Measurement of Vapor Pressure and Saturated Vapor Pressure

The following description is intended to provide an understanding of how, in principle, the SVP of a potent inhaled volatile anesthetic agent could be measured in a simple laboratory experiment and demonstrate the pressure that a vapor can exert. Figure 3-1, A, shows a simple (Fortin) barometer, which is essentially a long, glass mercury-filled test tube inverted to stand with its mouth immersed in a trough of mercury. When the barometer tube is first made vertical, the mercury column in the tube falls to a certain level, leaving a so-called Torricellian vacuum above the mercury meniscus. In this system, the pressure at the surface of the mercury in the trough is due to the atmosphere. In a communicating system of liquids, the pressures at any given depth are equal; therefore the pressure at the surface of the mercury in the trough is equal to the pressure exerted by the column of mercury in the vertical tube. In this example, atmospheric pressure is said to be equivalent to 760 mm Hg, because this is the height of the column of mercury in the barometer tube.

In Figure 3-1, B, sevoflurane liquid is introduced at the bottom of the mercury column. Being less dense than mercury, it rises to the top and evaporates into the space created by the Torricellian vacuum. The sevoflurane vapor exerts pressure and causes an equivalent decrease in the height of the mercury column. If liquid sevoflurane is added until a small amount remains unevaporated on the top of the mercury meniscus (Fig. 3-1, C), the space above the column must be fully saturated with vapor; the pressure now exerted by the vapor is the SVP of sevoflurane at that temperature, and adding more liquid sevoflurane will not affect the vapor pressure. If this experiment is repeated at different temperatures, a graph can be constructed that plots SVP against temperature. Such curves for some of the potent inhaled volatile anesthetic agents are shown in Figure 3-2. Contemporary technologies for measuring the partial pressures or SVPs of gases and vapors are described in Chapter 8.

Boiling Point

The SVP exerted by the vapor phase of a potent inhaled volatile agent is a physical property of that agent and depends only on the agent and the ambient temperature. The temperature at which SVP becomes equal to ambient (atmospheric) pressure and that at which all the liquid agent changes to the vapor phase (i.e., evaporates) is the boiling point of that liquid. Water boils at 100° C at 1 atm because at 100° C, the SVP of water is 760 mm Hg. The most volatile of the agents are those with the highest SVPs at room temperature. At any given temperature, these agents also have the lowest boiling points: desflurane and diethyl ether boil at 22.9° C and 35° C, respectively, at an ambient pressure of 760 mm Hg. Boiling point decreases with decreasing ambient barometric pressure, such as occurs at increasing altitude.

Units of Vapor Concentration

The presence of anesthetic vapor may be quantified either as an absolute pressure, expressed in millimeters of mercury (mm Hg) (or, less commonly, kilopascals [kPa]) or in volumes percent (vol%) of the total atmosphere (i.e., volumes of vapor per 100 volumes of total gas). From Dalton’s law of partial pressures, the volumes percent can be calculated as the fractional partial pressure of the agent:

Dalton’s Law of Partial Pressures

Dalton’s law states that the pressure exerted by a mixture of gases, or gases and vapors, enclosed in a given space such as a container is equal to the sum of the pressures that each gas or vapor would exert if it alone occupied that given space or container.⁴ A gas or vapor exerts its pressure independently of the pressure of the other gases present. For example, in a container of dry air at 1 atm (760 mm Hg), with oxygen representing 21% of all gases present, the pressure exerted by the oxygen—its partial pressure—is 159.6 mm Hg (21% × 760). Consider the same air at a pressure of 760 mm Hg but fully saturated with water vapor at 37° C (normal body temperature). Because vapor pressure depends on temperature, the SVP for water at 37° C is 47 mm Hg. The pressure from oxygen is therefore now 21% of 713 (i.e., 760 − 47) mm Hg. The partial pressure of oxygen is therefore 149.7 mm Hg.

Note that volumes percent expresses the relative ratio or proportion (%) of gas molecules in a mixture, whereas partial pressure (mm Hg) represents an absolute value. Anesthetic uptake and potency are directly related to partial pressure and only indirectly to volumes percent. This distinction become more apparent when hyperbaric and hypobaric conditions are considered.

Minimum Alveolar Concentration

The minimum alveolar concentration (MAC) of a potent inhaled anesthetic agent is the concentration that produces immobility in 50% of patients who undergo a standard surgical stimulus. Used as a measure of anesthetic potency or depth, MAC is commonly expressed as volumes percent of alveolar (end-tidal) gas at 1 atm pressure at sea level (i.e., 760 mm Hg). Table 3-1 shows how MAC expressed in familiar volumes percent can be expressed as a partial pressure in millimeters of mercury. Anesthesiologists should learn to think of MAC in terms of partial pressure rather than in terms of volumes percent because the partial pressure (tension) of the anesthetic in the central nervous system is responsible for the depth of anesthesia. This concept has been advocated by Fink,⁵ who proposed the term minimum alveolar pressure (MAP), and by James and White,⁶ who suggested minimum alveolar partial pressure (MAPP). In this text, the term P_MAC1 (see Table 3-1) is used to express the partial pressure of a potent inhaled agent at a concentration of 1 MAC; thus 1 MAC of isoflurane is equivalent to a P_MAC1 of 8.7 mm Hg.

Latent Heat of Vaporization

Vaporization requires energy to transform molecules from the liquid phase to the vapor phase. This energy is called the latent heat of vaporization and is defined as the amount of heat (calories) required to convert a unit mass (grams) of liquid into vapor. For example, at 20° C the latent heat of vaporization of isoflurane is 41 cal/g. The heat of vaporization is inversely related to ambient temperature in such a way that at lower temperatures, more heat is required for vaporization. The heat required to vaporize an anesthetic agent is drawn from the remaining liquid agent and from the surroundings. As vapor is generated and heat energy is lost, the temperatures of the vaporizer and the liquid agent fall. This causes the vapor pressure of the anesthetic to decrease. If no compensatory mechanism is provided, this will result in decreased output of vapor.

Specific Heat

Specific heat is the quantity of heat (calories) required to raise the temperature of a unit mass (grams) of a substance by 1° C. Heat must be supplied to the liquid anesthetic in the vaporizer to maintain the liquid’s temperature during the evaporation process, when heat is being lost.

Specific heat is also important when it comes to vaporizer construction material. For the same amount of heat lost through vaporization, temperature changes are more gradual for materials with a high specific heat than for those with a low specific heat. Thermal capacity, defined as the product of specific heat and mass, represents the quantity of heat stored in the vaporizer body.

Also of importance is the construction material’s ability to conduct heat from the environment to the liquid anesthetic. This property is called thermal conductivity, defined as the rate at which heat is transmitted through a substance. For the liquid anesthetic to remain at a relatively constant temperature, the vaporizer is constructed from materials that have a high specific heat and high thermal conductivity. In this respect, copper comes close to the ideal; however, bronze and stainless steel have been used more recently in vaporizer construction.

Regulating Vaporizer Output: Variable Bypass Versus Measured Flow

The SVPs of halothane, sevoflurane, and isoflurane at room temperature are 243, 160, and 241 mm Hg, respectively. Dividing the SVP by ambient pressure (760 mm Hg) gives the saturated vapor concentration (SVC) as a fraction (or percentage) of 1 atm. This is an application of Dalton’s law, as discussed earlier. The SVCs of halothane, sevoflurane, and isoflurane are therefore 32%, 21%, and 31%, respectively. These concentrations are far in excess of those required clinically (Table 3-2). Therefore the vaporizer first creates a saturated vapor in equilibrium with the liquid agent; second, the saturated vapor is diluted by a bypass gas flow. This results in clinically safe and useful concentrations flowing to the patient’s breathing circuit. Without this dilution of saturated vapor, the agent would be delivered in a lethal concentration to the anesthesia circuit.

Contemporary anesthesia vaporizers are concentration calibrated, and most are of the variable bypass design. In a variable bypass vaporizer, such as those made by GE Healthcare (Tec series) and the Dräger Vapor 2000 (Dräger Medical, Telford, PA), the total fresh gas flow from the anesthesia machine flowmeters passes to the vaporizer (Fig. 3-3). The vaporizer splits the incoming gas flow between two pathways: the smaller flow enters the vaporizing chamber, or sump, of the vaporizer and leaves it with the anesthetic agent at its SVC. The larger bypass flow is eventually mixed with the outflow from the vaporizing chamber to create the desired, or “dialed in,” concentration (see Fig. 3-3).

In the now-obsolete measured flow, non-concentration-calibrated vaporizers such as the Copper Kettle (Puritan-Bennett; Covidien, Mansfield, MA) or Verni-Trol (Ohio Medical Products, Gurnee, IL), a measured flow of oxygen is set on a separate flowmeter to pass to the vaporizer, from which vapor emerges at its SVP (Fig. 3-4). This flow is then diluted by an additional measured flow of gases (oxygen, nitrous oxide, air, etc.) from the main flowmeters on the anesthesia machine. With this type of arrangement, calculations are necessary to determine the anesthetic vapor concentration in the emerging gas mixture.

With both types of vaporizing systems, there must be an efficient method to create a saturated vapor in the vaporizing chamber. This is achieved by having a large surface area for evaporation. Flow-over vaporizers (Dräger Vapor 2000 series, GE Tec series) increase the surface area using wicks and baffles. In measured flow, bubble-through vaporizers, oxygen is bubbled through the liquid agent. To increase the surface area, tiny bubbles are created by passing the oxygen through a sintered bronze disk in the Copper Kettle, for example, which created large areas of liquid/gas interface, over which evaporation of the liquid agent could quickly occur.

Calculation of Vaporizer Output

At a constant room temperature of 20° C, the SVPs of two commonly used potent inhaled agents are 160 mm Hg for sevoflurane and 238 mm Hg for isoflurane. If ambient pressure is 760 mm Hg, these SVPs represent 21% sevoflurane (160/760) and 31% isoflurane (239/760), each in terms of volumes percent of 1 atm (760 mm Hg).

A concept fundamental to understanding vaporizer function is that under steady-state conditions, if a certain volume of carrier gas flows into a vaporizing chamber over a certain period, that same volume of carrier gas exits the chamber over the same period. However, because of the addition of vaporized anesthetic agent, the total volume exiting the chamber is greater than that entering it. In the vaporizing chamber, anesthetic vapor at its SVP constitutes a mandatory fractional volume of the atmosphere (i.e., 21% in a sevoflurane vaporizer at 20° C and 760 mm Hg). Therefore the volume of carrier gas will constitute the difference between 100% of the atmosphere in the vaporizing chamber and that resulting from the anesthetic vapor. In the case of sevoflurane, the carrier gas represents 79% of the atmosphere in the vaporizing chamber at any time. Thus if 100 mL/min of carrier gas flows through a vaporizing chamber containing sevoflurane, the carrier gas represents 79% (100% − 21%) of the atmosphere and the remaining 21% is sevoflurane vapor. By simple proportions, the volume of sevoflurane vapor exiting the chamber can be calculated to be 27 mL ([100/79] × 21) when rounded to the nearest whole number.

In other words, if 100 mL/min of carrier gas flows into the vaporizing chamber, the same 100 mL of carrier gas will emerge together with 27 mL/min of sevoflurane vapor. Another way of expressing this is shown below:

Continuing the above example for sevoflurane, y is 100 mL/min, and 160/760 = x/(100 + x), from which x can be calculated as 27 mL (rounded to the nearest whole number). Conversely, if x is known, the carrier gas flow y can be calculated. At steady state, the total volume of gas leaving the vaporizing chamber is greater than the total volume that entered, the additional volume being anesthetic vapor at its SVC.

Measured Flow Vaporizers

Although measured flow vaporizers are not mentioned in the ASTM anesthesia machine standards published after 1988, it is helpful to review the function of one example, the Copper Kettle. If 1% (vol/vol) isoflurane must be delivered to the patient circuit at a total fresh gas flow rate of 5 L/min (Fig. 3-5), the vaporizer must evolve 50 mL/min of sevoflurane vapor (1% × 5000 mL) to be diluted in a total volume of 5000 mL.

In the Copper Kettle, isoflurane represents 31% of the atmosphere, assuming a constant temperature of 20° C and a constant SVP of 238 mm Hg. If 50 mL of isoflurane vapor represents 31%, the carrier gas flow (x mL) of, oxygen flow x must represent the other 69% (100% − 31%). Thus

Therefore, if 111 mL/min of oxygen is bubbled through liquid isoflurane in a Copper Kettle vaporizer, 161 mL/min of gas emerges, of which 50 mL is isoflurane vapor and 111 mL is the oxygen that flowed into the vaporizer. This vaporizer output of 161 mL/min must be diluted by an additional fresh gas flow of 4839 mL/min (5000 mL − 161 mL) to create an isoflurane mixture of exactly 1% because 50 mL of isoflurane vapor diluted in a total volume of 5000 mL gives 1% isoflurane by volume.

Although this situation is highly unlikely to occur in contemporary practice because of the obsolescence of measured flow vaporizers, if a measured flow system had to be used to deliver isoflurane, the anesthesia provider would likely set flows of 100 mL/min oxygen to the Copper Kettle and 5 L/min of fresh gas on the main flowmeters, which would result in only slightly less than 1% isoflurane (44.9/5044.9 = 0.89%). Multiples of either of the vaporizer oxygen flow and main gas flowmeter flows would be used to create other concentrations of isoflurane from the Copper Kettle. Thus a 200 mL/min oxygen flow to the vaporizer and 5000 mL/min on the main flowmeters would create approximately 1.8% isoflurane. It is important to realize that if there is oxygen flow only to the Copper Kettle vaporizer and no bypass gas flow is set on the main machine flowmeters, lethal concentrations approaching 31% isoflurane would be delivered to the anesthesia circuit, albeit at low flow rates.

Because halothane and isoflurane have similar SVPs at 20° C, the Copper Kettle flows to be set for halothane would be essentially the same as those for isoflurane when a 1% concentration of isoflurane is to be created with a Copper Kettle. A Copper Kettle arrangement on an older model anesthesia machine is shown in Figure 3-6.

Because enflurane and sevoflurane have similar vapor pressures at 20° C (175 mm Hg and 160 mm Hg, respectively), similar flow settings could be used to create approximately the same agent concentrations with a measured flow system. In the case of sevoflurane, the measured flow vaporizer contains 21% sevoflurane vapor (160/760 = 21%). The oxygen flow therefore represents the remaining 79% of the atmosphere in the Copper Kettle. If precisely 1% sevoflurane is required at a 5 L/min total rate of flow, 50 mL/min of sevoflurane vapor must be generated. If 50 mL represents 21% of the atmosphere in the vaporizer, the carrier gas flow required is 188 mL/min ([50/21] × 79).

If 188 mL/min of oxygen are bubbled through liquid sevoflurane contained in a measured flow vaporizer, 238 mL/min of gas will emerge, 50 mL/min of which is sevoflurane vapor. This must be diluted by a fresh gas flow of 4762 mL/min (5000 − 238) to achieve exactly 1% sevoflurane.

Alternatively, using the formula given previously:

where y is the oxygen flow to the measured flow vaporizer.

Setting an oxygen flow of 200 mL/min to the vaporizer and 5 L/min on the main flowmeters would result in a sevoflurane concentration of 1.01%, or ([200/79] × 21)/5253.2.

In the preceding examples, calculations of both the oxygen flow to the measured flow vaporizer and the total bypass gas flow needed to produce the desired output concentrations of vapor were required. This is not only inconvenient, it also predisposes to clinical errors that could result in serious overdose (Fig. 3-7) or underdose of anesthetic. Because of the obvious potential for error with a measured flow vaporizing system, the concurrent continuous use of an anesthetic agent analyzer with high- and low-concentration alarms would be essential for patient safety.⁷

Variable Bypass Vaporizers

In the concentration-calibrated variable bypass vaporizer, the total flow of gas arriving from the anesthesia machine flowmeters is split between a variable bypass and the vaporizing chamber containing the anesthetic agent (see Fig. 3-3). The ratio of these two flows, known as the splitting ratio, depends on the anesthetic agent, temperature, and chosen vapor concentration set to be delivered to the patient circuit.

As previously discussed, to deliver 1% sevoflurane accurately, a total incoming gas flow of 4950 mL/min must be split so that 188 mL/min flows through the vaporizing chamber and 4762 mL/min flows through the bypass. This results in a splitting ratio of 25:1 (4762/188) between the bypass flow and the vaporizing chamber flow at a temperature of 20° C. A variable bypass vaporizer set to deliver 1% sevoflurane is therefore effectively set to create a splitting ratio of 25:1 for the inflowing gas (Fig. 3-8).

Consider a concentration-calibrated, variable bypass, isoflurane-specific vaporizer set to deliver 1% isoflurane. What splitting ratio for incoming gases must this vaporizer achieve? The SVP of isoflurane at 20° C is 238 mm Hg; therefore the concentration of isoflurane vapor in the vaporizing chamber is 31% (238/760). If carrier gas flows through the vaporizing chamber at a rate of 69 mL/min, isoflurane vapor emerges at 31 mL/min and must be diluted in 3100 mL/min of total gas flow to achieve a 1% concentration because 31/3100 equals 1%. Thus, if carrier gas enters the vaporizer from the flowmeters at 3069 mL/min and is split—such that 3000 mL/min flows through the bypass and 69 mL/min flows through the vaporizing chamber—when the two flows merge, 1% isoflurane is the result. The splitting ratio is therefore 44:1 (3000/69) (Fig. 3-9).

Table 3-3 shows the splitting ratios for variable bypass vaporizers used at 20° C. To ensure complete understanding, the reader is encouraged to calculate these ratios and apply them to different total fresh gas flows arriving from the main flowmeters to the inlet of a concentration-calibrated variable bypass vaporizer. An equation for the calculation of splitting ratios is provided in the Appendix to this chapter.

The concentration-calibrated vaporizer is agent specific and must be used only with the agent for which the unit is designed and calibrated. To produce a 1% vapor concentration, an isoflurane vaporizer makes a flow split of 44:1, whereas a sevoflurane vaporizer makes a flow split of 25:1 (see Table 3-3). If an empty sevoflurane vaporizer set to deliver a 1% concentration were to be filled with isoflurane, the concentration of the isoflurane vapor emerging would be in excess of 1%. Understanding splitting ratios enables prediction of the concentration output of an empty, agent-specific, variable bypass vaporizer that has been erroneously filled with an agent for which it was not designed. The change in concentration output when one agent-specific vaporizer is filled with a different agent can be calculated as the concentration set on the vaporizer dial multiplied by the ratio of the splitting ratios at 20° C (and not as the ratio of the SVPs of the two agents). In the case of the sevoflurane vaporizer set to deliver 1% sevoflurane but filled with isoflurane, the resulting isoflurane concentration will be 1.76% isoflurane (44/25).

Control of Splitting Ratio

In a variable bypass vaporizer, the bypass flow and the vaporizing chamber flow may be thought of as two resistances in parallel. The concentration control dial is used to adjust the ratio of the two resistances to achieve the dialed-in concentration by adjusting the size of a variable orifice. That orifice may be located at the inlet of the vaporizing chamber or at the outlet. In older model vaporizers the variable orifice was located at the inlet to the vaporizing chamber (see Fig. 8-11 in Chapter 8 for an example). In contemporary vaporizers (e.g., GE Healthcare Tec 5; Dräger Medical Vapor 19.n series) the orifice is located at the outlet of the chamber (see Fig. 3-19). The splitting ratios discussed in the previous section describe the effective flow split for the fresh gas entering the vaporizer but not where the split is achieved (i.e., whether by the inlet or the outlet of the vaporizing chamber). If the split is achieved at the outlet of the vaporizing chamber, a flow of saturated vapor is metered into the bypass flow and an “exit” splitting ratio can be calculated. In Figure 3-8, to create 1% sevoflurane a controlled flow of 100 mL/min of 21% sevoflurane is mixed with the bypass flow of 2000 mL/min. The ratio of flows is 2000/100 = 20:1. Compare this with the effective flow split of 25:1 for the fresh gas entering the vaporizer from the machine flowmeters.

Similarly, in Figure 3-9, to create 1% isoflurane a controlled flow of 100 mL/min of 31% isoflurane vapor is mixed with the bypass flow of 3000 mL/min; the “exit” splitting ratio is 3000/100 = 30:1. Compare this with the effective flow split of 44:1 for the fresh gas entering the vaporizer.

The location of the variable orifice is of little importance at 1 atm pressure but may have an effect when the vaporizer is used at ambient pressures that are higher or lower than 1 atm. (see later section on Effects of Changes in Barometric Pressure).

Efficiency and Temperature Compensation

Agent-specific concentration-calibrated vaporizers must be located in the fresh gas path between the flowmeter manifold outlet and the common gas outlet on the anesthesia workstation.³ The vaporizers must be capable of accepting a total gas flow of 15 L/min from the machine flowmeters and be able to deliver a predictable concentration of vapor.³ However, as the agent is vaporized and the temperature falls, SVP also falls. In the case of a measured flow vaporizer or an uncompensated variable bypass vaporizer, this results in delivery of less anesthetic vapor to the patient circuit. For this reason, all vaporizing systems must be temperature compensated, either manually or, as in contemporary vaporizers, automatically.

Measured flow vaporizers incorporate a thermometer that measures the temperature of the liquid agent in the vaporizing chamber. A higher temperature translates to a higher SVP in this chamber. Reference to the vapor pressure curves (see Fig. 3-2) enables a resetting of either oxygen flow to the vaporizer, bypass gas flow, or both to ensure correct output at the prevailing temperature. Although tedious, such an arrangement does ensure the most accurate and rapid temperature compensation. The original Dräger Vapor vaporizer (Fig. 3-10), to be distinguished from the more recent Vapor 19.n and 2000 models fitted to contemporary Dräger workstations, is a variable bypass vaporizer that incorporates a thermometer and a grid of lines on the vaporizer control dial for temperature compensation by which the desired output concentration is matched to the temperature of the liquid agent; turning the control dial changes the size of an orifice in the bypass flow.

Most of the contemporary variable bypass vaporizers, such as the Tec series and the Dräger Vapor 19.n and 2000, achieve automatic temperature compensation via a temperature-sensitive valve in the bypass gas flow. When temperature increases, the valve in the bypass opens wider to create a higher splitting ratio so that more gas flows through the bypass and less gas enters the vaporizing chamber. A smaller volume of a higher concentration of vapor emerges from the vaporizing chamber; this vapor, when mixed with an increased bypass gas flow, maintains the vaporizer’s output at reasonable constancy when temperature changes are not extreme.

Temperature-sensitive valves have evolved in design among the different types of vaporizers. Some older vaporizers, such as the Ohio Medical Calibrated Vaporizer, had in the vaporizing chamber, a gas-filled bellows linked to a valve in the bypass gas flow (Fig. 3-11).⁸ As the temperature increased, the bellows expanded, causing the valve to open wider. Contemporary vaporizers, such as the Tec series, use a bimetallic strip for temperature compensation.⁹ This strip is incorporated into a flap valve in the bypass gas flow. The valve is composed of two metals with different coefficients of expansion, or change in length per unit length per unit change in temperature. Nickel and brass have been used in bimetallic strip valves because brass has a greater coefficient of expansion than nickel. As the temperature rises, one surface of the flap expands more than the other, causing the flap to bend in a manner that opens the valve orifice wider, increasing the bypass flow. The principle of differential expansion of metals is applied similarly in the Dräger Vapor 19.n and 2000 series vaporizers, in which an expansion element increases bypass flow and reduces gas flow in the vaporizing chamber as temperature increases.¹⁰ When temperature decreases, the reverse occurs.

The vapor pressures of the volatile anesthetics vary as a function of temperature in a nonlinear manner (see Fig. 3-2). The result is that the vapor output concentration at any given vaporizer dial setting remains constant only within a certain range of temperatures. For example, the Dräger Vapor 2000 vaporizers are specified as accurate to ±0.20 vol% or ±20% of the concentration set when they are used within the temperature range of 15° C to 35° C at 1 atm.¹¹ The boiling point of the volatile anesthetic agent must never be reached in the current variable bypass vaporizers designed for halothane, enflurane, isoflurane, and sevoflurane; otherwise, the vapor output concentration would be impossible to control and could be lethal.

Incorrect Filling of Vaporizers

Contemporary concentration-calibrated variable bypass anesthesia vaporizers are agent specific. If an empty vaporizer designed for one agent is filled with an agent for which it was not intended, the vaporizer’s output will likely be erroneous. Because the vaporizing characteristics of halothane and isoflurane (SVP of 243 and 238 mm Hg, respectively) and enflurane and sevoflurane (SVP of 175 and 160 mm Hg, respectively) are almost identical at room temperature, this problem mainly applies when halothane or isoflurane is interchanged with enflurane or sevoflurane.

Bruce and Linde¹³ reported on the output of erroneously filled vaporizers (Table 3-4). Erroneous filling affects the output concentration and, consequently, the potency output of the vaporizer. In their study, an enflurane vaporizer set to 2% (1.19 MAC) but filled with halothane delivered 3.21% (4.01 MAC) halothane. This is 3.3 times the anticipated anesthetic potency output.

To summarize, if a vaporizer specific for an agent with a low SVP, such as enflurane or sevoflurane, is misfilled with an agent that has a high SVP, such as halothane or isoflurane, the output concentration of the agent will be greater than that indicated on the concentration dial. Conversely, if a vaporizer specific for an agent with a high SVP is misfilled with an agent that has a low SVP, the output concentration of the agent will be less than that indicated on the concentration dial.

In addition, the potency of the agent concentration must be considered in a misfilling situation. A sevoflurane vaporizer set to deliver 2% sevoflurane (1 MAC) misfilled with isoflurane would produce an isoflurane concentration of 3.5% (~3 MAC).

Erroneous filling of vaporizers may be prevented if careful attention is paid to the specific agent and the vaporizer during filling. A number of agent-specific filling mechanisms analogous to the pin index safety system for medical gases are used on modern vaporizers. Liquid anesthetic agents are packaged in bottles that have agent-specific and color-coded collars (Fig. 3-12). One end of an agent-specific filling device fits the collar on the agent bottle, and the other end fits only the vaporizer designed for that liquid agent. Although well designed, these filling devices cannot entirely prevent misfilling.

A number of different filling systems are available (e.g., Quik-Fil [Abbott Laboratories, Abbott Park, IL], Key-Fill [Harvard Apparatus, Holliston, MA]). The agent-specific filling device for desflurane, SAF-T-FILL (Zeneca Pharma, Inc., Mississauga, Canada), is particularly important because a non-desflurane vaporizer must never be filled with desflurane.

Vaporization of Mixed Anesthetic Liquids

Perhaps a more likely scenario is that an agent-specific vaporizer, partially filled with the correct agent, is topped off with an incorrect agent. This situation is more complex because it is much more difficult to predict vaporizer output, and significant errors in concentration of delivered vapor can occur. Korman and Ritchie reported that halothane, enflurane, and isoflurane do not react chemically when mixed, but they do influence the extent of each other’s ease of vaporization. Halothane facilitates the vaporization of both enflurane and isoflurane and is itself more likely to vaporize in the process.¹⁴ The clinical consequences depend on the potencies of each of the mixed agents and on the delivered vapor concentrations.

If a halothane vaporizer that is 25% full is filled to 100% with isoflurane and set to deliver 1%, the halothane output is 0.41% (0.51 MAC) and the isoflurane output is 0.9% (0.78 MAC; see Table 3-5). In this case, the output potency of 1.29 MAC is not far from the anticipated 1.25 MAC (1% halothane). On the other hand, an enflurane vaporizer that is 25% full and set to deliver 2% (1.19 MAC) enflurane filled to 100% with halothane has an output of 2.43% (3.03 MAC) halothane and 0.96% (0.57 MAC) enflurane. This represents a total MAC of 3.60—more than three times the intended amount.

If a vaporizer filling error is suspected, the vaporizer should be emptied and flushed using 5 L/min of oxygen (in the case of the Tec 4), with the concentration dial set to the maximum output, until no trace of the contaminant is detected in the outflow.^15,16 The vaporizer’s temperature should then be allowed to stabilize for 2 hours before it is used clinically, and with great caution. If the contaminant is not volatile, such as with water, the vaporizer should be returned to the manufacturer for servicing.

Contemporary anesthetic vaporizers now incorporate agent-specific filling devices designed to prevent erroneous filling and to reduce contamination of the atmosphere in the operating room while the vaporizing chamber is being filled.

Filling of Vaporizers

Vaporizers should be filled only in accordance with their manufacturer’s instructions. Overfilling or tilting a vaporizer—that is, either tilting a freestanding unit or tilting the whole anesthesia machine—may result in liquid agent entering parts of the anesthesia delivery system designed for gases and vapor only, such as a vaporizer bypass. This could lead to the delivery of lethal concentrations of agent to the patient circuit. If a vaporizer has been tilted, liquid agent may have leaked into the gas delivery system. A patient must never be left connected to such a system. Once the machine has been withdrawn from clinical service, the proper procedure is to purge the vaporizer with a high flow rate of oxygen from the flowmeter of the anesthesia machine or workstation—not the oxygen flush, which bypasses the vaporizer—and with the vaporizer concentration dial set to the maximum concentration.^12,15 The maximum concentration dial setting ensures the highest possible oxygen flow through the inflow and outflow paths of the vaporizing chamber and through the bypass. A calibrated anesthetic agent analyzer is essential to check the efficacy of the flush procedure before the vaporizer is returned to clinical service. In contemporary practice, it is probably prudent to withdraw the workstation and vaporizer from clinical use until both have been declared safe by authorized service personnel.

Table 3-2 shows that 1 mL of liquid volatile agent produces approximately 200 mL of vapor at 20° C. The theoretical derivation of this volume is presented later in this chapter (see Preparation of a Standard Vapor Concentration). Thus it is easy to see how very small volumes of liquid agent entering the gas delivery system might produce lethal concentrations. For example, if 1 mL of liquid isoflurane entered the common gas tubing, some 20 L of fresh gas would be required to dilute the resulting volume of vapor (195 mL) down to a 1% (0.87 MAC) concentration.

Effect of Carrier Gas on Vaporizer Output

The carrier gas used to vaporize the volatile agent in the vaporizing chamber can also affect vaporizer output because the viscosity and density of the gas mixture change as the mixture changes. Figure 3-13 shows the output concentration from an enflurane variable bypass vaporizer set to deliver 1% enflurane. For the first 10 minutes, the carrier gas is 70% nitrous oxide and 30% oxygen and the vaporizer delivers 1% enflurane. After 10 minutes, the carrier gas is changed to nitrogen and oxygen; at approximately 20 minutes, the vaporizer output is seen to increase to a peak of about 2.6%; at 30 minutes, it decreases to 1%, at which point it stabilizes. At 40 minutes, the carrier gas is changed back to nitrous oxide and oxygen, and the vaporizer output concentration transiently decreases to 0.75%. By 55 minutes, it gradually returns to 1%. At 60 minutes, the carrier gas is changed back to nitrogen and oxygen and the vaporizer output again increases.

The effect of carrier gas on vaporizer output can be explained by the solubility of nitrous oxide in a liquid volatile anesthetic agent. Thus, when nitrous oxide and oxygen begin to enter the vaporizing chamber, some nitrous oxide dissolves in the liquid agent, and the vaporizing chamber’s output decreases until the liquid agent has become saturated with nitrous oxide. Conversely, when nitrous oxide is withdrawn as the carrier gas, the nitrous oxide dissolved in the liquid anesthetic comes out of solution and represents, in effect, additional nitrous oxide gas flow to the vaporizing chamber.

The solubility of nitrous oxide in liquid anesthetics is approximately 4.5 mL per milliliter of liquid anesthetic¹⁷; therefore 100 mL of enflurane liquid, when fully saturated, can dissolve approximately 450 mL of nitrous oxide. When nitrous oxide is discontinued because it is added (by coming out of solution) to the vaporizing chamber flow over a brief period, the volume of nitrous oxide causes the observed increase in vaporizer output concentration.

Dräger vaporizers are calibrated using air as the carrier gas. When 100% oxygen is used, the output concentration, when compared with air, increases by 10% of the set value and by not more than 0.4 vol%. When a mixture of 30% oxygen and 70% nitrous oxide is used, the concentration falls by 10% of the set value at most and by not more than 0.4 vol%.¹¹ Tec series vaporizers are calibrated at 21° C with oxygen as the carrier gas. In these vaporizers, when air or nitrous oxide is the carrier gas, the output concentration is less than with oxygen. The effect is greatest when nitrous oxide is the carrier gas, but using nitrous oxide decreases the required concentration of volatile agent, thereby somewhat mitigating the decrease in output concentration.¹⁸

Effects of Changes in Barometric Pressure

Vaporizers are most commonly used at an ambient pressure of 760 mm Hg (1 atm at sea level). They may, however, be used under hypobaric conditions, such as at high altitudes, or under hyperbaric conditions, such as in a hyperbaric chamber.⁵

Vaporizing Chamber Flow Controlled at Inlet

When used at pressures above or below 1 atm, the location of the variable orifice controlling flow into or out from the vaporizing chamber affects vaporizer performance.

Vaporizing Chamber Flow Controlled at Outlet

The potency output of a variable bypass vaporizer in which the vaporizing chamber gas flow is controlled by a variable orifice located at the vaporizing chamber outlet is unaffected by changes in barometric pressure. With this design, the exit split ratio will apply and is unchanged. Consider the design of a vaporizer used to create 1% sevoflurane. In Figure 3-8, the exit split ratio to create 1% sevoflurane is 20:1. Under the same hypobaric conditions as in the previous section, PB is 500 mm Hg. In the vaporizing chamber, the sevoflurane vapor concentration is 160/500 = 32% by volume. A flow of 100 mL/min of 32% sevoflurane is mixed with a bypass flow of 2000 mL/min; the sevoflurane concentration will be 32/2100 = 1.52% by volume. The partial pressure of sevoflurane will be 1.52% × 500 = 7.6 mm Hg, which is the same partial pressure/potency as 1% sevoflurane at 760 mm Hg.

Under hyperbaric conditions of 2280 mm Hg, in the vaporizing chamber the sevoflurane vapor concentration is 160/2280 = 7% by volume. A flow of 100 mL/min of 7% sevoflurane is mixed with a bypass flow of 2000 mL/min. The sevoflurane concentration will be 7/2100 = 0.33% by volume.

Arrangement of Vaporizers

Very old, now-obsolete models of anesthesia machines had up to three variable bypass vaporizers arranged in series, making it possible for carrier gas to pass through each vaporizer, albeit all through a bypass chamber, to reach the common gas outlet of the anesthesia machine. Without an interlock system, which permits only one vaporizer to be in use at any one time, it was possible to have all three vaporizers turned on simultaneously. Apart from potentially delivering an anesthetic overdose to the patient, the agent from the upstream vaporizer could contaminate agents in any downstream vaporizer.¹⁶ During subsequent use, the output of any downstream vaporizer would be contaminated. The resulting concentrations in the emerging gas and vapor mixture would be indeterminate and possibly lethal.

When such a serial arrangement of vaporizers was present, it was important to ensure that a vaporizer designed for a less volatile agent—such as methoxyflurane, with a low SVP—was not placed downstream relative to more volatile anesthetics, such as halothane. In such a case, halothane upstream would dissolve in the less volatile agent downstream. If during subsequent use the methoxyflurane vaporizer were set to deliver 1% (6 MAC), more than 6% halothane (8 MAC) could have been delivered from the methoxyflurane vaporizer.¹⁹ The most desirable serial sequence of vaporizers from flowmeter manifold to common gas outlet was therefore methoxyflurane, sevoflurane, enflurane, isoflurane, then halothane.

These principles would also apply if a freestanding vaporizer were to be placed in series between the machine common gas outlet and the breathing circuit. Such arrangements, configured by the user and never by the machine manufacturer, are potentially dangerous and should not be used.²⁰ In addition to the contamination problem by agents upstream, such vaporizers are more easily tipped over, and use of the machine oxygen flush with the freestanding vaporizer turned on could pump a bolus of agent into the patient circuit, while disconnection of the vaporizer tubing could result in hypoxia in the patient circuit (see Chapter 30). Nevertheless, freestanding vaporizers are routinely used in conjunction with pump oxygenators for cardiopulmonary bypass. In such situations, the vaporizer should be securely mounted to the pump (see Fig. 3-16), and correct directional flow of gas through the vaporizer must be confirmed. Such vaporizers are subject to the same routine maintenance and calibration procedures as are all other anesthesia vaporizers.

With contemporary anesthesia workstations, only one vaporizer can be on at any given time. To prevent cross-contamination of the contents of one vaporizer with those of another, the ASTM standards require that a system be in place to isolate the vaporizers from one another and prevent gas from passing through more than one vaporizing chamber.³ This specification is met by an interlock system. All contemporary anesthesia workstations incorporate manufacturer-specific interlock/vaporizer exclusion systems; these are described in subsequent sections concerning specific vaporizer models.

Calibration and Checking of Vaporizer Outputs

Vaporizers should be serviced according to the manufacturer’s instructions, and their output should be checked to ensure that no malfunction exists. The vaporizer dial is set to deliver a certain concentration of the agent; the actual output concentration is measured by a calibrated anesthetic agent analyzer that analyzes gas sampled at the common gas outlet of the anesthesia machine. Currently available methods for practical vapor analysis are described in Chapter 8.

Preparation of a Standard Vapor Concentration

Although the physical methods for measurement described in Chapter 8 may be used to check vaporizer output, the agent analyzers themselves require calibration. For this purpose, standard vapor concentrations must be prepared and made available for use as the calibration gas standards. Standard mixtures are available from commercial suppliers.

Consider the preparation of a standard mixture of isoflurane in oxygen. Avogadro’s volume states that 1 g molecular weight of a gas or vapor will occupy 22.4 L at standard temperature and pressure (STP, which is 760 mm Hg pressure, 0° C, or 273 K). Because the molecular weight of isoflurane is 184.5 Da, it would occupy 22.4 L at STP, and 1 g would occupy 22.4/184.5 L.

Charles’ law states that the volume of a fixed mass of gas is proportional to absolute temperature if pressure remains constant; therefore 1 g of isoflurane occupies 0.13 L ([22.4 L/184.5 g] × [293 K/273 K]) at 20° C, or 293 K). One milliliter of liquid isoflurane weighs 1.5 g (specific gravity of 1.5; see Table 3-2); 1 mL of liquid isoflurane therefore generates 0.195 L of vapor ([22.4/184.5] × [293/273] × 1.5). Thus, 1 mL of liquid isoflurane produces 195 mL of vapor at 20° C.

By this type of calculation, a predetermined volume of liquid agent can be measured accurately and vaporized in a chamber of known volume to produce a calibration-standard gas mixture. As previously discussed, if a vaporizer is tipped on its side and liquid agent enters the bypass chamber or fresh gas piping, small volumes of liquid agent can generate very large volumes of vapor.

The above calculation by which volumes of liquid agent can be related to volumes of vapor at known temperatures and ambient pressures can be used to calculate the cost of an inhaled anesthetic. For example, an anesthetic of 1% isoflurane in 2 L/min N₂O and 1 L/min O₂ requires delivery of 30 mL/min (1% × 3 L), or 1800 mL/h of isoflurane vapor. This can be expressed as 1800/195, or 9.23 mL/h of liquid isoflurane. If, for example, a 100-mL bottle of isoflurane costs $10, the isoflurane anesthetic cost would be $0.92/h ([9.23/100] × $10).

Fresh Gas Flow Rate

The output of a concentration-calibrated vaporizer is normally a function of fresh gas inflow rate. Because 1 mL of liquid agent produces approximately 200 mL of vapor, the hourly consumption of liquid agent can be estimated by the following formula:

The derivation of this approximation is as follows:

Hence, the factor of 3 is used in the formula. Thus an isoflurane vaporizer set to deliver 1.5% at a flow rate of 4 L/min consumes approximately 18 mL/h (3 × 1.5 × 4) of liquid agent.

The output concentrations of contemporary concentration-calibrated vaporizers are virtually independent of the fresh gas flow rate when used with flows and vaporizer settings in the normal clinical range. At high concentration settings and with high fresh gas flows, output is slightly less than that set on the dial. Under these conditions, evaporation of the agent may be incomplete and temperature in the vaporizing chamber will fall. Thus, saturation of gas flowing through the vaporizing chamber is incomplete and output falls. The effects of flow rate on vaporizer output are shown for the Dräger Vapor 19.1 (Fig. 3-17). Again, note that these effects are of little clinical significance in most situations.

Fresh Gas Composition

As previously noted, changing the composition of the carrier gas, especially by adding or removing nitrous oxide, temporarily alters vaporizer output.¹⁷ In the case of nitrous oxide, this effect is mainly due to solubility of nitrous oxide, although changes in gas density and viscosity also contribute to changes in output by affecting the flow split between vaporizing chamber and bypass gas flows.

GE vaporizers are calibrated using 100% oxygen as the carrier gas.¹⁸ If the carrier gas is changed to air or nitrous oxide, the vapor output decreases at low flow rates. At high flow rates and low concentration dial settings, the output may increase slightly.

Dräger Vapor 19.n vaporizers are calibrated with air as the carrier gas.¹² If 100% oxygen is used, the delivered output concentration is approximately 5% to 10% greater than the dial setting (air calibration value). When a mixture of nitrous oxide and oxygen (70:30) is used, the output is 5% to 10% lower than the dial setting. In this model of vaporizer, deviations from the dial setting increase with lower fresh gas flows, small amounts of agent in the vaporizing chamber, higher concentration dial settings, and extreme changes in the composition of the carrier gas.¹¹

Effects of Temperature

As previously described, concentration-calibrated vaporizers are temperature compensated. The effects of changes in temperature are negligible under usual conditions of use. However, if the ambient temperature exceeds the vaporizer’s specified range of performance, the vaporizer’s output may become high. For example, the Dräger Vapor 19.n vaporizer is specified as accurate between 15° C and 35° C.¹² This is because as temperature increases, the vapor pressure of the anesthetic increases in a nonlinear manner, whereas the temperature compensation is linear. Indeed, the output may become unpredictable and uncontrolled if the boiling point of the agent is reached. Conversely, if the temperature falls below the specified range for use, the output may be unpredictably low.

Fluctuating Backpressure

A problem with older model vaporizers was that fluctuating or intermittent backpressure, the so-called pumping effect, may be applied to the vaporizer by changes in pressure downstream. Such pressure changes could be caused by intermittent positive-pressure ventilation (IPPV) in the patient circuit or operation of the oxygen flush control. These changes could produce changes in gas flow distribution within the vaporizer, which could lead to increased output if no compensatory mechanism existed. The effects of intermittent pressurization are greatest at low flow rates, low concentration settings, when small amounts of liquid agent are present in the vaporizer, and with large and rapid changes in pressure. Higher flow rates, higher dial settings, larger volumes of liquid agent in the vaporizer, and smaller, less frequent changes in pressure minimize the pumping effect.

Of the several explanations offered for the pumping effect, the most probable is that during pressurization, gas is compressed in the vaporizer in both the vaporizing chamber and the bypass. When the pressure decreases, anesthetic vapor leaves the vaporizing chamber, through both the normal exit pathway and the vaporizing chamber inlet, to enter the bypass flow. The intermittent addition of vapor to the bypass flow results in the observed intermittent increase in vaporizer output.

Contemporary vaporizers incorporate certain design features that minimize the significance of the pumping effect (discussed in the following section). Some older models, such as the Ohio Medical calibrated vaporizers, have a check valve in the vaporizer outlet to prevent transmission of increases in downstream pressure (see Fig. 3-11).⁸ Certain models of GE anesthesia machines use a check valve just upstream of the common gas outlet to prevent retrograde transmission of downstream pressures (see Chapter 2). However, while the check valve is closed, the pressure upstream of it—and hence, that in the vaporizers—increases because of continuous fresh gas flow from the machine flowmeters. Thus the use of check valves can limit, but not totally eliminate, the pumping effect. For this reason, the newest anesthesia machine models do not use check valves in their design (see Chapter 2).

Contemporary Vaporizers

Desflurane Vaporizers

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