors commented on previous versions of the manuscript.All authors read and approved the final manuscript.
Funding Open access funding provided by University of Eastern Finland (UEF) including Kuopio University Hospital.

Fig. 1
Fig. 1 Flow chart of the study selection process

Fig. 2
Fig. 2 Risk of bias in the included studies assessed in five domains and overall

Fig. 3
Fig. 3 First attempt success rate in lumbar punctures.Sitting position compared to lateral position

Table 1
Characteristics of the included studies

Table 2
Characteristics of the infants in the included studies

Table 3
Adverse events during lumbar punctures

Table 4
Summary of findings table for main outcomes *Downgraded due to imprecision **Downgraded due to risk of bias and uncertainty in the estimates as only one study assessed this intervention ***Downgraded due to risk of bias, clear heterogeneity in the outcome definitions, and lack of adverse event reporting 4ig.4Overall success rate in lumbar punctures.Sitting position compared to lateral position