A Critical Review on the Relevance of Paracetamol for Procedural Pain Management in Neonates

Allegaert, Karel

doi:10.3389/fped.2020.00089

Cited by 21 publications

(17 citation statements)

References 80 publications

(139 reference statements)

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“…In vivo, in vitro and ex vivo studies have shown that APAP directly perturbs hormone-dependent processes, including inhibition of androgen production and increased oestrogen production, disruption of steroidogenesis, depletion of sulfated sex hormones, perturbation of immune function, induction of oxidative stress and indirect activation of the endocannabinoid system 1,2,[61][62][63][64][65] . Independently of APAP, these processes have been implicated as mechanisms related to the development of neurodevelopmental [66][67][68][69][70][71][72][73][74][75][76] and reproductive disorders 2 . In addition to potential effects on neuronal and reproductive development, a combination of clinical studies together with experimental work in animal models and cell lines has also suggested that APAP exposure during pregnancy might decrease fetal haematopoietic stem cell numbers alter steroidogenesis in the placenta and induce placental damage 65,[77][78][79][80] .…”

Section: Nature Reviews | Endocrinologymentioning

confidence: 99%

Paracetamol use during pregnancy — a call for precautionary action

Bauer¹,

Swan

Kriebel³

et al. 2021

Nat Rev Endocrinol

114

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Paracetamol (N-acetyl-p-aminophenol (APAP), otherwise known as acetaminophen) is the active ingredient in more than 600 medications used to relieve mild to moderate pain and reduce fever. APAP is widely used by pregnant women as governmental agencies, including the FDA and EMA, have long considered APAP appropriate for use during pregnancy when used as directed. However, increasing experimental and epidemiological research suggests that prenatal exposure to APAP might alter fetal development, which could increase the risks of some neurodevelopmental, reproductive and urogenital disorders. Here we summarize this evidence and call for precautionary action through a focused research effort and by increasing awareness among health professionals and pregnant women. APAP is an important medication and alternatives for treatment of high fever and severe pain are limited. We recommend that pregnant women should be cautioned at the beginning of pregnancy to: forego APAP unless its use is medically indicated; consult with a physician or pharmacist if they are uncertain whether use is indicated and before using on a long-term basis; and minimize exposure by using the lowest effective dose for the shortest possible time. We suggest specific actions to implement these recommendations. This Consensus Statement reflects our concerns and is currently supported by 91 scientists, clinicians and public health professionals from across the globe.

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Section: Nature Reviews | Endocrinologymentioning

confidence: 99%

Paracetamol use during pregnancy — a call for precautionary action

Bauer¹,

Swan

Kriebel³

et al. 2021

Nat Rev Endocrinol

114

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“…The rising use of paracetamol as adjunct to opioids following major surgeries between the two timepoints of our study also supports the findings of other relevant publications. A recent meta-analysis and a review showed that existing data are not sufficient to support a role of paracetamol in reducing the procedural pain in neonates but may reduce the need for morphine following major surgery (36,37).…”

Section: Changes In Medications Usedmentioning

confidence: 99%

Changes in Physicians' Perceptions and Practices on Neonatal Pain Management Over the Past 20 Years. A Survey Conducted at Two Time-Points

et al. 2021

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Intense research for more than three decades expelled the view that neonates do not experience pain. The aim of this survey was to investigate whether the Greek physicians involved in neonatal intensive care have changed their perceptions regarding neonatal pain, adapting their management practices to the knowledge that have emerged in the past 20-years. This study is a survey conducted at two time-points, 20 years apart. Anonymous questionnaires were distributed to 117 and 145 physicians working in neonatal intensive care units (NICUs) all over Greece in years 2000 and 2019, respectively. The response rate was 90.6 and 80.7% in 2000 and 2019, respectively. All respondents, at both time-points, believed that neonates experience pain, which has serious acute and long-term consequences, while the vast majority considered analgesia-sedation (A-S) during painful interventions as obligatory. Utilization of NICU protocols and pain assessment tools remained low although increased significantly between 2000 and 2019. The use of systemic A-S postoperatively was high at both time-points, while its implementation in infants subjected to prolonged pain, specifically mechanical ventilation, increased significantly by 2019. Systemic or local analgesia for acute procedural pain was used by lower proportions of physicians in 2019, except for the tracheal intubation. In contrast, the use of sweet solutions and non-pharmacological measures prior to or during bedside procedures significantly increased over time. Opioid administration significantly increased, while a shift from morphine to fentanyl was observed. International literature and perinatal–neonatal congresses were stated as the main sources of updating physicians' knowledge and improving management practice on neonatal pain prevention and treatment. In conclusion, Greek NICU-physicians' perceptions that neonates can experience pain with potentially serious acute and long-term consequences remained strong over the past 20 years. Although physicians' practices on neonatal pain management improved, they are still suboptimal, while significant differences exist among centers. Continuing education, globally accepted management protocols, and readily applied pain assessment tools would further improve the management of procedural pain and stress in neonates.

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“…Paracetamol and ibuprofen have equal efficacy for the treatment of fever in infants [24], and paracetamol has evolved into a cornerstone of effective pain relief in neonates. Paracetamol allows for reduced dosing of opioids and may be used to effectively treat moderate pain after surgery, while there is insufficient evidence to support its use for painful procedures [68,69]. Paracetamol given after assisted vaginal birth may even increase the response to subsequent painful procedures [70].…”

Section: Postnatal Use Of Paracetamol In Term and Preterm Newborn Infantsmentioning

confidence: 99%

Paracetamol (Acetaminophen) and the Developing Brain

Bührer

Endesfelder

Scheuer

et al. 2021

IJMS

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Paracetamol is commonly used to treat fever and pain in pregnant women, but there are growing concerns that this may cause attention deficit hyperactivity disorder and autism spectrum disorder in the offspring. A growing number of epidemiological studies suggests that relative risks for these disorders increase by an average of about 25% following intrauterine paracetamol exposure. The data analyzed point to a dose–effect relationship but cannot fully account for unmeasured confounders, notably indication and genetic transmission. Only few experimental investigations have addressed this issue. Altered behavior has been demonstrated in offspring of paracetamol-gavaged pregnant rats, and paracetamol given at or prior to day 10 of life to newborn mice resulted in altered locomotor activity in response to a novel home environment in adulthood and blunted the analgesic effect of paracetamol given to adult animals. The molecular mechanisms that might mediate these effects are unknown. Paracetamol has diverse pharmacologic actions. It reduces prostaglandin formation via competitive inhibition of the peroxidase moiety of prostaglandin H2 synthase, while its metabolite N-arachidonoyl-phenolamine activates transient vanilloid-subtype 1 receptors and interferes with cannabinoid receptor signaling. The metabolite N-acetyl-p-benzo-quinone-imine, which is pivotal for liver damage after overdosing, exerts oxidative stress and depletes glutathione in the brain already at dosages below the hepatic toxicity threshold. Given the widespread use of paracetamol during pregnancy and the lack of safe alternatives, its impact on the developing brain deserves further investigation.

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A Critical Review on the Relevance of Paracetamol for Procedural Pain Management in Neonates

Cited by 21 publications

References 80 publications

Paracetamol use during pregnancy — a call for precautionary action

Paracetamol use during pregnancy — a call for precautionary action

Changes in Physicians' Perceptions and Practices on Neonatal Pain Management Over the Past 20 Years. A Survey Conducted at Two Time-Points

Paracetamol (Acetaminophen) and the Developing Brain

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