Bradykinin preconditions postischemic arterial endothelial function in humans

BACKGROUND: Arterial endothelial dysfunction is an important mechanism of tissue injury caused by ischemia-reperfusion (I/R). Earlier studies of I/R have shown that intracoronary preinfusion with 2.5-5 microg/mL bradykinin (BK) could alleviate the postischemic myocardial damage. Using an experimental human model of I/R, we investigated whether preceding infusion with BK could prevent the I/R-induced arterial endothelial dysfunction. METHODS: The left radial artery (LRA) from 16 healthy male adults, 18 to 30 years old, was submitted to I/R by completely occluding the left brachial artery with a pressure tourniquet for 20 minutes (ischemia), followed by its release (reperfusion). Prior to I/R, half of the subjects were randomly assigned to receive either BK (5 microg/mL) or saline, both being infused into the left brachial artery (0.5 mL/min, 10 min). The infusion was followed by a 10-minute drug-free period. The endothelial function of the LRA was studied by measuring the flow-mediated dilation (FMD) at baseline (prior to drug infusion), and at 15 minutes of reperfusion. In addition, baseline radial artery diameter, plasma nitrate, and von Willebrand factor were measured at these time points, and immediately before I/R (pre-I/R). RESULTS: BK had no effect on the pre-I/R plasma nitrate (p > 0.5 vs. saline) and diameter of LRA (p > 0.5 vs. baseline). At 15 minutes of reperfusion, FMD was significantly decreased in the saline group as compared to baseline (absolute dilation: 0.08 +/- 0.03 vs. 3.02 +/- 0.8 mm, respectively, p < 0.01; percentage dilation: 3 +/- 0.6 vs. 8 +/- 0.6%, respectively, p < 0.001), but it remained unaffected in the BK group (absolute dilation: 3.06 +/- 0.9 vs. 3.27 +/- 0.8 mm, respectively, p > 0.5; percentage dilation: 7 +/- 0.7 vs. 8 +/- 0.8%, respectively, p > 0.5). A similar trend was observed with regard to plasma nitrate, which remained unchanged in the BK group (37.01 +/- 4.14 vs. 39.14 +/- 4.49 micromol/L, p > 0.5) but decreased in the saline group (35.91 +/- 3.03 vs. 28.91 +/- 2.81 micromol/L, p < 0.1). CONCLUSION: Infusion of BK could protect the arterial endothelial function against I/R injury in humans, possibly in part by preserving the endothelial NO availability. The findings support the use of BK in the prevention of tissue injury due to I/R and might reveal an additional mechanism whereby ACE inhibitors exert their preconditioning effects on myocardium.     

Treatment of renal allograft polyoma BK virus infection with leflunomide

BACKGROUND: Polyoma BK virus produces an aggressively destructive nephropathy in approximately 3% to 8% of renal allografts, is associated with graft loss within one year in 35% to 67% of those infected and there is no therapy of proven efficacy. Leflunomide is an immune suppressive drug with anti viral activity in vitro and in animals. METHODS: We treated twenty-six patients with biopsy proven NK virus nephropathy (BKN) with either leflunomide alone (n=17) or leflunomide plus a course of cidofovir (n=9) and followed them for six to forty months. Leflunomide was dosed to a targeted blood level of active metabolite, A77 1726, of 50 microg/ml to 100 microg/ml (150 microM to 300 microM). Response to treatment was gauged by serial determinations of viral load in blood and urine (PCR), serum creatinine, and repeat allograft biopsy. RESULTS: In the 22 patients consistently sustaining the targeted blood levels of active drug, blood and urine viral load levels uniformly decreased over time (P<.001). Mean serum creatinine levels stabilized over the first six months of treatment, and with 12 months or more of follow-up in 16 patients the mean serum creatinine has not changed significantly from base line. Four patients who did not consistently have blood levels of active drug (A77 1726) above 40 microg/ml did not clear the virus until these levels were attained or cidofovir was added. CONCLUSIONS: Leflunomide inhibits Polyoma virus replication in vitro and closely monitored leflunomide therapy with specifically targeted blood levels appears to be a safe and effective treatment for Polyoma BK nephropathy.     

Evaluation of efficacy and plasma concentrations of ropivacaine in continuous axillary brachial plexus block: high dose for surgical anesthesia and low dose for postoperative analgesia

BACKGROUND AND OBJECTIVES: Ropivacaine is a potent local anesthetic that, experimentally at low concentrations, produces an effective block of pain conducting nerve fibers. Therefore, it was hypothesized that 0.1% and 0.2% ropivacaine would provide clinically adequate postoperative analgesia in continuous axillary plexus block. METHODS: Sixty patients (ASA I-II) scheduled for elective hand or forearm surgery received 5 mg/kg of 0.75% ropivacaine for axillary block using nerve stimulator technique. One hour later, in random order, a continuous infusion of either 0.1% ropivacaine (0.125 mg/kg/h), 0.2% ropivacaine (0.25 mg/kg/h) or saline 6 to 11 mL/h was started. RESULTS: The mean total ropivacaine dose for the surgical block was 5.1 to 5.2 mg/kg with the supplementation. All patients were pain free for the first 12 to 15 hours after the block. The need for postoperative analgesics during the infusion was similar in all groups. After the initial block, the maximum plasma concentrations (mean 2.5 microg/mL) were measured at 45 or 60 minutes after injection. The highest individual plasma concentration was 4.2 microg/mL. Despite the high venous peak concentration, no toxic reactions were observed. The mean peak plasma concentration (Cmax) was 2.2+/-0.5 microg/mL for saline, 2.6+/-0.8 microg/mL for 0.1% ropivacaine, and 2.6+/-0.7 microg/mL for 0.2% ropivacaine. During the continuous infusion of 24 hours, the ropivacaine concentration declined steadily. CONCLUSIONS: Ropivacaine is safe and effective for axillary brachial plexus block. The continuous infusion of 0.1% or 0.2% ropivacaine was no more beneficial than an infusion of saline in relieving postoperative pain in patients having elective hand surgery. None of the infusions were sufficient to adequately treat the patients' pain without the addition of adjunct agents.     

Geographic regional differences in rocuronium bromide dose-response relation and time course of action: an overlooked factor in determining recommended dosage

BACKGROUND: Geographic location is not acknowledged as a stratifying factor that can directly affect drug potency, because drugs are still licensed with the same recommended dose for different geographic regions. The aim of the current study was to compare the potency and duration of action of rocuronium bromide in 54 patients in three countries with different life habits, diet, and ambient conditions, namely white Austrians, white North Americans, and Han Chinese in China. METHODS: Neuromuscular block of six consecutive 50-microg/kg rocuronium incremental doses followed by 300 microg/kg was evaluated using the Relaxometer mechanomyograph (Groningen University, Groningen, Holland). Dose-response curves were created using log-dose-probit transformation. The authors compared rocuronium bromide ED50, ED90, and ED95 (effective doses required for 50%, 90%, and 95% first twitch depression, respectively) as well as Dur25 and Dur0.8 (times from last incremental dose administration until 25% first twitch and 0.8 train-of-four ratio recovery, respectively) in patients of the three countries. RESULTS: Rocuronium ED50, ED90, and ED95 were significantly higher in Austrian patients (258 +/- 68, 530 +/- 159, and 598 +/- 189 microg/kg) and Chinese patients (201 +/- 59, 413 +/- 107, and 475 +/- 155 microg/kg) compared with American patients (148 +/- 48, 316 +/- 116, and 362 +/- 149 microg/kg, respectively). Dur25 and Dur0.8 were significantly shorter in Austrian patients (22.3 +/- 5.5 and 36.9 +/- 12.8 min) and Chinese patients (30.4 +/- 7.5 and 45.7 +/- 15.9 min) compared with American patients (36.7 +/- 8.5 and 56.2 +/- 16.7 min, respectively). CONCLUSIONS: The authors demonstrated a significant difference in rocuronium potency and duration of action among patients in the three countries. Larger studies are required for determining dosage recommendations for different geographic regions.     

Plasma concentrations of fluconazole after a single oral dose and administration in drinking water in cockatiels (Nymphicus hollandicus)

Candidiasis frequently affects the oropharynx, esophagus, and crop of juvenile birds with immature immune systems and adult birds that have received long-term antibiotic treatment. Fluconazole is used extensively in human medicine to treat mucosal and invasive candidiasis and has been used in birds; however, there have been few pharmacokinetic studies in avian species to guide safe and effective treatment. The purpose of the present study was to investigate the disposition of fluconazole in cockatiels (Nymphicus hollandicus) after single oral dose administration and to determine if therapeutic plasma concentrations could be safely achieved by providing medicated water. Twenty-eight cockatiels were placed into 7 groups and were orally administered a 10 mg/kg fluconazole suspension. Blood samples were collected from each group for plasma fluconazole assay at serial time points. Fluconazole-medicated drinking water was prepared daily and offered to 15 cockatiels at a concentration of 100 mg/L for 8 days. Blood was collected for plasma fluconazole assay at 2 time points on days 3 and 7. When using naive averaged data in the single-dose study, pharmacokinetic parameters were similar for both compartmental and noncompartmental analyses. The elimination half-life of fluconazole was 19.01 hours, maximum plasma concentration was 4.94 microg/mL, time until maximal concentration was 3.42 hours, and the area under the plasma concentration versus time curve (AUC) was 149.28 h x microg/mL. Computer-simulated trough and peak plasma concentrations at steady-state after multiple doses of fluconazole at 10 mg/kg every 24 hours, 10 mg/kg every 48 hours, and 5 mg/kg every 24 hours were approximately 4.1-8.5 microg/mL, 1.2-6.0 microg/mL, and 2.0-4.3 microg/mL, respectively. Mean +/- SD plasma fluconazole concentrations for the 100 mg/L medicated water study at 0800 and 1600 hours on day 3 were 3.69 +/- 1.22 microg/mL (range, 1.73-5.26 microg/mL) and 4.17 +/- 1.96 microg/mL (range, 3.58-7.49 microg/mL), respectively, and at 0800 and 1600 hours on day 7 were 4.78 +/- 0.91 microg/mL (range, 2.62-6.11 microg/mL) and 6.61 +/- 1.67 microg/mL (range, 3.76-8.78 microg/ mL), respectively. Treatment with fluconazole administered orally at a dosage of 5 mg/kg once daily or 10 mg/kg every 48 hours or fluconazole administered in the drinking water at a concentration of 100 mg/L is predicted to maintain plasma concentrations in most cockatiels that exceed the minimum inhibitory concentration of 90% or therapeutic AUC:MIC of most strains of Candida albicans (by using susceptibility data from humans). The compounded oral suspension was stable for 14 days when stored at 5 degrees C (41 degree sF) and protected from light.     

Comparison of the anaesthetic requirement with target-controlled infusion of propofol to insert the laryngeal tube vs. the laryngeal mask

BACKGROUND AND OBJECTIVE: The target effect-site concentration of propofol to insert a laryngeal mask airway was recently reported as almost 5 microg mL(-1). The present study aimed to determine the target effect-site concentration with target-controlled infusion of propofol to place classical larnygeal mask airway or current laryngeal tube in adult patients. METHODS: We included 40 patients scheduled for short gynaecological and radiological procedures under general anaesthesia in a randomized, double-blind manner using the Dixon's up-and-down statistical method. Monitoring included standard cardiorespiratory monitors, and bispectral index monitoring was used for all patients. Anaesthesia was conducted with a target-controlled infusion system: Diprifusor. The initial target plasma concentration of propofol was 5 microg mL(-1), and was changed stepwise by 0.5 microg mL(-1) increments according to Dixon's up-and-down method. Criteria for acceptable insertion were: Muzi's score < or = 2, and mean arterial blood pressure, heart rate or bispectral index variation <20% the baseline values. RESULTS: Target effect-site concentration of propofol required to insert laryngeal tube was 6.3 +/- 0.3 microg mL(-1) with Dixon method and ED50 was 6.1 microg mL(-1) (5.9-6.4) with logistic regression method. In the case of larnygeal mask airway they were 7.3 +/- 0.2 microg mL(-1) (Dixon method) and 7.3 microg mL(-1) (7.1-7.5; with logistic regression) respectively (P < 0.05). ED95 (logistic regression) was 6.8 microg mL(-1) (5.9-7.6) for laryngeal tube and 7.7 microg mL(-1) (7.3-8.0) for larnygeal mask airway (P < 0.05). Haemodynamic incidents were 55% in the larnygeal mask airway group vs. 30% in the laryngeal tube group (P < 0.05). CONCLUSIONS: The target effect-site concentration of propofol for insertion of laryngeal tube was lower than for larnygeal mask airway (P < 0.05), with a consequent reduction of the propofol induced haemodynamic side-effects.     

The effects of intravenous lidocaine administration on the minimum alveolar concentration of isoflurane in cats

Lidocaine decreases the minimum alveolar concentration (MAC) of inhaled anesthetics and has been used clinically to reduce the requirements for other anesthetic drugs. In this study we examined the effects of lidocaine on isoflurane MAC in cats. Six cats were studied. In Experiment 1, the MAC of isoflurane was determined. An IV bolus of lidocaine 2 mg/kg was then administrated and venous plasma lidocaine concentrations were measured to determine pharmacokinetic values. In Experiment 2, lidocaine was administered to achieve target plasma concentrations between 1 and 11 microg/mL and the MAC of isoflurane was determined at each lidocaine plasma concentration. Actual lidocaine plasma concentrations were 1.06 +/- 0.12, 2.83 +/- 0.39, 4.93 +/- 0.64, 6.86 +/- 0.97, 8.86 +/- 2.10, and 9.84 +/- 1.34 microg/mL for the target concentrations of 1, 3, 5, 7, 9, and 11 microg/mL, respectively. The MAC of isoflurane in this study was 2.21% +/- 0.17%, 2.14% +/- 0.14%, 1.88% +/- 0.18%, 1.66% +/- 0.16%, 1.47% +/- 0.13%, 1.33% +/- 0.23%, and 1.06% +/- 0.19% at lidocaine target plasma concentrations of 0, 1, 3, 5, 7, 9, and 11 microg/mL, respectively. Lidocaine, at target plasma concentrations of 1, 3, 5, 7, 9, and 11 microg/mL, linearly decreased isoflurane MAC by -6% to 6%, 7% to 28%, 19% to 35%, 28% to 45%, 29% to 53%, and 44% to 59%, respectively. We conclude that lidocaine decreases the MAC of isoflurane.     

Evaluation of renal tubular function in children taking anti-epileptic treatment

AIM: To assess the effects of anti-epileptic drugs on renal tubular function. METHODS: Urinary N-acetyl-beta-D-glucosaminidase activity was measured in 114 epileptic children (mean age 5.6 +/- 1.1 years) who were undergoing monotherapy with valproate (n = 46), carbamazepine (n = 34), lamotrigine (n = 13) and combined therapy with valproate+carbamazepine (n = 21). RESULTS: The urinary N-acetyl-beta-D-glucosaminidase index of valproate (P < 0.01), carbamazepine (P < 0.05) and polytherapy group (P < 0.01) were significantly elevated when compared with that of the control group. No significant difference in N-acetyl-beta-D-glucosaminidase levels was found between the lamotrigine group and the control subjects. We found that the distribution of the N-acetyl-beta-D-glucosaminidase values of patients depended significantly on the length of therapy (P < 0.01). The level of urinary excretion of N-acetyl-beta-D-glucosaminidase was significantly higher in the patients who were taking long-term treatment (>10 years) with valproate, carbamazepine and combined therapy than those taking therapy shorter than 10 years (P < 0.01). The mean serum concentrations of valproate and carbamazepine were 68.7 +/- 17.44 microg/mL and 5.41 +/- 1.23 microg/mL, respectively. There was a significant correlation between the serum concentration of valproate and urinary N-acetyl-beta-D-glucosaminidase levels (r = 0.44, P < 0.01). There was also a significant correlation between the serum concentration of carbamazepine and N-acetyl-beta-D-glucosaminidase excretion (r = 0.52, P < 0.01). CONCLUSION: The present study demonstrated that in patients treated with valproate and carbamazepine, an impairment of tubular function can be present, whereas lamotrigine does not cause any significant change.     

Propofol and remifentanil effect-site concentrations estimated by pharmacokinetic simulation and bispectral index monitoring during craniotomy with intraoperative awakening for brain tumor resection

Different anesthetic techniques have been suggested for craniotomy with intraoperative awakening. We describe an asleep-awake-asleep technique with propofol and remifentanil infusions, with pharmacokinetic simulation to predict the effect-site concentrations and to modulate the infusion rates of both drugs, and bispectral index (BIS) monitoring. Five critical moments were defined: first loss of consciousness (LOC1), first recovery of consciousness (ROC1), final of neurologic testing (NT), second loss of consciousness (LOC2), and second recovery of consciousness (ROC2). At LOC1, predicted effect-site concentrations of propofol and remifentanil were, respectively, 3.6+/-1.2 microg/mL and 2.4+/-0.4 etag/mL. At ROC1, predicted effect-site concentrations of propofol and remifentanil were, respectively, 2.1+/-0.3 microg/mL and 1.8+/-0.3 etag/mL. At NT, predicted effect-site concentrations of propofol and remifentanil were, respectively, 0.9+/-0.3 microg/mL and 1.8+/-0.2 etag/mL. At LOC2, predicted effect-site concentrations of propofol and remifentanil were, respectively, 2.1+/-0.2 microg/mL and 2.5+/-0.2 etag/mL. At ROC2, predicted effect-site concentrations of propofol and remifentanil were, respectively, 1.2+/-0.5 microg/mL and 1.4+/-0.2 etag/mL (data are mean+/-SE). A significative correlation was found between BIS and predicted effect-site concentrations of propofol (r=0.547, P<0.001) and remifentanil (r=0.533, P<0.001). Multiple regression analysis between BIS and propofol and remifentanil predicted effect-site concentrations at the different critical steps of the procedure was done and found also significative (r=0.7341, P<0.001).     

Intraoperative wake-up test and postoperative emergence in patients undergoing spinal surgery: a comparison of intravenous and inhaled anesthetic techniques using short-acting anesthetics

Surgical procedures on the vertebral column may result in spinal cord damage, leading to neurological deficits that demand immediate therapeutical intervention. We designed this study to determine which anesthetic regimen allows a rapid wake-up test during and after surgery to detect neurological deficits. Fifty-four patients were randomly allocated to the following groups: group PR (propofol/remifentanil): target-controlled infusion with propofol (plasma concentration, 2-4 microg/mL) and remifentanil 0.2-0.5 microg . kg(-1) . min(-1); group PS (propofol/sufentanil): propofol (2-4 microg/mL) and repetitive boluses of 0.1-0.2 microg/kg of sufentanil adjusted to patients requirements; and group DR (desflurane/remifentanil): desflurane/air 3.0-4.0 vol% combined with remifentanil 0.2-0.5 microg . kg(-1) . min(-1). Group PS required significantly longer times for the onset of breathing (8.9 +/- 1.6 min), elevation of the head (17.0 +/- 3.8 min), and motion of the feet (17.0 +/- 7.4 min) than group PR (6.9 +/- 2.6 min, 9.3 +/- 2.2 min, and 9.4 +/- 2.4 min, respectively) or group DR (5.4 +/- 0.8 min, 6.1 +/- 1.0 min, and 6.2 +/- 1.0 min, respectively). The anesthetic regimen with desflurane and remifentanil allowed faster awakening during and after surgery that permitted immediate neurological examination after spinal surgery compared with propofol/remifentanil.     

Effect site concentrations of remifentanil maintaining cardiovascular homeostasis in response to surgical stimuli during bispectral index guided propofol anestesia in seriously obese patients

AIM: The aim of this prospective study was to determine the effect site concentrations of remifentanil maintaining cardiovascular homeostasis in response to surgical stimuli during bispectral index (BIS) guided propofol anesthesia in seriously obese patients. METHODS: Twenty-two patients, female/male 15/7, ASA physical status II - III, aged 29-69 years, body mass index (BMI) 54.5+/-12, undergoing major open bariatric surgery, were enrolled to receive a propofol-remifentanil total intravenous anesthesia. All patients were intubated by using a flexible fiberoptic bronchoscopic technique facilitated by a target controlled effect site concentration of remifentanil set at 2.5 ng/mL. After endotracheal intubation, anesthesia was started with a target controlled infusion of propofol initially set at 6 microg/mL, then adjusted to maintain a BIS value between 40 and 50. The mean effect site concentration of remifentanil was recorded at different intervals time during surgery: skin incision-opening of peritoneum (T1), bowel resection (T2), cholecystojejunal anastomosis (T3), ileojejunal anastomosis (T4), closing of peritoneum (T5). RESULTS: The mean plasma concentrations of propofol required to maintain a BIS value between 40 and 50 were 4+/-0.55, 3.8+/-0.64, 3.8+/- 0.63, 3.8+/-0.65 and 3.8+/-0.63 microg/mL at T1, T2, T3, T4 and T5 interval time, respectively. The mean values of remifentanil target effect site concentration were 5.2+/-1.3, 7.7+/-1.7, 9.1+/-1.8, 9.7+/- 2.2 and 9.9+/-2.5 ng/mL at T1, T2, T3, T4 and T5 interval time. CONCLUSIONS: This study suggests that tolerance to remifentanil infusion is profound and develops very rapidly in morbidly obese patients submitted to open bariatric surgery during BIS guided propofol anesthesia. The administration of opiates during anesthesia based on target-controlled infusion should include corrections for the development of tolerance.     

Buspirone and meperidine synergistically reduce the shivering threshold.

Mild hypothermia (i.e., 34 degrees C) may prove therapeutic for patients with stroke, but it usually provokes shivering. We tested the hypothesis that the combination of buspirone (a serotonin 1A partial agonist) and meperidine synergistically reduces the shivering threshold (triggering tympanic membrane temperature) to at least 34 degrees C while producing little sedation or respiratory depression. Eight volunteers each participated on four randomly-assigned days: 1) large-dose oral buspirone (60 mg); 2) large-dose IV meperidine (target plasma concentration of 0.8 microg/mL); 3) the combination of buspirone (30 mg) and meperidine (0.4 microg/mL); and 4) a control day without drugs. Core hypothermia was induced by infusion of lactated Ringer's solution at 4 degrees C. The control shivering threshold was 35.7 degrees C +/- 0.2 degrees C. The threshold was 35.0 degrees C +/- 0.8 degrees C during large-dose buspirone and 33.4 degrees C +/- 0.3 degrees C during large-dose meperidine. The threshold during the combination of the two drugs was 33.4 degrees C +/- 0.7 degrees C. There was minimal sedation on the buspirone and combination days and mild sedation on the large-dose meperidine day. End-tidal PCO2 increased approximately 10 mm Hg with meperidine alone. Buspirone alone slightly reduced the shivering threshold. The combination of small-dose buspirone and small-dose meperidine acted synergistically to reduce the shivering threshold while causing little sedation or respiratory toxicity. IMPLICATIONS: Mild hypothermia may be an effective treatment for acute stroke, but it usually triggers shivering, which could be harmful. Our results indicate that the combination of small-dose buspirone and small-dose meperidine acts synergistically to reduce the shivering threshold while causing little sedation or respiratory toxicity. This combination may facilitate the induction of therapeutic hypothermia in stroke victims.     

Antibiotic prophylaxis with cefazolin and gentamicin in cardiac surgery for children less than ten kilograms

OBJECTIVE: Antibiotic prophylaxis is recommended in pediatric cardiac surgery, but no data concerning the current antibiotic regimen were available. DESIGN: Prospective study from April to June 2000. SETTING: University hospital operating room and postoperative intensive care unit. PARTICIPANTS: Nineteen consecutive infants less than 10 kg with normal renal function undergoing cardiac surgery with cardiopulmonary bypass longer than 30 minutes. INTERVENTIONS: Intravenous administration of cefazolin, 40 mg/kg, and gentamicin, 5 mg/kg, at induction of anesthesia; followed by cefazolin, 35 mg/kg every 8 hours, and gentamicin, 2 mg/kg every 12 hours, over 48 hours. MEASUREMENTS AND MAIN RESULTS: Levels of serum antibiotics were measured: cefazolin (microbiologic) and gentamicin (fluorescence immunoassay) with 8 intraoperative and 5 postoperative samplings. Intraoperatively, cefazolin levels decreased from 166 +/- 44 (mean +/- standard deviation) down to 54 +/- 16 microg/mL and gentamicin from 20.8 +/- 9.5 down to 5.9 +/- 1.5 microg/mL. The postoperative trough levels were 12 +/- 7, 15 +/- 10, and 19 +/- 22 microg/mL for cefazolin and 1.1 +/- 0.5, 0.8 +/- 0.4, and 0.8 +/- 0.9 microg/mL for gentamicin. CONCLUSIONS: Antibiotic serum levels are consistent with satisfactory efficacy, but intraoperative gentamicin peak levels appeared too high.     

Sedation with target-controlled propofol infusion during shoulder surgery under interscalene brachial plexus block in the sitting position: report of a series of 140 patients

BACKGROUND AND OBJECTIVE: The aim of this study was to assess target-controlled propofol infusion as a technique of sedation for shoulder surgery under interscalene brachial plexus block in the sitting position and to evaluate the effect of sedation on hypotensive/bradycardic events during this procedure. METHODS: One hundred and forty patients undergoing elective shoulder surgery in the sitting position under interscalene brachial plexus block (with 30 mL of ropivacaine 0.75%) were prospectively enrolled. All patients were premedicated with hydroxyzine 1 mg kg(-1), none received beta-blockers. No patients were given atropine except for the patients who experienced a vasovagal event either during the block procedure or intravenous catheter placement. The target-controlled propofol infusion was started immediately after positioning the patient on the operating table. The initial target concentration was 1 microg mL(-1). The infusion rate was adjusted every 15 min by increasing or decreasing the target concentration by 0.2 microg mL(-1) steps to maintain the patient rousable to verbal commands (score of 3 on Wilson sedation scale). The following parameters were assessed: minimal, maximal, optimal target concentration, respiratory and haemodynamic parameters, total propofol dose, additional alfentanil needs, occurrence of hypotensive/bradycardic events, complications. Results are mean +/- SD. Statistical analysis used t-test and chi2-tests. RESULTS: The optimal propofol target concentration was 0.8 mug mL(-1). No respiratory complications or conversion to general anaesthesia was reported. Two patients experienced transient and inconsequential intraoperative agitation. The incidence of hypotensive/bradycardic events during the procedure was 5.7% (eight patients). CONCLUSION: Target-controlled propofol infusion (0.8-0.9 microg mL(-1)) following hydroxyzine premedication is a safe and effective technique for sedation when combined with interscalene brachial plexus block during shoulder surgery in the sitting position.     

Heparin versus danaparoid in off-pump coronary bypass grafting: results of a prospective randomized clinical trial

OBJECTIVE: The incidence of heparin-induced thrombocytopenia is increasing, and the thrombin inhibitor danaparoid could be a useful alternative. The objective of the present study was to compare danaparoid and heparin in patients undergoing off-pump coronary artery bypass grafting. METHODS: In a prospective, randomized, double-blind clinical trial comparing heparin (bolus of 1 mg/kg) with danaparoid (bolus of 40 U/kg), 71 patients underwent off-pump coronary artery bypass grafting with one of the study drugs. The amount of blood lost, the number of homologous blood products transfused, the troponin T levels, and the amount of anti-Xa activity were monitored. RESULTS: Thirty-four patients underwent 2.6 +/- 0.7 bypasses with danaparoid, and 37 patients underwent 2.5 +/- 0.9 grafts with heparin (P =.8). Postoperative blood losses averaged 1394 +/- 1033 mL in patients receiving danaparoid and 1130 +/- 868 mL in patients receiving heparin (P =.2). The number of homologous blood products transfused averaged 3.6 +/- 7 units in patients receiving danaparoid and 1.9 +/- 4.4 units in patients receiving heparin (P =.2). The number of patients requiring homologous blood transfusion was higher in patients receiving danaparoid (18/34 [53%]) than in patients receiving heparin (10/37 [27%], P =.03). Serum anti-Xa activity averaged 1.6 +/- 0.6 U/mL in patients receiving danaparoid and 1.9 +/- 0.8 U/mL in patients receiving heparin 30 minutes after injection of the drugs (P =.1) and 0.3 +/- 0.1 and 0.04 +/- 0.08 U/mL, respectively, 12 hours after coronary artery bypass grafting (P =.001). Troponin serum levels were similar 48 hours after coronary artery bypass grafting (0.5 +/- 0.6 and 0.4 +/- 0.6 microg/L, respectively). CONCLUSION: Although off-pump coronary artery bypass grafting with danaparoid versus heparin increases the number of patients exposed to homologous blood transfusion (relative risk, 2; 95% confidence limits, 1-4), off-pump coronary artery bypass grafting with danaparoid is a valuable alternative to heparin in patients with thrombocytopenia requiring surgical intervention.     

超滤离心法降低重组人脱细胞真皮基质牛血清白蛋白残留量检测中基质效应的实验研究

目的 探讨采用超滤离心法减少重组人脱细胞真皮基质(recombination human acellular dermal matrix,rhADM)样品浸提液对ELISA方法检测牛血清白蛋白(bovine semm albumin,BSA)残留量的基质效应.方法 清洗rhADM后,制备rhADM生理盐水浸提液.取超滤离心管若干,分别加入1 mg/mL BSA溶液(预饱和方式1,记作PR1)、10μg/mL BSA溶液(预饱和方式2,记作PR2)和rhADM浸提液2 mL(记作rhADM1和rhADM2),1 500×g离心20 min,重复操作3次后取出离心管内管,放入未使用的15 mL离心管中,在PRI和PR2管中加入10μg/mL BSA溶液4 mL,rhADM管中加入rhADM浸提液4 mL,同上法离心后,收集滤液.用ELISA法测定BSA含量.计算不同预饱和方式下10μg/mL BSA溶液的BSA回收率(以未经处理的10μg/mL BSA溶液作为基础样品,分别记作R10和R20);计算滤液稀释倍数的对数与测定吸光度(A)值的相关系数,并与未经超滤离心处理的浸提液检测结果进行比较.结果 采用预饱和方式1处理后,PRI1BSA浓度为(23.80±1.58)μg/mL,R10为(9.04±0.24)μg/mL,BSA回收率为263.4%±16.9%.采用预饱和方式2处理后,PR2 BSA浓度为(8.64±0.24)μg/mL,R20为(8.12±1.01)μg/mE,BSA的回收率为106.5%±3.O%.预饱和方式2的回收率符合检测要求.不同预饱和方式下BSA回收率差异有统计学意义(P＜0.01).经超滤离心处理后,滤液稀释倍数的对数与A值之间的相关性明显提高,相关系数由-0727提高至-0.960.超滤处理后的相关系数符合检测要求.结论 超滤离心处理可以有效减少rbADM样品浸提液的基质效应对BSA残留量检测的影响;样品浸提液自身对超滤离心管的预饱和处理,可得到较为理想的BSA回收率.     

Gender differences between predicted and measured propofol C(P50) for loss of consciousness

OBJECTIVE: To investigate gender differences in the effective dose of 50% for loss of consciousness (C(P50LOC)) for propofol using Diprifusor, the most commonly used target-controlled infusion system. DESIGN: Prospective, randomized, comparative study. SETTING: University-affiliated hospital. PATIENTS: 50 ASA physical status I and II patients, aged 20 to 50 years, scheduled for minor surgery. INTERVENTIONS: Patients were randomized into two groups of 25 patients each. A target-controlled infusion of propofol (Diprifusor) was maintained at a predetermined target concentration. After a 10-minute steady state, blinded investigators evaluated patients' consciousness using verbal commands. The propofol test concentration was predetermined using a modified version of Dixon's up-and-down method (starting at 2.5 mug/mL; step size of 0.1 microg/mL). MEASUREMENT: Predicted and measured C(P50LOC) values and bispectral index (BIS) were obtained by averaging the crossover midpoint (ie, consciousness to unconsciousness). Those values were analyzed by unpaired t test: P < 0.05 was considered significant. RESULTS: The predicted C(P50LOC) for men was 2.14 +/- 0.10 microg/mL, which was lower than that for women, 2.55 +/- 0.11 microg/mL (P < 0.0001). No significant difference was found for measured C(P50LOC) in men (2.37 +/- 0.41 microg/mL) and in women (2.30 +/- 0.28 microg/mL) or for BIS measurements. CONCLUSION: Predicted C(P50LOC) by Diprifusor for men tended to be underestimated; that for women tended to be overestimated. Our data support a review of Diprifusor (Astra Zeneca, Osaka, Japan) pharmacokinetic parameters to avoid awareness during operation, particularly for women.     

The effect of the addition of epinephrine on early systemic absorption of epidural ropivacaine in humans

The addition of epinephrine to ropivacaine has not been recommended because ropivacaine has intrinsic vasoconstrictor properties. However, few pharmacokinetic data are available on the addition of epinephrine to epidural ropivacaine in humans. In this prospective, double-blinded study, we randomized patients having elective abdominal hysterectomy to receive epidural ropivacaine 1.5 mg/kg, diluted in 15 mL, either with (epinephrine group, n = 12) or without (plain group, n = 12) epinephrine 5 microg/mL and then measured arterial and venous plasma concentrations of ropivacaine at intervals up to 180 min. We found that arterial and venous plasma ropivacaine concentrations were smaller in the epinephrine group compared with the plain group in the first 60 min after the drug administration (P < 0.01). Mean (+/- SD) maximum total plasma ropivacaine concentration was smaller in the epinephrine group (arterial, 0.92 +/- 0.32 microg/mL; venous, 0.82 +/- 0.33 microg/mL) compared with the plain group (1.31 +/- 0.39 microg/mL and 1.31 +/- 0.50 microg/mL, respectively; P = 0.01). Time to maximum total plasma ropivacaine concentration was not significantly different between groups (mean +/- SD; arterial, 16 +/- 2 min; venous, 23 +/- 2 min in the epinephrine group versus 9 +/- 2 min and 12 +/- 3 min, respectively, in the plain group; P = 0.08). Arterial plasma ropivacaine concentrations were larger than venous concentrations during the first hour (P < 0.01); the arterio-venous difference decreased exponentially, and the rate and magnitude of this decrease was unaffected by epinephrine. We conclude that the addition of epinephrine 5 microg/mL to ropivacaine reduced the early systemic plasma concentrations of ropivacaine after epidural injection and may be useful for decreasing the risk of toxicity from systemic absorption of epidural ropivacaine. IMPLICATIONS: The addition of epinephrine 5 microg/mL to epidural ropivacaine reduced the systemic arterial and venous plasma concentrations of ropivacaine in the first hour and the maximum plasma concentration of ropivacaine. Epinephrine may be a useful additive for reducing the risk of systemic toxicity when large doses of ropivacaine are given epidurally.     

The target plasma concentration of propofol required to place laryngeal mask versus cuffed oropharyngeal airway

To determine the target plasma concentration of propofol required to place either a laryngeal mask airway (LMA) or a cuffed oropharyngeal airway (COPA), we started a continuous target-controlled infusion of propofol in 60 ASA physical status I or II unpremedicated patients scheduled for minor orthopedic surgery with peripheral nerve block. The target plasma concentration of propofol was initially set at 2 microg/mL. When the effect-site calculated concentration of propofol was equal to the plasma concentration according to the computer simulation, the target plasma concentration was increased by 0.5-microg/mL steps until successful placement of either the LMA (n = 30) or the COPA (n = 30). The mean target plasma concentration of propofol required to place a LMA was 4.3 +/- 0.8 microg/mL compared with 3.2 +/- 0.6 microg/mL to place a COPA (P < 0.001). To successfully place the airways in 95% of patients, the target plasma concentration of propofol had to be increased up to 4 microg/mL for the COPA and 6 microg/mL for the LMA. We conclude that placing a LMA in healthy, unpremedicated patients requires target plasma concentrations of propofol higher than those required for placing a COPA. Implications: We evaluated the use of target-controlled infusion of propofol to place extratracheal airways in this prospective, randomized study and demonstrated that the target plasma concentration of propofol required to successfully place a laryngeal mask in >95% of healthy, unpremedicated patients is 6 microg/mL, compared with 4 microg/mL to place a cuffed oropharyngeal airway.     

A single-center experience with BK virus nephropathy

BACKGROUND: BK virus nephropathy has an increasing role in renal transplant dysfunction, since new, highly potent immunosuppressive drugs have been introduced into therapy following renal transplantation. Diagnosis of acute impairment of renal transplant function is complicated by difficulty in differentiating BK virus nephropathy from acute rejection. PATIENTS AND METHODS: We retrospectively described the findings and therapeutic approaches of 6 consecutive patients with BK virus nephropathy in our transplantation center (75 - 80 transplantations/ year). BK virus nephropathy was classified according to Drachenberg et al. [2004]. RESULTS: We observed an incidence rate of < 1% for BK nephropathy in our center. Four patients had a pattern B whereas 2 patients revealed a pattern C of BK virus nephropathy. Focal C4d-positive staining of peritubular capillaries were found in 2 of the 6 cases. For earlier detection of BK nephropathy, a diagnostic algorithm for each patient after renal transplantation was established. Urine was continuously monitored by cytology for decoy cells and PCR for BK virus DNA. If PCR was also positive for the BK virus in plasma, biopsy of the renal allograft was performed. Thereby diagnosis could be confirmed sooner. For treatment of BK nephropathy in our center, we reduced immunosuppressive agents and initiated a virustatic treatment with cidofovir in the first 3 cases. However, results were not satisfactory and two allografts were lost. We then reconsidered our therapeutic approach and switched the immunosuppressive treatment to leflunomide with consistent low dose steroids. We use therapeutic drug monitoring for leflunomide and aim at a target level of 40 - 100 microg/ml. We lost no allograft with BK nephropathy since using this therapeutic approach. CONCLUSION: In our center, leflunomide therapy, but not cidofovir, was effective in patients with BK virus nephropathy of the renal allograft.