Changes in the Dutch law on medical research.
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Biomedical subjects
Publications and source records attributed to Peter H J van der Voort.
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OBJECTIVE: To describe the pattern of defecation in critically ill ventilated patients and the influence of selective decontamination (SDD) and other medication. DESIGN: Descriptive cohort study. SETTING: Mixed surgical-medical ICU in a university Hospital. PATIENTS: Ventilated patients with a length of stay >or=7 days taking part in a study on SDD. MEASUREMENTS: Daily registration of defecation, SOFA (sepsis-related organ failure assessment score) score, administration of dopamine, noradrenaline, morphine and other medications. RESULTS: The first defecation occurred after a mean of 6.2 days. Patients with defecation within 6[Symbol: see text]days had lower mean SOFA scores, received more cisapride and lactulose and less dopamine, noradrenaline and morphine, and had a shorter duration of mechanical ventilation and ICU stay. On 57% of the days, no stools were produced; on 31% diarrhea, and on 12%, normal stools. Patients receiving SDD had more days with normal stools and less with diarrhea. Diarrhea was preceded by the administration of lactulose in the majority of patients. CONCLUSION: Time to first defecation correlated with severity of illness, vasoactive medication, administration of morphine, cisapride and lactulose, duration of mechanical ventilation and length of stay. Diarrhea seemed at least partially iatrogenic.
OBJECTIVES: To determine the effect of a change in the "Dutch Directive on Medical Research Involving Human Subjects" (DD) on the number of eligible intensive care unit (ICU) patients for medical research. In addition, we determined how family members experience their role as acting representative for giving informed consent, and in turn whether patients feel their representatives would do well representing them. DESIGN AND SETTING: Prospective observational study in three Dutch ICUs. PARTICIPANTS: 714 consecutive ICU patients. Analysis was restricted to 211 patients who were incapacitated for more than 24h after ICU admission. MEASUREMENTS AND RESULTS: The old DD left 45.5% of patients without a legal representative; with the new DD this figure declines to 8.1%. Older age was significantly associated with the impossibility of obtaining informed consent in the old DD; after the change there was no effect of age. The median grade of confidence that representatives had in giving informed consent for incapacitated patients was 8.0 (IQR 7.0-9.0) on a scale from 0 to 10. Patients gave an equal median grade to their representatives. CONCLUSION: When patients' adult children are not legally allowed to give informed consent, older patients are excluded from medical research, causing selection bias. The change in the DD has increased the number of surrogates allowed to give informed consent. Representatives felt very confident in their ability to represent the patients. In turn patients were equally confident that their representatives were able to represent them.
INTRODUCTION: Metabolic alkalosis is a commonly encountered acid-base derangement in the intensive care unit. Treatment with the carbonic anhydrase inhibitor acetazolamide is indicated in selected cases. According to the quantitative approach described by Stewart, correction of serum pH due to carbonic anhydrase inhibition in the proximal tubule cannot be explained by excretion of bicarbonate. Using the Stewart approach, we studied the mechanism of action of acetazolamide in critically ill patients with a metabolic alkalosis. METHODS: Fifteen consecutive intensive care unit patients with metabolic alkalosis (pH > or = 7.48 and HCO3- > or = 28 mmol/l) were treated with a single administration of 500 mg acetazolamide intravenously. Serum levels of strong ions, creatinine, lactate, weak acids, pH and partial carbon dioxide tension were measured at 0, 12, 24, 48 and 72 hours. The main strong ions in urine and pH were measured at 0, 3, 6, 12, 24, 48 and 72 hours. Strong ion difference (SID), strong ion gap, sodium-chloride effect, and the urinary SID were calculated. Data (mean +/- standard error were analyzed by comparing baseline variables and time dependent changes by one way analysis of variance for repeated measures. RESULTS: After a single administration of acetazolamide, correction of serum pH (from 7.49 +/- 0.01 to 7.46 +/- 0.01; P = 0.001) was maximal at 24 hours and sustained during the period of observation. The parallel decrease in partial carbon dioxide tension was not significant (from 5.7 +/- 0.2 to 5.3 +/- 0.2 kPa; P = 0.08) and there was no significant change in total concentration of weak acids. Serum SID decreased significantly (from 41.5 +/- 1.3 to 38.0 +/- 1.0 mEq/l; P = 0.03) due to an increase in serum chloride (from 105 +/- 1.2 to 110 +/- 1.2 mmol/l; P < 0.0001). The decrease in serum SID was explained by a significant increase in the urinary excretion of sodium without chloride during the first 24 hours (increase in urinary SID: from 48.4 +/- 15.1 to 85.3 +/- 7.7; P = 0.02). CONCLUSION: A single dose of acetazolamide effectively corrects metabolic alkalosis in critically ill patients by decreasing the serum SID. This effect is completely explained by the increased renal excretion ratio of sodium to chloride, resulting in an increase in serum chloride.
BACKGROUND: The objective of this study was to elucidate the most practical and effective laboratory measurement for monitoring citrate in critically ill patients undergoing citrate-anticoagulated continuous venovenous haemofiltration (CVVH). METHODS: This observational study was performed at the mixed medical and surgical intensive care unit of a regional teaching hospital. The study population comprised ten consecutive critically ill patients with acute renal failure and indication for haemofiltration with the use of regional anticoagulation with citrate. Serum samples for the measurement of citrate and total and ionised calcium were taken from the pre- and post-filter compartments and from the arterial circulation of patients during citrate-anticoagulated CVVH. RESULTS: Receiver operating characteristic (ROC) curve analysis showed that for detecting citrate overdose (defined as a citrate concentration >1.0 mmol/L) the best cut-off limits for total/ionised calcium and ionised calcium were 2.1 and 0.8 mmol/L, respectively. Sensitivity and specificity for the cut-off limit of 2.1 for total/ionised calcium were 89% and 100%, and 84% and 100%, respectively, for the cut-off limit of 0.8 mmol/L for ionised calcium. CONCLUSIONS: In patients without liver insufficiency, total/ionised calcium performed slightly better than ionised calcium in detecting elevated citrate concentrations. However, because of the simplicity of its measurement, ionised calcium is preferred. Measurement of citrate is not necessary.
INTRODUCTION: The introduction of orthogonal polarization spectral (OPS) imaging in clinical research has elucidated new perspectives on the role of microcirculatory flow abnormalities in the pathogenesis of sepsis. Essential to the process of understanding and reproducing these abnormalities is the method of quantification of flow scores. METHODS: In a consensus meeting with collaboraters from six research centres in different fields of experience with microcirculatory OPS imaging, premeditated qualifications for a simple, translucent and reproducible way of flow scoring were defined. Consecutively, a single-centre prospective observational validation study was performed in a group of 12 patients with an abdominal sepsis and a new stoma. Flow images of the microcirculation in vascular beds of the sublingual and stoma region were obtained, processed and analysed in a standardised way. We validated intra-observer and inter-observer reproducibility with kappa cross-tables for both types of microvascular beds. RESULTS: Agreement and kappa coefficients were >85% and >0.75, respectively, for interrater and intrarater variability in quantification of flow abnormalities during sepsis, in different subsets of microvascular architecture. CONCLUSION: Semi-quantitative analysis of microcirculatory flow, as described, provides a reproducible and transparent tool in clinical research to monitor and evaluate the microcirculation during sepsis.
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OBJECTIVE: To explore the relationship between cholesterol levels and the adrenal cortisol response to synacthen in critically ill patients. DESIGN: Prospective observational study. PATIENTS: Critically ill patients with multiple organ dysfunction syndrome (MODS) with possible adrenal dysfunction defined as unexplained hypotension, ongoing inotropic support, unexplained fever, unexplained hyponatraemia or a combination of these symptoms. MEASUREMENTS: HDL-cholesterol levels (HDL), total cholesterol levels (TC), and triglycerides (TG) before administration of synacthen. LDL-cholesterol was calculated using the Friedewald formula. Basal cortisol and response to 250 microg synacthen intravenously was measured. A cortisol rise of 0.25 micromol/l in a 30-min or 60-min blood sample after synacthen infusion was defined as a proper adrenal response. RESULTS: Patients with a proper response to synacthen showed higher HDL-cholesterol levels than patients without that response ( P=0.02). Severity of disease as measured by APACHE II or SOFA was not a confounder. LDL-cholesterol levels were extremely low in both responders and non-responders and were not associated with the absolute rise in cortisol. In linear and logistic regression analysis HDL-cholesterol was the sole predictor of cortisol response. CONCLUSIONS: Adrenal cortisol response to a "classic" 250-microg synacthen test relates in critically ill patients to HDL-cholesterol levels. LDL and TC levels did not show such a relation. These findings are in concordance with known biochemical pathways of cortisol production.
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OBJECTIVE: To evaluate whether calcium adjusted for albumin can be used to monitor calcium homeostasis in critically ill patients. DESIGN: Prospective single-single center observational study. SETTING: Clinical laboratory and critical care unit of a regional teaching hospital. PATIENTS: Fifty-three paired samples were from 36 patients requiring intensive care treatment. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Total calcium, albumin-adjusted calcium, and ionized calcium were measured in critically ill patients during an 8-wk period. Calcium was adjusted for albumin using the formula that is most frequently used in The Netherlands. Using ionized calcium as the gold standard, albumin-adjusted calcium overestimated hypercalcemia and totally missed hypocalcemia. The same seemed to be true for other formulas used for albumin or protein adjustment of calcium concentrations. CONCLUSIONS: Albumin-adjusted calcium cannot be used in an intensive care setting to monitor reliably the calcium levels in critically ill patients and should be replaced by measurement of ionized calcium.
OBJECTIVE: The study aimed to identify both the frequency and the determinants of drug administration errors in the intensive care unit. DESIGN: Administration errors were detected by using the disguised-observation technique (observation of medication administrations by nurses, without revealing the aim of this observation to the nurses). SETTING: Two Dutch hospitals. PATIENTS: The drug administrations to patients in the intensive care units of two Dutch hospitals were observed during five consecutive days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 233 medications for 24 patients were observed to be administered (whether ordered or not) or were observed to be omitted. When wrong time errors were included, 104 administrations with at least one error were observed (frequency, 44.6%), and when they were excluded, 77 administrations with at least one error were observed (frequency, 33.0%). When we included wrong time errors, day of the week (Monday, odds ratio [OR] 2.69, confidence interval [CI] 1.42-5.10), time of day (6-10 pm, OR 0.28, CI 0.10-0.78), and drug class (gastrointestinal, OR 2.94, CI 1.48-5.85; blood, OR 0.12, CI 0.03-0.54; and cardiovascular, OR 0.38, CI,0.16-0.90) were associated with the occurrence of errors. When we excluded wrong time errors, day of the week (Monday, OR 3.14, CI 1.66-5.94), drug class (gastrointestinal, OR 3.47, CI 1.76-6.82; blood, OR 0.21, CI 0.05-0.91; and respiratory, OR 0.22, CI 0.08-0.60), and route of administration (oral by gastric tube, OR 5.60, CI 1.70-18.49) were associated with the occurrence of errors. In the hospital without full-time specialized intensive care physicians (which also lacks pharmacy-provided protocols for the preparation of parenteral drugs), more administration errors occurred, both when we included (OR 5.45, CI 3.04-9.78) and excluded wrong time errors (OR 4.22, CI 2.36-7.54). CONCLUSIONS: Efforts to reduce drug administration errors in the intensive care unit should be aimed at the risk factors we identified in this study. Especially, focusing on system differences between the two intensive care units (e.g., presence or absence of full-time specialized intensive care physicians, presence or absence of protocols for the preparation of all parenteral drugs) may help reduce suboptimal drug administration.