Rik Carette

Desflurane consumption during automated closed-circuit delivery is higher than when a conventional anesthesia machine is used with a simple vaporizer-O2-N2O fresh gas flow sequence

BackgroundThe Zeus® (Dräger, Lübeck, Germany), an automated closed-circuit anesthesia machine, uses high fresh gas flows (FGF) to wash-in the circuit and the lungs, and intermittently flushes the system to remove unwanted N2. We hypothesized this could increase desflurane consumption to such an extent that agent consumption might become higher than with a conventional anesthesia machine (Anesthesia Delivery Unit [ADU®], GE, Helsinki, Finland) used with a previously derived desflurane-O2-N2O administration schedule that allows early FGF reduction.MethodsThirty-four ASA PS I or II patients undergoing plastic, urologic, or gynecologic surgery received desflurane in O2/N2O. In the ADU group (n = 24), an initial 3 min high FGF of O2 and N2O (2 and 4 L.min-1, respectively) was used, followed by 0.3 L.min-1 O2 + 0.4 L.min-1 N2O. The desflurane vaporizer setting (FD) was 6.5% for the first 15 min, and 5.5% during the next 25 min. In the Zeus group (n = 10), the Zeus® was used in automated closed circuit anesthesia mode with a selected end-expired (FA) desflurane target of 4.6%, and O2/N2O as the carrier gases with a target inspired O2% of 30%. Desflurane FA and consumption during the first 40 min were compared using repeated measures one-way ANOVA.ResultsAge and weight did not differ between the groups (P > 0.05), but patients in the Zeus group were taller (P = 0.04). In the Zeus group, the desflurane FA was lower during the first 3 min (P < 0.05), identical at 4 min (P > 0.05), and slightly higher after 4 min (P < 0.05). Desflurane consumption was higher in the Zeus group at all times, a difference that persisted after correcting for the small difference in FA between the two groups.ConclusionAgent consumption with an automated closed-circuit anesthesia machine is higher than with a conventional anesthesia machine when the latter is used with a specific vaporizer-FGF sequence. Agent consumption during automated delivery might be further reduced by optimizing the algorithm(s) that manages the initial FGF or by tolerating some N2 in the circuit to minimize the need for intermittent flushing.

Development and performance of a two-step desflurane-O2/N2O fresh gas flow sequence

STUDY OBJECTIVE To determine if the previously described single-step O(2)/N(2)O fresh gas flow (FGF) sequence could be combined with a simple desflurane vaporizer (F(D)) sequence to maintain the end-expired desflurane (F(A)des) at 4.5% with the anesthesia delivery unit machine (ADU Anesthesia Machine(R); General Electric, Helsinki, Finland). DESIGN Prospective randomized clinical study. SETTING Onze Lieve Vrouw Hospital, Aalst, Belgium, a large teaching hospital. PATIENTS 42 ASA physical status I and II patients requiring general endotracheal anesthesia and controlled mechanical ventilation. INTERVENTIONS In 18 patients undergoing general anesthesia with controlled mechanical ventilation, F(D) was determined to maintain F(A)des at 4.5% with O(2)/N(2)O FGF of two and 4 L per minute for three minutes and 0.3 and 0.4 L per minute thereafter. Using the same FGF sequence, we prospectively tested the F(D) schedule that approached this observed F(D) pattern with the fewest possible adjustments in another 24 patients. MAIN RESULTS F(D) of 6.5% for 15 minutes followed by 5.5% thereafter approximated the observed F(D) course well. When it was prospectively tested, the median (25th, 75th percentiles) performance error was -1% (-5.1%, 5.2%); absolute performance error, 7.1% (3.9%, 9.5%); divergence, -6.6% per hour (23.1%, 3.1%/h); and wobble, 2.2% (1.8%, 3.2%). Because F(A)des increased above 4.9%, F(D) was decreased in 5 patients after 23 minutes (0.5% decrement once or twice); in two patients, F(D) was temporarily increased. In one patient, FGF was temporarily increased because the bellows volume became insufficient. CONCLUSIONS One O(2)/N(2)O rotameter FGF setting change from 6 to 0.7 L per minute after three minutes and one desflurane F(D) change from 6.5% to 5.5% after 15 minutes maintained anesthetic gas concentrations within predictable and clinically acceptable limits during the first 20 minutes.

Can modern infrared analyzers replace gas chromatography to measure anesthetic vapor concentrations

BackgroundGas chromatography (GC) has often been considered the most accurate method to measure the concentration of inhaled anesthetic vapors. However, infrared (IR) gas analysis has become the clinically preferred monitoring technique because it provides continuous data, is less expensive and more practical, and is readily available. We examined the accuracy of a modern IR analyzer (M-CAiOV compact gas IR analyzer (General Electric, Helsinki, Finland) by comparing its performance with GC.MethodsTo examine linearity, we analyzed 3 different concentrations of 3 different agents in O2: 0.3, 0.7, and 1.2% isoflurane; 0.5, 1, and 2% sevoflurane; and 1, 3, and 6% desflurane. To examine the effect of carrier gas composition, we prepared mixtures of 1% isoflurane, 1 or 2% sevoflurane, or 6% desflurane in 100% O2 (= O2 group); 30%O2+ 70%N2O (= N2O group), 28%O2 + 66%N2O + 5%CO2 (= CO2 group), or air. To examine consistency between analyzers, four different M-CAiOV analyzers were tested.ResultsThe IR analyzer response in O2 is linear over the concentration range studied: IR isoflurane % = -0.0256 + (1.006 * GC %), R = 0.998; IR sevoflurane % = -0.008 + (0.946 * GC %), R = 0.993; and IR desflurane % = 0.256 + (0.919 * GC %), R = 0.998. The deviation from GC calculated as (100*(IR-GC)/GC), in %) ranged from -11 to 11% for the medium and higher concentrations, and from -20 to +20% for the lowest concentrations. No carrier gas effect could be detected. Individual modules differed in their accuracy (p = 0.004), with differences between analyzers mounting up to 12% of the medium and highest concentrations and up to 25% of the lowest agent concentrations.ConclusionM-CAiOV compact gas IR analyzers are well compensated for carrier gas cross-sensitivity and are linear over the range of concentrations studied. IR and GC cannot be used interchangeably, because the deviations between GC and IR mount up to ± 20%, and because individual analyzers differ unpredictably in their performance.

Severe ADU desflurane vaporizing unit malfunction.

To the Editor:—A 77-yr-old man undergoing insertion of a J-splint for renal obstruction received general anesthesia delivered with an ADU anesthesia machine (Anesthesia Delivery Unit; Datex-Ohmeda, Stockholm, Sweden). A 5% desflurane vaporizer concentration setting with an O2/N2O mixture (2 and 3 l/min, respectively) resulted in stable inspired and expired desflurane concentrations (fig. 1). Immediately after lowering the fresh gas flow (FGF) to 0.35 l/min O2 and 0.35 l/min N2O, and while maintaining the same vaporizer concentration setting, a dramatic increase in inspired and expired desflurane concentrations to about 14% (15:45) was noticed, as shown in figure 1. The duration of this high concentration was short-lived ( 2 min) and did not trigger an alarm; the vaporizer concentration setting was decreased to 4.5% and was left unchanged throughout the remainder of the procedure (until 16:13). After a rapid decrease of the inspiratory and end-expiratory desflurane concentrations to about 7–8.5%, the concentrations started to increase again, leading to a gradual decrease in blood pressure. Because vaporizer malfunction was suspected, the FGF was increased to 5 l/min O2/N2O and was decreased again (to the previous settings) within a period of 1 min (15:56). Inspired and expired concentrations were noticed to decrease and increase again. This maneuver was repeated at 16:03, confirming that indeed something was wrong with the vaporizer output with the use of lower FGF (0.7 l/min). At 16:05, the FGF was therefore increased to 5 l/min. Vaporizer output itself was then checked at low FGF (0.7 l/min) by interrupting ventilation and having the sampling line of the multigas analyzer (Compact Airway Module M-CAiOV, Datex-Ohmeda, Helsinki, Finland) sample gases leaving the common gas outlet (16:10). Desflurane output read 14.5% (at 16:10) during the use of low flows, but matched the dialed 4.5% (16:12) when the FGF was increased again to its previous settings (O2/N2O mixture, 2 and 3 l/min, respectively). An alarm message appeared (“Service fresh gas unit.”). Anesthesia was continued for a few more minutes for the remainder of the surgical procedure with desflurane and high FGF (5 l/min), and the patient was allowed to awaken without further incident. On the same day of our observation, a similar case was reported by the Anesthesiology Discussion Group on GASNet.† With FGF of 0.6 l/min O2 and 0.6 l/min air and a desflurane dial setting at 8%, the desflurane concentration on the agent analyzer display slowly approached 4.5–5.5%. Then, without warning, the desflurane concentration suddenly increased to 15%. It is unclear whether the events were the same as in our case. The ADU vaporizing unit is an electronically controlled, flow-over, variable bypass, and measured flow vaporizer, and its mechanism of action and performance have been described recently. Vaporizer output increased with lower FGF, with the largest error with FGF of 0.2 l/min (4.3 and 7.3% absolute output measured with 3% and 6% dialed, respectively, in a single instance). In the current case, however, substantially higher total FGFs (0.7 l/min) were used. Very preliminary testing by Datex-Ohmeda indicates that the one-way valve that prevents backflow of saturated vapor from the cassette via inspiratory channel toward the bypass channel may have failed to close after lowering the FGF (fig. 2). This problem may be more significant when desflurane is used because the pressure in the desflurane Aladin cassette (Datex-Ohmeda, Stockholm, Sweden) may exceed 1 atm because of its high vapor pressure when the temperature is greater than 22.8°C (boiling point of desflurane at 1 atm pressure). A similar problem in 1999 prompted a redesign of this one-way valve and an upgrading of all ADU anesthesia machines in service worldwide (Mr. Ola Lassborn, Quality Manager, Datex-Ohmeda, Stockholm, Sweden, verbal personal communication, March 2003). Despite the new design, this report suggests a continued problem with this valve with the possible delivery of unintended high concentrations of inhaled anesthetics. It is unclear whether the valve still has a design problem or whether only a few defective valves exist (a manufacturing issue). This safety issue is being addressed by Datex-Ohmeda. For now, it is advisable to monitor carefully for excessive agent concentrations when using the ADU Datex-Ohmeda anesthesia machines, especially if desflurane is administered.

Inhaled anaesthetics and nitrous oxide: Complexities overlooked: things may not be what they seem.

This review re-examines existing pharmacokinetic and pharmacodynamic concepts of inhaled anaesthetics. After showing where uptake is hidden in the classic FA/FI curve, it is argued that target-controlled delivery of inhaled agents warrants a different interpretation of the factors affecting this curve (cardiac output, ventilation and blood/gas partition coefficient). Blood/gas partition coefficients of modern agents may be less important clinically than generally assumed. The partial pressure cascade from delivered to inspired to end-expired is re-examined to better understand the effect of rebreathing during low-flow anaesthesia, including the possibility of developing a hypoxic inspired mixture despite existing machine standards. Inhaled agents are easy to administer because they are transferred according to partial pressure gradients. In addition, the narrow dose–response curves for the three end points of general anaesthesia (loss of response to verbal command, immobility and autonomic reflex control) allow the clinical use of MACawake, MAC and MACBAR to determine depth of anaesthesia. Opioids differentially affect these clinical effects of inhaled agents. The effect of ventilation–perfusion relationships on gas uptake is discussed, and it is shown how moving beyond Rileys useful but simplistic model allows us to better understand both the concept and the magnitude of the second gas effect of nitrous oxide. It is argued that nitrous oxide remains a clinically useful drug. We hope to bring old (but ignored) and new (but potentially overlooked) information into the educational and clinical arenas to stimulate discussion among clinicians and researchers. We should not let technology pass by our all too engrained older concepts.

Sevoflurane or desflurane: Which one is more expensive?

To the Editor, The report by Tabing et al. describes how limiting the accessibility of cost-prohibitive drugs reduces overall anesthetic drug costs. Their article is timely given the decreasing availability of healthcare dollars (and euros!). Before referring to desflurane as a costly agent, however, we have to ensure that all aspects of drug delivery have been taken into account. While desflurane may be the more expensive inhaled agent, cost differences do depend on the manner in which the drug is delivered and titrated to effect. First, there is no detailed information in the report on the actual fresh gas flows used. Second, was the synergy between opioids and potent inhaled anesthetics to provide unconsciousness, akinesia, and autonomic reflex control maximally exploited? Properly titrated opioids reduce the concentrations of the inhaled agents to achieve these clinical end goals by 15, 50, and 70%, respectively. Third, what anesthesia machine technology was used during the study? Automated low-flow anesthesia machines can drastically reduce desflurane usage. In target-controlled low-flow mode, the Aisys (GE, Madison, WI, USA), the FLOW-i (Maquet, Solna, Sweden), and the Zeus (Dräger, Lubeck, Germany) use maintenance fresh gas flows of 500, 300, and 180 mL min (closed-circuit anesthesia with O2/air), respectively. After one hour, the mean (SD) usage of desflurane with a target concentration of 6% is 21.6 (1.9) mL and 14.2 (2.2) mL with the Aisys and Zeus, respectively. Fourth, the report does not mention whether N2O was used. While the effect of N2O on desflurane usage is complex and can be time dependent, N2O does reduce desflurane usage because the MAC of N2O and desflurane are additive. 6 When desflurane is used with O2/N2O instead of O2/air to maintain 1.3 MAC, target-controlled low-flow delivery with the FLOW-i reduces desflurane usage after one hour from an average of 26.6 to 7.4 mL, a 72% reduction (unpublished observations, study in progress). For desflurane to be less expensive than sevoflurane at equivalent MAC values, the cost of 1 mL of desflurane has to be approximately one-third or less of the cost of sevoflurane. How Tabing et al. calculated the cost of desflurane and sevoflurane to be

Monitoring anaesthetic gas concentrations in the exhaust of the cardiopulmonary bypass oxygenator

13.20 and

Inhaled anaesthetics and nitrous oxide

0.63 per case, respectively, a more than 2,000% difference, is enigmatic. When the absolute amounts of agent mentioned above are considered, it can be appreciated that the difference in cost between both drugs is close to being trivial if they are used at the lower end of the fresh gas flow spectrum, considering the entire cost of a surgical procedure. It is rather a monolithic approach to limit the accessibility to desflurane by denoting it as a ‘‘costprohibitive drug’’ without having taken into account all the modalities of drug delivery. It is not the drug itself, but it is the delivery (i.e., the manner in which the agent is being used) that makes all the difference. As a profession, we have to be able to provide a more sophisticated approach to complex pharmacoeconomical questions lest we unnecessarily discard drugs whose properties may benefit our patients or a subset of patients. This letter is accompanied by a reply. Please see Can J Anesth 2016; 63: this issue.

Inhaled anaesthetics and nitrous oxide: Complexities overlooked

in the exhaust of the cardiopulmonary bypass oxygenator Editor—Nitzschke and colleagues recently studied sevoflurane plasma concentrations during cardiopulmonary bypass (CPB). The authors found no relationship between sevoflurane plasma concentrations and either sevoflurane concentrations in the exhaust of the oxygenator or bispectral index (BIS) values, prompting them to conclude that ‘Measuring the concentration of sevoflurane in the exhaust from the oxygenator is not useful for monitoring sevoflurane administration during bypass’. However, the authors failed to take into account the consequences of Henry’s law: at aconstant temperature, the amount of a given gas that dissolves in a given type and volume of liquid is directly proportional to the partial pressure of that gas in equilibrium with that liquid. Blood/gas partition coefficient changes for sevoflurane during CPB were not measured, and may have been considerable given the acute changes in blood temperature and haematocrit that routinely occur. For this reason, the partial pressure in the blood remains unknown. This is the important variable, because, like all gases, inhaled anaesthetics are transported down a partial pressure gradient (not a concentration gradient), and because their clinical effects correlate with the partial pressure. The appropriate technique to use is double headspace equilibration of blood samples, as described by many previous authors, which allows simultaneous measurement of partial pressure and solubility. – 6 To summarize, reporting plasma concentrations without blood solubility does not allow meaningful clinical recommendations to be made. By implication, trying to find a relationship between plasma sevoflurane concentration and BIS with these data is futile. Therefore we argue that the conclusions by Nitzschke and colleagues are premature: pending further evidence, it remains reasonable practice to monitor anaesthetic gas concentrations in the exhaust of the oxygenator.

Large volume N2O uptake alone does not explain the second gas effect of N2O on sevoflurane during constant inspired ventilation

This review re-examines existing pharmacokinetic and pharmacodynamic concepts of inhaled anaesthetics. After showing where uptake is hidden in the classic FA/FI curve, it is argued that target-controlled delivery of inhaled agents warrants a different interpretation of the factors affecting this curve (cardiac output, ventilation and blood/gas partition coefficient). Blood/gas partition coefficients of modern agents may be less important clinically than generally assumed. The partial pressure cascade from delivered to inspired to end-expired is re-examined to better understand the effect of rebreathing during low-flow anaesthesia, including the possibility of developing a hypoxic inspired mixture despite existing machine standards. Inhaled agents are easy to administer because they are transferred according to partial pressure gradients. In addition, the narrow dose–response curves for the three end points of general anaesthesia (loss of response to verbal command, immobility and autonomic reflex control) allow the clinical use of MACawake, MAC and MACBAR to determine depth of anaesthesia. Opioids differentially affect these clinical effects of inhaled agents. The effect of ventilation–perfusion relationships on gas uptake is discussed, and it is shown how moving beyond Rileys useful but simplistic model allows us to better understand both the concept and the magnitude of the second gas effect of nitrous oxide. It is argued that nitrous oxide remains a clinically useful drug. We hope to bring old (but ignored) and new (but potentially overlooked) information into the educational and clinical arenas to stimulate discussion among clinicians and researchers. We should not let technology pass by our all too engrained older concepts.