Awakening properties of isoflurane, sevoflurane, and desflurane in pediatric patients after craniotomy for supratentorial tumours.

BACKGROUND: The aim of this prospective, comparative, randomized study was to compare the inhalational anesthetics isoflurane, sevoflurane, and desflurane in pediatric patients undergoing craniotomy for excision of supratentorial tumors. We assessed early postoperative recovery outcome, intraoperative hemodynamics, and degree of brain swelling, as well as postoperative vomiting and shivering. METHODS: Sixty patients scheduled for supratentorial brain tumor excision, were randomly allocated into 1 of 3 groups (20 patients each); isoflurane, sevoflurane, and desflurane group. After IV induction of anesthesia, maintenance was achieved using the inhalational anesthetic according to the allocated group. Tracheal extubation time was the primary endpoint. The secondary endpoints included: emergence time and the interval time needed to reach Aldrete score ≥9, intraoperative degree of brain swelling, intraoperative heart rate and mean arterial blood pressure, as well as postoperative vomiting and shivering. RESULTS: The mean emergence time, extubation time, and the interval required to reach Aldrete score 9 were significantly shorter in the desflurane and sevoflurane groups than the isoflurane group. No statistically significant changes in the 3 groups regarding intraoperative brain swelling, hemodynamics, and postoperative shivering or vomiting were noted. CONCLUSIONS: Desflurane and sevoflurane can be used to facilitate early emergence from anesthesia in neurosurgical pediatric patients. Emergence times are shorter with desflurane or sevoflurane than with isoflurane. The patients who received desflurane or sevoflurane have similar intraoperative and postoperative incidence of adverse effects compared with those who received isoflurane. Thus, desflurane and sevoflurane can be considered as suitable for emergence in pediatric neurosurgical anesthesia.

Effects of intraperitoneal administration of gabapentin on the minimum alveolar concentration of isoflurane in adult male rats.

Gabapentin has been used to treat a variety of conditions in both human and veterinary medicine, including seizures, neuropathies and chronic pain. However, little information is known about the effects of gabapentin on the minimum alveolar concentration (MAC) of volatile anaesthetics. In this study, we investigated the effect of intraperitoneal administration of gabapentin on isoflurane MAC in adult male rats and hypothesized that gabapentin would decrease MAC in a dose-dependent manner. Using a standard MAC study protocol, we compared five treatment groups (G) receiving 0 (G(0)), 30 (G(30)), 100 (G(100)), 300 (G(300)) and 1000 (G(1000)) mg/kg gabapentin intraperitoneally and compared post-drug MAC values among groups and with corresponding baseline MAC values determined in each group prior to drug testing. The average baseline isoflurane MAC value was 1.45 ± 0.17%, which did not differ significantly between groups (1.47 ± 0.23% [G(30)], 1.46 ± 0.23% [G(100)], 1.48 ± 0.18% [G(300)] and 1.42 ± 0.2% [G(1000)]). In the G(300) and G(1000) groups, the isoflurane MAC value decreased significantly by 19% and 18%, respectively, from corresponding baseline values (P< 0.05, when compared with G(0)). Linear regression analysis revealed a negative correlation between blood gabapentin concentration and percent change in MAC (R(2) = 0.43; P< 0.05) but not dose. In conclusion, high-dose intraperitoneal gabapentin decreased isoflurane MAC. However, the effect was small and not dose-dependent, and is unlikely to be clinically significant.

Analysis of the effect of perioperative magnesium sulphate on minimal alveolar concentration of desflurane using bispectral index monitoring.

BACKGROUND: In this study we aimed to analyze the effect of perioperative magnesium sulphate (MgSO(4)) on minimal alveolar concentration (MAC) of desflurane using bispectral index (BIS) monitoring. PATIENTS AND METHODS: Sixty patients undergoing abdominal surgery under general anesthesia were randomized into two groups: Mg - receiving perioperative MgSO(4) supplementation and C - control. Anesthesia was titrated to maintain the BIS value between 45-55. RESULTS: MAC values, tachycardia and hypertension during intubation was found to be lower in group Mg compared to group C (p<0.001). Time to extubation, verbal cooperation and eye opening was longer in patients receiving infusion of MgSO(4) (p<0.001). CONCLUSION: We concluded that perioperative MgSO(4) infusion may be used as an adjunct as it decreases MAC of desflurane and suppresses the hemodynamic response to intubation.

A cascade feedback control approach for hypnosis.

This article studies the problem of controlling the drug administration during an anesthesia process, where muscle relaxation, analgesia, and hypnosis are regulated by means of monitored administration of specific drugs. On the basis of a seventh-order nonlinear pharmacokinetic-pharmacodynamic representation of the hypnosis process dynamics, a cascade (master/slave) feedback control structure for controlling the bispectral index (BIS) is proposed. The master controller compares the measured BIS with its reference value to provide the expired isoflurane concentration reference to the slave controller. In turn, the slave controller manipulates the anesthetic isoflurane concentration entering the anesthetic system to achieve the reference from the master controller. The advantage of the proposed cascade control structure with respect to its noncascade counterpart is that the former provides operation protection against BIS measurement failures. In fact, under a BIS measurement fault, the master control feedback is broken and the slave controller operates under a safe reference value. Extensive numerical simulations are used to illustrate the functioning of the proposed cascade control structure.

Comparisons of the effects of acupuncture, electroacupuncture, and transcutaneous cranial electrical stimulation on the minimum alveolar concentration of isoflurane in dogs.

OBJECTIVE: To compare the effects of acupuncture (AP), electroacupuncture (EA), and transcutaneous cranial electrical stimulation (TCES) with high-frequency intermittent currents on the minimum alveolar concentration (MAC) of isoflurane and associated cardiovascular variables in dogs. ANIMALS: 8 healthy adult female Beagles. PROCEDURE: Each dog was anesthetized with isoflurane on 4 occasions, allowing a minimum of 10 days between experiments. Isoflurane MAC values were determined for each dog without treatment (controls) and after treatment with AP and EA (AP points included the Large Intestine 4, Lung 7, Governing Vessel 20, Governing Vessel 14, San Tai, and Baihui) and TCES. Isoflurane MAC values were determined by use of noxious electrical buccal stimulation. Heart rate, mean arterial blood pressure (MAP), arterial blood oxygen saturation (Spo2) measured by use of pulse oximetry, esophageal body temperature, inspired and expired end-tidal isoflurane concentrations, end-tidal carbon dioxide concentration, and bispectral index (BIS) were monitored. Blood samples were collected for determination of plasma cortisol concentration. RESULTS: Mean +/- SD baseline MAC of isoflurane was 1.19 +/- 0.1%. Acupuncture did not significantly change MAC of isoflurane. Treatments with EA and TCES significantly lowered the MAC of isoflurane by 10.1% and 13.4%, respectively. The Spo2, heart rate, MAP, BIS, esophageal body temperature, and plasma cortisol concentration were not significantly different after AP, EA, TCES, and control treatments at any time interval. CONCLUSIONS AND CLINICAL RELEVANCE: Use of EA and TCES decreased MAC of isoflurane in dogs without inducing adverse hemodynamic effects. However, the reduction in isoflurane MAC by EA andTCES treatments was not considered clinically relevant.

Effect of electroacupuncture on minimum alveolar concentration of isoflurane in dogs.

The effect of electroacupuncture (EA) on minimum alveolar concentration (MAC) of isoflurane was evaluated in dogs. After determination of baseline MAC, EA was applied at each acupoints (LI-4, SP-6, ST-36 and TH-8) and nonacupoint for 30 min. MAC was determined again. EA at acupoints significantly lowered the MAC of isoflurane in dogs (17.5 +/- 3.1%, 21.3 +/- 8.0%, 21.2 +/- 7.5% and 15.4 +/- 3.1%, respectively). In control group and nonacupoint electrical stimulation group MAC were not decreased significantly. From these results, electroacupuncture at each acupoints used in the present study would have an advantage in isoflurane anesthesia with reducing its requirement.

Wash-in and wash-out curves of sevoflurane and isoflurane in morbidly obese patients.

BACKGROUND: The aim of this prospective, randomized study is to compare sevoflurane and isoflurane pharmacokinetics in morbidly obese patients. METHODS: With Ethical Committee approval and written informed consent, 14 obese patients (BMI >35 kg/m2), ASA physical status II, undergoing laparoscopic, silicone-adjustable gastric banding were randomly allocated to receive either sevoflurane (n=7) or isoflurane (n=7) as main anesthetic agents. General anesthesia was induced with 1 mg x kg-1 fentanyl, 6 mg x kg-1 sodium thiopental, and 1 mg x kg-1 succinylcholine followed by 0.4 mg kg-1 x h-1 atracurium bromide (doses were referred to ideal body weight). Intermittent positive pressure ventilation (IPPV) was applied using a Servo-900C ventilator with a nonrebreathing circuit and a 15 l x min-1 fresh gas flow (tidal volume: of 10 ml x kg-1; respiratory rate: 12 breaths/min; inspiratory to expiratory time ratio of 1:2) using an oxygen/air mixture (FiO2=50%), while supplemental boluses of thiopental or fentanyl were given as indicated in order to maintain blood pressure and heart rate values within +/-20% from baseline. After adequate placement of tracheal tube and stabilization of the ventilation parameters, 2% sevoflurane or 1.2% isoflurane was given for 30 min via a nonrebreathing circuit. End-tidal samples were collected at 1, 5, 10, 15, 20, 25 and 30 min, and measured using a calibrated infrared gas analyzer. General anesthesia was then maintained with the same inhalational agents, while supplemental fentanyl was given as indicated. After the last skin suture the inhalational agents were suspended, and the end tidal samples were collected at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, and 5 min. Then the lungs were manually ventilated until extubation. RESULTS: No differences in age, gender and body mass index were reported between the two groups. Surgical procedure required 91+/-13 in the sevoflurane group and 83+/-32 min in the isoflurane group. The FA/FI ratio was higher in the sevoflurane group from the 5th to the 30th min. Also the washout curve was faster in the sevoflurane group during the observation period; however, the observed differences were statistically significant only 30 and 60 sec after discontinuation of the inhalational agents. CONCLUSIONS: The results of this prospective, randomized study confirmed that sevoflurane provides more rapid wash-in and wash-out curves than isoflurane also in the morbid obese patient.

Effects of electroacupuncture on minimum alveolar concentration of isoflurane and cardiovascular system in isoflurane anesthetized dogs.

The effects of electroacupuncture (EA) on the minimum alveolar concentration (MAC) and on the cardiovascular system were evaluated with dogs under isoflurane anesthesia. Eight healthy male beagles were randomly assigned to six study groups (five heads/group) with washout intervals of 7 ~ 31 days between experiments for recovery and anesthetic clearance. MAC of isoflurane and cardiovascular parameters were determined after EA at nonacupoint and and at acupoints LI-4, SP-6, ST-36 and TH-8. Electroacupuncture for 30 minutes at LI-4, SP-6, ST-36 and TH-8 acupoints lowered the MAC of isoflurane by 17.5 +/- 3.1%, 21.3 +/- 8.0%, 20.5 +/- 8.2% and 15.6 3.1%, respectively (p < 0.05). However, electrical stimulation of nonacupoint did not induce a significant change in MAC of isoflurane. In the cardiovascular system, the ST-36 group did not induce any significant change in cardiovascular parameters. In the TH-8 group, the mean and diastolic arterial pressure and the systemic vascular resistance were decreased. In the LI-4 group, cardiac output and cardiac index decreased after EA. These results indicate that EA at LI-4, SP-6 and ST-36 have advantages in isoflurane anesthesia in terms of reducing the dose of anesthetics and minimizing cardiovascular side effects.

Effects of Electroacupuncture on Minimum Alveolar Concentration of Isoflurane and Cardiovascular System in Isoflurane Anesthetized Dogs

The effects of electroacupuncture (EA) on the minimum alveolar concentration (MAC) and on the cardiovascular system were evaluated with dogs under isoflurane anesthesia. Eight healthy male beagles were randomly assigned to six study groups (five heads/group) with washout intervals of 7 ~ 31 days between experiments for recovery and anesthetic clearance. MAC of isoflurane and cardiovascular parameters were determined after EA at nonacupoint and and at acupoints LI-4, SP-6, ST-36 and TH-8. Electroacupuncture for 30 minutes at LI-4, SP-6, ST-36 and TH-8 acupoints lowered the MAC of isoflurane by 17.5 +/- 3.1%, 21.3 +/- 8.0%, 20.5 +/- 8.2% and 15.6 +/- 3.1%, respectively (p < 0.05). However, electrical stimulation of nonacupoint did not induce a significant change in MAC of isoflurane. In the cardiovascular system, the ST-36 group did not induce any significant change in cardiovascular parameters. In the TH-8 group, the mean and diastolic arterial pressure and the systemic vascular resistance were decreased. In the LI-4 group, cardiac output and cardiac index decreased after EA. These results indicate that EA at LI-4, SP-6 and ST-36 have advantages in isoflurane anesthesia in terms of reducing the dose of anesthetics and minimizing cardiovascular side effects.

Modeling and closed-loop control of hypnosis by means of bispectral index (BIS) with isoflurane.

A model-based closed-loop control system is presented to regulate hypnosis with the volatile anesthetic isoflurane. Hypnosis is assessed by means of the bispectral index (BIS), a processed parameter derived from the electroencephalogram. Isoflurane is administered through a closed-circuit respiratory system. The model for control was identified on a population of 20 healthy volunteers. It consists of three parts: a model for the respiratory system, a pharmacokinetic model and a pharmacodynamic model to predict BIS at the effect compartment. A cascaded internal model controller is employed. The master controller compares the actual BIS and the reference value set by the anesthesiologist and provides expired isoflurane concentration references to the slave controller. The slave controller maneuvers the fresh gas anesthetic concentration entering the respiratory system. The controller is designed to adapt to different respiratory conditions. Anti-windup measures protect against performance degradation in the event of saturation of the input signal. Fault detection schemes in the controller cope with BIS and expired concentration measurement artifacts. The results of clinical studies on humans are presented.

Isoflurane blunts electroencephalographic and thalamic-reticular formation responses to noxious stimulation in goats.

BACKGROUND: Anesthetics, including isoflurane, depress the electroencephalogram (EEG). Little is known about the quantitative effects of isoflurane on EEG and subcortical electrical activity responses to noxious stimulation. The authors hypothesized that isoflurane would depress the results of EEG and subcortical response to noxious stimulation at concentrations less than those needed to suppress movement. Furthermore, determination of regional differences might aid in elucidation of sites of anesthetic action. METHODS: Ten goats were anesthetized with isoflurane, and minimum alveolar concentration (MAC) was determined using a noxious mechanical stimulus. Depth electrodes were inserted into the midbrain reticular formation and thalamus. Needle electrodes placed in the skull periosteum measured bifrontal and bihemispheric EEG. The noxious stimulus was applied at each of four anesthetic concentrations: 0.6, 0.9, 1.1, and 1.4 MAC. RESULTS: At an isoflurane concentration of 0.6 MAC, the noxious stimulus activated the midbrain reticular formation, thalamic, and bifrontal-hemispheric regions, as shown by decreased high-amplitude, low-frequency power. For all channels combined (mean +/- SD), total (-33+/-7%), delta (-47+/-12%), theta (-23+/-12%), and alpha (-21+/-6%) power decreased after the noxious stimulus (P < 0.001); beta power was unchanged. At 0.9 MAC, total (-35+/-5%), delta (-42+/-7%), theta (-35+/-8%), and alpha (-23+/-11%) power decreased after the noxious stimulus (P < 0.001); beta power was unchanged. At 1.1 MAC only one site, and at 1.4 MAC, no site, had decreased power after the noxious stimulus. CONCLUSIONS: Isoflurane blunted EEG and midbrain reticular formation-thalamus activation response to noxious stimulation at concentrations (1.1 MAC or greater) necessary to prevent movement that occurred after noxious stimulation. It is unknown whether this is a direct effect or an indirect effect via action in the spinal cord.

[The influence of intrathecal NMDA receptor antagonist on the isoflurane MAC and on the motor function].

The effect of intrathecal administration of NMDA (N-methyl-D-aspartate) receptor antagonists on the isoflurane MAC (minimum alveolar anesthetic concentration), and on the locomotor function, were studied in Wistar rats with catheters placed intrathecally. We determined the isoflurane MAC after the administration of either a competitive NMDA receptor antagonist, AP7 (0.044-132 nmole), or a non-competitive NMDA receptor antagonist, MK801 (0.3-90 nmole), as well as NMDA (0.068-204 nmole), and saline. AP7 (0.44-132 nmole) and MK801 (30-90 nmole) decreased the MAC. Intrathecal administration of NMDA reversed these decreases of MAC, but reversal effect is incomplete with AP7 132 nmole and MK801 90 nmole. In a locomotor dysfunction test, rats showed motor dysfunction with AP7 132 nmole (P < 0.05) and MK801 90 nmole (P < 0.05), but low doses did not exert these effects. Large doses of NMDA antagonist decreased the isoflurane MAC due to motor dysfunction, but low doses reduced the MAC without impairing motor function. We suspect that NMDA receptor antagonists play important roles in determining the isoflurane MAC in the spinal cord.

Polyhalogenated and perfluorinated compounds that disobey the Meyer-Overton hypothesis.

Fourteen polyhalogenated, completely halogenated (perhalogenated), or perfluorinated compounds were examined for their anesthetic effects in rats. Anesthetic potency or minimum alveolar anesthetic concentration (MAC) was quantified using response/nonresponse to electrical stimulation of the tail as the end-point. For compounds that produced excitable behavior, and/or did not produce anesthesia when given alone, we determined MAC by additivity studies with desflurane. Nine of 14 compounds had measurable MAC values with products of MAC x oil/gas partition coefficient ranging from 3.7 to 24.8 atm. Because these products exceed that for conventional inhaled anesthetics (1.8 atm), they demonstrate a deviation from the Meyer-Overton hypothesis. Five compounds (CF3CCIFCF3, CF3CCIFCCIFCF3, perfluorocyclobutane, 1,2-dichloroperfluorocyclobutane, and 1,2-dimethylperfluorocyclobutane) had no anesthetic effect when given alone, had excitatory effects when given alone, and tended to increase the MAC for desflurane. These five compounds had no anesthetic properties in spite of their abilities to dissolve in lipids and tissues, to penetrate into the central nervous system, and to be administered at high enough partial pressures so that they should have an anesthetic effect as predicted by the Meyer-Overton hypothesis. Such compounds will be useful in identifying and differentiating anesthetic sites and mechanisms of action. Any physiologic or biophysical/biochemical change produced by conventional anesthetics and deemed important for the anesthetic state should not be produced by nonanesthetics.