Anesthetics

Ether

• discovered by a dentist (Morton) and a surgeon (Warren) in Boston on October 16, 1846

• unstable, unpleasant, and explosive

Chloroform

• obstetrician (Simpson) from Scotland (1847)

• stable, more pleasant, and hepatotoxic

Injectables

• chloral hydrate: metabolized to trichloral ethanol (active ingredient). potentiates GABA

• morphine + scopolamine (twilight sleep): scopolamine is an antimuscarinic

• barbiturates (1932): cardiovascular depressant

• etomidate (1964): fewer cardiac side-effects

• ketamine (1962): IV or IM. severe hallucinations post-op

• propofol (1977): TIVA

Neuromuscular blockades

• curare (1942): used originally in electroconvulsive therapy

Regional anesthesia

• cocaine used in eye procedures

• high addiction rate

Further inhalants

• halogenated hydrocarbons

Patient Factors

• organ system status

  • anesthetic risks

    • CVD

    • obesity

    • pregnancy

• concomitant drug use

  • adjunct agents

  • may alter response

Stages of Anesthesia

• Stage I

  • diminished pain perception

  • some memory loss

• Stage II

  • agitation

• Stage III

  • surgical anesthesia

    • Plane 1: light. intubation possible, some eye movement, reflexes diminished

    • Plane 2: light surgical. eye movement usually ceases. muscle relaxation. reflexes diminished but present

    • Plane 3: surgical. slowed breathing, slow heart rate. also reflexes are diminished or absent

    • Plane 4: respiration is irregular. all reflexes absent. prolonged capillary refill time

• Stage IV

Procedure

• Induction

  • IV (cheaper and better)

  • inhalant (slow and expensive)

• Maintenance

  • inhalant (cheaper and better)

  • IV (more expensive)

• Recovery

  • reverse neuromuscular blockade

  • modern anesthetics require little or no metabolism

Inhalants

• require specialized equipment

  • some equipment is drug specific

• features

  • nonflammable and nonexplosive

• effects

  • bronchodilation

  • increased brain perfusion

  • interference with respiratory control

• potency (MAC)

  • minimum alveolar concentration (MAC)

  • end-tidal concentration required to eliminate movement in 50% of patients

  • lower MAC = higher potency

  • other patient factors affect MAC

• distribution

  • PALV = PBRAIN

  • steady state is achieved when PALV = PBODY

  • alveolar wash-in

  • uptake

    • solubility

    • cardiac output

    • alveolar-to-venous partial pressure gradient

  • distribution

    • based upon perfusion

  • wash out

• MOA

  • unknown

  • potentiates GABA

    • except N2O and ketamine

      • NMDA blocker

• Halothane

  • earliest halogenated hydrocarbon

    • original work done on refrigerants

    • high potency

    • limited analgesia

  • side effects

    • hepatotoxicity

    • cardiac sensitization

    • malignant hyperthermia

    • increased arrhythmias

    • increased sensitivity to catecholamines

    • decreased cardiac output

    • decrease BP

    • inhibits respiratory reflexes

    • low risk of renal toxicity

• Isoflurane

  • safe with limited metabolism

  • can cause hypotension

  • not good for induction

  • decreased cardiac output

  • decrease BP

  • initial simulation respiratory reflexes

  • low risk of hepatic toxicity

  • low risk of renal toxicity

• Desflurane

  • rapid onset

  • special vaporizer due to low volatility

  • not good for induction

  • decreased cardiac output

  • decrease BP

  • initial simulation respiratory reflexes

  • low risk of hepatic toxicity

  • low risk of renal toxicity

• Sevoflurane

  • hepatic metabolism

  • good for induction

  • decreased cardiac output

  • decrease BP

  • inhibit respiratory reflexes

  • low risk of hepatic toxicity

  • some risk of renal toxicity

• Nitrous Oxide

  • used as adjuvant

  • potent analgesic

  • weak anesthetic

  • can increase volume of closed compartments

  • will accumulate in enclosed organs

IV

• commonly used for induction

  • can also be used for maintenance

  • recovery due to re-distribution, not necessarily metabolism

  • impaired cardiac output requires careful titration - induction takes longer

• propofol

  • rapid onset + rapid redistribution

  • does not provide analgesia

• barbiturates

  • thiopental is commonly used

    • ultra-short acting

  • slow metabolism

  • may cause hypotension, apnea, bronchospasm, etc

• benzos

  • adjunct

  • hepatic metabolism

• opioids

  • analgesic

  • cause hypotension and respiratory depression

  • reversed by naloxone

• etomidate

  • used only in heart patients

  • rapid onset

  • suppresses cortisol and aldosterone

• ketamine

  • IM/IV induction

  • increases cardiac output

• dexmedetomidine

  • usually used post-op

  • sedation without respiratory depression

Local Anesthetics

• primarily used in regional anesthesia

  • local infiltration

    • sometimes ultrasound guided

  • epidural

    • can be used as a continuous infusion

  • spinal

• advantages

  • lower metabolic impact

  • patient preference

• MOA

  • blocking of voltage-gated Na+ channels

• metabolism

  • predominantly hepatic

  • plasma cholintesterase

• onset and duration

  • variable with formulations

    • affected by pH, lipid solubility, pKa, etc.

• actions

  • vasodilation (by blocking smooth muscle contraction)

    • often epinephrine is added to delay removal from site

  • duration not determined by metabolism, but by redistribution

• allergic reactions

• children and elderly

• toxicity