The pharmacokinetics of intravenous paracetamol in neonates: size matters most

Allegaert, Karel; Palmer, Greta M; Anderson, Brian J.

doi:10.1136/adc.2010.204552

Cited by 129 publications

(150 citation statements)

References 34 publications

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“…Recent data from Allegaert et al showed that variance in clearance of intravenous paracetamol is primarily explained by weight and suggests that dosing of intravenous paracetamol should be based on weight instead of PMA [15].…”

Section: Discussionmentioning

confidence: 99%

Pain Treatment of Newborns: Paracetamol Rectal Versus Intravenous Administration, A Randomised Open Clinical Trial

Arc¹,

Jm²,

Jcg³

et al. 2015

J Neonatal Biol

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Early recognition and treatment of pain is of great importance in the neonatal period. Moreover, exposure to pain without effective treatment of pain in this period might influence not only early but also later development [1,2]. Paracetamol is the most frequent prescribed medicine for pain treatment excluding neonates. In the neonatal intensive care unit (NICU) neonates are frequently exposed to painful procedures but most medication used for pain are opioids (morphine and fentanyl). These opioids can have severe adverse effects in premature neonates (depression of breathing, hypotension, urine retention) [3]. On the other hand a clear description of the exposure of rectal paracetamol in preterm and term neonates is lacking [4,5]. In addition, the administration, of rectal paracetamol has limitations such as administration problems, loss of paracetamol suppository with defecation and immaturity of the porta-rectal system especially in preterms leading to a variable absorption. Moreover, in some clinical conditions rectal administration of paracetamol is contraindicated such as necrotising enterocolitis (NEC) and severe thrombocytopenia (< 50×10 9 /l).Taken the adverse effects of opioids and limitations of rectal administration of paracetamol into account it is important to realize that (preterm) newborns has to be treated with medication characterized by good analgesic but less adverse effects or limitations in administration such as intravenous paracetamol. Currently rectal paracetamol is being used in preterm and terme neonates. We know that the effectiveness of rectal paracetamol can be variable in neonates [6,7]. Intravenous paracetamol being used in (preterm) neonates is not common. Improved understanding of the pharmacokinetics (PK) and pharmacodynamics (PD) of paracetamol will contribute to a safer, more effective and predictive analgesic dosing regimen for premature and term neonates. We think it is essential to estimate the effectiveness of intravenous paracetamol compared to rectal paracetamol, based on the hypothesis that intravenous paracetamol is well tolerated, less variable and therefore more reliable in preterm neonates compared to rectal paracetamol.In the present study we used the paracetamol dosing regimen for optimal dosing exposure according to the Dutch guidelines and the described literature [8-10] The rectal and intravenous (iv) dosing is based on the post menstrual age (PMA) and weight in (preterm) neonates during a period of pain. AbstractBackground and aim: Early recognition and treatment of pain is of great importance in the neonatal period.

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Section: Discussionmentioning

confidence: 99%

Pain Treatment of Newborns: Paracetamol Rectal Versus Intravenous Administration, A Randomised Open Clinical Trial

Arc¹,

Jm²,

Jcg³

et al. 2015

J Neonatal Biol

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show abstract

“…Data on the clinical pharmacology of acetaminophen, including pharmacokinetics and tolerance (hepatic, hemodynamics) in neonates following either enteral or intravenous route, have been published. Clearance mainly relates to weight, age, and-to a limited extent-hyperbilirubinemia [174,175]. Hepatic tolerance and hemodynamic tolerance have been documented during repeated administration [173].…”

Section: Acetaminophen (Paracetamol)mentioning

confidence: 99%

“…In addition to oral and rectal formulations, several intravenous (IV) formulations became available more recently. Such a formulation enables the administration of acetaminophen when the enteral route cannot (yet) be used and should improve the predictability by the reduction in variability related to absorption [173][174][175]. Intermittent (p.r.n.)…”

Section: Acetaminophen (Paracetamol)mentioning

confidence: 99%

Sedation in the Neonatal Intensive Care Unit: International Practice

Allegaert

Anker

2014

Pediatric Sedation Outside of the Operating Room

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Inadequate pain management in neonatal life impairs neurodevelopmental outcome because it alters pain thresholds, pain-or stress-related behavior, and physiological responses later in life. However, there are recently also emerging animal experimental and human epidemiological data on the impact of analgo-sedatives on neuro-apoptosis and impaired neurodevelopmental outcome. As a consequence, the management of neonatal pain is in search of a new balance, and these conflicting observations are the main drivers to tailor our pain management in neonates. Adequate pain management is based on prevention, assessment, and treatment with subsequent reassessment. Issues related to prevention and assessment tools are covered. Non-pharmacological (e.g., complementary interventions like facilitated tucking, nonnutritive sucking) and pharmacological (e.g., acetaminophen, opioids, ketamine, propofol) treatment modalities were reviewed and reflect the increased knowledge on neonatal pain management. Each topic ends with some take-home messages that in part also reflect our opinion on the current status of this topic.

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“…In stratified analysis, the cumulative morphine dose in the acetaminophen group compared with the morphine group was 49% lower among neonates aged 0 through 10 days (median dose, 111 g/kg per 48 hours vs 218 g/kg per 48 hours, respectively) and was 73% lower among infants aged 11 through 365 days (median dose, 152 g/kg per 48 hours vs 553 g/kg per 48 hours). For a study designed to investigate the efficacy of acetaminophen, it is arguable that collapsing the age-related strata should have been based on the pharmacokinetics of acetaminophen 7,8 rather than morphine. Nevertheless, reporting data on morphine dose reductions according to the age-group strata originally designed in this study will be of interest for clinicians.…”

mentioning

confidence: 98%

“…To allow clearer assessment of risk-benefit ratios, however, prospective studies evaluating the safety of intravenous acetaminophen are essential before any recommendations can be made regarding its routine clinical use in the postsurgical care of infants. Because acetaminophen clearance is decreased with lower gestational and postnatal age, 7,8 one major concern is that prescribing long-term, standard doses every 6 hoursparticularly for younger children or those with critical illness or poor enteral nutrition-may lead to toxicity. Future studies should not only monitor renal function and liver function but also should measure acetaminophen-protein adducts in all children, particularly neonates, receiving intravenous acetaminophen.…”

mentioning

confidence: 99%

Pain Panacea for Opiophobia in Infants?

Anand¹

2013

JAMA

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The pharmacokinetics of intravenous paracetamol in neonates: size matters most

Cited by 129 publications

References 34 publications

Pain Treatment of Newborns: Paracetamol Rectal Versus Intravenous Administration, A Randomised Open Clinical Trial

Pain Treatment of Newborns: Paracetamol Rectal Versus Intravenous Administration, A Randomised Open Clinical Trial

Sedation in the Neonatal Intensive Care Unit: International Practice

Pain Panacea for Opiophobia in Infants?

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