Distribution of cardiac output during pentobarbital versus midazolam/fentanyl/fluanisone anaesthesia in the rat

Differences in effects on central haemodynamics, organ blood flow, and serum corticosterone were studied in 11 rats anaesthetized with midazolam/fentanyl/fluanisone (MFF) and 11 other rats anaesthetized with sodium pentobarbital. Compared with pentobarbital, MFF reduced aortic blood pressure by 25%, increased heart rate by 20%, and increased cardiac output by 80%. Unlike most tissues, MFF produced a fivefold increase in blood flow to skeletal muscle, and decreased adrenal blood flow compared to pentobarbital anaesthesia. Initial serum corticosterone levels were lower in rats given MFF anaesthesia, indicating better stress protection. This study also indicates that MFF anaesthesia is preferable to pentobarbital because tissue perfusion generally was better preserved.     

Intraperitoneal propofol and propofol fentanyl, sufentanil and remifentanil combinations for mouse anaesthesia

The combination of propofol and a rapid-acting opioid, such as fentanyl, sufentanil or remifentanil, is a relatively safe, total intravenous anaesthesia technique, commonly used in humans and which has been investigated in laboratory animals. The objective of this study was to evaluate these combinations for anaesthesia of mice by the intraperitoneal (i.p.) route. Sixty-seven mice, divided into groups of four, were used to test 28 combinations of propofol alone and propofol with fentanyl, sufentanil or remifentanil administered i.p. The dose ranges of drugs studied were propofol 50-200 mg/kg, fentanyl 0.2-0.4 mg/kg, sufentanil 0.05-0.1 mg/kg and remifentanil 0.2-1.0 mg/kg. The loss of righting reflex (RR) and the loss of pedal withdrawal reflex (PWR) were recorded along with the duration and quality of recovery. The results obtained in these studies were unpredictable. The same dose combinations of propofol and opioids were associated with different responses in different individuals. Higher doses did not induce loss of RR and PWR in all animals and were associated with high mortality rates. An adequate hypnotic level was only observed with higher doses of propofol. The synergistic effect of propofol and the opioids was not sufficient to allow surgical procedures. Animals that reached PWR loss showed tail rigidity, shaking limbs and scratched their heads with their forefeet. Higher opioid doses induced respiratory depression and higher death rates. The inconsistency between and within groups may be associated with the i.p. route. The results reported here show that the i.p. route is not appropriate for mouse anaesthesia using propofol alone or in combination with fentanyl, sufentanil or remifentanil.     

Relationship of bispectral index values, haemodynamic changes and recovery times during sevoflurane or propofol anaesthesia in rabbits

The aim of this study was to determine and compare the degree of hypnosis achieved during propofol or sevoflurane anaesthesia in rabbits using bispectral index (BIS), and to evaluate its usefulness as a predictor of both haemodynamic changes during anaesthesia and recovery times. Twenty adult male New Zealand White rabbits, average weight 4.4 +/- 0.4 kg, were used for this study. Animals were randomly allocated to one of two groups with 10 rabbits/group. An electroencephalographic recording was obtained from each conscious rabbit prior to drug administration. All animals received buprenorphine as a preanaesthetic medication (0.05 mg/kg, intravenous [i.v.]). Anaesthesia was induced with propofol (8 mg/kg, i.v.) in all animals; 10 rabbits were maintained with sevoflurane via inhalation (1 minimum alveolar concentration--end-tidal sevoflurane concentration of 3.7%--at a fresh gas flow rate of 3 L/min; group I), and 10 were maintained with i.v. propofol (0.6 mg/kg/min; group II). The rabbits were orotracheally intubated and spontaneous ventilation was maintained throughout the study (100% oxygen). After abdominal surgery through a ventral midline laparotomy, rabbits were allowed to recover from anaesthesia. Cardiovascular variables and BIS values were recorded at intervals throughout the procedure, as was the duration of recovery from anaesthesia. In both groups, mean BIS values were significantly decreased immediately after induction, compared with baseline values obtained during consciousness. Anaesthetic depth (evaluated by clinical observation) was similar in both groups; however, group II rabbits had significantly higher (P<0.001) BIS values from 30 s before incision until anaesthesia was discontinued. There was no significant difference in BIS recorded 1 and 5 min after incision as compared with values obtained 30 s before incision in either group. During sevoflurane or propofol administration, correlations were found between BIS values and mean arterial blood pressure (MABP), and between BIS values and heart rate (HR). Mean BIS values at discontinuation of administration of the anaesthetic agent were greater in group II (69.1 +/- 6.0) than in group I (49.3 +/- 2.2). However, recovery from anaesthesia was significantly longer in group II (38.4 +/- 7.2 min) than in group I (11.5 +/- 2.5 min). In conclusion, BIS can be used to differentiate between conscious and unconscious states during anaesthesia in rabbits. BIS values derived from an electroencephalogram at the end of anaesthesia were not useful for predicting the speed of anaesthetic recovery in sevoflurane or propofol-anaesthetized rabbits undergoing abdominal surgery. Despite the correlation found between BIS and haemodynamic parameters, its usefulness as a predictor of clinically important changes in arterial blood pressure and HR in anaesthetized rabbits was limited.     

An outcome study comparing intravenous sedation with midazolam/fentanyl (conscious sedation) versus propofol infusion (deep sedation) for aesthetic surgery

The purpose of this study was to determine the differences in measurable outcomes following aesthetic procedures performed under intravenous sedation with incremental doses of midazolam and fentanyl and those performed under propofol infusion. The authors' hypothesis was that the differences in these outcome parameters are not significant between these intravenous sedation protocols. All intraoperative and perioperative records of 84 consecutive patients having aesthetic surgery under a conscious sedation protocol using incremental doses of intravenous midazolam and fentanyl were retrospectively reviewed and compared with the records of a second group of 85 patients having aesthetic surgery under a deep sedation regimen based primarily on propofol infusion. All procedures were hospital based and performed by two surgeons. Twenty-eight different parameters were examined by chart review. In addition, a patient questionnaire was used to assess patient satisfaction and patient recall of operative and perioperative pain, anxiety, nausea, and vomiting. Multivariate statistical analysis was conducted. The two sedation groups were similar with regard to aesthetic procedures performed and patient demographics. The mean duration of operative time was statistically equivalent (152 minutes and 153 minutes). In both groups, there were minor adverse intraoperative events reported but no significant complications. Transient hypotension was more common in the propofol infusion group (12.9 percent versus 2.4 percent, p = 0.018), but no patient required intervention beyond reducing the sedative agent or increasing intravenous fluids. The amount of supplemental fentanyl given intraoperatively was significantly higher in the group whose primary agent for sedation was propofol infusion than the group who received midazolam/fentanyl (209 mug and 143 mug, respectively). The overall questionnaire response rate was 80 percent for both groups. The midazolam/fentanyl sedation group had more recall of "unpleasant intraoperative events" (17 percent versus 3 percent, p = 0.007). However, both groups had low recall of intraoperative pain, anxiety, and nausea. The propofol infusion group experienced significantly more nausea in the recovery room (p = 0.002), nausea at the time of discharge (p = 0.009), and nausea the evening after the operation (p = 0.013). Greater than 90 percent of the patients in both groups would have the same anesthetic in the future rather than undergo general anesthesia. Patient safety, outcomes, and satisfaction are similar in plastic surgery procedures performed under sedation protocols using either incremental doses of midazolam and fentanyl or propofol infusion. All operative and postoperative outcomes for pain, anxiety, and vomiting were similar in the two groups except for immediate postoperative nausea, which was higher in the propofol infusion group. The overall satisfaction of patients undergoing plastic surgery procedures under these intravenous sedation protocols appears very high.     

Integrity of gut mucosa during anaesthesia in major abdominal surgery

The aim of the study was to examine a perfusion and integrity of small bowel in 60 subsequent patients during the major open abdominal surgery which lasted from 2 to 7 hours. Two samples of the intestinal mucosa were removed: at the beginning, and at the end of the surgical procedure in general anaesthesia. A mucosal injury was classified into 4 grades. pH, PCO2 and lactate level were measured in the blood samples from the arterial and mesenteric vein in one hour time intervals. The changes of intestinal mucosa were found in 31 patients (51.7%): in 19 patients (31.7%) grade 1 changes were recorded, in 10 patients (16.7%) grade 2, and in 2 patients (3.3%) grade 3. Grade 4 lesions were not recorded. There was a statistically significant correlation between grades of the mucosal damage and the surgery duration (p = 0.001). Analysis during the one hour intervals showed that there was no exact time point when the significant aggravation of the pathohistological changes in intestinal mucosa occurred. However, when patients were allocated into two subgroups with surgical procedures lasting less than 4 hours and more than 4 hours, there was a statistically significant difference in the grades of mucosal damage between subgroups (p < 0.05). More biopsies without pathohistological changes were observed in the patients whose procedure duration was < 4 hours. A significantly higher lactate concentrations in arterial and mesenteric venous blood were observed in the patients with pathohistological changes at 6 hours time point as compared to 2 hour time point in the patients without pathohistological changes (p < 0.05). During the open abdominal surgery in general anaesthesia, the length of the procedure influences the grade of the intestinal mucosa injury. Deterioration of the pathohistological findings in the intestinal mucosa correlates with high lactate blood level, suggesting that the cause of these changes may result from tissue hypoxia.     

Peripheral acting mediators pain and analgesia potentiate the central analgesic action of fentanyl and dipyrone

Intramuscular (i.m.) administration of the central analgesics fentanyl and dipyrone, and also mediators of pain such as L-glutamate, CCK, ATP, phenylephine and analgesic mediator adenosine, slightly penetrating in CNS, in the minimum effective dose (MED) cause the maximal analgesic effect in the tail flick test in rats. MED of dipyrone and fentanyl are decreased 50-220-fold after combined i.m. administration of each analgesic with L-glutamate, CCK, adenosine, ATP and phenylephrine in threshold, independently noneffective doses. The intragastric administration of lidocaine and also subdiaphragmatic vagotomy completely eliminate analgesic effects of the above mentioned combinations. Conclusion: the peripherically acting mediators of pain and analgesia after systemic administration potentiate central analgesic action of fentanyl and dipyrone as a result of the stimulation of vagal afferents of gastric mucosa.     

Effect of anaesthesia on insulin-induced hypoglycemia in rabbits

The aim of this study was to determine how anaesthetized rabbits survive much longer than awake rabbits after receiving an insulin overdose. Insulin appeared to act in both groups of rabbits because there was a prompt fall in circulating glucose, free fatty acids, and beta-hydroxybutyrate concentrations. Carbohydrate appeared to be the principal energy source for anaesthetized rabbits because their respiratory quotient approached unity. Although the fall in glycemia was similar in both groups of rabbits, the circulating lactate concentration rose only in the anaesthetized group. This rise in lactate in the initial 60 min after insulin was given could account for most of the fall in glycemia if the source of lactate was the glucose pool. The decline in hepatic glycogen was close to 100 mumol/g liver; this would account for about one-third of the total energy turnover and close to one-half of the measured glucose appearance in these anaesthetized rabbits. As judged from the rate of oxygen consumption, muscle glycogen seemed to supply two-thirds of the fuel to be oxidized in these rabbits. However, only one-third of the lactate released from muscle was first converted to glucose and the remainder was oxidized directly to CO2. Although insulin provided the metabolic setting for a rapid rate of glucose oxidation, this rate appeared to be diminished when the overall rate of oxygen consumption was lower during anaesthesia.     

Hemodynamic differences in sevoflurane versus propofol anesthesia

The aim of the study was to compare the effect of sevoflurane and propofol anesthesia on myocardial contractility during laparotomic cholecystectomy using transesophageal echo-Doppler. In the study, 40 patients were randomized into two groups, depending on whether they received sevoflurane or propofol anesthesia. Heart rate, cardiac index, stroke volume, left ventricular ejection time and acceleration were measured 10 minutes after induction of anesthesia, 1 minute and 25 minutes after incision. The results were analyzed using paired t-test and ANOVA. Significantly lower values were found for all parameters after the initial measurement (p < 0.05). In the sevoflurane group, stroke volume decreased from 66 +/- 6.2 ml/beat to 65 +/- 6.4 ml/beat and to 63 +/- 5.6 ml/beat 1 minute and 25 minutes after incision respectively. In the propofol group changes were from 64 ml/beat to 58 +/- 10.5 ml/beat to 58 +/- 8.6 ml/beat. Stroke volume was significantly higher in the sevoflurane than in the propofol group (p < 0.05). Sevoflurane anesthesia allows a better hemodynamic stability during laparotomic cholecystectomy.     

EEG power spectrum analysis for monitoring depth of anaesthesia during experimental surgery

The first attempts to introduce computerized power spectrum analysis of the electroencephalogram (EEG) as an intraoperative anaesthesia monitoring device started approximately 30 years ago. Since that time, the effects of various anaesthetic agents, sedative and analgesic drugs on the EEG pattern have been addressed in numerous studies in human patients and different animal species. These studies revealed dose-dependent changes in the EEG power spectrum for many intravenous and volatile anaesthetics. Moreover, EEG responses evoked by surgical stimuli during relative light levels of surgical anaesthesia have been classified as 'arousal' and 'paradoxical arousal' reaction, previously referred to as 'desynchronization' and 'synchronization', respectively. Contrasting reports on the correlation between quantitative EEG (QEEG) variables derived from power spectrum analysis (i.e. spectral edge frequency, median frequency) and simultaneously recorded clinical signs such as movement and haemodynamic responses, however, limited the routine use of intraoperative EEG monitoring. In addition, the appearance of EEG burst suppression pattern and isoelectricity at clinically relevant concentrations/doses of newer general anaesthetics (i.e. isoflurane, sevoflurane, propofol) may have weakened the dose-related EEG changes previously reported. Despite these findings, the EEG power spectrum analysis may still provide valuable information during intraoperative monitoring in the individual subject. The information obtained from EEG power spectrum analysis may be further supplemented by newer EEG indices such as bispectral index and approximate entropy or other neurophysiological monitors including auditory evoked potentials or somatosensory evoked potentials.     

瑞芬太尼、芬太尼及瑞芬太尼-芬太尼联合应用对肥胖患者麻醉后苏醒质量的研究

目的：探讨芬太尼和瑞芬太尼分别应用于肥胖患者全身麻醉中苏醒质量的优缺点,对比研究两药联合应用对于提高肥胖患者苏醒质量的可行性和有效性。方法：60例体重指数〉30的肥胖患者随机分为三组,分别应用芬太尼（F组）、瑞芬太尼（R组）和瑞芬太尼联合应用芬太尼（RF组）进行全身麻醉,麻醉时间2小时左右,从停止用药开始分别观察BIS值恢复时间,睁眼时间,5mi/kg潮气量恢复时间,每分通气量恢复时间,拔管时血压,定向力恢复时间,进行视觉模拟评分和镇静/警觉评分和拔管后动脉血气的测量。结果：RF组和R组的BIS值恢复时间和睁眼时间及每分通气量恢复时间无差异,均优于F组。而且RF组和R组中BIS值恢复时间和睁眼时间相关性良好,F组中两指标无相关性。停药后三组患者分别进行1小时、2小时4、4小时和24小时的VAS评分和OAA/S评分,VAS评分中R组在四个时相于其他两组比较均有统计学意义（P〈0.05）,均较两组高,F组和RF组在手术后1、2小时时相上比较无统计学意义（P〉0.05）。OAA/S评分中,F组在1、2及4小时三个时相均低于其他组,R组和RF组在四个时相比较均无统计学意义（P〉0.05）。定向力恢复时间三组比较,R组和RF组之间无统计学意义（P〉0.05）,F组均与其他两组有差别,且长于其他两组（P〈0.05）。血气分析结果中RF组优于其他组（P〈0.05）。全麻后的副反应中RF组的发生率较低。结论：瑞芬太尼联合应用芬太尼对于肥胖患者全身麻醉意识恢复快,通气恢复时间短,镇痛效果好,血流动力学平稳,苏醒质量高。     

异丙酚对家兔肝缺血/再灌注后抗氧化能力改变的影响

目的: 探讨氧自由基(OFR)在肝缺血/再灌注损伤(HI/RI)中的作用及异丙酚对其的影响.方法: 实验兔随机分为假手术对照组、肝缺血/再灌注组和肝缺血/再灌注加异丙酚治疗组,分别在肝缺血前、缺血45 min、再灌注45 min共3个时相点,检测血浆及肝组织超氧化物歧化酶(SOD)活性、黄嘌呤氧化酶(XO)活性、丙二醛( MDA)浓度及谷丙转氨酶(ALT)值,并行肝组织电镜观察.结果: 肝缺血/再灌注期间,血浆XO、MDA及ALT显著高于、SOD明显低于假手术对照组(P<0.05和P<0.01);肝组织XO及MDA显著高于、SOD明显低于假手术对照组(P<0.05和P<0.01);肝组织超微结构发生异常改变.异丙酚可逆转上述指标的异常变化,与肝缺血/再灌注组相比有显著性差异(P<0.05和P<0.01).结论: OFR在HI/RI发生发展中起介导作用;异丙酚可通过降低氧自由基水平(增强SOD活性、减弱XO活性),拮抗脂质过氧化反应(降低MDA浓度),从而减轻HIRI.     

Mass-spectrometry analysis of disflurane,propofol, and fentanyl in plasma and cerebrospinal fluid

Concentrations of anesthetic agents were measured in blood plasma and cerebrospinal fluid using mass spectrometry with a membrane interface. Sampling of biological fluids was performed during balanced inhalational (disflurane and fentanyl) anesthesia and total intravenous (propofol and fentanyl) anesthesia. A rapid test method for the concentration measurement of organic molecules in biological fluids is described. This method does not require long-term sample processing before injecting the sample into the mass spectrometer interface. The pervaporation properties (uptake, diffusion, and evaporation) of anesthetic agents from biological fluids in a silicone membrane were used in the mass spectrometry interface. We report on the possibility of using a mass spectrometer with a membrane interface for the measurement of the absolute concentration of anesthetic agents in blood plasma for study of the properties of the blood–brain barrier.     

Mini-pump: method of diabetic control during minor surgery under general anaesthesia.

A simple method for maintaining diabetic control during and after minor surgery requiring a general anaesthetic was studied in 20 insulin-treated diabetics. Long-acting insulin was omitted on the night before the operation, and a mini-pump delivering insulin at a rate of 0.5 units/h was strapped to the arm early on the morning of the operation regardless of the time of operation. Insulin was infused at this rate throughout the day, the usual evening dose of insulin given and followed by supper, and the pump then stopped. In all 20 patients studied blood glucose concentrations fell steadily throughout the day. Hypoglycaemia did not occur. The mini-pump is simple to use and with the same standard insulin dose for all patients maintains satisfactory blood glucose concentrations throughout the day of operation.     

Influence of time of day on propofol pharmacokinetics and pharmacodynamics in rabbits

This study evaluates the administration time-of-day effects on propofol pharmacokinetics and sedative response in rabbits. Nine rabbits were sedated with 5?mg/kg propofol at three local clock times: 10:00, 16:00, and 22:00?h. Each rabbit served as its own control by being given a single infusion at the three different times of day on three separate occasions. Ten arterial blood samples were collected during each clock-time experiment for propofol assay. A two-compartment model was used to describe propofol pharmacokinetics, and the pedal withdrawal reflex was used as the sedation pharmacodynamic response. The categorical data comprising the presence or absence of pedal withdrawal reflex was described by a logistic model. The typical volume of the central compartment equaled 7.67?L and depended on rabbit body weight. The elimination rate constant depended on drug administration time; it was lowest at 10:00?h, highest at 16:00?h, and intermediate at 22:00?h. Delay of the anesthetic effect, with respect to plasma concentrations, was described by the effect compartment, with the rate constant for the distribution to the effector compartment equal to 0.335?min(-1). Drug concentration had a large effect on the probability of anesthesia. The degree of anesthesia was largest at 10:00?h, lowest at 16:00?h, and intermediate at 22:00?h. In summary, both the pharmacokinetics and pharmacodynamics of propofol in rabbits depended on administration time. The developed population approach may be used to assess chronopharmacokinetics and chronopharmacodynamics of medications in animals and humans.     

Evaluation of fentanyl transdermal patches in rabbits: blood concentrations and physiologic response

In the study reported here, we sought to evaluate transdermal fentanyl patches for their ability to achieve detectable plasma concentrations with minimal adverse effects in New Zealand White rabbits. Fentanyl patches were applied to the dorsum after removing hair either by clipping or by application of a depilatory agent. Blood samples were collected every 12 h for a total of 96 h (24 h after patch removal) for determination of plasma fentanyl concentration. At those times, rabbits were assessed for changes in body temperature, heart rate, respiratory rate, and body weight. In rabbits with clipped hair, where rapid hair re-growth was not a mitigating factor, mean plasma fentanyl concentration reached a mean (+/- SEM) peak of 1.11 +/- 0.32 ng/ml at 24 h, decreased to 0.77 +/- 0.21 ng/ml at 72 h, and was negligible at 96 h. In rabbits with depilated hair, peak concentration was obtained at 12 h (6.7 +/- 0.57 ng/ml) and decreased gradually to 0.27 +/- 0.06 ng/ml at 72 h. In a second group of fentanyl-treated rabbits in which hair started growing back within 24 h, plasma fentanyl concentration was not detectable. Control and fentanyl-treated rabbits with clipped hair had no effect from the experimental manipulations other than slight loss in body weight. In the depilatory group, two rabbits appeared moderately sedated during the initial 12-h period, and had decreased respiratory rate for 24 h. In conclusion, rabbits tolerate the transdermal fentanyl patch well. Hair regrowth in rabbits may present a complicating factor that impedes dermal absorption of fentanyl. The application of a depilatory agent lead to early and rapid absorption of fentanyl causing undue sedation in some rabbits and lack of sustained plasma concentrations for the desired three-day period.     

Effect of propofol on oxidative stress status in erythrocytes from dogs under general anaesthesia

Background

Piglets are born with eight sharp teeth that during nursing can cause facial lesions on littermates and teat lesions on the sow. Teeth grinding in piglets is therefore often practiced to reduce these lesions. The aim of this study was to assess the consequences of grinding piglet teeth in regard to the occurrence of lesions. In this study the piglets' teeth were grinded in 28 litters, and in 36 litters the piglets' teeth were kept intact. Twice, one time during the first week and one time during the second week after birth facial lesions of the piglets were scored and the teats of the sows were examined for lesions. The facial lesion score accounted for the amount and severity of lesions. The individual observations on piglets in the litter were synthesized in a litter facial lesion score.

Findings

69.8% and 43.5% of the piglets had facial lesions in week 1 and week 2 respectively. The effect of treatment was not significant on litter facial lesion score. The litter facial lesion score was higher in week 1 than in week 2 (p < 0.001) and higher in large litters (p = 0.003) than in small litters. Mortality between week 1 and week 2 was higher in litters with intact teeth (p = 0.02). Sow teat lesions only occurred if litters had intact teeth.

Conclusions

According to our results teeth grinding is only justifiable in large litters.