Pharmacokinetics in Obesity:

General:

 Mainly affects Vd and elimination

 Distinguish between: TBW, Ideal BW (IBW) and Lean BW (LBW)

IBW: height (cm) - 100 (male) or 105 (female)

LBW: Male: 1.1 (wt) - 128 (wt/ht)2

Female: 1.07(wt) - 148 (wt/ht)2

 TBW not accurate in morbid obese. Need to scale TBW, or use IBW or
LBW (later).

Regarding volume of distribution (Vd):

 Highly lipophilic drugs have significantly increased Vd's. Exception =

Remifentanil (very high Cl limits distribution).
 Less lipophilic drugs' Vd not much influenced.
 Weak or moderately lipophilic drugs can be dosed on IBW (or more
accurately, on LBW)
 Strong lipophilic drugs (e.g. many anaesthetic drugs) = increased Vd, but
much more variability (end organ clearance differences and protein
binding differences)
 Hydrophilic drugs: may add 20% to IBW to account for concomitant
increase in LBM (e.g. the NDNMB's). Sux = exception, = should use TBW

Applied kinetics to anaesthetic drugs in the obese:

Volatiles:
 Halothane: relative high lipid sol, thus signif deposition in adipose tissue.
Furthermore, increased risk of signif hepatic reductive metabolism, with
risk of halothane hepatitis.
 Enflurane: B:G coeffic decreases with increasing obesity, with possibly
decreasing MAC. Both halothane + enflurane metabolised more in the
morbid obese, - incr risk of fluoride nephrotoxicity.
 More modern volatiles with low B:G coeff's, PK's minimally affected by
obesity. Rapid on - and offset.
 Controversy re Des: theoretically safest in obese because of lowest B:G
coeff, but some studies showed rel high fluoride ion prod. Iso = least
fluoride ion prod.

1
I.V. induction agents:
  TPS: Cl unchanged, but incr Vd and thus t1/2. Induction dose on IBW
 Propofol: induction dose on IBW. For maintenance infusion, pl [ ] depends
on TBW (even though highly lipophilic, no larger accumulation c/f lean
pts), however, this might lead to high dosages with CVS compromise.
Various models (Marsh, Schnider), - may use LBW or corrected BW ( =
LBW + (0.4 x excess wt)
 Midazolam: Cl unchanged, with parallel incr in Vd and t1/2. Use TBW for
adequate pl [ ], but prolonged sed may occur.
 Opioids: Incr Vd and t1/2.
- Fentanyl PK's not affected, - use IBW.
- Alfentanil has decr Cl, but max pl [ ] and Vd not affected. Incr'ed t1/2
(from decr Cl). Use LBM.
- Remi: PK's not much altered, use IBW or LBW (otherwise OD if TBW)

Paracetamol:
 Incr Vd, but also incr Cl. Should use IBW (otherwise OD if TBW)

NMB's:
 Sux: use TBW
 NDNMB's: Use IBW
 Neostig: use TBW