Inhalational Anesthetics

Mostly anesthetics are given intravenously, but different delivery systems are used for inhalational anesthetics:

Mode of Delivery

a. Open Drop method – Ether

Still used for animal experiments and in far flung areas for small procedures. Few drops of ether are dropped on wire gauze and patient is asked to inhale.

Advantage

Ether is a cheap anesthetic and is easily available

No special procedure is required

Disadvantage

Ether vaporizes in air, not only the patient but also the person around is affected.

b. Anesthetic machines assisted methods

Administered through anesthetic machines. Three systems are used:

i. Open System – accurate

In which administered anesthetic agent is taken once along with oxygen. Oxygen is exhaled and agent is not reused.

Advantage

Easily monitored.

Can determine the quantity of anesthetic agent delivered.

ii. Closed System – soda lime

After inhalation, when patient exhales out, the agent and carbon dioxide is passed through specialized machine, having soda lime, carbon dioxide is absorbed and anesthetic agent is reused by patient.

Used amount of anesthetic is supplemented.

Advantage

No wastage of anesthetic agent

Disadvantage

Difficult to determine the exact amount the patient has used up.

Trichloroethylene

This method cannot be used for trichloroethylene, as it makes toxic metabolites in soda lime like dichloroacetylene and phosgene

iii. Semi closed System

Inhaled anesthetic is partly used by partially closed valve, part is discarded.

Most commonly used as newer agents are expensive.

Depth of anesthesia

When general anesthetic is administered by increasing the levels and depth of anesthesia and the patient goes through different stages, depth depends upon

Potency
Partial pressure in brain

Dose-response characteristics

For general anesthetics it is difficult to quantify the dose response curve esp. graded response curve. Because if giving minimal quantity of anesthetic, it is not sufficient, and the person feels pain, responding to surgical procedure.

If higher doses are given (extreme of curve), there are chances of cardiovascular or respiratory collapse.

MAC – definition

So by taking into account the quintal dose curve, dose of general anesthetics can be determined by MAC (minimum alveolar concentration) defined as

“Concentration of anesthetic agent required to produce immobility in 50% of the patients in response to noxious stimuli e.g. surgical incision”

Different anesthetic agents have different MAC values.

As MAC value is inversely proportional to potency, more is the MAC value, less is the potency and vice versa.

– Example*

NO has MAC value of more than 100

Halothane has 0.75 MAC value, thus is very potent

– Dose

It is used to determine dose, usually patients have 0.5-1.5 MAC as dose to produce general anesthesia.

– Factors

Different factors affect MAC values

Age
Sex
Height

Do not affect MAC values

Hypothermia decreases the MAC value
Elderly patients have decreased MAC values
Pregnancy and chronic use of alcohol increase MAC values
Centrally acting drugs increase MAC values.

5. Partial Pressure (PP) in brain

Partial pressure in brain depends on:

Pharmacokinetics of that agent; how administered, distributed and reuptaken by body parts esp. brain and spinal cord.

Properties Of Inhaled Anaesthetics

Anesthetic	Blood: Gas Partition Coefficient	Minimal Alveolar Cone (MAC) %	Metabolism	Comments
Nitrous Oxide	0.47	>100	None	Incomplete anesthetic rapid onset & recovery
Desflurane	0.42	6-7	<0.05%	Low volatility; poor induction agent; rapid recover
Sevoflurane	0.69	2.0	2-5%	Rapid onset & recovery; unstable in soda-lime
Isoflurane	1.140	1.40	<2%	Medium rate of onset and recovery
Enflurane	1.80	0.75	>8%	Medium rate of onset & recovery
Halothane	2.30	0.75	>40%	Medium rate of onset and recovery
Methoxyflurane	12	0.16	>70 %	Slow onset & recovery

a. Induction & Recovery**

Due to Rate of change of Partial Pressure

During induction, gas in inspired air taken by arterial blood, then passed to brain and afterwards reach tissues, then passed through venous blood and exhaled out. As partial pressure builds up, it is responsible for induction. Uptake and distribution involves building up of pressure.

On the other hand, after discontinuation of anesthetic and elimination, recovery phase starts. When exhaled out, recovery occurs.

Thus change is partial pressure is required for induction and recovery.

Factors

Different factors affect pharmacokinetics, so building of partial pressure. These are divided into two main groups:

1. Related to drug

a. Concentration in inspired air

More the concentration more is the transfer from lungs into blood. Increased concentration leads to quicker induction.

b. Fick’s law

c. Solubility

Considered in two groups:

I. In blood – Blood: gas partition coefficient**

– Inverse relation with induction

Solubility in blood when transferred from inspired air to pulmonary circulation. This solubility is determined by blood gas partition coefficient. It is relative affinity of gas molecules for blood as compared to inspired air.

As more agent is soluble in blood, more will be the partition coefficient and vice versa.

Effect on induction is that when gas enters the compartment, it maintains pressure in it. If insoluble, rise in partial pressure is immediate and fewer molecules are required to raise the pressure. Thus induction is rapid.

If general anesthetic is soluble, blood goes on dissolving the anesthetic, and it takes time to raise the partial pressure. Thus partition coefficient is higher and rate of induction is less.

Rate of induction is inversely proportional to solubility.

NO has less blood gas partition coefficient, thus has lesser solubility and fewer molecules are required.

Halothane has partition coefficient of 2.3, thus is moderately soluble and induction is slower than NO.

II. In tissues – Tissue: blood partition coefficient*

– Arteriovenous concentration gradient

When blood has to enter tissues, mainly nervous, it is determined by tissue blood partition coefficient. If drug is more soluble in tissues, coefficient will be higher, and is readily taken up, and less is passed to venous circulation.

More solubility, more arteriovenous concentration gradient is produced. 75% of blood goes to highly perfused organs. If soluble drug is taken up esp. by brain rest is passed into venous circulation. More soluble drugs go to fatty tissues and muscles. On long exposure the drugs accumulate, responsible for slow recovery from these agents.

2. Related to body

a. Pulmonary ventilation

Affects transfer of drug molecules from alveoli into circulation.

Rate & depth

If rate and depth is increased, rate of transfer is also increased. Induction is rapid by increased pulmonary ventilation.

Hyperventilation / Respiratory depression

Rapid induction occurs in hyperventilation.

Slowed down in respiratory depression esp. by opioid analgesics.

b. Pulmonary blood flow / perfusion

As general anesthetic from inspired air enters blood and CNS, if pulmonary blood flow is higher, gas will be taken up at a rapid rate, washed away from site of administration rapidly. So more drug is required for certain level of partial pressure.

There is inverse relation between blood flow and induction.

Shock

When more blood flow to lungs occurs, like in shock, induction is rapid as partial pressure builds up rapidly.

c. Alveolar exchange

Pulmonary ventilation / perfusion

Routinely for optimal uptake, alveoli must be patent. Perfusion and ventilation should be matched for optimal uptake.

Lung disease

In emphysema and bronchitis, there may be mismatch between pulmonary ventilation and perfusion. Some areas and highly ventilated but not perfused and vice versa, which affects uptake of general anesthetic.

d. Cerebral blood flow

Higher the flow, more rapid will be the induction.

CO₂

If hyperkapnia:

Vasodilatation in cerebral blood vessels occurs

Hyperventilation is beneficial for induction

Elimination

During elimination or recovery, factors affect just like induction, and are almost the same but in reverse direction with some differences.

Routes

a. Lung

Elimination occurs mostly through lungs. Most are exhaled unchanged.

b. Hepatic Metabolism**

Part is metabolized in body e.g. hepatic metabolism.

This is different for different anesthetics e.g. none for NO, 40% for halothane, 60-80% is exhaled unchanged, while 20-40% is metabolized in liver.

Differences between induction and recovery

a. Concentration in lungs

During elimination, concentration of drug in lungs becomes zero, when anesthetic agent is discontinued. During induction, can be enhanced by increasing concentration. Rate of recovery cannot be changed by change in concentration.

b. Variable tissue concentration

During induction, all tissues have same concentration of drug i.e. zero. But during recovery, all tissues have variable concentration, due to solubility.

c. Duration of exposure

If patient undergoes large surgical procedure, anesthetic is applied for longer time; there are chances of accumulation of drug in body esp. in less perfused areas, fatty tissue, skin, making the recovery slower.

If short duration anesthetic taken, no accumulation takes place and recovery is immediate.

d. Second gas effect

Seen with nitrous oxide, mostly given at concentration of 70% with 30% oxygen, producing large concentration gradient, which makes the transfer rapid form air into circulation.

Some drugs, although very potent, are given at a lesser concentration, like halothane (0.5-3-4%) thus move at a slower rate, as concentration gradient is less.

Halothane is combined with nitrous oxide. Nitrous oxide concentration gradient and drug molecules of halothane produce the second gas effect.

e. Diffusion hypoxia

Phenomenon is seen with NO as given at a concentration of 70%, when administration of drug is stopped, and normal atmospheric air containing 21% oxygen is given, NO in blood is 70% which, during recovery, moves into lungs again, diluting 21% oxygen, producing hypoxia.

To avoid diffusional hypoxia, for some time 100% oxygen is given. If NO comes out, person still gets enough oxygen.