Matsuyuki Doi

Airway irritation produced by volatile anaesthetics during brief inhalation: comparison of halothane, enflurane, isoflurane and sevoflurane

Eleven male volunteers were studied to compare the airway irritation produced by the four anaesthetic agents: halothane, enflurane, isoflurane and sevoflurane at two concentrations, equivalent to one and two MAC. Tidal volume, respiratory frequency and functional residual capacity changes induced by 15 sec inhalation of the anaesthetics were measured using respiratory inductive plethysmograph. Appearance of the cough reflex was also observed. The order of subjective airway irritation was evaluated by the volunteers. Inhalation of the anaesthetic agents induced a decrease in tidal volume, increase in respiratory frequency and decrease in functional residual capacity. Significant changes were considered to have occurred if tidal volume and respiratory frequency changed by more than 30% from the resting values for at least ten seconds, or if functional residual capacity changed by more than 30% of the value at resting tidal volume, for at least ten seconds. Each change was induced most frequently by isoflurane followed by enflurane, halothane and, least frequently, by sevoflurane. The orders of appearance of the cough reflex and of subjective airway irritation were similar. Sevoflurane did not elicit a cough reflex. It is concluded that sevoflurane was the least irritant anaesthetic and is considered to be the most suitable for inhalational induction of anaesthesia.RésuméSept volontaires du sexe masculin font partie dune étude visant à comparer les ejfets irritants de quatre agents anesthésiques sur les voies respiratoires: l’halothane, l’enflurane, l’ isoflurane et le sévoflurane, à deux concentration qui équivalent soit à MAC 1, soit à MAC 2. On mesure les changements de volume courant, de fréquence respiratoire et de capacité résiduelle fonctionnelle à l’aide d’un pléthysmographie à induction. On note l’apparition du réflexe de toux. De plus, on évalue le degré subjectif d’irritation éprouvé par les sujets. L’inhalation d’agents anesthésiques cause une baisse du volume courant, une augmentation de la fréquence respiratoire et une diminution de la capacité résiduelle fonctionnelle. On considère significatifs les changements de volume courant et de fréquence respiratoire de plus de 30% des valeurs de repos pour au moins dix secondes, les changements de capacité résiduelle fonctionnelle de plus de 30% de sa valeur au volume courant de repos pour au moins dix secondes. Les changements sont initiés principalement par l’isoflurane, suivi par l’enflurane, l’halothane et moins fréquemment par le sévoflurane. L’ordre d’apparition du réflexe de toux et de l’impression subjective d’irritation des voies aériennes est identique. Le sévoflurane ne provoque pas de réflexe de toux. On conclut que le sévoflurane est le moins irritant des anesthesiques et qu’on peut le considerer comme celui qui convient le mieux à l’induction de l’anesthésie par inhalation.

Comparison of the Effect-site keOs of Propofol for Blood Pressure and EEG Bispectral Index in Elderly and Younger Patients

BACKGROUND Drug effect lags behind the blood concentration. The goal of this investigation was to determine the time course of plasma concentration and the effects of propofol demonstrated by electroencephalogram or blood pressure changes and to compare them between elderly and young or middle-aged patients. METHODS A target-controlled infusion was used to rapidly attain and maintain four sequentially increasing, randomly selected plasma propofol concentrations from 1 to 12 microg/ml in 41 patients aged 20-85 yr. The target concentration was maintained for about 30 min. Bispectral index (BIS), spectral edge frequency, and systolic blood pressure (SBP) were used as measures of propofol effect. Because the time courses of these measures following the started drug infusion showed an exponential pattern, the first-order rate constant for equilibration of the effect site with the plasma concentration (k(eO)) was estimated by fitting a monoexponential model to the effect versus time data resulting from the pseudo-steady-state propofol plasma concentration profile. RESULTS The half-times for the plasma-effect-site equilibration for BIS were 2.31, 2.30, 2.29, and 2.37 min in patients aged 20-39, 40-59, 60-69, and 70-85 yr, respectively (n = 10 or 11 each). The half-times for SBP were 5.68, 5.92, 8.87, and 10.22 min in the respective age groups. All were significantly longer than for BIS (P < 0.05). The propofol concentration at half of the maximal decrease of SBP was significantly greater (P < 0.05) in the elderly than in the younger patients. CONCLUSIONS The effect of propofol on BIS occurs more rapidly than its effect on SBP. Age has no effect on the rate of BIS reduction with increasing propofol concentration, whereas with increasing age, SBP decreases to a greater degree but more slowly.

Respiratory effects of sevoflurane.

The respiratory effects of sevoflurane were studied in seven patients and compared with values obtained in another seven patients anesthetized with halothane. Resting ventilation, resting Paco2, and ventilatory response to CO2 were measured awake and at 1.1 and 1.4 MAC levels of both anesthetic agents. We found that with sevoflurane, tidal volume and the slopes of the CO2 response curves decreased and Paco2 increased with increasing depth of anesthesia, as with other inhaled anesthetics. A compensatory increase in respiratory frequency was not enough to prevent a decrease in minute volume with increasing depth of anesthesia. At 1.1 MAC, sevoflurane produced almost the same degree of respiratory depression as halothane. At 1.4 MAC, sevoflurane produced more profound respiratory depression than halothane.

Auditory Evoked Potential Index Predicts the Depth of Sedation and Movement in Response to Skin Incision during Sevoflurane Anesthesia

Background The auditory evoked potential (AEP) index, which is a single numerical parameter derived from the AEP in real time and which describes the underlying morphology of the AEP, has been studied as a monitor of anesthetic depth. The current study was designed to evaluate the accuracy of AEPindex for predicting depth of sedation and anesthesia during sevoflurane anesthesia. Methods In the first phase of the study, a single end-tidal sevoflurane concentration ranging from 0.5 to 0.9% was assigned randomly and administered to each of 50 patients. The AEPindex and the Bispectral Index (BIS) were obtained simultaneously. Sedation was assessed using the responsiveness portion of the observer’s assessment of alertness–sedation scale. In the second phase of the study, 10 additional patients were included, and the 60 patients who were scheduled to have skin incisions were observed for movement in response to skin incision at the end-tidal sevoflurane concentrations between 1.6 and 2.6%. The relation among AEPindex, BIS, sevoflurane concentration, sedation score, and movement or absence of movement after skin incision was determined. Prediction probability values for AEPindex, BIS, and sevoflurane concentration to predict depth of sedation and anesthesia were also calculated. Results The AEPindex, BIS, and sevoflurane concentration correlated closely with the sedation score. The prediction probability values for AEPindex, BIS, and sevoflurane concentration for sedation score were 0.820, 0.805, and 0.870, respectively, indicating a high predictive performance for depth of sedation. AEPindex and sevoflurane concentration successfully predicted movement after skin (prediction probability = 0.910 and 0.857, respectively), whereas BIS could not (prediction probability = 0.537). Conclusions Auditory evoked potential index can be a guide to the depth of sedation and movement in response to skin incision during sevoflurane anesthesia.

The minimum alveolar concentration of sevoflurane in cats.

Eight adult cats of either sex were studied. The minimal alveolar concentration (MAC) for sevoflurane in the cats was found to be 2.58±0.30% (mean±SD). The ratios of MAC values between sevoflurane and halothane, enflurane and isoflurane in cats were very similar to those ratios found in humans and dogs. This observation suggests that the results of this study are correct and allows us to estimate unknown MAC values for sevoflurane in other species using known MAC values for other -anesthetic agents.

Respiratory effects of sevoflurane used in combination with nitrous oxide and surgical stimulation

STUDY OBJECTIVE To evaluate the respiratory effects of sevoflurane anesthesia with and without nitrous oxide (N2O) during surgical stimulation. DESIGN Randomized study. SETTING Operating theater at a university hospital. PATIENTS 10 patients scheduled for minor head or neck surgery. INTERVENTIONS Sevoflurane anesthesia was administered alone or in combination with N2O. After basal measurements were recorded, the following end-tidal anesthetic concentrations were administered: Group 1 = 1.3 minimum alveolar concentration (MAC) sevoflurane alone; Group 2 = 0.9 MAC sevoflurane with 0.4 MAC N2O; Group 3 = 1.5 MAC sevoflurane alone; Group 4 = 1.1 MAC sevoflurane with 0.4 MAC N2O. MEASUREMENTS AND MAIN RESULTS PaCO2, minute volume (VE), respiratory rate, tidal volume (VT), percentage of rib cage contribution to tidal volume (%RC), rate of inspiratory time in a breath cycle (TI/Ttot, where TI = inspiratory time and Ttot = tidal respiratory time), and mean inspired flow (VT/TI) were measured. The substitution of 0.4 MAC N2O for sevoflurane decreased PaCO2 and increased VE, with a consequent increase in VT. At 1.3 MAC sevoflurane-N2O anesthesia, spontaneous respiration maintained PaCO2 at appropriate levels (42.7 +/- 3.6 mmHg). At 1.3 MAC sevoflurane alone and 1.5 MAC sevoflurane-N2O anesthesia, spontaneous respiration was moderately depressed. Sevoflurane and N2O combined did not change %RC or TI/Ttot. CONCLUSION Sevoflurane administered at an appropriate anesthetic depth maintained spontaneous respiration at acceptable levels during surgical stimulation, especially when combined with N2O.

Plasma exposure of free linezolid and its ratio to minimum inhibitory concentration varies in critically ill patients.

The clinical implications of free linezolid monitoring have not been fully clarified in critically ill patients. The aim of this study was to evaluate the variability in pharmacokinetics of free linezolid and its relationship with susceptibility to meticillin-resistant Staphylococcus aureus (MRSA) in critically ill patients. Twenty critically ill MRSA-infected patients receiving intravenous linezolid were enrolled. Blood specimens were collected by 12-h sampling after dosing at Day 7. The medians (interquartile range) of the minimum free concentration, area under the concentration-time curve of total and free linezolid from 0 to 24 h (AUC(0-24) and fAUC(0-24), respectively) and percentage bound were 9.9 μg/mL (5.2-15 μg/mL), 495 μgh/mL (291-695 μgh/mL), 385 μgh/mL (242-528 μgh/mL) and 23% (15-28%), respectively. The medians of the AUC(0-24) and fAUC(0-24) to minimum inhibitory concentration ratios (AUC/MIC and fAUC/MIC) were 248 (144-347) and 192 (109-264), respectively. Two patients failed to achieve adequate levels of AUC/MIC and fAUC/MIC for linezolid. The percentage bound of linezolid in hypoalbuminaemic patients was significantly lower than in non-hypoalbuminaemic patients. A significant correlation was observed between fAUC(0-24) and creatinine clearance. In addition, the fAUC(0-24) was correlated with the minimum free concentration. In conclusion, the plasma level of free linezolid was variable in critically ill patients with renal dysfunction and hypoalbuminaemia. This finding suggests that the monitoring of free linezolid is necessary in critically ill patients.

Treatment of acute exacerbation of idiopathic pulmonary fibrosis with direct hemoperfusion using a polymyxin B-immobilized fiber column improves survival.

BackgroundAcute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) has an extremely poor prognosis and there is currently no effective treatment for this condition. Direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX-DHP) improves oxygenation, but it is unclear whether treatment of AE-IPF with PMX-DHP affects survival. This study elucidated the effectiveness and safety of PMX-DHP for the treatment of AE-IPF.MethodsThis study included 31 patients with 41 episodes of AE-IPF. All patients received steroids. Of 31, 14 patients (20 episodes) were treated with PMX-DHP. The laboratory and physiological test results after the start of therapy and survival were retrospectively compared between patients treated with and without PMX-DHP.ResultsPatients treated with PMX-DHP had a significantly greater change in PaO2/FiO2 ratio (mean ± SEM, 58.2 ± 22.5 vs. 0.7 ± 13.3, p = 0.034) and a smaller change in white blood cell count (−630 ± 959 /μL vs. 4500 ± 1190 /μL, p = 0.002) after 2 days of treatment than patients treated without PMX-DHP. The 12-month survival rate was significantly higher in patients treated with PMX-DHP (48.2% vs. 5.9%, p = 0.041). PMX-DHP was effective in patients with more severe underlying disease (GAP stages II or III; 12-month survival rate 57.1% with PMX-DHP vs. 0% without PMX-DHP, p = 0.021). Treatment with PMX-DHP was an independent predictor of better prognosis (hazard ratio 0.345, p = 0.037). Mild pulmonary thromboembolism occurred in one patient treated with PMX-DHP.ConclusionsTreatment of AE-IPF with PMX-DHP is tolerable and improves 12-month survival.

Stellate Ganglion Block Is Associated with Increased Tibial Nerve Muscle Sympathetic Activity in Humans

Background Left stellate ganglion block has been shown to increase heart rate and blood pressure, possible because of blockade of afferent vagal fibers from arterial baroreceptors in the aortic arch. Because efferent muscle sympathetic nerve activity (MSNA) is influenced by the arterial baroreflex, the hypothesis that left stellate ganglion block increases efferent MSNA recorded from the tibial nerve of humans was tested. Methods Twenty healthy male volunteers were sequentially assigned to one of three groups: stellate ganglion block (n = 10), in which 7 ml 1% mepivacaine was injected into the left stellate ganglion; placebo (n = 5), in which 7 ml of saline was injected into the left stellate ganglion; and intramuscular injection (n = 5), in which 7 ml mepivacaine was injected into the left deltoid muscle. Direct intraneural microneurographic recording with a tungsten microelectrode was used to record MSNA in the left tibial nerve. MSNA, heart rate, and blood pressure were recorded before and after injection in all groups. An additional five volunteers were studied with transthoracic echocardiography to examine the effect of stellate ganglion block on preload changes. Results Tibial nerve MSNA increased after mepivacaine injection to the left stellate ganglion but was unchanged after saline injection to the left stellate ganglion or mepivacaine injection into the deltoid muscle. Heart rate increased significantly after the left stellate ganglion block but did not change significantly after saline injection to the left stellate ganglion or after mepivacaine injection to the deltoid muscle. Systemic blood pressure did not change significantly in all groups. Left ventricular end-diastolic area and left ventricular end-diastolic circumference did not change after stellate ganglion block. Conclusions Tibial nerve MSNA increased during left stellate ganglion block with mepivacaine.

Frequently repeated fick cardiac output measurements during anesthesia

A computer-based system was developed for monitoring cardiac output using the Fick principle during general anesthesia. The variables of the oxygen-consumption Fick equation were measured using the following system: oxygen uptake by an originally developed respiratory gas monitoring system, arteriovenous oxygen saturation difference by pulse and fiberoptic oximetry, and hemoglobin concentration by an in vitro oximeter. Fick cardiac output and systemic vascular resistance were calculated every 30 seconds. Fick cardiac output was compared with thermodilution cardiac output in 11 anesthetized patients. A total of 208 corresponding cardiac output measurements showed a range of 2 to 9 L · min-1. The correlation coefficient between the thermodilution and Fick cardiac outputs was 0.961, with a regression equation of Fick cardiac output = 1.058 thermodilution cardiac output 0.359. The difference between the thermodilution and Fick cardiac outputs was 0.103 ± 0.395. The Fick cardiac output was significantly lower than the thermodilution cardiac output, especially in the low flow range. We demonstrated that this new monitoring system was clinically feasible and sufficiently accurate, under the limited circumstances of our study. The integration of routinely used equipment has made possible a frequently repcatable method for estimating cardiac output in patients.