Drug dosing in children with obesity: a narrative updated review

Gaeta, Francesca; Conti, Valeria; Pepe, Angela; Vajro, Pietro; Filippelli, Amelia; Mandato, Claudia

doi:10.1186/s13052-022-01361-z

Cited by 7 publications

(9 citation statements)

References 84 publications

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“…Expert opinion continues to presume that the dose in the obese child will be determined by pharmacokinetic understanding [ 3 , 8 ]. While this opinion is certainly valid, there are a number of thorns on this rose of an opinion.…”

Section: Discussionmentioning

confidence: 99%

“…There is often confusion as to which metric is best suited for an individual child and that metric may change between phases of anesthesia (e.g., lean body mass for propofol induction dose and total body weight for maintenance dose rate) [ 5 , 6 , 7 ]. Consequently, recommendations for any size scaler are tempered by expert opinion that presumes dose in the obese child will be determined by better pharmacokinetic understanding [ 3 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

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Considerations for Intravenous Anesthesia Dose in Obese Children: Understanding PKPD

Morse

Cortínez

Anderson

2023

JCM

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The intravenous induction or loading dose in children is commonly prescribed per kilogram. That dose recognizes the linear relationship between volume of distribution and total body weight. Total body weight comprises both fat and fat-free mass. Fat mass influences the volume of distribution and the use of total body weight fails to recognize the impact of fat mass on pharmacokinetics in children. Size metrics alternative to total body mass (e.g., fat-free and normal fat mass, ideal body weight and lean body weight) have been proposed to scale pharmacokinetic parameters (clearance, volume of distribution) for size. Clearance is the key parameter used to calculate infusion rates or maintenance dosing at steady state. Dosing schedules recognize the curvilinear relationship, described using allometric theory, between clearance and size. Fat mass also has an indirect influence on clearance through both metabolic and renal function that is independent of its effects due to increased body mass. Fat-free mass, lean body mass and ideal body mass are not drug specific and fail to recognize the variable impact of fat mass contributing to body composition in children, both lean and obese. Normal fat mass, used in conjunction with allometry, may prove a useful size metric but computation by clinicians for the individual child is not facile. Dosing is further complicated by the need for multicompartment models to describe intravenous drug pharmacokinetics and the concentration effect relationship, both beneficial and adverse, is often poorly understood. Obesity is also associated with other morbidity that may also influence pharmacokinetics. Dose is best determined using pharmacokinetic–pharmacodynamic (PKPD) models that account for these varied factors. These models, along with covariates (age, weight, body composition), can be incorporated into programmable target-controlled infusion pumps. The use of target-controlled infusion pumps, assuming practitioners have a sound understanding of the PKPD within programs, provide the best available guide to intravenous dose in obese children.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Considerations for Intravenous Anesthesia Dose in Obese Children: Understanding PKPD

Morse

Cortínez

Anderson

2023

JCM

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“…Expert opinion presumes that the dose in the obese child is best determined by pharmacokinetic understanding [ 2 , 3 , 4 ]. It is known that obesity has an effect on acetaminophen volume of distribution, notably through dissemination between lean body mass and fat mass, both of which increase independently in the obese individual.…”

Section: Current Acetaminophen Dose Estimationmentioning

confidence: 99%

“…Although recommendations for particular size scalers abound in the literature [ 21 ], most carry the caveat that the dose in the obese child will be determined by better pharmacokinetic understanding [ 2 , 3 , 4 ] and this remains lacking for many drugs used in the perioperative period. The use of pharmacokinetic (PK) and pharmacodynamic (PD) mathematical equations (known as models) is a central foundation for improving dose estimation [ 25 ].…”

Section: Size Model Foiblesmentioning

confidence: 99%

Perioperative Acetaminophen Dosing in Obese Children

Anderson

Cortínez

2023

Children

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Acetaminophen is a commonly used perioperative analgesic drug in children. The use of a preoperative loading dose achieves a target concentration of 10 mg/L associated with a target analgesic effect that is 2.6 pain units (visual analogue scale 1–10). Postoperative maintenance dosing is used to keep this effect at a steady-state concentration. The loading dose in children is commonly prescribed per kilogram. That dose is consistent with the linear relationship between the volume of distribution and total body weight. Total body weight is made up of both fat and fat-free mass. The fat mass has little influence on the volume of distribution of acetaminophen but fat mass should be considered for maintenance dosing that is determined by clearance. The relationship between the pharmacokinetic parameter, clearance, and size is not linear. A number of size metrics (e.g., fat-free and normal fat mass, ideal body weight and lean body weight) have been proposed to scale clearance and all consequent dosing schedules recognize curvilinear relationships between clearance and size. This relationship can be described using allometric theory. Fat mass also has an indirect influence on clearance that is independent of its effects due to increased body mass. Normal fat mass, used in conjunction with allometry, has proven a useful size metric for acetaminophen; it is calculated using fat-free mass and a fraction (Ffat) of the additional mass contributing to total body weight. However, the Ffat for acetaminophen is large (Ffat = 0.82), pharmacokinetic and pharmacodynamic parameter variability high, and the concentration–response slope gentle at the target concentration. Consequently, total body weight with allometry is acceptable for the calculation of maintenance dose. The dose of acetaminophen is tempered by concerns about adverse effects, notably hepatotoxicity associated with use after 2–3 days at doses greater than 90 mg/kg/day.

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“…Nevertheless, it is important to note that pediatric drug dosages cannot be directly standardized from an adult dose based solely on TBW (i.e., 60 kg adult is not equal to 60 kg child) when pediatric dosing data are unavailable [ 48 ]. Additionally of note is a very pressing issue in the last 15–20 years about drug dosing in obese children [ 49 ]. In obese children, dosing based on body weight and BSA might result in doses exceeding the maximum recommended for adults.…”

Section: The Need For Pediatric Drugsmentioning

confidence: 99%

Off-Label Prescribing in Pediatric Population—Literature Review for 2012–2022

Petkova,

Georgieva,

Dimitrov

et al. 2023

Pharmaceutics

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Off-label prescribing is widespread among pediatricians, and it is unlikely that this trend will soon be bound by a uniform legal framework. This is necessitated by the fact that there are four variables: the patient’s health condition, the physician’s experience and knowledge, the legislative measures (laws, directives, guidelines, and recommendations), and finally, the pharmaceutical industry. There is considerable concern worldwide about the use of off-label medicines in children. We may call it an enormous global problem that is much talked about and written about; however, we should not forget that the goal around which everyone should unite is the patient’s life. For healthcare providers, the most important thing will always be the health and preservation of the patient’s life, particularly when it comes to children with life-threatening conditions in neonatal and pediatric intensive care units (NICU and PICU). The study aimed to examine the prevalence of off-label drug use in pediatrics. Literature research was conducted, and we included studies from 2012 to 2022 that evaluated off-label drug prevalence in various pediatric patient populations.

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Drug dosing in children with obesity: a narrative updated review

Cited by 7 publications

References 84 publications

Considerations for Intravenous Anesthesia Dose in Obese Children: Understanding PKPD

Considerations for Intravenous Anesthesia Dose in Obese Children: Understanding PKPD

Perioperative Acetaminophen Dosing in Obese Children

Off-Label Prescribing in Pediatric Population—Literature Review for 2012–2022

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