General Anesthetics

Dr. Irfan Ahmad Khan, MBBS, MD

Assistant Professor

General anesthetics (GAs)

Drugs which produce reversible loss of

all sensation and consciousness.

Cardinal features of general

anaesthesia are:

Loss of all sensation, especially pain

Sleep (unconsciousness) and amnesia

Immobility and muscle relaxation

Abolition of somatic and autonomic

reflexes.

General Anesthetics Inahalational –

Gas: Nitrous oxide

Volatile liquids: Halothane, Isoflurane,

Desflurane, Sevoflurane (Halogenated

liquids), Ether

Intravenous -

Fast Inducers: Thiopental, Methohexital,

Propofol

Slow Inducers: Midazolam, Lorazepam,

Ketamine

Mechanism of Action

Ketamine and nitrous oxide inhibit NMDA

glutamate receptors (Ca2+ Channel)

Halogenated inhalation anesthetic –

decrease the duration of opening of

nicotinic receptors activated Na+

channels→ decrease the excitatory effects

of ACh at cholinergic synapse

Volatile anesthetics, Barbiturates,

Propofol, Benzodiazepines –

Potentiate GABA mediated inhibition at

GABAA receptors

Action of glycine in the spinal cord and

medulla is augmented by barbiturates,

propofol and many inhalational

anaesthetics.

Factors affecting the depth of

inhalational anesthetics

Partial pressure of anesthetic gas in the

lung alveoli

Minimal Alveolar Concetration (MAC)

produces immobility in 50% subjects in

response to painful stimulus

Higher MAC – lower anesthetic potency

(0.5 to 2 MAC adequate anesthesia)

Lipid solubility

Greater solubility - Greater effect

Blood solubility

Greater solubility - Slower induction

& recovery

Pharmacokinetic of inhalational anesthetics

Enters into blood from alveoli and maximum drug

taken out by pulmonary routes

20% Halothane and 2% Enflurane metabolized in

liver (liver insufficiency delays recovery from

halothane)

Second gas effect and diffusion hypoxia

During induction of general anesthesia, when a

large volume of a gas eg N2O is taken up from

alveoli into pulmonary capillary blood, the

concentration of gases remaining in the alveoli is

increased: Second gas effect

Because of the contraction of alveolar volume

associated with the uptake of the nitrous oxide.

During emergence from nitrous oxide anesthetic,

rapid elimination of nitrous oxide from the lungs

dilutes other alveolar gases, producing

“diffusion hypoxia.”

This phenomenon is driven by the same

mechanism as the second gas effect—but in

the reverse direction.

Pharmacological Action

CNS - analgesia to vasomotor centre

depression

CVS

Ether stimulatory effect – tachycardia,

increased cardiac output and

adrenaline secretion leading to

hypertension

Halogenated agents – cardiac

depression, increased susceptibility

to cardiac dysrhythmia

Respiration – decreased ventilation

volume (tidal volume X RR)

Kidney – decreased GFR

Preanesthetic medication

Use of drugs before anaesthesia to

make it more pleasant and safe

AIM

Relief of anxiety

Amnesia for pre and post operative events

Supplement analgesic action

Decrease secretions and vagal stimulation

Anti-emetic effect

Decrease acidity and volume of gastric secretion

1. Sedative-antianxiety drugs : Benzodiazepines like

diazepam (5–10 mg oral) or lorazepam (2 mg oral or

0.05 mg/kg i.m. 1 hour before)

2. Opioids: Morphine (10 mg) or pethidine (50–100 mg)

3. Anticholinergics : Atropine or hyoscine (0.6 mg or 10–

20 μg/kg i.m./i.v.) or glycopyrrolate (0.2–0.3 mg or 5–10

μg/kg i.m./i.v.)

4. H2 blockers/proton pump inhibitors

5. Antiemetics: Metoclopramide, Domperidone,

Ondansetron

Stages of anaesthesia (Guedel 1920)

Ether Stage of analgesia

Starts from anaesthetic inhalation and

lasts upto loss of consciousness

Stage of delirium

From loss of consciousness to

beginning of regular respiration

Stage of anesthesia

from onset of regular respiration to

cessation of spontaneous breathing

Stage of medullary paralysis

Cessation of breathing to failure of

circulation and death

Lieutenant Arthur

Guedel, "The

motorcycle anesthetist

of World War I

Ether

Highly volatile liquid

Potent anesthetic

High blood solubility

Induction unpleasant & slow

Recovery slow

Post anesthetic nausea & vomitingEther

Nitrous Oxide

Induction & recovery fast

Potency – low (65-70%)

Now used with halothane &

oxygen

Horace Wells undergoes tooth

extraction under nitrous oxide

anaesthesia

Advantage

More safe

Strong analgesic

Dose of other anesthetic is reduced

Non toxic to liver, kidney & brain

Drawbacks

Requires apparatus

CO2 accumulation

Contraindications

Intestinal obstruction

Pneumothorax – Nitrous oxide

expands closed gas filled chambers

of the body

Halothane

Induction: 2-3%, Maintenance: 1-2%

Commonly used potent anesthetic

Produce smooth & rapid anaesthesia

Narrow safety margin

Causes direct cardiac depression due

to decreased Ca+2 concentration

Potentiates the effect neuromuscular

blockers

Postoperative nausea & vomiting

Hepatitis: 1 in 10000

Metabolism in liver→ Trifluoroethanol

& Bromide ion (tissue toxic)

Disadvantages

Only unconsciousness

Expensive

Advantages

Induction & recovery fast

No laryngeal irritation

Bronchodilation

Isoflurane

Smooth and rapid induction

Rapid recovery

Induction - 3% with oxygen,

maintenance 1.0 to 2.0%

CVS

Coronary Steal - precipitate regional

myocardial ischemia

Vasodilator→ Hypotension

Advantage

Metabolism – negligible (0.2%)

No Hepatic and renal toxicity

Preferred in neurosurgery

Disadvantage

Costly & pungent

Sevoflurane

Potency less than isoflurane

Induction and recovery fast

Suitable for pediatrics patients

Drawback

Cost - high

Pediatric anesthesia

Parenteral General Anesthetics

Thiopental

Ultra short acting barbiturate

Advantages

Induction quick and pleasant

No irritation

Excitement - Nil

Nausea, vomiting - low

Pentothal

Disadvantage

Insignificant analgesic action and muscle

relaxation

Dose

Induction: 3-5 mg/kg body weight,

slow IV (rapid administration causes

severe hypotension)

Contraindication

Barbiturate allergy

Cardiovascular Disease

Pulmonary disease

Hepatic disease

Ketamine

Phencyclidine derivative

Cause sedation, amnesia, dissociation and

analgesia – dissociative anaesthesia

Advantage

Adequate analgesic activity

Less incidence of vomiting

Sympathomimetic effect – better in shock,

severely dehydrated, asthmatic and

pediatric patients

Disadvantages

Muscle relaxation – nil

Not suitable in CVD and neurosurgery

Emergence delirium (frightening dreams

& disorientation) - prevented by diazepam

0.2-0.3 mg/kg IV

Dissociative anaesthesia

Propofol

1% emulsion

Short term anaesthesia (10 min)

Suitable for OPD procedure

Nausea and vomiting low

Disadvantages

Hypotension due to vasodilation

Pain during injection

Respiratory depression > thiopental

ADR

Apnoea & pain at injection

Marked decrease in BP due to

vasodilation

Dose: 1.5 – 2.5 mg/kg IV

Fentanyl

Short acting OPIOID

Used as supplement anesthetic

(2-4 µg/kg body weight)

Combined with benzodiazepines

Patients remain drowsy but conscious

.

Neurolept Analgesia (fentanyl 50µg/ml &

droperidol 2.5 mg/ml)

Neurpolept- Anesthesia (fentanyl

50µg/ml & droperidol 2.5 mg/ml) +

nitrous oxide & oxygen