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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
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INHALED ANESTHETICS • DR. ABDUL KARIM B OTHMAN • CLINICAL SPECIALIST • ANESTHESIOLOGIST • HSNZ. 2013
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
SOLUBILITYIN 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.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 HYPOXIAOCCURS 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 ANESTHETICSMINIMUM 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
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 AGENTS • PHYSICAL PROPERTIES • BIOLOGICAL PROPERTIES