Total Propofol Research Articles

A Randomized Controlled Trial of Ketamine/Propofol Versus Propofol Alone for Emergency Department Procedural Sedation

We compare the frequency of respiratory depression during emergency department procedural sedation with ketamine plus propofol versus propofol alone. Secondary outcomes are provider satisfaction, sedation quality, and total propofol dose. In this randomized, double-blind, placebo-controlled trial, healthy children and adults undergoing procedural sedation were pretreated with intravenous fentanyl and then randomized to receive either intravenous ketamine 0.5 mg/kg or placebo. In both groups, this procedure was immediately followed by intravenous propofol 1 mg/kg, with repeated doses of 0.5 mg/kg as needed to achieve and maintain sedation. Respiratory depression was defined according to any of 5 predefined markers. Provider satisfaction was scored on a 5-point scale, sedation quality with the Colorado Behavioral Numerical Pain Scale, and propofol dose according to the total number of milligrams of propofol administered. The incidence of respiratory depression was similar between the ketamine/propofol (21/97; 22%) and propofol-alone (27/96; 28%) groups, difference 6% (95% confidence interval -6% to 18%). With ketamine/propofol compared with propofol alone, treating physicians and nurses were more satisfied, less propofol was administered, and there was a trend toward better sedation quality. Compared with procedural sedation with propofol alone, the combination of ketamine and propofol did not reduce the incidence of respiratory depression but resulted in greater provider satisfaction, less propofol administration, and perhaps better sedation quality.

Comparing Continuous Lumbar Plexus Block, Continuous Epidural Block And Continuous Lumbar Plexus Block With A Parasacral Sciatic Nerve Block On Post-Operative Analgesia After Hip Arthroplasty

Study Objective: To compare post-operative analgesia obtained by continuous lumbar epidural block (CLEB) versus continuous lumbar plexus block (CLPB) versus CLPB associated with a single shot parasacral sciatic nerve block (CLEBS) after total hip arthroplasty (THA). Study design: Randomized clinical trial. Setting: Operating room, postoperative care unit, orthopedic surgical ward. Methods: 78 ASA I-III patients undergoing elective THA were randomly assigned to receive CLEB (n=24, 15- 20 ml of 5 mg/ml ropivacaine, sufentanil 10 mg, clonidine 1 mg/ml), CLPB (n=22, 3mg/kg of 5 mg/ml of ropivacaine, max. 40 ml, clonidine 1 mg/ml, sufentanil 10 mg) or CLPBS (n=23, CLPB as described above; sciatic nerve: 20 ml of ropivacaine 5 mg/ml, clonidine 1 mg/ml). All patients received continuous infusion of 2 mg/ml of ropivacaine, 8 ml/h for 48 hours. Primary outcome was pain intensity assessment (VAS and VS). Secondary outcomes were postoperative total opioid consumption, hemodynamic stability, motor blockade, blood loss, intraoperative sufentanil and propofol consumption, patient satisfaction and complications. Results: VAS was lower in the CLEB group than in the CLPB and CLPBS groups respectively for 6 and 12 hours postoperatively (post-surgery p<0.001, 2h p<0.001, 6h p<0.001, 12h p<0.03)(Table 2). Moreover, CLPSB patients reported lower VAS than CLPB patients from the end of the surgery till the 12th follow up hour (Table 2). VS was lower in the CLEB group from the end of surgery to 6h postoperatively (Table 3). The CLPB group showed higher morphine consumption than the CLPSB and CLEB groups over 12 h postoperatively (p=0.05); thereafter, no statistically significant differences were observed between groups at the end of follow up (48h) (p=0.4) (Table 4). Conclusion: In conclusion, continuous lumbar plexus block in association with single shot sciatic nerve block is a valid alternative to epidural technique in managing postoperative analgesia after THA, with an improved riskbenefit balance.

Effects of different propofol injection speeds on blood pressure, dose, and time of induction

Blood concentration of propofol depends on many factors, such as age, gender, body weight, dose, infusion rate, and cardiac output. This study primarily investigated the effect of infusion rate on blood pressure changes. Secondarily induction time and induction dose were studied. Materials and methods: Propofol was administered at 200 (P200), 300 (P300), or 400 mL h-1 (P400) until loss of consciousness using bispectral index (BIS) monitoring in 72 adult patients. Change in blood pressure, induction time, and dose of propofol were compared among 3 groups. Results: The decreases in systolic and mean arterial pressure were statistically significant in the P200 group (P = 0.001, P = 0.014 respectively). Systolic blood pressure decreased significantly as the infusion rate increased. Diastolic blood pressure did not change in either group. The duration of induction was shortest with 400 mL h-1 infusion rate (177 s in P200, 182 s in P300, 134 s* in P400,*P = 0.003) and the total propofol dose was significantly higher in these patients (2.32 mg kg-1 in P200, 2.64 mg kg-1 in P300 , 2.85* mg kg-1 in P400, *P = 0.012). Conclusion: The induction dose required for loss of consciousness increased with a faster rate of infusion while time for induction was shorter in P400 compared to P200 and P300, and the decrease in mean blood pressure was less after induction in P200. Propofol injection should be slow enough to prevent any hemodynamic deterioration in anesthesia induction.

Sédation avec le propofol dans un service d’urgences. Étude prospective observationnelle

IntroductionWe describe the use of propofol for procedural sedation and analgesia (PSA) in a French adult Emergency Department (ED). We compare the results with those previously published.Materials and methodsA 44-month prospective observational study of the use of propofol in a French adult ED was conducted. Propofol was injected intravenously as a 1 mg/kg bolus, which could be followed by smaller aliquots if necessary. All patients were monitored for at least 30 minutes after the last injection.ResultsAmong the 115 patients who received propofol for PSA during the study period, 111 (69 males and 42 females) were completely evaluated. The mean age was 50 (SD: 21; range: 18–94), mean body weight was 75 kg (SD: 15; range: 48–140), mean total propofol dosing was 113 mg (SD: 58; range: 30–370), and mean propofol dosing per kg was 1.50 mg/kg (SD: 0.75; range: 0.5–5.6 mg/kg). The treatment was successful in 107/111 cases (97%). If hypotension or respiratory depression occurred, they were resolved in minutes. There were no cases of emesis, inhalation, or other side effects. These results compare favorably with those previously published.ConclusionPropofol is a useful and safe tool for PSA in French EDs, as it is elsewhere.

Lean Body Weight Scalar for the Anesthetic Induction Dose of Propofol in Morbidly Obese Subjects

The unique anesthetic risks associated with the morbidly obese (MO) population have been documented. Pharmacologic management of these patients may be altered because of the physiologic and anthropometric changes associated with obesity. Unfortunately, studies examining the effects of extreme obesity on the pharmacology of anesthetics have been sparse. Although propofol is the induction drug most frequently used in these patients, the appropriate induction dosing scalar for propofol remains controversial in MO subjects. Therefore, we compared different weight-based scalars for dosing propofol for anesthetic induction in MO subjects. Sixty MO subjects (body mass index ≥40 kg/m(2)) were randomized to receive a propofol infusion (100 mg · kg(-1) · h(-1)) for induction of anesthesia based on total body weight (TBW) or lean body weight (LBW). Thirty control subjects (body mass index ≤25 kg/m(2)) received a propofol infusion (100 mg · kg(-1) · h(-1)) based on TBW. Syringe drop was used as the marker for loss of consciousness (LOC), at which point the propofol infusion was stopped. The propofol dose required for syringe drop and time to LOC were recorded. Total propofol dose (mg/kg) required for syringe drop and time to LOC were similar between control subjects and MO subjects given propofol based on LBW. MO subjects receiving a propofol infusion based on TBW had a significantly larger propofol dose and significantly shorter time to LOC. There was a strong relationship between LBW and total propofol dose received in all 3 groups. LBW is a more appropriate weight-based scalar for propofol infusion for induction of general anesthesia in MO subjects.

A Randomized Controlled Trial Comparing Patient-Controlled and Physician-Controlled Sedation in the Emergency Department

We compare patient-controlled sedation (PCS) and emergency physician-controlled sedation (EPCS) with respect to propofol requirements, depth of sedation, adverse events, recovery time, physician satisfaction, and patient satisfaction in emergency department (ED) patients requiring brief but painful procedures. One hundred sixty-six patients in this randomized controlled trial received propofol sedation according to one of 2 regimens: infusion of propofol at doses determined by the treating physician (EPCS group) or infusion of propofol with a patient-controlled infusion pump (PCS group). The PCS group received an initial physician-controlled bolus following by self-administered doses. Depth of sedation was assessed at 3-minute intervals. Adverse events were recorded as they occurred. Physician and patient satisfaction were recorded with 100-mm visual analog scales. There was a nonsignificant trend toward lower total propofol doses with PCS relative to EPCS (medians 1.36 versus 1.60 mg/kg, respectively; median difference -0.15 mg/kg; 95% confidence interval of the difference -0.33 to 0.05 mg/kg; P=.14). Adverse events, requirement for treatment of adverse events, and recovery time did not differ in the 2 groups. Depth of sedation was lower in the PCS group. Procedural success, ease of procedure, and patient satisfaction were similar in both groups despite nearly twice as many patients recalling the procedure in the PCS group and 15% of patients requiring additional physician-administered doses in the PCS group. Compared with EPCS, PCS demonstrated similar propofol dosing, safety, recovery, and satisfaction but resulted in lighter sedation. Propofol PCS appears safe and effective for ED procedures requiring moderate rather than deep sedation.

Bispectral Index Monitoring to Facilitate Early Extubation Following Cardiovascular Surgery

Frequently, intensive care nurses assume responsibility for extubating patients after undergoing cardiac surgery. Bispectral index (BIS) monitoring assesses level of mental arousal and awareness when sedated. This study was to determine if the BIS might facilitate earlier extubation of patients following cardiac surgery. A study was conducted comparing 25 stable patients returning to the intensive care unit with a BIS with 25 patients managed without the BIS (N = 50). Data collected included age, sex, surgery, pH, CO2, and temperature on arrival/extubation, total intravenous propofol and pain medication, and BIS scores. Student t tests determined that there were no differences between groups for age, amount of propofol and pain medication received, or time to extubation (P > .05). Regression analysis determined that total propofol, total hydromorphone, and age were significant predictors of time to extubation. In this study, the BIS monitor did not facilitate earlier extubation in the stable patient after cardiac surgery.

Effect of menstrual cycle on the injection pain due to propofol

This prospective, double-blind and randomized study is designed to determine the effect of menstrual cycle on the injection pain of propofol. Seventy-two patients scheduled for elective surgery under general anaesthesia were divided into two groups according to the phase of the menstrual cycle. Patients were at follicular phase (Pd 8-12) in Group F (n = 36) and luteal phase (Pd 20-24) in Group L (n = 36). Injection pain was evaluated with 10-point numeric rating scale after 25% of the total propofol dose was injected over 20 s. There were no significant differences in terms of patient characteristics (P > 0.05). The mean propofol pain score was found 1.81 +/- 2.30 in Group F and 4.83 +/- 3.09 in Group L. Group L was found to have higher propofol injection pain scores than Group F (P < 0.001). We conclude that the menstrual phase changes the perception of pain due to propofol injection, which is higher in the lutheal phase. In clinical practice, the phases of the menstrual cycle may have a significant role on injection pain of propofol in woman.

The Effect of Aminophylline on Loss of Consciousness, Bispectral Index, Propofol Requirement, and Minimum Alveolar Concentration of Desflurane in Volunteers

Adenosine is a soporific neuromodulator; aminophylline, which is clinically used as a bronchodilator, antagonizes the action of adenosine in the central nervous system. Thus, we tested the hypothesis that aminophylline delays loss of consciousness (LOC) and speeds recovery of consciousness (ROC) with propofol anesthesia, and that aminophylline increases the minimum alveolar concentration (MAC) of desflurane. In this double-blind crossover study, volunteers were randomized to either aminophylline or saline on different days. Aminophylline 6 mg/kg was given IV, followed by 1.5 mg x kg(-1) x h(-1) throughout the study day. After 1 h of aminophylline or saline administration, propofol 200 mg was given at a rate of 20 mg/min. The bispectral index was continuously monitored, as were times to LOC and ROC. After recovery from propofol, general anesthesia was induced with sevoflurane and subsequently maintained with desflurane. The Dixon "up-and-down" method was used to determine MAC in each volunteer after repeated tetanic electrical stimulation. Eight volunteers completed both study days. Time to LOC was prolonged by aminophylline compared with saline (mean +/- SD) (7.7 +/- 2.03 min vs 5.1 +/- 0.75 s, respectively, P = 0.011). The total propofol dose at LOC was larger with aminophylline (2.2 +/- 0.9 vs 1.4 +/- 0.4 mg/kg, P = 0.01), and the time to ROC was shorter (6.18 +/- 3.96 vs 12.2 +/- 4.73 min, P = 0.035). The minimum bispectral index was greater with aminophylline (51 +/- 15 vs 38 +/- 9, P = 0.034). There was no difference in MAC. Aminophylline decreases the sedative effects of propofol but does not affect MAC of desflurane as determined by tetanic electrical stimulation.

Subcutaneous pre‐anaesthetic medication with acepromazine–buprenorphine is effective as and less painful than the intramuscular route

To compare reaction to injection, sedation and propofol induction dose in dogs receiving acepromazine-buprenorphine pre-anaesthetic medication by the intramuscular or subcutaneous routes. Fifty-two client owned dogs of American Society of Anesthesiologists grade I or II anaesthetised for diagnostic imaging. Dogs were randomly assigned to receive acepromazine 0.03 mg/kg and buprenorphine 0.02 mg/kg either intramuscular or subcutaneous. Reaction to injection was scored. Sedation was compared before and one hour after pre-anaesthetic medication. Propofol was administered in 1 mg/kg incremental injections until tracheal intubation was achieved. Total propofol dose was recorded. Reaction to injection was significantly greater (P=0.009) in the intramuscular group compared to the subcutaneous group. Sedation scores were not significantly different (P=0.523) between the intramuscular and the subcutaneous group. There was no statistically significant difference in propofol dose for induction (P=0.7). Acepromazine-buprenorphine pre-anaesthetic medication provides a similar degree of sedation whether administered by the intramuscular or subcutaneous route. The intramuscular route is more painful compared to the subcutaneous route.

The effect of Diprivan (propofol) on phosphorylcholine surfaces during cardiopulmonary bypass — an in vitro investigation

It is well known that extracorporeal surfaces have the ability to bind such drugs as fentanyl, nitroglycerine and propofol. Adsorption of the injectable anesthetic agent Diprivan (propofol) onto uncoated and heparin-coated extracorporeal surfaces during cardiopulmonary bypass (CPB) has been previously investigated; however, propofol adsorption onto synthetic-coated extracorporeal surfaces has not been published previously. The focus of this investigation was on the interaction of propofol and the synthetic biomimetic coating from the Sorin Group called Mimesys (phosphorylcholine (PC)). A randomized series of six in vitro experiments were done with propofol using both PC-coated circuits without arterial filters and those with arterial filters. The circuits were identical in all experiments and priming remained the same, with 750 mls of normal saline and 1250 mls of fresh bovine blood (hematocrit 41.0 +/- 1.0%). After circulation and collection of baseline samples, the first (low) dose of 4 mg (4000 mcg) of Diprivan 1% was added to the perfusate, followed by the second (high) dose of 40 mg (40,000 mcg) and the final challenge (extreme dose) of 356 mg (356,000 mcg) of Diprivan. Drug assay was done by an independent laboratory, using the standardized method of High Performance Liquid Chromatography (HPLC). Measurements of total propofol were done at baseline, 20 minutes, 40 minutes and 60 minutes after each injection. Oxygenator performance was also measured prior to the addition of propofol and repeated after exposure to 4 mg, 40mg and 356 mg propofol for 60 min, 120 min and 180 minutes of circulation. Results indicate that phosphorylcholine coating does not prevent the adsorption of propofol during extracorporeal circulation and the oxygenator's gas exchange ability is not affected by prolonged exposure to an extreme dose of the medication during high flow extracorporeal circulation.

The Analgesic Effect of Gabapentin as a Prophylactic Anticonvulsant Drug on Postcraniotomy Pain: A Prospective Randomized Study

Gabapentin is an anticonvulsant drug that has analgesic properties for acute postoperative pain. However, the analgesic effect of gabapentin as an antiepileptic prophylactic drug on patients undergoing craniotomy is unclear. In this study, we evaluated the postoperative effectiveness of gabapentin on acute postoperative pain when it is used for antiepileptic prophylaxis in patients undergoing craniotomy for supratentorial tumor resection. Eighty patients undergoing craniotomy for supratentorial tumor resection were randomly assigned into two groups. Patients in Group G (n = 40) received oral gabapentin (3 x 400 mg), and patients in Group P (n = 40) received oral phenytoin (3 x 100 mg) for 7 days before the operation and postoperatively. An identical anesthesia protocol was performed for both the groups. Anesthesia was maintained with propofol and remifentanil infusion. Patient-controlled analgesia with morphine was used, and pain levels were measured. The antiepileptic-related side effects, anesthetic consumption, duration of anesthesia and surgery, tracheal extubation time, postoperative pain scores, morphine consumption, and sedation scores were recorded. Thirty-seven patients in Group G and 38 patients in Group P completed the study. During the preoperative period in Group G, one patient had severe fatigue, one had severe dizziness, and one patient's surgical procedure was changed. The median plasma levels of gabapentin were 34 micromol/mL (range, 23-51 micromol/mL) in 34 patients. In Group P, one patient withdrew from the study preoperatively and one developed transient neurological symptoms postoperatively. The demographic data and mean duration of anesthesia and surgery were similar in both the groups. The total propofol and remifentanil consumption in Group G (1847 +/- 548 mg/3034 +/- 1334 microg) was significantly less than that of Group P (2293 +/- 580 mg/4287 +/- 1282 microg) (P = 0.01). However, tracheal extubation could be done earlier in Group P (4.5 +/- 2 min) than in Group G (16.6 +/- 22 min) (P < 0.001). Pain scores were significantly higher in Group P at 15 min, 30 min, and 1 h (P < 0.001). The total morphine consumption was also significantly higher in Group P (33 +/- 17 mg vs 24 +/- 19 mg) (P = 0.01). The postoperative sedation scores were significantly higher in Group G at 15 min, 30 min, 1 h, and 2 h (P < 0.001). The administration of gabapentin to patients undergoing craniotomy for supratentorial tumor resection was effective for acute postoperative pain. It also decreased analgesic consumption after surgery. However, it may lead to side effects such as delayed tracheal extubation and increased sedation postoperatively.

Deep Sedation in Advanced Endoscopy: Frequency and Clinical Characteristics of Patients Who Require Airway Modifications

Background: When administered by a trained professional, the safety and efficacy of propofol in advanced endoscopy is well described. While use of propofol requires advanced airway training, it is unclear how frequently airway modifications are employed during endoscopy and which patients may be most susceptible. Objectives: Define the frequency of airway modifications (AMs) and clinical characteristics of patients who require AMs during advanced endoscopic procedures. Methods: Patients referred for advanced endoscopic procedures, including endoscopic retrograde cholangiopancreatography (ERCP), endoscopic ultrasound (EUS) and small bowel enteroscopy (SBE), were prospectively enrolled. Sedative dosing and patient monitoring was determined by a certified registered nurse anesthetist (CRNA). Clinical, pharmacological and endoscopic characteristics were recorded. The primary outcome variable was frequency of one or more AMs, defined as chin lift, modified mask ventilation, nasal airway, bag-mask ventilation and endotracheal intubation. Characteristics of patients who required one or more AMs (AM+) were compared to those who did not require any maneuvers (AM-). Results: 629 patients were enrolled between May, 2008 and September, 2008. 40.8% received propofol alone while 59.2% received propofol in combination with low dose opiate and/or benzodiazepine. Procedures included EUS (329), ERCP (268), and SBE or other (38). All patients met criteria for deep sedation. While only 11.5% of patients developed a pulse oximetry of <90%, one or more AMs were performed in 101 (16.1%) patients, including chin lift (86), modified mask ventilation (27), placement of a nasal airway (24), or some combination. No patients required bag-mask ventilation or endotracheal intubation. Three patients developed hypotension requiring transient use of vasopressors. There were no other significant cardiopulmonary complications. Mean body mass index (kg/m2) was significantly higher among AM+ (29.5 ± 7.4) compared to AM- (26.7 ± 6.5) patients (p=0.0001). Induction and total propofol doses (mg/kg/min), use of propofol in combination with other sedatives, procedure time, prone position, ASA class, and Malampati scores were similar across both groups. Conclusion: Despite a low rate of cardiopulmonary complications, 16.1% of patients undergoing advanced endoscopic procedures required one or more maneuvers to maintain a stable airway. Higher BMI was a predictor of requiring AMs, but dose of propofol and its use in combination with other sedatives were not. For the safe administration of propofol in advanced endoscopy, advanced airway training is warranted.

Anomalous relationship between free drug fraction and its total concentration in drug–protein systems: II. Binding of different ligands to plasma proteins

As it was reported earlier, the free propofol percentage is dependent on its total concentration in human blood or plasma protein solution. At total propofol concentrations below 1 μg ml −1 the free fraction of the drug increases with the decrease of its total concentration. The results of the experiments performed in Part I indicate that the well-ordered water around a protein molecule (i.e. the hydration layer) is probably the main factor responsible for the mentioned anomalous free drug fraction changes. The experiments carried out in this study with different ligands (homologous saturated fatty acids, indomethacin and lidocaine) show that: 1. ligand hydrophobicity affects the run of the dependence between the free ligand fraction and its total concentration, which confirms the importance of the hydration layer in the drug binding process, 2. similar anomalous changes of the free drug fraction are observed not only for drugs interacting with different binding sites on human serum albumin (HSA), i.e. for propofol and indomethacin, but also for basic local anesthetic lidocaine which is known to bind to other plasma protein, alpha-1-acid glycoprotein (AGP). Therefore, the increase of the free drug fraction at its low total concentration does not appear to be an exclusive feature of propofol–HSA system. The results presented in this paper expand the present knowledge about drug–protein binding process and thereby encourage further research on this subject.

In vitro release of propofol and binding capacity with regard to plasma constituents

Purpose New evidence suggests that the anesthetic effect of parenteral propofol emulsions varies between commercial preparations. We examined and compared different propofol preparations to determine propofol release and binding capacity with regard to plasma lipoproteins and albumin. Methods We created a novel assay consisting of microtiter plates coated with either low-density lipoprotein (LDL) or albumin to analyze propofol binding kinetics. Using high performance liquid chromatography (HPLC), we measured propofol release from the oily phase and the corresponding amount of propofol bound to the plates in a time-dependent manner and at equilibrium conditions attained after 30 min of incubation at 37 °C. The concentrations of free propofol in the aqueous phase of different propofol preparations – Diprivan, and the generic formulations Propofol “Fresenius” (1% and 2% propofol) and Propofol-Lipuro – were analyzed using ultracentrifugation or dialysis for phase separation. Finally, we investigated the effect of isolated lipoprotein fractions on propofol release. Results Propofol bound to LDL-coated plates with approximately twofold higher affinity than to albumin-coated plates. No significant differences in total propofol release were observed between preparations. Moreover, similar amounts of free propofol were observed in the aqueous phase of all products tested (1% propofol preparations: 18 μg/ml; 2% propofol preparations: 35 μg/ml), except for the medium-chain and long-chain triglyceride (MCT/LCT) preparation studied, in which the concentration of free propofol was lower. Lipoproteins had no effect on propofol release, except for high-density lipoprotein (HDL), which triggered almost 100% release from the oily phase at HDL concentrations above 1000 μg/ml. Conclusions No differences were observed between the binding/release capacity and lipoprotein interactions of any of the propofol preparations tested. We propose that clinical observations of inconsistent propofol activity are related to variations in the lipoprotein profile, enzyme activity or genetic disorders of individual patients, rather than to the propofol preparation itself.

Both clonidine and metoprolol modify anesthetic depth indicators and reduce intraoperative propofol requirement

Beta-blockers have been used in the past to decrease the depth of anesthesia, but the results are conflicting. However, beta-blockers are known to suppress electroencephalographic activities. This study was carried out to assess the effect of metoprolol on anesthetic depth indicators. We also compared the effect of metoprolol in reducing propofol requirements. Ninety healthy adult patients undergoing peripheral nerve injury repair were enrolled in three groups to receive either: a tablet containing clonidine 200 microg, a tablet containing metoprolol tartrate 100 mg, or a placebo; 1 h prior to surgery. Standard anesthesia technique was followed. The bispectral index was monitored to guide propofol infusion and was maintained between 40 and 60. The total duration of anesthesia and surgery, and the total propofol consumption, were noted. Demographic variables were comparable in all three groups. Significantly less propofol was consumed by patients in the clonidine and metoprolol groups in comparison to that in the placebo group (P < 0.001). Heart rate and mean blood pressure values differed significantly in the placebo group in comparison to the values in the other two groups. Our study showed that, like clonidine, metoprolol attenuated the hemodynamic response to intraoperative stimuli and also had a sparing effect on the propofol dose requirement.

La administración de sufentanil intratecal pero no la sistémica reduce el consumo de propofol para sedación guiada mediante índice bi-espectral

The addition of opioids to local anesthetics in spinal anesthesia modulates some aspects of anesthesia and analgesia. We evaluate the effect of adding different doses of intrathecal and subcutaneous sufentanil on propofol requirements for sedation during spinal anesthesia. Prospective clinical trial randomizing patients undergoing knee arthroscopy to 4 groups. Group 1 received 12.5 mg of 0.75% hyperbaric bupivacaine (HBB); Group 2, 12.5 mg of HBB plus 2.5 microg of intrathecal sufentanil; Group 3, 12.5 mg of HBB plus 5 microg of intrathecal sufentanil; and Group 4, 12.5 mg of HBB plus 5 microg of subcutaneous sufentanil. When spinal anesthesia had been induced, a bispectral index (BIS) monitor was connected and baseline values were recorded for each patient. Sedation was then initiated with propofol at a dose of 2.5 microg/ml, using an effect-site target-controlled infusion system to maintain a BIS value between 60 and 75. BIS, vital signs, total propofol dose (TPD), mean infusion dose (MID), and awakening time were recorded. One hundred patients were included in the study. MID and TPD were lower in Groups 2 and 3 than in Groups 1 and 4 (P = .009). Consumption of propofol was 35.23% less in Group 2 and 37.50% less in Group 3 than in Group 1 (P = .001). The addition of 2.5 microg or 5 microg of intrathecal sufentanil to HBB reduces MID, TPD, and consumption of propofol in patients undergoing spinal anesthesia; the addition of 5 microg of subcutaneous sufentanil does not produce this effect.

Comparison of propofol-remifentail and propofol-fentanyl anesthesia for painless artificial abortion

Objective To observe and compare the efficacy and safety between propofol-remifentanil and propofol-fentanyl for anesthesia of artificial abortion.Methods 200 ASA I patients scheduled for painless artificial abortion were randomly divided into two groups.R group were given intravenous remifentanil 1.0μg/kg then propofol 1～1.5mg/kg(n=100);F group were given intravenous fentanyl 0.05mg then propofol 1～1.5mg/kg(n=100).Total propofol dosage,analgesic effect during intro-and post-operative,consciousness loss time,wake-up time and independenly leaving time were recorded.BP,HR,SpO2 and side effects such as nausea and vomiting were observed during intro-and post-operative.Results The dosage of propofol was less in group R than that in group F[(80.4±10.8)mg vs(110.1±13.6)mg,P＜0.01)];consciousness loss time,wake-up time and independenly leave hospital time were shorter in group R than that in group F(P＜0.05);SpO2 down range and rate were significandy higher in group R(P＜0.05);Incidence of nausea and somnolence in group R was obviously lesS than that in group F.Conclusion Artifical abortion can be preformed effectively and safely with propofol-remifentanil or propofol-fentanyl,but propofol-remifentanil especially fits for painless artificial abortion compared with propofol-fantanyl. Key words: Abortion,induced; General anesthesia; Remifentanil; Fentanyl; Anesthesia,goneral

Anomalous relationship between free drug fraction and its total concentration in drug–protein systems: I. Investigation of propofol binding in model HSA solution

According to contemporary knowledge, only the free form of a drug exhibits pharmacological activity due to its ability to cross the membranes and to interact with receptors. For the majority of drugs their free fraction in human plasma is usually constant, hence the therapeutic effect of a drug is most often correlated with its total concentration. However, in the case of certain drugs of narrow therapeutic window, for which a slight elevation of a free drug fraction (e.g., occurring in some pathological states) may exert a toxic effect, the therapeutic effect should be correlated with free concentration. As we reported earlier, at total propofol concentrations below 1 μg ml −1 the free fraction of the drug increases with the decrease of its total concentration. The presented paper discusses the results of several experiments performed in order to elucidate this anomalous phenomenon. The study is mainly focused on the investigation of the relationship between free drug percentage and total drug concentration in human serum albumin (HSA) solution, performed at different temperatures and in the presence of the salting-out agent. It was observed that a temperature increase leads to an increased propofol binding, which confirms the importance of hydrophobic interactions for the binding process. The addition of the salting-out agent significantly changing water structure of the drug–protein system is followed by disappearance of the anomalous relationship and results in constant value of the free drug fraction in the whole range of the studied total drug concentration. The results of the performed experiments indicate that the well-ordered water around a protein molecule (i.e., the hydration layer) constitutes the main factor responsible for the discussed anomalous free drug fraction changes.

Bispectral Index Monitoring for Nurse-Administered Propofol Sedation During Upper Endoscopic Ultrasound: A Prospective, Randomized Controlled Trial

Bispectral index monitoring (BIS) is a quantitative assessment of brain cortical activity. The aim of this study was to determine if BIS-guided nurse-administered propofol sedation would decrease by > or = 20% both recovery time and propofol dose compared to standard propofol sedation for endoscopic ultrasound (EUS). Prospectively, eligible outpatients were randomized to BIS-guided or standard propofol sedation during EUS. Propofol was given by nurses in intermittent boluses with sedation targeted at a BIS score of < 65-75. For the control group, the nurse was blinded to BIS scores and sedation was titrated to a modified observer's assessment of alertness/sedation scale (MOAA/S) score < or = 3. Of 50 patients enrolled, data for 44 randomized to BIS-guidance (n = 24) and the control group (n = 20) were evaluated. Between the BIS-guided and control group there was no difference between the mean procedure duration, total propofol dose, recovery time, mean intraoperative MOAA/S, and mean BIS score. Compared to standard propofol sedation for EUS, BIS-guided propofol sedation offers no significant decrease in postprocedure recovery times or propofol doses.