Diamorphine-bupivacaine mixture compared with plain bupivacaine for analgesia

We have studied the efficacy of two extradural infusions (10 ml h-1) in 50 patients in active labour. Patients in the diamorphine group (n = 25) received 0.0625% plain bupivacaine 6.25 mg h-1 mixed with 0.005% diamorphine 0.5 mg h-1 and those in the control group (n = 25) received 0.125% plain bupivacaine 12.5 mg h-1. Both groups received intermittent "top-ups" of 0.25% bupivacaine 10 ml when indicated. Although median pain scores during the infusion were similar in both groups, patients in the diamorphine group indicated greater satisfaction with the infusion (88% very satisfied, compared with 52% in the control group (P < 0.02)). There were no differences in the incidence of hypotension, instrumental vaginal delivery, number of "top-ups", duration of the second stage or extent of motor block. However, patients in the diamorphine group had a high incidence of pruritus (44%, compared with 0% in the control group (P < 0.01)).     

Pharmacology of local anesthetics and clinical aspects of segmental blocking. II. Spinal anesthesia

Clinical picture of development of segmental blocking after subarachnoidal injection of hyperbaric solutions of 0.75% bupivacaine, 5% ultracaine, and isobaric 0.5% bupivacaine is studied. A total of 152 patients operated on the lower part of the body and the lower limbs were examined under conditions of single, prolonged subarachnoidal, and combined spinal epidural anesthesia. Ultracaine and bupivacaine in different concentrations with different barism provided anesthesia equivalent by the efficacy, depth, and dissemination of sensory block. Segmental blocking with 5% ultracaine was characterized by the shortest latent period (3.14 +/- 0.16 min, p < 0.05) but was no shorter (124.1 +/- 3.37 min) than operative analgesia with 0.75% hyperbaric bupivacaine (120.0 +/- 5.10 min). Isobaric bupivacaine provided the longest effective analgesia (215.0 +/- 45.0 min, p < 0.05). Microcatheter technique improved the safety and control of subarachnoidal anesthesia in comparison with a single injection, and combined spinal epidural anesthesia shortened the latent period of segmental blocking and ensured intraoperative anesthesia and postoperative analgesia at the expense of the epidural component.     

The influence of epidural administration of fentanyl infusion on gastric emptying in labour

The effect of epidural infusions containing fentanyl on maternal gastric emptying in labour was examined using the rate of paracetamol absorption. Women were randomly allocated to receive one of two epidural infusions, bupivacaine 0.125% alone or bupivacaine 0.0625% with fentanyl 2.5 micrograms.ml-1 at a rate of 10-12 ml.h-1. Paracetamol 1.5 g was given orally to women after either 30 ml of the infusion solution had been given (mean time 2.5 h, study A) or 40-50 ml (mean time 4.5 h. study B). Six venous blood samples were taken over the next 90 min for measurement of plasma paracetamol concentration. There were no significant differences in maximum plasma paracetamol concentration, time to maximum paracetamol concentration and area under the concentration-time curve between the two groups for study A. In study B the time to maximum plasma paracetamol concentration was significantly delayed in women receiving > 100 micrograms fentanyl compared with controls (p < 0.05). We conclude that the dose of fentanyl that may delay gastric emptying when given by epidural infusion is greater than 100 micrograms.     

Epidural bupivacaine/fentanyl infusions vs. intermittent top-ups: a retrospective study of the effects on mode of delivery in primiparous women

This study was designed to determine whether the introduction of epidural infusions containing fentanyl and bupivacaine has affected the mode of delivery in primiparous women attending our maternity department. We reviewed retrospectively the computerized records of 4362 consecutive primiparous women in labour. All the women were admitted with the expectation of a vaginal delivery. The results were analysed using logistic regression analysis adjusted for age, weight, gestation, cervical dilatation at epidural insertion, use of oxytocin, the year of entry into the study and the type of epidural block received. In women receiving an epidural block at 3-6 cm cervical dilatation (n = 1534), those who received an infusion were significantly less likely to have an emergency Caesarean section than those having intermittent 'topups' (P = 0.0019). In the same subgroup of women, the Caesarean section rate specifically for failure to progress followed the same trend, but just failed to reach statistical significance (P = 0.058). This provides evidence to support the theory that epidural infusions containing a low dose bupivacaine/fentanyl combination may reduce the risk of Caesarean section in primiparous women.     

Arterial and pulmonary arterial concentrations of the enantiomers of bupivacaine after epidural injection in elderly patients

Bupivacaine HCl is a 50:50 racemic mixture of the levo [S(-)] and dex [R(+)] enantiomers. The R(+) enantiomer exhibits greater cardiac tissue binding and toxicity. To determine whether the lung exhibits selective uptake of one of the enantiomers of bupivacaine, we measured pulmonary artery and radial artery blood concentrations of the two enantiomers after a lumbar epidural injection of 20 mL of 0.75% bupivacaine in 10 elderly patients undergoing one-stage bilateral total knee arthroplasty. Significantly lower concentrations of R(+) than S(-) were noted in both pulmonary artery and arterial blood. Both enantiomers were absorbed by the lung to a similar extent within the first 5 min after epidural injection (extraction ratio approximately equal to 0.1 or 10%). Mean time of maximal concentration (Tmax) was 6 min. In 3 of the 10 patients, Tmax occurred in 1-3 min. We conclude that the lung absorbs both the R(+) and S(-) enantiomers of bupivacaine to a similar extent after epidural injection and that this is of doubtful clinical significance. This study also suggests that peak concentrations of bupivacaine may occur earlier after epidural injection in certain elderly patients than previously believed. Implications: In the first 5 min after epidural injection, approximately 10% of the local anesthetic bupivacaine was absorbed by the lung. Absorption of the two enantiomers (mirror images) of bupivacaine were similar. Lung absorption of bupivacaine is unlikely to influence local anesthetic toxicity.     

Schizophrenia and the dopamine-beta-hydroxylase gene: results of a linkage and association study

PURPOSE: A dose-finding study to investigate the use of epidural infusions of ropivacaine for postoperative analgesia following orthopaedic surgery. METHODS: This was a randomized, double-blind study. Surgery was performed using a combination of a lumbar epidural block utilizing ropivacaine 0.5% and a standardized general anaesthetic. Postoperatively, an epidural infusion of the study solution (saline, ropivacaine 0.1%, 0.2% or 0.3%) was started at the rate of 10 ml.hr-1 and continued for 21 hr after arrival in the PACU. Analgesia was supplemented with PCA morphine (dose = 1.0 mg, lock-out = 5 min). RESULTS: Forty-four patients completed the study. The ropivacaine 0.1%, 0.2%, 0.3% groups required less morphine over the 21 hr than the saline group (P < 0.01). The VAS pain scores were also lower in the three ropivacaine groups (P < 0.001). The ropivacaine groups maintained sensory anaesthesia to pinprick when compared with saline (P < 0.05). The motor block in the 0.3% group was significantly higher than the saline group at all times (P < 0.05), and higher than the 0.1% group at eight hours (P < 0.01), while the 0.2% group had higher Bromage scores than saline at 4 and 21 hr (P < 0.05). CONCLUSIONS: The use of continuous epidural infusions of ropivacaine 0.1%, 0.2% and 0.3% at 10 ml.hr-1 improved postoperative pain relief and decreased PCA morphine requirements in patients undergoing major orthopaedic surgery. The 0.1% and 0.2% concentrations produced similar sensory anaesthesia with less motor blockade than the 0.3% concentration.     

Epidural fentanyl produces labor analgesia by a spinal mechanism

BACKGROUND: The purpose of this study was to determine if epidural fentanyl produces analgesia in laboring patients by a primary spinal or supraspinal action. METHODS: Fifty-four parturients were randomized to receive epidural 0.125% bupivacaine plus one of three treatments: epidural saline-intravenous saline, epidural fentanyl (20 microg/h)-intravenous saline, or epidural saline-intravenous fentanyl (20 microg/h). The study treatments were administered by continuous infusion, whereas epidural bupivacaine use was patient controlled. RESULTS: Epidural bupivacaine use was significantly reduced by epidural (11.5+/-4.6 ml/h) but not by intravenous fentanyl (15.9+/-4.5 ml/h) compared with saline control (16+/-5.9 ml/ h). Analgesia characteristics and side effects were similar among groups. CONCLUSIONS: Low-dose epidural infusions of fentanyl produce labor analgesia by a primary spinal action.     

Analgesic effect of intra-articular bupivacaine or diamorphine after arthroscopic surgery of the knee joint in day-case patients

A prospective, randomized, double-blind, controlled study was conducted to assess the efficacy of intra-articular bupivacaine and diamorphine. Ninety-six day-case patients were allocated randomly to receive intra-articular injections of either 20 mL 0.9% saline (control, n = 35), 20 mL 0.5% plain bupivacaine (n = 31), or 20 mL 0.9% saline with 5 mg diamorphine (n = 30) prior to tourniquet release. Visual analogue scales (VAS) were completed at 1 h, 3 h (discharge) and 24 h, and supplementary analgesia noted. Intra-articular analgesics conferred a noticeable improvement in patient comfort. First, the quantity of supplementary analgesia required prior to discharge was significantly reduced (P = 0.016); second, patients reported a less disturbed night's sleep (P = 0.034).     

Levobupivacaine

Levobupivacaine is an enantiomer of the long-acting local anaesthetic bupivacaine, which, although currently the most widely used agent in surgery and obstetrics, is associated with potentially fatal cardiotoxicity. Levobupivacaine 75 to 122 mg was less arrhythmogenic than the same dose range of bupivacaine in healthy volunteers. Its effects on the corrected QT interval were significantly weaker than those of bupivacaine, and it tended to have a weaker effect on QRS duration. The CNS depressant effect of intravenous levobupivacaine 40 mg was less than that of bupivacaine 40 mg in healthy volunteers, both in terms of the magnitude of the effect and the regions of the cortex affected. Clinical studies have demonstrated that epidural levobupivacaine produces a sensory and motor block clinically similar to that of bupivacaine in patients requiring anaesthesia during surgery. However, the duration of sensory block was significantly longer with levobupivacaine 0.75% than with levobupivacaine 0.5% or bupivacaine 0.5% or 0.75% in one study. Levobupivacaine 0.25% was as effective as bupivacaine 0.25% in women requiring epidural anaesthesia during labour with respect to time to onset of pain relief, overall quality of analgesia, extent of sensory blockade and number of patients reporting motor block. Levobupivacaine is as well tolerated as bupivacaine. In a clinical study involving 88 patients who received either drug, intraoperative hypotension was the most commonly reported adverse event with levobupivacaine and no serious arrhythmias occurred.     

Phosphatidylcholine-associated aspirin accelerates healing of gastric ulcers in rats

In this double-blind study, we administered lumbar epidural bupivacaine or bupivacaine plus verapamil to investigate the possible role of the calcium channel blocker, verapamil, in postoperative pain. One hundred patients (ASA physical class I or II) scheduled for lower abdominal surgery were randomly assigned to one of four groups. Group 1 received 10 mL of 0.5% epidural bupivacaine injected 15 min before incision, followed by 10 mL of epidural normal saline 30 min after incision. Group 2 received 10 mL of epidural normal saline injected before incision, followed by 10 mL of 0.5% epidural bupivacaine 30 min after incision. Group 3 received 10 mL of 0.5% epidural bupivacaine plus 5 mg of verapamil injected before incision, followed by 10 mL of epidural normal saline 30 min after incision. Group 4 received the same drugs as Group 3, in the reverse order. Pain and mood numeric rating scores, sedation scores, Prince Henry scores, patient-controlled cumulative postoperative analgesic consumption, and the incidence of side effects were assessed 2, 6, 12, 24, and 48 h after the operation in each group. Cumulative postoperative analgesic consumption in Groups 3 and 4 was significantly lower (P < 0.05) than that in Groups 1 and 2 24 and 48 h after surgery. There were no differences in the pain, mood, and sedation scores and the incidence of side effects among the four groups. We conclude that epidural verapamil decreases postoperative pain, possibly by interfering with normal sensory processing and by preventing the establishment of central sensitization. Implications: Calcium plays an important role in pain physiology at the spinal cord level. We examined the effect of bupivacaine plus verapamil (calcium channel blocker) and of bupivacaine alone. We demonstrated that the combination, administered epidurally, resulted in less postoperative analgesic consumption than bupivacaine alone.     

A comparison of 0.5% bupivacaine, 0.5% ropivacaine, and 0.75% ropivacaine for interscalene brachial plexus block

The onset time and duration of action of ropivacaine during an interscalene block are not known. The potentially improved safety profile of ropivacaine may allow the use of higher concentrations to try and speed onset time. We compared bupivacaine and ropivacaine to determine the optimal long-acting local anesthetic and concentration for interscalene brachial plexus block. Seventy-five adult patients scheduled for outpatient shoulder surgery under interscalene block were entered into this double-blind, randomized study. Patients were assigned (n = 25 per group) to receive an interscalene block using 30 mL of 0.5% bupivacaine, 0.5% ropivacaine, or 0.75% ropivacaine. All solutions contained fresh epinephrine in a 1:400,000 concentration. At 1-min intervals after local anesthetic injection, patients were assessed to determine loss of shoulder abduction and loss of pinprick in the C5-6 dermatomes. Before discharge, patients were asked to document the time of first oral narcotic use, when incisional discomfort began, and when full sensation returned to the shoulder. The mean onset time of both motor and sensory blockade was <6 min in all groups. Duration of sensory blockade was similar in all groups as defined by the three recovery measures. We conclude that there is no clinically important difference in times to onset and recovery of interscalene block for bupivacaine 0.5%, ropivacaine 0.5%, and ropivacaine 0.75% when injected in equal volumes. IMPLICATIONS: In this study, we demonstrated a similar efficacy between equal concentrations of ropivacaine and bupivacaine. In addition, increasing the concentration of ropivacaine from 0.5% to 0.75% fails to improve the onset or duration of interscalene brachial plexus block.     

The gender difference on the Mental Rotations test is not due to performance factors

We have studied the antibacterial activity of different concentrations of 0.005-2% lidocaine (lignocaine) in mixtures with Diprivan (propofol), against micro-organisms commonly implicated in sepsis as a result of extrinsically contaminated Diprivan. Bacterial colony counts were reduced progressively with increasing concentrations of lidocaine. Bacteriostatic and bactericidal concentrations of lidocaine were 0.2-2%. Lidocaine 2% was not bactericidal for one of the seven organisms tested. By inhibiting bacterial replication, lidocaine, when added to Diprivan to reduce pain on injection, may possibly reduce the harmful consequences if extrinsic contamination occurs.     

Estimating the prevalence of delayed median nerve conduction in the general population

In a double-blind, randomized, crossover study of 25 patients after abdominal aortic surgery, we compared patient-controlled analgesia (PCA) with epidural versus intravenous pethidine. All patients received continuous epidural infusions of 0.125% bupivacaine adjusted to maintain appropriate sensory levels. The 48 hour study period commenced 36 to 48 hours after surgery and covered postoperative days 2 and 3. There was a crossover in PCA mode (epidural or intravenous) after 24 hours. Plasma pethidine concentration at the end of each 24 hour period and the total 24 hour pethidine dose did not change significantly between postoperative days 2 and 3. Pethidine plasma concentration was lower after 24 hours epidural than after intravenous PCA [125 (SD 108) ng/ml versus 171 (SD 107) ng/ml, P = 0.03], although pethidine dose did not differ significantly [mean 147 (SD 124) mg/24 h]. Visual analog pain scores (VAS) did not differ significantly between postoperative days 2 and 3, or at rest between epidural and i.v. groups. However, VAS with coughing and with abdominal palpation were lower in the epidural PCA group (P = 0.05, 0.008). With a background epidural infusion of 0.125% bupivacaine, PCA with epidural pethidine provided better pain control than PCA intravenous pethidine and this was achieved at lower plasma pethidine concentrations.     

Influence of anesthetic technique in postoperative analgesia in thoracic surgery

OBJECTIVE: To compare the intensity of postoperative pain after thoracotomy with 2 anesthetic techniques: 1) thoracic epidural block with bupivacaine administered before surgery (combined anesthesia with isoflurane) and 2) conventional balanced anesthesia with isoflurane and endovenous fentanyl. PATIENTS AND METHODS: Thirty patients scheduled for thoracotomy by lateral incision (T5-T6) were randomly divided into 2 groups of 15. Group A received 8 ml of 0.5% bupivacaine with adrenalin 1:200.000 30 min before start of surgery while group B received 8 ml saline solution through an epidural catheter inserted to T4-T8. Combined anesthesia (4 ml 0.5% bupivacaine through an epidural catheter 150 min after the first dose and isoflurane in 100% oxygen) was used in group A. Group B received balanced anesthesia with endovenous fentanyl 2.5 micrograms/kg and isoflurane in 100% oxygen. The difference in pain intensity during postoperative recovery was assessed by way of the following variables: number of boluses administered by epidural patient-controlled analgesia (bupivacaine 0.0625% and fentanyl 6 micrograms/ml); score on a visual analog scale of 10 at baseline and at 1, 3, 7, 11, 19 and 43 hours after surgery; and need for additional analgesia (diclofenac) during the 43 hours of study. Arterial gases were measured during the preoperative period and at 1, 3, 7, 19 and 43 hours after surgery. RESULTS: No significant differences in pain intensity measured on the visual analog scale, by the number of boluses per patients or by need for additional analgesia were found between the 2 groups. The total number of boluses administered and additional analgesic requirements were greater in the group receiving bupivacaine, although the difference was not significant (p = 0.095 and p = 0.056, respectively). Nor were there significant differences in pH and PaCO2 levels for the 2 groups. CONCLUSIONS: Analgesic efficacy after thoracotomy was similar for our 2 groups receiving either combined anesthesia (epidural bupivacaine at 0.5% and isoflurane) or balanced anesthesia with isoflurane and endovenous fentanyl.     

Streptokinase in acute stroke: effect on reperfusion and recanalization. Australian Streptokinase Trial Study Group

BACKGROUND: The minimum local analgesic concentration (MLAC) has been defined as the median effective local analgesic concentration in a 20-ml volume for epidural analgesia in the first stage of labor. The aim of this study was to determine the local anesthetic-sparing efficacy of epidural sufentanil by its effect on the MLAC of bupivacaine. METHODS: In this double-blind, randomized, prospective study, 147 parturients at < or = 7 cm cervical dilation who requested epidural analgesia were allocated to one of four study groups. After a lumbar epidural catheter was placed, study participants received 20 ml bupivacaine (n = 38), bupivacaine with sufentanil 0.5 microg/ml (n = 38), bupivacaine with sufentanil 1 microg/ml (n = 33), or bupivacaine with sufentanil 1.5 microg/ml (n = 38). The concentration of bupivacaine was determined by the response of the previous patient using up-down sequential allocation. The analgesic efficacy was assessed using 100-mm visual analog pain scores, with < or = 10 mm within 30 min defined as effective. RESULTS: The MLAC of bupivacaine alone was 0.104% wt/vol (95% CI, 0.090-0.117). The addition of sufentanil at doses of 0.5 microg/ml, 1 microg/ml, and 1.5 microg/ml resulted in significant reductions (P < 0.0001) in the MLAC of bupivacaine to 0.048% wt/vol (95% CI, 0.030- 0.065), 0.021% wt/vol (95% CI, 0-0.055), and 0.009% wt/vol (95% CI, 0-0.023), respectively. CONCLUSIONS: This study showed a significant (P < 0.0001) dose-dependent reduction in the MLAC ofbupivacaine by sufentanil.     

A retrospective cost-effectiveness analysis of interferon as adjuvant therapy in high-risk resected cutaneous melanoma

PURPOSE: To determine the relative corneal endothelial toxicities of the following topical anesthetic agents: bupivacaine HCl 0.75%, unpreserved lidocaine HCl 4%, proparacaine HCl 0.5%, and tetracaine HCl 0.5%. METHODS: The experiment was conducted using pigmented rabbits. Approximately nine animals each were randomly assigned to eight groups. Right eyes received injections of 0.2 ml of one of the four anesthetic agents at one of two concentrations and left eyes received injections of 0.2 ml of balanced salt solution. Corneal thickness and clarity were measured before surgery and on postoperative days 1, 3, and 7. RESULTS: A statistically significant increase (P < 0.05) in corneal thickness and opacification over preoperative measurements was noted with injections of bupivacaine, lidocaine, and proparacaine, controlling for changes occurring in control eyes from surgery alone. Proparacaine was statistically more toxic than were the others. The toxicity of tetracaine was statistically indistinguishable from balanced salt solution, although mild toxicity was evident clinically. Injection of 1:10 dilutions of the same anesthetic agents failed to produce a statistically significant increase in corneal thickness or opacification on any postoperative examination. CONCLUSIONS: Anterior chamber injection of bupivacaine HCl 0.75%, unpreserved lidocaine HCl 4%, and proparacaine HCl 0.5% produces corneal thickening and opacification that is clinically and statistically significant. Tetracaine HCl 0.5% injection produces corneal thickening and opacification that is clinically apparent in some eyes but statistically insignificant. Ophthalmic surgeons should be aware of the potential for endothelial cell injury if anesthetic agents enter or are injected into the eye during cataract surgery in the concentrations supplied commercially.     

Continuous epidural analgesia in the obstetric patient: a feasibility study using a mechanical infusion pump

Eleven patients in uncomplicated labour received a continuous infusion of 0-125 or 0-25% bupivacaine solutions into the epidural space, using a simple rotary pump. Maternal and umbilical cord venous plasma bupivacaine levels were measured and were found to be within safe limits for mother and baby. Incidence of complications were noted.     

Nutrient effects: discrepancy between data from controlled trials and observational studies

We describe the successful postoperative pain management in an 11-month-old infant who underwent bilateral thoracotomy, using continuous infusions of bupivacaine into two directly placed paravertebral catheters. Haemodynamic parameters and pain scores were measured 1-2 h for 60 h while the infusions were continued and, intermittently, blood samples were taken for subsequent measurement of serum bupivacaine concentrations. The technique provided effective pain relief and the infant required no other analgesia postoperatively. There were no adverse haemodynamic consequences or complications relating to either catheter placement or drug infusions. Serum concentrations of bupivacaine remained below toxic levels throughout the study period, though accumulation did occur.     

The action of VIRKON No Foam on the hepatitis B virus

The aim of this work was to verify the in vitro virucidal activity of VIRKON No Foam (VIRKON NF) against the HBV DNA, notoriously one the most resistant viruses to heat and to the most commonly used disinfectants. VIRKON NF, an oxidizing agent, has a synergic effect on nucleic acids, polypeptides, glycoproteins, and structural proteins. The experiment was conducted using the serum of a patient with HBsAg+/HBeAg+/HBVDNA+ with a DNA concentration 100 pg/ml. The virucidal activity was tested using the Slot Blot method, the result being evaluated as an inhibition of the autoradiographic signal because of contact of different concentrated solutions and various contact times with the serum. Preliminary tests were carried out after contact of VIRKON NF with serum solutions at 0.1-0.5-1-4% concentrations for a 15 min contact time. VIRKON NF showed an inhibition of autoradiographic signal equal respectively to 0%, 25-50%, 50-70%, 100%. Further experiments were carried out to compare VIRKON NF virucidal activity on HBV to the activity of the most common disinfectants, such as formic aldehyde, Amuchina, glutaraledhyde and phenol. In this way, the infected serum was put into contact with both the most common disinfectant and 1-1.5-2-3-4% VIRKON NF solutions in contact times of 15, 10, 5, 2 min. Using 3% concentrations for a contact time of 10 min, VIRKON NF showed an autoradiographic inhibition signal of 90%. Regarding other disinfectants, only a 2% glutaraldehyde solution for a contact time of 15 min showed similar virucidal activity.     

Experimental fetal transesophageal and intracardiac echocardiography utilizing intravascular ultrasound technology

The effects of epidural fentanyl on the incidence of maternal hypoxaemia during labour and on neonatal welfare were examined. Women were randomly allocated to receive one of two epidural infusions, bupivacaine 0.125% alone or bupivacaine 0.0625% with 2.5 micrograms.ml-1 fentanyl, and maternal arterial oxygen saturation was monitored continuously until delivery. The median incidence of desaturation (SpO2 < 95%) during the active phase of the second stage of labour was significantly greater in the fentanyl group than in controls (2.9 versus 0.6 min.h-1, p = 0.02). Similarly, the incidence of desaturation to SpO2 < or = 90% was greater in the fentanyl group than in controls (p = 0.02). There was no correlation between maternal oxygenation or plasma fentanyl concentration and neonatal welfare as measured by umbilical arterial and venous blood gas and acid base status, Apgar score and Neurologic and Adaptive Capacity Score.