Induction and recovery characteristics of propofol, thiopental and etomidate

Propofol, thiopental and etomidate, with 20 patients in each group, were compared for anesthesia of short duration in women undergoing termination of pregnancy, with respect to: 1: pain on injection (equally often after propofol and etomidate, but more rarely after thiopental); 2: apnea following induction (no difference); 3: involuntary muscular movements more frequent after etomidate); 4: blood pressure (larger drop after propofol); 5: heart rate (greater increase after thiopental); 6: time to eye opening on command (longer after propofol); 7: Steward score on eye opening (no difference); 8: coin counting after 15, 30 and 60 min (performance better after propofol at 15 and 30 min, producing even shorter times than preoperatively at 60 min); 9: reaction time after 15, 30 and 60 min (performance better after propofol, producing even shorter times than preoperatively at 60 min. It is concluded that the faster recovery gives propofol an advantage over thiopental and etomidate in outpatient anesthesia.     

Preliminary report: the effect of flumazenil on the hypnotic dose of propofol in ddY mice

The present investigation dealt with the effect of simultaneous administration of flumazenil on the hypnotic activity of propofol using a behavioral model of ddY mice. The mixed solution of propofol and flumazenil was administered intravenously into the mice tail vein and the achievement of hypnosis was defined as the loss of the righting reflex. Flumazenil 0.2 mg.kg-1 significantly decreased the required dose of propofol for hypnosis (8.43 +/- 0.46 mg.kg-1) compared to the control group (10.55 +/- 0.55 mg.kg-1). The mixture with a pH-3.9 acetate buffer solution did not change the hypnotic dose of propofol (10.88 +/- 0.62 mg.kg-1). The results suggest that flumazenil might potentiate the hypnotic activity of propofol in ddY mice.     

Flumazenil reduces the hypnotic dose of propofol in male patients under spinal anesthesia

Purpose. Flumazenil has been reported to produce a partial benzodiazepine-agonist-like effect in some psychopharmacological examinations. This study investigated the effect of flumazenil on the hypnotic activity of propofol in 60 men scheduled for minor surgical procedures done under spinal anesthesia. Methods. After a steady state of spinal anesthesia had been reached, patients were pretreated with saline or flumazenil, 5 μg·kg⁻¹, followed by the administration of saline or midazolam, 10 μg·kg⁻¹. Then, 250 μg·kg⁻¹·min⁻¹ of propofol was infused until hypnosis was achieved. Loss of response to a simple command with a slight stimulus, served as the end-point for hypnosis. Immediately after achievement of the end-point, propofol infusion was discontinued, and a 2-ml venous blood sample was obtained from the dorsal pedis vein to determine plasma propofol concentration. Results. Flumazenil significantly decreased the dose of propofol required and the time required to achieve hypnosis compared with values in the control group (55 ± 10 [mean ± SD] vs 71 ± 14 mg and 212 ± 42 vs 268 ± 48 s, respectively; P < 0.05), whereas flumazenil attenuated the effect of midazolam in reducing the plasma concentration of propofol at hypnosis (2.9 ± 0.5 and 2.5 ± 0.6 μg·ml⁻¹, respectively; P < 0.05). Conclusion. These results suggested that flumazenil may potentiate the hypnotic properties of propofol, despite flumazenil having an antagonistic effect on the enhanced hypnotic activity of propofol induced by the coadministration of midazolam. Received: January 11, 2001 / Accepted: July 25, 2001     

Anoxic depolarization of rat hippocampal slices is prevented by thiopental but not by propofol or isoflurane

Background. There is strong evidence to suggest that anoxicdepolarization (AD) is an important factor in hypoxia/ischaemia-inducedneural damage. Treatments that prevent the occurrence of ADmay be useful in providing neuronal protection against hypoxia.The current study was designed to determine whether generalanaesthetics which have been suggested to ‘induce prophylaxis’against hypoxia can attenuate the incidence of AD. Methods. The effects of anoxia (3 min) on evoked extracellularlyrecorded field potentials of CA1 neurons in rat hippocampalslices were assessed in the absence and presence of the i.v.general anaesthetics thiopental and propofol and the volatileanaesthetic isoflurane. Results. In the absence of anaesthetics, AD occurred in 81%of the preparations tested. Thiopental (2x10^–4 M) significantlyreduced the incidence of AD (16%, P=0.0006). In comparison,propofol (2x10^–4 M) and isoflurane (1.5 vol%) were ineffective(69% and 60%, respectively). Furthermore, in the presence ofthiopental, the population spike amplitude recovered with andwithout AD (90% and 94% of pre-anoxic value, respectively) following3 min anoxia. Conclusion. The prophylactic effect of thiopental against hypoxiamight be induced, in part, by preventing the generation of AD.     

Midazolam/propofol but not propofol alone reversibly depress the swallowing reflex

General anaesthetics depress swallowing and this is a reason to delay oral intake after general anaesthesia. The swallowing reflex was studied 2 h after general anaesthesia for patients undergoing colonoscopy. Forty–one patients were anaesthetized with midazolam 75 μgkg^-1 followed by a continuous infusion of propofol and 39 patients with propofol 1.5 mgkg^-1 bolus followed by an infusion. Swallowing reflex was measured by electromyography 2 h after induction of anaesthesia, before and 5 min after the administration of flumazenil (0.2 mg) or placebo. Two h after anaesthesia, the state of consciousness was almost normal in all patients and did not change after flumazenil. At two hours, the latency times for the swallowing reflex in patients treated with propofol alone were of 1.4 ± 0.4 s and were significantly shorter ( P < 0.05) than the value of 1.9 ± 0.8 s observed in patients who received midazolam with propofol. In the latter group the latency time of the swallowing reflex was significantly reduced following the administration of flumazenil but not placebo. In patients who received propofol without midazolam, the administration of flumazenil or placebo was not associated with significant changes in the latency times. There were also no significant differences in the latency times in the subgroup that received midazolam followed by flumazenil and the propofol alone groups that did or did not receive flumazenil. These results suggest that midazolam still exerts a depressive effect on the swallowing reflex 2 h after its administration despite the recovery of normal consciousness.     

异丙酚和硫喷妥钠对离体大鼠心脏功能和细胞质膜Ca^2＋—ATPase活性的影响

目的 观察不同浓度异丙酚或硫喷妥钠对离体灌流大鼠心脏收缩力和心肌细胞质膜Ｃａ＾２＋－ＡＴＰａｓｅ活性的影响。方法 （１）以含不同浓度（１０ｕｍｏｌ／Ｌ～１０００ｕｍｏｌ／Ｌ）异丙酚或硫喷妥钠的克－汉二氏重碳酸盐缓冲液（ＫＨＢ）灌流离体大鼠心脏,测定心率（ＨＲ）、左室收缩压（ＬＶＳＰ）、左室收缩压上升最大速率（＋ｄｐ／ｄｔｍａｘ）和左室舒张压下降最大速率（－ｄｐ／ｄｔｍａｘ）。（２）参照文献制备大鼠心肌细胞质膜,观察不同浓度异丙酚或硫喷妥钠对质膜Ｃａ＾２＋－ＡＴＰａｓｅ活性的影响。结果 随着药液浓度的升高,异丙酚或硫喷妥钠使ＬＶＳＰ、＋ｄｐ／ｄｔｍａｘ逐渐降低,在等摩尔浓度的抑制作用异丙酚〉硫喷妥钠,高浓度的异丙酚或硫喷妥钠还可以减慢心率。异丙酚对质膜Ｃａ＾２＋－ＡＴＰａｓｅ活性的影响呈双相,低浓度（≤２０ｕｍｏ     

The effects of etomidate, thiopental, and propofol in induction on hypoperfusion-reperfusion phenomenon during laparoscopic cholecystectomy

BACKGROUND: A hypoperfusion-reperfusion human model is observed during and soon after laparoscopic surgery. The aim of the study was to research the preventive effects of etomidate, thiopental, and propofol in induction on hypoperfusion- reperfusion phenomenon during laparoscopic cholecystectomy. METHODS: Thirty-six consecutive ASA I-II patients were randomized into three groups of 12 patients each. Anaesthesia was induced with etomidate in group 1, thiopental in group 2, and propofol in group 3. Venous blood samples were obtained at different time points for measurement of plasma malondialdehyde (MDA) levels. Arterial blood and gastric juice samples were obtained for the calculation of gastric intramucosal pH (pHi). Also changes in aminotransferases, alkaline phosphatase and total bilirubin levels were assessed. RESULTS: There was a significant decrease in pHi at 1 min before desufflation (BD) and 20 min after desufflation (AD) compared with before insufflation (BI) in all groups. Plasma level of MDA was significantly increased in group 1 at 1 min BD and 20 min AD compared with before induction of anaesthesia (baseline). Malondialdehyde levels were decreased significantly in group 3 and increased non-significantly in group 2 at the same time points. Also AST and ALT levels were significantly increased in both groups 1 and 2 at 24 h postoperatively. CONCLUSION: Propofol with antioxidant activity may offer many advantages by scavenging reactive oxygen species and their metabolites in case of anticipated hypoperfusion-reperfusion phenomenon, such as would occur in laparoscopic surgery.     

The effect of a 3 : 1 volume mixture of propofol 1% and thiopental 2.5% in reducing the pain on injection of propofol in children1

Background: In this prospective, randomized, double‐blind, controlled trial, our primary objective was to assess the effect of a 3 : 1 mixture of propofol and thiopental in reducing pain on injection in children. Our hypothesis was that a 3 : 1 mixture of propofol and thiopental (treatment) would reduce the incidence of pain on injection to 20% compared to the expected incidence of 40% in the control group of an 11 : 1 mixture of propofol and 2% lidocaine. Methods: Study subjects were patients 12–17 years old who were scheduled to undergo surgery and general anesthesia. Pain was assessed by a single‐blinded observer present in the operating room. The major statistical method used in the analysis was multiple logistic regression. Results: Among the 164 children analyzed, 96 patients (58.5%) were male. The average age was 14.3 (sd = 1.65). The incidence of pain in the control group was 32.1% (26/81), compared to 25.3% (21/83) in the treatment group. The logistic regression analysis showed that there was not sufficient evidence that the treatment group was better than control group in reducing pain (P = 0.24). There were no significant differences in postoperative recovery time, nausea, vomiting, or blood pressure between the two groups (all P values >0.10). Conclusion: There was not sufficient evidence to show that a 3 : 1 mixture of propofol and thiopental was better than an 11 : 1 volume admixture of propofol and lidocaine in reducing the incidence of pain on injection to 20%.     

Intubating conditions provided by propofol and alfentanil - acceptable, but not ideal

Background: The use of muscle relaxants to facilitate intubation is associated with several side effects regardless of whether depolarizing or non-depolarizing drugs are used. In the present study we compared the intubating conditions, haemodynamic responses and changes in oxygen saturation following induction with alfentanil and propofol or alfentanil, thiopental and suxamethonium.
Methods: Eighty patients (ASA I or II) were in a double-blind manner assigned to receive either of the two induction methods. Intubating conditions were assessed on the basis of jaw relaxation, ease of insertion of the endotracheal tube and coughing on intubation. Heart rate, systolic arterial pressure and oxygen saturation were monitored throughout the procedure.
Results: The use of alfentanil and propofol resulted in significantly lower scored intubation points. Systolic arterial pressure decreased and heart rate increased significantly in the alfentanil-thiopental-suxamethonium group as compared to the alfentanil-propofol group. There were no significant changes in oxygen saturation.
Conclusion: The results show that propofol and alfentanil in combination provides haemodynamic stability and unaltered oxygen saturation but less optimal intubating conditions.     

Time-frequency balanced spectral entropy as a measure of anesthetic drug effect in central nervous system during sevoflurane, propofol, and thiopental anesthesia

BACKGROUND: Time-frequency balanced spectral entropy of electroencephalogram (EEG) and frontal electromyogram (FEMG) is a novel measure of hypnosis during anesthesia. Two Entropy parameters are described: Response entropy (RE) is calculated from EEG and FEMG; and State Entropy (SE) is calculated mainly from EEG. This study was performed to validate their performance during transition from consciousness to unconsciousness under different anesthetic agents. METHODS: Response entropy, SE [S/5 Entropy Module, M-ENTROPY (later in text: Entropy), Datex-Ohmeda Division, Instrumentarium Corp., Helsinki, Finland] and BIS (BIS XP, A-2000, Aspect Medical Systems, Newton, MA) data were collected from 70 patients; 30 anesthetized with propofol 2 mg kg-1, 20 with sevoflurane inhalation, and 20 with thiopental 5 mg kg-1. Loss and regaining of consciousness (LOC, ROC) was tested every 10 s, and sensitivity, specificity, and prediction probability (Pk) were calculated. Behavior of the indices was studied. RESULTS: Sensitivity, specificity, and Pk values for consciousness were high and similar for all indices. During regaining of consciousness after propofol bolus, RE, SE, and BIS values recovered by 81 +/- 22%, 75 +/- 26%, and 59 +/- 18% (mean +/- SD), respectively, from the minimum relative to their baseline. After thiopental bolus, RE, SE, and BIS values recovered by 86+/-21%, 88 +/- 13%, and 63 +/- 14%, respectively. The relative rise was higher in RE and SE compared with BIS (P < 0.01). During deep levels of hypnosis, RE and SE decreased monotonously as a function of burst suppression ratio, while BIS showed biphasic behavior. On average, RE indicated emergence from anesthesia 11 s earlier than SE, and 12.4 s earlier than BIS. CONCLUSIONS: All indices, RE, SE, and BIS, distinguished excellently between conscious and unconscious states during propofol, sevoflurane, and thiopental anesthesia. During burst suppression, Entropy parameters RE and SE, but not BIS, behave monotonously. During regaining of consciousness after a thiopental or propofol bolus, RE and SE values recovered significantly closer to their baseline values than did BIS. Response entropy indicates emergence from anesthesia earlier than SE or BIS.     

Factors that influence the induction dose of propofol

Factors that influence the induction of anaesthesia with propofol were investigated in a prospective study of 1000 patients. Pre-operative albumin and urea concentrations correlated with the minimum induction dose of propofol, but less strong correlations were found with haemoglobin, globulin and total protein concentrations. Age was an important influence on the induction dose of propofol (r = -0.34) which was also closely related to ASA grade. Induction of anaesthesia with propofol is dependent on a number of variables, and this study suggests that pre-operative albumin and urea concentrations are important.     

Reinduction of the hypnotic effects of thiopental with NSAIDs by decreasing thiopental plasma protein binding in humans

The effects of 14 non-steroidal anti-inflammatory drugs (NSAIDs) -naproxen, ibuprofen, mefenamic acid, ketoprofen, indomethacin, fenoprofen, diclofenac sodium, aspirin, salicylic acid, piroxicam, sulindac, fenbufen, flurbiprofen and benzydamine, on the plasma protein binding of thiopental and the clinical consequences of such interactions were studied. Four of them, naproxen, ibuprofen, salicylic acid and aspirin, very significantly decreased the protein binding of thiopental in uitro in human plasma (P< 0.005). Structurally, they were salicylates and propionic acid derivatives among the six classes of NSAIDs studied. The aspirin study demonstrated that the protein-displacing phenomenon was temperature-dependent, and concentration-dependent. Clinically, aspirin administered intravenously resulted in a significant increase in the percentage of plasma free thiopental from 16.01 ± 3.59% to 22.27 ± 3.96% (P< 0.001, n = 10) in patients undergoing surgery, and resulted in three of seven patients sleeping again during recovery from thiopental-induced anesthesia. Although the effect of chronic use of NSAIDs before anesthesia is uncertain, studies should be carried out to find out if naproxen, ibuprofen, and aspirin influence the depth of anesthesia, time of recovery and duration of action of thiopental.     

Influence of thiopental and propofol on postoperative cognitive recovery in the elderly patient undergoing general anesthesia

Study Objective: To assess mental and psychomotor recovery following induction of anesthesia with thiopental or propofol in elderly patients undergoing general anesthesia.

Design: Randomized, prospective, double-blind study.

Setting: Large referral hospital.

Patients: 40 elderly patients ASA physical status I-III (>65 years) undergoing abdomino-pelvic surgery with an estimated surgical time of at least 90 minutes.

Interventions: All patients received combined epidural-general anesthesia. After establishing a T₆ sensory blockade, patients were randomized to receive either thiopental or propofol for induction of general anesthesia. The induction drug was slowly titrated until loss of eyelash reflex was noted. Thereafter, all patients received desflurane (2% to 3% end-tidal) and 70% nitrous oxide (N₂O) in oxygen for maintenance of general anesthesia. To facilitate tracheal intubation, intravenous alfentanil 10 μg/kg and atracurium 0.4 mg/kg were administered. Perioperative analgesia was maintained with epidural bupivacaine.

Measurements and Main Results: A digit substitution test (DSST) and shape-sorter test, as well as patient-generated 100-mm visual analog score (VAS; 0 = minimal and 100 = maximal) for anxiety, sleepiness, and coordination, were performed during the preanesthetic interview, on postanesthesia care unit admission, and at 15, 45, 90, and 120 minutes thereafter. To induce loss of consciousness, either thiopental 2.5 ± 1.0 mg/kg or propofol 1.6 ± 0.6 mg/kg was administered. The mean anesthetic time was 109 ± 30 minutes and 114 ± 38 minutes for the thiopental and propofol groups, respectively. Emergence, extubation, and orientation times, as well as time to follow commands, were unaffected by patient randomization. Similarly, the DSST and shape-sorter tests, in addition to the patient-generated VAS for pain, anxiety, and coordination, were similar among groups. However, irrespective of treatment modality, return to baseline digit substitution and shape-sorter scores were significantly delayed (p < 0.01).

Conclusion: When compared to thiopental, propofol does not facilitate improved cognitive recovery in geriatric patients undergoing prolonged surgery.     

Differential effects of propofol, ketamine, and thiopental anaesthesia on the skeletal muscle microcirculation of normotensive and hypertensive rats in vivo

Background. This study utilized the dorsal microcirculatorychamber (DMC) model to determine differential effects of i.v.propofol, ketamine, and thiopental anaesthesia on the skeletalmuscle microcirculation (10–180 µm) of normotensive(Male Wistar Kyoto, WKY) and hypertensive (spontaneously hypertensiveHarlan, SHR) rats, importantly, comparing responses to a consciousbaseline. Methods. Three weeks following implantation of the DMC in WKY(n=8) and SHR (n=6) (130 g) 0.25 ml 100 g^–1 FITC–BSA(i.v.) was administered and the microcirculation viewed usingfluorescent in vivo microscopy for a 30 min baseline (t=0–30min). This was followed by either propofol, thiopental, ketamine,or saline (i.v. bolus induction over 5 min (t=30–35 min)),then maintenance step-up infusion for 60 min (t=45–105min), so that animals received all four agents 1 week apart(56 experiments). Results. Dilation of A3 arterioles (15–30 µm) andV3 venules (20–40 µm) with propofol was greaterin SHR (t=95 min, A3 36.7 (12)%, V3 15.5 (2.3)%) than WKY (t=95min, A3 19.4 (7.4)%, V3 8.0 (2.3)%) (P<0.05). Constrictionof A3 with ketamine was greater in SHR (t=95 min, A3 –29.1(6.4)%) than WKY (A3 –17.5 (8.8)%) (P<0.05). This wasaccompanied by hypotension with propofol in SHR (–32%decrease in systolic arterial pressure), but not WKY (–6%)and hypertension with ketamine in WKY (–15%) and SHR (–24%)(P<0.05). During thiopental anaesthesia there was dilationof A1 (80–180 µm), A3, and V3 in WKY (P<0.05).Conversely, in SHR dilation of venules (29.2 (8.7)%) was accompaniedby constriction of A1 and A3 (t=95 min, A1 –25.1 (5.9)%,A3 –45.2 (3.1)%) (P<0.05). Conclusion. Within the skeletal muscle microcirculation of hypertensiverats there is enhanced dilation with propofol and constrictionwith ketamine, associated with exaggerated changes in arterialpressure. Thus, dysfunctional control mechanisms at the levelof the microcirculation alter responses to anaesthesia duringhypertension.      

椎管内麻醉下使病人意识消失的异丙酚ED50

目的本研究拟通过序贯法测定胸段硬膜外麻醉或腰麻下使50％病人入睡的异丙酚的剂量（催眠ED50）。并监测复合麻醉下BIS值的变化,分析其能否反映镇静深度。方法20例行开胸手术的病人及30例行下腹部或下肢手术的病人。分别予2％利多卡因15ml行硬膜外麻醉和丁卡因（10mg）腰麻。以半数效量序贯法测定异丙酚的催眠ED50：将异丙酚的首次剂量等比分为五阶梯：0．56mg／kg,0．68mg／kg,0．84mg／kg,1．02mg／kg,1．25mg／kg。按序贯法给药。以呼之不应和睫毛反射消失作为入睡指标,并监测脑电双频谱指数（BIS）和病人的血流动力学指标。结果胸段硬膜外麻醉下异丙酚的催眠ED50：0．82mg／kg（95％置信区间：0．71mg／kg～0．94mg／kg）。腰麻下异丙酚的催眠ED50：0．8095mg／kg（95％置信区间为0．7295mg／kg～0．8974mg／kg）。异丙酚诱导后入睡和未睡病人BIS值相比P〈0．001,有统计学意义。结论序贯法计算半数效量简单有效。BIS值可以有效反映椎管内麻醉合用异丙酚的麻醉深度。     

Comparison of the recovery characteristics of midazolam, alone or antagonised with flumazenil, and thiopental in ASA III-IV patients

Sixty non-premedicated male patients, physically ASA III-IV, 50–80 years of age, undergoing translumbar aor-thography, were randomly allocated into three groups. Group A received midazolam (0.13 mg·kg^-1), group B received thiopental (4 mg · kg^-1), and group C midazolam (0.13 mg · kg^-1) combined with flumazenil (6 μg · kg^-1) at the end of the operation. Three minutes before the anaesthesia began, fentanyl (1.5 μg · kg^-1) was administered to all the patients. An evaluation was made of the time they took to open their eyes spontaneously, of time-space orientation, comprehension-collaboration, hypnosedation, psychomotor performance and memory. In groups "C" and "B" spontaneous opening of the eyes took place before that of group "A". The recovery of orientation, comprehension and hypnosedation was fastest with thiopental, next with midazolam combined with flumazenil, and later with midazolam. Psychomotor performance in Trieger test was impaired for a shorter period with thiopental than in the other two groups. Recovery in group "C" was incomplete within the time, with the result that resedation was detected in 20% of the subjects.     

Dexmedetomidine and hydroxyzine synergistically potentiate the hypnotic activity of propofol in mice

Purpose

Investigation into the characteristics of anesthetic interactions may provide clues to anesthesia mechanisms. Dexmedetomidine, an ??₂-adrenergic receptor agonist, has become a popular sedative in intensive care, and hydroxyzine, a histamine receptor antagonist, is well known as a tranquilizing premedication for anesthesia. However, no experimental or pharmacological evaluation has been reported concerning their combination with propofol. Thus, we studied their combined effect with a hypnotic dose of propofol in ddY mice.

Methods

Male adult mice were intravenously administered either dexmedetomidine (30???g/kg) or hydroxyzine (5?mg/kg) with propofol (3.75?C10?mg/kg) to induce hypnosis, defined as a loss of the righting reflex (LRR). Other mice were intravenously administered propofol, dexmedetomidine (300???g/kg), or hydroxyzine (50?mg/kg) alone, and subsequent behavioral changes were observed. The 50% effective dose (ED₅₀) for LRR was calculated, and the duration of LRR was determined.

Results

The hypnotic dose of propofol was 9.95?±?1.04?mg/kg (ED₅₀?±?SEM) without combination. Dexmedetomidine and hydroxyzine reduced the ED₅₀ of propofol to 5.32?±?0.57 and 5.63?±?0.57?mg/kg, respectively. Coadministration of dexmedetomidine significantly extended LRR duration compared with propofol alone, whereas hydroxyzine significantly shortened LRR duration. A maximal dose of dexmedetomidine or hydroxyzine alone did not induce hypnosis.

Conclusions

Dexmedetomidine and hydroxyzine demonstrated no hypnotic action alone; however, their coadministration potentiated the hypnotic activity of propofol. Although reduction in the dose of propofol was similar, only dexmedetomidine prolonged the duration of hypnosis.     

Growth of Escherichia coli in propofol, lidocaine, and mixtures of propofol and lidocaine

BACKGROUND: Microorganisms grow rapidly in propofol. Extrinsic contamination of propofol is thought to be a source of postoperative sepsis and wound infection. We studied growth of a strain of Escherichia coli in thiopental, propofol, lidocaine, and mixtures of propofol and lidocaine. METHODS: The pathogen was exposed to 2.5% thiopental; 1.0% propofol; 1.0%, 2.0% and 4.0% preservative-free lidocaine; and propofol solutions containing 0.25%, 0.5%, 1.0%, 2.0%, or 4.0% lidocaine for 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 h at room temperature, respectively. The inocula from these suspensions were cultured for 48 h at 37 degrees C after the antimicrobial activity of the local anesthetics in the inocula was inactivated by a 1:1000 dilution with distilled water. RESULTS: No organisms grew after exposure to 2.5% thiopental. The exposure of E. coli to propofol increased the colony count to approximately 90 times the control count. The colony counts of E. coli after exposure to 1.0%, 2.0% and 4.0% lidocaine and 0.25%, 0.5%, 1.0%, 2.0% and 4.0% lidocaine in 1.0% propofol were lower than the counts after exposure to 1.0% propofol (P = 0.0048, 0.0027, 0.0003, 0.0503, 0.0188, 0.0080, 0.0044, and 0.0001, respectively). The growth rate of the microorganism was significantly higher in cultures exposed to 1.0% propofol than that in cultures exposed to lidocaine alone or lidocaine-propofol mixtures (P < 0.0001, respectively). CONCLUSION: Lidocaine possesses bacteriostatic activity against E. coli. Addition of lidocaine to propofol confers its bacteriostatic activity to the mixture and may decrease the hazard of infection associated with the extrinsic contamination of propofol.     

Comparative effects of thiopental and propofol on atrial vulnerability: electrophysiological study in a porcine model including acute alcoholic intoxication

Background. Atrial tachyarrhythmias (AT) frequently complicatethe perioperative period. Alcohol intoxication is a recognizedcausative factor for dysrrhythmias. We studied the effects ofpropofol and thiopental on atrial electrophysiology and vulnerabilityto AT in a closed-chest porcine model in which AT are facilitatedby ethanol. Methods. Thirty-eight pigs were randomly assigned to thiopental(T-group, n=19) or propofol (P-group n=19). All animals wereassigned to undergo a right atrial electrical stimulation protocol(RASP) at baseline. Thirty pigs were assigned to undergo additionalRASP during ethanol infusion, while the remaining eight wereassigned to undergo additional RASP during saline infusion (controlgroup). We analysed effective refractory period (ERP), and intra-atrialconduction interval (ICI) (between atrial sites 4 cm apart),at several cycle lengths (CL). Results. There were no significant differences at baseline.During ethanol infusion, propofol produced a greater rate-dependentdecrease in excitability, manifested by a longer minimum pacedCL with 1:1 atrial capture: 145 (11) vs 164 (27) ms in the T-and P-group, respectively (P=0.01). Propofol was associatedwith a greater rate-related slowing in conduction: differencebetween ICI at CL of 300 ms and ICI at minimum CL: 30 ms inP-group and 22 ms in T-group (P<0.03). In the P-group weobserved a longer duration of induced arrhythmias (145 (131)vs 74 (91) s, P<0.03) and a higher proportion with atrialflutter (AFl) (76 vs 19%, P<0.001). Conclusions. Propofol in this model was more arrhythmogenicthan thiopental, as manifested by a longer duration of inducedarrhythmias, particularly AFl. This work has been presented at the 9th Annual Meeting of EuropeanSociety of Anaesthesiology, 7–10 April 2001, Gothenburg,Sweden.     

Sustained intravascular exposure to propofol does not prolong pain at the site of injection

BACKGROUND: Pain at the site of intravenous injection of propofol is a common clinical finding. This double-blind, randomized cross-over study was designed to evaluate whether venous occlusion applied during injection of a low dose of propofol reduces the intensity of pain at the site of injection compared with no occlusion. METHODS: Bilateral 0.5-ml injections of an emulsion containing 10 mg/ml of propofol were given over 30 s in 75 adult surgical patients. Each patient was given one injection with and one without 60-s occlusion of the cannulated vein with a 10-min interval, and asked to score the maximal pain intensity on a visual analogue scale (VAS). RESULTS: The maximal pain intensity [median (25th percentile; 75th percentile), range] at the site of injection was 0.5 (0; 3.5), 0-8.0 VAS units with venous occlusion and 0.5 (0; 1.4), 0-6.0 VAS units without occlusion (P= 0.042). Pain was first reported within 20 s regardless of the study regimen and was not prolonged by local venous occlusion. CONCLUSION: Venous occlusion augments pain intensity at the site of propofol injection without prolonging pain, implying that propofol-induced pain is determined more by the blood concentration than by the duration of intravascular exposure. The low intensity of pain induced by low-dose propofol and the fading of pain despite sustained exposure suggest that initial low-dose administration of propofol should be evaluated for the attenuation of local pain induced by higher intravenous doses of propofol.