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Purpose: Hydrogen gas (H2) inhalation improved the survival rate of hemorrhagic shock. However, its mechanisms are unknown. We hypothesized that H2 protected the endothelial glycocalyx during hemorrhagic shock and prolonged survival time.Methods: 83 Sprague–Dawley rats were anesthetized with isoflurane. The animals were randomly assigned to 5 groups: room air with no shock, 1.2% H2 with no shock, room air with shock (Control-S), 1.2% H2 with shock (H2 1.2%-S), and 3.0% H2 with shock (H2 3.0%-S). Shock groups were bled to a mean arterial pressure of 30 to 35 mmHg and held for 60 min, then resuscitated with normal saline at 4-fold the amount of the shed blood volume.Results: The syndecan-1 level was significantly lower in the H2 1.2%-S [8.3 ± 6.6 ng/ml; P=0.01; 95% confidence interval (CI), 3.2–35.8] than in the Control-S (27.9 ± 17.0 ng/ml). The endothelial glycocalyx was significantly thicker in the H2 1.2%-S (0.15 ± 0.02 μm; P=0.007; 95% CI, 0.02–0.2) than in the Control-S (0.06 ± 0.02 μm). The survival time was longer in the H2 1.2%-S (327 ± 67 min, P=0.0160) than in the Control-S (246 ± 69 min). The hemoglobin level was significantly lower in the H2 1.2%-S (9.4 ± 0.5 g/dl; P=0.0034; 95% CI, 0.6–2.9) than in the Control-S (11.1 ± 0.8 g/dl). However, the H2 3.0%-S was not significant.Conclusions: Inhalation of 1.2% H2 gas protected the endothelial glycocalyx and prolonged survival time during hemorrhagic shock. Therapeutic efficacy might vary depending on the concentration.

Background Systemic anesthetic management of patients with mitochondrial disease requires careful preoperative preparation to administer adequate anesthesia and address potential disease-related complications. The appropriate general anesthetic agents to use in these patients remain controversial. Case presentation A 54-year-old woman (height, 145 cm; weight, 43 kg) diagnosed with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes underwent elective cochlear implantation. Infusions of intravenous remimazolam and remifentanil guided by patient state index monitoring were used for anesthesia induction and maintenance. Neither lactic acidosis nor prolonged muscle relaxation occurred in the perioperative period. At the end of surgery, flumazenil was administered to antagonize sedation, which rapidly resulted in consciousness. Conclusions Remimazolam administration and reversal with flumazenil were successfully used for general anesthesia in a patient with mitochondrial disease.

Heatstroke causes systemic inflammation, followed by vascular endothelial damage. The normal vascular endothelium is coated by endothelial glycocalyx (EGCX). Dexmedetomidine (DEX) has an anti-inflammatory effect, but there has been little investigation on the influence of heatstroke on EGCX and the effect of DEX on this condition. Therefore, we examined whether EGCX was disrupted in heatstroke and if DEX improved survival and preserves EGCX. Anesthetized Wistar rats were randomly assigned to three groups: a DEX group treated with DEX (5 µg/kg/h) and 0.9% saline infused continuously at 10 ml/kg/h during heat exposure; a NSS group given 0.9% saline during heat exposure; and a SHAM group given 0.9% saline alone without heat exposure. Heatstroke was induced by exposure to an ambient temperature of 40 °C with relative humidity of 60%. The survival rate was assessed up to 2 h after the start of heat exposure. Plasma levels of syndecan-1 and the thickness of EGCX using electron microscopy were measured when the systolic blood pressure fell to less than 80 mmHg. The survival rate after 2 h of heat exposure was significantly higher in the DEX group compared to the NSS group (89% vs. 22%, P = 0.004). Plasma levels of syndecan-1 were 0.6 ± 1.3, 9.7 ± 5.9, and 2.1 ± 3.4 ng/ml in the SHAM, NSS and DEX groups, respectively (P = 0.013). The thickness of EGCX was significantly higher in the DEX group compared with the NSS group (P = 0.001). EGCX was disrupted in heatstroke, and DEX improved survival and preserved EGCX.

Remimazolam, an ultra-short-acting benzodiazepine sedative is equally effective as propofol in induction and maintenance of general anesthesia with improved hemodynamic stability in American Society of Anesthesiologists (ASA) Class I and II patients. This trial investigated remimazolam’s efficacy and safety in vulnerable patients (ASA Class III) undergoing elective general surgery. A multicenter, randomized, double-blind, parallel-group trial in 67 adult surgical patients undergoing general anesthesia with two remimazolam induction doses (6 mg kg−1 h−1—group A and 12 mg kg−1 h−1—group B) has been conducted in 6 trials sites in Japan. Remimazolam was infused up to 2 mg kg−1 h−1 for maintenance of anesthesia in both groups. The functional anesthetic capability of the investigated drug was 100% in both arms. The mean time to loss of consciousness (LoC) was significantly shorter in group B (81.7 s) compared to group A (97.2 s), p = 0.0139. The mean bispectral index (BIS) value during maintenance of anesthesia ranged from 46.0 to 68.0 and from 44.7 to 67.5 in group A and B, respectively. There was no statistically significant difference between the remimazolam arms concerning the incidence of blood pressure (BP) decrease (67.7% in group B vs. 54.8% in group A), recovery profile or the incidence or severity of adverse events (AEs) or adverse drug reactions (ADRs). Both induction regimens (6 and 12 mg kg−1 h−1) were equally efficacious and safe in surgical patients ASA Class III. A significantly shorter time to LoC was observed with the higher remimazolam dosage. Clinical trial registration This trial is registered with the Japan Pharmaceutical Information Center—Clinical Trials Information (JapicCTI). JapicCTI number: 121977.

This trial was conducted to confirm the non-inferiority of remimazolam versus propofol in the induction and maintenance of general anesthesia in surgical patients. Surgical patients (n = 375) were randomized to remimazolam started at 6 or 12 mg/kg/h by continuous intravenous (IV) infusion until the loss of consciousness (LoC), followed by 1 mg/kg/h to be adjusted as appropriate until the end of surgery or IV propofol administered as a slow bolus of 2.0–2.5 mg/kg until LoC followed by 4–10 mg/kg/h until the end of surgery. Efficacy was measured via the combined primary endpoint of no intraoperative awakening/recall, no need for rescue sedatives, and no body movements. Adverse events and adverse drug reactions (ADRs) were monitored for safety. Efficacy rates were 100% in all treatment groups, and the non-inferiority of remimazolam was demonstrated [95% confidence interval (− 0.0487; 0.0250)]. The time to LoC was longer in the remimazolam 6 (p

Objective To compare the effects of remifentanil versus fentanyl during light sedation with dexmedetomidine in adults receiving mechanical ventilation (MV) in the intensive care unit. Methods In this retrospective cohort study, we compared the use of remifentanil versus fentanyl in adults receiving MV with dexmedetomidine sedation. The primary outcome was the proportion of time under light sedation (Richmond Agitation–Sedation Scale score between −1 and 0) during MV. Results We included 94 patients and classified 58 into the remifentanil group and 36 into the fentanyl group. The mean proportion of time under light sedation during MV was 66.6% ± 18.5% in the remifentanil group and 39.9% ± 27.3% in the fentanyl group. In the multivariate analysis with control for confounding factors, patients in the remifentanil group showed a significantly higher proportion of time under light sedation than patients in the fentanyl group (mean difference: 24.3 percentage points; 95% confidence interval: 12.9–35.8). Conclusions Remifentanil use might increase the proportion of time under light sedation in patients receiving MV compared with fentanyl administration.

Purpose We evaluated the safety and efficacy of long-term administration of dexmedetomidine in patients in the intensive care unit (ICU). Primary endpoint was the incidence of hypotension, hypertension, and bradycardia. Secondary endpoints were withdrawal symptoms, rebound effects, the duration of sedation with Richmond Agitation-Sedation Scale (RASS) ≤ 0 relative to the total infusion time of dexmedetomidine, and the dose of additional sedatives or analgesics. Methods Dexmedetomidine 0.2–0.7 μg/kg/h was continuously infused for maintaining RASS ≤ 0 in patients requiring sedation in the ICU. Safety and efficacy of short-term (≤24 h) and long-term (>24 h) dexmedetomidine administration were compared. Results Seventy-five surgical and medical ICU patients were administered dexmedetomidine. The incidence of hypotension, hypertension, and bradycardia that occurred after 24 h (long-term) was not significantly different from that occurring within 24 h (short-term) (P = 0.546, 0.513, and 0.486, respectively). Regarding withdrawal symptoms, one event each of hypertension and headache occurred after the end of infusion, but both were mild in severity. Increases of mean arterial blood pressure and heart rate after terminating the infusion of dexmedetomidine were not associated with the increasing duration of its infusion. The ratio of duration with RASS ≤ 0 was ≥ 85 % until day 20, except day 9 (70 %) and day 10 (75 %). There was no increase in the dose of additional sedatives or analgesics after the first 24-h treatment period. Conclusions Long-term safety of dexmedetomidine compared to its use for 24 h was confirmed. Dexmedetomidine was useful to maintain an adequate sedation level (RASS ≤ 0) during long-term infusion.

Lipopolysaccharide (LPS) is an endotoxin known to induce disseminated intravascular coagulation and multiple organ failure followed by septic shock in animals. Nafamostat is a synthetic protease inhibitor with anticoagulant effects. This study investigated the effect of systemic administration of nafamostat on thermogenic homeostasis and survival time in a mouse surgical model. Male C57Bl/6 mice were anesthetized with sevoflurane and implanted with intraabdominal telemetry transmitters. Following the surgery, three groups of animals were administered Escherichia coli LPS (0127: B8) subcutaneously at doses of 0.3, 1.0, or 3.0 mg kg(-1), and one group received saline without LPS. Three other groups received 3 mg.kg(-1) LPS with 1, 3, or 10 mg kg(-1) of nafamostat. In another group 10 mg kg(-1)1 of nafamostat only was administered. The times to the onset of hypothermia (body temperature < 30 degrees C) and death were determined. L LPS significantly shortened the duration of both normothermia and survival, and nafamostat prolonged the normothermic periods that were reduced b 3 mg.kg(-1) LPS. Survival time was significantly correlated with the duration of normothermia (n = 48; r (2) = 0.779; P < 0.000001). The results demonstrated the effect of systemic administration of nafamostat against LPS-induced hypothermia. Nafamostat prevented hypothermia, and the consequent normal thermoregulation may have prolonged the survival period.

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 pharmacokinetic characteristics of intravenous fentanyl have not been fully clarified in the early postsurgical period. The aim of this study was to evaluate the plasma exposure and urinary excretion of fentanyl and norfentanyl according to cytochrome P450 (CYP) 3A5 genetic polymorphism.Fifty-two adult Japanese postoperative patients receiving a continuous intravenous fentanyl infusion were enrolled. Plasma concentrations of fentanyl and norfentanyl were determined at 24 hours after the operation, and their urinary excretion from 12 to 36 hours was evaluated.Plasma concentrations of fentanyl normalized for infusion rate were significantly higher in the *3/*3 group than in the *1 carrier group. The plasma concentration ratio of norfentanyl to fentanyl was significantly lower in the *3/*3 group than in the *1 carrier group. Urinary excretion rates of fentanyl and norfentanyl were 4.4% and 71%, respectively, and no significant differences were observed between the CYP3A5 genotypes. Renal clearance ratios of fentanyl and norfentanyl to creatinine were 0.34 and 3.4, respectively. There were no significant differences in the renal clearance ratios between the genotypes. Free fractions of fentanyl and norfentanyl in human plasma were 4.9% and 95%, respectively. Total and nonrenal clearance of fentanyl were significantly lower in the *3/*3 group than in the *1 carrier group.CYP3A5*3 affected the plasma exposure of fentanyl but not urinary excretion in our postoperative patients. The renal clearance ratios of fentanyl and norfentanyl to creatinine were much higher than their free fractions in plasma. These findings suggest a slight contribution of renal tubular secretion of fentanyl and norfentanyl to their plasma exposures.

We have compared the auditory evoked potential (AEP) index (a numerical index derived from the AEP), 95% spectral edge frequency (SEF), median frequency (MF) and the bispectral index (BIS) during alternating periods of consciousness and unconsciousness produced by target-controlled infusions of propofol. We studied 12 patients undergoing hip or knee replacement under spinal anaesthesia. During periods of consciousness and unconsciousness, respective mean values for the four measurements were: AEP index, 60.8 (SD 13.7) and 37.6 (6.5); BIS, 85.1 (8.2) and 66.8 (10.5); SEF, 24.2 (2.2) and 18.7 (2.1); and MF, 10.9 (3.3) and 8.8 (2.0). Threshold values with a specificity of 100% for a state of unconsciousness were: AEP index, 37 (sensitivity 52%); BIS, 55 (sensitivity 15%); and SEF, 16.0 (sensitivity 9%). There was no recorded value for MF that was 100% specific for unconsciousness. Of the four measurements, only AEP index demonstrated a significant difference (P0.05) between all mean values 1 min before recovery of consciousness and all mean values 1 min after recovery of consciousness. Our findings suggest that of the four electrophysiological variables, AEP index was best at distinguishing the transition from unconsciousness to consciousness.

We have examined the effects of midazolam 0.06 mg kg-1 i.m. and diazepam 0.2 mg kg-1 orally as premedication on the spectral components of heart rate (HR) variability in 24 elderly patients aged 65-87 yr and 24 young patients aged 18-35 yr undergoing elective surgery. The low-frequency/high-frequency (LF/HF) ratio of HR variability increased after arrival in the operating room in elderly patients who received no premedication, but not in young patients. In elderly patients who received midazolam or diazepam, the LF/HF ratio did not increase. However, diazepam increased the low-frequency component and the total power of HR variability in both young and elderly patients. We conclude that cardiac sympathetic nerve activity increased after arrival in the operating room in the elderly, that midazolam or diazepam reduced this increase and that diazepam caused an increase in the total power of HR variability that has not been observed for other agents.

This study examined the sedative effect of, and hemodynamic response to dexmedetomidine administration in propofol-sedated swine. Sixteen swine were subjects. After anesthetic induction and preparation, the propofol infusion rate was adjusted to maintain a bispectral index (BIS) value between 55 and 65 (i.e., baseline). With the propofol infusion rate fixed at the baseline rate, dexmedetomidine was infused continuously at a rate of 0.2, 0.4, and 0.7 microg.kg(-1).h(-1) for one hour at each rate. The BIS value and hemodynamic parameters were recorded at each step. Dexmedetomidine decreased the BIS value, mean arterial blood pressure, heart rate, cardiac output, and mixed venous oxygen saturation in a dose-dependent manner. The systemic vascular resistance (SVR) did not change, but the pulmonary vascular resistance (PVR) increased. Oxygen delivery (DO(2)) and oxygen consumption (VO(2)) decreased. A small dose of dexmedetomidine (0.2 microg.kg(-1).h(-1)) greatly enhanced the sedative effects of propofol with only small changes in hemodynamics and systemic oxygen balance, suggesting it may be useful in reducing the propofol dose requirement. However, dexmedetomidine 0.4 microg.kg(-1).h (-1) suppressed cardiac contractility, and 0.7 microg.kg(-1).h(-1) induced hemodynamic instability and further systemic oxygen imbalance while the additional sedative effect was limited. A lower dose of dexmedetomidine may be recommended when using it in combination with propofol.

Central neurogenic hyperventilation (CNH) is a rare clinical condition that is sometimes difficult to treat. We report a 51-year-old female patient who was successfully treated with intravenous fentanyl followed by transdermal fentanyl. She had a transient epileptic episode with a temporary loss of consciousness. Immediately before her admission to the intensive care unit (ICU), her Pa(CO2) and pH were 6.7 mmHg and 7.64, respectively. Rebreathing from a paper bag and the intravenous administration of diazepam failed to improve the decreased Pa(CO2). Therefore, we administered intravenous fentanyl, at the rate of 50 microg x h(-1). Two days after her admission to the ICU, the Pa(CO2) had increased gradually to 22.9 mmHg, and the pH to 7.50. Although infiltration of recurrent lymphoma to the brain became apparent, she remained active, without epilepsy or loss of consciousness, in a general ward for 1 month with transdermal fentanyl, treatment until she again became drowsy; she died on hospital day 58. Transdermal fentanyl seems to be a good palliative measure to treat CNH in patients who have advanced neoplasms.

Pentobarbital is reported to inhibit ketamine-induced dopamine (DA) release in the rat nucleus accumbens. The accumbens is a part of the limbic dopaminergic system in the brain, and the dopaminergic neural activity of other components may also be sensitive to pentobarbital. We investigated the effect of pentobarbital administration on DA release in the striatum known as DA-rich basal ganglia, and the interaction between pentobarbital and l -DOPA, using in vivo microdialysis techniques. Male SD rats were implanted microdialysis probe into the right striatum. The probe was perfused with modified Ringer's solution and dialysate was directly injected to an HPLC. Every group of rats was consisted of six to seven animals. In the first experiment, rats were given saline, 25 and 50 mg kg −1 pentobarbital. The second, each rat was given a local administration of 2 and 5 μg ml −1 of l -DOPA with perfusate. Finally, other sets of rats were given 5 μg ml −1 of l -DOPA and 25, 50, or 100 mg kg −1 pentobarbital. Pentobarbital anaesthesia decreased the extracellular concentration of DA, and local administration of l -DOPA significantly increased DA concentration. Pretreatment with pentobarbital diminished the l -DOPA-induced DA increase. The results of the present investigation demonstrate that administration of pentobarbital might inhibit dopaminergic neural activity not only in the nucleus accumbens but also in the rat striatum. Pentobarbital anaesthesia antagonizes DA increase induced by l -DOPA and suggests the inhibition of metabolism of l -DOPA. The results of some animal experiments on dopaminergic activity under pentobarbital anaesthesia should be reconsidered.

We have studied 46 patients to compare the efficacy of the auditory evoked potential (AEP) index, bispectral index (BIS), 95% spectral edge frequency (SEF) and median frequency (MF) in predicting movement in response to insertion of the laryngeal mask airway (LMA). Anaesthesia was induced with target-controlled infusions of propofol and alfentanil. After loss of eyelash reflex and adequate jaw relaxation, the LMA was inserted without the assistance of a laryngoscope or neuromuscular blocker. Patients who showed any visible spontaneous muscle movement within 1 min of LMA insertion were defined as movers. Values in movers and non-movers at 30 s before LMA insertion were analysed. Only AEP index discriminated between movers and non-movers with a prediction probability of 0.872. BIS, SEF and MF could not predict movement at LMA insertion. AEP index was the most reliable predictor of movement in response to LMA insertion.

Background Left stellate ganglion block has been shown to increase heart rate and blood pressure, possible because of blockage 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.

The relationship between tumor size and the complexity of anesthetic management was studied using several values: plasma catecholamine concentrations, requirement of vasoactive agents, surgical time, blood loss, plasma glucose concentrations, and hemodynamic variables. Ten patients with clinical and laboratory diagnosis of pheochromocytoma were prospectively studied. Each anesthesia was maintained using inhalational anesthetic agents. Control of arterial blood pressure (ABP), heart rate (HR), and pulmonary artery blood pressure (PABP) was attempted with only titrating the inhalational anesthetics and adenosine triphosphate (ATP). If the titration of both the inhalational anesthetic and ATP failed to control ABP, HR, or PABP, then phentolamine, propranolol, trinitroglycerine, or norepinephrine was additionally used. Tumor weight was significantly correlated with amount of blood loss, surgical time, duration of ATP requirement, maximal dose of ATP infusion used, maximal plasma glucose concentration, and plasma total catecholamine concentration. However, the tumor weight was not correlated with hemodynamic variables. Patients who required propranolol generally had a significantly larger tumor than those who did not. In conclusion, surgical removal of large pheochromocytoma required more complicated anesthetic management than that of small pheochromocytoma.

Study Objective : To evaluate the respiratory effects of sevoflurane anesthesia with and without nitrous oxide (N 2 O) during surgical stimulation. Design: Randomized study. Setting: Operating theater at a university hospital. Patients: 10 patients scheduled for minor head or neck surgery. Interventions: Sevofurane anesthesia was administered alone or in combination with N 2 O. 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 N 2 O; Group 3=1.5 MAC sevofurane alone; Group 4=1.1 MAC sevoflurane with 0.4 MAC N 2 O. Measurements and Main Results: PaCO 2 , minute volume respiratory rate, tidal volume (V T ), percentage of rib cage contribution to tidal volume (%RC), rate of inspiratory time in a breath cycle (TITtot where T I = inspiratory time and T tot , = tidal respiratory time), and mean inspired flow (VTTI) were measured. The substitution of 0.4 MAC N 2 O for sevofurane decreased PaCO 2 and increased V E , with a consequent increase in V T . At 1.3 MAC sevoflurane-N 2 O anesthesia,, spontaneous respiration maintained PaCO 2 at appropriate levels (42.7 ± 3.6 mmHg). At 1.3 MAC sevofurane alone and 1.5 MAC sevoflurane-N 2 O anesthesia, spontaneous respiration was moderately depressed. Sevoflurane and N 2 O combined did not change %RC or TITtot. Conclusion: Sevoflurane administered at an appropriate anesthetic depth maintained spontaneous respiration at acceptable levels during surgical stimulation, especially when combined with N 2 O.

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.

The effect of low concentration sevoflurane and halothane on the ventilatory response to isocapnic hypoxia was studied in sixteen cats. The cats were divided into two groups, sevoflurane group and halothane group, of eight subjects each. As parameters of the hypoxic ventilatory response, A value [the slope of the hyperbolic curve, V(E) = V(0) + A/(Pa(O)(2)-32)] and ratio of V(50) (the minute volume obtained from the hyperbolic equation when Pa(O)(2) = 50 mmHg) to V(0) were studied. These two parameters were examined at three states, sedative state with ketamine as the control, ketamine plus 0.1 MAC inhalation anesthetic, and ketamine plus 0.5 MAC inhalation anesthetic. In the sevoflurane group, the A values were 4789 +/- 1518, 2187 +/- 1214, 1730 +/- 880 (mean +/- SE. ml.min(-1).mmHg) at the control state, 0.1 MAC and 0.5 MAC, respectively. In the halothane group, the A values were 6411 +/- 2368, 2529 +/- 842 and 2372 +/- 545, respectively. The ratios of V(50) to V(0) were 1.32 +/- 0.09, 1.22 +/- 0.09, 1.25 +/- 0.08 in the sevoflurane group, 1.47 +/- 0.18, 1.32 +/- 0.11, 1.54 +/- 0.18 in the halothane group, respectively. The A value at 0.1 MAC of the halothane group was less than the control value significantly. This proved that even low concentration halothane depressed the hypoxic ventilatory responses. The depression of hypoxic ventilatory response could cause postanesthetic hypoventilation. On the other hand, we could not find significant depression on the hypoxic ventilatory response in the sevoflurane group, but we should notice that variances of the hypoxic ventilatory response were large.

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.

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.

The postanesthetic respiratory depression with sevoflurane, isoflurane and halothane was studied in twenty-one patients. They were divided into three groups of seven patients each. One group underwent sevoflurane anesthesia, another group isoflurane and the third group halothane. Following extubation, the decrease in blood concentration of the anesthetic agent was most rapid with sevoflurane and slowest with halothane. Twenty minutes following extubation, resting ventilation and ventilatory response to carbon dioxide returned to the preanesthetic state with sevoflurane and isoflurane anesthesia. With halothane anesthesia, however, the depressive respiratory effects of halothane remained; depressed ventilatory response to carbon dioxide, decreased tidal volume and increased respiratory frequency. Although halothane has been reported to have the least depressive respiratory effect of the three, its elimination was slowest. Thus tfie respiratory effects of halothane persisted up to and past the twenty minute mark, far longer than with sevoflurane or isoflurane.

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.