INHALED INHALED ANESTHETICSANESTHETICS

DR. ABDUL KARIM B DR. ABDUL KARIM B OTHMANOTHMAN

CLINICAL SPECIALISTCLINICAL SPECIALISTANESTHESIOLOGISTANESTHESIOLOGIST

HSNZ. 2013HSNZ. 2013

HISTORY OF ANESTHETIC AGENTSHISTORY OF ANESTHETIC AGENTS

Physical and chemical properties of inhaled anesthetic agents

Pharmacokinetics of Inhaled Anesthetics

❖ absorption (uptake)

❖ distribution

❖ metabolism

❖ elimination

❖ How does aging influenced the pharmacokinetics of volatile anesthetics?

Principle objective of inhalation Principle objective of inhalation anesthesia is anesthesia is to achieve a constant to achieve a constant and optimal brain partial pressure and optimal brain partial pressure

of the inhaled anesthetic.of the inhaled anesthetic.

... THE DEPTH OF ANAESTHSIA VARIES ... THE DEPTH OF ANAESTHSIA VARIES DIRECTLY WITH THE TENSION OF THE AGENT DIRECTLY WITH THE TENSION OF THE AGENT

IN THE BRAIN, AND THEREFORE,IN THE BRAIN, AND THEREFORE,

... THE RATES OF INDUCTION AND EMERGENCE ... THE RATES OF INDUCTION AND EMERGENCE DEPEND UPON THE RATE OF CHANGE OF GAS DEPEND UPON THE RATE OF CHANGE OF GAS

TENSION IN THE BLOOD AND TISSUES .....TENSION IN THE BLOOD AND TISSUES .....THUS, FACTORS WHICH DETERMINE THIS MAY THUS, FACTORS WHICH DETERMINE THIS MAY

BE CONSIDERED AS ACTING IN SEPARATE BE CONSIDERED AS ACTING IN SEPARATE STAGESSTAGES

DETERMINED BY ..

❖ TRANSFER FROM INSPIRED AIR TO ALVEOLI

❖ TRANSFER FROM ALVEOLI TO ARTERIAL BLOOD

❖ TRANSFER FROM ARTERIAL BLOOD TO TISSUES

TRANSFER FROM INSPIRED AIR TO ALVEOLI

❖ THE INSPIRED GAS CONCENTRATION

❖ ALVEOLAR VENTILATION

❖ CHARACTERISTIC OF THE ANAESTHETIC CIRCUIT

TRANSFER FROM ALVEOLI TO ARTERIAL BLOOD

BLOOD : GAS PARTITION COEFFICIENT

CARDIAC OUTPUT

ALVEOLI TO VENOUS PRESSURE DIFFERENCE

TRANSFER FROM ARTERIAL BLOOD TO TISSUES

TISSUE : BLOOD PARTITION COEFFICIENT

TISSUE BLOOD FLOW

ARTERIAL TO TISSUE PRESSURE DIFFERENCE

PA is used as an index of

❖ depth of anesthesia

❖ recovery from anesthesia, and

❖ anesthetic equal potency (MAC

❖ equilibration between the two phases means same partial pressure NOT same concentrations

Determinants of Alveolar Partial PressureDeterminants of Alveolar Partial Pressure(P(PA A <> Pa <>P<> Pa <>Pbr br ))

Determined by input (delivery) - uptake (loss) from alveoli into arterial Determined by input (delivery) - uptake (loss) from alveoli into arterial bloodblood

Input depends on

❖ inhaled partial pressure (PI)

❖ alveolar ventilation

❖ characteristics of the anesthetic breathing (delivery) system

❖ Patient’s FRC influenced the PA that is achieved

Uptake depends on

❖ solubility of the anesthetic in the body tissues

❖ cardiac output

❖ alveolar to venous partial pressure differences (A-VD)

Inhaled Partial Pressure

❖ a high PI is required during initial administration

❖ to offsets the impact of uptake

❖ accelerating induction (PA <> Pbr)

❖ as uptake decreases, PI should be decreased

❖ to match the decreased in uptake and therefore maintain a constant and optimal Pbr

Concentration effect( the impact of PI on the rate of rise of the PA )

❖ states that; the higher the PI, the more rapidly the PA

approaches the PI

❖ Results from

❖ a concentrating effect

❖ an augmentation of tracheal inflow

Second-Gas effect

• ability of high-volume uptake of one gas (first gas) to accelerate the rate of increase of the PA of a concurrently administered “companion “ gas (second-gas)

Second-Gas effect

• increased uptake of second gas reflects

• increased tracheal inflow of first and second gases

• concentrating effect of second gas

SOLUBILITY IN BLOOD AND TISSUES IS DENOTED BY THE PARTITION COEFFICIENT

PARTITION COEFFICIENT IS A DISTRIBUTION RATIO DESCRIBING HOW THE INHALED ANESTHETIC DISTRIBUTES ITSELF BETWEEN TWO PHASES AT EQUILIBRIUM (PARTIAL PRESSURES EQUAL IN BOTH PHASES)

TEMPERATURE DEPENDENT

SOLUBILITY

Q :

BLOOD : GAS PARTITION COEFFICIENT OF 0.5 ?

BRAIN : BLOOD PARTITION COEFFICIENT OF 2 ?

REFLECTING THE RELATIVE CAPACITY OF EACH PHASE TO

ACCEPT ANESTHETIC

REFLECTING THE RELATIVE CAPACITY OF EACH PHASE TO

ACCEPT ANESTHETIC

BLOOD : GAS PARTITION COEFFICIENT

RATE OF INCREASE OF THE PA TOWARD THE PI (MAINTAINED CONSTANT BY MECHANICAL VENTILATION OF THE LUNGS) IS INVERSELY RELATED TO THE SOLUBILITY OF THE ANESTHETIC IN BLOOD

BLOOD : GASES PARTITION COEFFICiENT : ISSUES

HIGH BLOOD : GASS PARTITION

OVERPRESSURE : BY INCREASING THE PI ABOVE THAT REQUIRED FOR MAINTENANCE OF ANESTHESIA

LOW BLOOD : GAS PARTITION

IS ALTERED BY INDIVIDUAL VARIATIONS IN

WATER LIPID AND PROTEIN CONTENT

HEMATOCRIT OF WHOLE BLOOD

PARTITION COEFFICIENT : ISSUES

TISSUE : BLOOD PARTITION COEFFICIENT

OIL : GAS PARTITION COEFFICIENT

NITROUS OXIDE TRANSFER TO CLOSED GAS SPACES

BLOOD : GAS PARTITION COEFFICIENT OF

NITROUS OXIDE : 0.46

NITROGEN : 0.014

NITROUS OXIDE CAN LEAVE THE BLOOD TO ENTER AN AIR-FILLED CAVITY 34 TIMES MORE RAPIDLY THAN NITROGEN CAN LEAVE THE CAVITY TO ENTER BLOOD

INCREASES VOLUME OR PRESSURE OF AN AIR-FILLED CAVITY

NITROUS OXIDE TRANSFER TO CLOSED GAS SPACES

AIR-FILLED SURROUNDED BY A COMPLIANT WALL :

GAS SPACE TO EXPAND

AIR-FILLED CAVITY SURROUNDED BY A NONCOMPLIANT WALL :

INCREASES IN INTRACAVITARY PRESSURE

CARDIAC OUTPUT AND INHALED ANESTHETIC

CARDIAC OUTPUT (PULMONARY BLOOD FLOW) INFLUENCES UPTAKE AND THEREFORE PA BY CARRYING AWAY EITHER MORE OR LESS ANESTHETIC FROM THE ALVEOLI

ISSUES

HIGH CARDIAC OUTPUT

LOW CARDIAC OUTPUT

CONCEPTUALLY, A CHANGE IN C.O IS ANALOGOUS TO THE EFFECT OF A CHANGE IN

SOLUBILITY

CONCEPTUALLY, A CHANGE IN C.O IS ANALOGOUS TO THE EFFECT OF A CHANGE IN

SOLUBILITY

CARDIAC OUTPUT AND INHALED ANESTHETIC

CHANGES IN C.O MOST INFLUENCE THE RATE OF INCREASE OF PA OF A SOLUBLE ANESTHETIC

LOW CARDIAC OUTPUT VERSUS HIGH CARDIAC OUTPUT

SOLUBLE VERSUS POORLY SOLUBLE AGENTS

IMPACT OF SHUNT AND INHALED ANESTHESTIC

PA IS IDENTICAL TO Pa ( IN THE ABSENCE OF INTRACARDIAC OR INTRAPULMONARY R - TO - L SHUNT )

R - TO - L SHUNT

DILUTING EFFECT OF SHUNTED BLOOD

DECREASE THE Pa

SLOWING THE INDUCTION

PA UNDERESTIMATE Pa

L - TO - R SHUNT

OFFSET THE DILUTIONAL EFFECT OF R - TO - L SHUNT

DIFFUSION HYPOXIA OCCURS WHEN INHALATION OF NITROUS OXIDE IS DISCONTINUED ABRUPTLY

DIFFUSION HYPOXIA OCCURS WHEN INHALATION OF NITROUS OXIDE IS DISCONTINUED ABRUPTLY

DIFFUSION HYPOXIA

REVERSAL OF PARTIAL PRESSURE GRADIENTS (NITROUS OXIDE LEAVES THE BLOOD TO ENTER ALVEOLI)

DILUTE THE PAO2 AND DECREASE PaO2

DILUTE THE PACO2 (DECREASE STIMULUS TO BREATHE)

GREATEST DURING THE 1ST TO 5 MINUTES AFTER ITS DISCONTINUATION

PHARMACODYNAMICS OF INHALED PHARMACODYNAMICS OF INHALED ANESTHETICSANESTHETICS

MINIMUM ALVEOLAR CONCENTRATIONMINIMUM ALVEOLAR CONCENTRATION(MAC)(MAC)

MAC

❖ CONCENTRATION AT 1 ATM THAT PREVENTS SKELETAL MUSCLE MOVEMENT IN RESPONSE TO SUPRA MAXIMAL PAINFUL STIMULUS (SURGICAL SKIN INCISION) IN 50 % OF PATIENTS (MARKEL AND EGER, 1963)

MAC

❖ MAC IS AN ANESTHETIC 50 % EFFECTIVE DOSE (ED50)

❖ IMMOBILITY AS MEASURED BY MAC IS MEDIATED

❖ PRINCIPALLY BY EFFECTS ON SPINAL CORD

❖ MINOR COMPONENT FROM CEREBRAL EFFECTS

MAC

❖ ESTABLISHES A COMMON MEASURE OF POTENCY

❖ PROVIDE UNIFORMITY IN DOSAGES

❖ ESTABLISH RELATIVE AMOUNTS OF INHALED ANESTHETICS TO REACH SPECIFIC END-POINTS (MACawake , MACBAR)

❖ VARYING ONLY 10 % TO 15 % AMONG INDIVIDUALS

THE RATIONALE FOR THIS MEASURE OF ANAESTHETIC POTENCY IS ,

❖ ALVEOLAR CONCENTRATION CAN BE EASILY MEASURED

❖ NEAR EQUILIBRIUM , ALVEOLAR AND BRAIN TENSIONS ARE VIRTUALLY EQUAL

❖ THE HIGH CEREBRAL BLOOD FLOW PRODUCES RAPID EQUILIBRATION

FACTORS WHICH SUPPORT THE USE OF THIS MEASURE ARE ,

❖ MAC IS INVARIANT WITH A VARIETY OF NOXIOUS STIMULI

❖ INDIVIDUAL VARIABILITY IS SMALL

❖ SEX, HEIGHT, WEIGHT & ANAESTHETIC DURATION DO NOT ALTER MAC

❖ DOSES OF ANAESTHETICS IN MAC’S ARE ADDITIVE

MAC

• EXAMPLES OF MAC

• MAC awake : 0.3 MAC

• MAC BAR : 1.5 X MAC

• MAC intubation : 2 X MAC

FACTORS WHICH AFFECT MAC

INCREASE MAC

• HYPERTHERMIA

• HYPERNATRAEMIA

• DRUG INDUCED ELEVATION OF CNS CATECHOLAMINES STORES

• CHRONIC ALCOHOL ABUSE ? CHRONIC OPIOID ABUSE

• INCREASE IN AMBIENT PRESSURE

DECREASE MAC

• HYPOTHERMIA HALOTHANE MAC27 IS ABOUT 50% MAC37C

• HYPONATRAEMIA

• INCREASE AGE MACHAL < 3 MTHS IS ABOUT 1.1% MACHAL > 60 YRS IS ABOUT 0.64%

• HYPOXAEMIA PAO2 < 40 mmHg

• HYPOTENSION

• ANAEMIA

DECREASE MAC

• PREGNANCY ? PROGESTERONE

• CNS DEPRESSANT DRUGS BENZODIAZEPINES, OPIOIDS

• OTHER DRUGS LITHIUM, LIGNOCAINE, MAGNESIUM

• ACUTE ALCOHOL ABUSE

NO CHANGE IN MAC

• SEX

• WEIGHT , BSA

• TYPE OF SUPRAMAXIMAL STIMULUS

• DURATION OF ANAESTHESIA

• HYPO / HYPERKALAEMIA

• HYPO / HYPERTHYROIDISM

NO CHANGE IN MAC

• PaCO2 - 15 - 95 mmHg

• PO2 - 40 mmHg

• MAP > 40 mmHg

THE IDEAL ANESTHETIC AGENT

THE IDEAL ANESTHETIC AGENTS

PHYSICAL PROPERTIES

BIOLOGICAL PROPERTIES

PHYSICAL PROPERTIES

NONFLAMMABLE, NON-EXPLOSIVE AT ROOM TEMPERATURES

STABLE IN LIGHT

LIQUID AND VAPORISABLE AT ROOM TEMPERATURE (I.E LOW LATENT HEAT OF VAPORISATION)

STABLE AT ROOM TEMPERATURE, WITH A LONG SHELF LIFE

STABLE WITH SODA LIME, AS WELL AS PLASTICS AND METALS

ENVIRONMENTALLY FRIENDLY, NO OZONE DEPLETION

CHEAP AND EASY TO MANUFACTURE

BIOLOGICAL PROPERTIES

PLEASANT TO INHALE, NON-IRRITANT,INDUCE BRONCHODILATATION

LOW BLOOD : GAS SOLUBILITY, I.E FAST ONSET

HIGH OIL : WATER SOLUBILITY I.E HIGH POTENCY

MINIMAL EFFECTS ON OTHER SYSTEMS, I.E CVS, RESP, HEPATIC, RENAL OR ENDOCRINE

NO BIOTRANSFORMATION, SHOULD BE EXCRETED IDEALLY VIA THE LUNGS, UNCHANGED

NON-TOXIC TO OPERATING THEATRE PERSONNEL