The European Union Directive on Clinical Research: present status of implementation in EU member states' legislations with regard to the incompetent patient.
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Biomedical Research↗
Biomedical subjects
J Kesecioglu
Publications and source records attributed to J Kesecioglu.
[Clinical trials on medical products for human use in the case of acutely incapacitated patients within the fields of neurology and neurosurgery; implications of the new European legislation].
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Critical Care↗
[Mechanical ventilation in acute respiratory distress syndrome (ARDS): lung protecting strategies for improved alveolar recruitment].
For patients with acute respiratory distress syndrome (ARDS) the most important objective of mechanical ventilation is opening and keeping open the alveoli to achieve adequate oxygenation, without further damaging the lungs or negatively affecting the circulation. Alveolar recruitment is achieved by making use of positive end-expiratory pressure (PEEP). The best PEEP level is that with which the largest improvement in oxygen transport and lung compliance is achieved, without a decrease in the stroke volume of the left ventricle. In addition to the usual volume-controlled ventilation with PEEP, pressure-limited ventilation is also possible. In this a preselected pressure is never exceeded, whereas a maximum inspiratory airflow at the start of inspiration provides more opportunity for gaseous exchange. The oxygenation can possibly be further improved by increasing the inspiration-expiration ratio. As a result of the reduced expiratory period the alveoli which tend to collapse at the end of a normal expiration are kept open. Mechanical ventilation with a lower tidal volume decreases mortality. Ventilation in a prone position increases the end-expiratory lung volume and reduces the intrapulmonary shunt and the regional differences in the degree of ventilation. These factors possibly contribute to preventing ventilation-induced lung damage. Administration of natural surfactant during the ventilation of patients with ARDS seems to be a highly promising strategy; the clinical effectiveness still needs to be demonstrated.
Humans↗
Lodixanol inhibits exogenous surfactant therapy in rats with acute respiratory distress syndrome.
Optimal alveolar distribution of exogenous surfactant is an important determinant of its beneficial effect. This distribution can be determined by suspending surfactant in a radiological contrast medium before intratracheal instillation, followed by radiological imaging. Iodixanol is reported to be a safe contrast medium that causes no lung injury when instilled intratracheally. In this study, the effects of surfactant suspended in saline were compared with surfactant suspended either in 4:1 saline-iodixanol (64 mg iodine x mL(-1)) or in 1:1 saline-iodixanol (160 mg iodine x mL(-1)), on oxygenation and lung mechanics in a rat model of adult respiratory distress syndrome (ARDS) induced by lung lavage. After the induction of ARDS, surfactant instillation improved oxygenation, total lung volume at inflation with a distending pressure of 35 cmH2O, lung volume at transpulmonary pressure of 5 cmH2O and Gruenwald index. The effects of surfactant suspended in 4:1 saline-iodixanol were similar to those of surfactant alone. However, instillation of surfactant suspended in 1:1 saline-iodixanol resulted in significantly lower values in all measured parameters. Surface tension was the lowest in surfactant suspended in saline alone and addition of iodixanol led to an increase in surface tension in a dose-dependent manner. In conclusion, iodixanol at the higher dose caused an inhibition of the exogenous surfactant effect, characterized as a lack of improvement in oxygen tension in arterial blood, low total lung compliance, volume at 5 cmH2O end-expiration and Gruenwald index. This effect of iodixanol was probably due to its high surface tension, especially if a high concentration was used. Surfactant suspended in a lower concentration of iodixanol seems a better alternative, allowing for radiological imaging of the distribution of surfactant when intratracheally instilled.
Animals↗
Decreased circulating levels of von Willebrand factor after intravenous administration of a rapidly degradable hydroxyethyl starch (HES 200/0.5/6) in healthy human subjects.
OBJECTIVE: Impairment of haemostasis has been described with slowly degradable medium molecular weight hydroxyethyl starch (MMW-HES), whereas rapidly degradable MMW-HES is generally considered to have no important effects on blood coagulation. This study was undertaken to investigate the effects of a rapidly degradable MMW-HES plasma substitute on primary haemostasis and blood coagulation in human subjects. DESIGN: Randomised, cross-over study. SETTING: Research unit of a university hospital. PARTICIPANTS: Nine healthy, adult male volunteers. INTERVENTIONS: A 60-min intravenous infusion of 1 l HES 200/0.5/6 (HAES-steril 6%) or 4% albumin (control). MEASUREMENT AND RESULTS: The infusion of HES resulted in decreased circulating levels of von Willebrand factor antigen (from 85+/-8% to 59+/-6% after HES vs from 80+/-7% to 69+/-8% after albumin, p<0.05) and ristocetin cofactor activity (from 93+/-4 to 67+/-4% after HES vs from 79+/-5 to 75+/-5% after albumin, p<0.01). This was associated with an impairment of in vitro platelet function as determined with the PFA-100 platelet function analyser (closure time with collagen/epinephrine from 120+/-7 to 159+/-14 s after HES vs from 121+/-7 to 137+/-10 s after albumin, p<0.05; with collagen/ADP from 88+/-3 to 116+/-9 s and from 103+/-4 to 114+/-7 s after HES and albumin, respectively, p=0.01). CONCLUSIONS: The infusion of 1 l of HES 200/0.5/6 in healthy human subjects results in moderately decreased plasma levels of von Willebrand factor associated with impairment of platelet function.
Adult↗
Effect of preoperative oral immune-enhancing nutritional supplement on patients at high risk of infection after cardiac surgery: a randomised placebo-controlled trial.
BACKGROUND: Elderly patients and those with poor ventricular function have increased morbidity and mortality rates when undergoing surgery. We aimed to ascertain whether an oral immune-enhancing nutritional supplement could improve preoperative host defence, and subsequently lower postoperative infections and organ dysfunction in patients undergoing elective cardiac surgery who are at high risk of infection. METHODS: In this prospective, randomised, double-blind, placebo-controlled study, we randomly assigned 50 patients who were scheduled to undergo coronary artery bypass to receive either an oral immune-enhancing nutritional supplement containing L-arginine, omega3 polyunsaturated fatty acids, and yeast RNA (n=25), or a control (n=25) for a minimum of 5 days. Patients were included if they were aged 70 years or older, or had an ejection fraction of less than 0.4, or were scheduled to undergo mitral valve replacement. The main outcome was preoperative host defence (delayed-type hypersensitivity response to recall antigens, expression of HLA-DR epitopes on monocytes, and concentration of interleukin 6 in plasma). Analysis was per protocol. FINDINGS: Five patients (two in the treatment group) were excluded because they did not take the minimum dose. Preoperative expression of HLA-DR epitopes on monocytes was significantly higher in patients given the study treatment (109% [95% CI 92-128]) than those given the control (69% [58-82]) compared with baseline (100%) (p=0.02, repeated measures ANOVA). However, concentration of interleukin 6 was significantly lower in the treatment group (0.90 pg/L [0.69-1.18]) than in the control group (1.94 pg/L [1.45-2.59]) (p=0.032, repeated measures ANOVA). Additionally, delayed-type hypersensitivity response to recall antigens improved preoperatively and remained better until hospital discharge. INTERPRETATION: Intake of an oral immune-enhancing nutritional supplement for a minimum of 5 days before surgery can improve outlook in high-risk patients who are undergoing elective cardiac surgery.
Administration, Oral↗
Tissue factor pathway inhibitor does not influence inflammatory pathways during human endotoxemia.
Activation of coagulation induces a proinflammatory response in in vitro and animal experiments. Inhibition of the tissue factor-dependent pathway of coagulation inhibits cytokine release and prevents death in gram-negative sepsis models in primates. This study investigated the influence of blocking the coagulation system by tissue factor pathway inhibitor (TFPI) on endotoxin-induced inflammatory responses in healthy humans. Eight men were studied in a double-blind, randomized, placebo-controlled cross-over study. They received a bolus intravenous injection of 4 ng/kg of endotoxin, followed by a 6-h continuous infusion of either TFPI (0.2 mg/kg/h after a bolus of 0.05 mg/kg) or placebo. Endotoxin induced-activation of coagulation was prevented completely by TFPI. In contrast, TFPI did not influence leukocyte activation, chemokine release, endothelial cell activation, or the acute phase response. Thus, complete prevention of coagulation activation by TFPI does not influence activation of inflammatory pathways during human endotoxemia.
Acute-Phase Reaction↗
The Critical Nursing Situation Index for safety assessment in intensive care.
OBJECTIVE: The assessment of critical nursing situations can be a valuable tool in the detection of weak elements in the safety of patients and the quality of care in the ICU. A critical nursing situation can be defined as any observable situation, which deviates from good clinical practice and which may potentially lead to an adverse event. The aim of our study was to establish the feasibility, reliability and validity of the Critical Nursing Situation Index (CNSI) as a tool for assessing the safety and the quality of nursing in the ICU. DESIGN: We described the deviations from standards and protocols in daily ICU nursing care, selected those with an implicit, clear risk for the patients and translated them into explicitly observable items. If an item was applicable during observation of the ICU practice, a critical nursing situation could be recorded as either true or false. The reliability of the CNSI was defined in terms of inter-observer agreement. The validity was assessed by exploring the relationship between the nursing time available (more or less than 30 min per patient per hour) and the incidence of critical nursing situations. SETTING: The study was performed in the ICU of a teaching hospital (30 IC beds) in which all disciplines, including cardiothoracic surgery and neurosurgery, were represented. PATIENTS: The CNSI was randomly applied to 83 ICU patients over a period of 3 months (200 times). MEASUREMENTS AND RESULTS: The reliability of the index was substantial (Kappa values in the range > or =0.70 to > 0.80). In terms of validity, less nursing time resulted in more critical situations (pooled relative risk (RR) 1.36; 95% confidence limits 1.11/1.67). CONCLUSION: The CNSI is simple to use and has encouraging metric properties, whereas the assessments are closely related to direct patient care. Moreover, the CNSI provides a tool for safety assessment by monitoring potentially dangerous situations that are generally regarded as needing to be avoided.
Adult↗
Gut decontamination of critically ill patients reduces Helicobacter pylori acquisition by intensive care nurses.
The prevalence of Helicobacter pylori is increased in healthcare workers and in intensive care nurses. Exposure to H. pylori from gastric secretions and faeces are probably the main sources of transmission to healthcare workers. Routine use of selective decontamination of digestive tract (SDD) in an intensive care unit suppresses H. pylori in critically ill patients. It was questioned whether this suppression and the subsequent decreased exposure to H. pylori for intensive care nurses would lead to a lower prevalence of H. pylori infection. Helicobacter pylori infection prevalence in intensive care nurses from a unit routinely using SDD (group I) was compared to that of nurses from a unit not using SDD (group II). Heathcare workers from other departments of the hospital where no SDD was used (group III) served as a control group. Persons using proton pump inhibitors were excluded. Helicobacter pylori was detected by Laser Assisted Ratio Analyser(13)C-urea breath test (UBT) and serology. This could not be performed in three out of 64 in group I, five out of 55 in group II and five out of 55 in group III (total UBTs = 169). The prevalence of H. pylori infection was 11% (7/61) in group I and 25.5% (14/50) in group II (P= 0.027). In group III, the prevalence of H. pylori infection was 16% (8/45), which was not significantly different from both group I and II. Sero-prevalence in group I was 18.6%, 27% in group II (ns) and 24% in group III. Mean age in the three groups was 35.9, 37.8 and 36.6 years, respectively (ns). In conclusion, the prevalence of H. pylori infection among intensive care nurses is lower in nurses from a unit using SDD compared to a non SDD-using unit. Acquisition of H. pylori by transmission from critically ill patients appears to be diminished through SDD use.
Adult↗
Anticoagulant factor concentrates in disseminated intravascular coagulation: rationale for use and clinical experience.
Natural inhibitors of coagulation, in other words, antithrombin (AT), the protein C system, and tissue factor pathway inhibitor (TFPI), play an important role in controlling the activation of coagulation during disseminated intravascular coagulation (DIC). Furthermore, they may not only influence coagulation but also attenuate inflammatory responses during sepsis. Low circulating levels of AT and protein C have been associated with poor outcome. Replacement therapy with AT, activated protein C (APC), and TFPI has been shown to attenuate thrombin generation and to reduce mortality in experimental sepsis models. Experience with AT and APC in patients is promising. Data from large phase III trials of AT and APC as treatment of patients with severe sepsis will soon be available. Recombinant TFPI is currently in phase II clinical trials for severe sepsis.
Antithrombins↗
[Transhiatal esophagus resection without thoracotomy for carcinoma: complications, hospital mortality and prognosis in 115 patients].
OBJECTIVE: To evaluate the short-term and long-term clinical outcome of transhiatal oesophagectomy without thoracotomy for cancer. DESIGN: Retrospective. METHODS: In the period January 1993-August 1996, 115 patients underwent a transhiatal oesophagectomy with curative intent for adenocarcinoma or squamous cell carcinoma of the middle or distal oesophagus or oesophagogastric junction. There were 87 men and 28 women with a median age of 65 years (range: 37-83). Median duration of postoperative follow-up was 27 months (range: 1-74) for all patients, and 45 months (range: 30-74) for those alive at final follow-up. RESULTS: No emergency thoracotomies were necessary. In-hospital mortality was 3.5% (4 patients). Vocal cord dysfunction (24%) and pulmonary complications (23%) were the most frequent early postoperative complications. Clinical leakage of the cervical anastomosis occurred in 8 patients (7%). Forty per cent developed a benign anastomotic stricture which was treated by (repeated) endoscopic dilatation. A microscopically radical resection was achieved in 73% of the patients. Overall survival was 45% at 3 years. CONCLUSION: Transhiatal oesophagectomy without thoracotomy can be considered a safe procedure for resectable cancer of the midoesophagus, the distal oesophagus or the oesophagogastric junction. Long-term oncological treatment results were in line with the data reported for oesophageal resections via a transthoracic approach.
Adenocarcinoma↗
Tissue factor pathway inhibitor dose-dependently inhibits coagulation activation without influencing the fibrinolytic and cytokine response during human endotoxemia.
Inhibition of the tissue factor pathway has been shown to attenuate the activation of coagulation and to prevent death in a gram-negative bacteremia primate model of sepsis. It has been suggested that tissue factor influences inflammatory cascades other than the coagulation system. The authors sought to determine the effects of 2 different doses of recombinant tissue factor pathway inhibitor (TFPI) on endotoxin-induced coagulant, fibrinolytic, and cytokine responses in healthy humans. Two groups, each consisting of 8 healthy men, were studied in a double-blind, randomized, placebo-controlled crossover study. Subjects were studied on 2 different occasions. They received a bolus intravenous injection of 4 ng/kg endotoxin, which was followed by a 6-hour continuous infusion of TFPI or placebo. Eight subjects received 0.05 mg/kg per hour TFPI after a bolus of 0.0125 mg/kg (low-dose group), and 8 subjects received 0.2 mg/kg per hour after a bolus of 0.05 mg/kg (high-dose group). Endotoxin injection induced the activation of coagulation, the activation and subsequent inhibition of fibrinolysis, and the release of proinflammatory and antiinflammatory cytokines. TFPI infusion induced a dose-dependent attenuation of thrombin generation, as measured by plasma F1 + 2 and thrombin-antithrombin complexes, with a complete blockade of coagulation activation after high-dose TFPI. Endotoxin-induced changes in the fibrinolytic system and cytokine levels were not altered by either low-dose or high-dose TFPI. The authors concluded that TFPI effectively and dose-dependently attenuates the endotoxin-induced coagulation activation in humans without influencing the fibrinolytic and cytokine response. (Blood. 2000;95:1124-1129)
Adult↗
Magnesium levels in critically ill patients. What should we measure?
We studied the relation between ionized magnesium, total magnesium, and albumin levels in serum of 115 critically ill patients and the role of extracellular and intracellular magnesium in outcome prediction. Levels of serum total and ionized magnesium, serum albumin, and magnesium in mononuclear blood cells and erythrocytes were measured and the APACHE II score and 1-month mortality recorded. Of all patients, 51.3% had a serum total magnesium concentration below the reference range. In 71% of these hypomagnesemic patients, a normal serum ionized magnesium concentration was measured. None of the patients had an intracellular magnesium concentration below the reference limit. Except for serum total and ionized magnesium, none of the magnesium parameters correlated significantly with each other. A significantly negative correlation was found between serum albumin and the fraction ionized magnesium. There was no association between low extracellular or intracellular magnesium and clinical outcome. The observation of hypomagnesemia in critically ill patients depends on which magnesium fraction is measured. The lack of correlation with clinical outcome suggests hypomagnesemia to be merely an epiphenomenon. Reliable concentrations of serum ionized magnesium can be obtained only by direct measurement and not by calculation from serum total magnesium and albumin.
Cations, Divalent↗
Titrating PEEP therapy in patients with acute respiratory failure.
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Acute Disease↗
Effects of different mechanical ventilation modes on oxygenation in surfactant depleted rabbit lungs.
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Animals↗
Effect of ketanserine on oxygenation and ventilation inhomogeneity in pigs with ARDS.
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Animals↗
Effects of different modes of ventilation on oxygenation and intracranial pressure of pigs with surfactant depleted lungs.
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Animals↗
Respiratory and haemodynamic effects of conventional volume controlled PEEP ventilation, pressure regulated volume controlled ventilation and low frequency positive pressure ventilation with extracorporeal carbon dioxide removal in pigs with acute ARDS.
The purpose of this study was to evaluate whether any benefit of low frequency positive pressure ventilation with extracorporeal carbon dioxide removal (LFPPV-ECCO2R) existed over either volume controlled ventilation (VCV) with measured best-PEEP or pressure regulated volume controlled ventilation (PRVCV) with an inspiration/expiration (I/E) ratio of 4:1, with respect to arterial oxygenation, lung mechanics and haemodynamics, in acute respiratory failure. Fifteen adult pigs were used for the study. Respiratory failure was induced by surfactant depletion by repeated lung lavage. The different therapeutic approaches were applied randomly to each pig for 1 h. Measurements of gas exchange, airway pressures and haemodynamics were performed during ventilatory and haemodynamic steady state. Paco2 was kept constant in all modes. At almost similar total-PEEP, Pao2 values were significantly higher with LFPPV-ECCO2R compared to VCV with best-PEEP. Peak inspiratory pressure (PIP) and intrapulmonary pressure amplitude defined as the difference between PIP and total-PEEP were significantly lower with PRVCV and LFPPV-ECCO2R compared to VCV with best-PEEP. There was no significant difference between the modes concerning cardiocirculatory parameters. PRVCV with I/E ratio of 4:1 and LFPPV-ECCO2R proved to be better modes to achieve better gas exchange and lower PIP at lower intrapulmonary pressure amplitudes. It is concluded that PRVCV is an adequate form of treatment under these experimental conditions imitating acute respiratory failure, without necessitating other invasive measures.
Acute Disease↗