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

2. HISTORY OF ANESTHETIC AGENTS

4. Physical and chemical properties of inhaled anesthetic agents

5. Pharmacokinetics of Inhaled Anesthetics
absorption (uptake)
distribution
metabolism
elimination
How does aging influenced the pharmacokinetics of volatile anesthetics?

6. Principle objective of inhalation anesthesia is to achieve a constant and optimal brain partial pressure of the inhaled anesthetic.

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

8. ... 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

9. DETERMINED BY .. TRANSFER FROM INSPIRED AIR TO ALVEOLI
TRANSFER FROM ALVEOLI TO ARTERIAL BLOOD
TRANSFER FROM ARTERIAL BLOOD TO TISSUES

10. TRANSFER FROM INSPIRED AIR TO ALVEOLI
THE INSPIRED GAS CONCENTRATION
ALVEOLAR VENTILATION
CHARACTERISTIC OF THE ANAESTHETIC CIRCUIT

11. TRANSFER FROM ALVEOLI TO ARTERIAL BLOOD
BLOOD : GAS PARTITION COEFFICIENT
CARDIAC OUTPUT
ALVEOLI TO VENOUS PRESSURE DIFFERENCE

12. TRANSFER FROM ARTERIAL BLOOD TO TISSUES
TISSUE : BLOOD PARTITION COEFFICIENT
TISSUE BLOOD FLOW
ARTERIAL TO TISSUE PRESSURE DIFFERENCE

13. 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

14. Determinants of Alveolar Partial Pressure (PA <> Pa <>Pbr )
Determined by input (delivery) - uptake (loss) from alveoli into arterial blood

16. 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

17. Uptake depends on solubility of the anesthetic in the body tissues
cardiac output
alveolar to venous partial pressure differences (A-VD)

18. 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

19. 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

20. 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)

21. Second-Gas effect increased uptake of second gas reflects
increased tracheal inflow of first and second gases
concentrating effect of second gas

22. 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

23. SOLUBILITY Q : BLOOD : GAS PARTITION COEFFICIENT OF 0.5 ?
BRAIN : BLOOD PARTITION COEFFICIENT OF 2 ?

24. REFLECTING THE RELATIVE CAPACITY OF EACH PHASE TO ACCEPT ANESTHETIC

25. 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

26. 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

27. PARTITION COEFFICIENT : ISSUES
TISSUE : BLOOD PARTITION COEFFICIENT
OIL : GAS PARTITION COEFFICIENT

28. 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

29. 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

30. 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

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

32. 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

33. 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

34. DIFFUSION HYPOXIA OCCURS WHEN INHALATION OF NITROUS OXIDE IS DISCONTINUED ABRUPTLY

35. 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

36. PHARMACODYNAMICS OF INHALED ANESTHETICS MINIMUM ALVEOLAR CONCENTRATION (MAC)

37. 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)

38. 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

39. 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

40. 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

41. 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

42. MAC EXAMPLES OF MAC MAC awake : 0.3 MAC MAC BAR : 1.5 X MAC
MAC intubation : 2 X MAC

43. FACTORS WHICH AFFECT MAC

44. INCREASE MAC HYPERTHERMIA HYPERNATRAEMIA
DRUG INDUCED ELEVATION OF CNS CATECHOLAMINES STORES
CHRONIC ALCOHOL ABUSE ? CHRONIC OPIOID ABUSE
INCREASE IN AMBIENT PRESSURE

45. 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

46. DECREASE MAC PREGNANCY ? PROGESTERONE
CNS DEPRESSANT DRUGS BENZODIAZEPINES, OPIOIDS
OTHER DRUGS LITHIUM, LIGNOCAINE, MAGNESIUM
ACUTE ALCOHOL ABUSE

47. NO CHANGE IN MAC SEX WEIGHT , BSA TYPE OF SUPRAMAXIMAL STIMULUS
DURATION OF ANAESTHESIA
HYPO / HYPERKALAEMIA
HYPO / HYPERTHYROIDISM

48. NO CHANGE IN MAC
PaCO mmHg
PO mmHg
MAP > 40 mmHg

49. THE IDEAL ANESTHETIC AGENT

50. THE IDEAL ANESTHETIC AGENTS
PHYSICAL PROPERTIES
BIOLOGICAL PROPERTIES

51. 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

52. 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