Inhalational Agents

Inhalational pharmacokinetics has four phases: 1. Uptake (lungs → blood) 2. Distribution (blood → CNS, the site of action) 3. Metabolism (minimal for modern agents) 4. Elimination (mostly exhaled unchanged)

The goal is to develop an alveolar partial pressure that equilibrates with the CNS to render anesthesia. PARTIAL PRESSURE — not concentration — produces effect.

At altitude (Patm < 760 mmHg), the same vol% produces a lower partial pressure and therefore less anesthetic effect.

FI (inspired concentration) is set by fresh gas flow, circuit volume, and absorption by the machine/circuit. ↑ FGF and ↓ circuit absorption make FI ≈ delivered Fi.

FA (alveolar concentration) = input − uptake. Uptake depends on: - Blood solubility — higher solubility = more gas needed to saturate blood = slower rise of FA/FI. - Alveolar blood flow (≈ cardiac output) — higher CO = larger "tank" to fill = slower rise (esp. for soluble agents). - Alveolar-to-venous partial pressure difference — wider gradient = more uptake = slower rise.

Net: agents with low blood solubility (desflurane, sevoflurane, N₂O) reach the CNS fastest.

Concentration effect — ↑ FI not only ↑ FA but also ↑ the rate at which FA approaches FI. Most dramatic with N₂O (used in high concentrations).

Second gas effect — Rapid uptake of one gas (e.g., N₂O) concentrates a second gas in the alveoli. Questionably clinically relevant.

Shunts: - R-to-L shunt (intracardiac, mainstem intubation) — shunted blood without volatile dilutes arterial partial pressure → slower induction. IV agents become faster (bypass the lungs). - L-to-R shunt — little effect on speed.

Oil:gas coefficient determines potency (Meyer-Overton). Blood:gas determines onset/offset speed.

• 2/3 as potent as isoflurane (MAC 1.85–2.0%)
• Rapid uptake & elimination
• Sweet, non-pungent → workhorse for inhalational induction (especially pediatrics)
• Mild bronchodilator
• Degrades in dry CO₂ absorbent → Compound A (theoretical nephrotoxicity; use FGF ≥ 1–2 L/min for long cases)
• Minimal cardiovascular depression at clinical doses
• No catecholamine sensitization

• Lowest blood:gas coefficient → fastest emergence
• Pungent — never for inhalational induction (laryngospasm, breath-holding)
• Rapid increases in concentration → transient sympathetic surge (tachycardia, HTN) — increase slowly in CAD
• Requires heated, pressurized vaporizer (boiling point 23 °C)
• Best agent for obese patients and long cases (fast offset regardless of duration)

• Pungent (like des) → not for inhalational induction
• Most potent volatile vasodilator
• "Coronary steal" historically described, no longer clinically concerning
• Slow emergence relative to sevo/des — useful in long cases where slow wakeup is acceptable

• MAC 104% → impossible to give 1 MAC alone at sea level
• Often used as a 50–70% adjunct to reduce volatile requirement
• Expansion of closed gas spaces — 30× more soluble than nitrogen → diffuses in faster than nitrogen leaves
• Contraindicated: pneumothorax, bowel obstruction, middle-ear surgery, retinal gas bubbles, intracranial air after dural opening
• Inactivates vitamin B12 (methionine synthase) — risk with chronic exposure, megaloblastic anemia, myeloneuropathy
• Diffusion hypoxia at emergence — rapid outflow can dilute alveolar O₂; treat with 100% FiO₂ for several minutes

• Respiratory: dose-dependent ↓ tidal volume, ↑ RR (overall ↓ minute ventilation), blunted hypoxic and hypercapnic ventilatory drive, bronchodilation
• Cardiovascular: ↓ SVR, ↓ contractility, ↓ MAP. Halothane sensitized myocardium to catecholamines; modern agents do not (clinically).
• CNS: ↓ CMRO₂, vasodilation → ↑ CBF and ↑ ICP (significant > 1 MAC). N₂O is the worst offender for ↑ CBF.
• MH trigger: all halogenated agents and succinylcholine. N₂O does NOT trigger.
• PONV: all volatiles are emetogenic.