Alveolar Anesthetic Concentration Isoflurane Research Articles

The Influence of Hemorrhagic Shock on the Minimum Alveolar Anesthetic Concentration of Isoflurane in a Swine Model

Although hemorrhagic shock decreases the minimum alveolar concentration (MAC) of inhaled anesthetics, it minimally alters the electroencephalographic (EEG) effect. Hemorrhagic shock also induces the release of endorphins, which are naturally occurring opioids. We tested whether the release of such opioids might explain the decrease in MAC. Using the dew claw-clamp technique in 11 swine, we determined the isoflurane MAC before hemorrhage, after removal of 30% of the estimated blood volume (21 mL/kg of blood over 30 min), after fluid resuscitation using a volume of hydroxyethylstarch equivalent to the blood withdrawn, and after IV administration of 0.1 mg/kg of the mu-opioid antagonist naloxone. Hemorrhagic shock decreased the isoflurane MAC from 2.05% +/- 0.28% to 1.50% +/- 0.51% (P = 0.0007). Fluid resuscitation did not reverse MAC (1.59% +/- 0.53%), but additional administration of naloxone restored it to control levels (1.96% +/- 0.26%). The MAC values decreased depending on the severity of the shock, but the alterations in hemodynamic variables and metabolic changes accompanying fluid resuscitation or naloxone administration did not explain the changes in MAC. Consistent with previous reports, we found that hemorrhagic shock decreases MAC. In addition, we found that naloxone administration reversed the effect on MAC, and we propose that activation of the endogenous opioid system accounts for the decrease in MAC during hemorrhagic shock. Such an activation would not be expected to materially alter the EEG, an expectation consistent with our previous finding that hemorrhagic shock minimally alters the EEG.

The Comparative Effects of Sevoflurane Versus Isoflurane on Cerebrovascular Carbon Dioxide Reactivity in Patients with Diabetes Mellitus

The use of volatile anesthetics has been reported to alter cerebrovascular carbon dioxide (CO2) reactivity. We examined the comparative effects of sevoflurane versus isoflurane on cerebrovascular CO2 reactivity in 40 patients with diabetes mellitus. Anesthesia was maintained with either 1.0 minimum alveolar anesthetic concentration of sevoflurane or 1.0 minimum alveolar anesthetic concentration of isoflurane in 33% oxygen and 67% nitrous oxide. A 2.5-MHz pulsed transcranial Doppler probe was attached to the patient's head at the right temporal window for continuous measurement of mean blood flow velocity in the middle cerebral artery. After establishing baseline middle cerebral artery velocity values and cardiovascular hemodynamics, we increased end-tidal CO2 by decreasing ventilatory frequency by 2-5 breaths/min and repeated the measurements. These were then used to calculate absolute and relative CO2 reactivity. Absolute CO2 reactivity was less in insulin-treated patients with either sevoflurane or isoflurane compared with those patients on oral antidiabetic drugs or dietary therapy (sevoflurane group: diet = 2.6 +/- 0.6; oral antidiabetic drug = 2.5 +/- 0.8; insulin = 1.6 +/- 0.8*; isoflurane group: diet = 3.3 +/- i0.7; oral antidiabetic drug = 3.4 +/- 0.7; insulin = 1.9 +/- 0.7* cm.s(-1).mm Hg(-1); *P < 0.05, respectively). Relative CO2 reactivity showed a similar pattern in the diet-controlled and oral antidiabetic groups, absolute and relative CO2 reactivities were lower with sevoflurane versus isoflurane. Hence, we conclude that cerebrovascular CO2 reactivity in insulin-dependent patients is impaired under both sevoflurane and isoflurane anesthesia.

The Efficacy of Plethysmographic Pulse Wave Amplitude as an Indicator for Intravascular Injection of Epinephrine-Containing Epidural Test Dose in Anesthetized Adults

In this study, I evaluated the efficacy of plethysmographic pulse wave amplitude (PPWA) in detecting intravascular injection of a simulated epidural test dose containing 15 microg of epinephrine in adults during either sevoflurane or isoflurane inhaled anesthesia and compared its reliability to the classical heart rate (HR; positive if > or =10 bpm) and systolic blood pressure (SBP; positive if > or =15 mm Hg) criteria. Eighty patients were randomized to receive either 1 mean alveolar anesthetic concentration of sevoflurane or 1 mean alveolar anesthetic concentration of isoflurane (n = 40 for each anesthesia group). Patients in each anesthesia group microg of epinephrine IV or 3 mL of saline IV (n = 20 each). HR, SBP, and PPWA were monitored for 5 min after injection. Injection of the test dose resulted in peak PPWA decrease by 61% +/- 17% and 58% +/- 15% at 61 +/- 12 s and 63 +/- 13 s in the sevoflurane and isoflurane groups, respectively. Positive PPWA criterion, as determined from peak increases during saline administration, was a decrease in PPWA > or =10%. Using this value, the sensitivity, specificity, positive predictive, and negative predictive values of PPWA were 100% in both anesthetic groups. On the contrary, sensitivities of 85% and 95% were obtained based on HR criterion in the sevoflurane and isoflurane patients, respectively, and a sensitivity of 90% was obtained in both anesthesia groups on the basis of SBP criterion. In conclusion, PPWA is a reliable alternative to conventional hemodynamic criteria for detection of an intravascular injection of epidural test dose.

Isoflurane facilitates hiccup-like reflex through gamma aminobutyric acid (GABA)A- and suppresses through GABAB-receptors in pentobarbital-anesthetized cats.

The mechanism by which volatile anesthetics exert inconsistent effects on hiccups is unknown. We elicited a hiccup-like reflex by mechanical stimulation of the dorsal epipharynx in mechanically ventilated cats. The magnitude of the hiccup-like reflex was measured as the peak negative esophageal pressure (nPes) generated against an occluded airway. First, we examined the effects of different end-expiratory concentrations of isoflurane on nPes. Second, we determined the effects of 1.0 minimum alveolar anesthetic concentration of isoflurane on nPes after a peripherally restricted gamma aminobutyric acid (GABA)(A)-receptor antagonist, bicuculline methiodide (BM), a GABA(B)-receptor antagonist, CGP 35348, a peripherally restricted GABA(B)-receptor antagonist, CGP 54626, or saline had been administered IV. Third, BM, CGP 35348, or artificial cerebrospinal fluid was administered intracisternally before 1.0 minimum alveolar anesthetic concentration of isoflurane exposure. During isoflurane anesthesia, nPes was inversely proportional to the end-expiratory isoflurane concentration. The rank order of nPes values obtained after IV drug pretreatment and isoflurane exposure was BM < saline < CGP54626 < CGP35348. After intracisternal drug pretreatment and isoflurane administration, the order of nPes was BM < artificial cerebrospinal fluid < CGP35348. Isoflurane modulates the hiccup-like reflex in opposite directions through both central and peripheral GABA(A) and GABA(B) receptors, with the net effect being a dose-dependent suppression. Isoflurane facilitated the hiccup-like reflex through activation of central and peripheral gamma aminobutyric acid (GABA)(A) receptors but suppressed it via activation of central and peripheral GABA(B) receptors. The net result was that the hiccup-like reflex was inhibited in proportion to the alveolar isoflurane concentration.

Minimum alveolar anesthetic concentration of isoflurane with different xenon concentrations in Swine.

For patients requiring a fraction of inspired oxygen more than 0.3, the use of xenon (Xe) as the sole anesthetic is limited because of its large minimum alveolar anesthetic concentration (MAC) of 71%. This warrants investigating the combination of Xe with other inhaled anesthetics. We therefore investigated the influence of Xe on the MAC of isoflurane. The study was performed in 10 swine (weight, 28-35 kg) ventilated with Xe 0%, 15%, 30%, 40%, 50%, and 65% in oxygen. For each Xe concentration, various concentrations of isoflurane were administered in a step-wise design. For each combination, a supramaximal pain stimulus (claw-clamp) was applied, and the appearance of a withdrawal reaction was recorded. The isoflurane MAC was defined as the end-tidal concentration required to produce a 50% response rate. At each Xe concentration, the responses to the pain stimulus were categorized, and a logistic regression model was fitted to the results to determine isoflurane MAC. Isoflurane MAC was decreased by inhalation of Xe in a nonlinear manner from 1.92% (95% confidence interval, 1.70%-2.15%) with 0% Xe to 1.17% (95% confidence interval, 0.75%-1.59%) with 65% Xe. Although this indicates partial antagonism of the two anesthetics, a combination of Xe with isoflurane may prove valuable for patients requiring a fraction of inspired oxygen more than 0.3. We investigated the influence of the anesthetic gas xenon on the minimum alveolar anesthetic concentration (MAC) for isoflurane (another anesthetic gas). The study was performed in 10 swine ventilated with fixed xenon and various concentrations of isoflurane. The isoflurane MAC is decreased by inhalation of xenon in a nonlinear relationship.

Minimum Alveolar Anesthetic Concentration of Isoflurane with Different Xenon Concentrations in Swine

For patients requiring a fraction of inspired oxygen more than 0.3, the use of xenon (Xe) as the sole anesthetic is limited because of its large minimum alveolar anesthetic concentration (MAC) of 71%. This warrants investigating the combination of Xe with other inhaled anesthetics. We therefore investigated the influence of Xe on the MAC of isoflurane. The study was performed in 10 swine (weight, 28–35 kg) ventilated with Xe 0%, 15%, 30%, 40%, 50%, and 65% in oxygen. For each Xe concentration, various concentrations of isoflurane were administered in a step-wise design. For each combination, a supramaximal pain stimulus (claw-clamp) was applied, and the appearance of a withdrawal reaction was recorded. The isoflurane MAC was defined as the end-tidal concentration required to produce a 50% response rate. At each Xe concentration, the responses to the pain stimulus were categorized, and a logistic regression model was fitted to the results to determine isoflurane MAC. Isoflurane MAC was decreased by inhalation of Xe in a nonlinear manner from 1.92% (95% confidence interval, 1.70%–2.15%) with 0% Xe to 1.17% (95% confidence interval, 0.75%–1.59%) with 65% Xe. Although this indicates partial antagonism of the two anesthetics, a combination of Xe with isoflurane may prove valuable for patients requiring a fraction of inspired oxygen more than 0.3.

Effect of the deficiency of spinal PSD-95/SAP90 on the minimum alveolar anesthetic concentration of isoflurane in rats.

Spinal N-methyl-D-aspartate (NMDA) receptor activation has been demonstrated to play an important role in the processing of spinal nociceptive information and in the determination of the minimum alveolar anesthetic concentration (MAC) of inhalational anesthetics. Postsynaptic density-95 (PSD-95)/synapse-associated protein-90 (SAP90), a molecular scaffolding protein that binds and clusters the NMDA receptor perferentially at synapses, was implicated in NMDA-induced thermal hyperalgesia. The current study investigated the possible involvement of PSD-95/SAP9O in determining MAC for isoflurane anesthesia. Sprague-Dawley rats were pretreated intrathecally with PSD-95/SAP90 antisense oligodeoxyribonucleotide (ODN), sense ODN, missense ODN, or saline every 24 h for 4 days. After initial baseline determination of the MAC, NMDA or saline was injected intrathecally. Ten minutes later, MAC measurement was repeated. The rats also were evaluated for the presence of locomotor dysfunction by intrathecal administration of NMDA or saline in the saline- and ODN-treated rats. In the groups treated with antisense ODNs, but not in those treated with sense or missense ODNs, there was a significant decrease in isoflurane MAC that was not accompanied by marked changes in either blood pressure or heart rate. In the saline-treated group, intrathecal NMDA caused an increase in isoflurane MAC. In contrast, in the antisense ODN-treated group, intrathecal NMDA did not produce a significant change in isoflurane MAC. An NMDA-induced increase in blood pressure but not heart rate was found in both saline- and antisense ODN-treated groups. Locomotor activity was not changed in any of the treated animals. The results indicate not only a significant decrease in MAC for isoflurane but also an attenuation in the NMDA-induced increase in isoflurane MAC in the PSD-95/SAP90 antisense-treated animals, which suggests that PSD-95/SAP90 may mediate the role of the NMDA receptor in determining the MAC of inhalational anesthetics.

Nitrous oxide decreases solubility of isoflurane and halothane in blood.

This study investigated the effects of carrier gases on the solubility of isoflurane or halothane in blood. The blood/gas partition coefficients (lambda blood/gas) of 1 minimum alveolar anesthetic concentration of isoflurane or halothane in 100% oxygen, 30% oxygen with 70% nitrous oxide, 100% nitrous oxide or air were measured at 37 degrees C, with blood from four donors. The values of isoflurane or halothane in 100% nitrous oxide (1.42 +/- 0.03; 2.59 +/- 0.05) were lower (P < 0.05) than those obtained when using 100% oxygen (1.53 +/- 0.02; 2.71 +/- 0.05) or air (1.54 +/- 0.03; 2.74 +/- 0.05). To determine the effect of absence of oxygen in the blood containing nitrous oxide on solubility, lambda blood/gas of 1 minimum alveolar anesthetic concentration of isoflurane or halothane in 100% oxygen, a gas mixture (30% oxygen and 70% nitrous oxide) or 100% nitrous oxide were measured under the same conditions. The values of isoflurane or halothane in 100% nitrous oxide (1.29 +/- 0.03; 2.25 +/- 0.08) and in a gas mixture of 30% oxygen and 70% nitrous oxide (1.33 +/- 0.04; 2.29 +/- 0.05) were lower (P < 0.05) than those obtained with 100% oxygen (1.40 +/- 0.03; 2.37 +/- 0.04). We conclude that nitrous oxide decreases the lambda blood/gas of isoflurane or halothane, and that this change of solubility, although small, increases the uptake rate of halothane or isoflurane.