Soup to nuts: Finding the Right Dose: Optimizing Drug Therapy in Critically Ill Patients with Obesity

"Finding the Right Dose: Optimizing Drug Therapy in Critically Ill Patients With Obesity" by Lauren Finch, PharmD; Carolyne DaSilva, PharmD; and Uyen Diep, PharmD, BCCCP, FCCM (AACN Advanced Critical Care, Fall 2026;37:265-271; Drug Update column edited by Melissa Noble, PharmD, BCCCP, FCCM) reviews how obesity alters pharmacokinetics/pharmacodynamics in the ICU and offers drug-class–specific dosing and monitoring guidance. Roughly 20% of ICU patients have obesity, and excess adipose tissue chiefly expands the volume of distribution of lipophilic drugs while leaving hydrophilic drugs relatively unchanged—making choice of weight metric (total body weight [TBW], ideal body weight [IBW], or adjusted body weight [AdjBW]) central to safe dosing.

Pharmacokinetic/pharmacodynamic framework

• Absorption: Higher gastric pH (median 2.6 vs 1.2) and variable motility alter oral bioavailability; critical illness adds delayed gastric emptying and GI hypoperfusion from vasopressors.

• Distribution: Fluid overload, capillary leak, and hypoproteinemia shift distribution; lipophilic drugs gain markedly increased volume of distribution in obesity.

• Metabolism: Hepatomegaly, steatosis, and altered hepatic blood flow produce highly variable (increased, decreased, or unchanged) enzyme activity.

• Excretion: Obesity can raise GFR/renal blood flow (augmented clearance) but also carries higher CKD/AKI risk, so clearance varies widely and requires individualized assessment.

Drug-class dosing recommendations

• Vasopressors (hydrophilic, small Vd): weight-based dosing using IBW gives lower cumulative exposure with equivalent hemodynamic effect, potentially reducing AKI, arrhythmia, and limb ischemia.

• Analgesics/sedatives (opioids, ketamine/norketamine, propofol, dexmedetomidine, benzodiazepines—all lipophilic): dose on IBW. TBW-based propofol roughly doubles hypotension risk; TBW dexmedetomidine yields supratherapeutic levels; benzodiazepines have prolonged half-lives and delirium risk.

• Anticoagulants:

  • Enoxaparin (hydrophilic): prophylaxis 40 mg or 0.5 mg/kg SC twice daily for BMI >40; treatment at a reduced weight-based dose of 0.7–1 mg/kg TBW twice daily to avoid supratherapeutic anti-Xa/bleeding, with lower end favored at very high BMI.

  • Unfractionated heparin: TBW-based for VTE treatment, but obese patients often need lower weight-based infusion rates (~12–13 U/kg/h, as low as ~11.6 U/kg/h in the heaviest); prophylaxis 5000 U q8h (7500 U increased bleeding without fewer VTEs).

  • DOACs (apixaban, rivaroxaban): recent data show superior safety/efficacy over warfarin even at BMI >40–50.

• Antibiotics:

  • β-lactams (hydrophilic, time-dependent): use higher end of range; consider extended/continuous infusions.

  • Vancomycin: TBW-based loading with dose capping (~3 g load, ~4.5 g/day maintenance), guided by therapeutic drug monitoring.

  • Aminoglycosides: dose on AdjBW to limit nephro-/ototoxicity.

Nursing/monitoring emphasis runs throughout: continuous hemodynamic assessment for vasopressors; validated pain/sedation tools (CPOT, BPS, RASS, SAS) per SCCM; anti-Xa and Hgb for anticoagulants; and appropriately timed peak/trough levels for vancomycin and aminoglycosides. The authors conclude that applying evidence-based, weight-metric–appropriate dosing plus consistent monitoring optimizes efficacy while minimizing toxicity, with critical care nurses playing a vital role.