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uptake and distribution of inhalational agents.pptx
- 1. INHALATIONAL AGENTS UPTAKE AND DISTRIBUTION PRESENTER- DR ANANTHAKRISHNAN MODERATORS- DR DEEPA FRANKLIN
- 3. A series of partial pressures serves to propel the inhaled anesthetic across various barriers (alveoli, capillary, membranes) The principal objective is to attain a constant and optimal brain partial pressure of the agent The brain and other tissue equilibrate with partial pressure of inhaled agent delivered to them by arterial blood (PA) Arterial blood equilibrates* with the alveolar partial pressure (PA) Thus alveolar partial pressure(PA) of inhalational anesthetic agent mirrors the brain partial pressure (PB), at steady state.
- 5. Biophysical properties of inhaled anesthetics 1. PARTIAL PRESSURE Partial pressure is the portion of total pressure contributed by one component of a gas mixture, where each component contributes pressure in direct proportion to its molar fraction. The partial pressure of an anesthetic is usually reported as the percentage (or fraction) of the delivered gas mixture, where atmospheric pressure is near 1 atm (760 mm Hg).
- 6. 2. VAPOUR PRESSURE AND BOILING POINT The maximal partial pressure of volatile anesthetic is its vapor pressure;Partial pressure of volatile anesthetic within the drug reservoir of vapourizer Vapor Pressure dependent on temperature and physical characteristics of liquid, independent of atmospheric pressure ↑ Temperature→ ↑ Vapor Pressure Vapor pressure is a measure of the agent’s ability to evaporate (volatility) and is unique to eacg agent The greater the vapor pressure, the greater is the concentration of inhalant deliverable to the patient (and environment). Boiling Point Temperature at which vapor pressure equals atmospheric pressure
- 7. 3. HYDROPHOBICITY Hydrophobicity is a molecular property of certain chemicals, including most general anesthetics that do not readily form hydrogen bonds and therefore display low water solubility. Hydrophobic compounds are also usually lipophilic, demonstrating high solubility in low polarity solvents such as oils
- 8. Halothane
- 9. Volatile anesthetics are defined by vapor pressure less than 1 atm at 20 degree Celsius and a boiling point above 20 degree Celsius.* Gaseous anesthetics are defined by vapor pressure more than 1 atm at 20 degree Celsius and a boiling point below 20 degree Celsius*
- 10. 4. PARTITION COEFFICIENT Solubility of anesthetics in blood and tissue is determined by the partition coefficient It is a distribution ratio describing how the inhaled anesthetic distributes itself between two phases at equilibrium (partial pressures equal in both phases) For example, blood gas partition coefficient of 0.5 means that concentration of inhaled anesthetic in blood is half that is present in alveoli, when partial pressures of anesthetic in these two phases are identical Predicts the speed of induction, recovery, and change in anesthetic depth for an inhalant. Ideal inhaled anesthetics should have low blood/gas partition coefficient
- 11. Based on B:G partition coefficient, inhaled anesthetics are categorized traditionally as 1. Soluble - Methoxyflurane 2. Intermediary Soluble - Halothane, Isoflurane, Enflurane 3. Poorly Soluble - Nitrous Oxide, Desflurane, Sevoflurtane, Xenon The rate of rise of PA towards PI is inversely related to the solubility, that is When blood gas partition coefficient is more a large amount of anesthetic should be dissolved in the blood before PA equilibrates with Pa rate at which PA and Pa increase will be slower induction will be slower When blood gas partition coefficient is low only small amount of anesthetic should be dissolved in the blood before PA equilibrates with Pa rate at which PA and Pa increase will be faster induction will be rapid*
- 12. Over-Pressure Effect The impact of high blood solubility on the rate rise of Pa can be countered by increasing the inhaled partial pressure of inhalational agent. May be used to speed the induction of anesthesia Sustained delivery of high Pi can result in anesthetic overdose Blood:Gas Partition Coefficient is altered by individual variations in water, lipid and protein content
- 13. BLOOD GAS PARTITION COEFFICIENT OF DIFFERENT AGENTS Nitrous oxide-0.47 Halothane-2.5 Enflurane-1.9 Isoflurane-1.4 Sevoflurane-0.65 Desflurane-0.45 8
- 14. FACTORS AFFECTING INSPIRATORY CONCENTRATION Gas mixture leaving the vaporizer carries the concentration set on vaporizer but patient lung may receive a different concentration. It is affected by Breathing circuit volumes Fresh gas flow rate (FGF) Absorption of the inhaled anaesthetics in the components of the breathing system
- 15. FACTORS AFFECTING ALVEOLAR CONCENTRATION UPTAKE 1. Solubility 2. Cardiac output 3. Partial pressure difference between alveoli and venous blood VENTILATION CONCENTRATION
- 16. UPTAKE 1. SOLUBILITY If a drug is highly soluble in blood it will easily diffuse out of the alveolus into the pulmonary capillaries and concentration of the drug in alveolus will fall. Thus it will take longer time for alveolar concentration (FA) to become equal to inspired concentration. So highly soluble drugs with high blood/ gas coefficient takes longer time to achieve a given alveolar concentration. Delay in rise of alveolar concentration means delay in achieving a definite brain tissue concentration and finally delay in induction of anaesthesia. Thus, highly soluble drugs will take longer time for induction Influencing factors- Anemia(less solubility, hence faster induction) Lipid content of the blood(high solubility, slower onset of induction
- 17. ii. CARDIAC OUTPUT Cardiac output (pulmonary blood flow) influences uptake and therefore rate of rise PA by carrying away either more or less anesthetic from alveoli Analogous to the effect of solubility Increase in cardiac output More rapid uptake of anesthetic from the alveoli Rate of rise of PA will be slowed Induction slower Decrease in cardiac output Slower uptake of anesthetic from the alveoli Rate of rise of PA will be faster Induction faster*
- 18. Volatile anesthetics that depress cardiac output can exert a positive feedback response in contrast to negative feedback response on spontaneous breathing exerted by these drugs, that is Decrease in cardiac output due to excessive dose of volatile anesthetic result in an increase in PA, which further increase depth of anesthesia and thus cardiac depression
- 19. 3. PARTIAL PRESSURE DIFFERENCE BETWEEN ALVEOLAR GAS AND VENOUS BLOOD Depends on 3 factors Tissue solubility Tissue blood flow Partial pressure difference between arterial blood and tissues.
- 20. This represents tissue uptake of the inhaled agent - Blood cannot approach equilibrium with alveolar air until the distribution of anesthetic from the blood to the tissues is nearly complete With equilibration, the alveolar/mixed venous tension difference progressively falls as tissue tensions rises Tissue uptake affects uptake at the lung by controlling the rate of increase of mixed venous partial pressure of anesthetic Since diffusion is directly proportional to the tension difference, the rate of diffusion into the blood progressively slows
- 21. TISSUE:BLOOD PARTITION COEFFICIENT Determine uptake of anesthetic into tissues and time necessary for equilibration of tissues with Pa As tissue blood partition coefficient increases, capacity of tissue to hold anesthetic will be high, resulting in greater time for equilibration of partial pressure of anesthetics in tissue with blood (slower uptake).
- 22. Tissues are divided into 4 groups depending on the blood flow. Vessel rich group (brain, heart, kidney, endocrine organ) Muscles Fat Vessel poor group (bone, ligament, teeth, cartilage).
- 23. As blood is equilibrating with alveolar gas ,it also begins to equilibrate with the vessel rich groups, muscle and more gradually the fat compartments based on perfusion Muscle is not that different from VRG, having partition coefficients, just under threefold difference. Although VRG and muscle are lean tissues, muscle compartment equilibrates far more slowly than VRG-The perfusion of VRG is about 75 ml/min/100g of tissue, whereas the perfusion of muscle is only 3 ml/min/100gm.This 25 fold difference in perfusion between VRG and muscle means that even if the partition coefficients are equal, muscle would still take 25 times longer to equilibrate with blood
- 24. TIME CONSTANT Time for equilibration of inhaled anesthetic agent in tissues with blood Amount of inhaled anesthetic agent that is dissolved in tissue divided by tissue blood flow One time constant on an exponential curve represents 63% equilibration; three time constants 95% equilibration For volatile anesthetics, equilibration between p art and p brain depends on solubility in blood and requires 5-15 mts(3 time constants) Fat has an enormous capacity to hold anesthetics ,plus low blood flow to fat ,prolongs the time required for equilibration. Eg. - equilibration of fat with isoflurane - 25 to 46 hours
- 25. Fat is perfused to a lesser extend than muscle and its partition coefficients are much greater-time for equilibration with blood is much slower* Therefore, this does not play a major role in determining the speed of induction. But after long anesthetic exposures(>4hours), the high saturation of fat may play a role in delaying emergence
- 26. VENTILATION Increased alveolar ventilation lead to more rapid increase in rate of PA towards PI. Thus lowering of alveolar partial pressure of inhalational agent by uptake can be countered by increasing alveolar ventilation-induction* Decreased alveolar ventilation decreases the input and thus slows the establishment of Pressure alveoli and Pbrain, which is required for the induction of anesthesia In other words, constantly replacing the anesthetics taken up by pulmonary bloodstream results in better maintenance of alveolar concentration and thus concentration of drug in brain This effect is more obvious with soluble anesthetics as they are more subjected to uptake
- 27. In addition to increased input, the decreased paCO2 produced by hyperventilation of the lung decreases the cerebral blood flow. The impact of increased input on the rate of rise of PA will be offset by decreased delivery of anesthetic to brain* The greater the alveolar ventilation to FRC ratio, more rapid is the rate of increase in PA Note: In neonates the above ratio is 5:1*(1.5:1in adults) due to higher metabolic rate— rate of increase of PA is higher—induction is more rapid
- 29. CONCENTRATION Increasing the inspired concentration of an anaesthetic agent increases its rate of rise of alveolar concentration As partial pressure directly proportion to concentration, this can also be stated as “Greater the inspired concentration of an anesthetic, greater will be the alveolar concentration as well as the rate of rise of alveolar concentration of the anesthetic” 2 components 1. Concentrating effect 2. Augmented Gas Inflow Effect
- 30. A. CONCENTRATING EFFECT When the anesthetic represents a large fraction of the inhaled gas mixture, its rapid uptake results in a smaller relative alveolar anesthetic concentration drop, because the volume of alveolar gas also decreases. This is known as the concentration effect.
- 31. B. AUGMENTATION OF TRACHEAL INFLOW Loss of alveolar total gas volume due to absorption (uptake) of nitrous oxide will cause more anaesthetic mixture to be filled in from the airways into the alveolus. This will cause further rise in alveolar concentration of anaesthetic mixture
- 32. SECOND GAS EFFECT Nitrous oxide is more soluble in blood than nitrogen. When a patient is given an anesthetic mixture containing N2O; some part of nitrous oxide is absorbed in the pulmonary vasculature. As a result total volume of gas in the alveolus diminishes and fractional concentration of anaesthetic mixture increases.
- 33. FACTORS AFFECTING ARTERIAL CONCENTRATION SHUNTS A right to left shunt causes venous blood to mix with arterial blood without being exposed to anesthetic in the alveoli. This dilutional effect of right to left shunt causes decrease in partial pressure of anaesthetic in arterial blood. So induction of anaesthesia is slowed. A left to right shunt has opposite effect. It causes re-exposure of the arterial blood to alveolar ventilation and anaesthetic agent. As a result partial pressure of anesthetic in the blood rises.
- 34. DEAD SPACE: Increase in dead space increases the difference between alveolar partial pressure of anesthetic and the partial pressure of anesthetic in the arterial blood.
- 35. MAC Is defined as the conc. at 1 atmosphere of anesthetic in the alveoli that prevents movement in response to a supramaximal painful stimulus(surgical skin incision)in 50 % of patients *Inhaled anesthetic atmospheric pressure required to prevent movement in response to a defined noxious stimulus in 50% of the subjects(miller 9thedition) MAC is important to compare the potencies of various inhalational anesthetic agents* 1.2 -1.3 MAC prevent movement in 95% of patients
- 36. N2O = 104% Halothane = 0.75% Isoflurane = 1.28% Enflurane = 1.58% Sevoflurane = 2.05% Deslurane = 6% N2O alone is unable to produce adequate anesthesia ( require high conc. )
- 38. MAC Awake - Concentration of anesthetic that prevents consciousness in 50% of persons MAC Memory - Concentration of anesthetic that is associated with amnesia in 50% of patients MAC Awake > MAC memory MAC Intubation –end tidal concentration of volatile anesthetics at which a smooth tracheal intubation is possible in 50% of patients MAC BAR-is the alveolar concentration of anesthetic that blunts adrenergic response to noxious stimuli (50% higher than standard MAC)
- 39. MAC value of inhalational agents are additive - that is, 0.5 MAC of nitrous oxide +0.5 MAC of isoflurane has the same effect in brain as 1 MAC of either anesthetic alone.
- 40. FACTORS INCREASING MAC Hyperthermia Excessive pheomelanin production Drug induced elevation in CNS catecholamine levels Cyclosporine Hypernatremia Chronic alchoholism-upregulated CNS response to chronically decreased catecholamine levels
- 41. FACTORS DECREASING MAC Hypothermia Increasing age Preoperative medication Drug induced decrease in CNS catecholamine levels Alpha 2 agonists Acute alchohol ingestion Pregnancy Postpartum(returns to normal in 24-72 hours)
- 42. Lithium Lignocaine Neuraxial opioids Ketanserin Pao2<38mm of hg Mean blood pressure <40 mm of hg Cardiopulmonary bypass Hyponatremia
- 43. RECOVERY FROM ANAESTHESIA -Depicted by rate of decrease in Pbrain as reflected by PA. -the rate of washout of anesthetic from brain is rapid because inhaled anesthetics are not highly soluble in brain and brain receives a larger fraction of cardiac output -At the conclusion of every anesthetic,the concentration of inhaled anesthetic in tissue depends on solubility of drug and the duration of administration -Time to recovery is prolonged in proportion to the duration of anesthesia for soluble anesthetics(halothane and isoflurane),whereas the impact of duration of anesthesia on time to recovery is minimal with poorly soluble anesthetics(sevoflurane,desflurane)
- 44. -Anaesthetics that have been absorbed into the components of breathing system will pass from the components back into the gases in breathing circuit at the conclusion of anaesthesia and retard the rate of decrease in PA of anaesthetic -Exhaled gases of patient will contain anaesthetic that will be rebreathed,unless Fresh gas flow rates are increased at the conclusion anaesthesia - Metabolism also affects the rate of recovery-greater metabolism will result in rapid recovery as with halothane(having a larger bgpc than isoflurane,but greater rate of decrease in PA)
- 45. DIFFUSION HYPOXIA occurs when inhalation of nitrous oxide is discontinued abruptly lowering of partial pressure of nitrous oxide in alveoli nitrous oxide moves from blood to alveoli dilution of PAO2 -decrease in PaO2
- 46. DIFFUSION HYPOXIA -In addition to dilution of PAO2,dilution of PaCO2 also occurs-decreased stimulus to breathe -Greatest at first 1-5 minutes of discontinuation—fill lungs with oxygen at the end of anesthesia to prevent arterial hypoxemia