Publications by authors named "Helfried Metzler"

31 Publications

Platelet Inhibition and Bleeding in Patients Undergoing Non-Cardiac Surgery-The BIANCA Observational Study.

Thromb Haemost 2018 05 6;118(5):864-872. Epub 2018 Apr 6.

Inova Center for Thrombosis Research and Drug Development, Inova Heart and Vascular Institute, Falls Church, Virginia, United States.

Nearly 20% of patients will need non-cardiac surgery within 1 year of coronary stenting and their management is complicated by concomitant antiplatelet therapy. Platelet function testing may optimize the timing of surgery in these patients. In this prospective observational study, we explored the association between platelet reactivity and bleeding in patients undergoing non-cardiac surgery treated with clopidogrel with or without aspirin within 7 days before surgery. The timing of surgery was at the surgeon's discretion. Blood was drawn at induction of anaesthesia and platelet reactivity assessed by light transmittance aggregometry (LTA), vasodilator stimulated phosphoprotein (VASP) assay, Multiplate Analyzer and Innovance PFA-200. The primary endpoint was surgery-related thrombolysis in myocardial infarction (TIMI) bleeding. Among 197 patients enrolled, 72 and 12% underwent surgery within 24 and 48 hours of the last dose of clopidogrel, respectively. The median (interquartile range [IQR]) for pre-operative maximal adenosine diphosphate (ADP)-induced aggregation was 33.0% (21.0-57.5%), for VASP-platelet reactivity index was 61.5% (40.1-75.4%), for Multiplate was 22.0 (14.5-36.0) U*min and for Innovance PFA-200 was 224 (101.0-300.0) seconds. TIMI bleeding, observed in 25% of patients, decreased with increasing tertiles of platelet reactivity to ADP assessed by LTA ( = 0.031). Additionally, in a multivariable logistic regression analysis, platelet reactivity to ADP assessed by LTA was significantly associated with TIMI bleeding, as were age and urgency of surgery. These results demonstrate that in clopidogrel-treated patients, pre-operative platelet reactivity to ADP is associated with surgical bleeding risk. An objective assessment of pre-operative platelet function may optimize the timing of non-cardiac surgery in these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0038-1641153DOI Listing
May 2018

Pneumatic tube system transport does not alter platelet function in optical and whole blood aggregometry, prothrombin time, activated partial thromboplastin time, platelet count and fibrinogen in patients on anti-platelet drug therapy.

Biochem Med (Zagreb) 2017 Feb;27(1):217-224

Clinical Institute of Medical and Laboratory Diagnostics, Medical University Graz, Graz, Austria; Research Unit "Perioperative Platelet Function", Medical University of Graz, Graz, Austria.

Introduction: The aim of this study was to assess pneumatic tube system (PTS) alteration on platelet function by the light transmission aggregometry (LTA) and whole blood aggregometry (WBA) method, and on the results of platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen.

Materials And Methods: Venous blood was collected into six 4.5 mL VACUETTE® 9NC coagulation sodium citrate 3.8% tubes (Greiner Bio-One International GmbH, Kremsmünster, Austria) from 49 intensive care unit (ICU) patients on dual anti-platelet therapy and immediately hand carried to the central laboratory. Blood samples were divided into 2 Groups: Group 1 samples (N = 49) underwent PTS (4 m/s) transport from the central laboratory to the distant laboratory and back to the central laboratory, whereas Group 2 samples (N = 49) were excluded from PTS forces. In both groups, LTA and WBA stimulated with collagen, adenosine-5'-diphosphate (ADP), arachidonic acid (AA) and thrombin-receptor-activated-peptide 6 (TRAP-6) as well as platelet count, PT, APTT, and fibrinogen were performed.

Results: No statistically significant differences were observed between blood samples with (Group 1) and without (Group 2) PTS transport (P values from 0.064 - 0.968). The AA-induced LTA (bias: 68.57%) exceeded the bias acceptance limit of ≤ 25%.

Conclusions: Blood sample transportation with computer controlled PTS in our hospital had no statistically significant effects on platelet aggregation determined in patients with anti-platelet therapy. Although AA induced LTA showed a significant bias, the diagnostic accuracy was not influenced.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11613/BM.2017.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5382865PMC
February 2017

[Periprocedual management of vitamin K antagonist's with low molecular weight heparins during invasive procedures--Consensus of experts].

Wien Klin Wochenschr 2013 Jul;125(13-14):412-20

AKH Wien, Univ.-Klinik für Innere Medizin I, Währinger Gürtel 18–20, 1090 Wien, Österreich.

Interruption of an ongoing therapy with vitamin K antagonists (VKAs) is necessary in almost all patients undergoing major surgery. The purpose of the following expert recommendations is to provide easy to use guidance for the periprocedural management of patients on VKAs based on current evidence from the literature. Management of anticoagulation during the time of interruption of VKAs is based on balancing the thromboembolic (TE) risk of underlying conditions against the bleeding risk of the surgical procedure. VKAs should be stopped 3–7days prior to surgery. Low molecular weight heparin (LMWH) is used to cover (“bridge”) the progressive pre-operative loss of anticoagulation and the slow post-operative onset of anticoagulant activity of VKAs. Patients with high risk of TE should receive a therapeutic dose of LMWH, patients with a moderate risk of TE should receive half of this dose. Patients with a low risk of TE do not need bridging therapy with LMWH. In case of an uneventful postoperative course, patients with a therapeutic pre-operative dose should be treated post-operatively with the same dose, starting on day 4 in case of major surgery and on day 2 in case of minor procedures. Patients with a half-therapeutic preoperative dose should be treated post-operatively with the same dose, starting on day 3 in case of major surgery and on day 1 in case of minor procedures. Therapy with VKAs should be re-instituted on the second post-operative day based on the preoperative dosage. Procedure-related post-operative thromboprophylaxis should be given irrespective of these recommendations on days without “bridging” anticoagulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00508-013-0390-7DOI Listing
July 2013

Platelet function measurement-based strategy to reduce bleeding and waiting time in clopidogrel-treated patients undergoing coronary artery bypass graft surgery: the timing based on platelet function strategy to reduce clopidogrel-associated bleeding related to CABG (TARGET-CABG) study.

Circ Cardiovasc Interv 2012 Apr 6;5(2):261-9. Epub 2012 Mar 6.

Sinai Center for Thrombosis Research, Baltimore, MD 21215, USA.

Background: Aspirin and clopidogrel therapy is associated with a variable bleeding risk in patients undergoing coronary artery bypass graft surgery (CABG). We evaluated the role of platelet function testing in clopidogrel-treated patients undergoing CABG.

Methods And Results: One hundred eighty patients on background aspirin with/without clopidogrel therapy undergoing elective first time isolated on-pump CABG were enrolled in a prospective single-center, nonrandomized, unblinded investigation (Timing Based on Platelet Function Strategy to Reduce Clopidogrel-Associated Bleeding Related to CABG [TARGET-CABG] study) between September 2008 and January 2011. Clopidogrel responsiveness (ADP-induced platelet-fibrin clot strength [MA(ADP)]) was determined by thrombelastography; CABG was done within 1 day, 3-5 days, and >5 days in patients with an MA(ADP) >50 mm, 35-50 mm, and <35 mm, respectively. The primary end point was 24-hour chest tube drainage and key secondary end point was total number of transfused red blood cells. Equivalence was defined as ≤25% difference between groups. ANCOVA was used to adjust for confounders. Mean 24-hour chest tube drainage in clopidogrel-treated patients was 93% (95% confidence interval, 81-107%) of the amount observed in clopidogrel-naive patients, and the total amount of red blood cells transfused did not differ between groups (1.80 U versus 2.08 U, respectively, P=0.540). The total waiting period in clopidogrel-treated patients was 233 days (mean, 2.7 days per patient).

Conclusions: A strategy based on preoperative platelet function testing to determine the timing of CABG in clopidogrel-treated patients was associated with the same amount of bleeding observed in clopidogrel-naive patients and ≈50% shorter waiting time than recommended in the current guidelines.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00857155.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCINTERVENTIONS.111.967208DOI Listing
April 2012

Usefulness of pre-operative copeptin concentrations to predict post-operative outcome after major vascular surgery.

Am J Cardiol 2011 Oct 26;108(8):1188-95. Epub 2011 Jul 26.

3rd Department of Medicine, Cardiology and Emergency Medicine, Wilhelminenhospital, Vienna, Austria.

The aim of this study was to investigate whether preoperative determination of plasma copeptin levels in addition to plasma N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) could help improve risk stratification in patients who undergo major vascular surgery. One hundred ninety-eight consecutive patients who underwent major vascular surgery (58.6% infrainguinal aortic reconstruction, 23.7% abdominal aortic aneurysm surgery, 17.7% carotid endarterectomy) were included in this study. Patients were monitored for in-hospital and long-term (2-years) major adverse cardiac events, consisting of cardiac death, nonfatal myocardial infarction, and emergent coronary revascularization. Overall, 40 patients (20.2%) reached the primary end point, and most of these events occurred during the index hospital stay (n = 18 [45%]). In univariate Cox regression analysis, increasing concentrations of copeptin were significant determinants of outcome as a continuous variable (hazard ratio [HR] 1.012, p = 0.005) and as a dichotomized variable according to the recommended cutoff of 14.0 pmol/L (HR 4.116, p <0.001). Subgroup analyses revealed that especially patients at low estimated risk according to plasma NT-pro-BNP levels were at significantly higher risk for worse outcomes with higher copeptin levels (HR 5.983, p = 0.002). In multivariate Cox regression analysis, copeptin concentrations >14 pmol/L were significant independent predictors of outcome (HR 2.842, p = 0.002) in addition to type of surgery, history of myocardial infarction, elevated levels of cardiac troponin T, and NT-pro-BNP levels. In conclusion, the results of this study suggest that preoperative determination of this new biomarker could substantially improve prediction of perioperative and postoperative outcomes in vascular surgery patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjcard.2011.06.024DOI Listing
October 2011

Geographic differences in the target-controlled infusion estimated concentration of propofol: bispectral index response curves.

Can J Anaesth 2011 Apr 25;58(4):364-70. Epub 2011 Jan 25.

Department of Anaesthesiology and Intensive Care Medicine, Medical University of Graz, Auenbruggerplatz 29, 8036, Graz, Austria.

Purpose: Variability in drug responses could result from both genetic and environmental factors. Thus, drug effect could depend on geographic location, although regional variation is not generally acknowledged as a basis for stratification. There is evidence that the pharmacokinetic set developed in a European population for the target-controlled infusion (TCI) of propofol does not apply in Chinese patients; however, we are not aware of previous studies comparing the estimated concentration-bispectral index (BIS) response of Caucasian patients in Europe with that of Chinese patients in China.

Methods: The Diprifusor™ TCI pump, incorporating the pharmacokinetic model proposed by Marsh et al., was applied to 30 Caucasian patients in Austria and 30 Chinese patients in China. The estimated plasma concentration (C(p)) of propofol for the two groups was set at 1 μg·mL(-1) and increased by 1 μg·mL(-1) every minute to gradually reach 5 μg·mL(-1) after 5 min. The BIS values were fitted against the estimated C(p) and the predicted effect-site concentration (C(e)) in a sigmoid E(max) model.

Results: The sigmoid E(max) curves were shifted significantly to the left in the Chinese group compared with the Austrian group. After 5 min, the BIS value in the Chinese group was lower than in the Austrian group (mean ± standard deviation [SD], 47.2 ± 3.6 vs 63.6 ± 5.4, respectively; P = 0.0006). The estimated C(p) at loss of consciousness (LOC), predicted C(e) at LOC, and time to LOC, were lower in the Chinese group than in the Austrian group (3.3 ± 0.8 μg·mL(-1), 1.6 ± 0.4 μg·mL(-1), 2.8 ± 0.6 min, respectively, vs 4.6 ± 2.8 μg·mL(-1), 2.4 ± 1.5 μg·mL(-1), 3.9 ± 0.5 min, respectively; P < 0.0001).

Conclusion: When propofol is given using the same TCI protocol, Chinese patients in China lost consciousness faster and at a lower estimated plasma concentration than Caucasians in Austria. Larger studies are needed to map geographically appropriate TCI infusion models.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12630-011-9453-2DOI Listing
April 2011

Controversies in oral antiplatelet therapy in patients undergoing aortocoronary bypass surgery.

Ann Thorac Surg 2010 Sep;90(3):1040-51

Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria.

Oral antiplatelet therapy with aspirin and clopidogrel is a major strategy to prevent thrombotic events in patients with acute coronary syndromes and patients undergoing percutaneous coronary interventions. Although this therapy is associated with both short- and long-term clinical efficacy, irreversible platelet inhibition and ischemic events associated with premature withdrawal especially in patients treated with drug-eluting stents constitute a particular limitation in patients undergoing surgery. The current review article is focused on the central role of platelets in the occurrence of ischemic events, the significance of antiplatelet therapy, the potential hazards of drug withdrawal in patients needing coronary artery bypass grafting, and future perspectives.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.athoracsur.2010.04.041DOI Listing
September 2010

The utility of using the bispectral index-Vista for detecting cross-clamping decline in cerebral blood flow velocity.

Neurosurgery 2010 Sep;67(3 Suppl Operative):ons102-7; discussion ons107

Department of Anaesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria.

Background: Patients undergoing carotid endarterectomy for extracranial internal carotid artery stenosis are at risk of cerebral ischemia/hypoperfusion. Criterion recommended by European and American committees to determine whether to place a shunt consisted of a decline in transcranial Doppler ultrasonography-measured middle cerebral artery blood flow velocity (MCBFV) to < 30% to 40% of intraoperative preclamp value.

Objective: To assess the discriminative power of the bispectral index (BIS)-Vista monitor for detecting a 40% decline in MCBFV with cross-clamping.

Methods: In 20 patients undergoing carotid endarterectomy under remifentanil/propofol anesthesia, BIS-Vista data, MCBFV, and pulsatility index from bilaterally mounted BIS-Vista and transcranial Doppler monitors were continuously recorded.

Results: Coefficient of determination revealed good correlation (r = 0.763) between ipsilateral BIS-Vista and MCBFV after cross-clamping. BIS-Vista exhibited a high discriminative power of 0.850 (95% confidence interval, 0.455-0.966) area under the receiver-operating characteristic curve in detecting an ipsilateral 40% MCBFV decline. Two-way analysis of variance (location by time) suggests that BIS-Vista exhibited a global decline; ie, both BIS-Vistas declined when 1 carotid on either side was clamped because there was no significant interhemispheric difference (P = .112) in mean BIS-Vista values over time.

Conclusion: Although we demonstrated good correlation and high discriminative power of the BIS-Vista monitor in depicting a MCBFV decline that could serve as indicator of decline in cerebral activity, BIS-Vista cannot be considered a reliable indicator of cerebral ischemia/hypoperfusion that could replace transcranial Doppler monitoring to determine whether a shunt is to be placed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1227/01.NEU.0000383152.50183.81DOI Listing
September 2010

BIS-vista occipital montage in patients undergoing neurosurgical procedures during propofol-remifentanil anesthesia.

Anesthesiology 2010 Mar;112(3):645-51

Department of Anaesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria.

Background: Neurosurgical procedures that require a frontal approach could be an impediment for a successful Bispectral Index (BIS) frontal sensor placement. The aim of this study was to explore the utility of using the new BIS-Vista monitor (Aspect Medical Systems, Newton, MA) for occipital sensor placement in the patients undergoing brain neurosurgical procedures during propofol-remifentanil anesthesia.

Methods: Two BIS Quatro sensors (Aspect Medical Systems, Newton, MA) mounted on the occipital and frontal regions were connected to two BIS-Vista monitors at three anesthesia states: before induction, during anesthesia maintenance, and recovery.

Results: There were significant differences before induction (P = 0.0002) and at anesthesia maintenance (P = 0.0014) between mean +/- SD occipital (83.4 +/- 4.8, 66.7 +/- 7.2) and frontal (93.1 +/- 3.4, 56.9 +/- 9.1) BIS-Vista values. During anesthesia recovery, there was no difference (P = 0.7421) between occipital (54.6 +/- 9.3) and frontal (53.1 +/- 7.3) BIS-Vista values. Bland and Altman analysis revealed a BIS-Vista negative-bias (limits of agreement) of -9.7 (+1.1, -20.5) before anesthesia induction, +9.8 positive-bias (+22.8, -1.7) during anesthesia maintenance, and -0.9 bias (+10.9, -12.8) during anesthesia recovery.

Conclusion: We demonstrated that not only the regional limits of agreement are too wide to allow data of the two montages to be used interchangeably but also the variation is a function of anesthetic depth. However, keeping in mind a relatively consistent BIS-Vista -10 bias before induction and +10 bias during anesthesia maintenance with limits of agreement of approximately +/-11 BIS units, approximately double the clinically acceptable less than 10 BIS units level of agreement, BIS-Vista off-label occipital montage might be helpful in following a trend of propofol-remifentanil anesthesia in individual cases where frontal access is particularly difficult.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/ALN.0b013e3181cf4111DOI Listing
March 2010

The patient with coronary stents and antiplatelet agents: what to do and how to deal?

Eur J Anaesthesiol 2010 May;27(5):406-10

Department of Anaesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria.

The management of patients with recent coronary artery stents presenting for noncardiac surgery has become a major topic of interest and concern for all perioperative care givers. The present review will update recent reports and particularly new guidelines as well as recommendations. Based on the available literature, all experts recommend avoiding premature discontinuation of antiplatelet drug therapy if possible except for a few surgical procedures. Drug-eluting stents obviously carry more risks than bare-metal stents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/EJA.0b013e328335b284DOI Listing
May 2010

Premature preoperative discontinuation of antiplatelet drug therapy in cardiovascular risk patients: a preliminary study on the role of P2Y12 receptor monitoring.

Eur J Anaesthesiol 2010 Feb;27(2):138-45

Department of Anaesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria.

Background And Objective: In high-bleeding risk procedures, discontinuation of antiplatelet drug therapy with clopidogrel may be requested by surgeons, usually 7-10 days before the surgical procedure. New platelet function tests, such as the vasodilator-stimulated phosphoprotein phosphorylation assay, may help to assess the perioperative status of the clopidogrel-specific P2Y12 receptor.

Methods: Using vasodilator-stimulated phosphoprotein phosphorylation assay, the platelet reactivity index (PRI) was measured in 80 individuals, including 20 healthy volunteers, 20 cardiologic patients under full antiplatelet drug therapy with clopidogrel and aspirin, 20 surgical patients without any antiplatelet drugs and 20 patients under clopidogrel, discontinued 7 days before the surgical procedure.

Results: The mean PRI (95% confidence interval) in healthy volunteers was 86 (82-89%) and that in the surgical control group was 77% (72-81%). In cardiologic patients under full antiplatelet therapy, mean PRI was 51% (42-60%). In the clopidogrel discontinuation group, PRI increased from 51% (40-62%) on day 0 to 65% (57-74%) on day 3 and to 76% (69-84%) on day 5. On the morning of surgery, mean PRI was 85% (80-91%). The PRI values on the 5th day were equivalent to those of the surgical control group (mean difference -0.4%, 95% confidence interval -8.6% to 7.8%, P = 0.9). Fifty-five percent of the patients in the discontinuation group had a PRI of more than 50% on day 0.

Conclusion: The study using vasodilator-stimulated phosphoprotein phosphorylation assay, one of the new platelet function assays for the assessment of inhibition of platelet P2Y12 receptor, demonstrates that the PRI on day 5 after discontinuation of clopidogrel is equivalent to a surgical control group and it questions the rigid practice of delaying surgery for 7-10 days, particularly in patients without a clopidogrel effect.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/EJA.0b013e32832eb521DOI Listing
February 2010

Effect of flumazenil on bispectral index monitoring in unpremedicated patients.

Anesthesiology 2009 May;110(5):1036-40

Department of Anaesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria.

Background: Flumazenil is an imidazobenzodiazepine that promptly reverses via competitive inhibition the hypnotic/sedative effects of benzodiazepines on gamma-aminobutyric acid receptors. Endogenous benzodiazepine ligands (endozepines) were isolated in urine, cerebrospinal fluid, and breast milk of women who had not received benzodiazepines. The bispectral index (BIS), an electroencephalographically derived parameter widely used for monitoring the effects of anesthetic/hypnotic drugs, was shown to correlate to various conditions that could influence electroencephalography. The authors examined the hypothesis that 0.5 mg of flumazenil administered to healthy unpremedicated patients during deep surgical remifentanil/propofol anesthesia would increase the BIS value and might expedite recovery from anesthesia.

Methods: Sixty healthy unpremedicated patients were randomly allocated to the flumazenil or control groups. After study drug administration, the authors compared BIS values and various recovery parameters in the flumazenil and control groups.

Results: BIS baseline values in the flumazenil group (38.7 +/- 3.8) increased 15 min after flumazenil administration (53.2 +/- 4.7), with a significant difference over time (P < 0.0001) between the two groups. Mean recovery parameters time, comprising time to spontaneous breathing, eye opening/hand squeezing on verbal command, extubation, and date of birth recollection, was significantly shorter (P = 0.0002) in the flumazenil group (6.9 +/- 2.6 min) compared with the control group (9.8 +/- 2.9 min).

Conclusions: This study demonstrates that flumazenil given to healthy unpremedicated patients during propofol/remifentanil anesthesia significantly increased the BIS value and allowed earlier emergence from anesthesia. This may indicate that flumazenil could be used on a case-by-case basis to reverse endogenous or exogenous endozepines that might play a role during anesthesia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/ALN.0b013e31819db2c4DOI Listing
May 2009

The effects of fibrinogen levels on thromboelastometric variables in the presence of thrombocytopenia.

Anesth Analg 2009 Mar;108(3):751-8

Department of Anesthesiology, Medical School, Hannover, Germany.

Background: The binding of fibrinogen and fibrin to platelets is important in normal hemostasis. The extent of platelet-fibrin interaction can be measured as the viscoelastic strength of clot by rotational thromboelastometry (ROTEM). In this study, we investigated the effect of fibrinogen concentration and its relative contribution to overall clot strength using ROTEM.

Methods: Blood samples were collected from healthy volunteers. The effects of platelet count on clot strength, determined by maximum clot elasticity (MCE), were evaluated on ROTEM using platelet-rich plasma (PRP) adjusted with autologous plasma to generate a range of platelet counts. PRPs were adjusted to 10 x 10(3) mm(-3), 50 x 10(3) mm(-3), and 100 x 10(3) mm(-3) and spiked with fibrinogen concentrates at 550 and 780 mg/dL. The effect of fibrin polymerization on clot strength, independent of platelet attachment, was analyzed by the cytochalasin D-modified thromboelastometry (FIBTEM) method. Additional retrospective analysis of clot strength (MCE) in two groups of thrombocytopenic patients was conducted.

Results: Clot strength (MCE) decreased at a platelet count below 100 x 10(3) mm(-3), whereas increases in MCE peaked and reached a plateau at platelet counts from 400 x 10(3) mm(-3). Increasing fibrinogen concentrations in PRP increased clot strength in a concentration-dependent manner, even at low platelet counts (10 x 10(3) mm(-3)). The positive correlation between clot strength and plasma fibrinogen level was also confirmed in the analysis of the data obtained from 904 thrombocytopenic patients.

Conclusions: These in vitro and clinical data indicate that the clot strength increases in a fibrinogen concentration-dependent manner independent of platelet count, when analyzed by ROTEM. The maintenance of fibrinogen concentration is critical in the presence of thrombocytopenia. EXTEM (extrinsic activation) and FIBTEM may be useful in guiding fibrinogen repletion therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1213/ane.0b013e3181966675DOI Listing
March 2009

Bispectral index monitoring of a narcolepsy-cataplexy episode during regional anesthesia.

Anesth Analg 2009 Feb;108(2):613-5

Department of Anaesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria.

Narcolepsy or Gélineau syndrome is an extremely incapacitating chronic sleep disorder of unknown etiology that is characterized by uncontrollable attacks of deep sleep and is typically associated with cataplexy sudden loss of muscle tone. The Bispectral Index (BIS), an electroencephalographic-derived cerebral monitor, used for monitoring the effects of anesthetic/hypnotic drugs was shown to correlate to various conditions that could influence the eletroencephalogram. We assessed the utility of using BIS for monitoring a possible narcolepsy-cataplexy episode and whether a distinctive BIS profile might offer an early warning of an impending narcoleptic/cataplectic spell. We recorded both hemispheres, using two synchronized BIS-XP monitors, during a narcolepsy-cataplexy episode in a 57-yr-old male patient undergoing lower limb surgery under femoral nerve block regional anesthesia. The patient went through three stages: first a prodromal "intermittent low-vigilance" phase interrupted by high electromyographic activity. This was followed by a second "continuous low-vigilance" phase of BIS around 75 with low electromyographic activity, ending with a third "nonresponsive vigilance" phase of a full-blown narcolepsy-cataplexy episode of BIS around 45 with complete loss of muscle power. The purpose of presenting this report is to emphasize the fact that narcoleptic patients can still run the risk of loss of consciousness with atonia under regional anesthesia, and such an undesirable complication cannot be under-estimated. BIS monitoring is a simple method that could offer an early warning of an imminent episode, with its associated hazards, in patients with narcolepsy-cataplexy undergoing surgery under regional anesthesia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1213/ane.0b013e31818ec932DOI Listing
February 2009

Effect of somatostatin analogue octreotide on pain relief after major abdominal surgery.

Eur J Pain 2009 Sep 11;13(8):861-4. Epub 2008 Dec 11.

Department of Anaesthesiology and Intensive Care Medicine, Medical University of Graz, Auenbruggerplatz 29, A-8036 Graz, Austria.

Background: Octreotide acetate is an 8-amino-acids synthetic octapeptide analogue of somatostatin with much-enhanced duration of action and lower incidence of side effects. We assessed the utility of using intravenous octreotide as an adjuvant to opioid analgesia that might exert a post-operative opioid-sparing effect.

Methods: Forty-four patients were randomly allocated, to receive either a placebo or intraoperative octreotide 0.33 microg kg(-1)h(-1) intravenous infusion that was maintained in the post-operative period. Patients received for post-operative analgesia an intravenous piritramide patient controlled analgesia (PCA), set to deliver a piritramide 0.02 mgkg(-1) dose.

Results: Two-way ANOVA revealed significantly fewer (P=0.0003) mean+/-SD weighted piritramide dose requirements in the octreotide group (19.5+/-6.3 microg kg(-1)h(-1)) than in the control group (35.7+/-8.2 microg kg(-1)h(-1)). Dunnett's two-sided multiple-comparison post hoc test revealed a significant difference between the two groups during the first 22 post-operative hours, following which there were no differences between the two groups. There were no significant differences over time in the mean arterial pressure (P=0.722), heart rate (P=0.579) and respiratory rate (P=0.823) between the octreotide group (80+/-10mm Hg, 74+/-12, 14+/-2) and the control group (82+/-9 mm Hg, 76+/-11, 15+/-3), respectively.

Conclusion: We demonstrated that perioperative octreotide intravenous infusion could be an adjuvant to opioid analgesia as it exerted a piritramide opioid-sparing effect. We encountered more systemic side effects such as nausea, abdominal discomfort, and diarrhea in the octreotide group than in the control group. Our findings could be beneficial to patients who cannot tolerate the adverse effects of opioids.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejpain.2008.10.006DOI Listing
September 2009

Antiplatelet therapy and coronary stents in perioperative medicine--the two sides of the coin.

Best Pract Res Clin Anaesthesiol 2008 Mar;22(1):81-94

Department of Anaesthesiology and Intensive Core Medicine, Medical University of Graz, Auenbruggerplatz 29, A-8036 Graz, Austria.

New trends in interventional cardiology, e.g. the increasing practice of coronary intervention with stent implantation and the prolonged use of dual antiplatelet therapy--usually a combination of clopidogrel and aspirin--has also increased the number of patients presenting for non-cardiac surgery. The two most commonly used stent types, bare-metal stents (BMSs) and drug-eluting stents (DESs), mandate different lengths of dual antiplatelet drug therapy to avoid stent thrombosis. Perioperative caregivers face a knife-edge dilemma between perioperative stent thrombosis, due to preoperative discontinuation of antiplatelet drugs, or surgical bleeding, by continuation of therapy. Pre- and intraoperatively, the risk factors for thrombosis have to be balanced against the risk factors for surgical bleeding. As long as prospective trials are not available, the recommendations and guidelines of task forces and experts are based on retrospective studies and case reports. The perioperative management, decision trees and the importance of close interdisciplinary collaboration between cardiologists, surgeons and anaesthetists will be described.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bpa.2007.09.004DOI Listing
March 2008

Gastrointestinal motility in acute illness.

Wien Klin Wochenschr 2008 ;120(1-2):6-17

Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria.

Critical illness affects gastrointestinal motility - not only as a primary problem, which brings the patient to the intensive care unit (ICU), but also as a complication consecutive to the ICU stay. Motility disturbances may result from impaired function of gastrointestinal muscle, pacemaker cell function and nerve activity. The most important neural control system is the enteric nervous system that contains the largest collection of neurons (10(8) cells) outside the central nervous system. Through its organization it can operate independently of the brain and generate motility patterns according to need: a postprandial motility pattern starting after food intake, and an interdigestive motility pattern starting several hours after a meal. Undisturbed intestinal motility depends critically on a balanced interaction between inhibition and excitation, and a disturbance in this balance leads to severe derangements of intestinal motility. These motility disturbances differ in clinical appearance and location but can affect all parts of the gastrointestinal tract. This review focuses on select motility disturbances such as gastroparesis, postoperative ileus, and Ogilvie's syndrome. Generally effective methods to treat these conditions are given. Finally, we focus on special management options to prevent such motility disturbances or to reduce their severity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00508-007-0920-2DOI Listing
July 2008

Anaesthesia in patients with drug-eluting stents.

Curr Opin Anaesthesiol 2008 Feb;21(1):55-9

Department of Anaesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria.

Purpose Of Review: The management of patients with recent coronary artery stents presenting for noncardiac surgery has become a major topic of interest and concern for all perioperative caregivers. This review will update recent reports and particularly new guidelines as well as recommendations.

Recent Findings: Based on the available literature all experts recommend avoiding premature discontinuation of antiplatelet drug therapy if possible except for a few surgical procedures. Drug-eluting stents obviously carry more risks than bare-metal stents.

Summary: Anaesthesiologists may understand the specific problem of drug-eluting stents, the recent debate among cardiologists and the implications for the perioperative scenario.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/ACO.0b013e3282f357b6DOI Listing
February 2008

N-terminal pro-brain natriuretic peptide identifies patients at high risk for adverse cardiac outcome after vascular surgery.

Anesthesiology 2007 Jun;106(6):1088-95

Department of Anesthesiology and Intensive Care Medicine, Unit of Medical Engineering and Computing, Medical University of Graz, Austria.

Background: Preoperative N-terminal pro-BNP (NT-proBNP) is independently associated with adverse cardiac outcome but does not anticipate the dynamic consequences of anesthesia and surgery. The authors hypothesized that a single postoperative NT-proBNP level provides additional prognostic information for in-hospital and late cardiac events.

Methods: Two hundred eighteen patients scheduled to undergo vascular surgery were enrolled and followed up for 24-30 months. Logistic regression and Cox proportional hazards model were performed to evaluate predictors of in-hospital and long-term cardiac outcome. The optimal discriminatory level of preoperative and postoperative NT-proBNP was determined by receiver operating characteristic analysis.

Results: During a median follow-up of 826 days, 44 patients (20%) experienced 51 cardiac events. Perioperatively, median NT-proBNP increased from 215 to 557 pg/ml (interquartile range, 83/457 to 221/1178 pg/ml; P<0.001). The optimum discriminate threshold for preoperative and postoperative NT-proBNP was 280 pg/ml (95% confidence interval, 123-400) and 860 pg/ml (95% confidence interval, 556-1,054), respectively. Adjusted for age, previous myocardial infarction, preoperative fibrinogen, creatinine, high-sensitivity C-reactive protein, type, duration, and surgical complications, only postoperative NT-proBNP remained significantly associated with in-hospital (adjusted hazard ratio, 19.8; 95% confidence interval, 3.4-115) and long-term cardiac outcome (adjusted hazard ratio, 4.88; 95% confidence interval, 2.43-9.81).

Conclusion: A single postoperative NT-proBNP determination provides important additional prognostic information to preoperative levels and may support therapeutic decisions to prevent subsequent structural myocardial damage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/01.anes.0000267591.34626.b0DOI Listing
June 2007

Central pulmonary artery embolism after perihepatic packing because of liver trauma.

J Trauma 2007 Sep;63(3):E81-4

Department of Anesthesiology and Intensive Care Medicine, University of Graz, Graz, Austria.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/01.ta.0000246893.93386.e8DOI Listing
September 2007

Intestinal motility disturbances in intensive care patients pathogenesis and clinical impact.

Intensive Care Med 2007 Jan 18;33(1):36-44. Epub 2006 Nov 18.

Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Auenbruggerplatz 29, 8036, Graz, Austria.

Background: Gastrointestinal motility disturbances in critically ill patients are frequent in the ICU setting, causing considerable discomfort and are associated with increased rates of morbidity and mortality. This review focuses on the pathophysiological basis of intestinal motility, the major patterns of pathological motility alterations, the impact on patient outcome, and current therapeutic options.

Discussion: Intestinal motility is controlled by the enteric nervous system, modulated by hormones and extrinsic afferent and efferent neurons. Pathological motility disturbances can affect the stomach, small bowel, and colon separately or in combination. Changes in esophageal motor activity contribute to the aspiration of gastric juice, whereas early enteral feeding most frequently fails due to gastric intolerance. Disturbances in digestive and interdigestive motility patterns and the inability to switch motor activity from the interdigestive to the digestive pattern also contribute to feeding disability and thus to increased morbidity and mortality as well.

Conclusions: The therapeutic options for motility disturbances in critically ill patients include the adjustment of electrolyte imbalances, tailored fluid management, early enteral feeding, appropriate management of catecholamines and drugs used for analgosedation, and prokinetic drugs. Unfortunately, the therapeutic options for treating motility disturbances in ICU patients are still limited. This situation requires careful assessment of ICU patients with respect to gut motility disturbances and their pathophysiological mechanisms and an individually tailored treatment to prevent further aggravation of existing motility disturbances.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00134-006-0452-7DOI Listing
January 2007

Bispectral-index-guided versus clinically guided remifentanil/propofol analgesia/sedation for interventional radiological procedures: an observer-blinded randomized study.

Anesth Analg 2006 Aug;103(2):378-84, table of contents

Department of Anaesthesiology and Intensive Care Medicine, Graz Medical University, Graz, Austria. Auenbruggerplatz 29, A-8036, Graz, Austria.

Patients undergoing potentially painful interventional radiological procedures generally require a combination of analgesia and sedation. This sedation/analgesia should allow the patient to communicate while also remaining calm. Bispectral index (BIS) monitoring could be useful in achieving this. The primary end-point of our study was to compare the percentage time with optimal sedation, defined as Sedation Agitation Scale (SAS) grade 4, between a BIS-guided remifentanil/propofol regimen and a clinically guided regimen in 54 randomly allocated patients. The mean +/- sd percentage time with optimal sedation was significantly longer (P = 0.004) in the BIS group (76.6% +/- 14.7%) than in the SAS group (63.8% +/- 16.4%). There was a significant difference in the weighted mean infusion rates of remifentanil (P = 0.0067) and propofol (P = 0.0075) in the BIS group (0.066 +/- 0.027 microg.kg(-1) . min(-1) 1.59 +/- 0.44 mg.kg(-1) . h(-1)) compared with the SAS group (0.091 +/- 0.036 microg.kg(-1).min(-1) 1.92 +/- 0.43 mg.kg(-1).h(-1)), respectively. BIS values exhibited a temporal correlation to SAS scores (r2 = 0.72). In conclusion, a BIS-guided regimen was more effective than a SAS-guided regimen. The use of BIS resulted in fewer remifentanil and propofol doses. The targeted BIS range of 80-85 provided a sufficient functional level of sedation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1213/01.ane.0000223681.77120.caDOI Listing
August 2006

Geographic regional differences in rocuronium bromide dose-response relation and time course of action: an overlooked factor in determining recommended dosage.

Anesthesiology 2006 May;104(5):950-3

Department of Anaesthesiology and Intensive Care Medicine, Graz Medical University, Austria.

Background: Geographic location is not acknowledged as a stratifying factor that can directly affect drug potency, because drugs are still licensed with the same recommended dose for different geographic regions. The aim of the current study was to compare the potency and duration of action of rocuronium bromide in 54 patients in three countries with different life habits, diet, and ambient conditions, namely white Austrians, white North Americans, and Han Chinese in China.

Methods: Neuromuscular block of six consecutive 50-microg/kg rocuronium incremental doses followed by 300 microg/kg was evaluated using the Relaxometer mechanomyograph (Groningen University, Groningen, Holland). Dose-response curves were created using log-dose-probit transformation. The authors compared rocuronium bromide ED50, ED90, and ED95 (effective doses required for 50%, 90%, and 95% first twitch depression, respectively) as well as Dur25 and Dur0.8 (times from last incremental dose administration until 25% first twitch and 0.8 train-of-four ratio recovery, respectively) in patients of the three countries.

Results: Rocuronium ED50, ED90, and ED95 were significantly higher in Austrian patients (258 +/- 68, 530 +/- 159, and 598 +/- 189 microg/kg) and Chinese patients (201 +/- 59, 413 +/- 107, and 475 +/- 155 microg/kg) compared with American patients (148 +/- 48, 316 +/- 116, and 362 +/- 149 microg/kg, respectively). Dur25 and Dur0.8 were significantly shorter in Austrian patients (22.3 +/- 5.5 and 36.9 +/- 12.8 min) and Chinese patients (30.4 +/- 7.5 and 45.7 +/- 15.9 min) compared with American patients (36.7 +/- 8.5 and 56.2 +/- 16.7 min, respectively).

Conclusions: The authors demonstrated a significant difference in rocuronium potency and duration of action among patients in the three countries. Larger studies are required for determining dosage recommendations for different geographic regions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/00000542-200605000-00010DOI Listing
May 2006

Acute perioperative heart failure.

Curr Opin Anaesthesiol 2005 Apr;18(2):129-35

Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria.

Purpose Of Review: Changes in epidemiology and advances in the treatment of coronary artery disease, hypertension and diabetes mellitus have increased the prevalence of heart failure in the general population, and also the number of patients with heart failure presenting for surgery. Particularly in the perioperative period, patients with chronic heart failure are faced with numerous triggers of acute decompensation that can partly be avoided or treated. Patients without preexisting myocardial contractile dysfunction may sustain severe perioperative complications, e.g. myocardial infarction, with subsequent acute heart failure as a consequence. Approaches for diagnosis and treatment in these situations may vary considerably.

Recent Findings: Patients with preexisting heart failure undergoing non-cardiac surgery suffer substantial morbidity and mortality despite advances in perioperative care. The importance of heart failure as an independent risk factor is underlined by the fact that patients with coronary artery disease but without heart failure have a similar 30-day mortality rate to the general population. B-type natriuretic peptide testing is an attractive and non-invasive tool in non-surgical patients for the diagnosis of heart failure, but its role in the perioperative period for the diagnosis of myocardial contractile dysfunction is less clear. For inotropic support, levosimendan, a myofilament calcium sensitizer, has become available in several European countries, and encouraging positive reports have recently been published in this area.

Summary: The role of B-type natriuretic peptide testing in the perioperative period is confounded by several variables that limit its use in that setting. New developments in positive inotropic therapy are challenging older and potentially harmful treatment strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/01.aco.0000162830.59023.50DOI Listing
April 2005

Contractile action of levosimendan and epinephrine during acidosis.

Eur J Pharmacol 2005 Jan 24;507(1-3):199-209. Epub 2004 Dec 24.

Department of Anaesthesiology and Intensive Care Medicine, Medical University of Graz, Auenbruggerplatz 29, 8036-Graz, Austria.

We evaluated the inotropic actions of levosimendan and epinephrine, both singly and in combination, under isohydric (pH 7.4) and acidotic (pH 7.0) conditions in isolated guinea-pig hearts. Acidosis depressed contractility and myocardial relaxation by 25-30%, and both inotropes were less efficacious at pH 7.0, while their potencies were unaffected. In combination experiments, the presence of levosimendan increased the potency of epinephrine approximately 17-fold (pH 7.4) and 11-fold (pH 7.0), and the presence of epinephrine increased the potency of levosimendan approximately 12-fold (pH 7.4) and approximately 21-fold (pH 7.0). At pH 7.0, both inotropes augmented papillary muscle contraction to a similar extent, but in contrast to epinephrine, levosimendan non-significantly [corrected] raised cAMP levels. In conclusion, combining levosimendan with epinephrine helps to overcome the depressed inotropic actions of epinephrine during acidosis, suggesting that additional studies which might justify clinical evaluation of the concurrent use of the two agents should be performed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejphar.2004.11.049DOI Listing
January 2005

The effect of different stages of neuromuscular block on the bispectral index and the bispectral index-XP under remifentanil/propofol anesthesia.

Anesth Analg 2004 Sep;99(3):781-7, table of contents

Department of Anaesthesiology and Intensive Care Medicine, Faculty of Medicine, Karl-Franzens University, Auenbruggerplatz 29, A-8036 Graz, Austria.

Facial electromyographic activity and neuromuscular block could influence bispectral index (BIS) depth of anesthesia monitoring. In this study we examined, in 30 patients undergoing general surgical procedures, the effect of different stages of neuromuscular block on BIS monitoring and compared the conventional A-2000 BIS trade mark (BIS(3.4)) with the new BIS-XP trade mark (BIS(XP)). At deep surgical anesthesia BIS(3.4) of approximately 40, under a propofol 3.61 microg/mL target-controlled infusion and a 0.15-0.3 microg. kg(-1). min(-1) remifentanil infusion, mivacurium 0.15 mg/kg was administered. The onset of neuromuscular block triggered a brief transient odd divergence in response that manifested as a BIS(3.4) increase from 43 +/- 4 to 49 +/- 7 (P = 0.007) and a BIS(XP) decline from 41 +/- 3 to 35 +/- 3 (P = 0.003) at 1 +/- 0.2 min. Then, 2.5 +/- 1 min after mivacurium administration, both monitors returned to baseline values of 43 +/- 5 and 40 +/- 4, respectively. After that, BIS(3.4) and BIS(XP) did not significantly change during complete neuromuscular block or during various levels of neuromuscular recovery. At all phases, BIS(XP) was significantly lower than BIS(3.4). Our study indicated that the BIS(3.4)/BIS(XP) bias and the wide limits of agreement do not allow values given by the two monitors to be used interchangeably.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1213/01.ANE.0000132997.19872.BCDOI Listing
September 2004

Remifentanil versus morphine analgesia and sedation for mechanically ventilated critically ill patients: a randomized double blind study.

Anesthesiology 2004 Sep;101(3):640-6

Department of Anaesthesiology and Intensive Care Medicine, Graz University, Austria.

Background: The rapid onset and offset of action of remifentanil could make it quickly adjustable to the required level of sedation in critically ill patients. The authors hypothesized that the efficacy of a remifentanil-based regimen was greater than that of a morphine-based regimen.

Methods: Forty intent-to-treat patients were randomly allocated to receive a blinded infusion of either remifentanil 0.15 microg x kg(-1) x min(-1) or morphine 0.75 microg x kg(-1) x min(-1). The opioid infusion was titrated, in the first intent, to achieve optimal sedation defined as Sedation Agitation scale of 4. A midazolam open-label infusion was started if additional sedation was required.

Results: The mean percentage hours of optimal sedation was significantly longer in the remifentanil group (78.3 +/- 6.2) than in the morphine group (66.5 +/- 8.5). This was achieved with less frequent infusion rate adjustments (0.34 +/- 0.25 changes/h) than in the morphine group (0.42 +/- 0.22 changes/h). The mean duration of mechanical ventilation and extubation time were significantly longer in the morphine group (18.1 +/- 3.4 h, 73 +/- 7 min) than in the remifentanil group (14.1 +/- 2.8 h, 17 +/- 6 min), respectively. Remifentanil mean infusion rate was 0.13 +/- 0.03 microg x kg(-1) x min(-1), whereas morphine mean infusion rate was 0.68 +/- 0.28 microg x kg(-1) x min(-1). More subjects in the morphine group (9 of 20) than in the remifentanil group (6 of 20) required midazolam. The incidence of adverse events was low and comparable across the two treatment groups.

Conclusions: A remifentanil-based regimen was more effective in the provision of optimal analgesia-sedation than a standard morphine-based regimen. The remifentanil-based regimen allowed a more rapid emergence from sedation and facilitated earlier extubation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/00000542-200409000-00012DOI Listing
September 2004

Differential reversal of drug-induced small bowel paralysis by cerulein and neostigmine.

Intensive Care Med 2004 Jul 18;30(7):1414-20. Epub 2004 May 18.

Department of Anaesthesiology and Intensive Care Medicine, University of Graz, Auenbruggerplatz 29, 8036 Graz, Austria.

Objective: Cerulein and neostigmine are prokinetic drugs whose potency and effective dose range are barely known. The aim of this study was to assess their benefit for normal and compromised peristalsis.

Design: In vitro, isolated segments of guinea pig small intestine. Setting : University laboratory.

Interventions: Small bowel segments were mounted in tissue baths and luminally perfused with Tyrode solution. Test drugs (prokinetic: cerulein, neostigmine; inhibitory: atropine, hexamethonium, epinephrine, sufentanil) were added to the tissue bath.

Measurements And Results: Peristalsis was quantified via changes in the peristaltic pressure threshold. One-way and two-way analysis of variance (ANOVA) were used for statistical analysis. Cerulein (0.03-100 nM) stimulated normal peristalsis in a concentration-dependent manner and reversed paralysis of peristalsis induced by all inhibitory test drugs to a similar extent. The properistaltic effect of neostigmine was limited to a narrow concentration range (0.03-0.1 micro M), whereas concentrations >0.3 micro M inhibited peristalsis. Neostigmine more effectively counteracted blockage of peristalsis caused by atropine than that caused by hexamethonium. The inhibitory effects of epinephrine and sufentanil on peristalsis were reversed only at the concentration range of 0.1-0.3 micro M neostigmine.

Conclusions: Cerulein stimulates normal peristalsis in vitro at a wide concentration range and reverses blockage of peristalsis caused by drugs with a site of action either on the enteric nervous system or intestinal smooth muscle. Neostigmine's prokinetic effect, to the contrary, is limited to a small concentration range and best seen when peristalsis is depressed by blockage of cholinergic muscle activation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00134-004-2317-2DOI Listing
July 2004

Catecholamines potentiate LPS-induced expression of MMP-1 and MMP-9 in human monocytes and in the human monocytic cell line U937: possible implications for peri-operative plaque instability.

FASEB J 2004 Mar 8;18(3):603-5. Epub 2004 Jan 8.

Department of Internal Medicine II, University of Vienna, Vienna, Austria.

Plaque destabilization leading to myocardial infarction is observed after surgery even if the intervention is of noncardiovascular nature. Mediators of peri- or postoperative stress responsible for such events could include catecholamines and lipopolysaccharide (LPS). Monocytes may be involved in destabilization of atherosclerotic plaques by production of matrix metalloproteinases (MMP). We examined whether catecholamines could affect the expression of MMPs in human monocytes/macrophages and whether catecholamines could modulate LPS-stimulated expression of particular MMPs in these cells. Epinephrine and norepinephrine up-regulated MMP-1 and potentiated LPS-induced expression of MMP-1 in peripheral blood monocytes and monocyte-derived macrophages. We further characterized this effect employing the monocytic cell line U937 and showed that catecholamines potentiate LPS-induced effects on MMP-1 and MMP-9 antigen and activity. mRNA levels of the respective MMPs also increased. These effects did not result from higher mRNA stability but rather from increased transcription possibly induced by enhanced DNA binding of AP-1 and were mediated by either beta1- or beta 2-receptors. If this mechanism is also effective in vivo, our findings might, at least in part, help to explain the observation that cardiac events are important causes of morbidity and mortality after noncardiac surgery and support the findings that peri-operative beta-blockade has been shown to reduce postoperative mortality from cardiac events.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1096/fj.03-0454fjeDOI Listing
March 2004