Isoflurane General Anesthesia Research Articles

The Effect of Repeated Isoflurane Anesthesia on Spatial and Psychomotor Performance in Young and Aged Mice

Exposure to general anesthesia may contribute to postoperative cognitive impairment in elderly patients, but the relationship remains poorly understood. We investigated whether aged mice, 18-19 mo, are more susceptible to postanesthetic cognitive impairment than young mice, 3-4 mo, using spatial memory (Barnes maze) and psychomotor (rotarod) tasks. Initially we studied the effect of a single anesthetic episode on asymptotic maze performance. We then tested whether repeated anesthesia would impair spatial memory and psychomotor performance to a greater extent in aged mice. Mice were anesthetized with isoflurane (1.4% atm) for 30 min; controls received 90% oxygen. Anesthesia, administered during the asymptotic period of maze learning, did not impair performance tested the following day (P > 0.05). Repeated anesthesia, 2-3 h after each session, did not impair overall maze or rotarod performance in young or aged mice (P > 0.05). Spatial learning appeared to be facilitated by anesthesia, F(1,204) = 7.97, P < 0.01 for pooled results. Asymptotic performance-when learning had stabilized-remained unimpaired in both the maze and rotarod tasks. These results suggest that an age-related risk of anesthetic-induced impairment appears to be limited to acquisition of a novel motor skill and that anesthesia alone does not lead to prolonged cognitive impairments in aged mice. This study demonstrates that repeated isoflurane general anesthesia impaired psychomotor performance in aged mice during the initial learning period; however, spatial learning improved and, overall, spatial memory and psychomotor performance were unimpaired. Thus, general anesthesia alone does not appear to result in prolonged cognitive deficits in aged mice.

The Effect of Intravenous Adenosine Infusion on Temporal Intraoperative Blood Pressure Changes and Postoperative Pain Scores in Laparoscopic Cholecystectomy Patients

Background: Adenosine has been shown to exert an antinociceptive effect under experimental conditions in animals and humans. This study was performed to evaluate the effects of adenosine on postoperative pain and intraoperative blood pressure changes. Methods: We studied 30 patients, aged -isoflurane general anesthesia. Patients were randomized into two groups: an adenosine group (adenosine was infused continuously at 100-150 /kg/min, n = 15) and a control group (normal saline infused at 4 ml/min, n = 15). Mean arterial blood pressure during the intraoperative period, and pain score at 30 minutes, 6 hours, 24 hours, and 48 hours after operation were checked. On patient request, meperidine was administrated intravenously. Results: Pain scores and the cumulative doses of meperidine were much lower in the adenosine group than in the control group. The elevation of mean arterial pressure during pnemoperiton-eum was significantly attenuated in the adenosine group. Conclusions: This data suggests that intravenous adenosine infusion is effective at post-operative pain control following a laparoscopic cholecystectomy and that it is also effective at attenuating blood pressure elevation during pneumoperitoneum.

Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity

Background and Objectives: We previously demonstrated in rats that intravenous infusion of a lipid emulsion increases survival in resuscitation from severe bupivacaine cardiac toxicity. The present studies were undertaken to determine if this method is similarly effective in a non-rodent model using a larger animal. Methods: Bupivacaine, 10 mg/kg, was administered intravenously over 10 seconds to fasted dogs under isoflurane general anesthesia. Resuscitation included 10 minutes of internal cardiac massage followed with either saline or 20% lipid infusion, administered as a 4-mL/kg bolus followed by continuous infusion at 0.5 mL/kg/min for 10 minutes. Electrocardiogram (EKG), arterial blood pressure (BP), and myocardial pH (pHm) and pO2 (pmO2) were continuously measured. Results: Survival after 10 minutes of unsuccessful cardiac massage was successful for all lipid-treated dogs (n = 6), but with no survivors in the saline controls (n = 6) (P < .01). Hemodynamics, PmO2, and pHm were improved during resuscitation with lipid compared with saline treatment in which dogs did not recover. Conclusions: We found that infusing a lipid emulsion during resuscitation from bupivacaine-induced cardiac toxicity substantially improved hemodynamics, pmO2, and pHm and increased survival in dogs. Reg Anesth Pain Med 2003;28:198-202.

Changes in Serum Concentrations of Insulin-like Growth Factor-1 (IGF-1) during Different Methods of General Anesthesia

Background: IGFs (insulin-like growth factors) exert acute anabolic effects on protein and carbohydrate metabolism, and have a long-term impact on cell proliferation, differentiation, and apoptosis. The purpose of this study was to evaluate whether serum levels of IGF-1 were affected by the general anesthetics. Methods: Twenty patients, scheduled for a total abdominal hysterectomy were given either propofol (n = 10) or isoflurane (n = 10) general anesthesia. All patients were treated in a standardized manner in regard to surgical technique. Blood samples were taken before induction and at the time of peritoneal closure, postoperative 1 hour, and on postoperative days 2 and 5. Serum concentrations of IGF-1 were determined using an immunoradiometric assay. Results: IGF-1 levels decreased from the value before induction by 17.1% during surgery and 37.5% by day 5 in the propofol group. IGF-1 levels fell by 18.7% during surgery and returned to the preinduction level on day 5 after surgery in the isoflurane group. There were no differences in IGF-1 levels between the two groups with different methods of anesthesia. Conclusions: Our study suggests that general anesthesia with isoflurane is associated with a less effect in serum IGF-1 level than propofol. However, further experimental and clinical studies are needed to establish the definitive effect of general anesthetics on IGF.

Similar long-term cardiovascular effects of propofol or isoflurane anesthesia during ischemia/ reperfusion in dogs.

To compare the long-term functional and metabolic effects of propofol or isoflurane general anesthesia in a canine model of ischemia/reperfusion. Using magnetic resonance (MR) techniques, we monitored both regional metabolism ((31)P MR spectroscopy) and systolic function of the heart ((1)H MR imaging) throughout a two-hour occlusion of the left anterior descending coronary artery and ten days of reperfusion. Twenty-two beagles were randomized into isoflurane and propofol general anesthesia groups (n = 10, n = 12 respectively). Contrast-enhanced MR imaging was used to measure infarct size (% of left ventricle that was necrotic) and coronary blood flow was determined using radioactively labelled microspheres. Cardiac metabolism, as monitored by intracellular pH and high-energy phosphate ratios, was not significantly different between the two groups throughout the protocol. Relative to propofol, isoflurane reduced the depression of left ventricular ejection fraction (EF) during the ischemic period [isoflurane 68.5% +/- 4.2%, propofol 58.3% +/- 2.0% of baseline (B); P = 0.04], propofol increased the recovery of EF at day three (isoflurane 63.9% +/- 4.3%, propofol 74.0% +/- 2.5% of B; P = 0.05). By day ten, EF in both groups was similar. Infarct sizes were also similar at day ten (isoflurane 15.7% +/- 3.0%, propofol 13.2% +/- 2.2%). Normalizing these by the region at risk (volume of tissue with low blood flow during the occlusion) to assess infarct ratios was also not significant (isoflurane 0.58% +/- 0.08%, propofol 0.54% +/- 0.07%). There were no significant differences between the two anesthetic groups at day ten, suggesting that any apparent dissimilarities in early cardiovascular effects were short-term only. These results indicate that isoflurane and propofol produce equivalent long-term cardiovascular effects following ischemia/reperfusion.

Intravenous Cisplatin Administration in Sulphur-Crested Cockatoos (Cacatua galerita): Clinical and Pathologic Observations

The prevalence of neoplasia in birds is generally low; however, in some species of companion and aviary birds, the incidence is high and neoplasia is a common cause of death. Surgical excision or limb amputation has been performed as the therapeutic plan. Chemotherapy in the treatment of avian neoplasia is largely empirical and poorly documented. For example, cisplatin has been used intralesionally in macaws (Ara species) with limited clinical success. Eight sulphur-crested cockatoos (Cacatua galerita), under general isoflurane anesthesia, were infused intravenously with cisplatin at 6.4 or 1.0 mg/kg over 1 hour and hydrated with lactated Ringer's solution for 1 hour before and 2 hours after cisplatin infusion. Birds were euthanatized 96 hours after infusion, except for 2 birds given the low cisplatin dose, which were euthanatized on day 35 after dosing. All birds tolerated the study procedure while under anesthesia. Blood pressure, heart rate, and respiratory rate did not change significantly. In the low-dose group, the mean cloacal temperature decreased significantly during the infusion period (P < .001) and then rose progressively to preinfusion values by 24 hours. Also in this group, the mean body weight tended to increase during the infusion period before significantly decreasing (P < .05) by 5% at 96 hours after dosing. At 24 hours after dosing, all birds were bright and eating. However, intermittent regurgitation and fecal changes (moist, dark green feces and yellow urates) occurred in 3 of 8 birds, especially those given the high dose. By 72 hours after dosing, droppings in the low-dose group were normal in appearance. One bird in the high-dose group died by 94 hours after dosing. Myelosuppression was not observed in any bird and at necropsy, no evidence of cisplatin toxicity was found except in 1 bird given the high cisplatin dose. On histology, this bird showed nephrotoxicity, and its serum uric acid levels and mean estimated white blood cell count increased significantly by 24 hours after dosing. This paper reports for the first time the effect of systemic cisplatin administration in birds and provides veterinarians data for formulating efficacious and safe protocols for platinum-containing compounds when treating neoplasia in parrots and other companion birds.

Heart rate variability during artificial ventilation and apnea in brain-damaged rabbits.

The effect of artificial ventilation, apnea, and norepinephrine administration on heart rate variability was determined in brain-damaged rabbits. Electrocardiographic R-R intervals and circulatory variables were measured for 5 min at three different ventilatory frequencies, including apnea under isoflurane general anesthesia. The same measurements were repeated after brain damage was inflicted by an inflated intracranial balloon. In control rabbits (n = 8) and in those receiving norepinephrine (n = 8), power spectral analysis of R-R intervals was repeated, and spectral components of low (LF: 0.04-0.09 Hz), mid (MF: 0.09-0.15 Hz), and high (HF: 0.15-0.40 Hz) frequency band areas were assessed. LF + MF (P < 0.05) increased during apnea, whereas HF did not change under general anesthesia. However, after brain damage in both groups LF + MF did not change, whereas HF was depressed (P < 0.05). There was no intergroup difference in decreases of HF/(LF + MF) (P < 0.05) during apnea under either condition. Norepinephrine increased heart rate and arterial pressure (P < 0.05) but did not produce any intergroup difference in the spectral components. We suggest that sympathovagal balance is apt to be sympathotonic during apnea under general anesthesia, whereas it is vagolytic with brain damage.

Efficacy of Epidural Test Doses?

To the Editor: We are concerned that Tanaka et al. [1] did not prospectively determine appropriate hemodynamic criteria for identification of intravascular injection in their recent study examining epidural test doses during isoflurane general anesthesia. Instead, they used criteria previously derived from awake adults [2] and arbitrarily chosen alternate criteria. However, isoflurane produces dose-dependent decreases in baseline hemodynamic variability due to decreased sympathetic tone [3], as was also observed by Tanaka et al. Thus, criteria determined from either awake subjects or the arbitrarily chosen alternate criteria are probably of too large a magnitude for patients undergoing general anesthesia. Positive criteria should have been prospectively defined from the maximal increases in hemodynamics after injection of normal saline using 95% or 99% confidence intervals to determine what magnitude of change constitutes a significant hemodynamic increase. The use of inappropriately "large" hemodynamic criteria may not only call into question the reported incidences of sensitivity and specificity, but may also lead to unrecognized intravascular injection of local anesthetic during isoflurane general anesthesia. Paul D. Ware, MD Spencer S. Liu, MD Department of Anesthesiology Virginia Mason Medical Center Seattle, WA 98111

Preservation of Neurogenic Motor-Evoked Potentials During Isoflurane Electroencephalographic Burst Suppression in Rats

A prospective laboratory study was performed in a rat model. To test the hypothesis that neurogenic motor-evoked potentials are more resistant to suppressive changes from the volatile anesthetic isoflurane than cortically recorded somatosensory-evoked potentials and electroencephalography. Techniques for monitoring spinal cord motor tracts have been developed because sensory tract monitoring with somatosensory-evoked potentials is at times inadequate. Potentials from transcranial magnetic and electrical stimulation are very sensitive to anesthesia. Neurogenic motor-evoked potentials are thought to be more resistant. Eight mature Sprague-Dawley rats were studied during isoflurane general anesthesia. Two-channel raw and computer-processed electroencephalograms, somatosensory-evoked potentials, and neurogenic motor-evoked potentials were recorded at six levels of anesthetic depths. Neurogenic motor-evoked potential amplitudes and latencies were unaltered. The electroencephalograms were depressed to isoelectricity with periodic burst activity above 1.27% isoflurane. Processed electroencephalograms showed depression above 0.72%. The somatosensory-evoked potentials were suppressed by increasing isoflurane and were not discernible at 2.2%. Neurogenic motor-evoked potential signals are well preserved in rats during exposure to isoflurane concentrations that eliminate somatosensory-evoked potential waveforms and depress electroencephalograms to burst suppression.

Preservation of Neurogenic Motor-Evoked Potentials During Isoflurane Electroencephalographic Burst Suppression in Rats

Study Design A prospective laboratory study was performed in a rat model. Objectives to test the hypothesis that neurogenic motor-evoked potentials are more resistant to suppressive changes from the volatile anesthetic isoflurane than cortically recorded somatosensory-evoked potentials and electroencephalography. Summary of Background Data Techniques for monitoring spinal cord motor tracts have been developed because sensory tract monitoring with somatosensory-evoked potentials is at times inadequate. Potentials from transcranial magnetic and electrical stimulation are very sensitive to anesthesia. Neurogenic motor-evoked potentials are thought to be more resistant. Methods Eight mature Sprague-Dawiey rats were studied during isoflurane general anesthesia. Two channel raw and computer-processed electroencephalograms, somatosensory-evoked potentials, and neurogenic motor-evoked potentials were recorded at six levels of anesthetic depths. Results Neurogenic motor-evoked potential amplitudes and latencies were unaltered. The electroenceph-alograms were depressed to isoelectricity with periodic burst activity above 1.27% isoflurane. Processed electroencephalograms showed depression above 0.72%. The somatosensory-evoked potentials were suppressed by increasing isoflurane and were not discernible at 2.2%. Conclusions Neurogenic motor-evoked potential signals are well preserved in rats during exposure to isoflurane concentrations that eliminate somatosensory-evoked potential waveforms and depress electroencephalograms to burst suppression.

Spinal anaesthesia but not general anaesthesia enhances neutrophil biocidal activity in hip arthroplasty patients

The purpose of this study was to compare neutrophil cidal activity during general or spinal anaesthesia. Assays were performed on neutrophils extracted from the blood of patients after surgery had been under way for one hour. First, the ability of the neutrophils to kill a standard laboratory strain of S. aureus was examined. Neutrophils extracted from the blood during surgery in the spinal anaesthetic group and incubated with the staphylococci for one hour killed twice as many bacteria than those from two groups of patients that received halothane or isoflurane general anaesthesia (P < 0.05). This effect persisted, to a lesser extent, in the spinal group neutrophils after two hours of incubation with the bacteria. Second, neutrophils from patients under the same conditions of surgery and anaesthesia were tested to examine the effect of the different anaesthetic techniques on neutrophil biocidal mechanisms. Neutrophils extracted during surgery in the spinal group released more superoxide in response to phorbol-12-myristate-13-acetate (PMA) than those from both groups of patients that received general anaesthesia (P < 0.05). It is concluded that there is an increased state of reactivity of the neutrophil cell membrane NADPH oxidase system in patients receiving spinal anaesthesia than in patients receiving general anaesthesia.