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- Cederholm, Ingemar, 1951-
(author)
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Ropivacaine : An experimental and clinical study with special reference to analgesic, circulatory and antiinflammatory effects
- 1994
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Doctoral thesis (other academic/artistic)abstract
- Aims of the study: 1. to compare ropivacaine, a new long-acting amino-amide local anaesthetic drug, and bupivacaine (with/without adrenaline) concerning dermal analgesia and local vascular effects, 2. to design a suitable test procedure to evaluate changes in skin blood flow after intradermal injection of local anaesthetics, 3. to evaluate changes in skin blood flow of various concentrations of ropivacaine with/without adrenaline, 4. to investigate the influence of ropivacaine, bupivacaine, lidocaine, mepivacaine and prilocaine on the production of oxygen metabolites in human polymorphonuclear leukocytes (PMNL) (intra- and extracellular reactions), and 5. to examine the neural blocking characteristics on sensory, motor and sympathetic pathways using ropivacaine for epidural analgesia.72 male patients scheduled for transurethral surgery and 50 male volunteers participated in this work. Heparinized blood was obtained from a total of 29 healthy adult blood donors.Dermal analgesia was evaluated by pin-prick, skin colour changes by visual inspection, skin blood flow by laser Doppler flowmetry, sensory blockade by pin-prick, motor blockade by a modified Bromage scale, sympathetic blockade by assessments of skin resistance level (SRL) and response (SRR), skin temperature and skin blood flow (laser Doppler flowmetry). Production of oxygen metabolites by PMNLs was measured by luminal-enhanced chemiluminescence (intra- and extracellular reactions).Ropivacaine produced significantly longer duration of dermal analgesia, following intradermal injection (0.1 ml, 30-G needle), compared with bupivacaine, in comparable concentrations. Addition of adrenaline increased the duration of both local anaesthetics. Local blanching was more frequent for plain solutions of ropivacaine.The effect of drugs on local circulation may well be studied by intradennal injection (0.1 ml, 30-G needle, volar surface, forearms) and recording of changes in skin blood flow (laser Doppler flowmetry). The intradennal injection of a local anaesthetic drug may produce not only a further increase but also a decrease in skin blood flow, if the effect of an intradermal saline injection, causing a very reproducible flow increase, is considered in the evaluation of the net circulatory effect of the tested drug.Intradermal injection of lidocaine 1% and bupivacaine 0.75% produced an increase in skin blood flow. Ropivacaine 1% produced a flow similar to saline, while a decrease was seen for ropivacaine 0.75%. Ropivacaine0.5%, 0.375%, 0.25%, 0.125% and 0.063% showed a gradual further reduction in flow, where 0.063% produced a flow similar to adrenaline-injection (5 Jlg/ml) and almost as low as at the untreated control sites. The combination of ropivacaine 1%, 0.5% , 0.25% and adrenaline did not accentuate but instead decreased the vasoconstrictive effect of adrenaline.By and large a decrease in response of chemiluminescence for PMNLs was seen with the higher concentrations of the various local anaesthetics. Lidocaine showed a minor decrease even at lower concentrations. Ropivacaine 1000 J.Lg/ml showed a depression of both intra- and extracellular responses that was similar to, and even somewhat more pronounced than lidocaine 1000 J.Lg/ml. This effect could be of great interest e.g. for local antiinflammatory effects by topical administration, but it has to be further investigated. A marked increase for prilocaine (1000 Jlg/ml) in intracellular response accompanied with a reduction in extracellular response was noted.Ropivacaine (0.5%, 0.75% with/without adrenaline) 20 ml administered epidurally provided a good sensory blockade and a motor blockade satisfactory for transurethral surgery. The maximum sensory level of analgesia was high, median Th 2-3. The majority of patients had a marked or complete sympathetic blockade in the lower limbs. Besides mild or moderate hypotension, which responded well to treatment with ephedrine, no other serious adverse reactions were seen, Addition of adrenaline did not provide any significant prolongation of the epidural blockade, and did not alter the influence upon the sympathetic blockade nor the hemodynamic changes during onset.
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- Gonon, Adrian, et al.
(author)
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Effects of thoracic epidural analgesia on exercise-induced myocardial ischaemia in refractory angina pectoris
- 2019
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In: Acta Anaesthesiologica Scandinavica. - : WILEY. - 0001-5172 .- 1399-6576. ; 63:4, s. 515-522
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Journal article (peer-reviewed)abstract
- Background Thoracic epidural analgesia (TEDA) was offered to patients with refractory angina pectoris. Our primary objectives were to evaluate TEDAs influence on quality of life (QoL, base for power analysis), and hypothesising that TEDA with bupivacaine during 1 month counteracts exercise-induced myocardial hypoperfusion and increase physical performance. Methods Patients with refractory angina and exercise inducible hypoperfusion, as demonstrated by myocardial perfusion imaging (MPI), were randomised to 1-month treatment with TEDA with bupivacaine (B-group, n = 9) or saline (P-group, n = 10) in a double-blind fashion. MPI and bicycle ergometry were performed before TEDA and after 1 month while subjective QoL on a visual analogue scale (VAS) reported by the patients was checked weekly. Results During this month VAS (mean [95%CI]) increased similarly in both groups (B-group from 33 [18-50] to 54 [30-78] P P amp;lt; 0.05). The B-group reduced their exertional-induced myocardial hypoperfusion (from 32% [12-52] to 21% [3-39]; n = 9; P amp;lt; 0.05), while the P-group showed no significant change (before 21% [6-35]; at 1 month 23% [6-40]; n = 10). MPI at rest did not change and no improvement in physical performance was detected in neither of the groups. Conclusions In refractory angina, TEDA with bupivacaine inhibits myocardial ischaemia in contrast to TEDA with saline. Regardless of whether bupivacaine or saline is applied intermittently every day, TEDA during 1 month improves the quality of life and reduces angina, even when physical performance remains low. A significant placebo effect has to be considered.
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- Holm, Jonas, 1971-, et al.
(author)
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Biomarker dynamics in cardiac surgery: a prospective observational study on MR-proADM, MR-proANP, hs-CRP and sP-selectin plasma levels in the perioperative period
- 2020
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In: Biomarkers. - : TAYLOR & FRANCIS LTD. - 1354-750X .- 1366-5804. ; 25:3, s. 296-304
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Journal article (peer-reviewed)abstract
- Background: For many biomarkers in cardiac surgery, there is a lack of knowledge regarding the normal dynamics of plasma levels during the perioperative course. The aim of this study was to investigate the perioperative dynamics of MR-proADM, MR-proANP, hs-CRP and sP-selectin in cardiac surgery. Method: A prospective observational pilot study with 20 patients scheduled for open cardiac surgery procedures with cardiopulmonary bypass (CPB). Plasma samples were taken for each patient and biomarker during the pre-, per- and postoperative period until Day 6 postoperatively. Results: MR-proADM increased significantly from 0.62 [IQR; 0.54-0.93] nmol/L preoperatively to 1.20 [1.04-1.80] nmol/L postoperative Day 1. MR-proANP increased significantly from 125 [77-152] pmol/L preoperatively to 198 [168-307] pmol/L on weaning from CPB. hs-CRP increased significantly from 2.5 mg/L [0.4-12] preoperatively to peak at 208 mg/L [186-239] postoperative Day 3. The preoperative level of sP-selectin at 23.0 [21.3-26.3] ng/mL initially fell at weaning from CPB, followed by a significant peak of 25.5 [22.7-27.7] ng/mL 8 h postoperatively. Conclusions: The findings in this study may help to understand the physiology of the biomarkers analysed and their response to cardiac surgical trauma including CPB. Furthermore, these findings will guide us in further research on the clinical usefulness of these biomarkers.
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- Holm, Jonas, 1971-, et al.
(author)
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Copeptin Release in Cardiac Surgery : A New Biomarker to Identify Risk Patients?
- 2018
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In: Journal of Cardiothoracic and Vascular Anesthesia. - : Saunders Elsevier. - 1053-0770 .- 1532-8422. ; 32:1, s. 245-250
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To describe the dynamics of copeptin in open cardiac surgery during the perioperative course.DESIGN: Prospective cohort study.SETTING: Single tertiary hospital.PARTICIPANTS: Twenty patients scheduled for open cardiac surgery procedures with cardiopulmonary bypass (CPB).INTERVENTIONS: No intervention.MEASUREMENTS AND MAIN RESULTS: Copeptin concentrations were measured pre-, peri-, and postoperatively until day 6 after surgery. Patients were analyzed as a whole cohort (n = 20) and in a restricted "normal cohort" consisting of patients with normal preoperative copeptin concentration (<10 pmol/L) and perioperative uneventful course (n = 11). In the whole cohort, preoperative copeptin concentration was 7.0 pmol/L (interquartile range: 3.1-11 pmol/L). All patients had an early rise of copeptin, with 80% having peak copeptin concentration at weaning from CPB or upon arrival in the intensive care unit. Patients in the "normal cohort" had copeptin concentration at weaning from CPB of 194 pmol/L (98-275), postoperative day 1, 27 pmol/L (18-31); and day 3, 8.9 pmol/L (6.3-12).CONCLUSIONS: Regardless of cardiac surgical procedure and perioperative course, all patients had an early significant rise of copeptin concentrations, generally peaking at weaning from CBP or upon arrival in the intensive care unit. Among patients with normal copeptin concentration preoperatively and uneventful course, the postoperative copeptin concentrations decreased to normal values within 3-to-4 days after cardiac surgery. Furthermore, the restricted "normal cohort" generally tended to display lower levels of copeptin concentration postoperatively. Further studies may evaluate whether copeptin can be a tool in identifying risk patients in cardiac surgery.
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- Richter, Arina, et al.
(author)
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Effect of Long-Term Thoracic Epidural Analgesia on Refractory Angina Pectoris: A 10-Year Experience
- 2012
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In: Journal of Cardiothoracic and Vascular Anesthesia. - : Saunders Elsevier. - 1053-0770 .- 1532-8422. ; 26:5, s. 822-828
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Journal article (peer-reviewed)abstract
- ObjectivesIn patients with refractory angina, the adjuvant effects of long-term home self-treatment with thoracic epidural analgesia on angina, quality of life, and safety were evaluated.DesignA prospective, consecutive study.SettingA university hospital.Participants and InterventionBetween January 1998 and August 2007, 152 consecutive patients with refractory angina began treatment with thoracic epidural analgesia by intermittent injections of bupivacaine (139 home treatment and 13 palliative). Data were collected until August 2008; therefore, the follow-up for each patient was between 1 and 9 years.Measurements and Main ResultsAll but 7 of the patients improved symptomatically, and the improvement was maintained throughout the period of treatment (median = 19 months; range, 1 month-8.9 years). After 1 to 2 weeks, the median (interquartile range [IQR]) Canadian Cardiovascular Society angina class decreased from 4.0 (3.0-4.0) to 2.0 (1.0-2.0), the mean ± standard deviation frequency of anginal attacks decreased from 36 ± 19 to 4.4 ± 6.8 a week, the nitroglycerin intake decreased from 27.7 ± 15.7 to 2.7 ± 4.9 a week, and the median (IQR) overall self-rated quality of life assessed by the visual analog scale increased from 25 (20-30) to 70 (50-75) (all p < 0.001). About one-third of the patients had a dislodgement of the epidural catheter. Apart from 1 epidural hematoma that appeared in 1 patient with a previously undiagnosed bleeding defect, no other serious catheter-related complications occurred.ConclusionsLong-term self-administered home treatment with thoracic epidural analgesia is a safe, widely available adjuvant treatment for patients with severe refractory angina. It produces symptomatic relief of angina and improves quality of life. The technical development of the method to protect the catheter against dislodgement is needed.
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- Ricther, Arina, 1949-, et al.
(author)
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Effect of thoracic epidural analgesia on refractory angina pectoris : Long-term home self-treatment
- 2002
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In: Journal of Cardiothoracic and Vascular Anesthesia. - : Elsevier BV. - 1053-0770 .- 1532-8422. ; 16:6, s. 679-684
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Journal article (peer-reviewed)abstract
- Objectives: To evaluate the effects of long-term home self-treatment with thoracic epidural analgesia (TEA) on angina, quality of life, and safety. Design: Prospective consecutive pilot study. Setting: Department of Cardiology, Heart Center, Link÷ping University Hospital. Participants: Between January 1998 and January 2000, 37 consecutive patients with refractory angina began treatment with TEA, using a subcutaneously tunnelled epidural catheter. Interventions: The patients were trained to provide self-treatment at home with intermittent injections of bupivacaine. Data were collected until January 2001, and the follow-up for each patient was 1 to 3 years. Measurements and Main Results: All but 1 of the patients improved symptomatically. The improvement was maintained throughout the treatment period (4 days to 3 years). The Canadian Cardiovascular Society angina class decreased from 3.6 to 1.7, frequency of anginal attacks decreased from 46 to 7 a week, nitroglycerin intake decreased from 32 to 5 a week, and the overall self-rated quality of life assessed by visual analog scale increased from 24 to 76 (all p < 0.001). No serious catheter-related complications occurred, however, 51% of the catheters became displaced and a new one had to be inserted during the study. Conclusion: Long-term self-administered home treatment with TEA seems to be an effective and safe adjuvant treatment for patients with refractory angina. It produces symptomatic relief of angina and improves the quality of life.
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- Svensson, Anders S., et al.
(author)
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Changes in serum cystatin C, creatinine, and C-reactive protein after cardiopulmonary bypass in patients with normal preoperative kidney function.
- 2016
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In: Nephrology (Carlton. Print). - : Wiley-Blackwell. - 1320-5358 .- 1440-1797. ; 21:6, s. 519-525
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Journal article (peer-reviewed)abstract
- AIM: The use of cardiopulmonary bypass (CPB) can cause changes in serum creatinine and cystatin C independent of glomerular filtration rate. We aimed to quantify the temporal changes of these biomarkers and C-reactive protein (CRP) after CPB.METHODS: This was a prospective study at an academic medical center between April and October 2013. We compared postoperative changes in serum creatinine and cystatin C in 38 patients with normal preoperative kidney function who underwent cardiac surgery using CPB and did not develop perioperative acute kidney injury (AKI). The effect of inflammation on intra-individual changes was examined in mixed effects regressions, using measurements of pre- and postoperative CRP.RESULTS: Both serum creatinine (79.9 ± 22.7 vs. 92.6 ± 21.4 µmol/L, p = 0.001) and cystatin C (1.16 ± 0.39 vs. 1.33 ± 0.37 mg/L, p = 0.012) decreased significantly in the first 8 hours postoperatively compared to preoperatively, as a result of hemodilution. Thereafter serum creatinine returned to preoperative levels, whereas serum cystatin C continued to rise and was significantly elevated at 72 hours post-CPB compared to preoperative levels (1.53 ± 0.48 vs. 1.33 ± 0.37 mg/L, p = 0.003). CRP levels increased significantly post-CPB and were significantly associated with increases in both serum creatinine and cystatin C.CONCLUSIONS: Serum creatinine and cystatin C appear not to be interchangeable biomarkers during and immediately after CPB. Processes unrelated to kidney function such as acute inflammation have a significant effect on post-CPB changes in these biomarkers, and may result in significant increases in serum cystatin C that could erroneously be interpreted as AKI. This article is protected by copyright. All rights reserved.
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- Svensson, Anders S., et al.
(author)
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Comparison of serum cystatin C and creatinine changes after cardiopulmonary bypass in patients with normal preoperative kidney function
- 2013
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In: International Urology and Nephrology. - : Springer Netherlands. - 0301-1623 .- 1573-2584. ; 45:6, s. 1597-1603
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Journal article (peer-reviewed)abstract
- PurposeSerum creatinine is used ubiquitously to estimate glomerular filtration rate and to diagnose acute kidney injury after cardiac surgery. Serum cystatin C is a novel biomarker that has emerged as a possible diagnostic alternative to serum creatinine. It is unclear if the dynamic changes in serum cystatin C immediately following cardiopulmonary bypass (CPB) differ from those of serum creatinine in patients with normal preoperative kidney function.MethodsWe compared changes in serum levels of creatinine and cystatin C by measuring them serially in 19 patients undergoing CPB. Within-patient differences for serum creatinine and serum cystatin C were compared by repeated measures ANOVA.ResultsSerum creatinine and cystatin C levels showed significant correlation with each other. Both biomarkers showed a significant decrease after CPB, but their serum concentrations reverted to pre-CPB levels within 12 h. Serum levels of serum creatinine remained unchanged from baseline levels throughout 72-h post-CPB. In contrast, serum cystatin C levels rose further and became significantly higher compared to baseline within 48 h. Serum cystatin C remained significantly elevated at 48- and 72-h post-CPB.ConclusionsProcesses that determine the serum concentrations of serum creatinine and cystatin C in the post-CPB period affect the two biomarkers differently, suggesting that the two are not interchangeable as diagnostic markers of glomerular filtration rate. Future studies are needed to examine if these discrepancies are related to differences in their production rates, in their ability to detect small changes in glomerular filtration rate, or to a combination of these, and to determine the effect of such differences on the diagnostic and prognostic accuracy of the two biomarkers.
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