Quantifying noxious-evoked baseline sensitivity in neonates to optimise analgesic trials

Autor: Richard Rogers, Caroline Hartley, Gabrielle Green, Eugene P. Duff, Deniz Gursul, Luke Baxter, Gabriela Schmidt Mellado, Miranda Buckle, Amy Hoskin, María Mercedes Cobo, Rebeccah Slater, Marianne van der Vaart, Fiona Moultrie, Eleri Adams, Ria Evans Fry, Foteini Andritsou
Rok vydání: 2021
Předmět:
Male
Heel
Pain in babies
Therapeutic Touch
Psychological intervention
law.invention
0302 clinical medicine
Randomized controlled trial
law
Prospective Studies
Biology (General)
Pain Measurement
Blood Specimen Collection
Clinical Trials as Topic
General Neuroscience
Vaccination
Age Factors
Brain
Electroencephalography
Pain Perception
General Medicine
Analgesics
Non-Narcotic
3. Good health
Distress
Treatment Outcome
medicine.anatomical_structure
Research Design
Medicine
Female
Research Article
Human
Pain Threshold
medicine.medical_specialty
Endpoint Determination
QH301-705.5
Science
baseline sensitivity
Analgesic
Pain
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
Predictive Value of Tests
030225 pediatrics
medicine
Humans
Pain Management
Computer Simulation
Acetaminophen
Retrospective Studies
General Immunology and Microbiology
business.industry
Gold standard
Infant
Newborn
analgesic clinical trials
neonates
Clinical trial
Infant Behavior
Physical therapy
business
030217 neurology & neurosurgery
Neuroscience
Zdroj: eLife, Vol 10 (2021)
eLife
ISSN: 2050-084X
Popis: Despite the high burden of pain experienced by hospitalised neonates, there are few analgesics with proven efficacy. Testing analgesics in neonates is experimentally and ethically challenging and minimising the number of neonates required to demonstrate efficacy is essential. EEG (electroencephalography)-derived measures of noxious-evoked brain activity can be used to assess analgesic efficacy; however, as variability exists in neonate’s responses to painful procedures, large sample sizes are often required. Here, we present an experimental paradigm to account for individual differences in noxious-evoked baseline sensitivity which can be used to improve the design of analgesic trials in neonates. The paradigm is developed and tested across four observational studies using clinical, experimental, and simulated data (92 neonates). We provide evidence of the efficacy of gentle brushing and paracetamol, substantiating the need for randomised controlled trials of these interventions. This work provides an important step towards safe, cost-effective clinical trials of analgesics in neonates.
eLife digest Hospitalized newborns often undergo medical procedures, like blood tests, without pain relief. This can cause the baby to experience short-term distress that may have negative consequences later in life. However, testing the effects of pain relief in newborns is challenging because, unlike adults, they cannot report how much pain they are experiencing. One way to overcome this is to record the brain activity of newborns during a painful procedure and to see how these signals are modified following pain relief. Randomized controlled trials are the gold standard for these kinds of medical assessments, but require a high number of participants to account for individual differences in how babies respond to pain. Finding ways to reduce the size of pain control studies could lead to faster development of pain relief methods. Here, Cobo, Hartley et al. demonstrate a way to reduce the number of newborns needed to test potential pain-relieving interventions. In the experiments, the brain activity of nine babies was measured after a gentle poke and after a painful clinically required procedure. Cobo, Hartley et al. found that the babies’ response to the gentle poke correlated with their response to pain. Further data analysis revealed that this information can be used to predict the variability in pain experienced by different newborns, reducing the number of participants needed for pain relief trials. Next, Cobo, Hartley et al. used this new approach in two pilot tests. One showed that gently stroking an infant’s leg before blood is drawn from their heel reduced their brains’ response to pain. The second showed that giving a baby the painkiller paracetamol lessened the brain’s response to immunisation. The new approach identified by Cobo, Hartley et al. may enable smaller studies that can more quickly identify ways to reduce pain in babies. Furthermore, this work suggests that gentle brushing and paracetamol could provide pain relief for newborns undergoing hospital acute procedures. However, more formal clinical trials are needed to test the effectiveness of these two strategies.
Databáze: OpenAIRE
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