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Christian Lehmann,
Dragan Pavlovic,
Juan Zhou,
Ulrich Wuttke,
Daniela Saeger,
Alexander Spassov,
Orlando Hung,
Vladimir Cerny,
Tobias Witter,
Sara Whynot,
Ulrich Suchner,
Birgit Alteheld,
Peter Stehle, Matthias Gründling
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ABSTRACT: The administration of glutamine (Gln), which is depleted in critical illness, is associated with an improvement of gut metabolism, structure, and function. The aim of the present study was to evaluate the effects of intravenous Gln and its galenic formulation, l-alanyl-l-glutamine dipeptide (AlaGln), on the intestinal microcirculation during experimental endotoxemia using intravital fluorescence microscopy. Gln or AlaGln administration was performed as pretreatment or post-treatment, respectively. To identify further the underlying mechanisms, amino acid levels were studied.
Sixty male Lewis rats were randomly divided into six groups (n = 10/group): control, LPS (lipopolysaccharide 5 mg/kg intravenously), Gln/LPS (LPS animals pretreated with Gln 0.75 g/kg Gln intravenously), AlaGln/LPS (LPS animals pretreated with AlaGln intravenously, 0.75 g/kg Gln content), LPS/Gln (LPS animals post-treated with Gln 0.75 g/kg intravenously), and LPS/AlaGln (LPS animals post-treated with AlaGln intravenously, 0.75 g/kg Gln content). Two hours after the endotoxin challenge, the microcirculation of the terminal ileum was studied using intravital fluorescence microscopy. Blood samples were drawn at the beginning, during, and the end of the experiment to determine the amino acid levels.
The Gln and AlaGln pre- and post-treatment, respectively, prevented the LPS-induced decrease in the functional capillary density of the intestinal muscular and mucosal layers (P < 0.05). The number of adherent leukocytes in the submucosal venules was significantly attenuated after the Gln and AlaGln pre- and post-treatment (P < 0.05).
The Gln and AlaGln administrations improved the intestinal microcirculation by increasing the functional capillary density of the intestinal wall and decreasing the submucosal leukocyte activation.
Nutrition 01/2012; 28(5):588-93. · 3.03 Impact Factor
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ABSTRACT: The measurement of cardiac output in critically ill patients is complicated by rapid pathophysiological changes. The aim of this study was to compare the recently developed Arterial Pressure Cardiac Output algorithm (APCO) with transpulmonary thermodilution (TDCO). Clinical and hemodynamic parameters were tested for their impact on the measurements.
Twenty septic patients were examined. Cardiac output measurements were performed simultaneously on 3 consecutive days. The data were evaluated using regression analysis and the Bland Altman approach.
Bland Altman analysis presented a bias of 0.72 L/min and limits of agreement of 2.16 to 3.61 L/min for TDCO vs. APCO. Statistically significant covariables in the regression analysis were systemic vascular resistance (p<0.001), mean arterial pressure (p<0.001), cardiac function index (p=0.01), global end-diastolic index (p=0.02) and stroke volume index (p=0.005). Multiple linear regression analysis showed the residual percentage error decreased from 49.1% to 21.5%.
The APCO algorithm provides a broad range of hemodynamic measurements with a minimally invasive approach and simple access to the patient's hemodynamic state. However, an underestimation at high cardiac output and an overestimation at low cardiac output relative to transpulmonary thermodilution were observed in septic patients. Therefore, the APCO algorithm in its current state cannot be substituted for transpulmonary thermodilution.
Medical science monitor: international medical journal of experimental and clinical research 02/2010; 16(3):PR1-7. · 1.70 Impact Factor
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Axel Kramer,
Rainer Kranabetter,
Jörg Rathgeber,
Klaus Züchner,
Ojan Assadian,
Georg Daeschlein,
Nils-Olaf Hübner,
Edeltrut Dietlein,
Martin Exner, Matthias Gründling,
Christian Lehmann,
Michael Wendt,
Bernhard Martin Graf,
Dietmar Holst,
Lutz Jatzwauk,
Birgit Puhlmann,
Thomas Welte,
Antony R Wilkes
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ABSTRACT: An interdisciplinary working group from the German Society of Hospital Hygiene (DGKH) and the German Society for Anaesthesiology and Intensive Care (DGAI) worked out the following recommendations for infection prevention during anaesthesia by using breathing system filters (BSF). The BSF shall be changed after each patient. The filter retention efficiency for airborne particles is recommended to be >99% (II). The retention performance of BSF for liquids is recommended to be at pressures of at least 60 hPa (=60 mbar) or 20 hPa above the selected maximum ventilation pressure in the anaesthetic system. The anaesthesia breathing system may be used for a period of up to 7 days provided that the functional requirements of the system remain unchanged and the manufacturer states this in the instructions for use.THE BREATHING SYSTEM AND THE MANUAL VENTILATION BAG ARE CHANGED IMMEDIATELY AFTER THE RESPECTIVE ANAESTHESIA IF THE FOLLOWING SITUATION HAS OCCURRED OR IT IS SUSPECTED TO HAVE OCCURRED: Notifiable infectious disease involving the risk of transmission via the breathing system and the manual bag, e.g. tuberculosis, acute viral hepatitis, measles, influenza virus, infection and/or colonisation with a multi-resistant pathogen or upper or lower respiratory tract infections. In case of visible contamination e.g. by blood or in case of defect, it is required that the BSF and also the anaesthesia breathing system is changed and the breathing gas conducting parts of the anaesthesia ventilator are hygienically reprocessed.Observing of the appropriate hand disinfection is very important. All surfaces of the anaesthesia equipment exposed to hand contact must be disinfected after each case.
GMS Krankenhaushygiene interdisziplinär. 01/2010; 5(2).
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ABSTRACT: Evidence from both animal and human research suggests that the formation of emotional memories is triggered by the beta-adrenergic system. To confirm whether modulation of central beta-adrenergic transmission is specifically involved in the neural signature of memory performance, the pre-encoding effect of propranolol (80 mg) on event-related potentials (ERPs) was measured in a placebo-controlled, double-blind, parallel-group study in 46 male healthy subjects using high density EEG and source imaging analysis during encoding and retrieval (after 1 week) of IAPS pictures of unpleasant, neutral and pleasant contents; for recognition 90 old pictures were randomly mixed with 90 new pictures. During retrieval correctly remembered old pictures elicited a significantly larger positive voltage change over the centro-parietal cortex than new pictures. Propranolol significantly reduced this old/new difference of the mean ERP amplitudes (500-800 ms) for unpleasant but not for neutral and pleasant memories. This effect correlated with salivary alpha-amylase activity, a surrogate for central adrenergic stimulation. In conclusion, propranolol selectively blocked the neural signature of unpleasant memories by mechanisms in which the parietal cortex seems to be specifically involved.
NeuroImage 10/2009; 49(3):2800-6. · 5.89 Impact Factor
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Matthias Gründling,
Sandra Rickert,
Daniela Saeger,
Dragan Pavlovic,
Taras Usichenko,
Konrad Meissner,
Michael Wendt,
Orlando Hung,
Michael Murphy,
Sara Whynot,
Christian Lehmann
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ABSTRACT: We evaluated the effects of acute high-dose sodium selenite (SEL) administration on the intestinal microcirculation and the release of the cytokines TNF-alpha, IL-1beta, IL-6 and IL-10 in experimental endotoxemia (induced by lipopolysaccharide-LPS). Three groups of animals (n=30) were studied: control group, endotoxemic group (15 mg kg(-1) i.v. LPS from E. coli) and SEL-treated LPS group (100 microg kg(-1) SEL i.v.). SEL treatment resulted in a significant reduced number of firmly adhering leukocytes in intestinal submucosal venules and reduced significantly the impairment of the intestinal functional capillary density. Despite of the improvement of microcirculatory parameters, we did not detect any changes in the pattern of cytokine release. In conclusion, administration of high-dose sodium SEL attenuates leukocyte adhesion and improves capillary perfusion within the intestinal microcirculation without affecting release of the cytokines TNF-alpha, IL-1beta, IL-6 and IL-10 in experimental endotoxemia.
Journal of Trace Elements in Medicine and Biology 02/2009; 23(2):138-43. · 1.68 Impact Factor
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Konrad Meissner,
Thomas Iber,
Jan-Patrick Roesner,
Christian Mutz,
Hans-Erich Wagner,
Christina Layher,
Utz Bartels, Matthias Gründling,
Taras I Usichenko,
Michael Wendt,
Christian Lehmann,
Dragan Pavlovic
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ABSTRACT: Lung ventilation through a thin transtracheal cannula may be attempted in patients with laryngeal stenosis or "cannot intubate, cannot ventilate" situations. It may be impossible to achieve sufficient ventilation if the lungs are spontaneously emptying only through the thin transtracheal cannula, which imposes high resistance to airflow, resulting in dangerous hyperinflation. Therefore, the authors describe the use of a manual respiration valve that serves as a bidirectional pump providing not only inflation but also active deflation of the lungs in case of emergency transtracheal lung ventilation.
The effectiveness of such a valve was tested in vitro using mechanical lungs in combination with two different cannula sizes and various gas flows. The valve was then tested in five pigs using a transtracheal 16-gauge cannula with three different combinations of inspiratory/expiratory times and gas flows and an occluded upper airway.
In the mechanical lungs, the valve permitted higher minute volumes compared with spontaneous lung emptying. In vivo, the arterial oxygen and carbon dioxide partial pressures increased initially and then remained stable over 1 h (arterial oxygen tension, 470.8 +/- 86.8; arterial carbon dioxide tension, 63.0 +/- 7.2 mmHg). The inspiratory pressures measured in the trachea remained below 10 cm H2O and did not substantially influence central venous and pulmonary artery pressures. Mean arterial pressure and cardiac output were unaffected by the ventilation maneuvers.
This study demonstrated in vitro and in vivo in adult pigs that satisfactory lung ventilation can be assured with transtracheal ventilation through a 16-gauge cannula for a prolonged period of time if combined with a bidirectional manual respiration valve.
Anesthesiology 08/2008; 109(2):251-9. · 5.36 Impact Factor
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Konrad Meissner,
Thomas Iber,
Jan-Patrick Roesner,
Christian Mutz,
Hans-Erich Wagner,
Christina Layher,
Utz Bartels, Matthias Gründling,
Taras I. Usichenko,
Michael Wendt,
Christian Lehmann,
Dragan Pavlovic
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ABSTRACT: Background: Lung ventilation through a thin transtracheal cannula may be attempted in patients with laryngeal stenosis or cannot intubate, cannot ventilate situations. It may be impossible to achieve sufficient ventilation if the lungs are spontaneously emptying only through the thin transtracheal cannula, which imposes high resistance to airflow, resulting in dangerous hyperinflation. Therefore, the authors describe the use of a manual respiration valve that serves as a bidirectional pump providing not only inflation but also active deflation of the lungs in case of emergency transtracheal lung ventilation.
Anesthesiology 07/2008; 109(2):251-259. · 5.36 Impact Factor
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Christian Lehmann,
Ricardo Scheibe,
Michael Schade,
Konrad Meissner, Matthias Gründling,
Taras Usichenko,
Michael Wendt,
Orlando Hung,
Sara Whynot,
Michael Murphy,
Dragan Pavlovic
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ABSTRACT: Activated protein C (APC) is the first anti-inflammatory drug to be approved for the treatment of severe sepsis. However, the underlying mechanisms are not completely elucidated. Therefore, the aim of our study was to evaluate the effects of APC on the microcirculation (mesenteric leukocyte-endothelial interaction, plasma extravasation) using intravital microscopy (IVM) and on cytokine release during experimental endotoxemia in rats.
We divided forty, male, Lewis rats into four groups (n = 10 per group): Controls, LPS (15 mg x kg(-1) lipopolysaccharide iv), APC (2 mg x kg(-1) APC iv), and LPS+APC. We determined mesenteric leukocyte-endothelial interactions and plasma extravasation at zero, one and two hours following administration of LPS and APC by IVM. Plasma levels of tumour necrosis factor-alpha, IL-1beta, interleukin (IL)-6, and IL-10 were measured at zero and at two hours.
Leukocyte adherence (-74%) and plasma extravasation (-28%) during endotoxemia were diminished significantly following APC treatment, compared to untreated LPS animals (P = 0.0001 and P = 0.0004, respectively). Interleukin-1ss release was also significantly reduced by APC treatment (2567.4 +/- 320.9 pg x mL(-1) in the LPS group vs 1626.1 +/- 427.2 pg x mL(-1) in the LPS+APC group; P = 0.001).Conclusion: These rodent experiments showed that APC treatment significantly attenuated deterioration of the mesenteric microcirculation and systemic IL-1ss release caused by endotoxin challenge. Because of the crucial role of the microcirculation in ongoing sepsis pathogenesis and multiple organ dysfunction syndrome, these effects may be of clinical importance.
Canadian Journal of Anaesthesia 04/2008; 55(3):155-62. · 2.35 Impact Factor
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ABSTRACT: The colon ascendens stent peritonitis (CASP) procedure creates an intestinal leakage of feces, resulting in diffuse peritonitis and polymicrobial sepsis. Mouse models of CASP have been used to study sepsis experimentally. The aim of the present study was to establish CASP sepsis in rats and to provide basic functional characteristics of this model. In analogy to the mouse model, 3 degrees of severity of CASP sepsis, 2 sublethal and 1 lethal, were established depending on the stent diameter. Radio-telemetric recordings in a sublethal model showed that the nonsurvivors remained hemodynamically stable until approximately 1 h before death, when heart rate and blood pressure fell rapidly. Intestinal microcirculatory changes were analyzed 3, 6, 12, and 18 h after CASP surgery using intravital microscopy in a sublethal model. After 18 h, the numbers of the leukocytes firmly adhering to the endothelium and of the ones temporarily interacting were significantly increased. The levels of IL-6 and IL-1beta increased continuously during the CASP experiments while remaining unchanged in the sham group. TNF-alpha and IL-10 levels of CASP animals reached a maximum after 12 h. In conclusion, a rat model of CASP sepsis has been established and characterized with regard to alterations in cardiovascular and microcirculatory function as well as plasma cytokine levels. In experimental settings where genetically engineered animals are not required, it will facilitate detailed examination of dynamic changes in integrated organ function during the course of sepsis and the investigation of treatment strategies.
Shock 08/2007; 28(1):59-64. · 2.85 Impact Factor
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ABSTRACT: Treatment of peritonitis may include peritoneal lavage/instillation with anti-infective agents like taurolidine or chlorhexidine.
We examined the effects of peritoneal instillation (INST, 5-ml solution) with taurolidine (TAURO) or polihexanide (POLI-LS) on intestinal microcirculation using intravital microscopy (IVM) in experimental endotoxemia (15 mg/kg lipopolysaccharide i.v.; LPS) in the rat (n = 8 each group), their direct effects on local small blood vessels, aortal rings, and myocardial strips in vitro, as well as plasma interleukin levels.
It was found that LPS produced hypotension (98.8 +/- 9.5 vs 130.4 +/- 10.5 mmHg; mean arterial pressure [MAP], mean +/- standard deviation [SD]), which was further pronounced after INST of TAURO (78.8 +/- 10.8; P < 0.005) or POLI-LS (78.1 +/- 6.0; P < 0.001). IVM revealed a reduction in temporary adhering leucocytes and an increase in firmly adhering leucocytes after INST with TAURO and POLI-LS. Both agents reduced functional capillary density either in the mucosa (POLI-LS vs sham: 259.7 +/- 54 cm/cm(2) vs 337.1 +/- 35.5) or longitudinal muscular layer in LPS rats (TAURO vs sham: 119.8 +/- 14.8 vs 153.7 +/- 11.0). POLI-LS induced local vasodilatation, whereas TAURO induced small vasoconstriction; in vitro, both agents showed vasodilating properties and did not have any effect on myocardial strip contraction.
Some of the observed microcirculatory changes could be a result of the direct vascular effects of these agents.
International Journal of Colorectal Disease 07/2007; 22(7):807-17. · 2.38 Impact Factor
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ABSTRACT: Treatment of peritonitis may include abdominal lavage with a local disinfectant polihexanide, available as 0.04% solution, which is often accompanied by hypotension.
We examined the effects of peritoneal installation of polihexanide or NaCl 0.9% (10 ml each, for 10 min; polihexanide n=5, NaCl n=5) on mean arterial pressure in healthy rats and, using intravital microscopy, measured in seven other animals the diameter of terminal ileum submucosal arterioles and venules before and after local superfusion with polihexanide. Furthermore, in an in vitro isometric preparation of rat thoracic aortal rings, with and without endothelium, we tested the effects of cumulative concentrations of polihexanide on vascular basic tension and on tension elicited by phenylephrine and KCl.
It was found that polihexanide peritoneal instillation produced a decrease in mean arterial pressure, while superfusion with polihexanide caused local vasodilation of intestinal wall blood vessels. In vitro, polihexanide produced endothelium-dependent relaxation in the preparations pre-contracted with phenylephrine (EC(50), polihexanide 0.04% solution 2.53+/-0.16 vs. 1.36+/-0.16, n=4, P<0.05; polihexanide 4.02+/-0.12 vs. 3.21+/-0.10, n=12, P<0.001;+ vs. - endothelium, respectively; -log g%) which (in aortae +endothelium) could be attenuated by either N(G)-nitro-L-arginine methyl ester, a nitric oxide generation inhibitor, or 1H-(1,2,4)oxodiazolo-(4,3-a)quinoxalin-1-one, an inhibitor of guanylyl cyclase. The relaxing effect of polihexanide (aortae -endothelium) was not affected by K(+)-channel blocking agents charybdotoxin, tetraethylammoniumchloride, glibenclamide or 4-aminopyridine, while polihexanide had no effects on 40-mM KCl contractions.
This implies that polihexanide may promote nitric oxide liberation, potassium channel activation and vasodilation that may result in hypotension.
International Journal of Colorectal Disease 05/2006; 21(4):373-80. · 2.38 Impact Factor
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Jürgen Birnbaum,
Ortrud Vargas Hein,
Carsten Lührs,
Oskar Rückbeil,
Claudia Spies,
Sabine Ziemer, Matthias Gründling,
Taras Usichenko,
Konrad Meissner,
Dragan Pavlovic,
Wolfgang J Kox,
Christian Lehmann
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ABSTRACT: The objective of this study was to determine the effects of the administration of the coagulation factor XIII (F XIII) on intestinal functional capillary density, leukocyte adherence and mesenteric plasma extravasation during experimental endotoxemia.
In a prospective, randomized, controlled animal study 42 male Wistar rats were divided into three groups. Group 1 served as the control group. Groups 2 (lipopolysaccharide (LPS) group) and 3 (F XIII group) received endotoxin infusions (2.5 mg/kg/h for 2 hours). In group 3, 50 U/kg body weight F XIII was continuously administered during the first 30 minutes of endotoxemia. F XIII levels were measured in all animals. One half of the animals of each group were studied for intestinal functional capillary density (FCD) and leukocyte adherence on venular endothelium by intravital fluorescence microscopy (IVM). In the other half of each group, mesenteric plasma extravasation (FITC-albumin) was determined by IVM.
The F XIII level was significantly increased in the F XIII treatment group. In the LPS group, endotoxemia led to a significant reduction of mucosal FCD (-18.5%; p < 0.01 versus control group). F XIII administration in the F XIII group attenuated the decrease in mucosal FCD (-3.7% compared to control; p < 0.05 versus LPS group). During endotoxemia, a significant increase of leukocyte adherence at the endothelium could be noted in the LPS group compared to the control group. Leukocyte adherence at the endothelium and plasma extravasation in the F XIII group did not differ significantly from the LPS group.
Factor XIII protected mucosal capillary perfusion against endotoxin-induced impairment in an experimental sepsis model in rats, whereas leukocyte adherence and plasma extravasation remained unchanged.
Critical care (London, England) 03/2006; 10(1):R29. · 4.61 Impact Factor
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ABSTRACT: Successful treatment of severe sepsis and septic shock remains a major challenge in critical care medicine. The recently introduced recombinant human activated protein C (APC) remarkably improved the outcome of septic patients. The influence of APC on intestinal circulation is still poorly understood. Therefore, the present study aimed to investigate the effects of APC on intestinal microcirculation during experimental endotoxaemia in rats by using intravital microscopy.
A total of 44 male Lewis rats were randomly assigned to receive intravenous injections of 15 mg/kg lipopolysaccharide alone (LPS) (n = 11) or LPS followed by subsequent injection of 2 mg/kg recombinant human APC (LPS + APC) (n = 11), whereas control animals received either APC (n = 11) or saline (n = 11). Animals underwent observations of functional capillary density and leucocyte adherence on venular endothelium in the microcirculation of the intestinal wall by means of intravital fluorescence microscopy. Indicators of macrocirculation as well as plasma levels of tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-6, and IL-10 were measured.
Although APC administration of both LPS-treated and control rats did not change macrocirculation or release of inflammatory cytokines, it increased mucosal and muscular functional capillary density (p < 0.001 and p < 0.05, respectively) and reduced the number of firmly adhering leucocytes in intestinal submucosal V1 and V3 venules (p < 0.01) in LPS + APC-treated compared with LPS-treated animals, which did not receive APC. No remarkable differences that could be attributed to APC treatment were observed between the two control groups.
APC administration during experimental endotoxaemia improved intestinal microcirculation by protecting functional capillary density as a measure of microvascular perfusion and exerted anti-inflammatory effects by reducing leucocyte adherence to the endothelium in submucosal venules. Therefore, beneficial effects of APC in septic patients might be due, in part, to improved intestinal microcirculation.
Critical care (London, England) 02/2006; 10(6):R157. · 4.61 Impact Factor
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Chest 12/2005; 128(5):3774-5. · 5.25 Impact Factor
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ABSTRACT: Hospital medical activities are performed in various departments, such as general wards, functional units, outpatients' departments (OPD), and administrative areas. This study examined the possibility of redistributing medical performances from a normal ward to an OPD for an average accident surgery population. It is shown that up to 89% of the medical performances can be produced in an outpatients' clinic (OPC) in spite of only minimal shifts of medical care. The collected data only reflect the picture of routine medical care in accident surgery; in principle, however, the results should apply to other groups of patients, and promote a quality increase in parallel to a cost reduction of the overall hospital treatment.
Zeitschrift für ärztliche Fortbildung und Qualitätssicherung. 11/2004; 98(7):617-20.
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ABSTRACT: Catecholamines are often used for optimisation of cardiac index and oxygen delivery in high-risk surgical patients; however, infusions of dopamine and dopexamine are associated with dose-dependent hypophysiotropic and thyreotropic properties. The objective was to compare endocrine effects of equipotent inotropic doses of dopexamine, dobutamine and dopamine on prolactin and thyreotropin release perioperatively.
A prospective, randomised, blinded clinical trial.
Adult surgical intensive care unit in a university hospital.
Thirty male patients (ASA III) undergoing elective major abdominal surgery.
Patients were randomised to receive dopexamine (DX, n=10), dobutamine (DO, n=10) or dopamine (DA, n=10) on the first postoperative day for 8 h.
All patients received a catecholamine infusion in doses adjusted to increase cardiac index by 35% within the first hour. Blood samples were obtained and prolactin and thyreotropin serum concentrations were determined by radioimmunoassays. Mean doses of dopexamine, dobutamine and dopamine used were 0.73+/-0.27, 4.06+/-1.95 and 5.0+/-1.84 micro g kg(-1)min(-1), respectively. Cardiac index was increased by 36% (DX group), 38% (DO group) and 38% (DA group). Alterations of oxygen delivery and oxygen consumption were not significantly different between the study groups. Dopexamine and dobutamine had no hypophysiotropic effects. In contrast, dopamine suppressed prolactin and thyreotropin secretion with a maximal effect after 4 h. After dopamine withdrawal, a rebound release of prolactin and thyreotropin was observed.
In high-risk surgical patients dopexamine or dobutamine produced fewer effects on prolactin and thyreotropin serum concentrations in comparison with DA when used in equivalent dosages.
Intensive Care Medicine 07/2004; 30(6):1127-33. · 5.40 Impact Factor
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Christian Lehmann,
Jürgen Birnbaum,
Carsten Lührs,
Oskar Rückbeil,
Claudia Spies,
Sabine Ziemer, Matthias Gründling,
Dragan Pavlovic,
Taras Usichenko,
Michael Wendt,
Wolfgang J Kox
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ABSTRACT: To determine the effects of C1 esterase inhibitor (C1-INH) administration on intestinal functional capillary density, leukocyte adherence, and mesenteric plasma extravasation during experimental endotoxemia.
Prospective, randomized, controlled animal study in the experimental laboratory of a university.
42 male Wistar rats.
The animals were divided into three groups. One half of the animals of each group underwent studies of intestinal functional capillary density and leukocyte adherence on venular endothelium by intravital fluorescence microscopy. In the other half of the animals mesenteric plasma extravasation (FITC albumin) was determined by intravital fluorescence microscopy. Treatment groups received endotoxin infusion of 2.5 mg/kg per hour (group 2 and 3) and 100 U/kg b.w. C1-INH (group 3) during the 2 h of endotoxemia.
Endotoxemia resulted in a significant decrease in mucosal functional capillary density (18.5% vs. controls), which was reduced by C1-INH administration (9.5%). Treatment with C1-INH also significantly attenuated intestinal leukocyte adherence in submucosal venules (35% vs. endotoxin group) and mesenteric plasma extravasation (44% vs. endotoxin group).
C1-INH administration diminishes endotoxin-induced changes in the intestinal microcirculation during experimental endotoxemia.
Intensive Care Medicine 03/2004; 30(2):309-14. · 5.40 Impact Factor
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ABSTRACT: ObjectivesCatecholamines are often used for optimisation of cardiac index and oxygen delivery in high-risk surgical patients; however, infusions of dopamine and dopexamine are associated with dose-dependent hypophysiotropic and thyreotropic properties. The objective was to compare endocrine effects of equipotent inotropic doses of dopexamine, dobutamine and dopamine on prolactin and thyreotropin release perioperatively.DesignA prospective, randomised, blinded clinical trial.SettingAdult surgical intensive care unit in a university hospital.PatientsThirty male patients (ASA III) undergoing elective major abdominal surgery.InterventionsPatients were randomised to receive dopexamine (DX, n=10), dobutamine (DO, n=10) or dopamine (DA, n=10) on the first postoperative day for 8h.Measurements and resultsAll patients received a catecholamine infusion in doses adjusted to increase cardiac index by 35% within the first hour. Blood samples were obtained and prolactin and thyreotropin serum concentrations were determined by radioimmunoassays. Mean doses of dopexamine, dobutamine and dopamine used were 0.730.27, 4.061.95 and 5.01.84gkg–1min–1, respectively. Cardiac index was increased by 36% (DX group), 38% (DO group) and 38% (DA group). Alterations of oxygen delivery and oxygen consumption were not significantly different between the study groups. Dopexamine and dobutamine had no hypophysiotropic effects. In contrast, dopamine suppressed prolactin and thyreotropin secretion with a maximal effect after 4h. After dopamine withdrawal, a rebound release of prolactin and thyreotropin was observed.ConclusionsIn high-risk surgical patients dopexamine or dobutamine produced fewer effects on prolactin and thyreotropin serum concentrations in comparison with DA when used in equivalent dosages.
Intensive Care Medicine 01/2004; 30(6):1127-1133. · 5.40 Impact Factor
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Critical Care Medicine 05/2003; 31(4):1285-6. · 6.33 Impact Factor
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Jürgen Birnbaum,
Christian Lehmann,
Harald M Stauss,
Mathias Weber,
Alexander Georgiew,
Björn Lorenz,
Sven Pulletz, Matthias Gründling,
Dragan Pavlovic,
Michael Wendt,
Wolfgang J Kox
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ABSTRACT: Impairment of the intestinal microcirculation has been recognized as an important factor in the pathogenesis of endotoxin related sepsis syndrome. We investigated the effects of endotoxemia on the variability of intestinal microvascular blood flow (IMBF) and arterial blood pressure (BP) in a prospective, randomized, controlled animal study. Recordings of IMBF (laser Doppler fluxmetry) and BP were performed before, two and four hours after i.v. injection of either placebo or endotoxin (5 mg/kg b.w. lipopolysaccharide from E. coli, serotype O55:B5). Control experiments were performed with systemic (clonidine) and local intestinal (surgery) sympathectomy. Spectral analysis was performed using the autoregressive approach. Spectral power was determined in two frequency bands (low frequency (LF): 0.27-0.74 Hz; high frequency (HF): 0.76-3.00 Hz). Two hours after endotoxin challenge a significant decrease in IMBF was observed. LF spectral power of IMBF and BP increased significantly in the endotoxin challenged group, while no effects were observed in the placebo group. Four hours after endotoxin administration IMBF decreased further and LF spectral power of IMBF and BP remained elevated. Denervation prevented the decrease in IMBF but did not abolish the LF power increase. Clonidine administration attenuated the IMBF decrease and significantly diminished the increase in LF spectral power of IMBF and BP. We conclude that endotoxemia is associated with increased sympathetic outflow to the systemic vasculature, as indicated by the increase in LF spectral power of arterial blood pressure. The increase in LF variability of IMBF is secondary to the increase in LF spectral power of BP, since it could be attenuated by systemic and not by local intestinal sympathectomy.
Clinical hemorheology and microcirculation 02/2003; 28(4):209-20. · 3.40 Impact Factor