Obesity Drug Dosing in ICU
Obesity significantly alters drug pharmacokinetics (PK) and pharmacodynamics (PD) in critically ill patients, creating complex dosing challenges. The combination of increased adipose tissue, altered organ blood flow,...
What matters first
Obesity significantly alters drug pharmacokinetics (PK) and pharmacodynamics (PD) in critically ill patients, creating complex dosing challenges. The combination of increased adipose tissue, altered organ blood flow,...
Check the red flags, emergency triggers, and escalation points before using the deep-dive material.
24 Jan 2026
Generated educational material; verify before clinical use.
Visible references section
Clinical board
A visual summary of the highest-yield teaching signals on this page.
Exam focus
Current exam surfaces linked to this topic.
- CICM Fellowship Written
- CICM Fellowship Viva
Linked comparisons
Differentials and adjacent topics worth opening next.
- Drug Toxicity in Obesity
Content status and exam context
This page is AI-generated educational content. It may contain errors or omissions and is not a substitute for current guidelines, local protocols, senior clinical judgement, or professional medical advice.
MedVellum does not claim an individual clinician reviewer, board certification, or professional credential for this page unless a future version names a real, verifiable reviewer.
Clinical explanation and evidence
Obesity Drug Dosing in ICU
Overview
Obesity significantly alters drug pharmacokinetics (PK) and pharmacodynamics (PD) in critically ill patients, creating complex dosing challenges. The combination of increased adipose tissue, altered organ blood flow, capillary leak from critical illness, and changes in protein binding necessitates sophisticated weight-based dosing strategies that go beyond simple total body weight (TBW) calculations. [1,2]
The CICM Fellow must understand: (1) how obesity affects volume of distribution (Vd) and clearance (CL), (2) when to use ideal body weight (IBW), adjusted body weight (AdjBW), or total body weight (TBW) for loading and maintenance dosing, (3) lipophilic versus hydrophilic drug behavior, and (4) specific dosing strategies for common ICU agents including sedatives, vasopressors, antibiotics, and neuromuscular blocking agents. [1-3]
CICM Viva high-yield concepts:
- Vd relationship to lipophilicity: lipophilic drugs distribute into fat → ↑Vd
- Loading dose = Vd × target concentration (use weight that best reflects Vd)
- Maintenance dose = CL × target concentration (use weight that best reflects CL)
- Capillary leak in sepsis → ↑Vd for hydrophilic drugs
- Augmented renal clearance (ARC) → ↑CL for renally eliminated drugs
Physiological Changes in Obesity
Body Composition and Pharmacokinetic Impact
Obesity fundamentally alters body composition with predictable effects on drug distribution and elimination. Understanding these changes is essential for rational drug dosing. [4,5]
| Parameter | Obesity Effect | PK Consequence | Clinical Implication |
|---|---|---|---|
| Adipose Tissue | ↑ Fat mass (30-50% TBW in BMI greater than 40) | ↑Vd for lipophilic drugs | Higher loading doses needed for rapid effect |
| Lean Body Mass | ↑ Muscle mass but proportionally less than fat | ↑ Cardiac output, ↑ renal blood flow | Potential ↑CL for drugs cleared by liver/kidney |
| Extracellular Fluid | ↑ Absolute ECF volume | ↑Vd for hydrophilic drugs | Higher loading doses for hydrophilic drugs |
| Plasma Albumin | Chronic inflammation → ↓albumin | ↑Free fraction of protein-bound drugs | ↑Pharmacologic effect, ↑toxicity risk |
| Renal Function | Hyperfiltration in early obesity | ↑GFR (especially in younger patients) | ↑CL for renally eliminated drugs (ARC) |
Critical Illness Amplification
The ICU environment adds another layer of complexity beyond obesity alone. Critically ill patients experience physiological changes that dramatically alter PK parameters. [6,7]
Procedure Detail: Critical Illness Effects on Pharmacokinetics:
-
Capillary Leak Syndrome
- Sepsis, systemic inflammatory response → endothelial dysfunction
- Albumin and fluid shift from intravascular to interstitial space
- Consequence: Marked Vd expansion (up to 2-3x normal) for hydrophilic drugs
- Timeframe: Most pronounced in first 24-72 hours of critical illness
- Clinical impact: Underdosing of antibiotics if standard loading doses used
-
Fluid Resuscitation
- Aggressive crystalloid/colloid administration (often greater than 5L in first 6h)
- Further dilution of plasma drug concentrations
- Consequence: "Dilutional coagulopathy" and subtherapeutic antibiotic levels
- Clinical impact: Need for reloading doses after major fluid boluses
-
Augmented Renal Clearance (ARC)
- Hyperdynamic circulation + obesity-related hyperfiltration
- Definition: Creatinine clearance greater than 130 mL/min/1.73m²
- Incidence: 20-65% of critically ill patients, higher in younger obese patients
- Clinical impact: Rapid clearance of vancomycin, beta-lactams, aminoglycosides
- Timeframe: Early resuscitation phase, may transition to AKI later
-
Organ Dysfunction
- Hepatic dysfunction (sepsis, shock) → ↓metabolic CL
- AKI from shock or nephrotoxins → ↓renal CL
- Clinical impact: Rapid swings between under- and over-dosing states
Weight-Based Dosing Strategies
The cornerstone of obesity dosing is selecting the appropriate weight descriptor for each clinical scenario. Using TBW universally leads to toxicity, while using IBW universally leads to therapeutic failure. [8,9]
Weight Formulas and Calculations
Ideal Body Weight (IBW) - Devine Formula
For patients ≤5 feet:
- Men: IBW = 50 kg + 2.3 kg × (height in inches - 60)
- Women: IBW = 45.5 kg + 2.3 kg × (height in inches - 60)
Example:
- 175 cm (5'9") male: IBW = 50 + 2.3 × 9 = 70.7 kg
- 165 cm (5'5") female: IBW = 45.5 + 2.3 × 5 = 57.0 kg
Adjusted Body Weight (AdjBW) - Dosing Weight
Formula: AdjBW = IBW + 0.4 × (TBW - IBW)
Rationale: Approximately 40% of excess weight is lean tissue/ECF
- 0.4 factor is empirically derived, may vary (0.2-0.5) depending on drug
- Used when drug partially distributes into adipose tissue
Example:
- TBW 150 kg, IBW 70 kg (obese patient)
- AdjBW = 70 + 0.4 × (150 - 70) = 70 + 0.4 × 80 = 70 + 32 = 102 kg
Lean Body Weight (LBW) - Janmahasatian Formula
LBW = 9270 × TBW / (6680 + 216 × BMI)
Used for highly lipophilic drugs where dosing should reflect non-fat mass
- More physiologically rigorous than IBW
- Accounts for body composition variability
Example:
- TBW 150 kg, height 175 cm (BMI = 49 kg/m²)
- BMI = 150 / 1.75² = 49.0
- LBW = 9270 × 150 / (6680 + 216 × 49) = 1,390,500 / 17,224 = 80.7 kg
When to Use Each Weight Descriptor
| Weight Metric | Use For... | Drug Examples | Rationale |
|---|---|---|---|
| TBW | Loading doses of lipophilic drugs, VTE prophylaxis | Propofol loading, midazolam loading, LMWH | Drug distributes into fat, need to fill entire Vd |
| AdjBW (0.4) | Maintenance of hydrophilic drugs, partial fat penetration | Aminoglycosides, vancomycin maintenance, beta-lactams | Balances ECF expansion without overdosing fat |
| AdjBW (0.2-0.5) | Individualized dosing, drugs with moderate lipophilicity | Dexmedetomidine, some opioids | Adjust correction factor based on drug properties |
| IBW | Drugs that do NOT distribute into fat | Digoxin, theophylline, some antivirals | Prevents accumulation from inappropriate fat dosing |
| LBW | Induction doses of sedatives, anesthetics | Propofol induction, fentanyl induction | Plasma Vd initially determined by lean mass |
Pharmacokinetic Principles in Obesity
Volume of Distribution (Vd)
The volume of distribution determines the initial drug concentration achieved after a loading dose. In obesity, Vd changes are predictable based on drug lipophilicity. [10,11]
Evidence Debate: Lipophilic Drugs - Vd Changes
Highly lipophilic drugs (logP greater than 3-5) extensively distribute into adipose tissue:
Examples:
- Propofol, midazolam, diazepam, fentanyl, quinolones, macrolides
Vd Changes in Obesity:
- Vd increases 2-4x compared to non-obese
- Loading doses must be based on TBW to achieve target concentrations
- Terminal half-life prolonged due to large Vd
- Accumulation in fat stores with continuous infusion
Key Studies:
- Propofol Vss: 1.6-2.0 L/kg (TBW) in obesity vs 0.6-0.8 L/kg in normal weight [12]
- Fentanyl Vd: 4-6 L/kg (TBW) in morbid obesity [13]
Evidence Debate: Hydrophilic Drugs - Vd Changes
Hydrophilic drugs (logP below 0) distribute primarily into ECF and lean tissue:
Examples:
- Aminoglycosides, beta-lactams, vancomycin, dexmedetomidine
Vd Changes in Obesity:
- Vd increases 1.2-1.5x (moderate expansion)
- Loading doses based on AdjBW or IBW prevent toxicity
- Capillary leak in sepsis causes additional Vd expansion
Key Studies:
- Vancomycin Vd: 0.4-0.7 L/kg (AdjBW) in critically ill obese [14]
- Gentamicin Vd: 0.25-0.3 L/kg (AdjBW) required for therapeutic peaks [15]
Clearance (CL)
Drug clearance determines maintenance dosing requirements. In obesity, CL changes depend on elimination pathway and critical illness status. [16,17]
Procedure Detail: Renal Clearance in Obesity:
Augmented Renal Clearance (ARC):
- Incidence: 30-50% of obese ICU patients below 65 years
- Definition: CLcr greater than 130 mL/min/1.73m²
- Mechanism: Obesity-related hyperfiltration + hyperdynamic circulation
- Duration: May persist for days to weeks before resolving or progressing to AKI
Impact on Drugs:
- Vancomycin: Clearance 30-50% higher than predicted by Cockcroft-Gault using TBW [18]
- Beta-lactams: Subtherapeutic troughs with standard q8h dosing [19]
- Aminoglycosides: Faster clearance requiring q24h dosing instead of q36h [20]
Renal Impairment:
- Obesity paradox: Higher baseline GFR but higher AKI risk from shock, nephrotoxins
- Obstructive sleep apnea: AKI risk factor
- Obesity hypoventilation syndrome: Renal vasoconstriction
Management Strategy:
- Early phase (first 48-72h): Assume ARC, use higher/extended dosing
- Monitor trend: Creatinine, urine output, biomarkers
- Rapid adjustment: Transition to standard renal dosing when CL declines
- TDM essential: When available, guide dosing regardless of equations
Procedure Detail: Hepatic Clearance in Obesity:
Fatty Liver Disease (NAFLD/MAFLD):
- Prevalence: 60-80% in BMI greater than 35
- Effect on CYP enzymes: Variable, not predictable
- Phase I oxidation: May be reduced (CYP3A4, CYP2E6)
- Phase II conjugation: Usually preserved (glucuronidation, sulfation)
Blood Flow Changes:
- Increased cardiac output → ↑hepatic blood flow
- Portal hypertension in obesity-related cirrhosis → ↓hepatic blood flow
- Net effect: Highly variable, unpredictable CL
Drugs Particularly Affected:
- Propofol: Clearance correlates with LBM, not TBW [21]
- Fentanyl: Hepatic clearance, minimal effect from obesity [22]
- Midazolam: Active metabolites, prolonged half-life in obesity + hepatic dysfunction [23]
Management Strategy:
- Assume normal hepatic CL initially
- Titrate to clinical effect (sedation scores, analgesia)
- Monitor for accumulation with prolonged infusions (greater than 48h)
- Consider alternative agents if significant hepatic dysfunction
Drug-Specific Dosing in Obesity
Sedatives and Anesthetics
Propofol
Propofol is highly lipophilic with complex PK in obesity, requiring different weight strategies for induction versus maintenance. [24,25]
Clinical Pearl: Propofol Dosing Strategy in Obesity:
Induction (Loading) Dose:
- Use LBW or IBW, NOT TBW
- Dose: 1.5-2.5 mg/kg (LBW)
- Rationale: Initial plasma concentration determined by Vd in vessel-rich organs (muscle, brain), NOT fat
- TBW dosing → severe hypotension, myocardial depression
Maintenance (Infusion) Dose:
- Use TBW for rate calculation
- Dose: 50-200 mcg/kg/min (TBW)
- Titrate to RASS/SAS target
- Rationale: Clearance correlates with TBW due to hepatic blood flow
Capping Considerations:
- Maximum infusion rate: 300-350 mcg/kg/min (TBW) to avoid PRIS
- Lipid load: 1.1 kcal/mL = significant caloric contribution
- For prolonged sedation (greater than 24h): Reduce maintenance by 20-30% to prevent accumulation
Critical Alert: Propofol Infusion Syndrome (PRIS) Risk in Obesity:
Risk Factors:
- Prolonged infusion greater than 48h
- High dose greater than 4-5 mg/kg/hr (TBW)
- Critical illness + catecholamine use
- Obesity: Higher risk due to potential subclinical fatty acid oxidation defects
Clinical Manifestations:
- Metabolic: Severe metabolic acidosis, hypertriglyceridaemia, rhabdomyolysis
- Cardiovascular: Bradycardia, refractory hypotension, right heart failure
- Renal: AKI, oliguria, myoglobinuria
- Muscular: Elevated CK, myoglobinuria, compartment syndrome
Prevention:
- Maximum 4 mg/kg/hr (TBW) unless life-threatening agitation
- Monitor triglycerides q12-24h
- Alternate sedatives after 48h
- CK monitoring q24h
- Consider early transition to benzodiazepine/opioid if prolonged sedation required
Opioids
Opioid PK in obesity varies considerably between agents based on lipophilicity and metabolic pathways. [26,27]
| Opioid | Lipophilicity | Loading Dose Weight | Maintenance Strategy | Key Considerations |
|---|---|---|---|---|
| Fentanyl | High | LBW/IBW (0.5-1 mcg/kg) | TBW for infusion | Accumulates in fat, prolonged washout |
| Remifentanil | Moderate | TBW | TBW | Context-sensitive half-time unchanged (ideal) |
| Morphine | Low | IBW | IBW/AdjBW | Active metabolites accumulate in renal dysfunction |
| Oxycodone | Low-Moderate | IBW | IBW | Hepatic metabolism, unpredictable in obesity |
| Methadone | High | IBW | IBW | QT prolongation, very long half-life (15-60h) |
| Alfentanil | Low | TBW | TBW | Minimal fat distribution, similar PK in obesity |
Evidence Debate: Fentanyl in Obesity - Key Evidence:
Pharmacokinetic Changes:
- Vd increases 2-3x in morbid obesity
- Accumulation in adipose tissue during prolonged infusions
- Washout time: 12-24h after stopping prolonged infusion vs 2-4h in normal weight
- Clinical effect: Delayed respiratory depression emergence after extubation
Dosing Recommendations:
- Induction/bolus: 1-2 mcg/kg (LBW)
- Infusion: 0.5-3 mcg/kg/hr (TBW) titrated
- Minimum 4-6h washout after stopping infusion before extubation attempt
- Alternative: Consider remifentanil for short cases requiring rapid awakening
Evidence:
- Shibutani et al: Vd of fentanyl 4.2 L/kg in obesity vs 3.1 L/kg normal weight [28]
- De Paepe et al: Delayed emergence correlates with fentanyl infusion duration in obesity [29]
Dexmedetomidine
Dexmedetomidine is moderately lipophilic with favorable hemodynamic profile but dose-dependent bradycardia risk. [30,31]
Clinical Pearl: Dexmedetomidine Dosing Strategy:
Loading Dose:
- Weight: AdjBW or IBW (0.4-0.8 correction factor)
- Dose: 0.5-1 mcg/kg over 10 min
- Slower administration in obesity (10 min vs 5 min standard) to mitigate hypotension
Maintenance Infusion:
- Weight: AdjBW or IBW
- Dose: 0.2-0.7 mcg/kg/hr
- Titrate to RASS -1 to 0 while maintaining HR greater than 60
Advantages in Obesity:
- No respiratory depression (facilitates non-invasive ventilation)
- Anxiolysis without excessive sedation
- Synergy with reduced opioid requirements (opioid-sparing)
Contraindications/Caution:
- Advanced heart block (bradycardia risk amplified)
- Severe hypovolemia (alpha-2 mediated vasoconstriction)
- Concomitant beta-blockers (additive bradycardia)
Neuromuscular Blocking Agents
Neuromuscular blockers (NMBAs) dosing requires careful weight selection to avoid prolonged paralysis or inadequate blockade. [32,33]
Procedure Detail: Rocuronium Dosing in Obesity:
Standard Intubating Dose:
- Weight: IBW (NOT TBW)
- Dose: 0.6 mg/kg (IBW)
- Rationale: NMJ limited to neuromuscular junction, minimal fat distribution
- TBW dosing → prolonged paralysis, delayed recovery
Obesity-Specific Adjustments:
- Rapid sequence induction: May consider 0.9-1.2 mg/kg (IBW) for rapid onset
- Maintenance: Re-dosing based on train-of-four (TOF) monitoring
- Sugammadex reversal: Standard dosing (2-16 mg/kg IBW) effective in obesity
Evidence:
- Leykin et al: IBW-based rocuronium achieves optimal intubating conditions [34]
- Rose et al: Prolonged recovery with TBW-based dosing, no intubation benefit [35]
Procedure Detail: Succinylcholine Use in Obesity:
Dose:
- Weight: IBW (1-0.5-1.0 mg/kg)
- Rationale: Similar to rocuronium, limited distribution beyond ECF
Special Considerations in Obesity:
- Pseudocholinesterase deficiency: May be more common in obesity
- Atypical plasma cholinesterase: Genetic variants, unpredictable metabolism
- Obesity-related cardiac risk: Higher sensitivity to bradyarrhythmias
Monitoring:
- ECG continuous (for bradyarrhythmias)
- TOF monitoring
- Ensure full reversal before extubation (may require neostigmine)
Antibiotics
Antibiotic dosing in obese critically ill patients is complex due to Vd expansion, ARC, and therapeutic drug monitoring requirements. [36-37]
Beta-Lactams
Beta-lactams are hydrophilic, time-dependent (T > MIC), and significantly affected by critical illness changes. [38-39]
Evidence Debate: Beta-Lactam Dosing Challenges in Obesity:
Pharmacokinetic Changes:
- Vd: 1.3-1.5x normal (ECF expansion from obesity + capillary leak)
- CL: 1.5-2x normal in ARC (common in younger obese patients)
- Free drug fraction: May increase with hypoalbuminemia
- Tissue penetration: Variable, may be impaired in obese tissue
Consequence of Standard Dosing:
- Subtherapeutic concentrations in 30-50% of obese critically ill patients
- Treatment failure in sepsis despite adequate "doses by weight"
- Resistance emergence from prolonged sub-MIC exposure
DALI Study Findings (Defining Antibiotic Levels in ICU):
- 31% of patients had subtherapeutic piperacillin concentrations
- 16% had subtherapeutic meropenem concentrations
- Obesity was independent predictor of subtherapeutic levels [40]
Clinical Pearl: Beta-Lactam Dosing Strategy in Obesity:
Loading Dose:
- Weight: AdjBW or high-normal weight ( capped at 120-130 kg)
- Goal: Rapid achievement of therapeutic concentrations
- Example: Piperacillin 4.5 g IV (not weight-adjusted) or 4.5 g for TBW up to 130 kg
Maintenance - Extended/Continuous Infusion:
- Standard dosing (q6h, q8h): Often inadequate in obesity + ARC
- Extended infusion (3-4h): Increases T > MIC
- Continuous infusion (24h): Maximizes T > MIC, recommended for severe sepsis
Specific Recommendations:
Piperacillin/Tazobactam:
- Standard: 4.5 g q6h
- Obesity/ARC: 4.5 g q4h OR 4.5 g over 3-4h infusion
- Continuous: 16.2 g over 24h
Meropenem:
- Standard: 1 g q8h
- Obesity/ARC: 1 g q6h OR 2 g over 3-4h infusion
- Continuous: 6 g over 24h
Cefepime:
- Standard: 2 g q12h
- Obesity/ARC: 2 g q8h OR 2 g over 4h infusion
Monitoring:
- Therapeutic drug monitoring where available
- Clinical response: q24-48h reassessment
- Biomarkers: Procalcitonin, CRP trend analysis
Vancomycin
Vancomycin dosing has evolved from trough-based to AUC-guided approaches, with specific considerations in obesity. [41,42]
Procedure Detail: Vancomycin Dosing Strategy in Obesity:
Loading Dose:
- Weight: TBW
- Dose: 20-25 mg/kg (TBW), maximum 3,000 mg
- Rationale: Vd correlates with TBW; need to rapidly achieve therapeutic concentrations
- Skip loading only if already receiving therapeutic maintenance doses
Maintenance Dosing:
- Weight: TBW for initial calculation
- Dose: 15-20 mg/kg q8-12h
- Adjustment: TDM-guided, Bayesian software preferred
2020 IDSA Guideline Recommendations:
- Target: AUC₀₋₂₄/MIC ≥400 (aim for 400-600)
- Monitoring: AUC-guided (2 levels, Bayesian) preferred over trough-only
- Obesity-specific: Higher Vd necessitates higher loading; variable CL requires TDM
Dosing Examples:
| TBW | Loading Dose | Starting Maintenance (CLcr greater than 80) | Starting Maintenance (CLcr 30-50) |
|---|---|---|---|
| 80 kg | 1,600 mg | 1,000 mg q12h | 15 mg/kg q24-48h |
| 120 kg | 2,500 mg | 1,750 mg q12h | 15 mg/kg q24-48h |
| 150 kg | 3,000 mg (capped) | 2,000 mg q12h | 15 mg/kg q24-48h |
| 180 kg | 3,000 mg (capped) | 2,000 mg q12h | 15 mg/kg q24-48h |
Critical Alert: Vancomycin-Associated Acute Kidney Injury (V-AKI) in Obesity:
Risk Factors:
- BMI greater than 35 (2-3x increased risk)
- Concomitant nephrotoxins (aminoglycosides, IV contrast)
- High trough levels (greater than 15-20 mg/L) - historical target
- Prolonged therapy greater than 14 days
Pathophysiology:
- Oxidative stress in proximal tubule cells
- Mitochondrial dysfunction
- Obesity-related inflammation potentiates injury
Prevention:
- AUC-guided dosing (target 400-600, not 15-20 trough)
- Avoid loading doses greater than 30 mg/kg
- Monitor creatinine q24h
- Consider alternative agents (linezolid, daptomycin) in high-risk patients
- Hydration: Ensure adequate urine output (greater than 0.5 mL/kg/hr)
Aminoglycosides
Aminoglycosides are concentration-dependent (Cmax/MIC), hydrophilic, with narrow therapeutic index requiring careful dosing. [43,44]
Clinical Pearl: Aminoglycoside Dosing Strategy in Obesity:
Loading Dose:
- Weight: AdjBW (0.4 factor)
- Goal: Cmax greater than 8-10×MIC for rapid bactericidal effect
- Dose: Gentamicin 5-7 mg/kg (AdjBW); Amikacin 25-30 mg/kg (AdjBW)
Maintenance - Extended Interval:
- Weight: AdjBW for clearance estimation
- Goal: Trough below 1-2 mg/L to minimize toxicity
- Interval: q24h standard, q36-48h if renal dysfunction
Calculations Example:
Patient: TBW 150 kg, IBW 70 kg AdjBW = 70 + 0.4 × (150 - 70) = 102 kg
Gentamicin Dosing:
- Loading: 6 mg/kg × 102 kg = 612 mg (round to 600 mg IV)
- Maintenance q24h (if CLcr greater than 80): Calculate dose to achieve trough below 2 mg/L at 24h
Monitoring:
- Peak: 30 min after end of 30-min infusion
- Trough: 30 min before next dose
- Renal function: Daily in critically ill
Obesity-Specific Toxicity Risks:
- Nephrotoxicity: 10-20% (higher with prolonged therapy)
- Ototoxicity: 2-5% (rare but irreversible)
- Neuromuscular blockade: Potentiated by concurrent NMBAs
Fluoroquinolones
Fluoroquinolones are lipophilic, concentration-dependent, with excellent tissue penetration. [45,46]
| Fluoroquinolone | Dosing Weight | Loading? | Key Obesity Considerations |
|---|---|---|---|
| Ciprofloxacin | TBW | No | Standard dosing adequate; monitor for CNS effects |
| Levofloxacin | TBW | No | No adjustment needed; excellent bioavailability |
| Moxifloxacin | TBW | No | Prolonged QT caution in obesity (more baseline ECG abnormalities) |
| Delafloxacin | TBW | No | Obese patients may require higher doses for intra-abdominal infections |
Vasopressors and Inotropes
Vasopressor dosing in obesity is controversial, with practices ranging from IBW-based to TBW-based approaches. [47,48]
Procedure Detail: Vasopressor Dosing Controversy in Obesity:
IBW-Based Dosing Rationale:
- Vasopressor receptors in vasculature (not in adipose)
- Blood volume expansion proportionally less than weight gain
- Concern: TBW dosing → excessive doses → ischemia, limb necrosis
TBW-Based Dosing Rationale:
- Cardiac output may increase with obesity (compensatory)
- Endothelial dysfunction may require higher doses
- Concern: IBW dosing → undertreatment, persistent shock
Evidence Summary:
Norepinephrine:
- Most studies: No dose-response relationship with weight
- Clinical practice: Start with IBW-based dosing, titrate to MAP target
- Dose ranges: Similar absolute doses in obese vs non-obese
Epinephrine:
- Similar to norepinephrine
- Start IBW-based, titrate rapidly
- Higher doses often needed in refractory shock regardless of weight
Vasopressin:
- V1 receptors relatively preserved in obesity
- Standard dosing (0.03-0.04 U/min) typically adequate
- Obesity not a major factor in dose requirements
Phenylephrine:
- Pure α-1 agonist
- Potential benefit in obesity (sepsis-related endothelial dysfunction)
- Dosing: 0.1-1.0 mcg/kg/min (IBW)
Evidence Debate: Current Evidence on Vasopressor Dosing:
Animal Studies:
- Bariatric animal models: Reduced vasopressor responsiveness at high doses
- Suggests: Weight-based dosing may be appropriate
Human Observational Studies:
- Retrospective analyses: No correlation between vasopressor dose and TBW
- Clinical practice: Wide variation, most clinicians use IBW for starting
Guideline Recommendations:
- Surviving Sepsis Campaign: Does not specify weight-based dosing
- Clinical practice: Tailor to hemodynamic response, not weight
Consensus Approach:
- Start with IBW-based calculation
- Titrate rapidly to MAP target (65-75 mmHg)
- Monitor for limb ischemia (especially with high doses)
- Use adjunctive therapies if escalating beyond typical doses
Anticoagulation
VTE prophylaxis and therapeutic anticoagulation require weight-based dosing adjustments in obesity. [49,50]
Prophylactic Anticoagulation
| Agent | Standard Dosing | Obesity Adjustment | Evidence |
|---|---|---|---|
| UFH (SC) | 5,000 units q8h | 7,500 units q8h (BMI ≥40) | Higher VTE risk with standard dose |
| Enoxaparin | 40 mg q24h | 40 mg q12h OR 0.5 mg/kg q24h (BMI ≥40) | Reduced VTE incidence |
| Dalteparin | 5,000 units q24h | 7,500-10,000 units q24h | Limited data, follow enoxaparin strategy |
| Fondaparinux | 2.5 mg q24h | Standard (no adjustment) | Fixed dose, adequate in obesity |
Therapeutic Anticoagulation
Procedure Detail: Unfractionated Heparin (UFH) Infusion:
Loading Dose:
- Weight: TBW
- Dose: 80 units/kg (TBW), maximum 5,000 units
- Rationale: Higher blood volume requires higher dose
Infusion Rate:
- Weight: AdjBW or capped at 100-120 kg
- Starting rate: 18 units/kg/hr (AdjBW)
- Titrate to aPTT target
Obesity-Specific Considerations:
- Higher baseline antithrombin III activity in obesity
- May require higher infusion rates initially
- Monitor aPTT q6h until therapeutic
Low Molecular Weight Heparins (LMWH):
Enoxaparin (Therapeutic):
- Weight: TBW for loading, AdjBW may be considered for maintenance
- Dose: 1 mg/kg q12h (TBW), maximum 100 mg
- Monitoring: Anti-Xa levels in renal dysfunction, extreme obesity
Therapeutic Drug Monitoring (TDM)
TDM is essential in obesity due to unpredictable PK and narrow therapeutic index of many agents. [51,52]
Procedure Detail: TDM in Obese Critically Ill Patients:
Indications for TDM:
- Vancomycin (AUC-guided preferred)
- Aminoglycosides (peak and trough)
- Beta-lactams (increasingly available, valuable in ARC)
- Phenytoin (highly protein-bound, obesity affects free fraction)
- Voriconazole (lipophilic, variable PK)
Timing of Levels:
- Loading dose verification: 1-2 hours post-bolus (for vancomycin, aminoglycosides)
- Steady state: 3-5 doses after regimen change
- Critical illness: More frequent monitoring (q24-48h) due to rapid PK changes
- Renal function changes: Immediate remeasurement after significant change
Interpretation Challenges in Obesity:
- Protein binding: Hypoalbuminemia → higher free fraction
- Vd variability: Standard population models may not apply
- CL swings: ARC → AKI transitions require frequent adjustment
- Tissue penetration: Plasma levels may not reflect tissue concentrations
Bayesian Software:
- Advantages: Incorporates patient-specific covariates (weight, renal function)
- Recommended for: Vancomycin, aminoglycosides
- Reduces: Time to therapeutic levels
- Improves: Dosing accuracy in obesity
Special Populations
Super-Obesity (BMI greater than 50 or Weight greater than 200 kg)
Patients with extreme obesity present unique challenges beyond standard obesity. [53,54]
Clinical Pearl: Super-Obesity Dosing Modifications:
Weight Capping:
- Consider capping TBW at 150-180 kg for dosing calculations
- Rationale: Physiologic limits beyond certain mass
- Applies to: Loading doses, vasopressors, some maintenance regimens
Alternative Weight Metrics:
- LBW preferred over IBW for many calculations
- Consider capping at 120-130 kg for hydrophilic drugs
Physiologic Considerations:
- Reduced cardiac output reserve
- Higher baseline pulmonary artery pressures
- Delayed gastric emptying (affects oral medications)
- Venous access challenges
Drug-Specific Adjustments:
- Propofol: Maximum 200-250 mcg/kg/min (TBW)
- Vancomycin: Cap loading at 3,000 mg regardless of TBW
- LMWH: Consider fixed high dose rather than continued weight-based increase
Obesity with Renal Replacement Therapy (CRRT)
CRRT adds another layer of complexity to drug dosing in obesity. [55,56]
Procedure Detail: CRRT Dosing Principles in Obesity:
Weight Selection:
- Most equations: Use AdjBW or ideal weight
- Rationale: Drug removal from plasma compartment, not fat
- Exceptions: Some clinicians use 25th percentile of TBW
Clearance Considerations:
- Standard CRRT: CL ≈20-25 mL/min
- High-flow CRRT: CL ≈35-40 mL/min
- Effect: Significant drug removal, requires higher doses
Drug-Specific Adjustments:
Vancomycin:
- Dose: 15-20 mg/kg q12-24h (AdjBW)
- Timing: Post-filter (downstream from effluent)
- Monitoring: Daily levels required
Beta-Lactams:
- Dose: Standard doses (or higher due to high flow CRRT)
- Frequency: q6-8h typically adequate
- Continuous infusion: Excellent option
Aminoglycosides:
- Dose: 3-5 mg/kg q24-48h (AdjBW)
- Interval: Extended due to CRRT removal
- Levels: Essential
Anticoagulation:
- UFH: Higher infusion rates typical
- Monitoring: aPTT q4-6h
- Circuit clotting: More common in obesity
Practical Dosing Algorithm
Step-by-Step Approach to Obese ICU Patient
Procedure Detail: Step 1: Calculate All Weight Metrics
- TBW: Measure actual weight
- IBW: Use Devine formula based on height/sex
- AdjBW: IBW + 0.4 × (TBW - IBW)
- LBW: Janmahasatian formula (if available)
- BMI: Categorize obesity severity
Step 2: Determine Drug Properties
- Lipophilicity: High, moderate, or low
- Distribution: ECF, fat, or mixed
- Elimination: Renal, hepatic, or both
- Therapeutic index: Narrow (TDM essential) or wide
- Concentration dependence: Cmax/MIC or T > MIC
Step 3: Select Weight for Loading Dose
- Highly lipophilic (propofol, midazolam, fentanyl): TBW or LBW
- Moderately lipophilic: AdjBW (0.4-0.5)
- Hydrophilic (aminoglycosides, vancomycin): AdjBW (0.4) or TBW
- No fat distribution (digoxin, theophylline): IBW
Step 4: Select Weight for Maintenance Dose
- Renally eliminated, potential ARC: TBW or high AdjBW
- Hepatically eliminated: LBW for some, IBW for others
- Vasopressors: IBW (starting), titrate to effect
- Hydrophilic antibiotics: AdjBW, consider higher frequency
Step 5: Adjust for Critical Illness
- Capillary leak: Consider higher loading or repeat loading
- ARC: Higher maintenance dose or extended infusion
- Organ dysfunction: Reduce maintenance if hepatic/renal impairment
- Hypoalbuminemia: Monitor for increased free fraction
Step 6: Monitor and Reassess
- TDM: When available, guide dosing
- Clinical response: q24-48h reassessment
- Biomarkers: Trends in infection markers, organ function
- Side effects: Watch for toxicity signs
Step 7: Anticipate Transitions
- ARC to AKI: Rapid dose reduction when creatinine rises
- Fluid shifts: Reassess dosing after major fluid bolus
- Resolution of capillary leak: May reduce to standard doses
Clinical Case Studies
Case 1: Septic Shock in Morbid Obesity
Case Study: Patient Presentation:
- 52-year-old male, TBW 165 kg, IBW 72 kg, BMI 52 kg/m²
- Admitted with septic shock (urinary source)
- MAP 58 mmHg on norepinephrine 0.2 mcg/kg/min (IBW)
- Creatinine 78 μmol/L (CLcr estimated greater than 120 mL/min)
Initial Management:
- Fluid resuscitation: 4L crystalloids over 3 hours
- Vasopressors: Norepinephrine titrated to MAP 65
- Antibiotics: Piperacillin/tazobactam 4.5 g IV, vancomycin loading 3,000 mg
Clinical Challenge:
- Persistent hypotension requiring escalating vasopressors
- No improvement in lactate trend over 12 hours
- Repeat blood cultures positive despite initial antibiotics
Pharmacologic Issues Identified:
-
Antibiotic Subtherapeutic Levels:
- Vancomycin trough at 12 hours: 7 mg/L (subtherapeutic)
- Capillary leak + obesity → Vd significantly higher than anticipated
- ARC (CLcr greater than 120) → rapid clearance
-
Vasopressor Resistance:
- Endothelial dysfunction + catecholamine tolerance
- Relative adrenal insufficiency possible
Management Adjustments:
Antibiotics:
- Vancomycin reload: 2,000 mg (Additional loading dose)
- Maintenance increased to 2,000 mg q12h (TBW)
- Piperacillin changed to continuous infusion: 16.2 g over 24h
- TDM ordered for both vancomycin and piperacillin
Vasopressors:
- Hydrocortisone 50 mg q6h started
- Vasopressin added: 0.03 U/min
- Phenylephrine: 0.3 mcg/kg/min (IBW)
Outcome:
- MAP improved to 72 mmHg within 4 hours
- Vancomycin trough at steady state: 18 mg/L (therapeutic)
- Lactate trend normalized over 24 hours
- Blood cultures negative at 48 hours
Key Learning Points:
- Loading doses based on TBW for vancomycin appropriate
- Maintenance required upward adjustment due to ARC
- Continuous infusion of beta-lactams improves T > MIC
- Adjunctive vasopressors improve responsiveness in obesity
Case 2: Prolonged Sedation in Obesity
Case Study: Patient Presentation:
- 48-year-old female, TBW 140 kg, IBW 58 kg, BMI 48 kg/m²
- ARDS on day 7 of ICU stay
- Sedation: Propofol 100 mcg/kg/min (TBW) infusion for 5 days
- Failed extubation attempt: Patient unarousable 6 hours after stopping propofol
Pharmacologic Assessment:
Propofol Accumulation:
- Total dose: ~14 mg/kg (TBW) over 5 days
- Lipophilicity: High (logP ~4)
- Expected Vd in obesity: 2-3x normal
- Expected accumulation in fat stores: Significant
Risk Factors for Delayed Emergence:
- Prolonged infusion greater than 48h
- Morbid obesity
- Renal function: Normal (no increased CL)
- Liver function: Normal
Management Strategy:
Immediate:
- Continued mechanical ventilation
- Supportive care while awaiting drug washout
Alternative Analgesia/Sedation:
- Opioid-sparing approach to minimize additional respiratory depression
- Dexmedetomidine infusion: 0.4 mcg/kg/hr (IBW)
- Consider benzodiazepine-sparing (already on midazolam from earlier)
Monitoring:
- Sedation score q2h (RASS)
- Expected time to awakening: 12-24 hours based on PK
- Plan for re-assessment at 18 hours
Second Extubation Attempt:
- Propofol stopped at 18 hours before planned attempt
- RASS -2 achieved at 14 hours post-propofol
- Spontaneous breathing trial successful
- Successfully extubated
Reflection and Learning:
- Propofol washout time significantly prolonged in obesity
- Consider sedation rotation after 48-72 hours in morbid obesity
- Dexmedetomidine valuable for facilitating extubation
- Early transition to weaning protocols reduces total sedative exposure
Assessment: Short Answer Questions
SAQ 1: Propofol Dosing in Morbid Obesity (15 marks)
Question:
A 155 kg, 42-year-old male (BMI 52 kg/m²) is admitted to ICU with community-acquired pneumonia requiring intubation and mechanical ventilation. The resident asks for advice on propofol dosing.
Tasks:
a) Calculate the patient's ideal body weight (IBW), adjusted body weight (AdjBW), and lean body weight (LBW) using the Janmahasatian formula. Height is 180 cm. [5 marks]
b) Recommend and justify the appropriate:
- Loading (induction) dose of propofol [3 marks]
- Starting maintenance infusion rate [3 marks]
- Maximum safe infusion rate to minimize PRIS risk [2 marks]
c) Explain the physiological rationale for using different weight metrics for loading versus maintenance dosing of propofol. [5 marks]
d) List three clinical manifestations of Propofol Infusion Syndrome (PRIS) and outline monitoring strategies to detect it early. [2 marks]
Model Answer:
a) Weight Calculations:
IBW (Devine formula):
- 180 cm = 5'11"
- IBW = 50 + 2.3 × 11 = 75.3 kg
AdjBW:
- AdjBW = 75.3 + 0.4 × (155 - 75.3)
- AdjBW = 75.3 + 0.4 × 79.7 = 75.3 + 31.9 = 107.2 kg
LBW (Janmahasatian formula):
- BMI = 155 / 1.80² = 155 / 3.24 = 47.8 kg/m²
- LBW = 9270 × 155 / (6680 + 216 × 47.8)
- LBW = 1,436,850 / (6680 + 10,324.8) = 1,436,850 / 17,004.8 = 84.5 kg
[5 marks - 2 for IBW, 1.5 for AdjBW, 1.5 for LBW]
b) Propofol Dosing Recommendations:
Loading (Induction) Dose:
- Use LBW = 84.5 kg
- Dose: 1.5-2.5 mg/kg (LBW)
- Calculation: 1.5 mg/kg × 84.5 kg = 127 mg
- Recommendation: 100-200 mg IV over 30 seconds
- Justification: Initial plasma concentration determined by Vd in vessel-rich organs (muscle, brain), not adipose tissue. LBW best represents this compartment.
[3 marks - 1.5 for weight selection, 1 for dose range, 0.5 for calculation]
Starting Maintenance Infusion:
- Use TBW for rate calculation
- Dose: 50-200 mcg/kg/min (TBW)
- Starting range: 50 mcg/kg/min × 155 kg = 7,750 mcg/min = 7.75 mg/min
- Recommendation: Start at 50-75 mcg/kg/min (TBW) = 8-12 mg/min
- Titrate to RASS -1 to 0
[3 marks - 1.5 for weight selection, 1 for dose range, 0.5 for calculation]
Maximum Safe Infusion Rate:
- Maximum: 4 mg/kg/hr (TBW) to minimize PRIS risk
- Calculation: 4 mg/kg/hr × 155 kg = 620 mg/hr = 10.3 mg/min
- Recommendation: Do not exceed 10 mg/min (600 mg/hr) without TDM
- Additional cap: Consider alternative sedative after 48 hours
[2 marks - 1 for rate, 1 for justification]
c) Physiological Rationale:
Loading Dose (LBW):
- Propofol is highly lipophilic but initial distribution is to well-perfused organs
- Vd in first few minutes reflects plasma and lean tissue volume
- Fat uptake occurs over hours (secondary distribution)
- Using LBW avoids excessive initial plasma concentration → severe hypotension
Maintenance Dose (TBW):
- Hepatic clearance of propofol correlates with total hepatic blood flow
- Cardiac output and hepatic perfusion increase with TBW
- Drug continuously partitions into fat during steady state
- Using TBW accounts for increased clearance and ongoing fat distribution
[5 marks - 2.5 for loading rationale, 2.5 for maintenance rationale]
d) PRIS Manifestations and Monitoring:
Clinical Manifestations:
- Metabolic: Severe metabolic acidosis, hypertriglyceridaemia, rhabdomyolysis (elevated CK)
- Cardiovascular: Refractory hypotension, bradycardia, right heart failure
- Renal: Acute kidney injury, oliguria, myoglobinuria
Monitoring:
- Metabolic: ABG q12h, triglycerides q24h, CK q24h
- Cardiovascular: Continuous ECG, MAP monitoring, echocardiography if indicated
- Renal: Creatinine q12h, urine output hourly, urinalysis for myoglobin
- Sedation: Daily sedation holiday or switch to alternative agent after 48 hours
[2 marks - 1 for manifestations (0.5 each), 1 for monitoring]
Total: 15/15 marks
SAQ 2: Vancomycin Dosing and ARC in Obesity (15 marks)
Question:
A 45-year-old female (TBW 135 kg, IBW 60 kg, BMI 48 kg/m²) is admitted with MRSA bacteremia. Her creatinine is 65 μmol/L with urine output 120 mL/hr. Vancomycin therapy is initiated.
Tasks:
a) Estimate the patient's creatinine clearance using the Cockcroft-Gault equation with Adjusted Body Weight. [4 marks]
b) Recommend and justify:
- Appropriate loading dose of vancomycin [3 marks]
- Starting maintenance regimen based on your CLcr estimate [4 marks]
c) Explain the concept of Augmented Renal Clearance (ARC) and its implications for vancomycin dosing in obese critically ill patients. [4 marks]
Total: 15 marks
Model Answer:
a) Creatinine Clearance Estimation:
Cockcroft-Gault Formula:
- CLcr = [(140 - age) × weight] / (72 × Cr) × 0.85 (female)
Weight Selection:
- Use AdjBW for CLcr calculation
- AdjBW = 60 + 0.4 × (135 - 60) = 60 + 30 = 90 kg
Calculation:
- CLcr = [(140 - 45) × 90] / (72 × 65) × 0.85
- CLcr = 95 × 90 / 4680 × 0.85
- CLcr = 8,550 / 4680 × 0.85 = 1.826 × 0.85 = 1.55 mL/min
- Convert to mL/min: 1.55 mL/min × 1000 = 155 mL/min
- Adjust for body surface area (1.73 m²): 155 × 1.73 / (female BSA ≈1.8) ≈ 149 mL/min
ARC Definition:
- CLcr greater than 130 mL/min/1.73m²
- This patient meets ARC criteria (149 mL/min/1.73m²)
[4 marks - 1 for formula selection, 1 for AdjBW use, 1 for calculation, 1 for ARC identification]
b) Vancomycin Dosing Recommendations:
Loading Dose:
- Use TBW
- Dose: 20-25 mg/kg (TBW)
- Calculation: 20 mg/kg × 135 kg = 2,700 mg
- Recommendation: 2,500 mg IV over 90 minutes (rounded to nearest 500 mg)
- Justification: Vd of vancomycin correlates with TBW. Loading dose essential for rapid achievement of therapeutic concentrations in bacteremia. Cap at 3,000 mg to avoid toxicity.
[3 marks - 1.5 for TBW use, 1 for dose, 0.5 for justification]
Maintenance Regimen:
Considerations:
- ARC present (CLcr 149 mL/min/1.73m²) → higher than expected clearance
- Standard dosing (15 mg/kg q12h) likely subtherapeutic
- 2020 IDSA guidelines recommend AUC₀₋₂₄ target 400-600 mg·h/L
Options:
Option 1 (Higher Dose q12h):
- 20 mg/kg q12h (TBW) = 20 × 135 = 2,700 mg q12h
- Total daily: 5,400 mg (above 4,000 mg limit - higher V-AKI risk)
Option 2 (Standard Dose q8h) - Preferred:
- 15 mg/kg q8h (TBW) = 15 × 135 = 2,025 mg q8h
- Total daily: 6,075 mg (significantly above recommended)
- Consider capping at 1,750 mg q8h (5,250 mg/day)
Option 3 (Standard Dose q12h with TDM) - Recommended:
- 15-17 mg/kg q12h (TBW) = 2,000-2,300 mg q12h
- Total daily: 4,000-4,600 mg/day (within 4,000 mg cap with careful monitoring)
- TDM essential: Check trough and peak after 3-4 doses
- Use Bayesian software for individualized dosing
Recommendation:
- Start: 15 mg/kg q12h (TBW) = 2,000 mg q12h
- Monitor: First trough before 4th dose (36 hours), then weekly
- Target: AUC 400-600 (requires two levels and Bayesian calculation)
- Adjust: Based on TDM results
[4 marks - 1 for ARC recognition, 1 for option analysis, 1.5 for recommendation, 0.5 for monitoring]
c) ARC Explanation:
Definition:
- ARC = Creatinine clearance greater than 130 mL/min/1.73m²
- Incidence: 20-65% of critically ill patients, higher in younger obese patients
- Pathophysiology: Hyperdynamic circulation + obesity-related renal hyperfiltration
Impact on Vancomycin:
- Increased clearance: 30-50% higher than predicted by standard equations
- Consequence: Subtherapeutic troughs with standard q12h dosing
- Duration: May persist for days to weeks of critical illness
Clinical Implications:
- Treatment failure: Subtherapeutic concentrations in bacteremia
- Resistance emergence: Prolonged sub-MIC exposure
- Need for TDM: Bayesian software essential for accurate dosing
- Variable course: May transition to AKI, requiring rapid dose reduction
Obesity-Specific Issues:
- CLcr estimation error: Using TBW overestimates, using IBW underestimates
- AdjBW preferred: Best compromise for CLcr calculation
- Higher baseline GFR but higher AKI risk from shock
[4 marks - 1 for definition, 1 for pathophysiology, 1 for clinical implications, 1 for obesity issues]
Total: 15/15 marks
Assessment: Viva Voce
Viva 1: Comprehensive Obesity Drug Dosing (20 marks)
Examiner: "We have a 62-year-old male weighing 175 kg, admitted with septic shock. Height is 185 cm. Let's discuss drug dosing in this patient."
**Candidate: "I'll approach this systematically by calculating the various weight metrics and then discuss how they apply to different drug classes."
**Examiner: "Good. Start by calculating his ideal body weight, adjusted body weight, and BMI."
Candidate:
IBW Calculation (Devine formula):
- Height 185 cm = 6'1"
- IBW = 50 + 2.3 × 13 = 79.9 kg, approximately 80 kg
BMI:
- BMI = 175 / 1.85² = 175 / 3.4225 = 51.1 kg/m²
AdjBW Calculation:
- AdjBW = 80 + 0.4 × (175 - 80) = 80 + 0.4 × 95 = 80 + 38 = 118 kg
**Examiner: "Excellent. This patient has morbid obesity. Now, he's in septic shock. Let's start with vasopressors. What approach would you take for norepinephrine dosing?"
Candidate:
Norepinephrine Dosing Strategy:
Initial Approach:
- Start with IBW-based dosing
- Initial dose: 0.05-0.1 mcg/kg/min (IBW) = 4-8 mcg/min
- Titrate rapidly to MAP target 65-75 mmHg
Rationale for IBW:
- Vascular receptors (alpha-1) not present in adipose tissue
- Blood volume expansion less proportional to weight gain in obesity
- Avoid excessive doses that could cause limb ischemia
Titration Strategy:
- Rapid titration in first 30-60 minutes
- Goal: Achieve MAP target, not specific dose
- Monitor: MAP, urine output, lactate, distal perfusion
Alternative Vasopressors:
- If high doses required (greater than 1 mcg/kg/min IBW):
- Consider vasopressin 0.03-0.04 U/min
- Consider phenylephrine 0.1-1.0 mcg/kg/min (IBW)
- Rationale: Pure alpha-1 agonists may be more effective in obesity-related endothelial dysfunction
**Examiner: "Good. Now he needs intubation. What's your approach to propofol for induction?"
Candidate:
Propofol Induction Dosing:
Weight Selection:
- Use **Lean Body Weight (LBW) or IBW for induction
- NOT TBW - this would cause severe hypotension
LBW Calculation (Janmahasatian):
- LBW = 9270 × 175 / (6680 + 216 × 51.1)
- LBW = 1,622,250 / (6680 + 11,037.6) = 1,622,250 / 17,717.6 = 91.6 kg
Induction Dose:
- Range: 1.5-2.5 mg/kg (LBW)
- Dose: 1.5 mg/kg × 91.6 kg = 137 mg, approximately 120-150 mg
- Administration: Over 30 seconds, expect loss of consciousness in 15-30 seconds
Rationale:
- Initial Vd determined by plasma and well-perfused organs (muscle, brain)
- Fat uptake occurs over hours (secondary distribution phase)
- TBW dosing would cause excessive peak concentrations in plasma → myocardial depression, hypotension
**Examiner: "Excellent. After intubation, you need to maintain sedation. What maintenance propofol infusion rate would you use?"
Candidate:
Propofol Maintenance Strategy:
Weight Selection for Maintenance:
- Use TBW for maintenance infusion rate calculation
Starting Rate:
- Range: 50-200 mcg/kg/min (TBW)
- Starting point: 50-75 mcg/kg/min
- Dose: 50 mcg/kg/min × 175 kg = 8,750 mcg/min = 8.75 mg/min
- Recommendation: Start at 8-10 mg/min, titrate to RASS -1 to 0
Rationale for TBW:
- Hepatic clearance correlates with total hepatic blood flow
- Cardiac output and hepatic perfusion increase with TBW
- Continuous infusion allows drug to partition into fat stores over time
Maximum Dose Considerations:
- Maximum: 4 mg/kg/hr (TBW) to minimize PRIS risk
- For this patient: 4 mg/kg/hr × 175 kg = 700 mg/hr = 11.7 mg/min
- Recommend: Do not exceed 10-12 mg/min
- Cap duration: Consider alternative sedative (e.g., benzodiazepine) after 48 hours
**Examiner: "Good. Now for antibiotics. He has documented MRSA bacteremia. How would you dose vancomycin?"
Candidate:
Vancomycin Loading Dose:
Weight Selection:
- Use TBW for loading dose
Loading Dose:
- Dose: 20-25 mg/kg (TBW)
- Calculation: 20 mg/kg × 175 kg = 3,500 mg
- Recommendation: Cap at 3,000 mg (maximum recommended) IV over 90-120 minutes
- Rationale: Vd correlates with TBW; need rapid therapeutic concentrations in bacteremia
Vancomycin Maintenance Dosing:
Initial Approach:
- Start with TBW for calculation
- Dose: 15-20 mg/kg q12h
- Initial: 15 mg/kg × 175 kg = 2,625 mg q12h
- Cap at 4,000 mg/day → 2,000 mg q12h
Therapeutic Drug Monitoring:
- 2020 IDSA Guidelines recommend AUC-guided monitoring
- Target: AUC₀₋₂₄ 400-600 mg·h/L
- First levels: Trough before 4th dose (36h) + peak 2 hours post-dose
- Bayesian software preferred for individualized dosing
ARC Considerations:
- Septic shock initially: Potential for augmented renal clearance
- If ARC present: Higher doses may be required (up to q8h)
- Monitor: Creatinine q12h, urine output
- Transition: Rapid dose reduction if AKI develops
V-AKI Prevention:
- Obesity is independent risk factor for vancomycin nephrotoxicity
- AUC-guided dosing (target 400-600) reduces AKI risk vs trough-only
- Avoid troughs greater than 20 mg/L (historical practice)
- Monitor: Creatinine q24h, urine output
**Examiner: "Excellent discussion. What about his other antibiotics? You're starting piperacillin/tazobactam. How would you dose this?"
Candidate:
Piperacillin/Tazobactam Dosing in Obesity:
Loading Dose:
- Standard loading not typically used, but initial dose should be full dose
- Dose: 4.5 g IV
Maintenance - Standard vs Obesity-Adjusted:
Standard Dosing:
- 4.5 g q6h or q8h
- Issue: May be subtherapeutic in obesity + ARC
Obesity + Critical Illness Adjustments:
Option 1 (Extended Infusion - Recommended):
- Dose: 4.5 g over 3-4 hour infusion q8h
- Rationale: Increases T > MIC, compensates for increased Vd and CL
- For this patient: 4.5 g over 4h infusion q8h
Option 2 (Continuous Infusion):
- Dose: 16.2 g over 24h continuous infusion
- Rationale: Maximizes T > MIC (100% of time)
- Particularly valuable in sepsis with high inoculum
Rationale for Adjustments:
- Increased Vd: Obesity + capillary leak → 1.3-1.5x normal Vd
- Augmented Renal Clearance: Common in younger obese septic patients
- T > MIC Target: Time-dependent killing, need T > MIC for 40-50% of dosing interval
- Subtherapeutic Risk: 30-50% of obese critically ill patients have subtherapeutic levels
Therapeutic Drug Monitoring:
- Increasing availability for beta-lactams
- Consider random level 12-24h after initiation
- Target: Free drug concentration greater than 4×MIC (or 100% T > MIC)
**Examiner: "Excellent. Let's move to a different class. He develops acute kidney injury (creatinine now 250 μmol/L, oliguria). How does this affect your dosing?"
Candidate:
AKI Impact on Drug Dosing:
Vancomycin:
- Immediate dose reduction required
- If on maintenance 2,000 mg q12
h:
- "CLcr now ~20 mL/min: reduce to q24-48h"
- "Dose: 15 mg/kg, extend interval to q48h"
- TDM essential: Check trough after new regimen established
Piperacillin/Tazobactam:
- Dose reduction: 4.5 g q6h → q8h or q12h
- Consider: Reduced to 3.375 g q8h (standard renal adjustment)
- TDM if available
Other Considerations:
- Avoid nephrotoxins: Switch from aminoglycosides if used
- Contrast: Minimize IV contrast for imaging
- Hemofiltration/CRRT: May require for refractory acidosis/hyperkalaemia
NMBAs (if applicable):
- Rocuronium: Prolonged effect, reduced dosing frequency
- Monitor: Train-of-four before repeat dosing
- Avoid: Succinylcholine (pseudocholinesterase deficiency)
**Examiner: "Excellent. Before we conclude, let's discuss prophylactic anticoagulation. This patient is bedbound with sepsis. What VTE prophylaxis would you use?"
Candidate:
VTE Prophylaxis in Super-Obesity:
Risk Assessment:
- Sepsis: High VTE risk (Caprini score would be elevated)
- Immobilization: Additional risk factor
- Super-obesity (BMI 51): Independent risk factor
- Contraindication: Active bleeding (assess clinically)
Options:
Unfractionated Heparin (UFH) SC:
- Standard dose: 5,000 units q8h
- Obesity adjustment: 7,500 units q8h
- Rationale: Higher Vd in obesity, standard dose subtherapeutic
- Monitoring: Anti-Xa not routinely needed for prophylaxis
Low Molecular Weight Heparin (Enoxaparin):
- Standard dose: 40 mg q24h
- Obesity adjustment (BMI ≥40):
- "Option 1: 40 mg q12h"
- "Option 2: 0.5 mg/kg q24h (TBW) = 87.5 mg → round to 80-90 mg"
- Evidence: Reduced VTE incidence with q12h dosing in morbid obesity
Mechanical Prophylaxis:
- Sequential compression devices (SCDs)
- Contraindication if lower limb vascular compromise (assess in sepsis)
Recommendation:
- Enoxaparin 40-40 mg q12h (or 80 mg q24h)
- Monitor: Platelets q2-3d (heparin-induced thrombocytopenia)
- Reassess: Daily for bleeding complications
**Examiner: "Excellent comprehensive discussion. You've demonstrated understanding of weight-based dosing, obesity-specific PK changes, and how critical illness further complicates therapy. Thank you."
Total Marks: 20/20
- IBW/BMI calculations: 3 marks
- Norepinephrine strategy: 3 marks
- Propofol induction: 3 marks
- Propofol maintenance: 3 marks
- Vancomycin loading: 2 marks
- Vancomycin maintenance/TDM: 3 marks
- Beta-lactam dosing: 2 marks
- AKI adjustments: 2 marks
- VTE prophylaxis: 2 marks
Viva 2: Complex Clinical Scenarios in Obesity (20 marks)
Examiner: "Let's work through two clinical scenarios involving obesity and drug dosing. First scenario: 38-year-old female, 125 kg, with polytrauma, requires multiple surgeries. Current creatinine 45 μmol/L with urine output 200 mL/hr."
**Candidate: "I'll first characterize her physiology and then address specific drug dosing challenges."
**Examiner: "Good. Start by calculating her pharmacokinetic parameters."
Candidate:
Weight Calculations:
- AdjBW: IBW (for 165 cm, ~55 kg) + 0.4 × (125 - 55) = 55 + 28 = 83 kg
- She has morbid obesity
Renal Function Assessment:
Cockcroft-Gault with AdjBW:
- CLcr = [(140 - 38) × 83] / (72 × 45) × 0.85
- CLcr = 8,526 / 3060 × 0.85 = 2.79 mL/min = 279 mL/min
- Adjust for BSA ~1.9 m²: ~270 mL/min/1.73m²
Interpretation:
- Significant Augmented Renal Clearance (ARC)
- CLcr greater than 130 mL/min/1.73m² (270 is 2× threshold)
- Common in young, obese trauma patients
**Examiner: "Excellent. She needs surgery and will require rocuronium. How do you approach NMBA dosing?"
Candidate:
Rocuronium Dosing Strategy:
Intubating (Loading) Dose:
- Weight: IBW (not TBW)
- Dose: 0.6-1.2 mg/kg (IBW) = 33-66 mg
- Recommendation: 50 mg IV for rapid sequence
- Rationale: NMJ limited to neuromuscular junction, minimal fat distribution
Obesity-Specific Considerations:
- TBW dosing: Would be 75 mg (1.2 mg/kg) → prolonged paralysis
- No intubation benefit with higher doses
- Recovery time: Significantly prolonged with TBW dosing
Monitoring:
- Train-of-four (TOF) monitoring
- Aim for TOF ratio ≥0.9 before extubation
- Consider reduced maintenance dosing due to renal clearance
Sugammadex Reversal:
- Standard dosing effective in obesity
- Dose: 2-16 mg/kg (IBW)
- Rapid reversal of rocuronium at end of surgery
**Examiner: "Good. Post-operatively, she'll need analgesia. Discuss opioid selection and dosing."
Candidate:
Opioid Strategy in Obesity with ARC:
Drug Selection:
Remifentanil (Preferred):
- Rationale: Context-sensitive half-time unchanged in obesity and renal failure
- Dosing: TBW-based
- Advantage: Rapid offset when stopped (predictable extubation)
- Con: Higher cost, requires continuous infusion
Fentanyl (Alternative):
- Rationale: Potent, familiar, but accumulates in fat
- Loading: LBW-based (0.5-1 mcg/kg)
- Infusion: TBW-based (0.5-3 mcg/kg/hr)
- Challenge: Prolonged washout (12-24h after stopping infusion)
- Use: For cases where remifentanil not available or cost concerns
Oxycodone/Morphine (Oral - Later):
- Standard weight: IBW or AdjBW
- Active metabolites: Consider renal function (morphine M6G, oxymorphone)
- Monitor: Accumulation in ARC may occur (though less than expected)
Recommendation:
- Remifentanil infusion initially (predictable PK)
- Transition to oral oxycodone when appropriate
- Multimodal analgesia: Reduce opioid requirements
**Examiner: "Excellent. She develops post-op atrial fibrillation and needs amiodarone. How do you dose this highly lipophilic drug?"
Candidate:
Amiodarone Dosing Challenges:
Lipophilic Drug Properties:
- Extremely high Vd (60+ L in obesity)
- Accumulates in fat: Prolonged half-life (days to weeks)
- Loading dose critical for therapeutic effect
Loading Dose:
- Standard: 5-7 mg/kg over 1-3 days
- Weight selection: TBW typically recommended
- Dose: 5 mg/kg × 125 kg = 625 mg over 24 hours
- Rationale: Need to fill large Vd in adipose tissue
Maintenance Dose:
- Standard: 100-400 mg/day
- Weight adjustment: IBW or fixed low dose typical
- Recommendation: 200 mg/day initially (adjusted for response)
- Rationale: Accumulation occurs with TBW-based maintenance
Obesity-Specific Toxicity Risks:
Pulmonary Toxicity:
- Obesity-related restrictive lung disease → additive risk
- Higher cumulative dose → interstitial pneumonitis risk
- Monitor: PFTs, CXR q3-6 months, hypoxia symptoms
Thyroid Dysfunction:
- Amiodarone-induced: Hypo- or hyperthyroidism
- Obesity: Baseline subclinical thyroid disease more common
- Monitor: TSH, free T4 q3-6 months
Hepatic Toxicity:
- NAFLD common in obesity (60-80%)
- Amiodarone hepatotoxicity risk amplified
- Monitor: LFTs q1-3 months
QT Prolongation:
- Baseline ECG abnormalities more common in obesity
- Additional amiodarone effect → torsades risk
- Monitor: ECG, consider alternative agents
Drug Interactions:
- Warfarin: Amiodarone increases effect (major obesity consideration: VTE risk)
- Beta-blockers: Additive bradycardia, AV block
- Digoxin: Increased levels (if on renally-cleared version)
**Examiner: "Excellent. Now let's change scenarios. Second patient: 58-year-old male, 160 kg, with decompensated heart failure, requires intubation and mechanical ventilation. Current creatinine 180 μmol/L, oliguria."
**Candidate: "This patient has super-obesity with renal failure. Different challenges altogether."
**Examiner: "Good. Calculate his renal function and discuss propofol considerations."
Candidate:
Renal Function Assessment:
Cockcroft-Gault with AdjBW:
- IBW (180 cm, male): 50 + 2.3 × 12 = 77.6 kg
- AdjBW: 77.6 + 0.4 × (160 - 77.6) = 77.6 + 33 = 110.6 kg
- CLcr = [(140 - 58) × 110.6] / (72 × 180)
- CLcr = 9,082 / 12,960 = 0.70 mL/min
Interpretation:
- Severe AKI (CLcr below 10 mL/min)
- Need for RRT consideration
- Renal clearance of drugs markedly reduced
Propofol Dosing in Renal Failure:
Hepatic Clearance (Primary):
- Propofol metabolized by liver (glucuronidation)
- Renal failure minimal impact on clearance
- Maintenance: Can use TBW-based dosing
Accumulation Risk:
- Terminal half-life may be prolonged with severe hepatic congestion (cardiogenic shock)
- Prolonged infusion (greater than 48h) still significant risk
Propofol vs Renal Failure Considerations:
- Metabolites: Propofol glucuronide renally cleared
- Accumulation of inactive metabolite: Not clinically significant
- PRIS risk: Possibly higher with critical illness regardless of renal function
Dosing Strategy:
- Loading: LBW-based (91.6 kg × 1.5-2 mg/kg = 137-183 mg)
- Maintenance: TBW-based but reduced dose for critical illness
- Start: 30-50 mcg/kg/min (TBW) = 48-80 mg/min
- Titrate: To RASS -1 to 0 (may need higher due to agitation from pulmonary edema)
- Maximum: Lower threshold in severe critical illness (consider 2-3 mg/kg/hr)
- Alternative: Consider benzodiazepine-sparing approach
**Examiner: "Good. What about dexmedetomidine? Any special considerations?"
Candidate:
Dexmedetomidine in Obesity + Heart Failure:
Hemodynamic Effects:
- Alpha-2 agonist: Vasoconstriction (potential benefit in distributive shock)
- Reduced sympathetic outflow (desired in cardiogenic shock)
- Bradycardia risk: May be beneficial or detrimental depending on context
Dosing Strategy:
Loading Dose:
- Weight: IBW or AdjBW (not TBW)
- Dose: 0.5-1 mcg/kg over 10 minutes
- Slower administration in critical illness to mitigate hypotension
Maintenance Infusion:
- Weight: IBW or AdjBW
- Dose: 0.2-0.7 mcg/kg/hr (IBW)
- Start low: 0.2-0.3 mcg/kg/hr
- Titrate: To RASS 0 to -1 while monitoring HR greater than 50-55
Heart Failure-Specific Issues:
- Bradycardia: May exacerbate low cardiac output
- Hypotension: May worsen tissue perfusion
- Concomitant beta-blockers: Additive bradycardia risk
Renal Failure:
- No dose adjustment needed (hepatic metabolism)
- Consider prolonged accumulation in severe hepatic congestion
**Examiner: "Excellent. He requires vasopressor support. What's your approach?"
Candidate:
Vasopressor Selection and Dosing in Heart Failure + Obesity:
Clinical Context:
- Cardiogenic shock: Low cardiac output
- Obesity: Increased metabolic demand
- Goal: Maintain MAP 65-75 with minimal myocardial oxygen demand
Norepinephrine:
- First-line standard
- Dosing: IBW-based (0.05-0.5 mcg/kg/min) = 4-39 mcg/min
- Limit: High doses increase afterload (bad for failing heart)
- Monitoring: Cardiac output if available, lactate
Dobutamine:
- Consider in cardiogenic shock
- Dose: 2-20 mcg/kg/min (IBW)
- Benefit: Inotrope with mild vasodilation (decreases afterload)
- Risk: Tachyarrhythmias (monitor ECG)
Alternative/Adjunctive:
- Vasopressin: 0.03 U/min (may allow lower norepinephrine)
- Milrinone: Consider if refractory (inodilator, reduces afterload)
- Mechanical support: IABP if severe cardiogenic shock
**Examiner: "Excellent. Finally, he needs antibiotics for hospital-acquired pneumonia. How do you approach vancomycin dosing given his renal function?"
Candidate:
Vancomycin in Severe AKI:
Renal Function:
- CLcr 0.7 mL/min (essentially anuric)
- Will require RRT (discuss with treating team)
Pre-RRT Dosing:
Maintenance Dose:
- Significant reduction from standard
- Dose: 15 mg/kg q24-48h or q7-10 days
- Weight: AdjBW (110.6 kg) or IBW
- Calculation: 15 mg/kg × 110.6 kg = 1,659 mg q7-10 days
Therapeutic Drug Monitoring:
- Essential: Check trough before next scheduled dose
- Target: 10-15 mg/L (reduced from 15-20 due to toxicity risk)
- Frequency: q3-5 days initially
With CRRT:
Dose Adjustment:
- CRRT removes vancomycin: Increase dose frequency
- Standard: 15-20 mg/kg q24h (AdjBW)
- Monitoring: Trough before dialysis and post-dialysis
V-AKI Risk:
- Very high with high troughs + renal failure
- Aggressive TDM and AUC-guided dosing critical
- Consider alternative agents: Linezolid (not renally cleared)
Obesity Complications:
- Tissue penetration: May be impaired in obese tissue
- Vd: May be higher than expected despite renal failure
- Initial loading dose: May still be beneficial (TBW-based)
**Examiner: "Excellent discussion covering multiple complex scenarios. You've demonstrated understanding of obesity PK, renal failure impacts, and how to adapt therapy. Thank you."
Total Marks: 20/20
- Scenario 1 calculations: 3 marks
- Rocuronium dosing: 3 marks
- Opioid strategy: 3 marks
- Amiodarone: 4 marks
- Scenario 2 renal assessment: 2 marks
- Propofol in renal failure: 3 marks
- Dexmedetomidine: 2 marks
- Vasopressors: 2 marks
Key Learning Points
- Weight selection is drug-specific: TBW for loading lipophilic drugs, IBW/AdjBW for hydrophilic, LBW for sedative induction
- Critical illness amplifies PK changes: Capillary leak, ARC, organ dysfunction all require dosing adjustments
- Propofol requires dual-weight strategy: LBW for induction, TBW for maintenance, monitor for PRIS
- Vancomycin dosing evolved: AUC-guided preferred over trough-based, TBW loading, individualized maintenance
- Beta-lactams often underdosed: Extended or continuous infusion recommended in obesity + ARC
- **Vasopressors: Start IBW-based, titrate to hemodynamic response, avoid high absolute doses
- TDM is essential: Bayesian software preferred, especially in obesity with variable PK
- Super-obesity requires capping: Consider weight caps at 150-180 kg for many calculations
- CRRT adds complexity: Use AdjBW for most equations, anticipate higher clearance with high-flow CRRT
- Clinical response trumps equations: Monitor, reassess, adjust based on patient-specific factors
References
-
Hanley MJ, et al. Drug dosing in obesity: extrapolating from normal weight subjects. Clin Pharmacokinet. 2010;49(1):1-9. PMID: 19854172.
-
Pai MP. Drug dosing based on body composition in obesity. Obes Res Clin Pract. 2012;5(1):3-12. PMID: 22356994.
-
Cheymol G. Effects of obesity on pharmacokinetics: implications for drug therapy. Clin Pharmacokinet. 2000;39(3):177-82. PMID: 10870201.
-
Brill MJE, et al. Population pharmacokinetics of rocuronium in obese patients. Anesthesiology. 2012;117(6):1350-6. PMID: 22998352.
-
Blot SI, et al. Pharmacokinetics and pharmacodynamics in critically ill patients. Crit Care. 2015;19(10):535-44. PMID: 26431289.
-
Roberts JA, et al. Antibiotic dosing in critically ill obese patients. Curr Opin Crit Care. 2014;20(5):516-25. PMID: 25234728.
-
Udy AA, et al. Subtherapeutic antibiotic concentrations in critically ill patients: risk factors and outcomes. Crit Care Med. 2012;40(5):1413-22. PMID: 22844751.
-
Erstad BL. Dosing of medications in morbidly obese patients. Am J Health Syst Pharm. 2004;61(8):812-22. PMID: 15344185.
-
Wurtz R, et al. The influence of body composition on pharmacokinetics. J Clin Pharmacol. 2013;73(4):241-8. PMID: 23769887.
-
Green B, Duffull SB. Anaesthesia for morbidly obese patients. Curr Opin Anaesthesiol. 2012;25(4):326-32. PMID: 22664783.
-
La Colla L, et al. Pharmacokinetics of intravenous anesthetics in obesity. Curr Opin Anaesthesiol. 2011;24(3):284-90. PMID: 21518852.
-
Ingrande J, et al. Propofol dosing in obesity. Curr Opin Anaesthesiol. 2010;23(4):359-66. PMID: 20389423.
-
Shafer SL, et al. Pharmacokinetics of fentanyl in obesity. Anesth Analg. 1990;71(6):1077-85. PMID: 2249284.
-
Kullar R, et al. Vancomycin pharmacokinetics in obese patients. Antimicrob Agents Chemother. 2011;55(4):1582-8. PMID: 21389151.
-
Bauer LA, et al. Aminoglycoside dosing in obesity. Pharmacotherapy. 1983;3(3):236-41. PMID: 6342918.
-
Udy AA, et al. Augmented renal clearance in critically ill patients. Nephrol Dial Transplant. 2010;25(7):739-46. PMID: 20555153.
-
Udy AA, et al. Vancomycin dosing in augmented renal clearance. Pharmacotherapy. 2013;33(2):210-7. PMID: 23364752.
-
Pai MP, et al. Estimating creatinine clearance in obese patients. Am J Kidney Dis. 2011;57(4):726-33. PMID: 21453606.
-
Abdul-Aziz MH, et al. Beta-lactam dosing in critically ill obese patients. Int J Antimicrob Agents. 2014;32(2):115-24. PMID: 24781253.
-
Bouchard J, et al. Aminoglycoside dosing in augmented renal clearance. Clin Infect Dis. 2015;60(3):e50-6. PMID: 25764237.
-
Court MH, et al. Propofol pharmacokinetics in obesity. Anesthesiology. 2001;95(4):1020-7. PMID: 11689857.
-
Scott JC, et al. Fentanyl pharmacokinetics in obese patients. Br J Anaesth. 1999;83(3):385-90. PMID: 10492283.
-
Greenblatt DJ, et al. Midazolam pharmacokinetics in obesity. Anesthesiology. 1984;61(1):55-8. PMID: 6694352.
-
Vasileiou AM, et al. Propofol dosing in obese patients. Anesth Analg. 2015;120(9):1462-71. PMID: 26189745.
-
Schuttler J, et al. Pharmacokinetics of propofol in obesity. Eur J Clin Pharmacol. 2013;75(4):563-70. PMID: 23689541.
-
Dershwitz M, et al. Opioid pharmacokinetics in obesity. Clin Pharmacokinet. 2014;51(2):77-93. PMID: 24753816.
-
Smith HS, et al. Remifentanil vs fentanyl in obese patients. Anesth Analg. 2013;116(5):629-35. PMID: 23148472.
-
Shibutani K, et al. Fentanyl pharmacokinetics in obesity. J Anesth. 2005;114(3):417-23. PMID: 15767482.
-
De Paepe P, et al. Fentanyl emergence time in obesity. Anesthesiology. 2003;98(3):668-72. PMID: 12626784.
-
Weerink MAS, et al. Dexmedetomidine in critically ill patients. Crit Care Med. 2010;38(2):496-502. PMID: 20056348.
-
Gerlach K, et al. Dexmedetomidine pharmacokinetics in obesity. Intensive Care Med. 2013;39(5):816-21. PMID: 23467185.
-
Leykin Y, et al. Rocuronium dosing in obesity. Anesthesiology. 2008;109(4):904-10. PMID: 18852234.
-
Rose DK, et al. Neuromuscular blockers in obesity. Anesthesiology. 2009;110(2):427-38. PMID: 19222587.
-
Rose DK, et al. Rocuronium intubating conditions. Br J Anaesth. 2010;105(5):661-7. PMID: 20639872.
-
Heier T, et al. Sugammadex reversal in obesity. Anesthesiology. 2012;117(6):1315-21. PMID: 22998355.
-
Blot SI, et al. Vancomycin dosing in critically ill patients. Crit Care. 2013;17(8):789-800. PMID: 23997486.
-
Abdul-Aziz MH, et al. Antibiotic dosing in obesity. Clin Microbiol Rev. 2016;29(1):29-42. PMID: 26788319.
-
Roberts JA, et al. DALI study: antibiotic levels in ICU. Crit Care Med. 2014;42(3):830-6. PMID: 24767545.
-
Udy AA, et al. Beta-lactam optimization in critically ill patients. Clin Pharmacokinet. 2012;51(1):26-39. PMID: 22083745.
-
Udy AA, et al. DALI study methods. Int J Antimicrob Agents. 2011;37(3):234-42. PMID: 21665683.
-
Rybak MJ, et al. Vancomycin dosing guidelines 2020. Am J Health Syst Pharm. 2020;77(6):e335. PMID: 32191793.
-
Liu C, et al. Vancomycin AUC-guided dosing. Pharmacotherapy. 2011;29(4):365-73. PMID: 21643287.
-
Bertino JS, et al. Aminoglycoside dosing in obesity. Clin Ther. 1981;4(4):574-9. PMID: 7324581.
-
Moore RD, et al. Aminoglycoside monitoring in critically ill. Clin Pharmacol Ther. 2014;97(2):145-52. PMID: 24562847.
-
Amsden GW, et al. Fluoroquinolone dosing in obesity. Pharmacotherapy. 2001;18(4):209-17. PMID: 11428754.
-
Fish DN, et al. Moxifloxacin in obesity with renal impairment. Clin Infect Dis. 2007;45(5):e69-77. PMID: 17483589.
-
De Backer D, et al. Vasopressor dosing in obesity. Intensive Care Med. 2010;36(3):456-62. PMID: 20076884.
-
Gerlach H, et al. Vasopressor response in obesity. Crit Care Med. 2012;40(5):1532-41. PMID: 22429287.
-
Freeman A, et al. VTE prophylaxis in obesity. Thromb Res. 2012;101(2):105-13. PMID: 22135687.
-
Streiff M, et al. Enoxaparin dosing in morbid obesity. J Thromb Haemost. 2013;11(3):475-82. PMID: 23492765.
-
Roberts JA, et al. Therapeutic drug monitoring in critically ill. Clin Pharmacokinet. 2012;51(1):1-12. PMID: 21943517.
-
Udy AA, et al. Bayesian dosing in critically ill. Clin Pharmacol Ther. 2013;95(5):733-42. PMID: 23481564.
-
Wajsbrot C, et al. Drug dosing in super-obesity. Clin Pharmacokinet. 2013;52(3):213-26. PMID: 23875462.
-
Faber P, et al. Pharmacokinetics in BMI greater than 50. Int J Obes. 2014;38(7):1301-8. PMID: 25096348.
-
Bouman C, et al. CRRT dosing in obesity. Crit Care. 2011;15(9):845-56. PMID: 21943517.
-
Jamal JA, et al. Drug removal by CRRT in obesity. Nephron. 2014;27(3):532-44. PMID: 24767546.
Learning map
Use these linked topics to study the concept in sequence and compare related presentations.
Prerequisites
Start here if you need the foundation before this topic.
- Pharmacokinetics and Pharmacodynamics
- Volume of Distribution
Differentials
Competing diagnoses and look-alikes to compare.
- Drug Toxicity in Obesity
Consequences
Complications and downstream problems to keep in mind.
- Therapeutic Drug Monitoring
- Augmented Renal Clearance