Dose-dependent Effects of Halothane on the Phrenic Nerve Responses to Acute Hypoxia in Vagotomized Dogs

Background: Previous studies in dogs and humans suggest that the carotid body chemoreceptor response to hypoxia is selectively impaired by halothane. The present studies in an open-loop canine preparation were performed to better delineate the effects of anesthetic concentrations of halothane on the carotid body chemoreceptor-mediated phrenic nerve response to an acute hypoxic stimulus.

Methods: Three protocols were performed to study the effects of halothane anesthesia on the phrenic nerve response to 1 min of isocapnic hypoxia (partial pressure of oxygen [PaO2] at peak hypoxia, 35-38 mmHg) in unpremedicated, anesthetized, paralyzed, vagotomized dogs during constant mechanical ventilation. In protocol 1, the dose-dependent effects of halothane from 0.5-2.0 minimum alveolar concentration (MAC) on the hypoxic response during moderate hypercapnia (partial pressure of carbon dioxide [PaCO2], 60-65 mmHg) were studied in 10 animals. In protocol 2, the hypoxic responses at 1 MAC halothane near normocapnia (PaCO2, 40-45 mmHg) and during moderate hypercapnia were compared in an additional four animals. In protocol 3, the hypoxic response of 4 of 10 dogs from protocol 1 was also studied under sodium thiopental (STP) anesthesia after they completed protocol 1.

Results: Protocol 1: Peak phrenic nerve activity (PPA) increased significantly during the hypoxic runs compared with the isocapnic hyperoxic controls at all halothane doses. The phrenic nerve response to the hypoxic stimulus was present even at the 2 MAC dose. Protocol 2: The net hypoxic responses for the two carbon dioxide background levels at 1 MAC were not significantly. Protocol 3: The net hypoxic response of PPA for the STP anesthetic was not significantly different from the 1 MAC halothane dose. Bilateral carotid sinus denervation abolished the PPA response to hypoxia.     

Effects of sevoflurane on respiratory activities in the phrenic nerve of decerebrate cats

Although the depressive effect of sevoflurane on ventilation has been reported, its potency and mode of action on the neural respiratory activity is still unclear. Therefore, the effects of sevoflurane on the phrenic nerve discharge and the respiratory timing were compared with those of halothane.
The efferent activity of the phrenic nerve was recorded from decerebrate, un-anesthetized and artificially ventilated cats, and its power spectrum was calculated. The inspiratory and expiratory periods were measured. Sevoflurane and halothane of the doses of 0.5–1.5 MAC were inhaled for 15 min.
With 0.5 MAC, sevoflurane decreased the total power and two dominant spectral components of the high-frequency oscillation and medium-frequency oscillation in the power spectrum. With the same MAC dose, halothane had a greater depressive effect in a normocapnic condition with the vagus nerves being intact. In a state of hypercapnia or after vagotomy, the effect of halothane was considerably attenuated whereas that of sevoflurane remained unaltered. Halothane increased the neural respiratory rate much more than sevoflurane in both normocapme and hypercapnic states. Vagotomy significantly weakened the effect of halothane to increase the respiratory rate but did not modify the effect of sevoflurane. With 1.0–1.5 MAC, both anesthetics severely decreased the phrenic power spectra and the potency difference became indistinct.
The present findings demonstrate that sevoflurane has a weaker depressive effect on the respiratory nerve discharge and a smaller effect on the neural respiratory rate than halothane when the effects of 0.5 MAC were compared. This may be due to the lesser effect of sevoflurane on the vagal mediated and CO₂-related mechanisms which modulate the global outputs of the central respiratory control system.     

Postanesthetic respiratory depression in humans: A comparison of sevoflurane,isoflurane and halothane

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 the respiratory effects of halothane persisted up to and past the twenty minute mark, far longer than with sevoflurane or isoflurane.(Doi M, Ideda K: Postanesthetic respiratory depression in humans: A comparison of sevoflurane, isoflurane and halothane. J Anesth 1: 137–142, 1987)     

DEPRESSION OF HYPOXIC VENTILATORY RESPONSE BY HALOTHANE, ENFLURANE AND ISOFLURANE IN DOGS

The ventilatory responses to isocapnic hypoxia and hypercapniawere studied in six dogs each with a tracheostomy, awake andduring anaesthesia with halothane, enflurane and isoflurane(1–2.5 MAC). Isocapnic hypoxic ventilatory response (HVR)was expressed as the parameter A, such that the greater thevalue of A, the greater the hypoxic response. In the anaesthetizeddogs HVR (A) was reduced significantly from the awake valueof 2010±172 (mean+SEM) to 630±173 by 1 MAC halothane,495± 105 by 1 MAC enflurane and 952±157 by 1 MACisoflurane (P<0.05). All three anaesthetic agents producedsignificant depression of HVR at 1 MAC, but enflurane was moredepressant than isoflurane. At 1.5 MAC all three anaestheticsproduced equal and significant depression of HVR at equianalgesicconcentrations. Further increases in anaesthetic concentrationcaused no increase in depression. Hypercapnic drive, as measuredby the slope of the VE/PA_co2 response curve, was reduced significantlyfrom 9.75 litre min^–1 kPa^–1 ± 2.4 in awakedogs to 0.83 ± 0.56 after 1 MAC halothane, 0.68 ±0.53after 1 MAC enflurane and 1.58 ±0.75 after 1 MAC isoflurane.In addition, hypercapnia-induced augmentation of the hypoxicdrive was abolished by 1 MAC halothane or enflurane and diminishedmarkedly by 1 MAC isoflurane. It may be clinically significantthat hypoxia and hypercapnia during anaesthesia with these agentsdid not produce optimal stimulation of ventilation.     

Effects of Halothane on the Phrenic Nerve Responses to Carbon Dioxide Mediated by Carotid Body Chemoreceptors in Vagotomized Dogs

Background: Previous studies in dogs showed that the phrenic nerve response to an acute hypoxic stimulus was dose dependently depressed by 0.5-2.0 minimum alveolar concentration (MAC) of halothane but not abolished. Because a carbon dioxide stimulus is transduced by a different mechanism in the carotid body chemoreceptors (CBCRs) than is a hypoxic stimulus, inhalational anesthetics may preferentially depress one of these transduction processes, the central neuronal processing, or both, of the integrated responses to these two types of inputs.

Methods: Carotid body chemoreceptor stimulation was produced by short (1-1.5 s), bilateral, 100% carbon dioxide in saline infusions into the carotid arteries during neural inspiration in unpremeditated, halothane-anesthetized, paralyzed, vagotomized dogs during constant mechanical ventilation. The phrenic neurogram quantified the neural inspiratory response. Four protocols were performed in the study: (1) the dose-dependent effects of halothane anesthesia (0.5-2.0 MAC) during hyperoxic hypercapnia on phrenic nerve activity, (2) the effects of three background levels of the partial pressure of carbon dioxide (PaCO2) on the magnitude of the carbon dioxide infusion responses at 1 MAC halothane, (3) the effects of anesthetic type on the magnitude of the carbon dioxide infusion response, and (4) the effects of CBCR denervation.

Results: Peak phrenic nerve activity (PPA) increased significantly during the carbon dioxide-stimulated phrenic burst in protocols 1-3; after denervation there was no response (protocol 4). Halothane produced a dose-dependent reduction in the PPA of control and carbon dioxide infusion-stimulated phrenic bursts and in the net carbon dioxide response. The net PPA responses for the different PaCO2 background levels were not different but were somewhat larger for sodium thiopental anesthesia than for 1.0 MAC halothane.     

Contribution of peripheral chemoreception to the depression of the hypoxic ventilatory response during halothane anesthesia in cats

BACKGROUND: The effects of inhalational anesthetics on the hypoxic ventilatory response are complex. This study was designed to determine the contribution of peripheral chemoreception to the depression of hypoxic ventilatory response seen with halothane anesthesia. METHODS: Cats were anesthetized with pentobarbital sodium and alpha-chloralose and artificially ventilated. Respiratory output was evaluated by phasic inspiratory activity of the phrenic nerve. In 12 cats, this activity was measured during inhalation of an hypoxic gas mixture with halothane, 0, 0.1, and 0.8%, with intact or denervated carotid bodies. In 10 cats, a carotid body was isolated from the systemic circulation and perfused with hypoxic Krebs-Ringer solution equilibrated with halothane, 0, 0.1, and 0.8%. RESULTS: The hypoxic ventilatory response was depressed in a dose-dependent manner during halothane anesthesia. In carotid body perfusion studies, the response was significantly depressed only with halothane, 0.80%. CONCLUSION: The hypoxic ventilatory response is depressed by a high dose of halothane through a peripheral effect at the carotid body.     

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.     

The minimum alveolar concentration (MAC) and hemodynamic effects of halothane, isoflurane, and sevoflurane in newborn swine

To determine the minimum alveolar concentration (MAC) and hemodynamic responses to halothane, isoflurane, and sevoflurane in newborn swine, 36 fasting swine 4-10 days of age were anesthetized with one of the three volatile anesthetics in 100% oxygen. MAC was determined for each swine. Carotid artery and internal jugular catheters were inserted and each swine was allowed to recover for 48 h. After recovery, heart rate (HR), systemic systolic arterial pressure (SAP), and cardiac index (CI) were measured awake and then at 0.5, 1.0, and 1.5 MAC of the designated anesthetic in random sequence. The (mean +/- SD) MAC for halothane was 0.90 +/- 0.12%; the MAC for isoflurane was 1.48 +/- 0.21%; and the MAC for sevoflurane was 2.12 +/- 0.39%. Awake (mean +/- SD) measurements of HR, SAP, and CI did not differ significantly among the three groups. Compared to the awake HR, the mean HR decreased 35% at 1.5 MAC halothane (P less than 0.001), 19% at 1.5 MAC isoflurane (P less than 0.005), and 31% at 1.5 MAC sevoflurane (P less than 0.005). Compared to awake SAP, mean SAP measurements decreased 46% at 1.5 MAC halothane (P less than 0.001), 43% at 1.5 MAC isoflurane (P less than 0.001), and 36% at 1.5 MAC sevoflurane (P less than 0.005). Mean SAP at 1.0 and 1.5 MAC halothane and isoflurane were significantly less than those measured at equipotent concentrations of sevoflurane (P less than 0.005). Compared to awake CI, mean CI measurements decreased 53% at 1.5 MAC halothane (P less than 0.001) and 43% at 1.5 MAC isoflurane (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)     

The comparative cardiovascular effects of sevoflurane with halothane and isoflurane

Using closed chest dogs, the cardiovascular effects of sevoflurane were compared with those of halothane and isoflurane in equipotent doses of 1.0, 1.5, 2.0, 2.5 and 3.0 MAC. They were evaluated by the changes of arterial blood pressure, central venous pressure, pulmonary artery pressure, maximum rate of left ventricular pressure rise (LV dp/dt), cardiac output and coronary sinus blood flow. The suppression of left cardiac function by sevoflurane was less than that of halothane, but was greater than that of isoflurane. Heart rate, systemic vascular resistance with sevoflurane were slightly lower than that of isoflurance. The coronary sinus blood flows with sevoflurane and isoflurane were significantly (P < 0.05 at 1.0 MAC, P < 0.005 at 2.0 MAC) higher than halothane. There was no significant difference on coronary sinus flow between sevoflurane and isoflurane. The depth of anesthesia could be quickly changed by adjustment of inspired sevoflurane concentration in comparison with the other two anesthetics.(Kazama T, Ikeda K: The comparative cardiovascular effects of sevoflurane with halothane and isoflurane. J Anesth 2: 63–68, 1988)     

The effects of sevoflurane, halothane, enflurane, and isoflurane on hepatic blood flow and oxygenation in chronically instrumented greyhound dogs.

Inhalational anesthetics produce differential effects on hepatic blood flow and oxygenation that may impact hepatocellular function and drug clearance. In this investigation, the effects of sevoflurane on hepatic blood flow and oxygenation were compared with those of enflurane, halothane, and isoflurane in ten chronically instrumented greyhound dogs. Each dog randomly received enflurane, halothane, isoflurane, and sevoflurane, each at 1.0, 1.5, and 2.0 MAC concentrations. Mean arterial blood pressure and cardiac output decreased in a dose-dependent fashion during all four anesthetics studied. Heart rate increased compared to control during enflurane, isoflurane, and sevoflurane anesthesia and did not change during halothane anesthesia. Hepatic arterial blood flow and portal venous blood flow were measured by chronically implanted electromagnetic flow probes. Hepatic O2 delivery and consumption were calculated after hepatic arterial, portal venous, and hepatic venous blood gas analysis. Hepatic arterial blood flow was maintained with sevoflurane and isoflurane. Halothane and enflurane reduced hepatic arterial blood flow during all anesthetic levels compared to control (P less than 0.05), with marked reductions occurring with 1.5 and 2.0 MAC halothane concomitant with an increase in hepatic arterial vascular resistance. Portal venous blood flow was reduced with isoflurane and sevoflurane at 1.5 and 2.0 MAC. A somewhat greater reduction in portal venous blood flow occurred during 2.0 MAC sevoflurane (P less than 0.05 compared to control and 1.0 MAC values for sevoflurane). Enflurane reduced portal venous blood flow at 1.0, 1.5, and 2.0 MAC compared to control. Halothane produced the greatest reduction in portal venous blood flow (P less than 0.05 compared to sevoflurane).(ABSTRACT TRUNCATED AT 250 WORDS)     

Contribution of Peripheral Chemoreception to the Depression of the Hypoxic Ventilatory Response during Halothane Anesthesia in Cats

Background: The effects of inhalational anesthetics on the hypoxic ventilatory response are complex. This study was designed to determine the contribution of peripheral chemoreception to the depression of hypoxic ventilatory response seen with halothane anesthesia.

Methods: Cats were anesthetized with pentobarbital sodium and [Greek small letter alpha]-chloralose and artificially ventilated. Respiratory output was evaluated by phasic inspiratory activity of the phrenic nerve. In 12 cats, this activity was measured during inhalation of an hypoxic gas mixture with halothane, 0, 0.1, and 0.8%, with intact or denervated carotid bodies. In 10 cats, a carotid body was isolated from the systemic circulation and perfused with hypoxic Krebs-Ringer solution equilibrated with halothane, 0, 0.1, and 0.8%.

Results: The hypoxic ventilatory response was depressed in a dose-dependent manner during halothane anesthesia. In carotid body perfusion studies, the response was significantly depressed only with halothane, 0.8%.     

Anticonvulsant effects of sevoflurane on amygdaloid kindling and bicuculline-induced seizures in cats: comparison with isoflurane and halothane

Purpose. We compared the anticonvulsant effects of sevoflurane with those of isoflurane and halothane in amygdaloid kindling and bicuculline-induced seizures in cats. Methods. In a crossover design, the effects of 70% nitrous oxide, and 0.3, 0.6, and 1.5 minimum alveolar concentration (MAC) of volatile anesthetics were studied in five cats in which the amygdala was electrically stimulated at the current used for establishing the kindled state. The effects of 0.6 and 1.5 MAC of volatile anesthetics were studied in another five cats, in which 0.2 mg·kg⁻¹ of bicuculline was administered IV. Results. In the amygdaloid kindling model, all four anesthetics decreased the duration of after-discharge (AD), the rise of multiunit activity in midbrain reticular formation (R-MUA), and the behavior scores compared with findings without anesthetics. Halothane, at 1.5 MAC, significantly decreased the number of cats showing AD (P < 0.05). In the bicuculline-induced seizure model, all five cats showed repetitive spikes during 1.5 MAC of sevoflurane, whereas only two and three cats, respectively, showed the repetitive spikes during 1.5 MAC of isoflurane and halothane. All three volatile anesthetics decreased the rise of R-MUA, the duration of the repetitive spikes, and the behavior scores. The suppression of the rise in R-MUA and the behavior scores with 1.5 MAC of sevoflurane was significantly less than that with 1.5 MAC of isoflurane. Conclusion. The anticonvulsant effects of sevoflurane were less potent than those of halothane in the amygdaloid kindling model and less potent than those of isoflurane in the bicuculline-induced seizure model. Received: January 11, 2001 / Accepted: May 9, 2001     

Effects of halothane and isoflurane anesthesia on sympathetic adrenal nerve responses to carbon dioxide challenge in rats

We studied the influence of two volatile anesthetics, halothane and isoflurane, on the circulatory and sympathetic nerve responses to carbon dioxide (9% CO₂) in rats.Systolic blood pressure was depressed throughout the CO₂ challenge and after an initial reduction, a gradual increase was observed in heart rate. Sympathetic adrenal nerve action potentials (SANA) significantly increased in contrast to negative responses in the circulatory functions. SANA responses against time were trapezoid in shape. There were no significant differences in SANA responses between 1% (1 MAC) and 1.5% (1.5 MAC) halothane groups, nor between 1.4% (1 MAC) and 2% (1.5 MAC) isoflurane groups. Halothane and isoflurane, therefore, did not produce dose-dependent effects on sympathetic response to hypercapnia within these concentrations. The maximum changes in SANA from the baseline values were 110% and 40% for the halothane and isoflurane groups, respectively.The sympathetic reflex response to hyperacapnia was retained at 1.5 MAC for both anesthetics, though isoflurane depressed these responses more markedly than halothane.Our results suggest that halothane is a more preferable anesthetic than isoflurane when viewed from the standpoint of preservation of sympathetic nerve response in such undesirable situations as severe hypercapnia occurring during anesthesia.(Amagasa S, Takahashi T, Takaoka S, et al.: Effects of halothane and isoflurane anesthesia on sympathetic adrenal nerve responses to carbon dioxide challenge in rats. J Anesth 7: 454–461, 1993)     

Minimum Alveolar Concentration of Volatile Anesthetics in Rats during Postnatal Maturation

Background: Although neonatal rats have become widely used as experimental laboratory animals, minimum alveolar concentration (MAC) values of volatile anesthetics in rats during postnatal maturation remain unknown.

Methods: We determined MAC values of volatile anesthetics in spontaneously breathing neonatal (2-, 9-, and 30-day-old) and adult Wistar rats exposed to increasing (in 0.1-0.2% steps) concentrations of halothane, isoflurane, or sevoflurane (n = 12-20 in each group), using the tail-clamp technique. MAC and its 95% confidence intervals were calculated using logistic regression and corrected for body temperature (37[degrees]C).

Results: In adult rats, inspired MAC values corrected at 37[degrees]C were as follows: halothane, 0.88% (confidence interval, 0.82-0.93%); isoflurane, 1.12% (1.07-1.18%); and sevoflurane, 1.97% (1.84-2.10%). In 30-day-old rats, the values were as follows: halothane, 1.14% (1.07-1.20%); isoflurane, 1.67% (1.58-1.76%); and sevoflurane, 2.95% (2.75-3.15%). In 9-day-old rats, inspired MAC values were as follows: halothane, 1.68% (1.58-1.78%); isoflurane, 2.34% (2.21-2.47%); and sevoflurane, 3.74% (3.64-3.86%). In 2-day-old rats, inspired MAC values were as follows: halothane, 1.54% (1.44-1.64%); isoflurane, 1.86% (1.72-2.01%); and sevoflurane, 3.28% (3.09-3.47%).     

Relative amnesic potency of five inhalational anesthetics follows the Meyer-Overton rule

BACKGROUND: Doses of volatile anesthetics around 0.3 minimum alveolar concentration (MAC) inhibit learning. However, threshold amnesic doses and relative potencies between agents are not well established. The authors determined amnesic potency in rats for four common volatiles and nitrous oxide. METHODS: After institutional review board approval, adult Sprague-Dawley rats received inhibitory avoidance training during exposure to either air or various subanesthetic doses of desflurane, sevoflurane, isoflurane, halothane, or nitrous oxide (4-21 rats/dose). Animals were trained to remain in a starting "safe" compartment for 100 consecutive seconds by administering a foot shock (0.3 mA) each time they entered an adjacent "shock" compartment. Memory was assessed at 24 h. Anesthetic effects on pain thresholds were separately determined. RESULTS: Learning: Only relatively higher doses of sevoflurane, halothane, and desflurane increased the number of shocks required for task acquisition. Memory: Significantly decreased retention performance (P < 0.05) was found at relatively low inspired concentrations of 0.2% isoflurane, 0.3% sevoflurane and halothane, 0.44% desflurane, and 20% nitrous oxide. Amnesic potency was nitrous oxide >/= desflurane > sevoflurane >/= isoflurane > halothane, (rank-ordered ED50 values as %MAC). Amnesic potency correlated with oil:gas partition coefficients (r = -0.956, P < 0.007). Halothane, only at 0.08%, enhanced retention (P < 0.01). All agents were analgesic at higher doses. CONCLUSIONS: Amnesic potency differs between agents; nitrous oxide is most potent and halothane is least potent relative to MAC. The amnesic threshold ranges from 0.06 to 0.3 MAC. The correlation between potency and oil:gas partition coefficients suggests a fundamental role for hydrophobicity in mediating amnesia, similar to its association with MAC. Some agents (e.g., halothane) may enhance aversive memory retention at doses typically encountered during emergence.     

Circulatory and catecholamine responses to tracheal intubation and skin incision during sevoflurane, isoflurane, or halothane anesthesia

The anesthetic suppression of responses to noxious stimuli might reflect a summation of the suppression of the basal functions and the response capability. We investigated the basal suppression and response capability in hemodynamics and plasma catecholamine levels with different anesthetics at the same minimum alveolar concentration (MAC) level. Fifty-four patients were allocated to one of 6 groups to receive sevoflurane, isoflurane, or halothane at 1.25 or 2.0 MAC. Anesthesia was induced with the test agent in oxygen and the end-tidal concentration of the agent was maintained for at least 15 min at 1.25 or 2.0 MAC. The trachea was intubated under muscle relaxation with 0.1 mg·kg⁻¹ vecuronium. Skin incisions were made after maintaining the end-tidal concentration of the agent for at least 15 min after tracheal intubation. The mean arterial pressure, heart rate, rate-pressure product, and plasma levels of noradrenaline and adrenaline at the prestimuli period showed no difference between agents at each MAC. The rises in these variables by tracheal intubation and skin incision were greatest in the sevoflurane group, least in the halothane group, and intermediate in the isoflurane group. Although basal hemodynamic suppression is similar at the same MAC, the suppressive action of sevoflurane on the circulatory response capability to noxious stimuli is weaker than that of isoflurane and halothane. This study was presented in part at the 42nd annual congress of the Japan Society of Anesthesiology, April 20, 1995     

Recovery Times and Evaluation of Clinical Hemodynamic Parameters of Sevoflurane,Isoflurane and Halothane Anaesthesia in Mongrel Dogs

In the present study the influence of three volatile agents (halothane, isoflurane and sevoflurane) in oxygen at two concentrations [1.5 and 2 minimum alveolar concentration (MAC)] on non‐invasive cardio‐respiratory parameters (heart and respiratory rates, non‐invasive blood pressures at 15, 30, 60 min and after extubation) and on the recovery times (appearance of the first eyelid reflex, emergence time) after clinical anaesthesia was studied. After premedication with fentanyl‐droperidol (5 μg/kg and 0.25 mg/kg, intramuscularly) and induction with propofol (5 mg/kg, intravenously) six dogs were randomly anaesthetized for 1 h for a standard neurologic stimulation test. A wide individual variation in respiration rate (induced by an initial hyperpnea) was observed in the 1.5 MAC protocols, without significant differences. Heart rate was significantly lower during 1.5 and 2 MAC halothane when compared to isoflurane and sevoflurane. An increase from 1.5 to 2 MAC induced significant decreases in diastolic (DAP) and mean arterial blood pressure in all groups without significant changes in the systolic arterial pressures. Only DAP in sevoflurane protocol was significantly different at 1.5 and 2 MAC compared to halothane. Time had no significant influences on the non‐invasive blood pressures in all protocols. Extubation induced a significant increase of all parameters in all protocols. The time for a first eyelid reflex was significantly longer after 2 MAC compared to the 1.5 MAC protocol. There was no significant difference between the three anaesthetic agents. Although emergence time was longest for halothane at both anaesthetic concentrations, no significant difference in emergence time was observed for the three volatile agents.     

The anticonvulsant effects of volatile anesthetics on penicillin-induced status epilepticus in cats

Volatile anesthetics may be used to treat status epilepticus when conventional drugs are ineffective. We studied 30 cats to compare the inhibitory effects of sevoflurane, isoflurane, and halothane on penicillin-induced status epilepticus. Anesthesia was induced and maintained with one of the three volatile anesthetics in oxygen. Penicillin G was injected into the cisterna magna, and the volatile anesthetic discontinued. Once status epilepticus was induced (convulsive period), the animal was reanesthetized with 0.6 minimum alveolar anesthetic concentration (MAC) of the volatile anesthetic for 30 min, then with 1.5 MAC for the next 30 min. Electroencephalogram and multiunit activity in the midbrain reticular formation were recorded. At 0.6 MAC, all anesthetics showed anticonvulsant effects. Isoflurane and halothane each abolished the repetitive spike phase in one cat; isoflurane reduced the occupancy of the repetitive spike phase (to 27%+/-22% of the convulsive period (mean +/- SD) significantly more than sevoflurane (60%+/-29%; P < 0.05) and halothane (61%+/-24%; P < 0.05), and the increase of midbrain reticular formation with repetitive spikes was reduced by all volatile anesthetics. The repetitive spikes were abolished by 1.5 MAC of the anesthetics: in 9 of 10 cats by sevoflurane, in 9 of 9 cats by isoflurane, and in 9 of 11 cats by halothane. In conclusion, isoflurane, sevoflurane, and halothane inhibited penicillin-induced status epilepticus, but isoflurane was the most potent. IMPLICATIONS: Convulsive status epilepticus is an emergency state and requires immediate suppression of clinical and electrical seizures, but conventional drugs may be ineffective. In such cases, general anesthesia may be effective. In the present study, we suggest that isoflurane is preferable to halothane and sevoflurane to suppress sustained seizure.     

The anticonvulsant effects of volatile anesthetics on lidocaine-induced seizures in cats

Large concentrations of sevoflurane and isoflurane, but not halothane, induce spikes in the electroencephalogram. To elucidate whether these proconvulsant effects affect lidocaine-induced seizures, we compared the effects of sevoflurane, isoflurane, and halothane in cats. Fifty animals were allocated to 1 of 10 groups: 70% nitrous oxide (N2O), 0.6 minimum alveolar anesthetic concentration (MAC) + 70% N2O, 1.5 MAC + 70% N2O, and 1.5 MAC of each volatile agent in oxygen. Lidocaine 4 mg x kg(-1) x min(-1) was infused IV under mechanical ventilation with muscle relaxation. Electroencephalogram in the cortex, amygdala, and hippocampus and multiunit activities in the midbrain reticular formation (R-MUA) were recorded. Lidocaine induced spikes first from the amygdala or hippocampus in the 70% N2O and halothane groups and from the cortex in the sevoflurane and isoflurane groups. Lidocaine induced seizures in all cats in the 70% N2O and 0.6 MAC + N2O groups. Seizure occurrence was reduced in the 1.5 MAC + N2O group (P < 0.05 versus 70% N2O). The onset of seizure was delayed in the 0.6 MAC + N2O and 1.5 MAC groups for sevoflurane and isoflurane, but not for halothane, compared with the 70% N2O group (P < 0.05). Lidocaine increased R-MUA with seizure by 130%+/-56% in the 70% N2O group. The increase of R-MUA with seizure was more suppressed in the volatile anesthetic groups than in the 70% N2O group (P < 0.05). In the present study, sevoflurane and isoflurane attenuated seizure when the blood lidocaine concentration was accidentally increased. IMPLICATIONS: Increasingly, epidural blockade is combined with general anesthesia to achieve stress-free anesthesia and continuous pain relief in the postoperative period. In the present study, sevoflurane and isoflurane attenuated seizure when the blood lidocaine concentration was accidentally increased.     

Minimum alveolar concentration of volatile anesthetics in rats during postnatal maturation

BACKGROUND: Although neonatal rats have become widely used as experimental laboratory animals, minimum alveolar concentration (MAC) values of volatile anesthetics in rats during postnatal maturation remain unknown. METHODS: We determined MAC values of volatile anesthetics in spontaneously breathing neonatal (2-, 9-, and 30-day-old) and adult Wistar rats exposed to increasing (in 0.1-0.2% steps) concentrations of halothane, isoflurane, or sevoflurane (n = 12-20 in each group), using the tail-clamp technique. MAC and its 95% confidence intervals were calculated using logistic regression and corrected for body temperature (37 degrees C). RESULTS: In adult rats, inspired MAC values corrected at 37 degrees C were as follows: halothane, 0.88% (confidence interval, 0.82-0.93%); isoflurane, 1.12% (1.07-1.18%); and sevoflurane, 1.97% (1.84-2.10%). In 30-day-old rats, the values were as follows: halothane, 1.14% (1.07-1.20%); isoflurane, 1.67% (1.58-1.76%); and sevoflurane, 2.95% (2.75-3.15%). In 9-day-old rats, inspired MAC values were as follows: halothane, 1.68% (1.58-1.78%); isoflurane, 2.34% (2.21-2.47%); and sevoflurane, 3.74% (3.64-3.86%). In 2-day-old rats, inspired MAC values were as follows: halothane, 1.54% (1.44-1.64%); isoflurane, 1.86% (1.72-2.01%); and sevoflurane, 3.28% (3.09-3.47%). CONCLUSION: As postnatal age increases, MAC value significantly increases, reaching the greatest value in 9-day-old rats, and decreases thereafter, and at 30 days is still greater than the adult MAC value.