General anesthetics

• The general anesthesia is the temporary, completely reversible inhibition of sensory activity and
consciousness with medicines

• Very important in surgery

• Davy proposed in1799 the use of nitrous oxide in surgical interventions

• In 1818 Faraday important experiments with ether

• In 1846 Warren: the first surgical intervention in ether narcosis

• In 1847 Simpson first surgical intervention in chloroform narcosis

• The anesthetic medicine causes: analgesy, amnesia, loss of consciousness, abolition of sensorial
and autonomic reflexes and relaxation of the striated muscle.

Stages of anesthesia
• Neuropharmacological base: different sensitivity to the drug of the different brain regions and
structures

• The less sensitive structures are the bulbar vital centers: respiratory and cardiovascular

• This makes possible the narcosis without endangering this vital centers

• Modern automatic devices

• Monitoring of the brain functions throughout the anesthesia

I. stage (stadium analgesiae)

• From the start of the anesthesia until the lost of consciousness

• The cells of substantia gelatinosa are the most sensible, no sensorial (pain) transmission on
tractus spinothalamicus

• After the loss of consciousness: start of amnesia

• Some small surgical interventions can be performed in this stage

II. stage (stadium excitationis)

• Because some inhibitory neurons are blocked by the drug

• The normal inhibitor effect of the cortex is suspended

• The unconscious patient reacts strongly to the smallest stimuli: tries to escape, shouts,
hallucinations

• muscle tone increase, respiratory and heart rate increase, red face, mydriasis, nystagmus
 • Frequently vomiting and hiccup

• Reflexes are present

• Can be harmful

• Recommended: proper premedication (this stage to be short and less intense)

• Especially dangerous: in alcoholics, drug abusers, hyperthyreotic patients, strong males

• Ether: very expressed

III. stage (surgical narcosis, stadium tolerantiae)

• progressive inhibition of the ascendent stimulator reticular formation leads to stage III.

• starts when respiration becomes normal

III/1. stage:

Normal respiration.

Normal eyeball movements

No mydriasis or miosis

No conjuntival reflex

Weakened other reflexes

Increased lacrimation

III/2. stage:

• Starts when the eye movements stops..

• Mydriasis, photomotor reflex still present.

• No cornea reflex

• Decreased respiratory amplitude and frequency

• Decreased muscle tone

• Best for surgical interventions

III/3. stage

• No thoracic respiration (only diaphragmatic)

• Respiration has 3 phases (inspiration, pause, expiration

• Stronger mydriasis, no lacrimation (no tears)

• No glottis reflex (increased danger of aspiration !), easy endotracheal intubation

• Decreased skeletal muscular tone.

III/4. stage (pretoxic):

• Starts from thoracic muscle paralysis

• Decreased respiration (evident 3 phases)

• Strong mydriasis, no photomotor reflex (fix eyes) fénymerevek.

• Decreased arterial tension followed by ?

• Cyanosis

IV. stage (toxic, stadium asphyxia)

• No spontaneous respiration

• Cardiovascular failure

• EMERFENCY:

➢ Stop the anesthetic administration

➢ Respiration with 100% oxygen

➢ Cardiovascular failure therapy

➢ If heart stops: resuscitation

Preoperative medication
• Aims:

➢ To reduce the patients anxiety,

➢ To stabilize his psychic status

➢ To reduce the anesthetic amount

➢ To counteract the anesthetics side effects

• Anxiolytics

• All causes amnesia

• BD: (Diazepam) has specific antagonist (flumazenil)

• H1 blokckers

• Phenotiazines (chlorpromazine, promethazine) sedatíve, antihistaminic, antiemetic effects

• Pain relieve
 • Also post surgery

• Opioids (morphine, meperidine, fentanyl)

• NSAID

•
Antivomiting agents

• Usually sedatives are enough, sometimes, scopolamine or antiserotoninics (ondansetron) is

given

•
To prevent the side effects

• PSL:

➢ atropine: 0,4 - 0,6 mg, to prevent bradycardia and to dry the mouth (Not to be given in fever, as
inhibits sweating)

➢ scopolamine more central effects

➢ To prevent GER and aspiration: H2-blockers (famotidine, ranitidine) and metoclopramide

➢ a2-agonists (clonidine): decrease the amount pf anesthetic, potentiate the effects of morphine,
increase hemodynamic stability and are anti-stress

Intraoperative medication
• Classic trias: - narcosis, analgesia, muscle relaxation – with different drugs

Postoperative medication
• To antagonize neuromuscular blockers

• To relieve pain

• To support circulation

• To support gut peristaltics (prokinetics)

INHALATORY ANESTHETICS
• Pharmacodynamics

- Inhibit the ascendant polysynaptic activator formatio reticularis

- hippocampus inhibition (loss of „short term memory”)

- Heterogenic group from chemical structure point of view (probably no receptors)

•
 • They are all with high liposolubility

• They inhibit some ligand-coupled ion channels

• They inhibit the function of excitatory ionotropic glutamate receptors, the nicotinic and 5-HT
receptors, but they potentiate the inhibitory GABAA and glycine receptor activity

•
MAC

• MAC (minimal alveolar concentration) relative potency: when a pain stimulus has no reaction in
50% of patients (1 MAC, 1 atm pressure)

• Premedication can influence the MAC: in the presence of opioids or sedatohipnotics MAC
usually significantly decreases

• Pharmacokinetics

Absorption and distribution

• Depth of anesthesia: the brain concentration of the drug

• Concentration of the drug un the inspired air, pulmonary ventillation, pulmonary blood flow,
the difference between narcotic concentrations in the venous and arterial blood

• If the anesthetic has bad blood solubility, his effect will be quick and smooth. In this case the
cardiac output becomes important

• Distribution and redistribution

• If the anesthetic concentration shows big difference between the arterial and venous blood,
takes more time to reach the equilibrium

• Subcutaneous fat

• Elimination

• Important, to be quick and smooth, without headache and other unpleasant side effects

• Pulmonary ventilation importance

• Usually after long narcosis the wakeup is longer

• Metabolisation

• Important especially in some older anesthetics (ether, chloroform – increased renal and liver
toxicity)

• Halothane 40%, enflurane 10%, nitrous oxide 0%

• Halothane

• Quick, smooth asleep and wakeup

• Dose dependent arterial pressure decrease

• Respiratory depression

• Muscle relaxation

• Bronchorelaxant (good in patients with asthma)

• Uterorelaxant

• Nausea, vomiting: rare

• Sometime hepato- and cardiotoxic

• After wakeup: restlessness, shaking chill (algor)

• Enflurane

• Quicker effect, then halothane

• Less arterial pressure decrease, not cardiotoxic

• Dose dependent respiratory depression

• Good muscle relaxation

• Uterorelaxant

• Nephrotoxic (only in long narcosis)

• Nausea, vomiting (3-15% of patients)

• Main problem: epilepsy

• Isoflurane

• Quick, smooth asleep and wakeup

• No epileptogenesis

• hypotension

• Good cardiac output

• Respiratory depression

• Good muscle relaxation, increases the effect of curare-like drugs

• Malignant hyperthermia

• Uterorelaxant

• No metabolisation

• Desflurane

• Quick asleep and wakeup

 • Good in ambulatory surgery

• Cardiovascular effects similar to isoflurane

• Respiratory depression

• Good muscle relaxation

•
Sevoflurane

• Very effective, used mainly in pediatric surgery

• Ether

• Chloroform

• Nitrous oxide

INTRAVENOUS ANESTHETICS
• Barbiturates (thiopental, methohexital)

• Benzodiazepines (diazepam, midazolam)

• Opioids

• Propofol

• Etomidate

• Ketamine

• Neuroleptanalgesia

• Recently increased use for short (small) surgery or induction of general inhalatory anesthesia

• Induction and awake is quick

• Barbiturates

• ultra short: thiopental, methohexital

• No analgesia (they even sometimes increase pain)

• No specific antagonist

- Decrease the brain metabolism, the brain circulation and the brain oxygen supply

- Decrease the pressure in cranial cavity (including the intraocular pressure)

• Benzodiazepines

• diazepam, lorazepam, flunitrazepam, midazolam usually for premedication and induction of

anesthesia
• specific antagonist: flumazenil.

• Neuroleptanalgesia

• Intravenous neuroleptic: droperidol

• Intravenous analgetic: fentanyl

• Sometimes with oxygen and nitrous oxide