INHALED ANESTHETICS DR. ABDUL KARIM B OTHMAN CLINICAL SPECIALIST ANESTHESIOLOGIST HSNZ. 2013

HISTORY 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 anesthesia is to achieve a constant and optimal brain partial pressure of the inhaled anesthetic.

... THE DEPTH OF ANAESTHSIA VARIES DIRECTLY WITH THE TENSION OF THE AGENT IN THE BRAIN, AND THEREFORE,

... THE RATES OF INDUCTION AND EMERGENCE DEPEND UPON THE RATE OF CHANGE OF GAS TENSION IN THE BLOOD AND TISSUES ..... THUS, FACTORS WHICH DETERMINE THIS MAY BE CONSIDERED AS ACTING IN SEPARATE STAGES

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 Pressure (PA <> Pa <>Pbr ) Determined by input (delivery) - uptake (loss) from alveoli into arterial blood

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

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 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 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 ANESTHETICS MINIMUM ALVEOLAR CONCENTRATION (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