Perioperative Acetaminophen Dosing in Obese Children.

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.

Considerations for Intravenous Anesthesia Dose in Obese Children: Understanding PKPD.

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.

Surgical interventions in children with meningococcal purpura fulminans--a review of 117 procedures in 21 children.

BACKGROUND/PURPOSE: There are few reports describing the surgical management and outcome of children suffering purpura fulminans secondary to meningococcal sepsis. New Zealand is in the grips of a meningococcal epidemic, and, with the attendant sequalae of the disease process, the authors sought to formally review the children who have required surgical involvement. METHODS: A retrospective case review of children with the sequalae of meningococcal disease presenting to the Orthopedic and Plastic Surgical Units in a university teaching hospital was undertaken. RESULTS: There were 117 procedures in 21 children performed over a 12-year period. Surgical management was separated into 2 phases-early and late. The mean delay from admission with acute sepsis to the first surgical procedure (ie, early intervention) was 15.9 days. Debridement and autologous skin grafting was the mainstay of managing the necrotic defects; however, allograft skin proved a useful adjunct as a physiologic dressing. Local flaps were used with deep defects down to bone, but in the extremities amputation to viable tissue was required once gangrene was demarcated. Amputations were carried out in 9 of 21 children. Late interventions were related to relief of contractures or fibula overgrowth causing stump ulceration. Clinical follow-up showed that all children interviewed over 5 years of age (9 children) attend ordinary regular school classes and were physically active within the context of their physical disabilities. CONCLUSIONS: The data would suggest that children requiring surgery for purpura fulminans achieve age-appropriate milestones and are primarily limited by their physical disability related to amputations, scarring, and abnormal bone growth.