Development and validation of a model to calculate anesthetic agent consumption from inspired and end-expired concentrations, minute ventilation, fresh gas flow and dead space ventilation.

Anesthetic agent consumption is often calculated as the product of fresh gas flow (FGF) and vaporizer dial setting (FVAP). Because FVAP of conventional vaporizers is not registered in automated anesthesia records, retrospective agent consumption studies are hampered. The current study examines how FVAP can be retrospectively calculated from the agent's inspired (FIN) and end-expired concentration (FET), FGF, and minute ventilation (MV). Theoretical analysis of agent mass balances in the circle breathing reveals FVAP = [FIN - (dead space fraction * FIN + (1 - dead space fraction) * FET) * (1 - FGF/MV)]/(1-(1 - FGF/MV)). FIN, FET, FGF and MV are routinely monitored, but dead space fraction is unknown. Dead space fraction for sevoflurane, desflurane, and isoflurane was therefore determined empirically from an unpublished data set of 161 patient containing FVAP, FIN, FET, MV and FGF ranging from 0.25 to 8 L/min delivered via an ADU® (GE, Madison, WI, USA). Dead space fraction for each agent was determined empirically by having Excel's solver function calculate the value of dead space fraction that minimized the sum of the squared differences between dialed FVAP and predicted FVAP. With dead space fraction known, the model was then prospectively tested for sevoflurane in O2/air using data collected over the course of two weeks with one FLOW-i (Getinge, Solna, Sweden) and one Zeus workstation (Dräger, Lübeck, Germany). Because both workstations use an electronically controlled vaporizer/injector, the dialed FVAP were available to allow the calculation of median performance error (MDPE) and median absolute performance error (MDAPE). MDPE and MDAP are reported as median and interquartiles. The empirical dead space fraction for isoflurane, sevoflurane, and desflurane were 0.59, 0.49, and 0.66, respectively. For prospective testing, a total of 149.4 h of useful data were collected from 78 patient with the Zeus and Flow-i combined, with FGF ranging from 0.18 to 8 L/min. The model predicted dialed FVAP well, with a MDPE of -1 (-11, 6) % and MDAPE of 8 (4, 17) %. FVAP can be retrospectively calculated from FIN, FET, FGF, and MV plus an agent specific dead space fraction factor with a degree of error that we believe suffices for retrospective sevoflurane consumption analyses. Performance with other agents and N2O awaits further validation.

In vitro performance of prefilled CO2 absorbers with the Zeus®.

Low fresh gas flows (FGFs) decrease the use of anesthetic gases, but increase CO2 absorbent usage. CO2 absorbent usage remains poorly quantified. The goal of this study is to determine canister life of 8 commercially available CO2 absorbent prepacks with the Zeus®. Pre-packed CO2 canisters of 8 different brands were tested in vitro: Amsorb Plus, Spherasorb, LoFloSorb, LithoLyme, SpiraLith, SpheraSorb, Drägersorb 800+, Drägersorb Free, and CO2ntrol. CO2 (160 mL min- 1) flowed into the tip of a 2 L breathing bag that was ventilated with a tidal volume of 500 mL, a respiratory rate of 10/min, and an I:E ratio of 1:1 using the controlled mechanical ventilation mode of the Zeus® (Dräger, Lubeck, Germany). In part I, canister life of 5 canisters each of 2 different lots of each brand was determined with a 350 mL min- 1 FGF. Canister life is the time it takes for the inspired CO2 concentration (FICO2) to rise to 0.5%. In part II, canister life was measured accross a FGF range of 0.25 to 4 L min- 1 for Drägersorb 800+ (2 lots) and SpiraLith (1 lot). In part III, the calculated canister life per 100 g fresh granule content of the different brands was compared between the Zeus and (previously published data for) the Aisys. In vitro canister life of prefilled CO2 absorber canisters differed between brands, and depended on the amount of CO2 absorbent and chemical composition. Canister life expressed as FCU0.5 (the fraction of the canister used per hour) was proportional to FGF over 0.2-2 L min-1 range only, but was non-linear with higher FGF: FCU0.5 was larger than expected with FGF > 2 L min-1, and even with FGF > minute ventilation FCU0.5 did not become zero, indicating some CO2 was being absorbed. Canister life on a per weight basis of the same brand is higher with the Zeus than the Aisys. Canister life of prefilled CO2 absorber canisters differs between brands. The FCU0.5-FGF relationship is not linear across the entire FGF range. Canister life of prepacks of the same brand for the Zeus and Aisys differs, the exact etiology of which is probably multifactorial, and may include differences in the absolute amount of absorbent and different rebreathing characteristics of the machines.

Performance of an active inspired hypoxic guard.

Current hypoxic guards systems fail to maintain the inspired O2 concentration (FIO2) ≥ 21 % across the entire fresh gas flow (FGF) range when a second carrier gas is used (N2O or air). We examined the performance of the Maquet O2 Guard(®), a smart hypoxic guard that increases O2 delivery if an inspired hypoxic mixture is formed. After obtaining IRB approval and informed consent, 12 ASA I-II patients were enrolled. During anesthesia with sevoflurane in O2/air, the O2 Guard(®) was tested by administering O2/air at the following delivered hypoxic guard limits [expressed as (total FGF in L min(-1); FDO2 in %)] for 4 min each: [0.3;67], [0.4;50], [0.6;34], [0.8;25], [1.0;21], [1.2;21], [1.5;21], [2;21], [3;21], and [5;21]. The following data were collected: (1) time from FIO2 = 30 to 20 %; (2) time from FIO2 = 20 % to O2 Guard(®) activation; (3) time from O2 Guard(®) activation to FIO2 = 25 %; (4) FGF and FDO2 used by the O2 Guard. If SpO2 was <90 % for 10 s or longer at any time, the patient was excluded. Three patients were excluded for low SpO2. The incidence of FIO2 < 21 % was 100 % within the 1-2 L min(-1) FGF range. The O2 Guard(®) was activated within 20 s after FIO2 became 20 %, except in one patient where FIO2 oscillated between 20 and 21 %. FDO2 was increased to 60 % and FGF to 1 L min(-1) (the latter only if it was lower than 1 L min(-1) prior to activation of the O2 Guard). FIO2 increased to 25 % within 55 s after O2 Guard activation in all patients. The O2 Guard(®), an active inspired hypoxic guard, rapidly reverses and limits the duration of inspired hypoxic episodes when the delivered hypoxic guard fails to do so.

In vitro performance of prefilled CO2 absorbers with the Aisys®.

Low flow anesthesia increases the use of CO2 absorbents, but independent data that compare canister life of the newest CO2 absorbents are scarce. Seven different pre-packed CO2 canisters were tested in vitro: Amsorb Plus, Spherasorb, LoFloSorb, Medisorb, Medisorb EF, LithoLyme, and SpiraLith. CO2 (160 mL min(-1)) flowed into the tip of a 2 L breathing bag that was ventilated with a tidal volume of 500 mL, a respiratory rate of 10/min, and an I:E ratio of 1:1 using the controlled mechanical ventilation mode of the Aisys (®) (GE, Madison, WI, USA). In part I, canister life of each brand (all of the same lot) was tested with 12 different fresh gas flows (FGF) ranging from 0.25 to 4 L min(-1). In part II, canister life of six canisters each of two different lots of each brand were tested with a 350 mL min(-1) FGF. Canister life is presented as "FCU", fractional canister usage, the fraction of a canister used per hour, and is defined for the inspired CO2 concentration (FICO2) that denotes exhaustion. In part III, canister life per 100 g fresh granule content was calculated. FCU decreased linearly with increasing FGF. The relative position of the FCU-FGF curves of the different brands depends on the FICO2 threshold because the exhaustion rate (the rate of rise once FICO2 starts to increase) differs among the brands. Intra-lot variability was 18 % or less. The different prepacks can be ranked according their efficiency (least to most efficient) as follows: Amsorb Plus = Medisorb EF < LoFloSorb < Medisorb = Spherasorb = LithoLyme < SpiraLith (all for an FICO2 threshold = 0.5 %). Canister life per 100 g fresh granule content is almost twice as long when LiOH is used as the primary absorbent. The most important factors that determine canister life of prepacks in a circle breathing system are the chemical composition of the canister, the absolute amount of absorbent present in the canister, and the FICO2 replacement threshold. The use of the fractional canister usage allows cost comparisons among different prepacks. Results should not be extrapolated to prepacks that fit onto other anesthesia machines.

Hypoxic guard systems do not prevent rapid hypoxic inspired mixture formation.

Because a case report and theoretical mass balances suggested that hypoxic guard systems may not prevent the formation of hypoxic inspired mixtures (FIO2 ≤ 21 %) over the clinically used fresh gas flow (FGF) range, we measured FIO2 over a wide range of hypoxic guard limits for O2/N2O and O2/air mixtures. After IRB approval, 16 ASA I-II patients received sevoflurane in either O2/N2O (n = 8) or O2/air (n = 8) using a Zeus(®) anesthesia machine in the conventional mode. After using an 8 L/min FGF with FDO2 = 25% for 10 min, the following hypoxic guard limits were tested for 4 min each, expressed as [total FGF in L/min; FDO2 in %]: [0.3;85], [0.4;65], [0.5;50], [0.7;36], [0.85;30], [1.0;25], [1.25;25], [1.5;25], [2;25], [3;25], [5;25], and [8;25]. In between these [FGF;FDO2] combinations, 8 L/min FGF with 25% O2 was used for 4 min to return to the same baseline FIO2 (25%) before the start of the next combination. This sequence was studied once in each patient receiving O2/air (n = 8), but twice in each patient who received O2/N2O (n = 8) to examine the effect of decreasing N2O uptake over time, resulting in three groups: early O2/N2O, late O2/N2O, and O2/air group. The [FGF;FDO2]-FIO2 relationship was examined. The overall [FGF;FDO2]-FIO2 relationship in the three groups was similar. In all 1, 1.25, and 1.5 L/min FGF groups, FIO2 decreased below 21% in all but one patient; this occurred within 1 min in at least one patient. In the 0.7 L/min O2/air group and the 3 L/min late O2/N2O and O2/air groups, FIO2 decreased below 21% in one patient. Current hypoxic guard systems do not reliably prevent a hypoxic FIO2 with O2/N2O and O2/air mixtures, particularly between 0.7 and 3 L/min.

Agent consumption with the Zeus® in the automated closed circuit anesthesia mode with O2/air mixtures.

BACKGROUND: Earlier software versions of the Zeus® (Lübeck, Dräger, Germany) failed to provide true closed circuit anesthesia (CCA) conditions. We examined whether the latest software (SW 4.03 MK 04672-00) achieves this goal. METHODS: In 8 ASA I-III patients, the CCA mode of the Zeus® was used to maintain the inspired O2 (FIO2) and end-expired sevoflurane % (FAsevo) at 50 and 1.8%, respectively. The fresh gas flow (FGF) of O2 and air and the sevoflurane injection rate (=Vinjsevo, mL liquid sevo/h) were videotaped from the control screen and entered offline into a spreadsheet. Cumulative sevoflurane usage during early wash-in (=0-1 min, CDsevo0-1), late wash-in (=1-5 min, CDsevo1-5), and maintenance (=5-60 min, CDsevo5-60) was calculated, and Vinjsevo between 1 and 60 min was compared with published uptake data. RESULTS: FAsevo reached 1.8% within 101 (23) sec. CDsevo0-1 was between 1.24 (0.03) and 3.01(0.25) mL (a range is provided because no absolute Vinjsevo values were displayed once Vinjsevo was > 100 mL/h, which occurred between 15 ± 2 and 46 ± 6 sec). CDsevo1-5 was 0.81 (0.37) mL, and CDsevo5-60 was 4.63 (0.94) mL. The Vinjsevo pattern between 1 and 60 min matched previously published uptake data. Brief high FGF periods were used to maintain the target FIO2, and to refill the reservoir bag after external pressure had been applied to the abdomen; subsequent "spikes" wasted 0.08-0.19 mL and 0.14-0.49 mL sevoflurane (1-3% and 3-9% of total agent usage between 1 and 60 min, respectively). CONCLUSION: Under the conditions specified, the Zeus® approaches CCA conditions so closely that further reductions in agent usage would have minimal economic significance.

Theoretical effect of hyperventilation on speed of recovery and risk of rehypnotization following recovery - a GasMan® simulation.

BACKGROUND: Hyperventilation may be used to hasten recovery from general anesthesia with potent inhaled anesthetics. However, its effect may be less pronounced with the newer, less soluble agents, and it may result in rehypnotization if subsequent hypoventilation occurs because more residual anesthetic will be available in the body for redistribution to the central nervous system. We used GasMan® simulations to examine these issues. METHODS: One MAC of isoflurane, sevoflurane, or desflurane was administered to a fictitious 70 kg patient for 8 h with normoventilation (alveolar minute ventilation [VA] 5 L.min-1), resulting in full saturation of the vessel rich group (VRG) and >95% saturation of the muscle group. After 8 h, agent administration was stopped, and fresh gas flow was increased to 10 L.min-1 to avoid rebreathing. At that same time, we continued with one simulation where normoventilation was maintained, while in a second simulation hyperventilation was instituted (10 L.min-1). We determined the time needed for the partial pressure in the VRG (FVRG; representing the central nervous system) to reach 0.3 MAC (MACawake). After reaching MACawake in the VRG, several degrees of hypoventilation were instituted (VA of 2.5, 1.5, 1, and 0.5 L.min-1) to determine whether FVRG would increase above 0.3 MAC(= rehypnotization). RESULTS: Time to reach 0.3 MAC in the VRG with normoventilation was 14 min 42 s with isoflurane, 9 min 12 s with sevoflurane, and 6 min 12 s with desflurane. Hyperventilation reduced these recovery times by 30, 18, and 13% for isoflurane, sevoflurane, and desflurane, respectively. Rehypnotization was observed with VA of 0.5 L.min-1 with desflurane, 0.5 and 1 L.min-1 with sevoflurane, and 0.5, 1, 1.5, and 2.5 L.min-1 with isoflurane. Only with isoflurane did initial hyperventilation slightly increase the risk of rehypnotization. CONCLUSIONS: These GasMan® simulations confirm that the use of hyperventilation to hasten recovery is marginally beneficial with the newer, less soluble agents. In addition, subsequent hypoventilation results in rehypnotization only with more soluble agents, unless hypoventilation is severe. Also, initial hyperventilation does not increase the risk of rehypnotization with less soluble agents when subsequent hypoventilation occurs. Well-controlled clinical studies are required to validate these simulations.

Mathematical method to build an empirical model for inhaled anesthetic agent wash-in.

BACKGROUND: The wide range of fresh gas flow - vaporizer setting (FGF - FD) combinations used by different anesthesiologists during the wash-in period of inhaled anesthetics indicates that the selection of FGF and FD is based on habit and personal experience. An empirical model could rationalize FGF - FD selection during wash-in. METHODS: During model derivation, 50 ASA PS I-II patients received desflurane in O2 with an ADU® anesthesia machine with a random combination of a fixed FGF - FD setting. The resulting course of the end-expired desflurane concentration (FA) was modeled with Excel Solver, with patient age, height, and weight as covariates; NONMEM was used to check for parsimony. The resulting equation was solved for FD, and prospectively tested by having the formula calculate FD to be used by the anesthesiologist after randomly selecting a FGF, a target FA (FAt), and a specified time interval (1 - 5 min) after turning on the vaporizer after which FAt had to be reached. The following targets were tested: desflurane FAt 3.5% after 3.5 min (n = 40), 5% after 5 min (n = 37), and 6% after 4.5 min (n = 37). RESULTS: Solving the equation derived during model development for FD yields FD=-(e(-FGF*-0.23+FGF*0.24)*(e(FGF*-0.23)*FAt*Ht*0.1-e(FGF*-0.23)*FGF*2.55+40.46-e(FGF*-0.23)*40.46+e(FGF*-0.23+Time/-4.08)*40.46-e(Time/-4.08)*40.46))/((-1+e(FGF*0.24))*(-1+e(Time/-4.08))*39.29). Only height (Ht) could be withheld as a significant covariate. Median performance error and median absolute performance error were -2.9 and 7.0% in the 3.5% after 3.5 min group, -3.4 and 11.4% in the 5% after 5 min group, and -16.2 and 16.2% in the 6% after 4.5 min groups, respectively. CONCLUSIONS: An empirical model can be used to predict the FGF - FD combinations that attain a target end-expired anesthetic agent concentration with clinically acceptable accuracy within the first 5 min of the start of administration. The sequences are easily calculated in an Excel file and simple to use (one fixed FGF - FD setting), and will minimize agent consumption and reduce pollution by allowing to determine the lowest possible FGF that can be used. Different anesthesia machines will likely have different equations for different agents.

Development and performance of a two-step desflurane-O(2)/N(2)O 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.

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.

BACKGROUND: The 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. METHODS: Thirty-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. RESULTS: Age 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. CONCLUSION: Agent 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.