Brian K. Parker, MD, MS; Sara Manning, MD; Michael E. Winters, MD, MBA

Disclosures

Western J Emerg Med. 2019;20(2):323-330. 

In This Article

Pharmacotherapy

As highlighted in the preceding intubation section, medication dosing in the obese patient is challenging. Importantly, almost all dosing recommendations have been developed for non-obese patients and are then extrapolated to the obese population. This extrapolation can lead to dosing errors and result in medication toxicity or treatment failure. Proper medication dosing is determined by many factors. Perhaps the most important one is the lipophilicity of the medication. In general, when a medication is highly lipophilic, it rapidly distributes to the peripheral tissues and should be dosed based on total body weight. In contrast, when a medication is hydrophilic, the volume of distribution is lower, so the dose should be based on ideal or adjusted body weight. An additional factor that affects medication dosing is renal function. If a medication is cleared by the kidney, it should be dosed on actual creatinine clearance rather than calculated creatinine clearance.[69] In the obese patient, the EP should pay special attention to cardiovascular, sedative, antimicrobial, and anticoagulant medications.

Cardiovascular Medications

Beta (β)-adrenergic receptor blockers, calcium channel blockers, digoxin, lidocaine, and procainamide are commonly administered cardiovascular medications in the ED. β-Adrenergic receptor blockers, digoxin, and procainamide are relatively hydrophilic medications and should be dosed on ideal body weight, whereas calcium channel blockers are more lipophilic and should be dosed based on total body weight. Vasoactive medications (e.g., norepinephrine, epinephrine, dobutamine) do not require dosing adjustments in the obese patient.

Sedative Medications

Sedative medications are used frequently in the ED for post-intubation sedation, procedural sedation, severe agitation, and induction for intubation. Sedatives are generally highly lipophilic medications that can have prolonged half-lives in the obese patient. To prevent accidental oversedation, the initial dose of a sedative should be based on ideal body weight, with subsequent doses based on the patient's response and anticipated duration of treatment. The EP should use extra caution with benzodiazepines in the obese patient. When given via continuous infusion, benzodiazepines (along with the analgesic fentanyl) can have an extremely long duration of action.[70]

Antimicrobial Medications

Given the emphasis on early recognition of sepsis and early administration of broad-spectrum antimicrobial agents, it is imperative to dose them correctly in the obese patient. Fuller and colleagues demonstrated an eightfold increase in the likelihood of underdosing of vancomycin for every 10-kg increase in body weight.[71] For vancomycin, total body weight should be used to determine the proper initial loading dose.[72] For penicillins, cephalosporins, and carbepenems, the EP should use the higher end of dosing recommendations. In contrast to these agents, the dose of aminoglycosides should be calculated based on ideal body weight. If the patient has a total body weight that is more than 130% of his or her ideal body weight, then adjusted body weight should be used to calculate the aminoglycoside dose.[73]

Anticoagulant Medications

Obese patients and those with metabolic syndrome are at increased risk for venous thromboembolic events (VTE).[74–77] Anticoagulant medications used to treat thromboembolism are considered high-risk medications; therefore, proper dosing, especially in the obese patient, is imperative.[78] Low-molecular-weight heparin (LMWH) is commonly used to treat VTE and is dosed at 1 mg/kg/day. Some LMWH formulations have maximum dosing recommendations, which may lead to subtherapeutic levels in the obese patient.[79] If the obese patient's total body weight exceeds 190 kg, anti-Xa levels should be monitored to ensure appropriate levels of anticoagulation.[80] Unfractionated heparin could be used if LMWH is not available, but LMWH has been shown to be at least equivalent in head-to-head comparisons, with less frequent dosing and less total volume infused.[81,82] X To date, no large, randomized controlled trials have evaluated the use of newer, direct oral anticoagulants in the obese patient. If these medications are being considered for treatment of VTE in an obese ED patient, the EP should consider consulting with a pharmacist for dosing recommendations.

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