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.     

舒芬太尼在胆囊切除术后镇痛的临床效果观察

目的:探讨舒芬太尼在开腹胆囊切除术后病人自控静脉镇痛(PCIA)的效果和安全性。方法:60例全麻开腹胆囊切除术病人随机分为舒芬太尼(Suf)组和芬太尼(Fen)组,各30例。分别使用舒芬太尼或芬太尼进行PCIA,不给负荷量。记录术后0h、4h、12h、24h、40h各时间点的疼痛评分、镇静评分,PCA按压次数、并发症和病人的满意度等。结果:Suf组4h、12h、24hVAS评分明显低于Fen组(P<0.05),其它点差异无统计学意义(P>0.05);Suf组各时间点镇静评分均小于Fen组(P<0.05);Suf组PCA按压次数显著低于Fen(P<0.05);两组并发症发生率无统计学差异(P>0.05);Suf组病人对PCIA满意率显著高于Fen组(P<0.05)。结论:舒芬太尼用于开腹胆囊切除术后PCIA,镇痛安全有效,镇痛镇静效果优于芬太尼。     

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.     

异丙酚复合芬太尼静脉麻醉镇痛对门诊人工流产术的影响

目的:观察异丙酚复合芬太尼静脉麻醉对于人工流产术时及术后的影响。方法:选择2001年3月——2001年9月在本院计划生育门诊就诊、自愿要求无痛人工流产的妇女120例作为无痛人工流产组(简称:无痛组),同期按常规方法行人工流产的妇女120例作为对照组(简称:对照组),进行配对研究。无痛组用异丙酚1.5mg/kg复合芬太尼2μg/kg诱导,术中用异丙酚维持,人工流产术按常规方法施行。结果:无痛组术中异丙酚用量为2.7±0.7mg/kg,芬太尼2μg/kg,术中无知觉,120例妇女均无疼痛主诉。对照组轻度疼痛82例(68.3％),中度疼痛33例(27.5％),重度疼痛3例(4.2％)。无痛组在麻醉诱导及维持期间均出现呼吸频率下降,通过控制呼吸、面罩吸氧,SaO_2可以保持在99％以上,不需气管插管。两组妇女术前及术后宫腔深度无明显差异(P>0.05)。无痛组术中出血量为32.2±23.2ml,对照组为19.8±15.9ml,无痛组较对照组明显增多,有极显著统计学差异(P<0.01)。结论:异丙酚复合芬太尼静脉麻醉对人工流产术的主要影响是手术的出血量略增多,但不影响子宫收缩及术后恶露持续时间,该麻醉是一种有效镇痛方法,适用于门诊人工流产术。     

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。     

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。     

Short-term propofol anaesthesia down-regulates clock genes expression in the master clock

ABSTRACT

Background: Propofol anesthesia triggers phase-advances of circadian rhythms controlled by the suprachiasmatic nuclei (SCN), the master clock. Besides, inhalational anesthesia has been associated with a subsequent reduction of Per2 mRNA levels in the whole brain of rodents. The acute effects of propofol anesthesia per se on the SCN molecular clockwork remain unclear. Here we aim to study the expression of Per1 and Per2 clock genes in the SCN of rats exposed to constant darkness after a single dose of propofol. Methods: Thirty 2-months old rats were randomly divided into 2 groups receiving a single dose of either 120 mg/kg propofol 1% (n=15), or intralipid® 10% (n=15) in late day (projected circadian time (CT) 10, i.e., 10h after the expected time of lights on). Thereafter, rat brains were sampled in darkness 1h, 2h or 3h after the treatment (projected CT11, CT12 or CT13). Expression of Per1 and Per2 mRNA was analyzed by in situ hybridization in SCN coronal sections. Results: Per1 expression was affected by time and treatment. Per1 expression in the SCN after propofol treatment decreased at CT11 and CT12 when compared to the vehicle group. For Per2 expression, we observed only a treatment effect. Observed in dark conditions without hypothermia or/and concomitant surgery, such down-regulation of clock genes Per is only correlated to propofol treatment. This may explain “jet-lag-like” symptoms described by patients after anesthesia. Conclusion: We show here for the first time that short-term propofol anesthesia leads to a transient down-regulation of Per1 and Per2 expression in the SCN.     

Rib cage versus abdominal displacement in rabbits during forced oscillations to 30 Hz

We measured relative displacement of the rib cage (RC) and abdomen (ABD) in 12 anesthetized rabbits during forced oscillations. Sinusoidal volume changes were delivered through a tracheostomy at frequencies from 0.5 to 30 Hz and measured by body plethysmography. Displacements of the RC and ABD were measured by inductive plethysmography. During oscillation at fixed tidal volume (VT = 1.3 ml/kg) the ratio ABD/RC, normalized to unity at 0.5 Hz, was 0.88 +/- 0.06 at 2 Hz and increased to 1.28 +/- 0.13 at 6 Hz (P less than 0.01). As frequency increased further ABD/RC fell sharply but between 20 and 30 Hz reached a plateau of 0.17 +/- 0.02 (P less than 0.001). Displacements of RC and ABD were nearly synchronous from 0.5 to 2 Hz, but as frequency increased ABD lagged RC progressively, reaching a phase difference of 90 degrees between 6 and 8 Hz and 180 degrees between 16 and 20 Hz. In six additional rabbits we measured chest wall displacements while varying VT from 0.5 to 3.7 ml/kg. ABD/RC was independent of VT at low frequencies (less than or equal to 6 Hz) but fell sharply with increasing VT at the higher frequencies. We interpreted these findings using a chest wall model having an RC compartment whose displacements are governed primarily by a nonlinear compliance, in parallel with an ABD compartment whose displacements are governed by a series resistance, inertance, and in addition a nonlinear compliance. The experimental findings are in large measure accounted for by such a model if the degree of nonlinearity of ABD and RC compliances are comparable.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.