Do we need inhaled anaesthetics to blunt arousal, haemodynamic responses to intubation after i.v. induction with propofol, remifentanil, rocuronium?

BACKGROUND: The aim of this study was to determine whether, after propofol, rocuronium and remifentanil rapid sequence induction, inhaled anaesthetic agents should be started before intubation to minimize autonomic and arousal response during intubation. METHODS: One hundred ASA I and II patients were randomized to receive 1 MAC of desflurane or sevoflurane during manual ventilation or not. Anaesthesia was induced with an effect-site-controlled infusion of remifentanil at 2 ng ml(-1) for 3 min. Patients then received propofol to induce loss of consciousness (LOC). Rocuronium (0.6 mg kg(-1)) was given at LOC and the trachea was intubated after 90 s of manual breathing support (=baseline) with or without inhaled anaesthetics. Vital signs and bispectral index (BIS) were recorded until 10 min post-intubation to detect autonomic and arousal response. RESULTS: A significant increase in BIS value after intubation was seen in all groups. The increases were mild, even in those not receiving pre-intubation inhaled anaesthetics. However, in contrast to sevoflurane, desflurane appeared to partially blunt the arousal response. Heart rate, systolic and diastolic pressure increase similarly in all groups. CONCLUSIONS: Desflurane and sevoflurane were unable to blunt the arousal reflex completely, as measured by BIS, although the reflex was significantly less when desflurane was used. Rapid sequence induction with remifentanil, propofol and rocuronium and without inhaled anaesthetics before intubation can be done without dangerous haemodynamic and arousal responses at intubation after 90 s.

The mechanisms of carbon monoxide production by inhalational agents.

Carbon monoxide can be formed when volatile anaesthetic agents such as desflurane and sevoflurane are used with anaesthetic breathing systems containing carbon dioxide absorbents. This review describes the possible chemical processes involved and summarises the experimental and clinical evidence for the generation of carbon monoxide. We emphasise the different conditions that were used in the experimental work, and explain some of the features of the clinical reports. Finally, we provide guidelines for the prevention and detection of this complication.

Production of compound A and carbon monoxide in circle systems: an in vitro comparison of two carbon dioxide absorbents.

Two new generation carbon dioxide absorbents, DrägerSorb Free and Amsorb Plus, were studied in vitro for formation of compound A or carbon monoxide, during minimal gas flow (500 ml x min(-1)) with sevoflurane or desflurane. Compound A was assessed by gas chromatography/mass spectrometry and carbon monoxide with continuous infrared spectrometry. Fresh and dehydrated absorbents were studied. Mean (SD) time till exhaustion (inspiratory carbon dioxide concentration >or= 1 kPa) with fresh absorbents was longer with DrägerSorb Free (1233 (55) min) than with Amsorb Plus (1025 (55) min; p < 0.01). For both absorbents, values of compound A were < 1 ppm and therefore below clinically significant levels, but were up to 0.25 ppm higher with DrägerSorb Free than with Amsorb Plus. Using dehydrated absorbents, values of compound A were about 50% lower than with fresh absorbents and were identical for DrägerSorb Free and Amsorb Plus. With dehydrated absorbents, no detectable carbon monoxide was found with desflurane.

Treatment of postoperative pain after ophthalmic surgery.

For ophthalmic surgery we have to deal with a wide range of different patient characteristics. We treat young healthy children, in some cases even neonates, but on the other hand we have debilitated aging patients with multiple concomitant diseases. Treatment of postoperative pain is imperative for inpatients, but is even more important for patients who are treated on an outpatient basis. There also is a wide range of different types of ophthalmic surgical procedures. The postoperative care after a cataract extraction is only seldom complicated by severe pain and is completely different of that after a vitrectomy with scleral buckling. More aggressive surgery as enucleation or evisceration of an eye often is a very stressful and painful procedure. We certainly have some excellent strategies to cope with postoperative pain. We can use topical anesthetics or non-steroidal anti-inflammatory medication. Regional anesthesia of the globe is extremely useful for anticipating on postoperative pain, especially when long-acting agents are used. We can administer analgesics by mouth or parenterally. Acetaminophen or paracetamol is widely used and can be supplemented with NSAIDs or opioids. Especially for children one has to use optimal doses of minor analgesics by an adequate route of administration in order to achieve a timely and efficient analgesia.

Compound A production from sevoflurane is not less when KOH-free absorbent is used in a closed-circuit lung model system.

In an in vitro study, less compound A was formed when a KOH-free carbon dioxide absorbent was used. To confirm this observation we used a lung model in which carbon dioxide was fed in at 160 ml min(-1) and sampling gas was taken out for analysis at 200 ml min(-1); ventilation aimed for a PE'CO2 of 5.4 kPa. The soda lime canister temperatures in the inflow and outflow ports (Tin and Tout) were recorded. In six runs of 240 min each, a standard soda lime, Sodasorb (Grace, Epernon, France) was used and in eight runs KOH-free Sofnolime (Molecular Products, Thaxted, UK) was used. Liquid sevoflurane was injected using a syringe pump to obtain 2.1% E'. Compound A was measured by capillary gas chromatography combined with mass spectrometry. Median (range) compound Ainsp increased to a maximum of 22.7 (7.9) ppm for Sodasorb and 33.1 (20) for Sofnolime at 60 min and decreased thereafter; the difference between groups was significant (P<0.05) at each time of analysis up to 240 min. The canister temperatures were similar in both groups and increased to approximately 40 degrees C at 240 min. Contrary to expectation, compound A concentrations were greater with the KOH-free absorbent despite similar canister temperatures with both absorbents.

Only carbon dioxide absorbents free of both NaOH and KOH do not generate compound A during in vitro closed-system sevoflurane: evaluation of five absorbents.

BACKGROUND: Insufficient data exist on the production of compound A during closed-system sevoflurane administration with newer carbon dioxide absorbents. METHODS: A modified PhysioFlex apparatus (Dräger, Lübeck, Germany) was connected to an artificial test lung (inflow at the top of the bellow approximately/= 160 ml/min CO2; outflow at the Y piece of the lung model approximately/= 200 ml/min, simulating oxygen consumption). Ventilation was set to obtain an end-tidal carbon dioxide partial pressure of approximately 40 mmHg. Various fresh carbon dioxide absorbents were used: Sodasorb (n = 6), Sofnolime (n = 6), and potassium hydroxide (KOH)-free Sodasorb (n = 7), Amsorb (n = 7), and lithium hydroxide (n = 7). After baseline analysis, liquid sevoflurane was injected into the circuit by syringe pump to obtain 2.1% end-tidal concentration for 240 min. At baseline and at regular intervals thereafter, end-tidal carbon dioxide partial pressure, end-tidal sevoflurane concentration, and canister inflow (T degrees(in)) and canister outflow (T degrees(out)) temperatures were measured. To measure compound Ainsp concentration in the inspired gas of the breathing circuit, 2-ml gas samples were taken and analyzed by capillary gas chromatography plus mass spectrometry. RESULTS: The median (minimum-maximum) highest compound Ainsp concentrations over the entire period were, in decreasing order: 38.3 (28.4-44.2)* (Sofnolime), 30.1 (23.9-43.7) (KOH-free Sodasorb), 23.3 (20.0-29.2) (Sodasorb), 1.6 (1.3-2.1)* (lithium hydroxide), and 1.3 (1.1-1.8)* (Amsorb) parts per million (*P < 0.01 vs. Sodasorb). After reaching their peak concentration, a decrease for Sofnolime, KOH-free Sodasorb, and Sodasorb until 240 min was found. The median (minimum-maximum) highest values for T degrees(out) were 39 (38-40), 40 (39-42), 41 (40-42), 46 (44-48)*, and 39 (38-41) degrees C (*P < 0.01 vs. Sodasorb), respectively. CONCLUSIONS: With KOH-free (but sodium hydroxide [NaOH]-containing) soda limes even higher compound A concentrations are recorded than with standard Sodasorb. Only by eliminating KOH as well as NaOH from the absorbent (Amsorb and lithium hydroxide) is no compound A produced.

Comparison of closed-loop controlled administration of propofol using Bispectral Index as the controlled variable versus "standard practice" controlled administration.

BACKGROUND: This report describes a new closed-loop control system for propofol that uses the Bispectral Index (BIS) as the controlled variable in a patient-individualized, adaptive, model-based control system, and compares this system with manually controlled administration of propofol using hemodynamic and somatic changes to guide anesthesia. METHODS: Twenty female patients, American Society of Anesthesiologists physical status I or II, who were scheduled for gynecologic laparotomy were included to receive propofolremifentanil anesthesia. In group I, propofol was titrated using a BIS-guided, model-based, closed-loop system. The BIS target was set at 50. In group II, propofol was titrated using classical hemodynamic signs of (in)adequate anesthesia. Performance of control during induction and maintenance of anesthesia were compared between both groups using BIS as the controlled variable in group I and the reference variable in group II, and, conversely, the systolic blood pressure as the controlled variable in group II and the reference variable in group I. At the end of anesthesia, recovery profiles between groups were compared. RESULTS: Although patients undergoing manual induction of anesthesia in group II at 300 ml/h reached a BIS level of 50 faster than patients undergoing open-loop, computer-controlled induction in group I, manual induction caused a more pronounced initial overshoot of the BIS target. This resulted in a more pronounced decrease in blood pressure in group II. During the maintenance phase, better control of BIS and systolic blood pressure was found in group I compared with group II. Recovery was faster in group I. CONCLUSION: A closed-loop system for propofol administration using the BIS as a controlled variable together with a model-based controller is clinically acceptable during general anesthesia.

Quantitative determination of vapor-phase compound A in sevoflurane anesthesia using gas chromatography-mass spectrometry.

BACKGROUND: During low-flow or closed-circuit anesthesia with the fluorinated inhalation anesthetic sevoflurane, compound A, an olefinic degradation product with known nephrotoxicity in rats, is generated on contact with alkaline CO(2) adsorbents. To evaluate compound A formation and thus potential sevoflurane toxicity, a reliable and reproducible assay for quantitative vapor-phase compound A determination was developed. METHODS: Compound A concentrations were measured by fully automated capillary gas chromatography-mass spectrometry with cryofocusing. Calibrators of compound A in the vapor phase were prepared from liquid volumetric dilutions of stock solutions of compound A and sevoflurane in ethyl acetate. 1,1,1-Trifluoro-2-iodoethane was chosen as an internal standard. The resulting quantitative method was fully validated. RESULTS: A linear response over a clinically useful concentration interval (0.3-75 microL/L) was obtained. Specificity, sensitivity, and accuracy conformed with current analytical requirements. The CVs were 4.1-10%, the limit of detection was 0.1 microL/L, and the limit of quantification was 0.3 microL/L. Analytical recoveries were 100.6% +/- 10.1%, 102.5% +/- 7.3%, and 99.0% +/- 4.1% at 0.5, 10, and 75 microL/L, respectively. The method described was used to determine compound A concentrations during simulated closed-circuit conditions. Some of the resulting data are included, illustrating the practical applicability of the proposed analytical approach. CONCLUSIONS: A simple, fully automated, and reliable quantitative analytical method for determination of compound A in air was developed. A solution was established for sampling, calibration, and chromatographic separation of volatiles in an area complicated by limited availability of sample volume and low concentrations of the analyte.

In vitro compound A formation in a computer-controlled closed-circuit anesthetic apparatus. Comparison with a classical valve circuit.

BACKGROUND: Few data exist on compound A during sevoflurane anesthesia when using closed-circuit conditions and sodalime with modern computer-controlled liquid injection. METHODS: A PhysioFlex apparatus (Dräger, Lübeck, Germany) was connected to an artificial test lung (inflow approximately 160 ml/min carbon dioxide, outflow approximately 200 ml/min, simulating oxygen consumption). Ventilation was set to obtain an end-tidal carbon dioxide partial pressure (Petco2) approximately 40 mmHg. Canister inflow (T degrees in) and outflow (T degrees out) temperatures were measured. Fresh sodalime and charcoal were used. After baseline analysis, sevoflurane concentration was set at 2.1% end-tidal for 120 min. At baseline and at regular intervals thereafter, Petco2, end-tidal sevoflurane, T degrees in, and T degrees out were measured. For inspiratory and expiratory compound A determination, samples of 2-ml gas were taken. These data were compared with those of a classical valve-containing closed-circuit machine. Ten runs were performed in each set-up. RESULTS: Inspired compound A concentrations increased from undetectable to peak at 6.0 (SD 1.3) and 14.3 (SD 2.5) ppm (P < 0.05), and maximal temperature in the upper outflow part of the absorbent canister was 24.3 degrees C (SD 3.6) and 39.8 degrees C (SD 1.2) (P < 0.05) in the PhysioFlex and valve circuit machines, respectively. Differences between the two machines in compound A concentrations and absorbent canister temperature at the inflow and outflow regions were significantly different (P < 0.05) at all times after 5 min. CONCLUSION: Compound A concentrations in the high-flow (70 l/min), closed-circuit PhysioFlex machine were significantly lower than in conventional, valve-based machines during closed-circuit conditions. Lower absorbent temperatures, resulting from the high flow, appear to account for the lower compound A formation.

Comparison of plasma compartment versus two methods for effect compartment--controlled target-controlled infusion for propofol.

BACKGROUND: Target-controlled infusion (TCI) systems can control the concentration in the plasma or at the site of drug effect. A TCI system that targets the effect site should be able to accurately predict the time course of drug effect. The authors tested this by comparing the performance of three control algorithms: plasmacontrol TCI versus two algorithms for effect-site control TCI. METHODS: One-hundred twenty healthy women patients received propofol via TCI for 12-min at a target concentration of 5.4 microg/ml. In all three groups, the plasma concentrations were computed using pharmacokinetics previously reported. In group I, the TCI device controlled the plasma concentration. In groups II and III, the TCI device controlled the effect-site concentration. In group II, the effect site was computed using a half-life for plasma effect-site equilibration (t1/2k(eo)) of 3.5 min. In group III, plasma effect-site equilibration rate constant (k(eo)) was computed to yield a time to peak effect of 1.6 min after bolus injection, yielding a t1/2keo of 34 s. the time course of propofol was measured using the bispectral index. Blood pressure, ventilation, and time of loss of consciousness were measured. RESULTS: The time course of propofol drug effect, as measured by the bispectral index, was best predicted in group III. Targeting the effect-site concentration shortened the time to loss of consciousness compared with the targeting plasma concentration without causing hypotension. The incidence of apnea was less in group III than in group II. CONCLUSION: Effect compartment-controlled TCI can be safely applied in clinical practice. A biophase model combining the Marsh kinetics and a time to peak effect of 1.6 min accurately predicted the time course of propofol drug effect.

Influence of methane on infrared gas analysis of volatile anesthetics.

Contemporary multigas analyzers determine anesthetic gas concentrations using (near) infrared analysis at either 3.3 or 8-9 microns. Methane also absorbs infrared light at 3.3 microns, but not at 8-9 microns. Consequently, erroneous anesthetic agent readings may result when methane is present in the circuit (e.g. during closed circuit anesthesia), potentially compromising patient safety. We have analyzed in laboratory conditions the influence of different known methane concentrations (100, 500 and 1000 ppm) on the gas-analysis readings provided by some clinical monitoring devices that use infrared absorption for the measurement of inhalation anesthetic concentration. At 3.3 microns wavelength the influence on the measurement of halothane was important, whereas the influence on that of enflurane and isoflurane was less pronounced. For desflurane and sevoflurane measurements, the influence of methane at 3.3 microns wavelength proved to be minimal. At higher wavelengths (8-9 microns) no influence of methane could be demonstrated.

Haemodynamic and electroencephalographic response to insertion of a cuffed oropharyngeal airway: comparison with the laryngeal mask airway.

We have compared the cuffed oropharyngeal airway (COPA), a modified Guedel airway device with a specially designed cuff at its distal end, with the laryngeal mask airway (LMA), on haemodynamic and electroencephalographic (EEG) responses to insertion. In addition, we examined the haemodynamic and EEG changes during initiation of the effect-compartment controlled infusion. We studied 35 female patients undergoing ambulatory gynaecological surgery allocated randomly to received an LMA or COPA to manage the airway. After premedication with midazolam 0.03 mg kg-1 i.v. and low-dose alfentanil (0.01 mg kg-1), anaesthesia was induced and maintained with propofol, using an effect-compartment controlled infusion set at an effect-site concentration of 4 micrograms ml-1. After intercompartmental equilibration, the LMA (group I) or COPA (group II) was inserted and haemodynamic (arterial pressure, heart rate) and EEG (bispectral index (BIS)) responses to insertion studied. The effect-compartment controlled infusion of propofol caused only mild haemodynamic changes during induction. Changes in arterial pressure and heart rate after insertion were similar in both groups and not significantly different from baseline values before insertion. Changes in BIS after insertion were minor and similar between groups.

Closed-loop controlled administration of propofol using bispectral analysis.

Ten patients, undergoing elective orthopaedic surgery under spinal anaesthesia, were sedated with propofol using a closed-loop feedback control system. The bispectral index (BIS), a new processed EEG parameter, was used as control variable. Propofol administration was controlled by a patient individualised adaptive model-based controller incorporating target-controlled infusion technology combined with a pharmacokinetic-dynamic model. This feedback control system for propofol administration proved to be adequate and safe. BIS was found to be well suited as control variable.

Comparison of spontaneous frontal EMG, EEG power spectrum and bispectral index to monitor propofol drug effect and emergence.

BACKGROUND: The aim of this study was to investigate the accuracy of frontal spontaneous electromyography (SEMG) and EEG spectral edge frequency (SEF 95%), median frequency (MF), relative delta power (RDELTA) and bispectral index (BIS) in monitoring loss of and return of consciousness and hypnotic drug effect during propofol administration at different calculated plasma target concentrations. METHODS: Propofol was administered by using a target-controlled infusion at different propofol steady-state concentrations. All variables were measured simultaneously at specific calculated concentrations and endpoints. RESULTS: Loss of consciousness was accurately monitored by BIS, SEMG and SEF 95%, and propofol drug effect by BIS only. Return of consciousness was predicted by BIS, MF and SEF 95%. Due to the biphasic EEG pattern of propofol and the lack of reproducible data at specific propofol concentrations, the clinical usefulness of SEF 95%, MF and RDELTA was very limited. SEMG was useful to detect loss and return of consciousness, but without predictive value. CONCLUSIONS: The BIS might be an accurate measure to monitor depth of anaesthesia and hypnotic drug effect. Other neurophysiologic measures have limited value to monitor depth of anaesthesia and hypnotic drug effect.

Methane influences infrared technique anesthetic agent monitors.

OBJECTIVE: During closed-circuit anesthesia, anesthetic vapor analysis by infrared absorption at 3.3 microm can be influenced by the concentration of accumulated methane, resulting in inaccurate readings of anesthetic concentrations. The current study examined the influence of different known methane concentrations on the analysis of halothane or isoflurane concentrations by the infrared absorption technique. METHODS: Three different gas mixtures containing 100, 500 and 1000 ppm methane were given through an experimental sampling bar. Four infrared technique anesthetic agent monitors were examined: (1) the Ultima (Datex), (2) the Andros analyzer (Cato anesthesia machine, Driger), (3) the anesthetic gas monitor 1304 (Brüel & Kjaer) and (4) the mainstream analyzer Irina (Drager). All devices, except the Brüel & Kjaer anesthetic gas monitor, function at 3.3 microm wavelength. The Brüel & Kjaer apparatus functions at 10.3-13 microm wavelength. The readings were recorded with and without addition of halothane (or isoflurane) at a halothane (or an isoflurane) dedicated sensitivity after application of methane. RESULTS: At the two highest methane concentrations (500 and 1000 ppm) all studied devices except the Brüel & Kjaer anesthetic gas monitor 1304 displayed inaccurate anesthetic concentrations. This was more pronounced at halothane than at isoflurane sensitivity. Introduction of halothane (0.8%) or isoflurane (0.8%) vapor into the experimental sampling bar resulted in values that were additive to the falsely recorded ones. CONCLUSIONS: In closed circuit or low-flow anesthesia, in which methane can accumulate, infrared measuring techniques for potent inhalation anesthetics that do not use the 3.3 microm wavelength appear to be preferable.

Influence of pre-anaesthetic medication on target propofol concentration using a 'Diprifusor' TCI system during ambulatory surgery.

The effects of pre-anaesthetic medication on target propofol concentration, induction dose, time to induction, and discomfort on infusion were studied in 45 female patients undergoing ambulatory gynaecological procedures using 'Diprifusor' target controlled infusion of propofol. The patients were randomly allocated to receive either no premedication (group 1) or premedication with diazepam alone (group 2) or in combination with alfentanil (group 3). Induction was more successful in premedicated than unpremedicated patients with an initial target propofol concentration of 4 micrograms.ml-1 (87% in group 2 and 93% in group 3 vs. 38% in group 1, p < 0.01). Premedication was also associated with the requirement of a lower mean target concentration for induction, a lower induction dose and a shorter time to induction. There were no significant between-group differences in discomfort on infusion or target concentration during maintenance. For short ambulatory procedures, the recommended initial target concentration of propofol is 4 micrograms.ml-1 in premedicated and 6 micrograms.ml-1 in unpremedicated patients.

Clinical usefulness of the bispectral index for titrating propofol target effect-site concentration.

The bispectral index, a new processed electroencephalographic parameter which may give information on depth of anaesthesia, was used in 58 patients undergoing outpatient gynaecological surgery in order to study if the addition of bispectral index monitoring to standard clinical monitoring could improve the titration of target propofol concentration when using effect-site target-controlled propofol infusion for sedation. In Group 1 (n = 30), the bispectral index was recorded but the anaesthetist was unaware of the readings and therefore only classical signs of depth of anaesthesia were used to guide the anaesthetist in controlling the effect-site concentration. In Group 2 (n = 28), bispectral index readings were available to the anaesthetist and effect-site concentration was adjusted to ensure that bispectral index was maintained between 40 and 60. Similar propofol induction and maintenance doses, blood and effect-site concentrations and mean bispectral index were found in the two groups. A greater percentage of bispectral index readings lying outside the target range (i.e. < 40 or > 60) and more movement at incision and during maintenance were found in Group 1. There was a trend towards more implicit awareness in patients in Group 1. Bispectral index was found to be useful for measuring depth of sedation when using propofol target-controlled infusion. Propofol dosage could not be decreased but a more consistent level of sedation could be maintained due to a more satisfactory titration of target effect-site concentration.

Comparison of computer-controlled administration of propofol with two manually controlled infusion techniques.

Ninety women were studied in order to compare dose requirements and quality of anaesthesia between target-controlled infusion and two manually controlled infusion schemes for propofol administration: group I received target-controlled infusion for induction (4 micrograms.ml-1 target blood concentration, increased by 2 micrograms.ml-1 after 3 min of consciousness not lost), groups II and III received an induction bolus of propofol at infusion rates of 1200 or 600 ml.h-1, respectively, until loss of consciousness. Anaesthesia was maintained with propofol target-controlled infusion in group 1 or by constant rate infusion in the other two groups. Computer simulations were used to calculate blood and effect-site propofol concentrations. Mean induction times (SD) were 78 (65)s in group I versus 51 (10)s and 62 (12)s in groups II and III, respectively (p < 0.05 between groups II and III). Mean induction doses were: 1.31 (0.44), 2.74 (0.56) and 1.77 (0.43) mg.kg-1 and mean maintenance doses were 13.4 (3.55), 9.32 (1.72) and 9.97 (1.53) mg.kg-1 h-1 in groups I, II and III, respectively (p < 0.05 between all groups). There was a lower incidence of apnoea in group I than in groups II and III. There were no significant differences between the groups in other objective parameters of anaesthetic quality studied. Computer simulations showed an "overshoot' in propofol blood and effect-site concentration with manual induction and significantly higher maintenance levels with target-controlled infusion.