Minimum infusion rates and recovery times from different durations of continuous infusion of fospropofol, a prodrug of propofol, in rabbits: a comparison with propofol emulsion

ObjectiveTo explore, in rabbits, the minimum infusion rates (MIR) required and recovery time from long duration (≤8 hours) continuous infusion of fospropofol disodium, a novel water-soluble prodrug of propofol, and compare it with propofol.Study designProspective, randomized, blinded experimental trial.AnimalsNinety-six adult laboratory rabbits, mean ± SD weight 2.20 ± 0.15 kg.MethodsStage 1. 16 rabbits were assigned to receive fospropofol disodium or propofol to measure MIR, using an up-and-down method with response to tail-clamping stimulus (TCS). Stage 2. Eighty rabbits were allocated to group F (fospropofol disodium) or group P (propofol), and further subdivided (n = 10 in each subgroup) according to infusion time (2, 4, 6 or 8 hours), to groups F_2h, F_4h, F_6h, F_8h and P_2h, P_4h, P_6h, P_8h. Fospropofol or propofol were infused, and tail clamping applied to maintain the same depth of anaesthesia until infusion was completed. Times to recover righting reflex (RR), to respond to TCS, and total recovery to different durations of continuous infusion of two anaesthetic drugs were noted. Respiratory and pulse rates and oxygen saturation were analyzed. The plasma concentrations of fospropofol disodium, the active metabolite propofol (propofol_F) and propofol emulsion were measured with respect to loss and recovery of RR and TCS.ResultsMIR of fospropofol disodium was 2.0 mg kg^?1 minute^?1, and MIR of propofol was 0.9 mg kg^?1 minute^?1. Times in minutes to total recovery from anaesthesia in groups F and P were as follows, F_2h 15 ± 3; F_4h 26 ± 4; F_6h 52 ± 6; F_8h 84 ± 10; and P_2h 10 ± 1; P_4h 19 ± 7; P_6h 36 ± 7; P_8h 48 ± 5.Conclusions and clinical relevanceAfter continuous intravenous infusion in rabbits (≤8 hours), fospropofol disodium and propofol both show an extension of recovery time with increasing infusion time, fospropofol disodium showing a significantly greater prolongation compared to propofol emulsion when infusion time increases to 6 and 8 hours.     

Effects of propofol administration rates on cardiopulmonary function and anaesthetic depth during anaesthetic induction in rats

Objective  To compare the effect of three different administration rates of one dose of propofol on the depth and duration of anaesthesia and cardiopulmonary function during induction of anaesthesia in rats using electroencephalogram (EEG) and clinical signs.
Study design  Prospective, randomized experimental trial.
Animals  Twenty-one, adult, male Sprague-Dawley rats weighing 341 ± 26 g (mean ± SD) (325 to 480 g).
Methods  Animals were randomly divided into three groups to receive 20 mg kg⁻¹ propofol as a bolus injection over 1, 2 or 3 minutes (groups P1, P2 and P3 respectively) intravenously (IV). The total duration and number of burst suppression (BS) episodes in the EEG, the time to loss of righting reflex, reflex score from electrical stimulation, respiratory rate, mean arterial pressure and pulse rate were measured from the beginning of propofol injection.
Results  While loss of reflex to electrical stimulus and time to loss of righting reflex in group P3 were slower than in other groups, the total duration and number of BS episodes in group P3 were significantly higher than in groups P1 and P2 and cardiopulmonary depression was less prominent in group P3 than in groups P1 and P2 up to 2 minutes after the start of administration.
Conclusions  Twenty milligram per kg propofol administration IV for 3 minutes increased the duration of anaesthesia and decreased cardiopulmonary depression in rats.
Clinical relevance  Slower infusion of propofol produced surgical anaesthesia with less cardiopulmonary depression in rats.     

Bispectral index in dogs at three intravenous infusion rates of propofol

ObjectiveTo establish the correlation between the bispectral index (BIS) and different rates of infusion of propofol in dogs.Study designProspective experimental trial.AnimalsEight adult dogs weighing 6–20 kg.MethodsEight animals underwent three treatments at intervals of 20 days. Propofol was used for induction of anesthesia (10 mg kg⁻¹ IV), followed by a continuous rate infusion (CRI) at 0.2 mg kg⁻¹ minute⁻¹ (P2), 0.4 mg kg⁻¹ minute⁻¹ (P4) or 0.8 mg kg⁻¹ minute⁻¹ (P8) for 55 minutes. The BIS values were measured at 10, 20, 30, 40, and 50 minutes (T10, T20, T30, T40, and T50, respectively) after the CRI of propofol was started. Numeric data were submitted to analysis of variance followed by Tukey test (p < 0.05).ResultsThe BIS differed significantly among groups at T40, when P8 was lower than P2 and P4. At T50, P8 was lower than P2. The electromyographic activity (EMG) in P2 and P4 was higher than P8 at T40 and T50.ConclusionsAn increase in propofol infusion rates decreases the BIS values and EMG.     

Effects of 2 different medetomidine infusion rates on selected neurohormonal and metabolic parameters in dogs

The effects of 2 different 8-hour continuous rate infusions (CRIs) of medetomidine on epinephrine, norepinephrine, cortisol, glucose, and insulin levels were investigated in 6 healthy dogs. Each dog received both treatments and a control as follows: MED1 = 2 μg/kg bodyweight (BW) loading dose followed by 1 μg/kg BW per hour CRI; MED2 = 4 μg/kg BW loading dose followed by 2 μg/kg BW per hour CRI; and CONTROL = saline bolus followed by a saline CRI. Both infusion rates of medetomidine decreased norepinephrine levels throughout the infusion compared to CONTROL. While norepinephrine levels tended to be lower with the MED2 treatment compared to the MED1, this difference was not significant. No differences in epinephrine, cortisol, glucose, or insulin were documented among any of the treatments at any time point. At the low doses used in this study, both CRIs of medetomidine decreased norepinephrine levels over the 8-hour infusion period, while no effects were observed on epinephrine, cortisol, glucose, and insulin.     

Effects of medetomidine premedication on propofol infusion anaesthesia in dogs

Observations of cardiovascular and respiratory parameters were made on six dogs anaesthetized on two separate occasions for 120 minutes with a propofol infusion, once without premedication and once following premedication with 10 μg kg-¹ of intramuscular medetomidine. During anaesthesia the heart rate and cardiac index tended to be lower following medetomidine premedication, while the mean arterial pressure was significantly greater (p<0.05). Although the differences were not statistically significant, the systemic vascular resistance, pulmonary vascular resistance and stroke volume index were also greater in dogs given medetomidine. The mean arterial oxygen and carbon dioxide tensions were similar under both regimens, but in 2 dogs supplementary oxygen had to be administered during anaesthesia to alleviate severe hypoxaemia on both occasions they were anaesthetized. Minute and tidal volumes of respiration tended to be greater in dogs not given medetomidine but medetomidine premedication appeared to have no effect on venous admixture. Dogs given medetomidine received intramuscular atipamezole at the end of the 120 min. propofol infusion; the mean time from induction of anaesthesia to walking without ataxia was 174. min in the unpremedicated dogs and 160 min. in the dogs given atipamezole. The mean blood propofol concentration at which the dogs walked without ataxia was higher in the unpremedicated animals (2.12 ± 0.077 μg. ml-¹ compared with 1.27 ± 0.518 μg. ml-¹ in the premedicated dogs). The oxygen delivery to the tissues was lower after medetomidine premedication (p = 0.03) and the oxygen consumption was generally lower after medetomidine premedication but the difference did not achieve statistical significance. No correlation could be demonstrated between blood propofol concentration and cardiac index, systemic or pulmonary vascular resistance indices, systolic, diastolic or mean arterial blood pressures.     

The effects of propofol, isoflurane and sevoflurane on vecuronium infusion rates for surgical muscle relaxation in dogs

OBJECTIVE: To compare the constant rate infusion (CRI) of vecuronium required to maintain a level of neuromuscular blockade adequate for major surgeries, e.g. thoracotomy or laparotomy, in dogs anaesthetized with a CRI of fentanyl and either propofol, isoflurane or sevoflurane. STUDY DESIGN: Prospective, randomized, cross-over study. ANIMALS: Thirteen male beagles (age, 9-22 months; body mass 6.3-11.3 kg). MATERIALS AND METHODS: Dogs were anaesthetized with propofol (24 mg kg(-1) hour(-1) IV CRI; group P), isoflurane (1.3% end-tidal concentration; group I) or sevoflurane (2.3% end-tidal concentration; group S) with fentanyl (5 microg kg(-1) hour(-1) IV, CRI). Sixty to seventy minutes after induction of anaesthesia, vecuronium was administered at a rate of 0.4, 0.3 and 0.2 mg kg(-1) hour(-1) in groups P, I and S respectively. To determine the degree of neuromuscular block, a peripheral nerve was stimulated electrically using the train-of-four (TO4) stimulus pattern. Evoked muscle contractions were evaluated using a neuromuscular monitoring device. Once the TO4 ratio reached 0, the continuous infusion rate was decreased and adjusted to maintain a TO4 count of 1. Continuous infusion was continued for 2 hours. The infusion rate of vecuronium was recorded 20, 40, 60, 80, 100 and 120 minutes after the start of infusion. RESULTS: The mean continuous infusion rates of vecuronium during stable infusion were 0.22 +/- 0.04 (mean +/- SD), 0.10 +/- 0.02 and 0.09 +/- 0.02 mg kg(-1) hour(-1) in groups P, I and S respectively. There were statistically significant differences between the rates in groups P and I and between the rates in groups P and S. Conclusions and clinical relevance In healthy dogs, the recommended maintenance infusion rate of vecuronium is 0.2 mg kg(-1) hour(-1) under CRI propofol-fentanyl anaesthesia and 0.1 mg kg(-1) hour(-1) during CRI fentanyl-isoflurane or sevoflurane anaesthesia.     

Effects of propofol and fentanyl on duodenal motility activity in pigs

To investigate the effects of propofol and fentanyl on the postprandial duodenal motility the intraluminal impedance technique was used. Six pigs were instrumented with a central venous catheter, a percutaneous enterogastrostomy (PEG), and an impedance catheter, which was introduced via the PEG into the duodenum through endoscopy. Over the following 3 d, duodenal motility was measured for 8-hour periods. Measurements were taken on each subject under 3 different sets of conditions: in the conscious unrestrained pig, during propofol sedation, and during sedation with propofol-fentanyl. Both, after morning feeding and during gastric nutrition via the PEG, duodenal feeding patterns and duodenal phase II of the migrating motor cycle were shortened during propofol and propofol-fentanyl sedation. In contrast, the duration of phase I was prolonged by propofol and propofol-fentanyl. In conclusion, either propofol or propofolfentanyl sedation shortens duodenal feeding patterns, as well as phase II of the migrating motor cycle.     

A comparison of propofol infusion and propofol/isoflurane anaesthesia in dexmedetomidine premedicated dogs

The effects of propofol infusion were compared with propofol/isoflurane anaesthesia in six beagles premedicated with 10 microg/kg intramuscular (i.m.) dexmedetomidine. The suitability of a cold pressor test (CPT) as a stress stimulus in dogs was also studied. Each dog received isoflurane (end tidal 1.0%, induction with propofol) with and without CPT; propofol (200 microg/kg/min, induction with propofol) with and without CPT; premedication alone with and without CPT in a randomized block study in six separate sessions. Heart rate and arterial blood pressures and gases were monitored. Plasma catecholamine, beta-endorphin and cortisol concentrations were measured. Recovery profile was observed. Blood pressures stayed within normal reference range but the dogs were bradycardic (mean heart rate < 70 bpm). PaCO2 concentration during anaesthesia was higher in the propofol group (mean > 57 mmHg) when compared with isoflurane (mean < 52 mmHg). Recovery times were longer with propofol than when compared with the other treatments. The mean extubation times were 8 +/- 3.4 and 23 +/- 6.3 min after propofol/isoflurane and propofol anaesthesia, respectively. The endocrine stress response was similar in all treatments except for lower adrenaline level after propofol infusion at the end of the recovery period. Cold pressor test produced variable responses and was not a reliable stress stimulus in the present study. Propofol/isoflurane anaesthesia was considered more useful than propofol infusion because of milder degree of respiratory depression and faster recovery.     

Effects of 2 different infusion rates of medetomidine on sedation score,cardiopulmonary parameters,and serum levels of medetomidine in healthy dogs

The effects of 2 different continuous rate infusions (CRIs) of medetomidine over an 8-hour period on sedation score, selected cardiopulmonary parameters, and serum levels of medetomidine were evaluated in 6 healthy, conscious dogs using a crossover study design. The treatment groups were: CONTROL = saline bolus followed by saline CRI; MED1 = 2 μg/kg body weight (BW) medetomidine loading dose followed by 1 μg/kg BW per hour CRI; and MED2 = 4 μg/kg BW medetomidine loading dose followed by 2 μg/kg BW per hour CRI. Sedation score (SS), heart rate (HR), respiratory rate (RR), temperature (TEMP), systolic arterial pressure (SAP), mean arterial pressure (MAP), and diastolic arterial pressure (DAP), arterial and mixed venous blood gas analyses, lactate, and plasma levels of medetomidine were evaluated at baseline, at various intervals during the infusion, and 2 h after terminating the infusion. Statistical analysis involved a repeated measures linear model. Both infusion rates of medetomidine-induced dose-dependent increases in SS and dose-dependent decreases in HR, SAP, MAP, and DAP were measured. Respiratory rate (RR), TEMP, central venous pH, central venous oxygen tension, and oxygen extraction ratio also decreased significantly in the MED2 group at certain time points. Arterial oxygen and carbon dioxide tensions were not significantly affected by either infusion rate. In healthy dogs, both infusion rates of medetomidine-induced clinically relevant sedative effects, accompanied by typical alpha₂ agonist-induced hemodynamic effects, which plateaued during the infusion and subsequently returned to baseline. While additional studies in unhealthy animals are required, the results presented here suggest that medetomidine infusions at the doses studied may be useful in canine patients requiring sedation for extended periods.     

Cardiovascular effects of continuous propofol infusion in horses

We examined the influence of propofol infusion on cardiovascular system at the rate of 0.14, 0.20 and 0.30 mg/kg/min in six adult Thoroughbred horses. The cardiovascular parameters were heart rate (HR), mean arterial pressure (MAP), mean right atrial pressure (MRAP), stroke volume (SV), cardiac output (CO), systemic vascular resistance (SVR), pre-ejection period (PEP) and ejection time (ET). In order to keep the ventilation conditions constantly, intermittent positive pressure ventilation was performed, and the partial arterial CO(2) pressure was maintained at 45 to 55 mmHg during maintenance anesthesia. SV showed a significant dose-dependent decrease however, CO did not show significant change. SVR decreased significantly at higher dose. PEP was prolonged and PEP/ET increased significantly at the highest dose. From these results, it became clear that SV decreases dose-dependently due to decrease of cardiac contractility during anesthesia with continuous propofol infusion in horses. On the other hand, since MAP and CO did not show significant changes, total intravenous anesthesia with propofol was suggested to be suitable for long-term anesthesia in horses.     

鹿特异性复合麻醉剂对大鼠不同脑区ATP酶活性的影响

为研究鹿特异性复合麻醉剂麻醉与大鼠各脑区突触体ATP酶活性的关系,探讨其麻醉机理。将20只SD大鼠分为对照组和麻醉组,对照组大鼠腹腔注射30mL/kg生理盐水,试验组腹腔注射30mg/kg鹿特异性复合麻醉剂,采集大鼠各脑区,利用比色法测定脑区内Na＋-K＋-ATP、Ca2＋-AT P和Mg2＋-ATP酶活性。结果显示,药物作用后大鼠大脑皮层和脑干Na＋、K＋-ATP酶活性与对照组比较降低显著（P〈0.05或P〈0.01）,小脑、脑干和海马Ca2＋-ATP酶活性与对照组比较显著降低（P〈0.05或P〈0.01）,大脑Mg2＋-AT P酶活性低于对照组（P〈0.05或P〈0.01）。结果表明,麻醉引起大鼠大脑皮层、脑干中Na＋-K＋-ATP酶活性降低,大脑皮层中Mg2＋-ATP酶活性低,小脑、脑干和海马脑区中Ca2＋-ATP酶活性降低可能是鹿特异性复合麻醉剂麻醉作用的机理之一。     

Continuous infusion of propofol in dogs premedicated with methotrimeprazine

Objective To evaluate the cardiopulmonary and clinical effects of three different infusion rates of propofol in dogs premedicated with methotrimeprazine. Study design Randomized experimental trial. Animals Ten healthy adult mixed‐breed male and female dogs, weighing from 14 to 20 kg. Methods Dogs were premedicated with methotrimeprazine [1 mg kg^?1 intravenously (IV)] followed by induction of anesthesia with 4.5 mg kg^?1 of propofol IV and maintenance with propofol for 60 minutes as follows: T1, 0.2 mg kg^?1 minute^?1; T2, 0.3 mg kg^?1minute^?1; and T3, 0.4 mg kg^?1minute^?1. Heart rate (HR), respiratory rate (RR), mean arterial pressure (MAP), end‐tidal CO₂ (P_ETCO₂), arterial hemoglobin O₂ saturation, arterial blood gases, and pedal and cutaneous reflexes were measured before and 5, 10, 20, 30, 45 and 60 minutes after the beginning of the propofol infusion. Statistical analysis was performed using an anova . Results Heart rate increased during anesthesia in all cases and arterial blood pressure decreased only in dogs in the T3 category. Respiratory depression was proportional to the infusion rate of propofol. Muscle relaxation was satisfactory, but analgesia was inadequate in the three treatments. Conclusions The infusion of 0.2–0.4 mg kg^?1 minute^?1 of propofol produced a dose‐dependent respiratory depression. The presence of a pedal withdrawal reflex and marked cardiovascular responses to this noxious stimulus suggests that anesthesia may not be of sufficient depth for surgery to be carried out. Clinical relevance Although several studies have been performed using propofol in animals, few studies have investigated the cardiopulmonary and analgesic effects with different doses. The determination of an adequate propofol infusion rate is necessary for the routine use of this intravenous anesthetic for the maintenance of anesthesia during major surgical procedures in dogs.     

A clinical trial of propofol infusion anaesthesia in dogs

Studies were carried out on 40 dogs premedicated with acepromazine (0·05 mg. kg^-1) and atropine (0·02 mg. kg^-1) to determine the minimum infusion rate of propofol needed to maintain anaesthesia and to compare the quality of the anaesthesia with that produced by halothane/nitrous oxide/oxygen. In 30 dogs anaesthesia was induced with propofol and maintained with a continuous infusion and in the other ten dogs anaesthesia was induced with thiopentone and maintained with the inhalation agents. An infusion rate of 0·4 mg. kg^-1 min^-1 of propofol produced surgical anaesthesia in dogs breathing oxygen or oxygen-enriched air. Cardiovascular and respiratory effects were similar to those in dogs anaesthetized with halothane/nitrous oxide and with both anaesthetic regimens myocardial oxygen consumption appeared to increase with increasing duration of anaesthesia. A possible familial susceptibility resulting in a more prolonged recovery was revealed and propofol infusion was associated with a 16 per cent incidence of vomiting in the recovery period. It was concluded that in canine anaesthesia the continuous infusion of propofol to maintain anaesthesia in healthy dogs was safe but less satisfactory than the use of halothane/nitrous oxide.     

对扬州地区不同播量多花黑麦草生产性能的研究

以多花黑麦草“特高”为材料,研究了5个不同播量水平1.5,2.0,2.5,3.0和3.5 g/m2对其生长特性及产量的影响.结果表明:不同播种量下,全年生长高度和生长速度不同,播量为3.5 g/m2时全年生长高度最高为268.04 cm,生长速度最快1.75 cm/d;随着播种量的增加分蘖能力有下降趋势,播量为1.5 ...     

不同施磷水平对饲用柠条营养和产量的影响

在石灰性土壤上采用单因子随机区组设计进行了饲用柠条的营养与生长研究。结果显示,施用磷肥的柠条干物质产量、氮(N)磷(P)钾(K)以及钙(Ca)铁(Fe)养分吸收量和粗蛋白产量明显提高;施磷可使柠条叶的N、P、K含量增加以及茎的N、P含量增加,却减少了柠条茎叶中Ca、Fe含量以及茎中K含量。不同施磷水平与干物质产量以及粗蛋白产量之间存在相关性,相关关系均达到显著水平(P<0.05)。施磷可以调节饲喂柠条的Ca/P值,达到家畜日粮的Ca/P标准。结果还表明,180kg/hm²P₂O₅是最佳的磷施用量,干物质产量和粗蛋白产量在所有处理中最高,与不施磷对照相比,干物质产量定植当年提高76.5%,第2年提高73.9%;粗蛋白产量当年提高83.97%,定植第2年提高91.05%。同时,该磷用量下柠条的Ca/P较理想。另外,结果分析还表明,柠条单纯作为饲料资源时,建议在养分管理上要隔年施1次磷肥,用量以P₂O₅180kg/hm²为准,以满足柠条生长的营养需求和维持柠条的高产稳产。     

Effects of epidural xylazine on EEG responses to surgical stimulation during isoflurane anaesthesia in dogs

The effects of epidural administration of 250 μg/kg xylazine on EEG responses to surgical stimulation of 5 different intensities were evaluated during isoflurane anaesthesia for an experimental orthopaedic procedure in dogs. The dogs were assigned randomly to one of 2 treatment groups receiving either xylazine (n = 4) or equal volumes of sterile water (n = 4) (control group) epidurally. Intense surgical stimulation during removal of a bone graft from the dorsoiliac spine of the ileum was associated with a significantly (P = 0.0339) higher increase in EEG alpha/delta ratio after epidural administration of sterile water than after epidural injection of 250 μg/kg of xylazine. In addition, the preincision baseline values for 80% spectral edge frequency were significantly (P = 0.0339) lower in the xylazine group compared to control dogs. Our results suggest that epidural administration of 250 μg/kg of xylazine during orthopaedic procedures in dogs exerts antinociceptive effects which may be in part mediated by a supraspinal effect of xylazine.     

Effects of remifentanil infusion regimens on cardiovascular function and responses to noxious stimulation in propofol-anesthetized cats

OBJECTIVE: To evaluate the effects of 2 remifentanil infusion regimens on cardiovascular function and responses to nociceptive stimulation in propofol-anesthetized cats. ANIMALS: 8 adult cats. PROCEDURES: On 2 occasions, cats received acepromazine followed by propofol (6 mg/kg then 0.3 mg/kg/min, i.v.) and a constant rate infusion (CRI) of remifentanil (0.2 or 0.3 microg/kg/ min, i.v.) for 90 minutes and underwent mechanical ventilation (phase I). After recording physiologic variables, an electrical stimulus (50 V; 50 Hz; 10 milliseconds) was applied to a forelimb to assess motor responses to nociceptive stimulation. After an interval (> or = 10 days), the same cats were anesthetized via administration of acepromazine and a similar infusion regimen of propofol; the remifentanil infusion rate adjustments that were required to inhibit cardiovascular responses to ovariohysterectomy were recorded (phase II). RESULTS: In phase I, heart rate and arterial pressure did not differ between remifentanil-treated groups. From 30 to 90 minutes, cats receiving 0.3 microg of remifentanil/kg/min had no response to noxious stimulation. Purposeful movement was detected more frequently in cats receiving 0.2 microg of remifentanil/kg/min. In phase II, the highest dosage (mean +/- SEM) of remifentanil that prevented cardiovascular responses was 0.23 +/- 0.01 microg/kg/min. For all experiments, mean time from infusion cessation until standing ranged from 115 to 140 minutes. CONCLUSIONS AND CLINICAL RELEVANCE: Although the lower infusion rate of remifentanil allowed ovariohysterectomy to be performed, a CRI of 0.3 microg/kg/min was necessary to prevent motor response to electrical stimulation in propofol-anesthetized cats. Recovery from anesthesia was prolonged with this technique.     

Green discolouration of urine following propofol infusion in a dog

A three‐year‐old, female neutered Weimaraner was presented with a history of neck pain and tetraparesis. MRI revealed an extradural mass at the level of C3 vertebra, which was thought to be a spinal abscess, and the dog was scheduled for surgical exploration the following morning. Overnight the dog developed an exaggerated ventilatory pattern, with paradoxical inward movement of the thorax on inspiration. Arterial blood gas analysis revealed respiratory acidosis and ventilator support was initiated to prevent excessive respiratory fatigue. During mechanical ventilation, anaesthesia was maintained using a propofol target‐controlled infusion system and, subsequently, the dog produced bright green urine in the urine collection system. Although previously documented in humans, this appears to be the first report of green urine in a dog following propofol use.