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Biomedical subjects

G A McLeod

Publications and source records attributed to G A McLeod.

17 recordsLinked to original sources
PubMed2007

Mechanisms influencing the vasoactive effects of lidocaine in human skin.

The vasodilator properties of lidocaine are believed to be due mainly to the inhibition of action potentials via sodium channel blocking in vasoconstrictor sympathetic nerves. However, mechanisms involving the vascular endothelium may also play a role, and in this study we investigated the potential influences of nitric oxide release, the cyclo-oxygenase pathway and the beta-adrenoceptors of vascular smooth muscle. Laser Doppler imaging was used to measure microvascular blood flow responses to intradermal injection of lidocaine 2%, with or without the addition of preservatives, in eight healthy, male volunteers. Co-injection of the nitric-oxide-synthase inhibitor Nomega-nitro-L-arginine methyl ester caused a 60% reduction in the response after about 20 min, and this reduction was enhanced with the lidocaine solution containing the preservatives methylhydroxybenzoate and propylhydroxybenzoate. No reduction in response was seen after blocking the cyclo-oxygenase or beta-adrenoceptor pathways. Nitric oxide release contributes to the vasoactivity of lidocaine in human skin.

Adult↗
PubMed2006

Intermittent vs continuous administration of epidural ropivacaine with fentanyl for analgesia during 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.

Adult↗
PubMed2006

Measuring the quality of continuous epidural block for abdominal surgery.

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.

Abdomen↗
PubMed2005

Vasoactive characteristics of bupivacaine and levobupivacaine with and without adjuvant epinephrine in peripheral human skin.

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.

Adjuvants, Anesthesia↗
PubMed2004

Is the clinical efficacy of epidural diamorphine concentration-dependent when used as analgesia for labour?

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 </=5 cm cervical dilatation were recruited to determine whether the mode of action of diamorphine in the epidural space is concentration-dependent. After insertion of a lumbar epidural catheter, patients received epidural diamorphine 3 mg either as a high-volume, low-concentration solution (group A) or a low-volume, high-concentration solution (group B). The concentration of diamorphine was determined by the response of the previous patient in the same group using up-down sequential allocation. Pain corresponding to the previous contraction was assessed using a 100-mm visual analogue score and effective analgesia was defined as </=10 mm within 30 min of epidural injection. RESULTS: There was no significant difference in EC50 for diamorphine between the groups: the difference was 15.0 microg ml(-1) (95% CI -40.3 to 10.3). The EC50 for group A was 237.5 microg ml(-1) (95% CI 221.2 to 253.8) and the EC50 for group B was 252.5 microg ml(-1) (95% CI 232.2 to 272.8). The EC50 ratio was 0.95 (95% CI 0.87 to 1.06). The groups exhibited parallelism (P=0.98). The overall EC50 for all data was 244.2 microg ml(-1) (95% CI 230.8 to 257.2). CONCLUSION: We conclude that diamorphine provides analgesia in labour by a concentration-dependent effect.

Adult↗
PubMed2004

Density of spinal anaesthetic solutions of bupivacaine, levobupivacaine, and ropivacaine with and without dextrose.

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]

Amides↗
PubMed2003

Mechanisms contributing to the vaso-active effects of prilocaine in human skin.

We investigated the roles of the endothelial nitric oxide and cyclo-oxygenase pathways in mediating the vasoactivity of prilocaine in the skin. We injected prilocaine 1% intradermally into forearm skin of 10 healthy, male subjects. Nitric oxide synthesis was inhibited at a second site by co-injecting prilocaine with l-NAME 1%. We then repeated the injections while blocking the cyclo-oxygenase pathway with aspirin (4 x 600 mg). We measured blood flow responses to the injections using laser Doppler imaging. We found that, after the traumatic effects of injection had subsided, l-NAME reduced the vascular response to prilocaine by a third (p = 0.012), indicating an influence specifically on the drug response. Aspirin had no effect on the response (p = 0.588). We conclude that the vasoactive effects of prilocaine in human skin are mediated partly through the release of endothelial nitric oxide and, although other mechanisms might also be involved, the cyclo-oxygenase pathway does not appear to play a role.

Adolescent↗
PubMed2001

Levobupivacaine.

Regional anaesthesia has seen the development of a new local anaesthetic: levobupivacaine. This review aims to outline the rationale underlying the development of levobupivacaine and to consider its place in modern regional anaesthesia.

Anesthesia, Conduction↗
PubMed2001

Spinal anaesthesia for Caesarean section with bupivacaine 5 mg ml(-1) in glucose 8 or 80 mg ml(-1).

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.

Adolescent↗
PubMed1999

Comparison of 0.25% S(-)-bupivacaine with 0.25% RS-bupivacaine for epidural analgesia in labour.

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.

Adolescent↗
PubMed1995

Shaping attitudes to postoperative pain relief: the role of the acute pain team.

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.

Attitude of Health Personnel↗
PubMedDate not supplied

Skin blood flow changes in response to intradermal injection of bupivacaine and levobupivacaine, assessed by laser Doppler imaging.

BACKGROUND AND OBJECTIVES: The vascular effects of local anesthetics are important determinants of their therapeutic activity. Drugs that vasoconstrict have the potential clinical advantages of limited systemic uptake and prolonged duration of effect. The aim of this study was to assess quantitatively the cutaneous vasoactivity of racemic bupivacaine and one of its enantiomers, levobupivacaine. METHODS: Four concentrations of each drug (0.1 mL each of 0.125%, 0.25%, 0.5%, and 0.75%), as well as normal saline, were injected intradermally into randomly assigned sites on the forearms of 10 volunteers. We measured skin blood perfusion using laser Doppler imaging before injection and at 2.5, 10, 20, 40, 60, and 90 minutes thereafter. RESULTS: Both drugs produced a rapid, dose-dependent increase in skin perfusion (P <.001). Saline also caused an increase in perfusion, although less sustained. By 40 minutes, most responses had returned to baseline levels. However, after this time, perfusion continued to decrease, below baseline, for both bupivacaine and levobupivacaine. The exception to this was 0.75% bupivacaine, the response to which was significantly higher than the same concentration of levobupivacaine over this later period (P <.05). CONCLUSIONS: Bupivacaine and levobupivacaine both have a biphasic effect on skin microvessels. The vasoconstriction observed after 40 minutes may occur when the quantity of drug remaining at the administration site has decreased to a lower level. The continued vasodilatation caused by bupivacaine is more difficult to interpret. The results suggest that these local anesthetics cause vasodilatation at high doses and vasoconstriction at lower, subclinical doses. This hypothesis and the clinical relevance of these effects warrant further investigation.

Administration, Cutaneous↗