Drug Dosing in Patients with Obesity

Last updated: 03/22/2023

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Key Points

Total body weight (TBW), lean body weight (LBW), and ideal body weight (IBW) are important parameters to consider when dosing medications in a patient with obesity. Incorrect application of these measurements may result in underdosing or overdosing of certain medications.
Patients with obesity have differential proportions of lean body mass and fat mass when compared to patients of normal weight. Fat mass increases proportionally faster than lean body mass as weight increases above a normal body mass index (BMI).
Patients with obesity have an increased volume of distribution and cardiac output, leading to differences in the plasma concentrations of medications.
Dosing induction medications based on total body weight may result in hemodynamic instability. Agents such as propofol and etomidate should be dosed according to LBW and titrated to effect.
Dosing of nondepolarizing neuromuscular blockers should be based on IBW, while succinylcholine dosing should be based on TBW.

Body Mass Scalars

Obesity is defined by a BMI > 30 kg/m2. Class III obesity (formerly morbid obesity) is defined as BMI ≥ 40 or BMI ≥ 35 with an obesity-related medical comorbidity (e.g., hypertension or diabetes mellitus).
Total body weight (TBW): the measured weight or mass of an individual (typically in kg).
Ideal body weight (IBW): theoretically, the optimal weight associated with maximum life expectancy for an individual of a given height and sex.
- IBW (men) = 50 kg + 2.3 x (Height [inches] – 60)
- IBW (women) = 45.5 kg + 2.3 x (Height [inches] – 60)
- IBW (children) = BMI at 50th percentile x Height [m]² – best used for children older than 3 years.
Lean body weight (LBW): the difference between TBW and fat mass and consists of vital organs, muscle, bone, and extracellular fluid.¹ Fat mass increases proportionally faster than lean body mass as weight increases above a normal BMI (Figure 1).
- LBW (men) = [9270 x TBW (kg)] / [6680 + (216 x BMI (kg/m²))]
- LBW (women) = [9270 x TBW (kg)] / [8780 + (244 x BMI (kg/m²))]
- Several online calculators exist for LBW that are generally accurate and can be used when dosing hydrophilic medications based on LBW. An example includes: Link
Adjusted body weight (ABW): calculation intended to correct for an altered volume of distribution in patients with obesity.
- ABW = IBW + correction factor x (TBW – IBW).

Figure 1. Relationship of TBW to LBW and fat mass. As TBW increases above a normal BMI, fat weight increases more quickly than LBW. Figure adapted from data based on Janmahasatian et al. Quantification of lean body weight. Clinical Pharmacokinetics. 2005; 44:1051-65.¹

Pharmacokinetic Changes in Obesity

Volume of distribution is a proportionality constant (theoretical volume) relating the total amount of a drug administered to the measured plasma concentration (Vd = amount of drug administered (mg) ÷ measured plasma concentration (mg/L).
Higher volumes of distribution represent greater drug distribution into tissues (and by definition, lower plasma concentrations available for drug effect).
The effect of obesity on the volume of distribution for lipophilic vs. hydrophilic drugs is variable.
Cardiac output in obesity increases by ~20-30 mL/kg of excess fat, but the proportion of blood flow to fat decreases from ~5% to 2% in patients with obesity.
Serum albumin levels are generally stable in obesity, but serum alpha-1-acid glycoprotein (AGP) levels may be increased. Higher levels of AGP may lead to increased protein binding and therefore decreased free plasma concentration of drugs that bind AGP.²
Obesity often coexists with hepatic steatosis leading to functional degeneration of the liver and altered drug metabolism.
- Different CYP450 enzymes are variably affected by obesity which may lead to an increase or decrease in drug metabolism.
Obesity has strong associations with the development of hypertension and diabetes mellitus (the two leading causes of chronic kidney disease).³
- Glomerular filtration rate and, therefore, renal clearance of drugs may be increased in younger, otherwise healthy patients with obesity (due to increased cardiac output).²
- As chronic kidney disease develops, renal clearance of drugs diminishes.
- Drug dosing should incorporate measured creatinine clearance for patients with obesity, particularly those with obesity-related comorbidities.

Drug Dosing in Obesity

Recommended dosing scalar for commonly used anesthetic medications is shown below in Table 1.

Table 1. Dosing of common anesthetic drugs in patients with obesity.

References

Janmahasatian S, Duffull SB, Ash S, et al. Quantification of lean bodyweight. Clin Pharmacokinet. 2005; 44:1051-65. PubMed
Hanley MJ, Abernethy DR, Greenblatt DJ. Effect of obesity on the pharmacokinetics of drugs in humans. Clin Pharmacokinet. 2010;49(2):71-87. PubMed
Kovesdy CP, Furth SL, Zoccali C, et al. Obesity and kidney disease: Hidden consequences of the epidemic. Can J Kidney Health Dis. 2017; 4:2054358117698669. PubMed
Servin F, Farinotti R, Haberer JP, et al. Propofol infusion for maintenance of anesthesia in morbidly obese patients receiving nitrous oxide. A clinical and pharmacokinetic study. Anesthesiology. 1993; 78:657-65. PubMed
Schwenk ES, Viscusi ER, Buvanendran A, et al. Consensus guidelines on the use of intravenous ketamine infusions for acute pain management from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018;43(5):456-66. PubMed
Meyhoff CS, Lund J, Jenstrup MT, et al. Should dosing of rocuronium in obese patients be based on ideal or corrected body weight? Anesth Analg. 2009;109(3):787-92. PubMed
Lemmens HJ, Brodsky JB. The dose of succinylcholine in morbid obesity. Anesth Analg. 2006;102(2):438-42. PubMed
Llaurado S, Sabate A, Ferreres E, et al. Sugammadex ideal body weight adjusted by level of neuromuscular blockade in laparoscopic bariatric surgery. Anesthesiology. 2012; 117:93-8. PubMed
De Baerdemaeker LEC, Mortier EP, Struys M. Pharmacokinetics in obese patients. Continuing Education in Anaesthesia Critical Care & Pain. 2015; 15:60-3. Link
Erstad BL, Barletta JF. Drug dosing in the critically ill obese patient: a focus on medications for hemodynamic support and prophylaxis. Crit Care. 2021; 25:77. PubMed

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