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Pharmacology II
Inhalation Anesthesia
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General anesthesia state in which the body is rendered insensible to pain or other stimuli.

An inhalation anesthetic must be delivered to the body in such a manner that a satisfactory partial pressure
   of the agent is developed in the brain without producing excessive depression within the patient.

GOAL: - to produce and maintain a constant partial pressure of inhalational anesthetic in the brain. The mechanism to accomplish this is to produce a partial pressure in the alveoli (PA) which produces a partial pressure in the blood (Pa) which in turn produces a partial pressure in the brain (Pbr).

Uptake and Distribution
Within the body this can be divided into 4 phases:
1.Developing an inspired anesthetic concentration
2.Development of an alveolar anesthetic concentration
3.Development of a blood anesthetic concentration
4.Distribution of the anesthetic agent from the blood to the tissue

Developing an inspired anesthetic concentration:
Begins with introduction of an anesthetic agent into the delivery system of the anesthesia machine and circuitry.
Ventilation introduces the gas into the lungs called "inspired gas" or Fi.
Using "high flows" of delivery gases (O2, N2O/O2) in the 5-10L/min range, can precisely control the partial pressure of an anesthetic agent inspired and accomplish what is called a "wash in".

CONCENTRATION EFFECT
High concentrations of inspired gases are rapidly removed from the lungs by the blood. This tends to encourage increased inspired volumes of fresh gases at a high concentration, increasing minute ventilation as a result.

Increased inspired volumes promotes an increase in alveolar partial pressure (PA) and helps to offset the decrease in partial pressure of the gases brought on by pulmonary capillary uptake, which in turn promotes the rapid induction of anesthesia.

High concentrations mean greater uptake and the greater the uptake the greater the inspired volume is augmented.

Developing an alveolar anesthetic concentration:
Involves the uptake of the inspired anesthetic from the delivery system into the lungs at the alveolar level.

The rate at which the alveolar partial pressure of the anesthetic rises is determined by 2 factors:
   -inspired concentration
   -alveolar ventilation
When alveolar ventilation is high, the partial pressure of the anesthetic in the alveolar increases rapidly.
When there are 2 anesthetic gases present in the lungs phenomenon of "SECOND GAS EFFECT" can occur.
   When first gas (N2O) is used, it is picked up rapidly from the alveoli by the blood. This rapid crossing of N2O into the blood tends to pull the second gas (eg, isoflurane) along with it, so that the arterial partial pressure of the second gas rises more rapidly than it would if it were alone in the alveoli.



Developing a blood-anesthetic concentration:
Three (3) factors determine how rapidly anesthetics pass from the inspired gases to the blood:
Solubility of the agent
Rate of blood flow through the lungs (CO)
Partial pressure of the agents in the arterial/venous blood (Pa)

SOLUBILITY OF AGENT IN BLOOD
Expressed as blood:gas partition coefficient. Represents ratio of anesthetic concentration in the blood to the anesthetic concentration in a gas (alveolar) when the two are in a state of equilibrium.

   SOLUBILITY OF AGENT IN BLOOD =    ANESTHETIC BLOOD CONCENTRATION
                  ANESTHETIC ALVEOLAR CONCENTRATION

            Pa
            PA

The more soluble the agent is, the more of it must be dissolved in the blood in order to raise its partial pressure. These agents require a longer induction time because of the amount required to develop a partial pressure in the blood.
Insoluble gases, very little needs to be dissolved before the partial pressure needed is reached and the induction time for these agents would be very rapid (eg, N20, Desflurane)

The higher the number the longer it takes to anesthetize patient.

RATE OF PULMONARY BLOOD FLOW (CO)
The rate of blood passing through the pulmonary tissue influences how fast the anesthetic agent will be picked up from the alveoli.

The higher the blood flow, the more blood that is exposed to the agent, the faster the agent is picked up from the alveoli and delivered to the tissues.

PARTIAL PRESSURE OF ARTERIAL/MIXED VENOUS BLOOD
As arterial blood leaves the lungs it circulates through the tissue where the anesthetic agent is transferred.

Initially as the venous blood returns to the lung, the partial pressure of the agent will be very low as most was delivered to the tissue which also had very low to no partial pressure.

With each circulation time more anesthetic is delivered to the tissue and their partial pressure rises, the returning venous blood will also begin to have higher partial pressure as it returns to the lungs.

As the venous partial pressure rises there is less picked up from the alveoli and uptake decreases.

4. Distribution of the anesthetic agent from the blood to the brain and other tissues:
When the agent is delivered to the tissues by the arterial blood, the partial pressure in the tissues begins to rise and approach the partial pressure of the blood. The rate at which this occurs depends upon several factors:
Solubility of the gas in tissues:
Expressed as the tissue:blood partition coeficient (similar to blood/gas coefficient)
Most agents are equally soluble in lean tissue and blood, so that their partial pressures are very similar at equilibrium.
Tissue blood flow:
The higher the blood flow to a particular tissue, the faster the anesthetic is delivered and the faster the partial pressure and concentration will rise in that area.


Four categories of tissue groups:
VESSEL RICH: Brain, heart, liver, kidney, endocrine
MUSCLE: Skin and muscle
FAT: Adipose tissue
VESSEL POOR: Bone, ligaments, teeth, hair cartilage
Partial pressure in arterial blood/tissues:
As tissues take up the agent, the partial pressure of the agent increases toward that of blood and uptake will begin to slow.

The rise in alveolar (FA) anesthetic concentration toward the inspired (Fi) concentration is most rapid with the least soluble agents: nitrous oxide (N2O), desflurane, and sevoflurane. The moderately soluble anesthetic agents halothane and isoflurane have a slower rate of FA to Fi ratio rise.


MINIMUM ALVEOLAR CONCENTRATION (MAC)
Defined as that partial pressure of an inhalation anesthetic at 1 atmosphere that prevents skeletal muscle movement in response to a surgical skin incision in 50% of the patient population. Index of potency for inhalation agents.

MAC is measured in alveoli:
The partial pressure of a gas can be easily measured in the lung.
The partial pressure of an anesthetic in the alveoli and brain are nearly equal at equilibrium.
High blood flow to the brain ensures a rapid equilibration between brain and alveoli.

MAC is a reliable indicator of dose and potency of an anesthetic.

The lower the MAC, the more potent the agent and the higher the blood:gas partition coefficient.

MAC influenced by different factors.
Factors that decrease MAC:
Hypoxia: decreased PaO2 causes narcosis itself
Anemia: decreased PaO2, decreases MAC
Hypotension: decreased MAP decreases MAC
Drugs: lithium, narcotics, sedatives, calcium channel blockers, acute alcohol ingestion, etc., all reduce MAC
Pregnancy: due partially to hormonal influences
Age: elderly, decreased CBF, CMRO2
Factors that increase MAC:
Age: infants, MAC usually greatest in newborn due to BMR
Hyperthermia
Drugs: alcohol, barbiturates, narcotics, etc., chronic use


STAGES OF ANESTHESIA
STAGE I:
Stage of Analgesia
Brain gas tension is very low. Dorsal horn activity decreases and there is decreased synaptic transmission in the spinothalamic tract. It begins with the administration of anesthesia and ends with the loss of consciousness.
STAGE II:
Stage of Delirium or Excitement
The partial pressure of the brain (Pbr) rises and there is blockade of inhibitory neurons, which enhances and facilitates synaptic transmission. Will see increased muscle tone, irregular breathing, jaw clenching, involuntary activity, pupils dilate, blood pressure and HR is elevated. This stage extends from the loss of consciousness to the beginning of surgical anesthesia.

STAGE III:
Stage of Anesthesia
Partial pressure of the brain (Pbr) further increases giving rise to progressive depression of the ascending (sensory) pathways of the reticular activating system, producing a suppression of spinal reflex activity or skeletal muscle relaxation. Movement into this stage is characterized by the return of regular respiration, excitement subsides, pupils become centered, cough, gag and eyelid reflex are absent.
Stage IV:
Stage of Depression
Partial pressure of brain (Pbr) continues to increase and there is depression of the vital medullary centers which results in a profound respiratory and cardiac depression.

Guidelines that are appropriate today include:
Reflexes present eyelid, cough, swallowing, gag, respirations irregular surgical anesthesia not present.
With loss of reflexes and rhythmic respirations, there is indication that surgical anesthesia is beginning.
Signs of "LIGHT" anesthesia include:
Increase respirations
Increase BP, HR
Increase muscle tone
Swallowing, coughing returns
Tear formation (abolished at surgical stage)
Signs of "DEEP" anesthesia include:
Hypotension
Diaphragmatic breathing
Pupils become dilated, lack luster
Bradycardia

Common sense, experience along with constant observation of patients response to agents and stimuli will allow accurate estimation of anesthetic depth.

EMERGENCE
On emergence there is the potential for "DIFFUSION HYPOXIA" to occur. This occurs when N2O is abruptly discontinued. N2O still in the body rapidly diffuses across capillary/aveoli membrane diluting the O2 concentration to a point where it can cause the PaO2 to drop and hypoxia develops. This is easily avoided by administering 100% O2 for 5-10 minutes after the N2O has been discontinued.

Other factors that influence the rate of emergence:
Duration of procedure
Temperature of the patient
Physical condition of the patient
Obesity may initially wake up, but then as agent is mobilized from fat stores they may reanesthetize thenselves.

INHALATION ANESTHETICS POTENCY OF AGENT
AGENT 1 MAC BLOOD/GAS PC
Methoxyflurane 0.16 12.0
Halothane 0.75 2.4
Enflurane 1.68 1.9
Isoflurane 1.15 1.4
Sevoflurane 2.0 0.65
Nitrous Oxide 105 0.47
Desflurane 6.0 0.42




Factors affecting MAC:
VARIABLE EFFECT ON MAC COMMENTS
Temperature
   Hypothermia decrease   
   Hyperthermia decrease if > 42oC
Age
   Young increase
   Elderly decrease
Alcohol
   Acute intoxication decrease
   Chronic abuse increase
Anemia
   Hematocrit < 10% decrease
PaO2
   < 40 mmHg decrease
PaO2
   > 95 mm Hg decrease Caused by < pH in CSF
Thyroid
   Hyperthyroid No change
   Hypothyroid No change
Blood Pressure
   MAP < 40 mm Hg decrease
Electrolytes
   Hypercalcemia decrease
   Hypernatremia increase Caused by altered CSF
   Hyponatremia decrease Caused by altered CSF
Pregnancy decrease
Drugs
   Local anesthetics decrease Except cocaine
   Opiods decrease
   Ketamine decrease
   Barbiturates decrease
   Benzodiazepines decrease
   Verapamil decrease
   Lithium decrease
   Sympatholytics
    Methydopa decrease
    Reserpine decrease
    Clonidine decrease
   Sympathomimetics
    Amphetamine
    Chronic decrease
    Acute increase
    Cocaine increase
    Ephedrine increase

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Last Updated 04/10/00 12:26:56 PM
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