ANESTHESIA

Claro M. Isidro md

Anesthesia

• Loss of consciousness• Analgesia• Adequate muscle relaxation

Analgesia

•Loss of sensation to pain

Types of Anesthetics:

•General Anesthetics• Reversible loss of consciousness• Loss of CNS activity

•Local Anesthetics• No loss of consciousness• Reversible loss of pain sensation

GENERAL ANESTHETICS:

INHALATIONAL ANESTHETICS

INTRAVENOUS ANESTHETICS

STAGES OF GENERAL ANESTHESIA(Guedel)

• Stage I: Analgesia• Stage II:Excitement/ Delirium• Stage III: Surgical Anesthesia

– Plane I: reg. breathing loss of eye movement

– Plane II initiation of IC muscle paralysis

– Plane III: completion ICM paralysis– Plane IV: diaphragmatic paralysis

• Stage IV: Medullary Paralysis

Pharmacokinetics:• tension (partial pressure) in the brain

depth• tension in this tissues rate of

induction and recovery

• Flow of anesthetic during induction:Anesthesia Lungs Arterial Brain &

machine blood tissues

GENERAL ANESTHETICS:

Pharmacokinetics: • absorption (uptake)• distribution• metabolism• elimination lungs

Principal objective:To achieve a constant and optimal brain partial pressure of the inhaled anesthetic

GENERAL ANESTHETICS:

• 2 PHASES:2 PHASES:

– Pulmonary PhasePulmonary Phase

– Circulatory PhaseCirculatory Phase

GENERAL ANESTHETICS: UPTAKEGENERAL ANESTHETICS: UPTAKE

• Pulmonary Phase Concentration of the anesthetic

agent in the inspired gas

Pulmonary ventilation

Transfer of anesthetic gases from alveoli to blood• solubility of the agent• rate of pulmonary blood flow• partial pressure in the alveoli

and mixed venous blood

GENERAL ANESTHETICS: UPTAKEGENERAL ANESTHETICS: UPTAKE

GENERAL ANESTHETICS: SOLUBILITYPartition Partition

CoefficientCoefficientBlood:GasBlood:Gas Brain:BloodBrain:Blood

SolubleSoluble

MethoxyfluraneMethoxyflurane 1212 22

IntermediateIntermediate

HalothaneHalothane 2.42.4 1.91.9

EnfluraneEnflurane 1.91.9 1.51.5

IsofluraneIsoflurane 1.41.4 1.61.6

Poorly solublePoorly soluble

Nitrous OxideNitrous Oxide 0.460.46 1.11.1

DesfluraneDesflurane 0.420.42 1.31.3

SevofluraneSevoflurane 0.590.59 1.71.7

As a rule, the more soluble an anesthetic in the blood the more of it must be dissolved to raise the partial pressure.

• Pulmonary Phase Concentration of the anesthetic

agent in the inspired gas

Pulmonary ventilation

Transfer of anesthetic gases from alveoli to blood• solubility of the agent• rate of pulmonary blood flow• partial pressure in the alveoli

and mixed venous blood

GENERAL ANESTHETICS: UPTAKEGENERAL ANESTHETICS: UPTAKE

GENERAL ANESTHETICS: UPTAKEGENERAL ANESTHETICS: UPTAKE

• Circulatory or Distribution Phase SolubilitySolubility

tissue:blood solubility coefficienttissue:blood solubility coefficient

Tissue Blood FlowTissue Blood Flow Vessel-Rich group – 75% of COVessel-Rich group – 75% of CO Muscle Group – 3%Muscle Group – 3% Fatty Group – 2%Fatty Group – 2% Vessel-Poor group - <1%Vessel-Poor group - <1%

Partial Pressure of Gas in Arterial Partial Pressure of Gas in Arterial Blood and TissuesBlood and Tissues

• RECOVERY and EMERGENCEFactors affecting rate of Elimination

• SOLUBILITY IN BLOOD & TISSUE• BLOOD FLOW

• Flow of anesthetic during elimination:

Tissue/ Blood Lungs AnesthesiaBrain Machine

GENERAL ANESTHETICS:GENERAL ANESTHETICS:

Ideal Characteristics of Inhalational Anesthetics:

• Rapid & pleasant induction & recovery• Rapid changes in depth of anesthesia• Adequate relaxation of smooth muscle• Wide margin of safety• Absence of toxic effect

INHALATIONAL ANESTHETICS

• GASEOUS ANESTHETIC:• NITROUS OXIDE• CYCLOPROPANE

• VOLATILE ANESTHETIC:

A. HalogenatedA. Halogenated B. Non B. Non HalogenatedHalogenated

1. 1. HalothaneHalothane 1. Ether1. Ether

2. Enflurane2. Enflurane 2.2. Chloroform Chloroform

3.3. Isoflurane Isoflurane

4. Methoxyflurane4. Methoxyflurane

5. Sevoflurane5. Sevoflurane

6.6. Desflurane Desflurane

Halothane• 2 bromo-111 triflouroethane • is a non ether derivative ( an ethane)• vapor is pleasant to smell and non-irritating• can cause a dose dependent reduction of arterial

blood pressure due to: 1.  Direct depression of the myocardium 2. The normal baroreceptor mediated tachycardia

in response to hypotension is obtunded • sensitizes the myocardium to catecholamines

leading to cardiac arrhythmia’s • causes a dose related reduction in the ventilatory

response to carbon dioxide • produce adequate muscle relaxation• has no toxic effect on the kidneys

• Repeatedadministration over a short period of time has been implicated to produce halothane hepatitis

• another dreaded complication is malignant hyperthermia, which is characterized by the following:

1. Rapid rise in body temperature 2. massive increase in oxygen consumption 3. increase production of carbon dioxide• Cardiotoxic, Hepatotoxic but not Nephrotoxic

Enflurane• 2 chloro-112 trifluroethyl difluromethyl ether• an halogenated ether derivative • produce mild stimulation of salivation and bronchial• cause dose dependent myocardial depression

similar to that of halothane• sensitizes the myocardium to the effect of

catcholamines , no unusual effect on the GIT • muscle relaxation is greater than that of halothane• contraindicated in patient with seizure disorder

because it cause CNS irritability in high doses• the free fluoride radical a metabolite of enflurane

has been implicated to its renal toxicity so it is contraindicated in patient with renal disorder

• Cadiotoxic, Nephrotoxic but not Hepatotoxic

Isoflurane• 1 chloro-222 trifluroethyl difluromethyl ether • an halogenated ether derivative• the chemical and physical properties are similar to

those of its isomer enflurane• does not sensitize the myocardium to the effect of

cathecholamines • cerebral blood flow is increased while the cerebral

metabolism is reduced• produce adequate muscle relaxation • less nephrotoxic than enflurane • less hepatotoxic than halothane• agent of choice for cardiac surgery• non Cardiotoxic, non Hepatotoxic, non

Nephrotoxic• Least vicerotoxic

Methoxyflurane• 2,2dichloro- 1,1 difluroethyl methyl ether • it is clear, colorless liquid with sweet fruity odor • non flammable and non explosive in air • most potent of the inhalational anesthetic• induction of anesthesia is slow due to its high

solubility coefficient• respiratory and cardiovascular depression is

generally similar to that of halothane • sensitize the myocardium to the effects of

catecholamines • nephrotoxicity and hepatotoxicity are the major

disadvantage • most toxic of the inhalational anesthetic• Cardiotoxic, Hepatotoxic, and Nephrotoxic

Desflurane• a fluorinated methyl ethyl ether that differ from

isoflurane only by substitution of a fluoride atom from chlorine

• can produce a dose related decrease in blood pressure and cardiac output

• non Cardiotoxic, non Hepatotoxic, non Nephrotoxic

Sevoflurane• also a fluorinated methyl ethyl ether• not irritating to the airways• cardivascular effect is similar to isoflurane

Non Hologenated

Ether • first anesthetic discovered • seldom use today because of its flammability and

explosive property

Chloroform• no longer use today because of liver toxicity • non explosive and non flammable • has rapid induction and recovery

Gaseous Anesthetics

Nitrous Oxide

• sweet smelling, non irritating, colorless gas• the only inorganic gas in common use

possessing anesthetic properties• potent analgesic but a weak anesthetic in

the sense that it does not produce adequate muscular relaxation

• ventilatory drive is not affected• little or no cardiovascular effect

Cyclopropane• explosive and flammable property

INHALATIONAL ANESTHETICS

• GASEOUS ANESTHETIC:• NITROUS OXIDE• CYCLOPROPANE

• VOLATILE ANESTHETIC:

A. HalogenatedA. Halogenated B. Non B. Non HalogenatedHalogenated

1. 1. HalothaneHalothane 1. Ether1. Ether

2. Enflurane2. Enflurane 2.2. Chloroform Chloroform

3.3. Isoflurane Isoflurane

4. Methoxyflurane4. Methoxyflurane

5. Sevoflurane5. Sevoflurane

6.6. Desflurane Desflurane

BARBITURATES• the most commonly use barbiturates is the ultra short acting

thiopental• following a single IV anesthetic dose of thiopental

unconsciousness occur after 10-20 seconds and returns in 20-30 minutes

• poor analgesic and may even increase the sensitivity to pain (hyperalgesia) when administered in inadequate amounts.

• Not irritating to the respiratory tract• Cerebral blood flow and cerebral metabolic rate are reduced• Produce a dose related depression of respiration and circulation• Agent of choice for induction of anesthesia in patient with

increased intracranial pressure and hypertension• Contraindicated in patient with acute intermittent porphyria and

hypotension

INTRAVENOUS ANESTHETICSINTRAVENOUS ANESTHETICS

Benzodiazepines (Diazepam) • first introduced for the treatment of anxiety• rapidly absorbed from the GIT after oral

administration• hypnosis and unconsciousness may be produced

with large doses• cause amnesia in 50% of patients

characteristically Anterograde type• may cause moderate depression of circulation

and respiration• they are not analgesic and it is necessary to

combine several drugs to achieve surgical levels of anesthesia

Ketamine HCl • used for induction of dissociative anesthesia• a sensation of dissociation is noticed within 15

seconds and unconsciousness becomes apparent within another 30 seconds and lasts for some 40 minutes

• intense analgesia and amnesia are established rapidly

• muscular relaxation is poor• cardiovascular and respiratory system are stable• drug of choice for induction of anesthesia in

children and hypotensive patients• contraindicated in patients with hypertension

because it increase sympathetic activity • can cause increase intraocular pressure• contraindicated in patient with glaucoma

Propofol

• 2,6 Diisoprophylpenol• produces anesthesia at a rate similar to

that of barbiturates• cause marked decrease in systemic blood

pressure during induction• post operative vomiting is less common

and may have anti-emetic property • hypersensitivity is less common

Properties of a Desirable Local Anesthetic

• should not be irritating to tissues• should not cause permanent damage

to nerves• have low systemic toxicity• must be effective • should have rapid onset but long

duration of action

• MOA: block nerve conduction

• Structure:– aromatic group (Hydrophobic lipophilic)– amide group (hydrophilic)

• tertiary amine or secondary amine– intermediate chain

•Ester or Amide

LOCAL ANESTHETICSLOCAL ANESTHETICS

Structure

CH2-

CH3

NH2 O-O-CH2-CH2-N

O CH2-CH3

Aromatic grp Alkyl Amide grpLipophilic chain Hydrophilic

• METABOLISM:

Ester plasma and liver esterases metabolite: PABA

Amide liver

• EXCRETION:

kidneys

LOCAL ANESTHETICSLOCAL ANESTHETICS

• ROUTES OF ADMINISTRATION:

1. Topical2. Local Infiltration3. Nerve Block4. Spinal or Intrathecal injection5. Epidural 6. Caudal

LOCAL ANESTHETICSLOCAL ANESTHETICS

LOCAL ANESTHETICSLOCAL ANESTHETICS

ESTERS:ESTERS:

1.1. CocaineCocaine

2.2. ProcaineProcaine

3.3. ChloroprocaineChloroprocaine

4.4. TetracaineTetracaine

AMIDES:AMIDES:

1.1. LidocaineLidocaine

2.2. BupivacaineBupivacaine

3.3. MepivacaineMepivacaine

4.4. DibucaineDibucaine

5.5. PrilocainePrilocaine

6.6. EtidocaineEtidocaine

May also be classified into

a. Short acting – cocaine, procaineb. Intermediate acting – lidocaine,

mepivacaine, dibucaine, prilocainec. Long acting – tetracaine,

bupivacaine, etidocaine

1. Hepatotoxic agent a. Isoflurane

2. Nephrotoxic agent b. Barbiturate3. Cardiotoxic agent c. Enflurane4. Thiopental d. Halothane5. Flammable agent e. Ether

a.Amide LA b. Esther LA6. Lidocaine7. Tetracaine8. Cocaine9. Bupivacaine10. Etidocaine