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Biomedical subjects

L G Thijs

Publications and source records attributed to L G Thijs.

At least 19 recordsLinked to original sources
PubMed2001

Accuracy and reliability of APACHE II scoring in two intensive care units Problems and pitfalls in the use of APACHE II and suggestions for improvement.

Acute Physiology and Chronic Health Evaluation (APACHE) II scoring is widely used as an index of illness severity, for outcome prediction, in research protocols and to assess intensive care unit performance and quality of care. Despite its widespread use, little is known about the reliability and validity of APACHE II scores generated in everyday clinical practice. We retrospectively re-assessed APACHE II scores from the charts of 186 randomly selected patients admitted to our medical and surgical intensive care units. These 'new' scores were compared with the original scores calculated by the attending physician. We found that most scores calculated retrospectively were lower than the original scores; 51% of our patients would have received a lower score, 26% a higher score and only 23% would have remained unchanged. Overall, the original scores changed by an average of 6.4 points. We identified various sources of error and concluded that wide variability exists in APACHE II scoring in everyday clinical practice, with the score being generally overestimated. Accurate use of the APACHE II scoring system requires adherence to strict guidelines and regular training of medical staff using the system.

APACHE↗
PubMed2001

alpha-atrial natriuretic peptide, cyclic guanosine monophosphate, and endothelin in plasma as markers of myocardial depression in human septic shock.

OBJECTIVE: To assess the value of alpha-atrial natriuretic peptide (alpha-ANP), second messenger cyclic guanosine monophosphate (cGMP,) and endothelin as markers of myocardial depression in septic shock. DESIGN: Prospective observational study. SETTING: Medical intensive care unit (ICU) of a university hospital. PATIENTS: Fourteen consecutive patients with septic shock and arterial and pulmonary artery catheters in place. MEASUREMENTS AND MAIN RESULTS: Hemodynamic variables and plasma levels of alpha-ANP, cGMP, and endothelin were measured every 6 hrs for 3 days after admission. Eight patients died from shock in the ICU. The nadir left ventricular stroke work index (LVSWI) was below 35 g/m2 in all patients, and the median peak circulating alpha-ANP (n < 68 pg/mL) was 276 pg/mL (range, 79-1056), the median peak cGMP (n < 2.1 ng/mL) was 8.1 ng/mL (range, 3.2-29.7), and the median peak endothelin (n < 5.3 pg/mL) was 15.5 pg/mL (range, 8.5-33.9), supranormal in all patients. Outcome groups differed in the course of cardiac index and LVSWI, which were lower in nonsurvivors despite similar filling pressures and more intensive inotropic treatment (p < .01). The course of alpha-ANP, cGMP, and endothelin plasma levels also differed between groups, with higher levels in nonsurvivors (p < .05). As for pooled data, the mean daily or nadir LVSWI inversely related to mean daily or peak alpha-ANP, cGMP, and endothelin levels, respectively (p < .05). The area under the receiver operating characteristic curve for myocardial depression (LVSWI < 35 g/m2) was for alpha-ANP and endothelin 0.77, and for cGMP 0.85 (p < .01). The optimum cutoff values for alpha-ANP, cGMP, and endothelin were 172 pg/mL, 4.5 ng/mL, and 10.0 pg/mL, respectively. The sensitivity for myocardial depression of alpha-ANP, cGMP, and endothelin was 68%, 77%, and 72%, and the specificity was 82%, 93%, and 69%, respectively. CONCLUSIONS: Circulating alpha-ANP, endothelin, and, particularly, cGMP may be markers of the myocardial depression of human septic shock, which is associated with mortality.

Adult↗
PubMed2000

Antithrombin III in patients with severe sepsis: a pharmacokinetic study.

OBJECTIVES: To evaluate the safety, pharmacokinetics, and the practicability of two different antithrombin III (AT III) high-dose regimens in patients with severe sepsis. DESIGN: Prospective, open, randomized, 2 parallel groups, multinational clinical trial. SETTING: Eleven academic medical center intensive care units (ICU) in Austria, Belgium, Denmark, Germany, Norway and Sweden. PATIENTS: Thirty-three patients with severe sepsis who received standard supportive care and antimicrobial therapy, in addition to the administration of AT III. INTERVENTIONS: Patients received an intravenous loading dose of 6,000 IU AT III followed by either intermittent bolus infusions of 1,000 IU AT III every 4 h or a continuous infusion of 250 IU AT III/h for 4 days, resulting in a total dose for both dosage regimens of 30,000 IU AT III. MEASUREMENTS: All patients were evaluated for safety and all but one for pharmacokinetics. RESULTS AND CONCLUSIONS: The administration of AT III was safe and well tolerated. The overall 28-day all-cause mortality was 30% (43% intermittent bolus infusions; 21% continuous infusion). The mean probability of dying according to the SAPS II was 48%. The difference in mortality between both groups was within the range of chance. AT III plasma levels were elevated from low baseline levels to above 120% soon after onset of AT III therapy and remained at these levels for the treatment phase of 4 days. Functional and immunologic levels of AT III corresponded very well. With an overall median volume of distribution of 4.5 l (range: 2.4-6.5 l), AT III only moderately extended beyond plasma. The overall median elimination half-life was 18.6 h (range: 5.1-37.4). Overall, median response was 1.75% per IU/kg (range: 1.14-2.8). The variability of elimination parameters was quite noteworthy (CV = 41-59%), whereas distribution-related parameters showed a moderate variability (CV = 24%). In spite of this variability, both high-dose IV regimens reliably provided AT III levels above 120% for all but one patient. An increased mortality was observed for patients with a distribution volume exceeding 4.5 l (or a response < 1.7% per IU/kg). AT III distribution volumes above 4.5 l might indicate a capillary leak phenomenon. The continuous infusion regimen was slightly preferred by the investigators with regard to practicability.

Adult↗
PubMed2000

The effect of mild endotoxemia during low arginine plasma levels on organ blood flow in rats.

OBJECTIVE: Arginine is the sole precursor in the generation of the vasodilating agent nitric oxide. Arginine plasma levels are low in situations associated with endotoxemia such as major trauma, sepsis, and experimental obstructive jaundice. The aim of the study was to evaluate hemodynamics at low arginine plasma levels during a low-grade endotoxemia. DESIGN: Randomized, placebo-controlled animal laboratory investigation. SUBJECTS: Male Wistar rats (n = 29), anesthetized. INTERVENTIONS: Rats were randomly assigned to receive (at t = 0 mins) an intravenous infusion of 1.5 mL of 0.9% NaCl (SAL, n = 12) or 1.5 mL of an arginase (3200 IU) solution (ASE, n = 17) over a 20-min period. After the SAL or ASE infusion, rats were randomly assigned to receive an intravenous endotoxin (lipopolysaccharide [LPS], 150 microg/kg in 1.0 mL of 0.9% NaCl; ASE/LPS, n = 10 and SAL/LPS, n = 6) challenge or a control infusion (1.0 mL of 0.9% NaCl; ASE/SAL, n = 7 and SAL/SAL, n = 6) at t = 30 mins. MEASUREMENTS AND MAIN RESULTS: Organ blood flow was measured at t = 270 mins, using radiolabeled microspheres. At this time point, arginine plasma levels were lower in the ASE-treated rats (ASE/SAL vs. SAL/SAL and ASE/LPS vs. SAL/LPS, both p < .005, respectively). Cardiac output, mean arterial pressure, and therefore total peripheral resistance were similar for all groups. In the LPS-treated animals (SAL/LPS and ASE/LPS), cardiac output was maintained by a higher heart rate compensating the lower stroke volume. Organ blood flow to the small intestine and splanchnic blood flow was lower in the ASE/LPS-treated rats (both p < .05 when compared with other groups). Total liver blood flow was similar for all groups; the lower splanchnic blood flow was compensated for by a higher hepatic arterial blood flow. CONCLUSION: The present study shows that low arginine plasma levels do not influence organ blood flow, whereas, during a low-grade endotoxemia, low arginine plasma levels result in reduced blood flow to the small intestine.

Animals↗
PubMed2000

Coagulation inhibitor replacement in sepsis is a potentially useful clinical approach.

In sepsis, levels of the endogenous coagulation inhibitors antithrombin III and protein C are lowered as a result of complex formation with multiple activated clotting factors. In addition, their activity can further be curtailed by proteolytic inactivation. Loss of antithrombin III and protein C activity blocks the endogenous control mechanism for thrombin generation resulting in a state of systemic activation of coagulation and inflammatory processes. Levels of tissue factor pathway inhibitor, a third endogenous coagulation inhibitor, are increased in sepsis rather than decreased, probably reflecting a depletion of the endothelial cell bound tissue factor pathway inhibitor pool with loss of its endothelial protective function. Administration of any of these three inhibitors in various animal species and sepsis models reduces morbidity and mortality. In addition to their anticoagulant effects, these inhibitors also have various anti-inflammatory activities that may contribute to their protective effects. Phase II studies in patients with severe sepsis using coagulation inhibitors have indicated that this therapeutic approach may be useful. Large-scale phase III trials will ultimately decide whether adjunctive coagulation inhibitor replacement will have a place in the treatment of patients with severe sepsis.

Animals↗
PubMed2000

Inflammatory mediators in dengue virus infection in children: interleukin-8 and its relationship to neutrophil degranulation.

The chemokine interleukin-8 (IL-8) has chemoattractant activity for neutrophils and is able to activate and degranulate these cells. We investigated whether IL-8 may exert these effects in children with dengue virus infection. Circulating levels of IL-8, neutrophilic elastase (a constituent of the azurophilic granula of neutrophils), and lactoferrin, released from specific granula, were measured in 186 children with dengue virus infection, 33 healthy children as negative controls and 11 children with bacterial infections as positive controls. Levels of IL-8 on admission were elevated in 71% of the dengue patients, while the elastase and lactoferrin levels were increased in 68 and 17% of patients, respectively. These levels were significantly higher than in healthy children (P < 0.05) for IL-8 and elastase but not for lactoferrin (by the Wilcoxon-Mann-Whitney [WMW] U test). Similar levels of IL-8 were found in patients with bacterial infections. Levels of IL-8 and elastase in patients with shock were significantly higher than in patients without shock (P = 0.02; WMW), but those of lactoferrin were not. IL-8 correlated with elastase and lactoferrin (r = 0.19 and P = 0.009 versus r = 0.24 and P = 0.001, respectively; two-tailed Spearman rank correlation). Thus, IL-8 levels are increased in most patients with dengue virus infection and correlate with degranulation of neutrophils as well as with some clinical and hemodynamic variables. These findings suggest a role for IL-8 in the pathogenesis of dengue virus infection.

Cell Degranulation↗
PubMed2000

Effect of the mechanical ventilatory cycle on thermodilution right ventricular volumes and cardiac output.

The purpose of this study was to evaluate right ventricular (RV) loading and cardiac output changes, by using the thermodilution technique, during the mechanical ventilatory cycle. Fifteen critically ill patients on mechanical ventilation, with 5 cmH(2)O of positive end-expiratory pressure, mean respiratory frequency of 18 breaths/min, and mean tidal volume of 708 ml, were studied with help of a rapid-response thermistor RV ejection fraction pulmonary artery catheter, allowing 5-ml room-temperature 5% isotonic dextrose thermodilution measurements of cardiac index (CI), stroke volume (SV) index, RV ejection fraction (RVEF), RV end-diastolic volume (RVEDV), and RV end-systolic volume (RVESV) indexes at 10% intervals of the mechanical ventilatory cycle. The ventilatory modulation of CI and RV volumes varied from patient to patient, and the interindividual variability was greater for the latter variables. Within patients also, RV volumes were modulated more by the ventilatory cycle than CI and SV index. Around a mean value of 3.95 +/- 1.18 l. min(-1). m(-2) (= 100%), CI varied from 87.3 +/- 5.2 (minimum) to 114.3 +/- 5.1% (maximum), and RVESV index varied between 61.5 +/- 17.8 and 149.3 +/- 34.1% of mean 55.1 +/- 17.9 ml/m(2) during the ventilatory cycle. The variations in the cycle exceeded the measurement error even though the latter was greater for RVEF and volumes than for CI and SV index. For mean values, there was an inspiratory decrease in RVEF and increase in RVESV, whereas a rise in RVEDV largely prevented a fall in SV index. We conclude that cyclic RV afterloading necessitates multiple thermodilution measurements equally spaced in the ventilatory cycle for reliable assessment of RV performance during mechanical ventilation of patients.

Aged↗
PubMed1999

[Stress ulcer prophylaxis in the intensive care unit].

In the early years of intensive care a stress ulcer related bleeding, occurring in 20-30% of the IC population, became recognized as a significant cause of morbidity and mortality. Due to improved intensive care medicine (including adequate early resuscitation, analgesia, sedation) the incidence of stress ulcer-related bleeding in the IC has decreased markedly. Without pharmacological prophylaxis incidences ranging from 0.6 to 6% were reported. It is not recommended to apply stress ulcer prophylaxis on a routine basis, it should be reserved for patients with an increased risk of a stress ulcer-related bleeding. In patients with neurotrauma, severe burn, recent peptic ulcer or bleeding and those with coagulopathy prophylaxis with ranitidine is advised.

Anti-Ulcer Agents↗
PubMed1999

Case report of a patient with an intimal sarcoma of the pulmonary trunk presenting as a pulmonary embolism.

A fatal case of an 89-year-old woman with an intimal sarcoma obstructing the pulmonary trunk and an open foramen ovale is presented. Clinical symptoms, physical examination and further evaluation originally raised suspicion of a pulmonary embolism. Recent classification systems, specific radiological and pathological characteristics of sarcomas of the pulmonary trunk are discussed.

Aged↗
PubMed1999

Exploding the albumin myth.

In this article arguments are given to stop the current practise of infusing albumin in patients in shock and low levels of serum albumin. Correcting the albumin levels is not correlated with better survival or change in morbidity. Fluid therapy including the use of synthetic plasma expanders is the accepted therapy for patients in sceptic shock.

Albumins↗
PubMed1999

Prediction of microbial infection and mortality in medical patients with fever: plasma procalcitonin, neutrophilic elastase-alpha1-antitrypsin, and lactoferrin compared with clinical variables.

Fever suggests the likelihood of severe microbial infection. Abnormal temperature, tachycardia, tachypnea, and abnormal white blood cell counts define the systemic inflammatory response syndrome (SIRS). In 300 hospitalized medical patients with fever, we determined clinical variables and procalcitonin, elastase-alpha1-antitrypsin, and lactoferrin levels in plasma. Of the patients, 71% had clinical infection (by clinical judgment) and 44% had microbial infection (by microbiological testing). SIRS occurred in 95%, and the 28-day mortality rate was 9%. The sensitivity for predicting microbial infection, bacteremia, and mortality was less but the specificity was greater for supranormal procalcitonin, elastase-alpha1-antitrypsin, and lactoferrin levels than for SIRS. The area under the receiver operating characteristic curve (AUC) for microbial infection was higher for procalcitonin and elastase-alpha1-antitrypsin levels than for clinical variables and lactoferrin level. The AUC for bacteremia was also higher for inflammatory factors (>0.70; P < .001) than for clinical variables. The AUC for mortality (P < .05) was 0.79 for the respiratory rate, 0.69 for elastase-alpha1-antitrypsin level, 0.65 for heart rate, 0.61 for procalcitonin level, and 0.60 for white blood cell count. In febrile medical patients, plasma procalcitonin and elastase-alpha1-antitrypsin levels may predict microbial infection and bacteremia better than (and mortality as well as) do clinical symptoms.

Adolescent↗
PubMed1999

Continuous cardiac output in septic shock by simulating a model of the aortic input impedance: a comparison with bolus injection thermodilution.

BACKGROUND: To compare continuous cardiac output obtained by simulation of an aortic input impedance model to bolus injection thermodilution (TDCO) in critically ill patients with septic shock. METHODS: In an open study, mechanically ventilated patients with septic shock were monitored for 1 (32 patients), 2 (15 patients), or 3 (5 patients) days. The hemodynamic state was altered by varying the dosages of dopamine, norepinephrine, or dobutamine. TDCO was estimated 189 times as the series average of four automated phase-controlled injections of iced 5% glucose, spread equally over the ventilatory cycle. Continuous model-simulated cardiac output (MCO) was computed from radial or femoral artery pressure. On each day, the first TDCO value was used to calibrate the model. RESULTS: TDCO ranged from 4.1 to 18.2 l/min. The bias (mean difference between MCO and TDCO) on the first day before calibration was -1.92 +/- 2.3 l/min (mean +/- SD; n = 32; 95% limits of agreement, -6.5 to 2.6 l/min). The bias increased at higher levels of cardiac output (P < 0.05). In 15 patients studied on two consecutive days, the precalibration ratio TDCO:MCO on day 1 was 1.39 +/- 0.28 (mean +/- SD) and did not change on day 2 (1.39 +/- 0.34). After calibration, the bias was -0.1 +/- 0.8 l/min with 82% of the comparisons (n = 112) < 1 l/min and 58% (n = 79) < 0.5 l/min, and independent of the level of cardiac output. CONCLUSIONS: In mechanically ventilated patients with septic shock, changes in bolus TDCO are reflected by calibrated MCO over a range of cardiac output values. A single calibration of the model appears sufficient to monitor continuous cardiac output over a 2-day period with a bias of -0.1 +/- 0.8 l/min.

Adult↗
PubMed1999

Hypernatremia in the intensive care unit: an indicator of quality of care?

OBJECTIVE: To assess the frequency of hypernatremia in patients who were admitted to an intensive care unit (ICU) and to determine the correlation of hypernatremia with the clinical outcomes, durations of the patients' stays in the ICU, and other clinical variables. DESIGN: Retrospective survey. SETTING: University teaching hospital. PATIENTS: All patients (total, 389) who were admitted to the medical ICU of the department of internal medicine during 1 yr. MEASUREMENTS: The database of our hospital's mainframe computer was searched for sodium values > or = 150 mmol/L that were registered in the year 1995. These data were then matched with the registration numbers of all patients who were admitted to our medical ICU between January 1 and December 31, 1995. In this way, we identified all patients in whom hypernatremia was present at admission or those who developed hypernatremia in the course of their stay in our ICU. The prevalence and duration of hypernatremia (defined as a serum sodium concentration of > or = 150 mmol/L or more) were determined; the correlation of hypernatremia with clinical outcome, duration of ICU stay, Acute Physiology and Chronic Health Evaluation II scores, and other clinical variables were evaluated; and changes in fluid administration in response to hypernatremia and fluid regimens in the period preceding hypernatremia were examined. MAIN RESULTS: Of a total of 389 patients who were admitted in 1995, hypernatremia was present at admission in 34 patients (8.9%). The average duration of hypernatremia in these patients was 16.2 (range, 4-56) hrs. A total of 22 patients (5.7%) developed hypernatremia in the course of their stay in the ICU. The average duration of hypernatremia in this group was 34.7 (range, 4-89) hrs. Moderately elevated levels of sodium had been detected in most of these patients (n = 21) in the days before the development of severe hypernatremia; however, adjustments in fluid infusion aimed at preventing the occurrence of hypernatremia were either lacking (n = 7) or inadequate (n = 11). Hospital-acquired hypernatremia vs. hypernatremia present at admission to the ICU was associated with a higher mortality rate (32% vs. 20.3%, respectively; p < .01). CONCLUSIONS: Despite frequent measurement of sodium levels in patients in the ICU, hypernatremia is a relatively common occurrence. Initial treatment of hypernatremia is often inadequate, and sometimes treatment is delayed. The development of hypernatremia is associated with adverse outcomes for patients developing hypernatremia in the ICU. Hypernatremia could potentially be used as an indicator of quality of care in the medical ICU.

APACHE↗
PubMed1999

Continuous infusion of lorazepam versus medazolam in patients in the intensive care unit: sedation with lorazepam is easier to manage and is more cost-effective.

OBJECTIVE: To evaluate the effectiveness of lorazepam and midazolam for long-term sedation of critically ill, mechanically ventilated patients. DESIGN: Double-blind, randomized, controlled study. SETTING: Medical intensive care unit in a university teaching hospital. PATIENTS: Sixty-four evaluable adult patients admitted to the intensive care department requiring mechanical ventilation for >3 days. INTERVENTIONS: Patients were randomized to receive blinded solutions of either lorazepam or midazolam by continuous infusion. The lowest dose that achieved an adequate sedation was infused. The maximum dose allowed for each drug was 60 mg/hr for midazolam and 4 mg/hr for lorazepam. Sedation was assessed initially and at least every 8 hrs thereafter on a seven-point scale if the sedation was adequate and every 2 hrs if it was not. MEASUREMENTS AND MAIN RESULTS: Measurements included the score on the sedation scale, the time between determination of the desired level of sedation and the achievement of that level, and plasma concentrations. It is significantly easier to reach a desired level of sedation with lorazepam than with midazolam. No difference in recovery was found in the 24 hrs after discontinuation of therapy. The fact that there are many factors influencing midazolam pharmacokinetics may explain the more difficult management of desired sedation levels. The equipotent dose of 10 mg of midazolam proved to be 0.7 mg of lorazepam in long-term sedation. The average cost for therapy with midazolam was approximately ten times more than that with lorazepam. CONCLUSIONS: Lorazepam is a useful alternative to midazolam for the long-term sedation of patients in the medical intensive care unit and provides easier management of the sedation level. Sedation with lorazepam offers a significant cost-savings.

Adult↗
PubMed1999

Circulating endothelin and nitrate-nitrite relate to hemodynamic and metabolic variables in human septic shock.

Activation of the nitric oxide (NO) pathway over that of endothelin in the vessel wall, as judged from circulating endothelin and nitrate-nitrite (NN) levels, may partly account for the hypotension associated with vasodilation, diminished catecholamine sensitiveness and O2 extraction, and lactic acidemia in human septic shock. In a prospective study, 14 consecutive patients with septic shock and a pulmonary artery catheter in place were included. For 3 days after admission, serial measurements of hemodynamic variables and plasma levels of endothelin and NN were done. The patients had a hyperdynamic circulation. Except for a higher final blood lactate level and more treatment with vasoconstricting catecholamines in nonsurvivors, global hemodynamic and O2-related variables did not differ between outcome groups. On the day of admission, circulating endothelin and NN levels were elevated and related to elevated levels of tumor necrosis factor-alpha and interleukin-6. The levels of endothelin increased in time in nonsurvivors as compared with survivors. The NN levels declined in survivors but not in nonsurvivors. The systemic vascular resistance indices (SVRI), global O2 extraction ratios, and blood lactate levels directly related to the endothelin levels. SVRI and global O2 extraction ratios inversely, and the lactate blood levels directly, related to NN levels, and the hemodynamic and metabolic parameters related directly to the ratio between endothelin and NN plasma levels on the days of the study. The vessel wall factors did not relate to the creatinine levels. The results suggest that the hemodynamic and metabolic peripheral abnormalities of human septic shock are mediated in part by cytokine-activated endothelin and NO systems in the vessel wall. They also suggest that increased production rather than diminished renal clearance accounts for elevated levels of NN and endothelin and that the latter are associated with a poor outcome.

Adult↗
PubMed1999

Reduced arginine plasma levels are the drive for arginine production by the kidney in the rat.

In bile duct ligated rats, arginase (ASE) release from damaged hepatocytes results in low arginine (ARG) levels despite maximal renal ARG production. Plasma ARG levels were restored by reducing gut-derived endotoxemia that lowered circulating ASE activity although maintaining increased renal production. From this it was not clear if the higher renal ARG production was induced by the low grade endotoxemia or the low arginine plasma levels. The separate and combined influence of both factors on ARG metabolism was studied in the rat. Male Wistar rats received either bovine liver ASE, to lower ARG levels, or saline (SAL). Following the ASE or SAL infusion, rats were randomized to receive a low dose endotoxin (LPS) or SAL infusion. In ASE/SAL- and ASE/LPS-treated rats, ARG levels were lower compared with SAL/SAL (p<.005) and SAL/LPS (p<.005). The increased ARG production by the kidneys and gut proved to be independent of LPS but related to reduced ARG plasma levels (both p<.05 when compared with SAL/SAL and SAL/LPS). Metabolism of related amino acids was not explanatory. The study concluded that a low grade endotoxemia did not influence the metabolism of ARG by the gut, kidney, and liver. Reductions in ARG plasma by ASE treatment, irrespective a low dose endotoxin, were the drive for ARG production by the gut and the kidney.

Animals↗