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Biomedical subjects

S F Evans

Publications and source records attributed to S F Evans.

17 recordsLinked to original sources

Patient-controlled epidural analgesia following caesarean delivery: a comparison of pethidine and fentanyl.

Pethidine and fentanyl have both been used to provide patient-controlled epidural analgesia (PCEA) following caesarean delivery. Both have been compared with epidural morphine but these drugs have not been compared with each other. Patient-controlled epidural analgesia was used in a prospective, randomized, double-blind, cross-over trial to compare fentanyl and pethidine for postoperative epidural analgesia in women having elective caesarean deliveries. Two groups received either PCEA fentanyl or pethidine with a cross-over to the other drug after 24 hours. Results from 45 patients showed no difference in pain level outcomes, but pethidine scored better in all side-effects except for drowsiness at 48 hours. Patients were more satisfied with pethidine (P = 0.015) and overall 65% of patients preferred pethidine. We conclude that pethidine is a suitable drug for patient-controlled epidural analgesia and leads to greater patient satisfaction than does fentanyl.

Adult

Catecholamine response to ultrasonographically guided percutaneous blood sampling in fetal sheep.

OBJECTIVE: The purpose of this study was to investigate the fetal catecholamine and arterial blood gas responses to ultrasonographically guided percutaneous needle aspiration of blood from a fetal cardiac ventricle. STUDY DESIGN: A crossover trial design was used. Nine pregnant sheep of 120 to 130 days' gestation were stratified to either percutaneous fetal blood sampling or a sham experiment performed on the first day, and the alternative study on the following day. Arterial blood samples were withdrawn from chronically implanted catheters. RESULTS: Percutaneous fetal blood sampling caused small but statistically significant increases in mean plasma epinephrine and norepinephrine levels 5 seconds after the procedure. Levels thereafter were similar to baseline values. Arterial pH and PCO2 values were unaltered except in one fetus, where blood sampling was followed by bradycardia with acidosis and elevated catecholamine levels. CONCLUSIONS: Ultrasonographically guided percutaneous fetal blood sampling from a cardiac ventricle in sheep produces a rise in catecholamine levels that return to baseline values within 5 minutes. This technique provides an alternative to chronic catheterization for some experiments in which blood sampling or drug injection is required. The results also indicate that needle insertion produces only a modest and transient stress response in the fetus.

Animals

Meperidine for patient-controlled analgesia after cesarean section. Intravenous versus epidural administration.

BACKGROUND: Although meperidine has been used for patient-controlled analgesia both intravenously (PCIA) and epidurally (PCEA), these routes have not been compared, and many studies have suggested that there is no advantage to the epidural route for administration of lipophilic opioids. METHODS: A randomized, double-blind, crossover study was conducted for 24 h after cesarean section to compare the analgesic efficacy, side effects, patient satisfaction, drug use, and plasma drug concentrations with meperidine administered either as PCIA or as PCEA. Two groups, stratified for time of cesarean section during epidural anesthesia, postoperatively received either PCEA (group 1) or PCIA (group 2) with identical variables for 12 h before crossing to the other route for an additional 12 h. RESULTS: Results from 45 patients showed a similar speed of analgesic onset but, subsequently, significantly lower pain scores both at rest and with coughing in those receiving PCEA (P = 0.0001). Nausea and pruritus scores did not differ between the groups in the first 12 h postoperatively, but sedation scores were significantly higher with PCIA (P = 0.0001). Patient satisfaction scores and preference significantly favored PCEA (P = 0.0001), with almost 90% of participants preferring the epidural route. Meperidine use was reduced approximately 50% with PCEA (P = 0.0001), and plasma meperidine and normeperidine concentrations were significantly lower (P = 0.0001). CONCLUSIONS: We conclude that after cesarean section, PCEA with meperidine produces high-quality pain relief with few side effects and has significant advantages over PCIA meperidine. With the caveat that neonatal effects in breast-feeding mothers have yet to be evaluated, it can be highly recommended in this population.

Adult

C-reactive protein as a diagnostic tool of sepsis in very immature babies.

Three hundred and nine septic screens were performed on 123 consecutively admitted infants of < 30 weeks gestation. As part of the septic screen, serial quantitative measurements of C-reactive protein (CRP) were performed daily until discontinuation of antibiotic therapy. Complete blood counts were performed daily for the first 2 days of each septic episode. The babies had a mean birth weight of 1035.8 g s.d. 273.2 and a mean gestational age of 27 weeks s.d. 1.8. A CRP level of 10 mg/L or above was considered abnormal. Subsequently the receiver operator characteristic curve for CRP was constructed to demonstrate the ideal cut off value. Of the 309 septic screens, there were 51 instances of proven sepsis and 39 instances of deep culture negative sepsis. In the remaining 219, a diagnosis of proven or deep culture negative sepsis could not be made. On the first day of the septic episode CRP showed a sensitivity of 62.7%, specificity of 87.2% and negative predictive value of 92.2% for proven sepsis. There was a significant increase in the sensitivity (90.2%) and negative predictive value (97.7%) of CRP with a specificity of 80.6 when both day 1 and 2 estimations were combined. We conclude that when the CRP is elevated on day 1 and/or day 2, the diagnosis of sepsis is extremely likely and when the CRP is within normal limits on days 1 and 2 of the septic episode, neonatal sepsis can be confidently excluded and antibiotic therapy ceased.

C-Reactive Protein

Effects of frequent ultrasound during pregnancy: a randomised controlled trial.

Despite widespread application of ultrasound imaging and Doppler blood flow studies, the effects of their frequent and repeated use in pregnancy have not been evaluated in controlled trials. From 2834 women with single pregnancies at 16-20 weeks gestation, 1415 were selected at random to receive ultrasound imaging and continuous-wave Doppler flow studies at 18, 24, 28, 34, and 38 weeks gestation (the intensive group) and 1419 to receive single ultrasound imaging at 18 weeks (the regular group). Outcome data was obtained from 99% of women who entered the study. The only difference between the two groups was significantly higher intrauterine growth restriction in the intensive group, when expressed both as birthweight < 10th centile (relative risk 1.35; 95% confidence interval 1.09 to 1.67; p = 0.006) and birthweight < 3rd centile (relative risk 1.65; 95% confidence intervals 1.09 to 2.49; p = 0.020). While it is possible that this finding was a chance effect, it is also plausible that frequent exposure to ultrasound may have influenced fetal growth. Repeated prenatal ultrasound imaging and Doppler flow examinations should be restricted to those women to whom the information is likely to be of clinical benefit.

Adult

Vertebral deformity, bone mineral density, back pain and height loss in unscreened women over 50 years.

Bone mineral density (BMD) was measured in the lumbar spine using dual-energy X-ray absorptiometry in 222 unscreened women (aged 50-82 years), and information on back pain and historic loss of standing height was obtained at interview. Vertebral morphometry was performed on lateral spinal radiographs. The shape of the vertebral body was quantified using appropriate vertebral shape indices (VSIs), and vertebral deformities were identified using thresholds defined in terms of the means (M) and standard deviations (SD) of these VSIs for the whole group. Severity of deformity was defined as either grade 1 (M+2SD < VSI < M+3SD), grade 2 (M+3SD < VSI < M+4SD or grade 3 (VSI > M+4SD). Subjects with grade 1 vertebral deformities were older than subjects without such deformities, but did not have a reduced age-related Z-score of BMD. Grade 2 wedge and concave deformities were associated with a reduced age-related Z-score of BMD, suggesting that the aetiology of such deformities is closest to conventional concepts of 'osteoporotic fracture'. Grade 3 deformities were associated with neither increased age nor decreased BMD. Stature decreased in these subjects with age. Subjects reporting historic height loss had a higher mean number of wedge deformities. Subjects with back pain did not have a higher incidence of vertebral deformity than subjects without, confirming that many deformities were asymptomatic. Neither back pain nor historic loss of height were found to be associated with low spinal BMD.

Absorptiometry, Photon

Vertebral morphometry in women aged 50-81 years.

Vertebral dimensions and vertebral shape indices (VSI) were investigated in T4-L4 in 926 females aged 50-81 years. The most consistent finding was the increase of inferior antero-posterior dimension with age. Wedging and concavity also increased with age but the changes were not significant at all vertebral levels. The value of VSIs also varied with level. Thus a particular degree of VSI, considered normal at one level or at one age, would be outside the reference range at a different level or age group. The number of subjects identified as osteoporotic by skewness (5.4%) or in excess of three standard deviations from the mean (6.5%) was much lower than in recent reports from North America. The number of subjects contributing to a skewed distribution increased with age from 0.5% at 55-59 years to 10.0% at 75-79 years. Change with age in the antero-posterior dimension could increase load-bearing area in older subjects, but the decline in bone density will be increased as a declining bone mineral content occupies a larger volume.

Aged

A computerized technique for vertebral morphometry.

A new technique for morphometric measurement of vertebral bodies has been described, in which a computerized image analysis system was used to digitize and measure standardized lateral radiographs of the thoracic and lumbar spine. The sources of error in the radiographic system and the image analysis system were assessed using vertebral phantoms and test images. Oblique projection in the radiographic image of a vertebra did not produce a significant error in the measured area. The radiographic magnification was approximately 35%. Optical non-uniformity was detected in the image analysis system, and was ascribed to the lens optics. The maximum intra-observer and inter-observer variations in vertebral area were 3.1% and 5.3% respectively for experienced observers. The technique is applicable to clinical studies of large populations, and has value in investigating vertebral deformity in the management of metabolic bone disease.

Female

Characterization of circulating pro-opiomelanocortin-related peptides in human septic shock.

The nature of circulating pro-opiomelanocortin (POMC)-related peptides was investigated in patients with a diagnosis of septic shock. Also, changes following administration of methylprednisolone were monitored using established chromatographic techniques and three radioimmunoassays directed towards the N-terminal, mid-portion and C-terminal regions of the precursor. Adrenocorticotrophin and beta-endorphin-like peptides were identified in the circulation. By 60 min after a pharmacological dose of methylprednisolone (30 mg/kg) concentrations of these peptides were reduced and continued to fall up to 180 min. beta-Lipotrophin and N-terminal POMC(1-76) were also detected by the beta-endorphin and gamma 3-MSH assays respectively. The concentrations of these peptides were noticeably reduced only after 180 min. The 31,000 Da MSH/ACTH/beta-endorphin (POMC) and the 22,000 Da MSH/ACTH precursors were also present in the circulation in septic shock and their concentrations increased following steroid treatment.

Adrenocorticotropic Hormone

Nitrous oxide inhalation does not influence plasma concentrations of beta-endorphin or Met-enkephalin-like immunoreactivity.

The possibility that nitrous oxide releases endogenous opioid peptides into the circulation has been tested in 10 pain-free, unstressed volunteers breathing 30% nitrous oxide in oxygen. Despite achieving plateau concentrations in venous blood, accompanied by subjective effects, there were no significant changes in plasma concentrations of immunoreactive beta-endorphin, methionine-enkephalin or ACTH. These results indicate that, in the absence of nociceptive input, the effects of the inhalation of nitrous oxide are unrelated to alterations in peripheral concentrations of these endogenous opioid peptides.

Adrenocorticotropic Hormone

Neuroendocrine and cardiovascular changes in septic shock and after cardiac surgery: effect of high-dose corticosteroid therapy.

Plasma levels of beta-endorphin-like immunoreactivity (BLI) were similarly elevated in patients with septic shock (group A) and in normotensive subjects recovering from cardiac surgery (group B) (1231 +/- 483 pg ml-1 and 1,240 +/- 355 pg ml-1, respectively). In neither group was cardiac output reduced, but total peripheral resistance index (TPRI) was low in group A and low or normal in group B. Intravenous methylprednisolone (MP) 30 mg kg-1 variably suppressed BLI by a mean of only 30% in group A, while in group B, BLI usually rose and then fell following MP. In group A percentage changes in BLI were positively correlated with percentage changes in cardiac index (CI) and mean arterial pressure (MAP) (r = .83, P less than .01, r = .59, P less than .05 respectively). No such correlations were found in group B. These findings suggest that increases in circulating beta-endorphin are unlikely to be responsible for myocardial depression or hypotension in septic shock. ACTH levels were in general normal in group A but were consistently elevated in group B, although plasma cortisol was similarly elevated in both groups. Furthermore there was a good correlation between percentage changes in ACTH and BLI following MP in group B (r = .87, P less than .01) but not in group A. Possible explanations for these findings are discussed.

Adrenocorticotropic Hormone

A secondary immune deficiency in the Fatty/Orl-op rat.

The response of T and B lymphocytes to the mitogens PHA and LPS was studied in the Fatty/Orl-op rat. Whereas T and B cells from op/op spleen showed no lack of responsiveness compared with that of normal (op/+) littermate rats, the response of thymic cells to the T cell mitogen was lower in op/op rats over 12 days of age compared with normal rats of the same age. Osteopetrotic rats of 10 days and younger did not show this T cell deficiency. The responsiveness of T cells from op/op lymph nodes to PHA was less than that of normal rats at 12 days and older. Thus, though splenic T and B cell populations were well maintained in the adult op/op rat despite the severe depletion of marrow cells in this mutant, the thymus and lymph node T cell populations were qualitatively or quantitatively deficient. Since osteopetrotic obliteration of the marrow cavities precedes the appearance of the immune deficiency we suggest that the immune deficiency may be caused by a failure of T cell supply to the thymus and lymph nodes.

Animals

Plasma levels and biochemical characterisation of circulating met-enkephalin in canine endotoxin shock.

Endogenous opioid peptides have been implicated in the pathophysiology of shock (1-5). In anaesthetised mongrel dogs, administration of E coli endotoxin caused a rise in plasma met-enkephalin-like immunoreactivity (MLI). Biochemical characterisation of MLI by gel filtration chromatography revealed various molecular forms: 31K, 8K, 3-5K and the native pentapeptide in approximately equal amounts. After enzymatic treatment of column fractions the 31K form predominated (90.7%). This is the first demonstration of elevated MLI in endotoxin shock.

Animals

A new canine model of endotoxin shock.

A new canine model of endotoxin shock has been developed in which spontaneous recovery of cardiovascular function is largely prevented, the haemodynamic effects of anaesthesia are minimized and intravascular volume replacement is given. This model has been evaluated using two groups of five adult mongrel dogs anaesthetized with alpha-chloralose and breathing spontaneously. Animals in one group were anaesthetized, instrumented and given Escherichia coli (E. coli) endotoxin intravenously, whilst those in the control group were subjected only to anaesthesia and instrumentation. E. coli endotoxin was given to dogs in the shock group as a bolus dose of 5 mg kg-1 followed by a continuous infusion at 2 mg kg-1 h-1. This produced immediate, severe, cardiovascular depression, with precipitous falls in mean arterial pressure (MAP), cardiac index (CI), stroke index (SI) and left ventricular (LV) dp/dt max. There were associated increases in systemic and pulmonary vascular resistances. Arterio-venous oxygen content difference (C(a-v)O2) increased after induction of shock, and animals developed a progressive metabolic acidosis. Increasing haemoconcentration occurred, as evidenced by a rising haematocrit (PCV). Hypovolaemia was reflected by a concurrent fall in pulmonary capillary wedge pressure (PCWP). One hour after induction of shock, intravascular volume replacement was given in the form of a colloidal gelatin solution, as a bolus dose of 10 ml kg-1, followed by a continuous infusion at 10 ml kg-1 h-1. Volume replacement reversed haemoconcentration, restored PCWP and produced some haemodynamic improvement, although in general, severe cardiovascular depression persisted throughout a three hour observation period. This severe endotoxin shock model has proved to be stable, reproducible and economical. It provides a useful preliminary test for new methods of treatment in hypodynamic endotoxin shock, as well as allowing investigation of acute metabolic and physiological changes.

Acid-Base Equilibrium

Effects of intravascular volume expansion on the cardiovascular response to naloxone in a canine model of severe endotoxin shock.

The specific opiate receptor antagonist, naloxone, can produce haemodynamic improvement and increased survival in experimental shock. The efficacy of naloxone therapy in a canine model of endotoxin shock has been evaluated both with and without intravascular volume replacement. Animals were anaesthetized with alpha-chloralose and allowed to breathe spontaneously. A large bolus dose of endotoxin was followed by a continuous infusion and treatment was instituted one hour after the endotoxin bolus. In the absence of volume replacement, naloxone caused only limited and transient increases in mean arterial pressure (MAP) and left ventricular (LV) dp/dt max, with little effect on cardiac index (CI). Total peripheral resistance index (TPRI) tended to rise in both control and naloxone-treated dogs. In volume-replaced animals, naloxone produced substantial and sustained increases in the MAP and LV dp/dt max with an associated rise in the CI. TPRI rose initially in this series and then fell progressively. Further analysis of the improvements in the CI showed an increase in stroke index with a tendency for heart rate to fall. These findings suggest a myocardial action of naloxone in endotoxin shock, which is augmented by volume replacement. An initial, transient vasoconstrictor effect cannot, however, be excluded. Further work is required to determine the mechanism of the effects described.

Animals