G. G. Lockwood

True patient‐controlled sedation

A modified patient‐controlled analgesia pump provided doses ofpropofol 3 mg or midazolam 0.1 mg in 0.3 ml, over 5.4 s, with no lockout, during transvaginal oocyte retrieval. Alfentanil 0.2 mg was administered at three points during the procedure, and on request. Patients were randomly assigned to receive either propofol (25 patients) or midazolam (22 patients). The mean age, weight, duration of procedure and dose ofalfentanil were similar in both groups. Onset of sedation with propofol or midazolam took 70.6 (SD 22.4) and 106.3 (50.7) s respectively. Mean doses over the first 5 min were midazolam 2.7 (1.2) mg, and propofol 54 (18) mg. Thereafter requirements decreased: midazolam 0.065 (0.065) mg.min−1, propofol 2.1 (1.3) mg.min−1. All patients successfully completed the procedure; none required additional sedation. P‐deletion, reaction time, and critical flicker fusion tests revealed similar depression in both groups immediately postoperatively. After 30 min the p‐deletion and critical flicker fusion scores were still impaired in the midazolam, but not in the propofol, group.

Feasibility and safety of delivering xenon to patients undergoing coronary artery bypass graft surgery while on cardiopulmonary bypass : Phase I study

Background: Postoperative neurocognitive deficit is prevalent after cardiac surgery. Xenon may prevent or ameliorate acute neuronal injury, but it also may aggravate injury during cardiac surgery by increasing bubble embolism. Before embarking on a randomized clinical trial to test the safety and efficacy of xenon for postoperative neurocognitive deficit, we undertook a phase I study to investigate the safety of administering xenon to patients undergoing coronary artery bypass grafting while on cardiopulmonary bypass and to assess the practicability of our xenon delivery system. Methods: Sixteen patients scheduled for coronary artery bypass grafting surgery with hypothermic cardiopulmonary bypass gave their informed consent to participate in an open-label dose-escalation study (0, 20, 35, 50% xenon in oxygen and air). Xenon was delivered throughout surgery using both a standard anesthetic breathing circuit and the oxygenator. Gaseous and blood xenon partial pressures were measured five times before, during, and after cardiopulmonary bypass. Middle cerebral artery Doppler was used to assess embolic load, and major organ system function was assessed before and after surgery. Results: Middle cerebral artery Doppler showed no evidence of increased emboli with xenon. Patients receiving xenon had no major organ dysfunction: Troponin I and S100β levels tended to be lower in patients receiving xenon. Up to 25 l xenon was used per patient. Xenon partial pressure in the blood tracked the delivered concentration throughout. Conclusions: Xenon was safely and efficiently delivered to coronary artery bypass grafting patients while on cardiopulmonary bypass. Prevention of nervous system injury by xenon should be tested in a large placebo-controlled, randomized clinical trial.

Theoretical context-sensitive elimination times for inhalation anaesthetics

BACKGROUND Context-sensitive times to 50%, 80%, and 90% elimination from the brain have been calculated for volatile anaesthetics. This does not represent complete recovery because there are important residual effects even at 90% elimination, and the effect of anaesthetic metabolism on the rate of elimination has not been considered. METHODS A physiologically based model of anaesthetic uptake and distribution was elaborated to include anaesthetic metabolism and fluoride kinetics. It was validated by comparing its predictions with real data, then experiments were undertaken to calculate the partial pressure of anaesthetic in the brain after the administration of 1 MAC of halothane, enflurane, isoflurane, sevoflurane or desflurane, or 50% of inspired nitrous oxide or xenon, for up to 6 h. RESULTS The model generated data that were compatible with many published measurements of anaesthetic kinetics and fluoride production. Metabolism had a negligible effect on kinetics. After 4 h of anaesthesia, the model predicted body content to be 28 g nitrous oxide, 26 g desflurane, 14 g sevoflurane, or 15 g isoflurane, and 99.9% brain elimination times were then 9 h for nitrous oxide, 33 h for desflurane, 52 h for sevoflurane, and 71 h for isoflurane. At this stage of elimination, the whole body still retained between 4% and 13% of the absorbed dose. Differences between sevoflurane and desflurane were obvious only during the final stages of elimination (>99% from the vessel-rich group). CONCLUSIONS Large amounts of anaesthetics are absorbed during anaesthesia and significant amounts remain in the body for days after apparent recovery.

A comparison of anaesthetic tensions in arterial blood and oxygenator exhaust gas during cardiopulmonary bypass

This study evaluates the usefulness of the analysis of gas sampled from the exhaust port of a membrane oxygenator in the estimation of anaesthetic tension in arterial blood. Sixty‐seven arterial blood samples were drawn from patients undergoing hypothermic cardiopulmonary bypass with anaesthesia maintained by either isoflurane or desflurane. Anaesthetic tensions in the oxygenator exhaust gas were measured using an infrared analyser and in arterial blood using a two‐stage headspace technique with a gas chromatograph. Both measurement systems were calibrated with the same standard gas mixtures. There was no difference in anaesthetic tension measured in arterial blood and gas leaving the oxygenator exhaust (isoflurane: n = 29, range: 0.3–0.8%, 95% limits of agreement: − 0.08% to 0.09%; desflurane: n = 38, range: 1.5–5.4%; 95% limits of agreement − 0.65% to 0.58%). We conclude that anaesthetic tensions in arterial blood can be accurately monitored by analysis of the gas emerging from the exhaust port of a membrane oxygenator.

The uptake of sevoflurane during anaesthesia

The rate of uptake of sevoflurane during clinical anaesthesia (1.3 MAC) was measured by computer‐controlled injection of liquid anaesthetic into a closed breathing system. The cumulative uptake of sevoflurane was 4.8 ml, 7.4 ml. 9.5 ml and 11.5 ml at 30, 60, 90 and 120 min, respectively. The ratio of inspired to end‐expired sevoflurane was greater than similar measurements we have made for desflurane in the past, but the absolute rate of sevoflurane uptake was less than the rate of uptake of desflurane in these cases. The rate of uptake was equivalent to 0.59e−0.32t + 0.039e−0.036t + 0.105e−0.0034t mlmin−1 liquid sevoflurane. Plasma urea and creatinine measured on the first postoperative day were not significantly different from pre‐operative values.

Eeg changes during cardiopulmonary bypass surgery and postoperative neuropsychological deficit : the effect of bubble and membrane oxygenators

OBJECTIVE Quantitative electroencephalography was used during cardiopulmonary bypass surgery to determine the point in time of most neuronal functional change which may result in postoperative neuropsychological deficit. It was also used to determine any relationship between quantitative electroencephalography changes and type of oxygenator used in surgery. METHODS We studied 61 coronary artery bypass graft patients. Anaesthesia included thiopental, fentanyl and N2O. Surgery was performed with hypothermic bypass (28 degrees C), arterial pressure of 50-70 mmHg, and alpha-stat, using bubble (Harvey 1700), or membrane (Cobe CML) oxygenators, both with arterial line filters (Pall 40 microns). RESULTS The main finding was a significant increase in delta power at the end of perfusion (P < 0.01), which showed a positive association with delta power before the start of perfusion. Marked quantitative electroencephalography change at the end of perfusion was not related to systemic hypotension, temperature, type of oxygenator, bypass time, or patient age. Intraoperative quantitative electroencephalography changes found in most patients were transient and could not be related to postoperative cerebral function. However, 16 of the 18 patients who had neuropsychological deficit 2 months after surgery, also had a significant quantitative electroencephalography change at the end of perfusion. CONCLUSIONS While no difference in anaesthetic technique was found between patients, the variation in quantitative electroencephalography power before perfusion may indicate a difference in individual response to anaesthetic. Usefulness of quantitative electroencephalography to predict postoperative cerebral functional deficit remains doubtful.

The uptake of isoflurane during anaesthesia.

The uptake of isoflurane at a constant end‐expired concentration of 1.5% in oxygen was studied in 15 women, ASA 1 or 2, undergoing elective total abdominal hysterectomy. The anaesthetic was administered by a simple computer‐controlled to‐and‐fro closed system. After an initial period of wash‐in to the system, the rate of uptake of isoflurane decreased bi‐exponentially with a rapid reduction during the first 15 min. Perturbations from this bi‐exponential decline reflect changes in cardiac output. The mean (SD) cumulative use of isoflurane was 4.5 (0.43) ml after 30 min and 7.3 (0.79) ml after 60 min.

The effect of sevoflurane on implicit memory: a double-blind, randomised study

Forty‐eight gynaecological patients were randomly allocated to three groups (target end‐tidal sevoflurane concentration 1.2, 1.5 or 2%), and into subgroups for positive or neutral suggestion. Anaesthesia was induced by inhalation of sevoflurane in oxygen. When the target concentration was achieved, the bispectral index, computed from a bi‐frontal electroencephalogram, was noted. One of two eight‐word lists was then played to prime implicit memory, followed by a positive or neutral suggestion. After surgery, each patient tried to identify 24 words obscured by background noise. Priming increased the likelihood of identifying words in the 1.2% group only, i.e. there was evidence of implicit memory in this group. There was no evidence of a therapeutic effect of positive suggestion (p = 0.3), but the power of this part of the study was low. The bispectral index did not achieve statistical significance as an indicator of susceptibility to priming.

A computer-controlled closed anaesthetic breathing system.

We describe the design and working of a computer‐controlled, closed anaesthetic breathing system which rapidly achieves and maintains a prescribed end‐tidal concentration ofisoflurane in oxygen. The system is simple to set up and not expensive; the only nonstandard component is a modified glass syringe. We have demonstrated that gas analysers may contribute as much as the patient to the accumulation of nitrogen within the breathing system. Details of our clinical experience with the system are presented in an accompanying article.

Uptake of desflurane during anaesthesia

The amount of desflurane required to maintain an end‐expired concentration of 8% was measured in 30 ASA 1 and 2 patients undergoing elective spinal surgery. The anaesthetic was administered using a computer‐controlled closed circle system. After an initial period during which the expired concentration of desflurane was stabilised (4 min) the rate of uptake showed a bi‐exponential decline. Mean cumulative usage of desflurane was 10.1 ml of liquid at 30min, 14.8ml at 60min, 25.4ml at 120min, 35.8 at 180min.