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Pharmacological interventions for the management of pain and discomfort during lumbar puncture in newborn infants

Pessano, Sara ; Romantsik, Olga LU ; Olsson, Emma ; Hedayati, Ehsan and Bruschettini, Matteo LU orcid (2023) In Cochrane Database of Systematic Reviews 2023(9).
Abstract

Background: Lumbar puncture (LP) is a common invasive procedure, most frequently performed to diagnose infection. Physicians perform LP in newborn infants with the help of an assistant using a strict aseptic technique; it is important to monitor the infant during all the steps of the procedure. Without adequate analgesia, LP can cause considerable pain and discomfort. As newborns have increased sensitivity to pain, it is crucial to adequately manage the procedural pain of LP in this population. Objectives: To assess the benefits and harms, including pain, discomfort, and success rate, of any pharmacological intervention during lumbar puncture in newborn infants, compared to placebo, no intervention, non-pharmacological interventions, or... (More)

Background: Lumbar puncture (LP) is a common invasive procedure, most frequently performed to diagnose infection. Physicians perform LP in newborn infants with the help of an assistant using a strict aseptic technique; it is important to monitor the infant during all the steps of the procedure. Without adequate analgesia, LP can cause considerable pain and discomfort. As newborns have increased sensitivity to pain, it is crucial to adequately manage the procedural pain of LP in this population. Objectives: To assess the benefits and harms, including pain, discomfort, and success rate, of any pharmacological intervention during lumbar puncture in newborn infants, compared to placebo, no intervention, non-pharmacological interventions, or other pharmacological interventions. Search methods: We searched CENTRAL, PubMed, Embase, and three trial registries in December 2022. We also screened the reference lists of included studies and related systematic reviews for studies not identified by the database searches. Selection criteria: We included randomized controlled trials (RCTs) and quasi-RCTs comparing drugs used for pain management, sedation, or both, during LP. We considered the following drugs suitable for inclusion. • Topical anesthetics (e.g. eutectic mixture of local anesthetics [EMLA], lidocaine)
• Opioids (e.g. morphine, fentanyl)
• Alpha-2 agonists (e.g. clonidine, dexmedetomidine)
• N-Methyl-D-aspartate (NMDA) receptor antagonists (e.g. ketamine)
• Other analgesics (e.g. paracetamol)
• Sedatives (e.g. benzodiazepines such as midazolam). Data collection and analysis: We used standard Cochrane methods. We used the fixed-effect model with risk ratio (RR) for dichotomous data and mean difference (MD) or standardized mean difference (SMD) for continuous data, with their 95% confidence intervals (CIs). Our main outcomes were successful LP on first attempt, total number of LP attempts, episodes of bradycardia, pain assessed with validated scales, episodes of desaturation, number of episodes of apnea, and number of infants with one or more episodes of apnea. We used the GRADE approach to evaluate the certainty of the evidence. Main results: We included three studies (two RCTs and one quasi-RCT) that enrolled 206 newborns. One study included only term infants. All studies assessed topical treatment versus placebo or no intervention. The topical anesthetics were lidocaine 4%, lidocaine 1%, and EMLA. We identified no completed studies on opioids, non-steroidal anti-inflammatory drugs, alpha-2 agonists, NMDA receptor antagonists, other analgesics, sedatives, or head-to-head comparisons (drug A versus drug B). Based on very low-certainty evidence from one quasi-RCT of 100 LPs in 76 infants, we are unsure if topical anesthetics (lidocaine), compared to no anesthesia, has an effect on the following outcomes. • Successful LP on first attempt (first-attempts success in 48% of LPs in the lidocaine group and 42% of LPs in the control group)
• Number of attempts per LP (mean 1.9 attempts, [standard error of the mean 0.2] in the lidocaine group, and mean 2.1 attempts [standard error of the mean 2.1] in the control group)
• Episodes of bradycardia (0% of LPs in the lidocaine group and 4% of LPs in the control group)
• Episodes of desaturation (0% of LPs in the lidocaine group and 8% of LPs in the control group)
• Occurrence of apnea (RR 3.24, 95% CI 0.14 to 77.79; risk difference [RD] 0.02, 95% CI −0.03 to 0.08). Topical anesthetics compared to placebo may reduce pain assessed with the Neonatal Facial Coding System (NFCS) score (SMD −1.00 standard deviation (SD), 95% CI −1.47 to −0.53; I² = 98%; 2 RCTs, 112 infants; low-certainty evidence). No studies in this comparison reported total number of episodes of apnea. We identified three ongoing studies, which will assess the effects of EMLA, lidocaine, and fentanyl. Three studies are awaiting classification. Authors' conclusions: The evidence is very uncertain about the effect of topical anesthetics (lidocaine) compared to no anesthesia on successful lumbar puncture on first attempt, the number of attempts per lumbar puncture, episodes of bradycardia, episodes of desaturation, and occurrence of apnea. Compared to placebo, topical anesthetics (lidocaine or EMLA) may reduce pain assessed with the NFCS score. One ongoing study will assess the effects of systemic treatment.

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Contribution to journal
publication status
published
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in
Cochrane Database of Systematic Reviews
volume
2023
issue
9
article number
CD015594
publisher
Wiley-Blackwell
external identifiers
  • pmid:37767875
  • scopus:85173936154
ISSN
1465-1858
DOI
10.1002/14651858.CD015594.pub2
language
English
LU publication?
yes
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ae874a84-baf9-486c-9780-fd1d3146ce16
date added to LUP
2023-12-15 11:37:17
date last changed
2024-04-14 03:28:04
@article{ae874a84-baf9-486c-9780-fd1d3146ce16,
  abstract     = {{<p>Background: Lumbar puncture (LP) is a common invasive procedure, most frequently performed to diagnose infection. Physicians perform LP in newborn infants with the help of an assistant using a strict aseptic technique; it is important to monitor the infant during all the steps of the procedure. Without adequate analgesia, LP can cause considerable pain and discomfort. As newborns have increased sensitivity to pain, it is crucial to adequately manage the procedural pain of LP in this population. Objectives: To assess the benefits and harms, including pain, discomfort, and success rate, of any pharmacological intervention during lumbar puncture in newborn infants, compared to placebo, no intervention, non-pharmacological interventions, or other pharmacological interventions. Search methods: We searched CENTRAL, PubMed, Embase, and three trial registries in December 2022. We also screened the reference lists of included studies and related systematic reviews for studies not identified by the database searches. Selection criteria: We included randomized controlled trials (RCTs) and quasi-RCTs comparing drugs used for pain management, sedation, or both, during LP. We considered the following drugs suitable for inclusion. • Topical anesthetics (e.g. eutectic mixture of local anesthetics [EMLA], lidocaine)
• Opioids (e.g. morphine, fentanyl)
• Alpha-2 agonists (e.g. clonidine, dexmedetomidine)
• N-Methyl-D-aspartate (NMDA) receptor antagonists (e.g. ketamine)
• Other analgesics (e.g. paracetamol)
• Sedatives (e.g. benzodiazepines such as midazolam). Data collection and analysis: We used standard Cochrane methods. We used the fixed-effect model with risk ratio (RR) for dichotomous data and mean difference (MD) or standardized mean difference (SMD) for continuous data, with their 95% confidence intervals (CIs). Our main outcomes were successful LP on first attempt, total number of LP attempts, episodes of bradycardia, pain assessed with validated scales, episodes of desaturation, number of episodes of apnea, and number of infants with one or more episodes of apnea. We used the GRADE approach to evaluate the certainty of the evidence. Main results: We included three studies (two RCTs and one quasi-RCT) that enrolled 206 newborns. One study included only term infants. All studies assessed topical treatment versus placebo or no intervention. The topical anesthetics were lidocaine 4%, lidocaine 1%, and EMLA. We identified no completed studies on opioids, non-steroidal anti-inflammatory drugs, alpha-2 agonists, NMDA receptor antagonists, other analgesics, sedatives, or head-to-head comparisons (drug A versus drug B). Based on very low-certainty evidence from one quasi-RCT of 100 LPs in 76 infants, we are unsure if topical anesthetics (lidocaine), compared to no anesthesia, has an effect on the following outcomes. • Successful LP on first attempt (first-attempts success in 48% of LPs in the lidocaine group and 42% of LPs in the control group)
• Number of attempts per LP (mean 1.9 attempts, [standard error of the mean 0.2] in the lidocaine group, and mean 2.1 attempts [standard error of the mean 2.1] in the control group)
• Episodes of bradycardia (0% of LPs in the lidocaine group and 4% of LPs in the control group)
• Episodes of desaturation (0% of LPs in the lidocaine group and 8% of LPs in the control group)
• Occurrence of apnea (RR 3.24, 95% CI 0.14 to 77.79; risk difference [RD] 0.02, 95% CI −0.03 to 0.08). Topical anesthetics compared to placebo may reduce pain assessed with the Neonatal Facial Coding System (NFCS) score (SMD −1.00 standard deviation (SD), 95% CI −1.47 to −0.53; I² = 98%; 2 RCTs, 112 infants; low-certainty evidence). No studies in this comparison reported total number of episodes of apnea. We identified three ongoing studies, which will assess the effects of EMLA, lidocaine, and fentanyl. Three studies are awaiting classification. Authors' conclusions: The evidence is very uncertain about the effect of topical anesthetics (lidocaine) compared to no anesthesia on successful lumbar puncture on first attempt, the number of attempts per lumbar puncture, episodes of bradycardia, episodes of desaturation, and occurrence of apnea. Compared to placebo, topical anesthetics (lidocaine or EMLA) may reduce pain assessed with the NFCS score. One ongoing study will assess the effects of systemic treatment.</p>}},
  author       = {{Pessano, Sara and Romantsik, Olga and Olsson, Emma and Hedayati, Ehsan and Bruschettini, Matteo}},
  issn         = {{1465-1858}},
  language     = {{eng}},
  number       = {{9}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Cochrane Database of Systematic Reviews}},
  title        = {{Pharmacological interventions for the management of pain and discomfort during lumbar puncture in newborn infants}},
  url          = {{http://dx.doi.org/10.1002/14651858.CD015594.pub2}},
  doi          = {{10.1002/14651858.CD015594.pub2}},
  volume       = {{2023}},
  year         = {{2023}},
}