· Obesity
· Absorption
· Distribution
· Metabolism
· Excretion
· Modelling
|
Definition |
BMI >30kg/m2 body surface area |
|
Changes |
· ↑Fat mass o Accounts for 60-80% excess o -> Chest wall compression, diaphragm displacement · ↑Fat-free mass o Accounts for 20-40% excess. Rarely >70kg in women, >100kg in men o ->↑Metabolic rate (BMR), ↑blood volume, ↑cardiac output (CO) · ↑Visceral fat o ↑Inflammatory cytokines (e.g. TNFα, IL-1, IL-6 in metabolic syndrome) · Comorbid disease o Much more likely with central obesity |
|
Oral |
· Delayed gastric emptying -> slow onset o e.g. ineffective oral pre-medication |
|
Inhalational |
· ↑VA:FRC -> ↑rate of rise FA/FI o ↑Metabolic rate -> ↑VCO2 -> ↑VA awake (but ↓VA under GA due to poor compliance) o Diaphragm compression -> ↓↓FRC (e.g. ↓25% when erect at BMI 35) (worse supine, even worse under GA) |
|
Intramuscular |
· Risk of subcut injection -> ↓onset, risk of dose stacking |
|
Circulation |
· ↑CO ∝ ↑lean mass o ↑Rate of drug distribution o ↓Peak plasma [propofol] after bolus -> risk of awareness o ↓Rate of rise FA/FI volatile anaesthetic (partly offsets resp changes) · ↑Blood volume o ↑Central VD -> ↓Plasma concentration after loading dose o Risk of awareness post-induction |
|
Plasma proteins |
· Altered profile in metabolic syndrome · ↓Albumin -> ↑unbound % of acidic drugs -> toxicity if low HER (e.g. phenytoin) · ↑AAG -> ↓unbound % basic drugs (e.g. morphine) |
|
Tissues |
*Dosing by total body weight may cause toxicity* · ↑Total body water o ↑VD water-soluble drug -> resistance to effect of muscle relaxants o Note overdose likely if loading dose calculated with total body weight · ↑Muscle o ↑Time constant -> slow emergence from volatile anaesthetic o ↑Time to emergence from volatile anaesthetic · ↑Fat o ↑VD fat-soluble drugs -> ↑t1/2β (e.g. fentanyl) o ↑Time constant -> slow emergence only if very long volatile anaesthetic |
|
Hepatic |
· Significant impairment only if NAFLD-induced cirrhosis · Phase 1: variable effect on CYP450 enzymes o ↓3A4 (most drugs) o ↑2E1 (volatiles) · Phase 2: ↑activity |
|
Other |
·
↑Plasma cholinesterase -> ↑resistance to
suxamethonium |
|
Urine |
· ↑Renal blood flow ∝ ↑lean mass o ↑Excretion of small and/or hydrophilic drugs and metabolites o e.g. morphine 6 glucuronide |
|
Bile |
· Unaffected by simple obesity |
|
Lung |
· ↑VA:FRC -> ↑rate of fall FA/FA0 (causes as above) |
|
Marsh TCI |
· Entry of total body weight inappropriate o ↑Dose -> toxicity (i.e. hypotension) |
|
Schnider TCI |
· Poor estimate of lean mass (James equation) o Paradoxical ↓infusion rate at BMI >42 in men, >35 in women o Risk of awareness |
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