General anesthesia

Muhammad Faisal Nadeem

What is general anesthesia?

A. pain relief (analgesia) B. blocking memory of the procedure (amnesia) C. producing unconsciousness D. inhibiting normal body reflexes to make surgery safe and easier to perform E. relaxing the muscles of the body

Definition

General anesthesia is anesthetics-induced reversible suppression on CNS. Anesthesia is a state of narcosis sever central nervous system depression produced by pharmacological agents). Patient under anesthesia are not arousable, even to painful stimuli. They loss the ability to maintain ventilatory function and require assistance in maintaining air way patent.

Early history
Ancient/Medieval period Opium Alcohol Cannabis

History of Anesthesia

History

1845- Horace Wells- N2O 1846- William Morton- Ether 1847- Simpson- Chloroform 1853-John Snow 1878- Endotracheal tube discovered 1884- Local anesthesia with cocaine

1895-98- Spinal analgesia/anaesthesia

History
1921- Epidurals 1934- Thiopental first used, cyclopropane 1942- Curare first used- opened the Age of Anesthesia 1946- Lignocaine 1951- Suxamethonium 1952- IPPV 1956-Halothane

Definition
Loss of sensation General Regional Local

Hypotheses of General Anesthesia

1.

Lipid Theory: based on

the fact that anesthetic action is correlated with the oil/gas coefficients.

2. Protein (Receptor) Theory: based on the

fact that anesthetic potency is correlated with the ability of anesthetics to inhibit enzymes activity of a pure, soluble protein. Also, attempts to explain the GABAA receptor is a potential target of anesthetics acton.

The higher the solubility of anesthetics is in oil, the greater is the anesthetic potency. Meyer and Overton Correlations Irrelevant

Other Theories included

Binding theory:
Anesthetics bind to hydrophobic portion of the ion channel

Mechanism of Action
UNKNOWN!! Most Recent Studies:
General Anesthetics acts on the CNS by modifying the electrical activity of neurons at a molecular level by modifying functions of ION CHANNELS. This may occur by anesthetic molecules binding directly to ion channels or by their disrupting the functions of molecules that maintain ion channels.

Cont on Mechanism

Scientists have cloned forms of receptors in the past decades, adding greatly to knowledge of the proteins involved in neuronal excitability. These include:
Voltage-gated ion channels, such as sodium, potassium, and calcium channels Ligand-gated ion channel superfamily and G protein-coupled receptors superfamily.

Basic Principles of Anesthesia

Anesthesia

defined as the abolition of sensation Analgesia defined as the abolition of pain Triad of General Anesthesia
need for unconsciousness need for analgesia need for muscle relaxation

Triad of General anaesthesia

Hypnosis

Analgesia

Muscle relaxation

General anesthesia Stages

Take off (Induction). Maintenan ce (Maintenan ce). Cruising (Recovery) .

Course of General Anesthesia

Maintenance period
Lost consciousness

IV+Inhale

quickly Exhale

IV

awake

Hypnosis
Death

Coma Hypnosis

sedation
Amnesia Awake

Route of Action
Inhalation anesthetics Intravenous anesthetics

Alveolar

blood

Central nervous system

Anesthesia

Anesthetics

Inhalational Anesthetic Agents

Inhalational anesthesia refers to the delivery of gases or vapors from the respiratory system to produce anesthesia Pharmacokinetics--uptake, distribution, and elimination from the body Pharmacodyamics-- MAC value

Inhalation anesthetics

Through airway

Maintenance (most); induction (some)

Most are halogenated hydrocarbons Mechanism: interact with the brain cell membrane, details are not clear

Pharmacokinetics of Inhaled Anesthetics

1.

Amount that reaches the brain

1. Indicated by oil:gas ratio (lipid solubility)

2.

Partial Pressure of anesthetics

1. 5% anesthetics = 38 mmHg

3.

Solubility of gas into blood

1. The lower the blood:gas ratio, the more anesthetics will arrive at the brain

4.

Cardiac Output
1. Increased CO= greater Induction time

Pathway for General Anesthetics

How to compare anesthetic potency?

MAC (minimum alveolar concentration)

The concentration (at 1atm) required to prevent movement in 50% of subjects following a surgical stimulus

Oil-gas partition coefficient

Anesthetic potency MAC

MAC is also an index for depth of anesthesia

Inhalational anesthesia
Lower MAC
Elder hypotension hypothermia hypothyroidism concurrent use of opioids

higher potency

Infant pyrexia drug abuser

MAC

MAC

How to determine its controllability?

Blood-gas partition coefficient (solubility)

The lower the blood-gas partition coefficient

the easier for the partial pressure in alveolar, blood and brain to get equilibrium

the easier to control its concentration in brain

Rate of Entry into the Brain: Influence of Blood and Lipid Solubility

Factors determining blood gas

1. 2.

Effect of ventilation Effect of concentration

3.
4.

Cardiac output
Blood-gas partition coefficient (solubility)

5.

Alveolar-to-venous anesthetic gradient

Metabolism of inhalation anesthetics

Major: eliminated by lung Minor: metabolized in liver metabolic rate, media product and the final product decide toxicity
ether
2.1-3.6

N2O
0.004

halothane enflurane isoflurane sevoflurane

15-20 2-5 0.2 2-3

desflurane
0.02

General Actions of Inhaled Anesthetics

Respiration
Depressed respiration and response to CO2

Kidney
Depression of renal blood flow and urine output

Muscle
High enough concentrations will relax skeletal muscle

Cont

Cardiovascular System
Generalized reduction in arterial pressure and peripheral vascular resistance. Isoflurane maintains CO and coronary function better than other agents

Central Nervous System

Increased cerebral blood flow and decreased cerebral metabolism

Nitrous Oxide (N2O)

MAC: 105%, low anesthetic potency, inhalation conc.:5070% (FiO2>0.3) , in combination with other agent

B/G: 0.47, fast Respiratory system: non-irritant, no injury

Cardiovascular system: almost no-depression

Diffuse hypoxia: inhale 100% O2 5-10min Increase cavity pressure: forbidden in colon obstruction

Enflurane

Properties clear colourless volatile anesthesia, pleasant smell MAC 1.7, B/G 1.9, Metabolism 2%

Cardiovascular: Myocardial contractility reduced Systemic vascular resistanceBP Sensitivity of myocardium to catecholamine

Respiratory: non-irritant; dose dependent inhibition Muscle relaxation Induction and maintenance, unavailable in USA Patient with epilepsy history should be avoided (seizure activity on EEG)

Isoflurane
Properties clear colourless volatile anesthesia, pungent odor

MAC 1.15

B/G 1.4

Metabolism 0.2 %

Cardiovascular: mild depression of myocardial contractility systemic vascular resistanceBP coronary steal little sensitization of myocardium to Catecholamine

Respiratory: dose dependent inhibition

Muscle relaxation Maintanence

Sevoflurane

Properties clear colourless volatile anesthetic; pleasant smell MAC 2% B/G 0.65 (rapid induction in children) Metabolism 2%

Cardiovascular: similar to isoflurane Respiratory: dosedependent inhibition, no irritate to airway Muscle relaxation: similar to isoflurane Both Induction and maintenance Decomposition in soda lime and when temperature rises

Desflurane

Properties: clear colorless volatile anesthesia

MAC 6.0-7.25%

B/G 0.42 (very rapid onset) Metabolism 0.02%

Cardiovascular: similar to isoflurane but no coronary steal Respiratory: no pungent odor but irritant Muscle relaxation: stronger than isoflurane Induction and maintenance

Nausea and vomiting

Special vaporizer, expensive

Halothane

Properties: clear colorless volatile anesthesia; pleasant smell MAC 0.75 B/G 2.4 Metabolism 20 %

Cardiovascular: Myocardial contractility reduced Systemic vascular resistanceBP

Increase sensitization of myocardium to catecholamine

Respiratory: non-irritant; pleasant smell; dilate bronchial; inhibition Muscle relaxation Induction and maintenance Halothane associated hepatitis: seldom in use now, unavailable in

China

Which has the best anesthetic potency? Which takes effect fastest?
Molecular weight nitrous oxide 44 Oil-gas 1.4 Blood-gas 0.47 MAC 105

enflurane
isoflurane sevoflurane desflurane xenon ether

184
184 200 168 131.3 74

98
98 53.4 18.7 1.9 65

1.9
1.4 0.65 0.42 0.14 12

1.7
1.15 2.0 6.0 71 1.9

halothane

197

224

2.4

0.75

Thank you!

Intravenous anesthetics

Ideal Intravenous anesthetic

Water-soluble, no pain on injection Rapid onset, rapid recovery, little accumulation, little depression on respiratory-cardiovascular system. No nausea and vomiting, no interact with muscle relaxant, no release of histamine.

Intravenous Anesthetic Agents

Advantages of Intravenous Anesthesia

Speed of induction Smooth induction Low incidence of side effect Patient acceptability

Intravenous Anesthetic Agents

Characteristics of the ideal intravenous induction

Smooth and rapid onset A rapid recovery No pain on injection Minimal side effect No toxicity

Intravenous anesthetics
Induction dose(mg/kg) CVS hypotension RS depression CNS (CBF) yes Side-effect Pain on injection Movement Pain on injection movement rare Other comments TIVA

propofol

1.5-2.5

etomidate

0.15-0.3

Less depression

depression

yes

Suppress steroid synthesis

thiopentone

4-6

hypotension

depression

yes

Delayed recovery after repeated use

ketamine

1-2 (iv) 6-10(im)

minimal

minimal

No

hallucination

Analgesia Dissociated anesthesia amnesia

midazolam

0.1-0.3

hypotension

depression

yes

Thiopentone

Sedation&hypnosis 2.5% Onset Analgesic effect CNS Cardiovascular Respiratory Indications

lost consciousness 4-6mg/kg 30s poor cerebral metabolic rate anticonvulsant myocardial contractility vasodiltation, BP VT RR bronchial muscle tone induction/anticonvulsant/anesthesia.

Thiopental

Water soluble. Alkaline. mild direct cardiac depression. lowers blood pressure. compensatory tachycardia (baroreflex). Tissue necrosis. Gangrene. Non compatibility. Tissue stores.

SIDE EFFECTS

Thiopental

Redistribution

Propofol

Out-patient anesthesia Induction: 2mg/kg; maintenance: TCI/TIVA Supplement to local anesthesia Sedation in ICU Side effect :cardiovascular& respiratory suppression, excitatory phenomenon, pain on injection

Etomidate

Structure similar to ketoconozole Direct CNS depressant (thiopental) and GABA agonist Redistribution

Etomidate Systemic Effects

Little change in cardiac function in healthy and cardiac patients Mild dose-related respiratory depression Decreased cerebral metabolism

Side Effects
Pain on injection (propylene glycol) Myoclonic activity Nausea and vomiting (50%) Cortisol suppression

Ketamine

Interrupts cerebral association pathways - dissociative anesthesia

Stimulates central sympathetic pathways

Ketamine Systemic and Side Effects Characteristic of sympathetic nervous system stimulation-- increase HR, BP, CO Maintains laryngeal reflexes and skeletal muscle tone Emergence can produce hallucinations and unpleasant dreams (15%)

Benzodiazepines

Produce sedation and amnesia Potentiate GABA receptors Slower onset and emergence

Diazepam
Often used as premedication or seizure activity, rarely for induction Minimal systemic effects-- respirations decreased with narcotic usage Not water soluble-- venous irritation Metabolized by liver-- not redistributed

Lorazepam
Slower onset of action (10-20 minutes)-not used for induction Used as adjunct for anxiolytic and sedative properties Not water soluble-- venous irritation

Midazolam
More potent than diazepam or lorazepam Induction slow, recovery prolonged May depress respirations when used with narcotics Minimal cardiac effects Water soluble

Sodium hydroxybutyrate

Site: Cortex hippocampus limbic system Normal physical sleeping CirculationBP slightly increaseHR reduce Respiration: TV increasefrequency slow IndicationInduction and maintenance basal anesthesia+ketamine (poor analgesia effect)

Dosage: 50-100mg/kg

Onset 5-10min, duration45-60min

Muscle relaxants

Skeletal muscle relaxants No anesthetic effect Cannot make patient lost consciousness Cannot produce amnesia

Suitable condition for surgery

Avoid hazardous of deep anesthesia No analgesia

Mechanism: interfere with the normal action of acetylcholine (ACH) at the motor end plate, block the receptors on the postsynaptic muscle membrane

ACH ACH Presynaptic synaptic gap Postsynaptic membrane membrane ACH ACH ACH ACH Impulse

Depolarization Muscle contraction

ACH

repolarization

Classification

Depolarizing muscle relaxants

suxamethonium (Succinylcholine, scoline)

Nondepolarizing muscle relaxants Pancuronium Vecuronium Atracurium Tubocurarine

Depolarizing muscle relaxant Suxamethonium ()

similar to acetylcholine (ACH)binding to receptor,

depolarizing contraction (fasciculation)

cant be hydrolyzed by cholinesteraseNO responses to further actionflaccid-muscle relaxant

Indication tracheal intubate 1-2mg/kg

peak at 1min, 4-5min, recover at 10min

Side effects: muscle pains intraocular, intragastric, intracranial pressure hyperkalaemia Malignant hyperthermia

Nondepolarizing muscle relaxant

tubocurarine
binding to receptor , but non-depolarizing
compete for the receptors

antagonist by inhibitor of cholinesterase

neostigmine

Muscle relaxants
agents intubating dose (mg/kg) 1-2 onset (min) 0.5 action duration (min) 3-8

Scoline

Tubocurarine

0.6
0.1

4-6
3-6

30-40
30-6

Pancuronium

Atracurium

0.6
0.1

3-5
2-3

15-35
25-30

Vecuronium

Muscle relaxants
dvantage Scoline side effect rapid metabolisam histamine release cholinesterase - fasciculation,K+ pressure

Tubocurarine
Pancuronium Atracurium Vecuronium Cis-atracurium Hoffmann Hoffmann

asthma
HR

kidney bile
liver kidney bile Hoffmann liver kidney bile Hoffmann

++
+ -

Atracurium and cisatracurium

Dose intubation 0.5-0.6mg/kg maintenance 0.15-0.2mg/kg

Time intubation 90-120s duration 20-25min

Release histamine, hypotension Spontaneous degradation in plasma, unaffected by liver or renal function

Cisatracurium: more potent

Rocuronium

Dose intubation 0.6-0.7mg/kg maintenance 0.15-0.2mg/kg

Time intubation 90-100s duration 20-30min

Can be used for rapid sequence intubation

Vecuronium

Dose intubation 0.1mg/kg

maintenance 0.02-0.03mg/kg

Time intubation 90-120s

duration 15-20min

No histamine release, can be used in patients with asthma

Pancuronium
Dose

intubation 0.15-0.2mg/kg

maintenance 0.1mg/kg
Time

intubation 100-120s duration 10-15min

Hypertension

and tachycardia may occur

Long-acting

Thanks for attention