Physics
Lung Mechanics
December 05, 2009, 19:42
Lung Mechanics & Mechanical Ventilation
By Donald R. Elton, MD, FCCP
Lexington Pulmonary and Critical Care
Who Cares?
Why do we care about lung mechanics during mechanical ventilation? We all should if we want to provide adequate ventilatory support with a minimum of adverse effects. It would be useful if we could easily measure lung compliance, airway resistance, functional residual capacity, and other pulmonary function parameters during mechanical ventilation. Unfortunately, it is difficult to conduct formal pulmonary function testing on critically ill patients who frequently require high airway pressures and flows and may be paralyzed or otherwise unable to cooperate with testing. This paper will explore the theory and application of a few simple bedside maneuvers that anyone can perform either with or without patient cooperation to assess lung mechanics.
Compliance
Compliance is a measurement of the distensibility of the lung. It is expressed as a change in volume divided by a change in pressure. The standard units of Liters/cm H20. The normal lung+thorax compliance of an adult is around 0.1 L/cm H20. When the compliance is low, more pressure will be need to deliver a given volume of gas to a patient. Disease states resulting in low compliance include the Adult Respiratory Distress Syndrome (ARDS), pulmonary edema, pneumonectomy, pleural effusion, pulmonary fibrosis, and pneumonia among others. Emphysema is a typical cause of increased lung compliance.
Airway Resistance
Resistance is the amount of pressure required to deliver a given flow of gas and is expressed in terms of a change in pressure divided by flow. The standard units of resistance are cm H20/L/second and the normal value for an adult is around 0.5 - 1.5 cm H20/L/sec while in states of disease this value may be 100.0 cm H20/L/sec or higher. There really aren't any diseases characterized by decreased airway resistance since normal values are so low but there are many disease states that result in increased airway resistance including use of artificial airways, asthma, emphysema with airway collapse, mucus plugging, vocal cord paralysis, and endobronchial obstruction either from tumors or foreign bodies.
Time Constant
The Time Constant of the lung (TC) is a concept borrowed from electrical engineering which describes the phenomenon whereby a given percentage of a passively exhaled breath of air will require a constant amount of time to be exhaled regardless of the starting volume given constant lung mechanics. That's quite a mouth-full of a definition but consider what determines how long it takes to exhale a tidal breath passively. At the start of exhalation, the initial flow of gas out of the lung depends upon the driving pressure (i.e. alveolar pressure - mouth pressure) and it depends on the airway resistance. For any given volume of gas, the alveolar pressure at the start of exhalation is only dependent upon the lung compliance. Mathematically, the time constant is defined as compliance multiplied by the airway resistance and the resulting value has units of seconds of time..
Airway Pressure & Alveolar Pressure
Airway pressure is the pressure measured at the patient's airway during mechanical ventilation. Airway pressure is determined by the sum of the alveolar pressure and the pressure required to deliver flow across the airways which is determined by the airway resistance. Alveolar pressure is the pressure in the distensible parts of the respiratory tract and is determined by the tidal volume and the lung/chest compliance. Airway pressure is equal to alveolar pressure when there is no flow occurring. At the end of a mechanical inspiration, flow to the distal parts of the lung continues even after inspiratory flow from the ventilator stops as time is required for gas to reach the periphery of the lung. To measure alveolar pressure, one must measure the airway pressure at a time when both pressures are equal, i.e. when there is no flow. Measuring Compliance To measure lung compliance one must know the delivered tidal volume and must also know the change in alveolar pressure that results from the addition of that known tidal volume. We normally assume that alveolar and airway pressure start out at atmospheric (our zero reference) before an inspiration starts. To equalize airway and alveolar pressures we only have to prevent exhalation after inspiration has ceased by utilizing an inspiratory hold maneuver. The actual calculation is to divide the delivered tidal volume by the plateau pressure where the plateau pressure is the steady-state pressure measured during an inspiratory hold maneuver. If precise measurement is necessary then the pressure should be the plateau pressure minus any end expiratory pressure (or the pleural pressure or Auto-PEEP if it is available) and the volume should be either measured at the airway itself or should be corrected for compressible volume loss. In most cases, approximate values are adequate for clinical use so the plateau pressure minus the end expiratory pressure is divided into the exhaled tidal volume as measured by the ventilator. This compliance measurement is sometimes called the static compliance since it is measured after an inspiratory hold such that there is no gas flow during its measurement.
Measuring Resistance
Airway resistance can be estimated by dividing the difference between peak and plateau airway pressures by the mean inspiratory flow rate. Some ventilators have an inspiratory flow rate setting such that you can read the control for an estimate of delivered flow rate while others give an inspiratory time setting where you have to divide the tidal volume by the inspiratory time to determine the inspiratory flow rate. An alternative way of following airway resistance is to calculate a nonsense parameter known as the dynamic compliance . The dynamic compliance is the result of dividing the delivered tidal volume by the peak airway pressure. Since peak airway pressure is determined by a combination of the lung compliance, the airway resistance, inspiratory flow rate, and the tidal volume, this value does not really give a quantitative estimate of airway resistance itself but can be used to detect changes in the airway resistance if all other factors are held constant. This makes the value useful for comparing measurements on a single patient over a short period of time but it is too much to ask to expect that all of the other variables affecting peak airway pressure will stay the same from day to day or certainly from patient to patient. Because of the limitations of dynamic compliance measurements, it makes more sense to just follow the peak pressure to plateau pressure gradient since it requires less math and is just as useful (or useless) as the dynamic compliance calculation. A third way to estimate airway resistance can be used if the patient is exhaling passively. This method works based on the time constant. The practitioner times how long it takes for the patient to exhale completely and then divides this result by 3 to estimate the time constant. The lung compliance is then measured and divided into the time constant to result in the airway resistance thus: Raw = Time Constant / Clung
Auto PEEP
Auto PEEP is the popular name used to describe increased alveolar pressure caused by gas trapping during mechanical ventilation. Gas trapping occurs when there is inadequate time to exhale the mechanical tidal volume. Recall that the time constant determines the length of time needed for a passive exhalation and that the time constant is the product of airway resistance and lung compliance. The lower the compliance, the higher the driving pressure pushing gas out of the lungs during exhalation; the lower the resistance, the higher the expiratory flow rate can be when driven by the alveolar pressure. If the time constant is known (or can be estimated) then the maximum mechanical respiratory rate that can be used before Auto PEEP results can be estimated. Consider that at least 3 time constants are required to exhale passively any volume of gas. The combination of inspiratory and expiratory time leads to a give respiratory rate such that:
Total Breath Time = Insp time + Exp time
Respiratory Rate = 60 / Total Breath Time
Maximum Rate = 60 / (Insp time + 3 x TC)
A patient with a compliance of 0.05 L/cm H20 and an airway resistance of 30 cm H20/L/sec. This would give a time constant of 1.5 seconds. A complete exhalation would take around 4.5 seconds. If inspiratory time is 1 second then total breath time is 5.5 seconds and the maximum respiratory rate without gas trapping would be 11 breaths per minute. When gas trapping occurs, the functional residual capacity (FRC) is increased. As the FRC increases, the alveolar pressure increases by an amount of pressure determined by the patient's lung compliance. As the FRC rises in relation to the total lung capacity (TLC), the lung compliance will decrease. This decrease in lung compliance shortens the time constant for the next breath and thus shortens the time required to exhale the next breath and lessens the amount of trapping that will occur with each subsequent breath until the time constant shortens enough that gas trapping no longer occurs. When this steady state is reached, the FRC is at its maximum and the auto-PEEP is also at its maximum. This fact gives us a way to measure how much auto-PEEP exists since we can serially measure exhaled tidal volumes and then interrupt ventilation (by turning the respiratory rate to zero for several seconds) and measuring how much gas the patient exhales as the patient exhales back to the FRC level that existed prior to ventilation. If we take the difference between the exhaled volume during ventilation and the exhaled volume after interrupting ventilation then we have the amount of gas that was trapped. If we divide this volume by the lung compliance we will have calculated the amount of auto-PEEP applied to the alveoli during ventilation. Normally we are more interested in avoiding auto-PEEP than in measuring it though there are many patients in whom it cannot be avoided so it is useful to be able to quantitate it. Another way to detect auto-PEEP is to watch a patient's chest movement and/or breath sounds during exhalation to see if exhalation stops prior to initiation of inspiration by the ventilator. If exhalation doesn't finish then auto-PEEP is occurring. When exhaled tidal volumes cannot be measured (which is seldom with modern ventilators) the level of auto-PEEP can be very roughly estimated by interrupting exhalation just prior to initiation of inspiration and watching to see if there is a pressure increase at the airway as exhalation continues into the circuit between the patient and the point of your interruption. This is not an accurate measurement since the interruption necessarily cuts exhalation shorter than it would normally be and because the circuit volume dampens the pressure measurement but this technique can be useful if you are unable to use the more reliable methods outlined above.
References
Shapiro BA, Harrison RA, Trout CA: Clinical Application of Respiratory Care, Year Book Medical Publishers, Inc, Chicago, 1982.
Tobin, MJ, Lodato, RF: PEEP, Auto-PEEP, and Waterfalls, Editorial, Chest 1989, 96:449-51.
Lain, DC, Chaudhary, BA et al: Auto-PEEP and Proximal Airway Pressure, Need for clarification, Editorial, Chest 1990, 97:771.
Duncan, SR, Rizk, NW, Raffin, TA: Inverse Ratio Ventilation, PEEP in Disguise?, Chest 1987, 92:390-1.
Wright, J, Gong, H: "Auto-PEEP": Incidence, magnitude, and contributing factors, Heart and Lung 1990, 19:352-7.
Hoffman, RA, Ershowsky, P, Krieger, P: Determination of Auto-PEEP During Spontaneous and Controlled Ventilation by Monitoring Changes in End-Expiratory Thoracic Gas Volume, Chest 1989, 96:613-6.
By Donald R. Elton, MD, FCCP
Lexington Pulmonary and Critical Care
Who Cares?
Why do we care about lung mechanics during mechanical ventilation? We all should if we want to provide adequate ventilatory support with a minimum of adverse effects. It would be useful if we could easily measure lung compliance, airway resistance, functional residual capacity, and other pulmonary function parameters during mechanical ventilation. Unfortunately, it is difficult to conduct formal pulmonary function testing on critically ill patients who frequently require high airway pressures and flows and may be paralyzed or otherwise unable to cooperate with testing. This paper will explore the theory and application of a few simple bedside maneuvers that anyone can perform either with or without patient cooperation to assess lung mechanics.
Compliance
Compliance is a measurement of the distensibility of the lung. It is expressed as a change in volume divided by a change in pressure. The standard units of Liters/cm H20. The normal lung+thorax compliance of an adult is around 0.1 L/cm H20. When the compliance is low, more pressure will be need to deliver a given volume of gas to a patient. Disease states resulting in low compliance include the Adult Respiratory Distress Syndrome (ARDS), pulmonary edema, pneumonectomy, pleural effusion, pulmonary fibrosis, and pneumonia among others. Emphysema is a typical cause of increased lung compliance.
Airway Resistance
Resistance is the amount of pressure required to deliver a given flow of gas and is expressed in terms of a change in pressure divided by flow. The standard units of resistance are cm H20/L/second and the normal value for an adult is around 0.5 - 1.5 cm H20/L/sec while in states of disease this value may be 100.0 cm H20/L/sec or higher. There really aren't any diseases characterized by decreased airway resistance since normal values are so low but there are many disease states that result in increased airway resistance including use of artificial airways, asthma, emphysema with airway collapse, mucus plugging, vocal cord paralysis, and endobronchial obstruction either from tumors or foreign bodies.
Time Constant
The Time Constant of the lung (TC) is a concept borrowed from electrical engineering which describes the phenomenon whereby a given percentage of a passively exhaled breath of air will require a constant amount of time to be exhaled regardless of the starting volume given constant lung mechanics. That's quite a mouth-full of a definition but consider what determines how long it takes to exhale a tidal breath passively. At the start of exhalation, the initial flow of gas out of the lung depends upon the driving pressure (i.e. alveolar pressure - mouth pressure) and it depends on the airway resistance. For any given volume of gas, the alveolar pressure at the start of exhalation is only dependent upon the lung compliance. Mathematically, the time constant is defined as compliance multiplied by the airway resistance and the resulting value has units of seconds of time..
Airway Pressure & Alveolar Pressure
Airway pressure is the pressure measured at the patient's airway during mechanical ventilation. Airway pressure is determined by the sum of the alveolar pressure and the pressure required to deliver flow across the airways which is determined by the airway resistance. Alveolar pressure is the pressure in the distensible parts of the respiratory tract and is determined by the tidal volume and the lung/chest compliance. Airway pressure is equal to alveolar pressure when there is no flow occurring. At the end of a mechanical inspiration, flow to the distal parts of the lung continues even after inspiratory flow from the ventilator stops as time is required for gas to reach the periphery of the lung. To measure alveolar pressure, one must measure the airway pressure at a time when both pressures are equal, i.e. when there is no flow. Measuring Compliance To measure lung compliance one must know the delivered tidal volume and must also know the change in alveolar pressure that results from the addition of that known tidal volume. We normally assume that alveolar and airway pressure start out at atmospheric (our zero reference) before an inspiration starts. To equalize airway and alveolar pressures we only have to prevent exhalation after inspiration has ceased by utilizing an inspiratory hold maneuver. The actual calculation is to divide the delivered tidal volume by the plateau pressure where the plateau pressure is the steady-state pressure measured during an inspiratory hold maneuver. If precise measurement is necessary then the pressure should be the plateau pressure minus any end expiratory pressure (or the pleural pressure or Auto-PEEP if it is available) and the volume should be either measured at the airway itself or should be corrected for compressible volume loss. In most cases, approximate values are adequate for clinical use so the plateau pressure minus the end expiratory pressure is divided into the exhaled tidal volume as measured by the ventilator. This compliance measurement is sometimes called the static compliance since it is measured after an inspiratory hold such that there is no gas flow during its measurement.
Measuring Resistance
Airway resistance can be estimated by dividing the difference between peak and plateau airway pressures by the mean inspiratory flow rate. Some ventilators have an inspiratory flow rate setting such that you can read the control for an estimate of delivered flow rate while others give an inspiratory time setting where you have to divide the tidal volume by the inspiratory time to determine the inspiratory flow rate. An alternative way of following airway resistance is to calculate a nonsense parameter known as the dynamic compliance . The dynamic compliance is the result of dividing the delivered tidal volume by the peak airway pressure. Since peak airway pressure is determined by a combination of the lung compliance, the airway resistance, inspiratory flow rate, and the tidal volume, this value does not really give a quantitative estimate of airway resistance itself but can be used to detect changes in the airway resistance if all other factors are held constant. This makes the value useful for comparing measurements on a single patient over a short period of time but it is too much to ask to expect that all of the other variables affecting peak airway pressure will stay the same from day to day or certainly from patient to patient. Because of the limitations of dynamic compliance measurements, it makes more sense to just follow the peak pressure to plateau pressure gradient since it requires less math and is just as useful (or useless) as the dynamic compliance calculation. A third way to estimate airway resistance can be used if the patient is exhaling passively. This method works based on the time constant. The practitioner times how long it takes for the patient to exhale completely and then divides this result by 3 to estimate the time constant. The lung compliance is then measured and divided into the time constant to result in the airway resistance thus: Raw = Time Constant / Clung
Auto PEEP
Auto PEEP is the popular name used to describe increased alveolar pressure caused by gas trapping during mechanical ventilation. Gas trapping occurs when there is inadequate time to exhale the mechanical tidal volume. Recall that the time constant determines the length of time needed for a passive exhalation and that the time constant is the product of airway resistance and lung compliance. The lower the compliance, the higher the driving pressure pushing gas out of the lungs during exhalation; the lower the resistance, the higher the expiratory flow rate can be when driven by the alveolar pressure. If the time constant is known (or can be estimated) then the maximum mechanical respiratory rate that can be used before Auto PEEP results can be estimated. Consider that at least 3 time constants are required to exhale passively any volume of gas. The combination of inspiratory and expiratory time leads to a give respiratory rate such that:
Total Breath Time = Insp time + Exp time
Respiratory Rate = 60 / Total Breath Time
Maximum Rate = 60 / (Insp time + 3 x TC)
A patient with a compliance of 0.05 L/cm H20 and an airway resistance of 30 cm H20/L/sec. This would give a time constant of 1.5 seconds. A complete exhalation would take around 4.5 seconds. If inspiratory time is 1 second then total breath time is 5.5 seconds and the maximum respiratory rate without gas trapping would be 11 breaths per minute. When gas trapping occurs, the functional residual capacity (FRC) is increased. As the FRC increases, the alveolar pressure increases by an amount of pressure determined by the patient's lung compliance. As the FRC rises in relation to the total lung capacity (TLC), the lung compliance will decrease. This decrease in lung compliance shortens the time constant for the next breath and thus shortens the time required to exhale the next breath and lessens the amount of trapping that will occur with each subsequent breath until the time constant shortens enough that gas trapping no longer occurs. When this steady state is reached, the FRC is at its maximum and the auto-PEEP is also at its maximum. This fact gives us a way to measure how much auto-PEEP exists since we can serially measure exhaled tidal volumes and then interrupt ventilation (by turning the respiratory rate to zero for several seconds) and measuring how much gas the patient exhales as the patient exhales back to the FRC level that existed prior to ventilation. If we take the difference between the exhaled volume during ventilation and the exhaled volume after interrupting ventilation then we have the amount of gas that was trapped. If we divide this volume by the lung compliance we will have calculated the amount of auto-PEEP applied to the alveoli during ventilation. Normally we are more interested in avoiding auto-PEEP than in measuring it though there are many patients in whom it cannot be avoided so it is useful to be able to quantitate it. Another way to detect auto-PEEP is to watch a patient's chest movement and/or breath sounds during exhalation to see if exhalation stops prior to initiation of inspiration by the ventilator. If exhalation doesn't finish then auto-PEEP is occurring. When exhaled tidal volumes cannot be measured (which is seldom with modern ventilators) the level of auto-PEEP can be very roughly estimated by interrupting exhalation just prior to initiation of inspiration and watching to see if there is a pressure increase at the airway as exhalation continues into the circuit between the patient and the point of your interruption. This is not an accurate measurement since the interruption necessarily cuts exhalation shorter than it would normally be and because the circuit volume dampens the pressure measurement but this technique can be useful if you are unable to use the more reliable methods outlined above.
References
Shapiro BA, Harrison RA, Trout CA: Clinical Application of Respiratory Care, Year Book Medical Publishers, Inc, Chicago, 1982.
Tobin, MJ, Lodato, RF: PEEP, Auto-PEEP, and Waterfalls, Editorial, Chest 1989, 96:449-51.
Lain, DC, Chaudhary, BA et al: Auto-PEEP and Proximal Airway Pressure, Need for clarification, Editorial, Chest 1990, 97:771.
Duncan, SR, Rizk, NW, Raffin, TA: Inverse Ratio Ventilation, PEEP in Disguise?, Chest 1987, 92:390-1.
Wright, J, Gong, H: "Auto-PEEP": Incidence, magnitude, and contributing factors, Heart and Lung 1990, 19:352-7.
Hoffman, RA, Ershowsky, P, Krieger, P: Determination of Auto-PEEP During Spontaneous and Controlled Ventilation by Monitoring Changes in End-Expiratory Thoracic Gas Volume, Chest 1989, 96:613-6.
Aerosol Therapy
December 05, 2009, 19:38
Aerosol Therapy
By Donald R. Elton, MD, FCCP
Lexington Pulmonary and Critical Care
Introduction
An aerosol is a suspension of small particles of liquid or solid in a gas. The particles, synthetic or natural, fall within the size range of 0.005 to 50 in diameter. Those that are medically important are less than 3 in diameter. Gravity begins to lose its influence on particles at this mass size. Examples of aerosols include dusts, bacteria, yeast, water, and smoke.
Terminology
Stability of an aerosol is the ability to remain in suspension and maintain its integrity as an aerosol. Stability is dependent upon the size and nature of the particle, the concentration of particles, ambient humidity, and movement of the suspending gas. Instability is the propensity of a suspended particle to remove itself from suspension. For therapeutic aerosols, penetration refers to the depth to which an aerosol particle can be carried by a tidal breath. Deposition refers to the aerosol becoming unstable as particles rain-out or are retained within the respiratory tract. Clearance refers to removal of deposited particles by biologic mechanisms.
Aerosol Generation
There are two main types of aerosol generators in general clinical use today. They are jet nebulizers and ultrasonic nebulizers. A Jet nebulizer works by directing a high flow of gas over a capillary tube that is immersed into the fluid to be nebulized (made into an aerosol). The suction generated at the top of the capillary tube draws fluid up the tube and into the air. Particles of improper size (from a stability stand-point) are frequently directed against a baffle that will encourage rain-out such that the fluid to be nebulized is not wasted by the creation of unstable particles. The particles that rain-out fall back into the fluid reservoir so they can be nebulized again. Many nebulizers have an air intake or venturi to allow the entrainment of room air for dilution of the primary gas, usually oxygen.
An ultrasonic nebulizer consists of a power chamber and a nebulizing chamber. The power chamber includes a ceramic transducer that is described as piezoelectric because is changes electrical energy into pressure energy. The transducer vibrates at a very high frequency (that requires FCC certification) up to about 1.5 mHz. The transducer sits at the bottom of a water filled power chamber. The vibrational energy is transmitted through the water and focused on a flexible diaphragm that vibrates in sympathy. The diaphragm is in contact with the solution to be aerosolized and shakes the solution into particles. At low frequencies, waves are produced that may produce some larger aerosol particles. At high frequencies a fine mist is generated. At low power (amplitude) the particles are produced intermittently as waves break while at higher power settings the particles are liberated continuously. At very high power settings, the chemical makeup of some medications can be disrupted. Ultrasonic nebulizers tend to produce a more consistent particle size than do jet nebulizers and can produce very large volumes of respirable particles with much greater deposition into the lungs. There is some experimental evidence to suggest that long-term use of ultrasonic nebulization can result to disruption of surface tension stability in the lung, perhaps owing to the large amount of fluid deposited into the lungs. Ultrasonic nebulizers are limited in that they cannot aerosolize viscous solutions though this is not a problem clinically.
Aerosol Behavior
Once an aerosol is generated, there is initially quite a variety of particle sizes. As the aerosol ages, however, larger particles aggregate and become unstable, falling out of suspension. This results in a decrease in the size deviation of an aerosol such that the resulting aerosol tends to consist of particles close to 0.1 micron. The depth of penetration of an aerosol particle into the respiratory tract increases as the particle size decreases. The nose will completely filter particles down to 5 to 10 microns in diameter while particles of 1 micron and down can get past the upper airway and into the terminal alveoli. Particles of around 1 micron are retained in alveoli while particles much below this size do not deposit and are exhaled. The rate at which a particle will settle is related to physical properties such as gravity, mass, volume, density, and viscous resistance of air. For particles within the size range of 0.1 to 70 microns, the settling velocity of a particle is proportional to the product of its density and the square of its diameter: Settling rate = Density x Diameter squared. Particles, as they approach 0.1 micron in size, become almost molecular in character and are influenced greatly by the kinetic activity of the suspending gas to a greater extent than gravity. A smaller particle is actually kept in suspension by collisions with adjacent gas molecules as it has a high surface area to mass ratio compared to the larger, more massive particle which is more influenced by gravity. Below a given size (about 0.25 microns) particle deposition/retention is actually increased. Rain-out, or retention, of an aerosol can be facilitated by the inertia of a particle tending to keep the particle moving in a straight line when the flow of inspired air changes direction suddenly. Particles at the edge of a stream of gas are more likely to impact by this mechanism. Particle composition also influences particle stability. A hygroscopic particle will tend in accumulate water vapor and increase the size of itself while other particles might tend to dry out and decrease in size. This mechanism is influenced by the relative humidity of the suspending gas. Ventilatory patterns influence particle deposition and retention. Deposition and retention are directly related to inhaled tidal volume and inversely related to flow rate. These factors are only important in conducting airways and become less important as the inspired gas approaches the alveoli where there is little air movement. Aerosolized particles are cleared from the lung by means of ciliary mucus clearance and by means of pulmonary tissue clearance which is a combination of phagocytosis by macrophages and diffusion and dissolving into tissue fluids.
Medical Aerosols
The two main areas where aerosols are used therapeutically are for humidification therapy and medication delivery. Humidification therapy depends on both the bulk delivery of water or saline solutions to the airways and alveoli as well as the tendency of evaporating particles to increase the relative humidity of the suspending gas. Ultrasonic nebulizers, in particular, are very efficient at delivering large amounts of liquid to the respiratory tract. There is controversy regarding what fluid is best to deliver in this manner. Fluids that are very hypertonic or hypotonic tend to be irritating and lead to coughing and bronchospasm in susceptible individuals. The tonicity of aerosolized fluids also tends to change enroute to the alveoli depending on the humidity of the suspending gas. What starts out as an isotonic solution may be either hypertonic or hypotonic by the time it arrives as the site of deposition. There is also controversy as to whether delivery of liquids to the airways is of any therapeutic value in decreasing the viscosity of or increasing the clearance of mucus.
Medication Delivery
Aerosols are an attractive way to delivery drugs, particularly those whose site of action is the lungs themselves as relatively high doses are delivered to the site of action, sparing high systemic doses that might otherwise cause adverse systemic effects. Unfortunately, there are many problems with using aerosols to deliver medications to include inconsistent dose delivery, inadvertent gastrointestinal delivery, non-uniform distribution of medication in the lungs, and elicitation of bronchospasm. There are even those that theorize that the use of suspending gasses like fluorocarbons might be causing cardiac arrests secondary to cardiac toxicity in some asthmatics.
Dosage delivery
Aerosolized medications are inconsistently delivered to the patient. When one places a given amount of medication in a nebulizer, it is difficult, if not impossible, to predict how much of the medication will actually be delivered to the patient, much less to the site of action in the alveoli where it is theorized that most systemic absorption takes place. The initial site of lost medication is into the room as most aerosols are delivered without the benefit of a closed delivery system. Continuous aerosols such as those delivered by hand held, gas powered nebulizers deliver as much as 2/3 of their output during the patient's exhalation. Of the amount of aerosol produced during inspiration, some still leaks out of the mask or mouthpiece, some rains out in the nose and/or oropharynx and some is actually delivered to the lower airways and lungs. Metered dose inhalers are subject to many of the same limitations and those with very short ejection periods are even more susceptible to asynchronous delivery. Commercially available metered dose inhalers eject about 15cc of gas per actuation. Many text books recommend dosing aerosolized medications the way oral or parenteral medications are dosed, i.e. based on body weight. The problem with this is that patients of different sizes already have different deposition rates. For example, say you have a drug that you'd give to a patient at 1 mg/kg of body weight if given IV. If you are going to use a gas powered continuous nebulizer you would have to use at least 3 times this dose to just get the usual dose directed in the general direction of the patient during inspiration. Since deposition is also minute volume dependent, patients with smaller minute volumes (i.e. pediatric patients) will get less delivery of drug to the lungs than those with larger minute volumes. This means that if you put 2 mg of Terbutaline in a nebulizer for an adult that the same 2 mg of Terbutaline would give a proportionately smaller delivered dose to a newborn. Further complicating the picture is the fact that there is a greater tendency to trap the medication in the upper airway of an infant such that you really have to greatly increase the dose to the nebulizer to treat an infant so it might take 6 mg of Terbutaline in the nebulizer to give an infant the same dose per kg of body weight that an adult would receive with 2 mg of drug in the nebulizer. Basing the amount of medication you place in the nebulizer on the body weight of the patient in a linear fashion will not accurately predict dose delivery to the patient's lungs as they are really inversely related at best. Aerosolized medication dosing is further complicated by the variety of devices used to create the aerosol. There is no simple way to compare doses unless the same nebulizer is used. A case in point is the aerosolization of Pentamidine. There are plenty of recommendations as to what dose of medication to deliver but whatever dose you choose, you must use the same nebulizer used in the study you like or your dose delivery will be different than that which was recommended, perhaps more, perhaps less, perhaps not even close to what you thought you were delivering. Particle Size vs Site of delivery To further complicate matters, the particle size produced by various nebulizers, greatly influences where the aerosol will be deposited and also determines whether it will be retained or simply exhaled. Nebulizers are frequently called efficient if a large percentage of their delivered dose is retained but this usually means that they produce larger particles that are more likely to impact in the upper airway and not be delivered to the alveoli, if indeed, that is the intended target of delivery. In the case of Pentamidine, for example, it is recommended that the Respigard II be used. The retention of the 0.9 particles is only 5.3% meaning that only 5.3% of the dose from the nebulizer is retained. This sounds inefficient and is but if one of the other nebulizers were used then the particle size would result in more of the medication being delivered to airways instead of the alveoli where you want the medicine to go. Rain-out in airways is responsible for at least some of th e complications of therapy and is thus avoided by using a nebulizer producing smaller particles even if much of the aerosol is stable enough to be exhaled again. If one wanted to increase the delivered dose a rebreathing circuit could be used but this would increase the delivered dose to a level greater than what is recommended since the dosage recommendations are made assuming the intentional inefficiency of the the Respigard II.
Intubated patients
Nebulizers and metered dose inhalers have been used with intubated and mechanically ventilated patients. Factors influencing delivery include whether a continuous or inspiration-only nebulizer is used, where the nebulizer is placed in the circuit, and whether a nebulizer or a metered dose inhaler is used. Ventilator settings also influence drug delivery. In general, intubated patients will get less lung deposition and retention than non-intubated patients so dosing has to be adjusted accordingly. So what gives? If you've gotten the idea that it's a joke to pretend that medications can be precisely delivered by aerosol then you have the right idea. Given the many confounding factors influencing drug delivery, the only real ways to sensibly choose a dose is to use secondary indicators such as response to therapy (in the case of bronchodilators) or perhaps measurement of drug levels in serum or urine in the case of Pentamidine. Perhaps it would be more sensible if medications prepared for aerosol delivery were available in standard solutions with no particular dosage ordered and actual dose usage determined strictly on the basis of response.
References
Patel P, Mukai D, Wilson AF: Dose-response effects of two sizes of monodisperse isoproterenol in mild asthma. ARRD (1990 Feb) 141(2): 357-60.
Simonds AK, Newman SP, Johnson MA, Talaee N, Lee CA, Clarke SW: Alveolar targeting of aerosol pentamidine. Toward a rational delivery system. ARRD (1990 Apr) 141(4 Pt 1):827-9.
Kim CS, Trujillo D, Sackner MA: Size aspects of metered-dose inhaler aerosols. ARRD (1985 Jul) 132(1):137-42.
Ilowite JS, Baskin MI, Sheetz MS, Abd AG: Delivered dose and regional distribution of aerosolized pentamidine using different delivery systems. Chest (1991 May) 99(5):1139-44.
Hiller C, Mazumder M, Wilson D, Bone R: Aerodynamic size distribution of metered-dose bronchodilator aerosols. ARRD (1978 Aug) 118(2):311-7.
Peters JA: Humidity and Aerosol Therapy, in Spearman CB, Sheldon RL, Egan DF: Egan's Fundamentals of Respiratory Therapy, 4th edition, The C.V. Mosby Co., 1982.
Hess D, Daugherty A, Simmons M: The Volume of Gas Emitted from Metered Dose Inhalers, abstract, Resp Care, (1991 Nov), 36(11):1320.
ink JB, Cohen NH, Covington J, Mahlmeister MJ: Titration for Optimal Do se Response to Bronchodilators Using MDI and Spacer in Ventilated Adults, abstract, Resp Care, (1991 Nov), 36(11):1321.
Don Elton
Lexington, South Carolina
http://www.lexingtonpulmonary.com
By Donald R. Elton, MD, FCCP
Lexington Pulmonary and Critical Care
Introduction
An aerosol is a suspension of small particles of liquid or solid in a gas. The particles, synthetic or natural, fall within the size range of 0.005 to 50 in diameter. Those that are medically important are less than 3 in diameter. Gravity begins to lose its influence on particles at this mass size. Examples of aerosols include dusts, bacteria, yeast, water, and smoke.
Terminology
Stability of an aerosol is the ability to remain in suspension and maintain its integrity as an aerosol. Stability is dependent upon the size and nature of the particle, the concentration of particles, ambient humidity, and movement of the suspending gas. Instability is the propensity of a suspended particle to remove itself from suspension. For therapeutic aerosols, penetration refers to the depth to which an aerosol particle can be carried by a tidal breath. Deposition refers to the aerosol becoming unstable as particles rain-out or are retained within the respiratory tract. Clearance refers to removal of deposited particles by biologic mechanisms.
Aerosol Generation
There are two main types of aerosol generators in general clinical use today. They are jet nebulizers and ultrasonic nebulizers. A Jet nebulizer works by directing a high flow of gas over a capillary tube that is immersed into the fluid to be nebulized (made into an aerosol). The suction generated at the top of the capillary tube draws fluid up the tube and into the air. Particles of improper size (from a stability stand-point) are frequently directed against a baffle that will encourage rain-out such that the fluid to be nebulized is not wasted by the creation of unstable particles. The particles that rain-out fall back into the fluid reservoir so they can be nebulized again. Many nebulizers have an air intake or venturi to allow the entrainment of room air for dilution of the primary gas, usually oxygen.
An ultrasonic nebulizer consists of a power chamber and a nebulizing chamber. The power chamber includes a ceramic transducer that is described as piezoelectric because is changes electrical energy into pressure energy. The transducer vibrates at a very high frequency (that requires FCC certification) up to about 1.5 mHz. The transducer sits at the bottom of a water filled power chamber. The vibrational energy is transmitted through the water and focused on a flexible diaphragm that vibrates in sympathy. The diaphragm is in contact with the solution to be aerosolized and shakes the solution into particles. At low frequencies, waves are produced that may produce some larger aerosol particles. At high frequencies a fine mist is generated. At low power (amplitude) the particles are produced intermittently as waves break while at higher power settings the particles are liberated continuously. At very high power settings, the chemical makeup of some medications can be disrupted. Ultrasonic nebulizers tend to produce a more consistent particle size than do jet nebulizers and can produce very large volumes of respirable particles with much greater deposition into the lungs. There is some experimental evidence to suggest that long-term use of ultrasonic nebulization can result to disruption of surface tension stability in the lung, perhaps owing to the large amount of fluid deposited into the lungs. Ultrasonic nebulizers are limited in that they cannot aerosolize viscous solutions though this is not a problem clinically.
Aerosol Behavior
Once an aerosol is generated, there is initially quite a variety of particle sizes. As the aerosol ages, however, larger particles aggregate and become unstable, falling out of suspension. This results in a decrease in the size deviation of an aerosol such that the resulting aerosol tends to consist of particles close to 0.1 micron. The depth of penetration of an aerosol particle into the respiratory tract increases as the particle size decreases. The nose will completely filter particles down to 5 to 10 microns in diameter while particles of 1 micron and down can get past the upper airway and into the terminal alveoli. Particles of around 1 micron are retained in alveoli while particles much below this size do not deposit and are exhaled. The rate at which a particle will settle is related to physical properties such as gravity, mass, volume, density, and viscous resistance of air. For particles within the size range of 0.1 to 70 microns, the settling velocity of a particle is proportional to the product of its density and the square of its diameter: Settling rate = Density x Diameter squared. Particles, as they approach 0.1 micron in size, become almost molecular in character and are influenced greatly by the kinetic activity of the suspending gas to a greater extent than gravity. A smaller particle is actually kept in suspension by collisions with adjacent gas molecules as it has a high surface area to mass ratio compared to the larger, more massive particle which is more influenced by gravity. Below a given size (about 0.25 microns) particle deposition/retention is actually increased. Rain-out, or retention, of an aerosol can be facilitated by the inertia of a particle tending to keep the particle moving in a straight line when the flow of inspired air changes direction suddenly. Particles at the edge of a stream of gas are more likely to impact by this mechanism. Particle composition also influences particle stability. A hygroscopic particle will tend in accumulate water vapor and increase the size of itself while other particles might tend to dry out and decrease in size. This mechanism is influenced by the relative humidity of the suspending gas. Ventilatory patterns influence particle deposition and retention. Deposition and retention are directly related to inhaled tidal volume and inversely related to flow rate. These factors are only important in conducting airways and become less important as the inspired gas approaches the alveoli where there is little air movement. Aerosolized particles are cleared from the lung by means of ciliary mucus clearance and by means of pulmonary tissue clearance which is a combination of phagocytosis by macrophages and diffusion and dissolving into tissue fluids.
Medical Aerosols
The two main areas where aerosols are used therapeutically are for humidification therapy and medication delivery. Humidification therapy depends on both the bulk delivery of water or saline solutions to the airways and alveoli as well as the tendency of evaporating particles to increase the relative humidity of the suspending gas. Ultrasonic nebulizers, in particular, are very efficient at delivering large amounts of liquid to the respiratory tract. There is controversy regarding what fluid is best to deliver in this manner. Fluids that are very hypertonic or hypotonic tend to be irritating and lead to coughing and bronchospasm in susceptible individuals. The tonicity of aerosolized fluids also tends to change enroute to the alveoli depending on the humidity of the suspending gas. What starts out as an isotonic solution may be either hypertonic or hypotonic by the time it arrives as the site of deposition. There is also controversy as to whether delivery of liquids to the airways is of any therapeutic value in decreasing the viscosity of or increasing the clearance of mucus.
Medication Delivery
Aerosols are an attractive way to delivery drugs, particularly those whose site of action is the lungs themselves as relatively high doses are delivered to the site of action, sparing high systemic doses that might otherwise cause adverse systemic effects. Unfortunately, there are many problems with using aerosols to deliver medications to include inconsistent dose delivery, inadvertent gastrointestinal delivery, non-uniform distribution of medication in the lungs, and elicitation of bronchospasm. There are even those that theorize that the use of suspending gasses like fluorocarbons might be causing cardiac arrests secondary to cardiac toxicity in some asthmatics.
Dosage delivery
Aerosolized medications are inconsistently delivered to the patient. When one places a given amount of medication in a nebulizer, it is difficult, if not impossible, to predict how much of the medication will actually be delivered to the patient, much less to the site of action in the alveoli where it is theorized that most systemic absorption takes place. The initial site of lost medication is into the room as most aerosols are delivered without the benefit of a closed delivery system. Continuous aerosols such as those delivered by hand held, gas powered nebulizers deliver as much as 2/3 of their output during the patient's exhalation. Of the amount of aerosol produced during inspiration, some still leaks out of the mask or mouthpiece, some rains out in the nose and/or oropharynx and some is actually delivered to the lower airways and lungs. Metered dose inhalers are subject to many of the same limitations and those with very short ejection periods are even more susceptible to asynchronous delivery. Commercially available metered dose inhalers eject about 15cc of gas per actuation. Many text books recommend dosing aerosolized medications the way oral or parenteral medications are dosed, i.e. based on body weight. The problem with this is that patients of different sizes already have different deposition rates. For example, say you have a drug that you'd give to a patient at 1 mg/kg of body weight if given IV. If you are going to use a gas powered continuous nebulizer you would have to use at least 3 times this dose to just get the usual dose directed in the general direction of the patient during inspiration. Since deposition is also minute volume dependent, patients with smaller minute volumes (i.e. pediatric patients) will get less delivery of drug to the lungs than those with larger minute volumes. This means that if you put 2 mg of Terbutaline in a nebulizer for an adult that the same 2 mg of Terbutaline would give a proportionately smaller delivered dose to a newborn. Further complicating the picture is the fact that there is a greater tendency to trap the medication in the upper airway of an infant such that you really have to greatly increase the dose to the nebulizer to treat an infant so it might take 6 mg of Terbutaline in the nebulizer to give an infant the same dose per kg of body weight that an adult would receive with 2 mg of drug in the nebulizer. Basing the amount of medication you place in the nebulizer on the body weight of the patient in a linear fashion will not accurately predict dose delivery to the patient's lungs as they are really inversely related at best. Aerosolized medication dosing is further complicated by the variety of devices used to create the aerosol. There is no simple way to compare doses unless the same nebulizer is used. A case in point is the aerosolization of Pentamidine. There are plenty of recommendations as to what dose of medication to deliver but whatever dose you choose, you must use the same nebulizer used in the study you like or your dose delivery will be different than that which was recommended, perhaps more, perhaps less, perhaps not even close to what you thought you were delivering. Particle Size vs Site of delivery To further complicate matters, the particle size produced by various nebulizers, greatly influences where the aerosol will be deposited and also determines whether it will be retained or simply exhaled. Nebulizers are frequently called efficient if a large percentage of their delivered dose is retained but this usually means that they produce larger particles that are more likely to impact in the upper airway and not be delivered to the alveoli, if indeed, that is the intended target of delivery. In the case of Pentamidine, for example, it is recommended that the Respigard II be used. The retention of the 0.9 particles is only 5.3% meaning that only 5.3% of the dose from the nebulizer is retained. This sounds inefficient and is but if one of the other nebulizers were used then the particle size would result in more of the medication being delivered to airways instead of the alveoli where you want the medicine to go. Rain-out in airways is responsible for at least some of th e complications of therapy and is thus avoided by using a nebulizer producing smaller particles even if much of the aerosol is stable enough to be exhaled again. If one wanted to increase the delivered dose a rebreathing circuit could be used but this would increase the delivered dose to a level greater than what is recommended since the dosage recommendations are made assuming the intentional inefficiency of the the Respigard II.
Intubated patients
Nebulizers and metered dose inhalers have been used with intubated and mechanically ventilated patients. Factors influencing delivery include whether a continuous or inspiration-only nebulizer is used, where the nebulizer is placed in the circuit, and whether a nebulizer or a metered dose inhaler is used. Ventilator settings also influence drug delivery. In general, intubated patients will get less lung deposition and retention than non-intubated patients so dosing has to be adjusted accordingly. So what gives? If you've gotten the idea that it's a joke to pretend that medications can be precisely delivered by aerosol then you have the right idea. Given the many confounding factors influencing drug delivery, the only real ways to sensibly choose a dose is to use secondary indicators such as response to therapy (in the case of bronchodilators) or perhaps measurement of drug levels in serum or urine in the case of Pentamidine. Perhaps it would be more sensible if medications prepared for aerosol delivery were available in standard solutions with no particular dosage ordered and actual dose usage determined strictly on the basis of response.
References
Patel P, Mukai D, Wilson AF: Dose-response effects of two sizes of monodisperse isoproterenol in mild asthma. ARRD (1990 Feb) 141(2): 357-60.
Simonds AK, Newman SP, Johnson MA, Talaee N, Lee CA, Clarke SW: Alveolar targeting of aerosol pentamidine. Toward a rational delivery system. ARRD (1990 Apr) 141(4 Pt 1):827-9.
Kim CS, Trujillo D, Sackner MA: Size aspects of metered-dose inhaler aerosols. ARRD (1985 Jul) 132(1):137-42.
Ilowite JS, Baskin MI, Sheetz MS, Abd AG: Delivered dose and regional distribution of aerosolized pentamidine using different delivery systems. Chest (1991 May) 99(5):1139-44.
Hiller C, Mazumder M, Wilson D, Bone R: Aerodynamic size distribution of metered-dose bronchodilator aerosols. ARRD (1978 Aug) 118(2):311-7.
Peters JA: Humidity and Aerosol Therapy, in Spearman CB, Sheldon RL, Egan DF: Egan's Fundamentals of Respiratory Therapy, 4th edition, The C.V. Mosby Co., 1982.
Hess D, Daugherty A, Simmons M: The Volume of Gas Emitted from Metered Dose Inhalers, abstract, Resp Care, (1991 Nov), 36(11):1320.
ink JB, Cohen NH, Covington J, Mahlmeister MJ: Titration for Optimal Do se Response to Bronchodilators Using MDI and Spacer in Ventilated Adults, abstract, Resp Care, (1991 Nov), 36(11):1321.
Don Elton
Lexington, South Carolina
http://www.lexingtonpulmonary.com
Pressure, Flow, Resistance
December 05, 2009, 19:38
Pressure, Flow, and Resistance Measurement
By Donald R. Elton, MD, FCCP
Lexington Pulmonary and Critical Care
Introduction
To study hemodynamics, it is necessary that you understand what you are measuring. Most hemodynamic measurements are based upon measuring pressures, flows, and resistances.
Pressure
Pressure is defined by physicists as force divided by area. Force can be thought of as mass or weight in simple terms. A given force applied to a small area will result in more pressure than that same force applied over a larger area. This is the basis for using snow shoes that spread out the weight of a man or woman over a larger area of snow to decrease the pressure applied to the snow thus preventing the snow-walker from falling into the snow.
Typical units for pressure include cm H2O and mm Hg which refer to the amount of pressure necessary to raise a column of a given height of either water or mercury. Hemodynamic pressures can be measured by three methods, column methods, occlusion methods, or transducer methods. In a column method, a column of fluid with the top open to the atmosphere is attached to tubing that leads to the place where you want to measure pressure.
Blood pressure was first measured, for example, by sticking a hollow cane pole into the carotid artery of a horse and watching to see how high in the pole the blood rose. Such a blood pressure might be measured in units of feet of blood or cm of blood or whatever.
Central venous pressure can be measured by the column method by using a vertical tube filled with water or IV fluid and attaching it to a catheter that's inserted into the right atrium and seeing how high the water or IV fluid rises in the column which usually has marks for cm of water (cm H2O). The column method has the advantage of low cost but the disadvantage that it can normally only be used to measure things of low pressure so the column size can be limited to something that would fit in the room with the patient.
The occlusion method of pressure measurement is how a sphygmomanometer (blood pressure cuff) works. The cuff is pumped up until flow is stopped and you note the pressure required on a gauge and assume that the occlusion pressure equals the vascular pressure you're interested in.
A transducer is an electrical device that converts pressure into electricity or a measurable electrical resistance. They work by the pressure of interest bending or distorting a strain gauge that changes its electrical properties based upon the degree of distortion. These are more expensive than the other methods but offer the advantage of accuracy and can be used over a wide range of pressures. They must be calibrated frequently during use and must be calibrated correctly if correct data is to be obtained from them. Some transducers can be placed directly into the vessel where pressure is to be measured but most are positioned outside of the patient and the patient's pressures are transmitted to the transducer via fluid filled non-compressible tubing. An external transducer must be placed at the same height above the floor as the place where you want to measure pressure (i.e. at the level of the heart if that's where you want to measure pressure) so the weight of the fluid conduit does not influence the pressure measured at the transducer.
Flow
Flow describes the movement of a volume fluid (gas or blood for example) over a given time. Typical units would be liters per minute or barrels per hour etc. The flow we are most frequently interested in is the cardiac output, normally expressed in liters per minute. We sometimes divide this value by a patient's body surface area (BSA) to come up with the cardiac index which is cardiac output normalized for variations in patient size. The cheapest way to measure cardiac output is to open the patient's chest and let the aortic outflow pour into a bucket for one minute. At the end of a minute you measure the volume of blood in the bucket and call that the cardiac output. This method has fallen out of clinical use. Most cardiac outputs today are measured by thermal dilution. In this method, cool water is injected into the circulation while the temperature is measured downstream. If one knows the distance downstream and can do some calculus, you can relate the rate of cooling and warming at the downstream location to the flow of blood by the temperature measuring point such that the temperature will rise and fall more quickly if the cardiac output is high. Radioactive dyes can also be used in place of cool water but cool water is cheaper, safer, and is easier to find. There are some high-tech ways to measure blood flow that are not yet in widespread clinical use and include doppler techniques and inductive plethysmography.
Resistance
Resistance describes the change in pressure that results from a given flow and is expressed in units of pressure over flow. Airway resistance would be in units of cm H2O per liter per second where cm H2O is the pressure and liters per second is the flow. The pressure part of resistance is found by subtracting the downstream pressure from the upstream pressure so you need to know three things to calculate a resistance: upstream pressure, downstream pressure, and flow. When dealing with vascular (blood vessel) resistances we normally use units of dynes.sec/cm5 by convention. To make life interesting, we first calculate a vascular resistance by taking the upstream - downstream pressures in mm Hg and then divide this result by the flow (normally cardiac output) in liters per minute. This results in a value of units mm Hg / liter / minute. To get this into the standard units of dynes.sec/cm5 we multiply the result by 80. Resistances are not measured directly but are calculated based on pressures and flows that are measured directly.
By Donald R. Elton, MD, FCCP
Lexington Pulmonary and Critical Care
Introduction
To study hemodynamics, it is necessary that you understand what you are measuring. Most hemodynamic measurements are based upon measuring pressures, flows, and resistances.
Pressure
Pressure is defined by physicists as force divided by area. Force can be thought of as mass or weight in simple terms. A given force applied to a small area will result in more pressure than that same force applied over a larger area. This is the basis for using snow shoes that spread out the weight of a man or woman over a larger area of snow to decrease the pressure applied to the snow thus preventing the snow-walker from falling into the snow.
Typical units for pressure include cm H2O and mm Hg which refer to the amount of pressure necessary to raise a column of a given height of either water or mercury. Hemodynamic pressures can be measured by three methods, column methods, occlusion methods, or transducer methods. In a column method, a column of fluid with the top open to the atmosphere is attached to tubing that leads to the place where you want to measure pressure.
Blood pressure was first measured, for example, by sticking a hollow cane pole into the carotid artery of a horse and watching to see how high in the pole the blood rose. Such a blood pressure might be measured in units of feet of blood or cm of blood or whatever.
Central venous pressure can be measured by the column method by using a vertical tube filled with water or IV fluid and attaching it to a catheter that's inserted into the right atrium and seeing how high the water or IV fluid rises in the column which usually has marks for cm of water (cm H2O). The column method has the advantage of low cost but the disadvantage that it can normally only be used to measure things of low pressure so the column size can be limited to something that would fit in the room with the patient.
The occlusion method of pressure measurement is how a sphygmomanometer (blood pressure cuff) works. The cuff is pumped up until flow is stopped and you note the pressure required on a gauge and assume that the occlusion pressure equals the vascular pressure you're interested in.
A transducer is an electrical device that converts pressure into electricity or a measurable electrical resistance. They work by the pressure of interest bending or distorting a strain gauge that changes its electrical properties based upon the degree of distortion. These are more expensive than the other methods but offer the advantage of accuracy and can be used over a wide range of pressures. They must be calibrated frequently during use and must be calibrated correctly if correct data is to be obtained from them. Some transducers can be placed directly into the vessel where pressure is to be measured but most are positioned outside of the patient and the patient's pressures are transmitted to the transducer via fluid filled non-compressible tubing. An external transducer must be placed at the same height above the floor as the place where you want to measure pressure (i.e. at the level of the heart if that's where you want to measure pressure) so the weight of the fluid conduit does not influence the pressure measured at the transducer.
Flow
Flow describes the movement of a volume fluid (gas or blood for example) over a given time. Typical units would be liters per minute or barrels per hour etc. The flow we are most frequently interested in is the cardiac output, normally expressed in liters per minute. We sometimes divide this value by a patient's body surface area (BSA) to come up with the cardiac index which is cardiac output normalized for variations in patient size. The cheapest way to measure cardiac output is to open the patient's chest and let the aortic outflow pour into a bucket for one minute. At the end of a minute you measure the volume of blood in the bucket and call that the cardiac output. This method has fallen out of clinical use. Most cardiac outputs today are measured by thermal dilution. In this method, cool water is injected into the circulation while the temperature is measured downstream. If one knows the distance downstream and can do some calculus, you can relate the rate of cooling and warming at the downstream location to the flow of blood by the temperature measuring point such that the temperature will rise and fall more quickly if the cardiac output is high. Radioactive dyes can also be used in place of cool water but cool water is cheaper, safer, and is easier to find. There are some high-tech ways to measure blood flow that are not yet in widespread clinical use and include doppler techniques and inductive plethysmography.
Resistance
Resistance describes the change in pressure that results from a given flow and is expressed in units of pressure over flow. Airway resistance would be in units of cm H2O per liter per second where cm H2O is the pressure and liters per second is the flow. The pressure part of resistance is found by subtracting the downstream pressure from the upstream pressure so you need to know three things to calculate a resistance: upstream pressure, downstream pressure, and flow. When dealing with vascular (blood vessel) resistances we normally use units of dynes.sec/cm5 by convention. To make life interesting, we first calculate a vascular resistance by taking the upstream - downstream pressures in mm Hg and then divide this result by the flow (normally cardiac output) in liters per minute. This results in a value of units mm Hg / liter / minute. To get this into the standard units of dynes.sec/cm5 we multiply the result by 80. Resistances are not measured directly but are calculated based on pressures and flows that are measured directly.