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This paper explores the issues that contribute to unintentional over and under-dosing in children with obesity in the hospital setting. Pragmatic solutions to these issues and possible barriers to their implementation are discussed.
Children with obesity are at risk of overdose if total body weight (TBW) is used inappropriately during weight-based dose calculations.1–3 Potentially serious toxic effects include opioid-induced respiratory depression, paracetamol-induced hepatic injury and antibiotic-induced renal injury. Such drugs are routinely prescribed by very junior medical staff, who may be unaware of the risks of overdose when using TBW to calculate drug doses.
Inadvertent drug overdose is just one of several risks faced by children with obesity during hospital admission. They are twice as likely as healthy weight children to experience life-threatening airway and breathing-related complications during anaesthesia and the perioperative period. They may have increased length of stay, and they are more likely to undergo certain types of surgery such as tonsillectomy. Coexisting conditions can complicate drug effects such as sleep apnoea and non-alcoholic fatty liver disease.4 5
Therapeutic failure can result from underdosing if dose reduction is inappropriately performed using ideal body weight (IBW), guesswork or age-based dosing.2 6 IBW can be a much lower value than an obese child’s actual weight, and the dosing of many drugs requires an adjustment above IBW as a result of the additional fat and lean mass that develops in obesity. Size descriptors that are between IBW and TBW, such as lean body mass (LBM) or adjusted body weight (ABW), are often more appropriate.1 2
The dose adjustment methods recommended in obesity are complex and time consuming. This is an important potential barrier to safe dose calculation and may explain why confusion and a ‘best guess’ approach is observed in clinical practice. Clinicians with some awareness of the risks may undertake arbitrary reduction of doses in an attempt to prevent toxic effects. This is a tempting solution in the time-pressured healthcare setting and may be the best option available to staff in centres where dose adjustment guidelines have not been implemented.
Why and how should doses be adjusted in obesity?
Dose adjustment is necessary in obesity due to the increased proportion of fat and lean mass that leads to alterations in cardiac output, total body water, organ size and organ function. This complicates the distribution, metabolism and excretion of drugs. There is no simple ‘rule of thumb’ which can be applied to all dose calculations, and the majority of evidence to guide dose adjustments in children with obesity is extrapolated from adult practice or based on expert opinion.
Of the studies and reviews that describe dose adjustment in obesity, many have adopted the use of size descriptors that are more appropriate than TBW, such as LBM, IBW and ABW (using a specified cofactor for adjustment) and the choice of descriptor depends on the specific drug.1–3 7 For example, in the case of morphine, IBW dosing has been recommended, with titration to effect.7 For fentanyl boluses and certain anaesthetic agents, LBM is a recommended size descriptor,3 and for cephalosporins, vancomycin and suxamethonium the use of TBW is appropriate.2 The recommended size descriptor for use in enoxaparin and gentamicin dosing is ABW with a cofactor 0.4.2 8 9 Calculation of drug dose therefore depends on the accurate calculation of the appropriate size descriptor, and the complexity of this poorly understood step is an important barrier to accurate dose adjustment.
Recent reviews1–3 of pharmacokinetics in obese patients have greatly improved the availability of information in the case of many drugs, and a selection of commonly used drugs and their corresponding size descriptors is given in table 1. At the time of writing there is little or no research to guide optimal dosing for common agents such as paracetamol, intravenous fluids and local anaesthetics. In these circumstances, a balance must be found which prevents overdose and toxicity but also prevents inadequately low doses. A simple, pragmatic solution is to consider the use of LBM for dose adjustment of such drugs until robust data is available to clarify specific drug dose adjustments in more detail.
Size descriptors and their calculation
Ideal body weight
IBW is a concept that cannot be measured. It is defined as the healthiest weight of a child for their height, gender and age and represents the weight associated with the longest life expectancy. IBW can be derived from the reverse body mass index (BMI) equation:
where BMI50 represents the 50th centile of a BMI chart, which is the ideal BMI for their height, age and gender. Other methods exist for estimation of IBW, such as Moore’s method, McLaren’s method and linear equations such as [2 x (age +4)]. These methods have shown to be useful for certain age subgroups of children, but the reverse BMI method is superior across a wider range of ages and heights.10
Adjusted body weight
The ABW approach uses the IBW of the child and adds a specified cofactor, which is a fraction of the excess weight gain between IBW and TBW, and has been recommended for the dosing of certain drugs such as aminoglycosides which require a dosing scalar higher than IBW, but lower than TBW. The following example uses an ABW cofactor of 0.4:
Lean body mass
LBM is the mass of the lean tissues that remain once adipose tissue mass is subtracted. It can be measured using various techniques such as dual-energy X-ray absorptiometry (DEXA) but the methods are complex, expensive and not immediately available. Obese children are, on average, taller and have increased organ size, increased cardiac output and increased lean tissue, particularly in the legs.11 12 This lean tissue comprises 20%–40% (mean 29%) of the excess weight gained over and above ideal weight in obesity. This has led to the development of a calculation to estimate LBM as follows7 13:
The LBM equation above requires the IBW to be calculated first and is effectively an ABW with a cofactor of 0.29. The calculation is only relevant for patients who are overweight and those who are ambulatory. Children with obesity who are non-ambulatory may develop less lean tissue, and in these circumstances, an individual assessment of LBM is advisable.
In the absence of a simple, easily accessible method for calculation of IBW, ABW and LBM, then the temptation to make an ‘educated guess’ becomes an appealing option. Given that overdosing and underdosing can lead to harm, it follows that improvement of the simplicity and accessibility of the above equations, while maintaining accuracy, may benefit clinicians and pharmacists. With this objective in mind, the author has previously published a simple, accurate and rapid method to perform calculation of LBM and IBW in children with obesity (see figure 1).14
How and why should we identify the children at risk and alert prescribers of the need to adjust doses?
Identification of the children at risk of misdosing is crucial to their safety, but despite this potential harm, many paediatric units lack routine screening for obesity on admission to hospital. Healthcare workers in this situation must rely on their own visual assessment for the presence of obesity on an ad hoc basis. Adults are known to be poor at recognising the presence of obesity in children, which may lead to missed cases.15 In the absence of a robust system to identify obese children and alert clinical staff, it is therefore difficult to prevent dosing errors. The perfect screening tool to measure adiposity in all paediatric admissions does not exist, but the most widely used method is BMI, which has high specificity for adiposity.16 The clinical cut-off used in the UK is the 98th BMI centile. This should not be confused with the WHO cut-off, which is slightly higher, or the cut-off used in UK epidemiological data collection, such as the National Child Measurement Programme, which is the 95th BMI centile.
A potential barrier to the implementation of BMI screening is lack of routine height measurement for all children at the point of admission to hospital. Without a recent height it is not possible to assess BMI, and therefore identify which children are obese, or calculate doses using the methods discussed. Another potential barrier is the task of performing BMI calculation and assessing BMI centile which requires additional staff time, training and equipment. It may be helpful to quantify financial and patient safety benefits in order to motivate stakeholders that screening is necessary. Price and colleagues17 highlighted huge potential for cost savings in growth hormone prescribing by using dose adjustment in children with obesity, and this approach may be transferrable to other drugs. Evidence for patient safety benefits is currently limited to retrospective analysis of individual cases of harm, which are often addressed locally. The impact of inaccurate dosing in paediatric obesity is unknown and cannot be quantified or improved unless institutions monitor prescribing in all patients at risk. The author believes that this process should begin with BMI screening for all paediatric admissions in order to identify patients at risk.
Harm due to overdose and underdosing in childhood obesity is a risk unless preventative measures are taken, and a possible way forward is suggested in box 1.
Suggested dosing safety care pathway for children with obesity
Height, weight and BMI centile for all paediatric admissions
Children with BMI centile>98th enter obesity dosing pathway
Calculate IBW, LBM and ABW using methods shown
Alerting system to warn all potential prescribers of need to adjust doses
For example, prescription chart warning box or alert embedded within electronic prescribing software
An easily accessible, locally agreed obesity guideline indicating which size descriptor to be used for each drug
Prioritise common and harmful drugs such as paracetamol, antibiotics, opioids, expensive drugs such as growth hormone and drugs with a narrow therapeutic range
Consider using a pragmatic compromise such as LBM if dosing information is unavailable, for example, paracetamol
ABW, adjusted body weight; BMI, body mass index; IBW, ideal body weight; LBM, lean body mass.
Institutions should focus on identification of children on admission before they are exposed to risk, and the most widely used screening method is BMI centile assessment. This should be followed by the triggering of an alert to warn prescribers of the need for dose adjustment for those with a BMI above the 98th centile; either on the written prescription chart or embedded within electronic prescribing software. Individual doses can then be calculated following selection of the appropriate size descriptor for each drug using the simple method found in figure 1 or the three equations discussed above. Priority should be given to potentially harmful, commonly used drugs such as paracetamol, opioids and antibiotics, expensive drugs and those with a narrow therapeutic range where dosing accuracy is likely to be important. The author believes that future efforts should concentrate on the development of a nationally approved software application to simplify the entire process.
Test your knowledge
LBM and IBW are the same value in obesity.
All of the excess weight gained by obese children is fatty tissue.
LBM is the dosing scalar recommended for calculating paracetamol dose.
LBM can be measured.
IBW can be measured.
IBW is the weight of the child which remains when adipose tissue mass is subtracted.
IBW is the size descriptor recommended for gentamicin dosing.
The calculation of cephalosporin dose using IBW may lead to under dosing.
Regarding obesity screening in children:
Visual assessment of children is a reliable screening method for obesity.
The UK clinical cut-off for obesity is the 98th BMI centile.
The BMI is a direct measure of adiposity.
The 50th centile of a BMI chart represents ideal BMI for a child’s age, height and gender.
BMI, body mass index; IBW, ideal body weight; LBM, lean body mass.
Answers are at the end of the references.
Competing interests None declared.
Provenance and peer review Commissioned; externally peer reviewed.