Search

Background: As few anaesthetists provide lumbar erector spinae block for disc surgery, there is a need to provide training to enable a randomised controlled trial investigating analgesia after painful spinal surgery (NIHR153170). The primary objective of the study was to develop and measure the construct validity of a checklist for assessment of skills in performing lumbar and thoracic erector spinae fascial plane injection using soft-embalmed Thiel cadavers., Methods: Twenty-four UK consultant regional anaesthetists completed two iterations of a Delphi questionnaire. The final checklist consisted of 11 steps conducive to best practice. Thereafter, we validated the checklist by comparing the performance of 12 experts with 12 novices, each performing lumbar and thoracic erector spinae plane injections or fascia iliaca, serrato-pectoral (PEC II) and serratus injections, randomly allocated to the left and right sides of six soft-embalmed Thiel cadavers. Six expert, trained raters blinded to operator and site of block examined 120 videos each., Results: The mean (95% confidence interval) internal consistency of the 11-item checklist for erector spinae plane injection was 0.72 (0.63-0.79) and interclass correlation was 0.88 (0.82-0.93). The checklist showed construct validity for lumbar and thoracic erector spinae injection, experts vs novices {median (interquartile range [range]) 8.0 (7.0-10.0 [1-11]) vs 7.0 (5.0-9.0 [4-11]), difference 1.5 (1.0-2.5), P<0.001}. Global rating scales showed construct validity for lumbar and thoracic erector spinae injection, 28.0 (24.0-31.0 [7-35]) vs 21.0 (17.0-24.0 [7-35]), difference 7.5 (6.0-8.5), P<0.001. The most difficult items to perform were identifying the needle tip before advancing and always visualising the needle tip. Instrument handling and flow of procedure were the areas of greatest difficulty on the global rating scale (GRS). Checklists and GRS scores correlated. There was homogeneity of regression slopes controlling for status, type of injection, and rater. Generalisability analysis showed a high reliability using the checklist and GRS for all fascial plane blocks (Rho [ρ 2 ] 0.93-0.96: Phi [ϕ] 0.84-0.87)., Conclusions: An 11-point checklist developed through a modified Delphi process to provide best practice guidance for fascial plane injection showed construct validity in performing lumbar and thoracic erector spinae fascial plane injection in soft-embalmed Thiel cadavers., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Spatial life course epidemiological approaches offer promise for prospectively examining the impacts of air pollution exposure on longer-term health outcomes, but existing research is limited. An essential aspect, often overlooked is the comprehensiveness of exposure data across the lifecourse. The primary objective was to meticulously reconstruct historical estimates of air pollution exposure to include prenatal exposure as well as annual exposure from birth to 10 years (1977-1987) for each cohort member. We linked these data from a birth cohort of 1,265 individuals, born in Aotearoa/New Zealand in mid-1977 and studied to age 40, to historical air pollution data to create estimates of exposure from birth to 10 years (1977-1987). Improvements in air quality over time were found. However, outcomes varied by demographic and socioeconomic factors. Future research should examine how inequitable air pollution exposure is related to health outcomes over the life course., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Erector spinae plane (ESP) block spread can be unpredictable. We previously improved the spread of ESP injection by addition of retrolaminar (RL) injection. However, it is not clear whether spread at high thoracic levels is similar to spread at midthoracic levels. Our primary objective was to demonstrate that craniocaudal dye spread was equivalent after combined ESP and RL injection using a 19 G Tuohy needle at the third (T3) and sixth (T6) vertebrae in soft embalmed Thiel cadavers., Methods: We randomised 20 combined ESP and RL injections to the T3 and T6 vertebral levels on both sides of 10 prone Thiel cadavers. A 3-8 MHz transducer was placed in the paramedian sagittal plane and a single anaesthetist injected 10 ml dye onto the transverse process, then 10 ml dye onto the laminae of T3 or T6. Cadavers were dissected 24 h later., Results: Mean (sd) craniocaudal spread of dye after combined ESP + RL injection at T3 and T6 vertebral levels was equivalent: 8.6 (1.8) vs 8.7 (2.3) levels, respectively; difference (90% confidence interval): -0.1 (-1.4 to 1.6), P=0.904. Dye extended uniformly, cranially and caudally, from the point of injection. A 3D prosection created from a Thiel cadaver confirmed that the dorsal ramus emerges from the costotransverse foramen deep to the intertransverse ligament within the retro-superior costotransverse ligament space. Combined ESP and RL block in six patients before mastectomy achieved extensive anterior, lateral, and posterior chest wall paraesthesia over four to six dermatomes., Conclusions: Combined ESP and RL injections showed equivalent and consistent spread at T3 and T6 injection sites. A pilot study confirmed translation to patients., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Nerve damage is consistently demonstrated after subepineural injection in animal studies, but not after purposeful injection in patients participating in clinical studies. There is a need to better visualise nerves in order to understand the structural changes that occur during subepineural injection., Methods: We scanned the brachial plexuses of three anaesthetised pigs using micro-ultrasound imaging (55-22 MHz probe), inserted 21 gauge block needles into the radial, median, and axillary nerves, and injected two 0.5 ml boluses of saline into nerves at a rate of 12 ml min -1 . Our objectives were to measure the area and diameter of nerves and fascicles, and to describe changes in nerve anatomy, comparing our findings with histology., Results: Images were acquired at 42 sites across 18 nerves in three pigs and compared dimensions (geometric ratio; 95% confidence interval; P value). As expected, the nerve cross-sectional area was greater in the proximal brachial plexus compared with the mid-plexus (2.10; 1.07-4.11; P<0.001) and the distal plexus (2.64; 1.42-4.87; P<0.001). Nerve area expanded after 0.5 ml injection (2.13; 1.48-3.08; P<0.001). Using microultrasound, subepineural injection was characterised by nerve and fascicle rotation, uniform, or localised swelling and epineural rupture. Micro-ultrasound revealed a unique pattern suggestive of subperineural injection after a median nerve injection, and good face validity with histology. Histology showed epineural trauma and inflammation to the perineurium., Conclusion: We accurately identified fascicles and real-time structural changes to peripheral nerves using micro-ultrasound. This is the first study to visualise in vivo and in real-time the motion of nerves and fascicles in response to anaesthetic needle insertion and fluid injection., (Copyright © 2021 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: The authors declare that they have no conflicts of interest.

Background: Our goal is to develop metrics that quantify the translation of performance from cadavers to patients. Our primary objective was to develop steps and error checklists from a Delphi questionnaire. Our second objective was to show that our test scores were valid and reliable., Methods: Sixteen UK experts identified 15 steps conducive to good performance and 15 errors to be avoided during interscalene block on the soft-embalmed cadaver and patients. Thereafter, six experts and six novices were trained, and then tested. Training consisted of psychometric assessment, an anatomy tutorial, volunteer scanning, and ultrasound-guided needle insertion on a pork phantom and on a soft-embalmed cadaver. For testing, participants conducted a single interscalene block on a dedicated soft-embalmed cadaver whilst wearing eye tracking glasses., Results: We developed a 15-step checklist and a 15-error checklist. The internal consistency of our steps measures were 0.83 (95% confidence interval [CI]: 0.78-0.89) and 0.90 (95% CI: 0.87-0.93) for our error measures. The experts completed more steps (mean difference: 3.2 [95% CI: 1.5-4.8]; P<0.001), had less errors (mean difference: 4.9 [95% CI: 3.5-6.3]; P<0.001), had better global rating scores (mean difference: 6.8 [95% CI: 3.6-10.0]; P<0.001), and more eye-gaze fixations (median of differences: 128 [95% CI: 0-288]; P=0.048). Fixation count correlated negatively with steps (r=-0.60; P=0.04) and with errors (r=0.64; P=0.03)., Conclusions: Our tests to quantify ultrasound-guided interscalene nerve block training and performance were valid and reliable., (Copyright © 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Errors may occur during regional anaesthesia whilst searching for nerves, needle tips, and test doses. Poor visual search impacts on decision making, clinical intervention, and patient safety., Methods: We conducted a randomised single-blind study in a single university hospital. Twenty trainees and two consultants examined the paired B-mode and fused B-mode and elastography video recordings of 24 interscalene and 24 femoral blocks conducted on two soft embalmed cadavers. Perineural injection was randomised equally to 0.25, 0.5, and 1.0 ml volumes. Tissue displacement perceived on both imaging modalities was defined as 'target' or 'distractor'. Our primary objective was to test the anaesthetists' perception of the number and proportion of targets and distractors on B-mode and fused elastography videos collected during femoral and sciatic nerve block on soft embalmed cadavers. Our secondary objectives were to determine the differences between novices and experts, and between test-dose volumes, and to measure the area and brightness of spread and strain patterns., Results: All anaesthetists recognised perineural spread using 0.25 ml volumes. Distractor patterns were recognised in 133 (12%) of B-mode and in 403 (38%) of fused B-mode and elastography patterns; P<0.001. With elastography, novice recognition improved from 12 to 37% (P<0.001), and consultant recognition increased from 24 to 53%; P<0.001. Distractor recognition improved from 8 to 31% using 0.25 ml volumes (P<0.001), and from 15 to 45% using 1 ml volumes (P<0.001)., Conclusions: Visual search improved with fusion elastography, increased volume, and consultants. A need exists to investigate image search strategies., (Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: The incidence of intraneural injection during trainee anaesthetist ultrasound guided nerve block varies between 16% in experts and up to 35% in trainees. We hypothesized that elastography, an ultrasound-based technology that presents colour images of tissue strain, had the potential to improve trainee diagnosis of intraneural injection during UGRA, when integrated with B-Mode ultrasound onto a single image., Methods: We recorded 40 median nerve blocks randomly allocated to 0.25 ml, 0.5 ml, 1 ml volumes to five sites, on both arms of two soft embalmed cadavers, using a dedicated B-Mode ultrasound and elastography transducer. We wrote software to fuse elastogram and B-Mode videos, then asked 20 trainee anaesthetists whether injection was intraneural or extraneural when seeing B-Mode videos, adjacent B-Mode and elastogram videos, fusion elastography videos or repeated B-Mode ultrasound videos., Results: Fusion elastography improved the diagnosis of intraneural injection compared with B-Mode ultrasound, Diagnostic Odds Ratio (DOR) (95%CI) 21.7 (14.5 - 33.3) vs DOR 7.4 (5.2 - 10.6), P < 0.001. Compared with extraneural injection, intraneural injection was identified on fusion elastography as a distinct, brighter translucent image, geometric ratio 0.33 (95%CI: 0.16 - 0.49) P < 0.001. Fusion elastography was associated with greater trainee diagnostic confidence, OR (95%CI) 1.89 (1.69 - 2.11), P < 0.001, and an improvement in reliability, Kappa 0.60 (0.55 - 0.66)., Conclusions: Fusion elastography improved the accuracy, reliability and confidence of trainee anaesthetist diagnosis of intraneural injection., (© The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Posterior variants of abdominal wall block include the quadratus lumborum type I, quadratus lumborum type II and quadratus lumborum transmuscular blocks. Our objectives were to compare the spread of injectate and nerve involvement, after conducting blocks using ultrasound guidance in soft embalmed cadavers., Methods: After randomization, an experienced anaesthetist conducted three quadratus lumborum 1, three quadratus lumborum 2 and four transmuscular blocks on the left or right sides of five cadavers. All cadavers were placed in the lateral position and the quadratus lumborum muscle seen using a 3-9 MHz ultrasound probe placed in the flank. For each block, a 20 ml mixture of 17.75 ml water, 2 mls latex and 0.25 ml India ink was injected. The lumbar region and abdominal flank were dissected 72 h later., Results: We conducted 10 blocks. Two quadratus lumborum 1 and two quadratus lumborum 2 blocks were associated with spread of dye within the TAP plane. One quadratus lumborum 1 block spread to the deep muscles of the back and one quadratus lumborum 2 block dispersed within the subcutaneous tissue surrounding the abdominal flank. All transmuscular quadratus lumborum blocks spread consistently to L1 and L3 nerve roots and within psoas major and quadratus lumborum muscles., Conclusions: Consistent spread to lumbar nerve roots was achieved using the transmuscular approach through the quadratus lumborum., (© The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: We evaluated the physical properties and functional alignment of the soft-embalmed Thiel cadaver as follows: by assessing tissue visibility; by measuring its acoustic, mechanical and elastic properties; by evaluating its durability in response to repeated injection; and by aligning images with humans., Methods: In four soft-embalmed Thiel cadavers, we conducted three independent studies. We assessed the following factors: (i) soft tissue visibility in a single cadaver for 28 weeks after embalming; (ii) the displacement of tissues in response to 1 and 5 ml interscalene and femoral nerve blocks in a single cadaver; and (iii) the stiffness of nerves and perineural tissue in two cadavers. We aligned our findings with ultrasound images from three patients and one volunteer. Durability was qualified by assessing B-mode images from repetitive injections during supervised training., Results: There was no difference in visibility of nerves between 2 and 28 weeks after embalming {geometric mean ratio 1.13 [95% confidence interval (CI): 0.75-1.68], P=1.0}. Mean tissue displacement was similar for cadaver femoral and interscalene blocks [geometric mean ratio 1.02 (95% CI: 0.59-1.78), P=0.86], and for 1 and 5 ml injection volumes [geometric mean ratio 0.84 (95% CI: 0.70-1.01), P=0.19]. Cadavers had higher intraneural than extraneural stiffness [Young's modulus; geometric mean ratio 3.05 (95% CI: 2.98-3.12), P<0.001] and minimal distortion of anatomy when conducting 934 left-sided interscalene blocks on the same cadaver throughout a 10 day period., Conclusions: The soft-embalmed Thiel cadaver is a highly durable simulator that has excellent physical and functional properties that allow repeated injection for intensive ultrasound-guided regional anaesthesia training., (© The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: For patients with autosomal dominant hypercholesterolemia (ADH), it remains unclear whether differences exist in the risk of premature coronary heart disease (CHD) between patients with confirmed mutations in low-density lipoprotein receptor (LDLR) vs those without detectable mutations., Objective: This study sought to assess the risk of premature CHD in ADH patients with mutations in LDLR (referred to as familial hypercholesterolemia [FH]) vs those without detectable mutations (unexplained ADH), stratified by sex., Methods: Comparative study of premature CHD in a multiethnic cohort of 111 men and 165 women meeting adult Simon-Broome criteria for ADH., Results: Women with FH (n = 51) had an increased risk of premature CHD compared with unexplained ADH women (n = 111; hazard ratio [HR], 2.74; 95% confidence interval, 1.40-5.34; P = .003) even after adjustment for lipid levels and traditional CHD risk factors (HR, 2.53 [1.10-5.83]; P = .005). Men with FH (n = 42), in contrast, had a similar risk of premature CHD when compared with unexplained ADH men (n = 66; unadjusted: HR, 1.48 [0.84-2.63]; P = .18; adjusted: HR, 1.04 [0.46-2.37]; P = .72). To address whether mutation status provides additional information beyond LDL-cholesterol level, we analyzed premature CHD risk for FH vs unexplained ADH at various percentiles of LDL-cholesterol: the risk ratios were significant for women at 25th percentile (HR, 4.90 [1.69-14.19]) and 50th percentile (HR, 3.44 [1.42-8.32]) but not at 75th percentile (HR, 1.99 [0.95-4.17]), and were not significant for men at any percentile., Conclusions: Our findings suggest that genetic confirmation of ADH may be important to identify patient's risk of CHD, especially for female LDLR mutation carriers., (Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Background and Aims: To assess ultrasound as a method for (i) measuring body composition (BC) of preterm infants and for (ii) assessing the influence of macronutrient intakes on tissue accretion rates., Methods: Preterm ultrasound studies of four anatomical sites were performed approximately every three weeks from birth to corrected-term age. Preterm measurements were compared to foetal reference data. Duplicate scans at each site were taken on a subset of infants to test the reproducibility of the method, assessed as the coefficient of variation (CV). The influence of measured macronutrient intakes on preterm BC was assessed by regression analysis., Results: Median (range) gestation and birth weight of 40 preterm infants were 27 (23-29) weeks and 1022 (480-1475) g, respectively. Accretion rates of adipose and muscle tissues were not uniform across the four sites. Relative to the foetus, preterm adipose tissue thickness was reduced at an equivalent (corrected) gestation, but towards term, a faster accretion rate of subcutaneous abdominal adipose and limb muscle tissue was evident. Timing of fortification (p=0.012), enteral carbohydrate intake (p=0.008) and the protein energy ratio of intakes (p=0.038) moderated the ratio of adipose to muscle tissue accretion over the four sites by -0.004, -0.048 and -0.042, respectively., Conclusions: Ultrasound provides a non-invasive, portable method of assessing changes in subcutaneous adipose tissue and muscle accretion and appears sufficiently sensitive to detect influences of macronutrient intakes on accretion rates from birth. The method warrants further investigation as a bedside tool for measuring BC of preterm infants., (Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.)

Knee arthroplasty provides not only pain relief but also an improvement in function and range of movement. Limited joint mobility is a common complication of diabetes mellitus. We therefore examined functional outcome post total knee arthroplasty in a cohort of subjects with (n=367) and a cohort matched for age, sex, BMI and functional movement at baseline, without diabetes mellitus (n=367). Participants were examined at baseline (pre-operatively), 1, 5 and 10 years post TKA. There was no significant difference in fixed flexion, maximal flexion or total range of movement between the two groups at baseline. By 1 year the group with diabetes had a significantly lower maximal flexion (p<0.001), total range of movement (p<0.001) and Knee Society Score (p=0.034). Similar results were observed at years 5 (except for the KSS) and 10 post procedure. At 5 years post arthroplasty a significant increase was observed in fixed flexion (p=0.026) in the diabetic group. Ten years post arthroplasty yielded similar results. This study demonstrates that the pre-operative presence of diabetes mellitus leads to a worse outcome post knee arthroplasty, although no significant difference was demonstrable in KSS at 5 years (p=0.35) suggesting patient satisfaction remains high during this period., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Rapid intravenous injection of oxytocin is associated with marked hypotension secondary to decreased venous return. Reductions in dose and rate of bolus administration have reduced the incidence of cardiovascular side effects, but no study has yet investigated cardiovascular stability when oxytocin is infused for several hours after delivery. This study compared maternal haemodynamics during a 4-h 30-unit oxytocin infusion and during a placebo infusion following caesarean section., Methods: Women booked for elective caesarean section were randomised to receive either oxytocin 5-unit bolus and placebo infusion or oxytocin 5-unit bolus and oxytocin 30-unit infusion. Before, during and for 4 h after surgery electrocardiogram, oxygen saturation, systolic and diastolic pressure and heart rate were monitored non-invasively and cardiac index (CI), left ventricular work index (LVWi) and systemic vascular resistance index (SVRi) by thoracic bioimpedance., Results: A total of 74 women agreed to haemodynamic measurements. Heart rate, systolic and diastolic pressure, CI, LCWi and SVRi all fell following the onset of spinal anaesthesia, and, with the exception of SVRi, continued to decrease throughout surgery. After delivery of the baby, slow injection of oxytocin 5 units was associated with a temporary rise in CI, LCWi and heart rate, a decrease in SVRi and no change in systolic or diastolic pressure. Thereafter, haemodynamic measures returned to normal over 60 min with no adverse effects apparent from the additional oxytocin infusion., Conclusions: An additional oxytocin infusion at elective caesarean section did not adversely affect maternal haemodynamics either during or after surgery., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Background: Infusion of local anaesthetic through femoral and sciatic catheters is an accepted method of providing pain relief after knee arthroplasty. However, the minimum effective concentration of perineural local anaesthetics is not known., Methods: Twenty-four patients received femoral and sciatic perineural infusions of levobupivacaine in order to prevent pain relief after total knee arthroplasty. The primary endpoint of the study was patient request for analgesic rescue for anterior or posterior knee pain within the first 36 h of perineural infusion. Treatment was determined by the method of sequential allocation, with a dosing interval of 0.002% w/v., Results: Thirteen patients did not require rescue analgesia for anterior knee pain and 16 patients did not require rescue analgesia for posterior knee pain. Median duration of failed blocks until rescue analgesia was 25 h (24-27 h) for the femoral block and 27 h (24-29 h) for the sciatic block. The minimum concentration at which patients did not require rescue analgesia was 0.024% for the femoral nerve and 0.014% for the sciatic nerve. Comparison of EC(50) showed that local anaesthetic requirements were significantly (P=0.03) higher by a factor of 1.25 (95% CI 1.03-1.55) for the femoral compared with the sciatic nerve., Conclusions: The EC(50) for femoral perineural infusion is greater than the EC(50) for sciatic perineural infusion.

Background: Few studies have investigated efficacy and side effects of the combination of diclofenac and paracetamol used for pain relief after major surgery., Methods: After ethical approval, 78 patients, presenting for elective caesarean section, were recruited to this double-blind trial and randomised to receive one of three analgesic modalities: paracetamol, diclofenac, or diclofenac and paracetamol. Anaesthesia was standardised with 2.25-2.5 mL of spinal bupivacaine 5 mg/mL in dextrose 80 mg/mL and fentanyl 12.5 mug. Study drugs were given as a suppository at the end of surgery then orally for 24 h. The primary outcome was i.v. morphine use when administered as patient-controlled analgesia for the first 24 h after surgery. Secondary outcomes were visual analogue pain scores measured 2, 4, 6, 10 and 24 h after surgery and verbal rating pain scores and side effects measured 2-hourly for the first 12 h and 4-hourly thereafter., Results: Patients given the combination of diclofenac and paracetamol required less morphine than did patients given paracetamol alone (mean+/-SD: 33.8+/-23.9 mg versus 54.5+/-28.5 mg, P=0.02). Morphine use in patients given diclofenac alone (42.2+/-26.0 mg) was not significantly different from morphine use in the other two groups. Eight out of 26 patients receiving paracetamol alone were not satisfied with pain management; two required intravenous morphine injections., Conclusions: Patients given a combination of diclofenac and paracetamol used 38% less morphine compared to patients given paracetamol.

Unlabelled: Nutrition guidelines and growth targets for preterm infants are currently based upon the reference standard of intrauterine growth and fetal nutrient accretion rates. This may not be an entirely appropriate standard--it is rarely achieved in clinical practice. Postnatal growth failure of very preterm infants is a universal problem with potentially significant, adverse neurological and health outcomes. The nutrient deficit that accumulates in the early weeks postdelivery when the preterm infant is clinically unstable is difficult to recover. Weight, length and head circumference measurements remain important clinical indicators of growth but composition of weight gain is emerging as a necessary measure in determining the adequacy of nutrition intake and growth. Recommended protein and energy intakes for very preterm infants are difficult to achieve with commercial human milk fortifiers and during hospitalisation, targeting the fortification of human milk to optimise the protein to energy ratio of milk feeds is necessary to ensure appropriate composition of weight gain. Postdischarge, continued fortification of human milk feeds may be required for a limited period of time for preterm infants with suboptimal weight for corrected age., Aim and Methods: The following systematic review is aimed to derive evidence-based best practice guidelines for prevention of postnatal growth failure of very preterm infants who are clinically stable and growing. The focus is on reviewing the standard upon which ideal growth and nutrition guidelines are based and targeting fortification to maximise the protein to energy ratio in human milk feeds to ensure appropriate composition of weight gain. Directions for future research are provided. For the literature review the data bases Medline, EMBASE, CINAHL, the Cochrane Library and reference lists of review articles were reviewed to December 2006. A hand search of paediatric and perinatal journals was also conducted.

Background: Few data describe the pharmacological interactions between local anaesthetics and opioids. The aim of this study was to measure the median effective concentration (MEC) of diamorphine and levobupivacaine when given separately and as mixtures for epidural analgesia, and determine whether the combination is additive or synergistic., Methods: One hundred and twenty patients were enrolled in this prospective randomized, two-phase, double-blind study. In the first phase, 60 women were randomized to receive a fixed 20 ml volume of either levobupivacaine or diamorphine epidurally . Dosing was determined using up-down sequential allocation with testing intervals, respectively, of 0.01%w/v and 12.5 microg ml(-1). After estimations of the MEC of levobupivacaine and diamorphine, a further 60 patients were randomized in the second phase to one of the three mixtures: (a) diamorphine 70 microg ml(-1) (fixed) and levobupivacaine (testing interval 0.004%w/v, starting at 0.044%w/v); (b) levobupivacaine 0.044%w/v (fixed) and diamorphine (testing interval 7 microg ml(-1), starting at 70 microg ml(-1)); and (c) bivariate diamorphine and levobupivacaine (testing intervals of 7 microg ml(-1) and 0.004%w/v starting at 70 microg ml(-1) and 0.044% w/v respectively)., Results: The MEC estimates from the first phase were 143.8 microg ml(-1) (95% CI 122.2-165.3) for diamorphine and 0.083%w/v (95% CI 0.071-0.095) for levobupivacaine. In the second phase, the MEC and interaction index (gamma) of the three combinations were: diamorphine 65.5 microg ml(-1) (56.8-74.2), gamma = 0.99; levobupivacaine 0.041%w/v (0.037-0.049), gamma = 0.98; and for the fixed combination diamorphine 69.5 microg ml(-1) (60.5-78.5) and levobupivacaine 0.044%w/v (0.039-0.049), gamma = 1.02., Conclusion: The combination of diamorphine and levobupivacaine is additive and not synergistic when used for epidural analgesia in the first stage of labour.

Background: Many years ago regular intermittent bolus administration of epidural local anaesthetic solution was recognized to produce more effective analgesia than continuous infusion, but only recently has the development of suitable pumps allowed the former technique's wider evaluation., Methods: In this randomized, double-blind trial, 40 primigravid patients had a lumbar epidural catheter inserted, and plain ropivacaine 0.2% 15-20 ml was titrated until analgesia and bilateral sensory block to T10 were produced (time zero). Patients were then given either an infusion of ropivacaine 2 mg ml(-1) with fentanyl 2 microg ml(-1) at 10 ml h(-1), or hourly boluses of 10 ml of the same solution. Pain, sensory block and motor block were measured frequently. If requested, additional 10 ml boluses of the study mixture were given for analgesia., Results: There were no differences between the two groups in patient characteristics, obstetric/neonatal outcome, or in sensory or motor block. A total of 12 (60%) patients in the continuous group required one or more additional boluses compared with 4 (20%) patients in the intermittent group (95% CI 9.6-61.7%, P=0.02). Therefore the intermittent group received a lower total drug dose than the infusion group (P=0.02). Duration of uninterrupted analgesia (time to first rescue bolus) was longer in the intermittent group (P<0.02)., Conclusions: The intermittent group required fewer supplementary injections and less drug to maintain similar pain scores, sensory and motor block compared with the continuous group. This represents a more efficacious mode of analgesia.

Background: In view of the wide variation in pain experience between patients, a clinical standard -- the time from the end of surgery to the first experience of pain -- was applied to 1359 consecutive patients in order to investigate whether the initial quality of epidural block has an effect on the overall quality of postoperative pain relief., Methods: Clinical data were recorded in 58,118 out of 72,412 h in 1359 patients, and transferred to a database. Data collected included pain scores on a four-point verbal rating scale; nausea and vomiting; motor block; sedation scores; systolic blood pressure <100 and <90 mm Hg; ventilatory frequency <10 and <8 bpm; and hourly epidural infusion rate., Results: As the time to first experience of pain increased from nil to >24 hours, the time from the first to last experience of pain shortened from 34 (19-50) h to 3 (1-12) h (p<0.001) and the proportion of patients receiving an epidural bolus decreased from 53 to 8% (p<0.001). Increases in the initial pain free time increased the proportion of patients with systolic BP<100 mmHg from 59 to 77%, (p<0.001) and increased the proportion of patients with respiratory rate <10 bpm from 13 to 26%, (p<0.001)., Conclusion: Extending pain relief for more than 12 h beyond the end of abdominal surgery significantly improves the overall quality of postoperative pain relief, but is associated with an increase in side-effects.

Background: Epinephrine is added to local anaesthetic preparations to prolong their action and reduce their systemic absorption. Bupivacaine and levobupivacaine cause vasodilatation at clinical doses, but lower doses appear to cause vasoconstriction. The aim of this study was to characterize fully the vasoactive effects of these anaesthetics, using an objective measure of blood flow, and to assess the influence of adding epinephrine., Methods: Laser Doppler imaging was used to measure the forearm skin blood flow responses to intradermal injection of eight doses of bupivacaine and levobupivacaine in 10 healthy male volunteers. The doses tested ranged from 0.008% to 0.75%, and the five highest doses were administered both with and without adjuvant epinephrine 2.5 microg ml(-1)., Results: The cumulative responses to the lower subclinical concentrations (0.008-0.0625%) of both anaesthetics were smaller than or similar to that produced by saline alone, indicating a net vasoconstrictive effect. Higher doses caused net vasodilatation, and the levobupivacaine responses were generally lower than the corresponding bupivacaine responses (P=0.022). Epinephrine 2.5 microg ml(-1) significantly reduced the responses to clinical doses of both drugs (P<0.001), producing net vasoconstriction., Conclusions: Bupivacaine and levobupivacaine have a biphasic vascular effect when injected intradermally, with subclinical doses causing net vasoconstriction. The addition of epinephrine 2.5 microg ml(-1) decreases these responses markedly.

Background: The physicochemical properties of diamorphine (3,6-diacetylmorphine) enhance its bioavailability compared with more lipid-soluble opioids when administered into the epidural space. However, the influence of concentration, volume or mass on the clinical efficacy of diamorphine is not known., Method: In this double-blind, randomized, prospective study, 62 women in active labour and

Background: Spread of intrathecal local anaesthetics is determined principally by baricity and position of the patient. Hypobaric solutions of bupivacaine are characterized by an unpredictable spread of sensory block whereas addition of dextrose 80 g ml(-1) provides a predictable spread but to high thoracic levels. In contrast, dextrose concentrations between 8 and 30 g ml(-1) have shown reliable and consistent spread for surgery. Hence, the aim of this study was to determine the density of bupivacaine, levobupivacaine, and ropivacaine with and without dextrose at both 23 and 37 degrees C before embarking on clinical studies., Methods: Density (g ml(-1)) was measured using the method of mechanical oscillation resonance, accurate to five decimal places on 1250 samples. 500 density measurements were performed in a randomized, blind fashion at 23 and 37 degrees C on 10 plain solutions of bupivacaine (2.5, 5, and 7.5 g ml(-1)) levobupivacaine (2.5, 5, and 7.5 g ml(-1)) and ropivacaine (2, 5, 7.5, and 10 g ml(-1)). Following this, 750 density measurements were taken at 23 and 37 degrees C on the 5 g ml(-1) solutions of bupivacaine, levobupivacaine, and ropivacaine with added dextrose (10, 20, 30, 50, and 80 g ml(-1))., Results: There was a linear relationship between density and dextrose concentration for all three local anaesthetics (R(2)=0.99) at 23 and 37 degrees C. The mean density of levobupivacaine 5 g ml(-1) was significantly greater than the densities of bupivacaine 5 g ml(-1) and ropivacaine 5 g ml(-1) after adjusting for dextrose concentration using analysis of covariance. This difference existed both at 23 and 37 degrees C. The mean (sd) density of levobupivacaine 7.5 g ml(-1) was 1.00056 (0.00003) g ml(-1), the lower 0.5% percentile (1.00047 g ml(-1)) lying above the upper limit of hypobaricity for all patient groups., Conclusions: The density of local anaesthetics decreases with increasing temperature and increases in a linear fashion with the addition of dextrose. Levobupivacaine 5 g ml(-1) has a significantly higher density compared with bupivacaine 5 g ml(-1) and ropivacaine 5 g ml(-1) at 23 and 37 degrees C both with and without dextrose. Levobupivacaine 7.5 g ml(-1) is an isobaric solution within all patient groups at 37 degrees C [corrected]

The standard spinal preparation of bupivacaine contains a high concentration of glucose (80 mg ml(-1)). However, the addition of only a small amount of glucose (8 mg ml(-1)) to plain solutions of bupivacaine results in a solution which, although no more than marginally hyperbaric, produces a more predictable block when used for spinal anaesthesia in non-pregnant patients. However, bupivacaine 5 mg ml(-1) in glucose 8 mg ml(-1) has a density [1.00164 (SD 0.00008) at 37 degrees C] which is relatively greater than that of the cerebrospinal fluid (CSF) of the pregnant patient at term (1.0003 at 37 degrees C) because CSF density decreases during pregnancy. Therefore, a double-blind, randomized, controlled study was carried out to compare intrathecal bupivacaine (glucose 8 mg ml(-1)) with bupivacaine (glucose 80 mg ml(-1)) in 40 pregnant patients at term. Although there was no difference between groups in onset of sensory block, dose of ephedrine or patient satisfaction, patients receiving bupivacaine (5 mg ml(-1)) with glucose (8 mg ml(-1)) had persistently higher sensory blocks between 60 and 120 min after intrathecal injection, suggesting that the spread of spinal solutions in the pregnant patient at term is not dependent on density.

We have compared the efficacy of 0.25% S(-)-bupivacaine with 0.25% RS-bupivacaine in providing epidural analgesia for labour in a randomized, multicentre, double-blind study. Analgesia was initiated with 10 ml of the study solution and maintained with 10-ml top-ups. We studied 137 women and treatments were found to be equivalent for onset, duration and quality of block. Median onset of pain relief was 12 min for both drugs and median duration was 49 (range 3-129) min and 51 (7-157) min for S(-)-bupivacaine and RS bupivacaine, respectively. The estimated treatment difference for duration of pain relief was -4 (90% CI -13, 6) min. Thirty patients failed to achieve pain relief after the first injection (20 patients after S(-)-bupivacaine and 10 after RS-bupivacaine; P = 0.039). However, median duration of pain relief from the first top-up was 82 (range 3-164) min for S(-)-bupivacaine and 76 (22-221) min for RS-bupivacaine. There were no significant differences in the quality of analgesia, as assessed by the investigators. There were no significant differences in the extent of sensory block, percentage of patients with motor block or incidence of adverse events.

Postoperative pain relief is often inadequate. Ignorance and misconceptions about opioids by ward staff contribute to this poor management. The introduction of acute pain teams has done much to improve pain relief for patients. It may also have contributed to changes in attitudes and knowledge of medical and nursing staff. We questioned 48 doctors and nurses on their knowledge and beliefs about postoperative pain relief. Staff members were questioned on two units, one with access to an acute pain team and one without. Over half those on the unit using traditional postoperative care thought patients did not receive adequate pain relief (58%). In comparison, only one respondent from the unit with the pain team thought this was the case (P < 0.001). More staff members that had experience of patient-controlled analgesia (PCA) were optimistic about its benefits than those in the unit with no experience; they were also less concerned about possible side effects. Only one respondent on the unit using PCA thought it carried a risk of drug dependence, compared to over half (55%) of those on the unit with no experience in this technique (P < 0.001). Over two-thirds of staff familiar with PCA thought nursing workload had decreased. Acute pain teams have an important role in educating ward staff. The impact of establishing such teams on staff knowledge and attitudes needs further study to ensure that they can carry out this role most effectively.

We have studied the effects of choice of local anaesthetic and temperature of extradural injectate on speed of onset of sensory block for elective extradural Caesarean section in a double-blind trial in 120 women allocated randomly to one of four groups to receive either plain 0.5% bupivacaine or 2% lignocaine with 1:200,000 adrenaline at either room temperature or 38 degrees C. The onset time of lignocaine with adrenaline was shorter than that of bupivacaine regardless of temperature (P < 0.01). Warmed lignocaine produced the most rapid block overall (P < 0.025). The incidence of hypotension, ephedrine requirement, shivering, quality of analgesia and additional analgesic requirements were similar for all groups.

The evaluation of interferons in the treatment of malignant melanoma has been mainly in the treatment of advanced disease using interferons as the sole agent or in combination with other agents. Studies of the value of interferons as adjuvant therapy in high-risk primary melanoma patients are necessary, but no results have been published to date. Human interferon alpha produces low response rates as a sole agent, but in combination with cimetidine, a 30% response rate has been achieved. Recombinant alpha interferons give responses of 15%-20% in advanced melanomas, and combination with cimetidine does not enhance the response rate. Recombinant alpha interferons have been used in combination with other interferons, cimetidine, monoclonal antibodies, and cytotoxics, with either no or small improvement in response rates. DTIC with recombinant interferon alpha-2a has been shown to produce objective response rates of 26%, with low toxicity and maintenance of quality of life. A randomized trial with DTIC as the sole agent, compared with combination treatment, is being conducted to determine the significance of this finding.