[Cochrane group for anesthesia].
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Anesthesia↗
Biomedical subjects
T Pedersen
Publications and source records attributed to T Pedersen.
Evidence-based medicine and the Cochrane Collaboration in anaesthesia.
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Anesthesiology↗
The Cochrane Anaesthesia Review Group.
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Anesthesiology↗
[The effect of tobacco smoking on risks in connection in anesthesia and surgery. Development of complications and the preventive effect of smoking cessation].
About one third of the patients presenting for surgery are smokers. Smoking has acute and chronic effects on the cardiovascular, respiratory and immune systems, microcirculatory function and drug metabolism. Smoking is related to a wide range of per- and postoperative complications. Short term smoking cessation will probably reduce the disadvantageous acute effects of nicotine and carbon monoxide on the cardiovascular system, while the changes in lung function take about eight weeks to improve. Whether the rate of postoperative complications can be reduced by preoperative smoking cessation is unknown. The preoperative period might be a beneficial time for a greater smoking cessation intervention by an interdisciplinary hospital staff team.
Anesthesia↗
[Tobacco smoking among surgical patients. Smoking habits and information to smokers in Danish departments of anesthesiology].
Smoking is related to a wide range of intra- and post-operative complications. In relation to the idea of health promoting hospitals, we investigated how Danish departments of anaesthesia dealt with tobacco smoking and the surgical patient. We sent a questionnaire to 44 Danish departments of anaesthesia with seven questions about practical management of tobacco related problems in anaesthetic practice, the information of patients and the state of preventive initiatives. At about half of the departments patients are not asked about their smoking habits and at only seven departments is the patient given oral information about their increased intra- and postoperative risks. Half of the departments advocate smoking abstinence in the six fasting hours. Two departments offer assistance to preoperative smoking cessation within a scientific preventive project. In conclusion, the idea of prevention of intra- and postoperative complications by means of preoperative smoking cessation has not gained interest at Danish departments of anaesthesia so far.
Anesthesia Department, Hospital↗
Synthesis and in vitro evaluation of aminoacyloxyalkyl esters of 2-(6-methoxy-2-naphthyl)propionic acid as novel naproxen prodrugs for dermal drug delivery.
PURPOSE: To synthesize and evaluate various novel aminoacyloxyalkyl esters of naproxen (3a-i) and naproxenoxyalkyl diesters of glutamic and aspartic acids (3j-m) as potential dermal prodrugs of naproxen. METHODS: The prodrugs 3a-m were synthesized, and their aqueous solubilities, lipophilicities and hydrolysis rates were determined in a buffered solution and in human serum. The permeation of selected prodrugs across excised postmortem human skin was studied in vitro. RESULTS: The aminoacyloxyalkyl prodrugs showed higher aqueous solubilities and similar lipid solubilities, in terms of octanol-buffer partition coefficients (log Papp) at pH 5.0, when compared with naproxen. At pH 7.4 the prodrugs were significantly more lipophilic than naproxen. Prodrugs 3a-i showed moderate chemical stability in aqueous solutions at pH 5.0 and were rapidly converted to naproxen in human serum (t1/2 = 4-19 min). The selected aminoacyloxyalkyl prodrugs possessed a higher flux across the skin than naproxen, with a maximum enhancement of 3-fold compared to naproxen. Prodrugs 3j-m showed poor aqueous solubility and permeation across the skin. CONCLUSIONS: Combinations of adequate aqueous solubility and lipophilicity of naproxen aminoacyloxyalkyl prodrugs having fast rates of enzymatic hydrolysis resulted in improved dermal delivery of naproxen.
Anti-Inflammatory Agents, Non-Steroidal↗
In vitro evaluation of new surface coatings for extracorporeal circulation.
Cardiopulmonary bypass (CPB) exposes blood to large, foreign surfaces. This exposure may activate the cellular and humoral inflammatory systems, resulting in inflammatory reactions and organ dysfunction. Coating the inner surfaces of the bypass circuit may help alleviate these side-effects. The objective of this study was to determine the influence of two new surface treatments on blood cell and complement activation. Oxygenator and tubing sets coated with synthetic polymers (n = 7) or heparin (n = 7) were compared to uncoated sets (n = 7) in an in vitro model of CPB. The circuits were run at 4 l/min and recirculated for 120 min. The inflammatory response was assessed at regular intervals by platelet counts, and activation of complement, leucocytes and platelets. We found that the median platelet counts decreased from 127 to 122 x 10(9)/l (not significant, NS) in the synthetic polymer sets, from 96 to 88 x 10(9)/l (NS) in the heparin-coated sets, and from 93 to 54 x 10(9)/l (p < 0.01) in the uncoated sets after 2 h of recirculation. There were significant differences in platelet counts between the coated sets and the uncoated set at end of experiments (p < 0.05). Beta-thromboglobulin (BTG) concentrations increased in the synthetic polymer sets from 166 to 352 ng/ml (p < 0.01), in the heparin coated sets from 336 to 1168 ng/ml (p < 0.01), and in the uncoated sets from 301 to 3149 ng/ml (p < 0.01) after 2 h of recirculation. The differences in BTG at termination of the experiments were significant among all three sets (p < 0.05). Myeloperoxidase (MPO) concentrations in the synthetic polymer sets increased from 63 to 86 micrograms/l (p < 0.01), in the heparin-coated sets from 90 to 208 micrograms/l (p < 0.01), and in the uncoated sets from 122 to 513 micrograms/l (p < 0.01) after 2 h of recirculation. The differences in MPO at termination of the experiments were significant among all three groups (p < 0.01). There were no significant differences at termination of the experiments among the three sets regarding complement activation as measured by C3 activation products and the terminal complement complex. We conclude that in the current in vitro model of a CPB circuit, the synthetic polymer coating and the heparin coating caused significantly less platelet loss and granulocyte and platelet activation than the uncoated surface (p < 0.05). The synthetic polymer coating caused significantly less granulocyte and platelet activation than the heparin coating (p < 0.05). There was moderate complement activation within each group, but no significant differences among the three groups.
Complement Activation↗
Comparison of three oxygenator-coated and one total-circuit-coated extracorporeal devices.
The present study was designed to compare the biocompatibility of three cardiopulmonary bypass setups with different surface coatings, and to determine if coating of the whole circuit with one of the coatings was more beneficial than coating of the oxygenator only. Extracorporeal devices entirely coated with synthetic polymers (Avecor, n = 6) were compared to oxygenators coated with synthetic polymers (Avecor, n = 6), end-point, covalently attached heparin (CBAS, n = 6) or absorbed heparin (Duraflo 2, n = 6) in an in vitro model of a heart lung machine. The circuits were primed with fresh human whole blood and Ringer's acetate and recirculated at 4 l/min at 30 degrees C for 2 h. Test samples were obtained at regular intervals and analysed for myeloperoxidase (MPO), platelet counts, beta-thromboglobulin, heparin, prothrombin fragment 1+2, plasmin anti-plasmin complexes, and complement activation products. The mean MPO concentrations increased in the Avecor-coated oxygenator group (AV) from 247 at the start to 671 microg/l at the termination of the experiments, in the Avecor-coated total circuit group (AV-T) from 116 to 288 microg/l, in the Duraflo 2 coated oxygenator group (DU) from 160 to 332 microg/l, and in the CBAS-coated oxygenator (CA) group from 172 to 311 microg/l. The MPO concentrations increased significantly in all groups (p < 0.03). The increase in group A was significantly higher than in the other three groups (p = 0.007). The mean platelet counts decreased in the Avecor-coated total circuit group from 117 at start to 99 x 10(9)/l at termination of the experiments, in the Avecor-coated oxygenator group from 119 to 103 x 10(9)/l, in the Duraflo 2 group from 96 to 86 x 10(9)/l, and in the CBAS group from 132 to 123 x 10(9)/l. The platelet counts decreased significantly in all groups (p < 0.01), but the intergroup differences were not significant (p = 0.15). The mean beta-thromboglobulin concentrations increased in the Avecor-coated total circuit group from 193 at the start to 754 ng/ml at the termination of the experiments, in the Avecor-coated oxygenator group from 474 to 1654 ng/l, in the Duraflo 2 group from 496 to 1280 ng/l, and in the CBAS group from 418 to 747 ng/l. The beta-thromboglobulin increase was significant in each group (p < 0.01), but not between the groups (p = 0.49). The mean heparin concentrations in the Duraflo 2 group increased from 2460 at the start to 2897 IU/l at termination of the experiments, in the CBAS group from 2468 to 2518 IU/l. In the Avecor-coated oxygenator group heparin concentrations decreased from 2010 to 1968 IU/l, and in the Avecor-coated total circuit group from 2002 to 1927 IU/l. The differences in heparin concentrations were significant between the Duraflo 2 group and the other groups (p < 0.05). The mean prothrombin fragment 1+2 concentrations increased in the CBAS group from 0.4 at the start to 2.1 nmol/l at the end of the experiments, in the Avecor-coated oxygenator group from 0.4 to 0.6 nmol/l, in the Avecor-coated total circuit group from 0.3 to 0.4 nmol/l, and in the Duraflo 2 group from 1.2 to 1.3 nmol/l. The prothrombin fragment 1+2 increase was significant in all groups (p < 0.05), but there were no significant intergroup differences (p = 0.54). There were no significant differences at the termination of the experiments among the four groups regarding complement activation as measured by C3 activation products and the terminal complement complex. In the present in vitro model of a heart-lung machine, none of the three specific setups with different coatings was superior with regard to all test parameters. The CBAS group generated the highest levels of prothrombin fragment 1+2 formation, but least complement activation. The increasing plasma heparin concentrations in the Duraflo 2 group indicated more unstable heparin bonding. The Avecor-coated total circuit group were superior to the Avecor-coated oxygenator group regarding plasma concentrations of MPO, but not compa
Antifibrinolytic Agents↗
Thyroid function during and after cardiopulmonary bypass in children.
BACKGROUND: The aim of the study was to elucidate the changes in thyroid function during and after cardiopulmonary bypass (CPB) in children. METHODS: Triiodothronine (T3), thyroxine (T4), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were determined preoperatively, at specific times throughout CPB, and serially up to 48 h postoperatively, in 10 children (median age 35, range 23-68 months) undergoing elective surgery for congenital heart disease. RESULTS: T3 decreased from 2.01 +/- 0.08 preoperatively to 0.94 +/- 0.10 nmol/l 24 h postoperatively (P < 0.05). T4 levels followed a pattern similar to changes in T3. FT4 increased from 17.4 +/- 0.7 preoperatively to 30.0 +/- 0.4 pmol/l after 30 min of CPB (P < 0.05). TSH decreased from 2.44 +/- 0.43 preoperatively to 0.93 +/- 0.21 24 h postoperatively (P < 0.05). CONCLUSION: T3, T4 and TSH are significantly depressed after open heart surgery in children.
Cardiopulmonary Bypass↗
Leucocyte filtration during cardiopulmonary bypass hardly changed leucocyte counts and did not influence myeloperoxidase, complement, cytokines or platelets.
In some patients, coronary artery bypass surgery induces postoperative organ dysfunction despite an apparently adequate revascularization and good haemodynamic performance. This complication may be caused by activation of the body's inflammatory systems on blood contact with large foreign surfaces in the extracorporeal circuit. Activated leucocytes may play an important role in organ damage, and it is conceivable that leucocyte removal by filtration may decrease the potential side-effects of cardiopulmonary bypass (CPB). The aim of the present study was to investigate possible effects of leucocyte filtration during the whole CPB period in elective coronary artery bypass surgery on biochemical and clinical parameters. Forty patients were randomized to extracorporeal circulation using a leucocyte-depleting filter (group L, n = 20) or to extracorporeal circulation with no leucocyte filter (group C, n = 20). In the leucocyte-depleted group, the mean total white blood cell counts increased from 6.3 (95% confidence interval, 5.5-7.0) x 10(9)/l to 7.0 (5.7-8.3) x 10(9)/l during extracorporeal circulation and in the control group from 6.3 (5.2-7.3) x 10(9)/l to 8.5 (7.2-9.8) x 10(9)/l. The intergroup difference was not statistically significant (p = 0.84). A substantial increase in concentrations of interleukin-6, myeloperoxidase and complement activation products were observed in both groups without statistically significant intergroup differences. It is concluded that the leucocyte-depletion filter did not cause a significant reduction of circulating white blood cells during CPB, and there were no significant differences between the groups with respect to the inflammatory markers studied.
Aged↗
A controlled, prospective, 1-year trial of citalopram in the treatment of panic disorder.
BACKGROUND: The objective of this study was to evaluate the efficacy and tolerability of citalopram in the long-term treatment of adult outpatients with panic disorder with or without agoraphobia. METHOD: Patients in this double-blind, parallel-group trial were assigned to 1 of 3 fixed dosage ranges of citalopram (10 or 15 mg/day, 20 or 30 mg/day, or 40 or 60 mg/day), 1 dosage range of clomipramine (60 or 90 mg/day), or placebo. After the completed 8-week acute treatment period, the eligible patients could continue the treatment for up to 1 year. Of the 475 patients who were randomly assigned for the short-term trial, 279 agreed to continue double-blind treatment at their assigned doses. The primary efficacy measure used was the Clinical Anxiety Scale panic attack item, and the response was defined as no panic attacks (score of 0 or 1). The other key measures used were the Physician's Global Improvement Scale, the Patient's Global Improvement Scale, and the Hamilton Rating Scale for Anxiety (HAM-A). RESULTS: In all drug-treated groups, except the group receiving the lowest citalopram dose, the treatment outcome was generally better than with placebo. As determined by a life table analysis of response, the probability of response during the 12 months was significantly greater with all treatment regimens than with placebo (p < .05), with citalopram 20 or 30 mg/day demonstrating the best response. Panic attacks tended to disappear in all patients remaining in the study until the end of follow-up. Analysis of the difference in the number of patients in different treatment groups remaining in the study (perhaps the best measure of long-term efficacy) also demonstrated that the patients treated with citalopram in dosage ranges of 20 or 30 mg/day and 40 or 60 mg/day had better response than placebo-treated patients (p < .0002 and p < .004, respectively). HAM-A and Global Improvement Scale scores also showed that patients treated with active drug showed greater improvement than placebo-treated patients. All treatment groups showed no new or exceptional adverse event clusters. CONCLUSION: Citalopram in the dosage range of 20 to 60 mg/day is effective, well tolerated, and safe in the long-term treatment of patients who have panic disorder.
Adolescent↗
Microvesicles bind soluble fibrinogen, adhere to immobilized fibrinogen and coaggregate with platelets.
In the present study we have investigated whether platelet derived microvesicles can bind soluble fibrinogen, bind to immobilized fibrinogen, and coaggregate with platelets. Flow cytometry was used for studies on binding of soluble fibrinogen and coaggregation, whereas ELISA wells were used to study binding of microvesicles to immobilized fibrinogen. Biotinylated microvesicles produced by stimulation with A23187, thrombin or SFLLRN of platelets which had been surface-labelled with biotin, were used both for the coaggregation experiments and for the binding studies with immobilized fibrinogen. Unlabelled microvesicles and biotinylated fibrinogen were employed when studying binding of soluble fibrinogen to the microvesicles. For the flow cytometry, the biotinylated proteins were reacted with avidin or streptavidin which was PE-conjugated, whereas the same substances were conjugated with alkaline phosphatase for the ELISA studies. The microvesicles formed after stimulation of platelets by SFLLRN or A23187 clearly bound the soluble, biotinylated fibrinogen. Moreover, isolated biotinylated microvesicles added to washed platelets prior to activation, were associated to the microaggregates that formed after stimulation. A significant binding of biotinylated microvesicles to immobilized fibrinogen could also be detected. The binding of microvesicles to soluble and immobilized fibrinogen and association to platelets was clearly specific and at least partly dependent on the GPIIb-IIIa complex, as all of these phenomena could be prevented or reduced by addition of the c7E3 Fab which blocks the activated form of this receptor complex. From these in vitro results it is clear that microvesicles can bind to immobilized fibrinogen, bind soluble fibrinogen and are able to coaggregate with platelets. It may be speculated that these results also reflect a haemostatic role of microvesicles in vivo.
Blood Platelets↗
Cholesterol-lowering therapy in women and elderly patients with myocardial infarction or angina pectoris: findings from the Scandinavian Simvastatin Survival Study (4S)
BACKGROUND: The Scandinavian Simvastatin Survival Study (4S) demonstrated pronounced reductions in mortality and major coronary events in a cohort of patients with established coronary heart disease (CHD). The present study provides a detailed, post hoc assessment of the efficacy and safety of simvastatin therapy in the following subgroups of 4S patients: those > or = 65 years of age, those < 65 years of age, women, and men. METHODS AND RESULTS: The 4S cohort of 4444 CHD patients included 827 women and 1021 patients > or = 65 years of age. Total cholesterol at baseline was 5.5 to 8.0 mmol/L with triglycerides < or = 2.5 mmol/L. Patients were randomized to therapy with simvastatin 20 to 40 mg daily or placebo for a median follow-up period of 5.4 years. End points consisted of all-cause and CHD mortality, major coronary events (primarily CHD death and nonfatal myocardial infarction), other acute CHD and atherosclerotic events, hospitalizations for CHD and cardiovascular events, and coronary revascularization procedures. Mean changes in serum lipids were similar in the different subgroups. In patients > or = 65 years of age in the simvastatin group, relative risks (95% confidence intervals) for clinical events were as follows: all-cause mortality, 0.66 (0.48 to 0.90); CHD mortality, 0.57 (0.39 to 0.83); major coronary events, 0.66 (0.52 to 0.84); any atherosclerosis-related event, 0.67 (0.56 to 0.81); and revascularization procedures, 0.59 (0.41 to 0.84). In women, the corresponding figures were 1.16 (0.68 to 1.99); 0.86 (0.42 to 1.74), 0.66 (0.48 to 0.91), 0.71 (0.56 to 0.91), and 0.51 (0.30 to 0.86), respectively. CONCLUSIONS: Cholesterol lowering with simvastatin produced similar reductions in relative risk for major coronary events in women compared with men and in elderly (> or = 65 years of age) compared with younger patients. There were too few female deaths to assess the effects on mortality in women. Because mortality rates increased substantially with age, the absolute risk reduction for both all-cause and CHD mortality in simvastatin-treated subjects was approximately twice as great in the older patients.
Adult↗
[Is behaviorism dangerous for nursing?].
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Behaviorism↗
[We will produce behavior].
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Behavior Therapy↗
[Continuing medical education via questionnaire studies. Three pilot projects for anesthesiology, cardiology and neurology].
The Danish Medical Association and the scientific societies have initiated three studies to evaluate the use of questionnaires for continuous medical education. One study was a questionnaire in anaesthesiology with 30 questions with answers yes/no/no answer, which was sent to 600 specialists in anaesthesiology. One study was in cardiology with a multiple choice questionnaire, sent to 300 general practitioners and 75 specialists in internal medicine outside cardiology. One study concerned the educational value of State-of-the-Art articles about neurology in Ugeskrift for Laeger (Journal of the Danish Medical Association) sent to 500 doctors outside neurology. All questionnaires were sent anonymously, with one general reminder. For the anaesthesiology study 234 questionnaires were returned (40.5%). In the cardiology study 195 questionnaires were returned (52%). For the study on neurology 278 answered (56%). Only about half of the questionnaires were returned for the three studies, and a lot of effort and resources were put into the studies. An extension from these small pilot studies to a general systematic continuous methodology with updated questionnaires in the postgraduate medical education seems troublesome. An optional self-registration for medical education such as The Canadian "Mocomp concept" might be a more realistic suggestion.
Anesthesiology↗
Putting low-density lipoproteins at center stage in atherogenesis.
This article argues that major risk factors such as diabetes or hypertension increase the risk of vascular disease principally by amplifying the malign interactions of low-density lipoprotein (LDL) particles with the arterial wall and, consequently, that LDL is the first and foremost factor in the pathogenesis of vascular disease. We conclude that marked reduction of the LDL particle number should be the cornerstone of therapy in those with vascular disease or in those at high risk of vascular disease.
Apolipoproteins B↗
Percutaneous technique for venovenous bypass including a heat exchanger is safe and reliable in liver transplantation.
We have introduced and evaluated several modifications of the conventional venovenous bypass (VVBP) in 29 adult patients undergoing liver transplantation (OLT). A percutaneous technique for insertion of a jugular venous return cannula and a femoral vein cannula was applied. The inferior mesenteric vein (IMV) was used for splanchnic decompression, which facilitated dissection of the recipient liver and allowed portal anastomosis to be performed without disconnecting the portal bypass. A heat exchanger was introduced into the bypass circuit to prevent heat loss. The percutaneous technique prevented complications related to dissection in the axilla and groin. Hemodynamic characteristics corresponded to those found using the traditional technique. Complications related to the VVBP were seen in only one patient in whom the femoral catheter was accidentally introduced into the femoral artery. We conclude that percutaneous cannulas, use of the IMV for splanchnic decompression and the introduction of a heat exchanger offer significant benefits and that they are safe and reliable.
Adult↗