Ventilator setting in ICUs: comparing a Dutch with a European cohort.

BACKGROUND: From data collected during the third International Study on Mechanical Ventilation (ISMV), we compared data from a Dutch cohort with a European cohort. We hypothesised that tidal volumes were smaller and applied positive end-expiratory pressure (PEEP) was higher in the Netherlands, compared with the European cohort. We also compared use of non-invasive ventilation (NIV) and outcomes in both cohorts. METHODS: A post-hoc analysis of a prospective observational study of patients receiving mechanical ventilation. RESULTS: Tidal volumes were smaller (7.6 vs. 8.1 ml÷kg predicted bodyweight) in the Dutch cohort and applied PEEP was higher (8 vs. 6 cm H2O). Fewer patients admitted in the Netherlands received NIV as first mode of mechanical ventilation (7.1 vs. 16.7%). Fewer patients in the Dutch cohort developed an ICU-acquired pneumonia (4.5 vs. 12.3%, p < 0.01) and sepsis (5.7 vs. 10.9%, p = 0.03), but more patients were diagnosed as having delirium (15.8 vs. 4.6%, p < 0.01). ICU and in-hospital mortality rates were 19% and 25%, respectively, in Dutch ICUs vs. 26% and 33% in Europe (p = 0.06 and 0.03). CONCLUSION: Tidal volumes were smaller and applied PEEP was higher in the Dutch cohort compared with international data, but both Dutch and international patients received larger tidal volumes than recommended for prevention or treatment of acute respiratory distress syndrome. NIV as first mode of mechanical ventilation is less commonly used in the Netherlands. The incidence of ICU-acquired pneumonia is lower and of delirium higher in the Netherlands compared with international data.

[A young woman with a labile mood, hyperactivity, hyperthermia and exhaustion: symptoms of lethal catatonia]. / Een jonge vrouw met een labiele stemming, hyperactiviteit, hyperthermie en uitputting: symptomen van letale catatonie.

A 22-year-old woman went through a period with a labile mood that first turned into psychotic hyperactivity and was then followed by hyperthermia and exhaustion. This was accompanied by diminished consciousness, sinus arrhythmia and respiratory insufficiency. With a working diagnosis of 'lethal catatonia' she was treated by electroshock and later also with the antipsychotic agent quetiapine. After a few electroshock treatments her vital functions improved and ultimately, the patient recovered. Lethal catatonia is characterised by acute excitation, catalepsy, autonomic instability and fever, which can lead to death. The syndrome often starts with mood instability, which turns into hyperactivity accompanied by hyperthermia and exhaustion. The creatine kinase, blood-sedimentation rate and leukocyte count are often raised. Lethal catatonia must be distinguished from the neuroleptic malignant syndrome, serotonin syndrome and encephalitis. The pathophysiology is unclear, but most reports suggest a hypodopaminergic state. The syndrome is associated with affective disorders and schizophrenia. Early recognition is made difficult by the low frequency of appearance, diversity in nomenclature, and strong resemblance to other syndromes.

Filter run time in CVVH: pre- versus post-dilution and nadroparin versus regional heparin-protamine anticoagulation.

BACKGROUND/AIMS: To study the effect of different modes of continuous veno-venous haemofiltration (CVVH) on filter run time (FRT). METHODS: We studied, in two consecutive prospective, randomised and crossover studies, 16 and 15 patients with acute renal failure during critical illness. Study A compared pre- versus post-dilution, and study B compared regional anticoagulation with heparin (pre-filter) and protamine (post-filter) (HP) versus nadroparin (NP) pre-filter. All CVVH sessions were standardised. Analyses were by Wilcoxon rank sum tests. RESULTS: Study A: During pre-dilution the median FRT was 45.7 vs. 16.1 h in post-dilution CVVH (p = 0.005). The median creatinine clearance during pre-dilution was 33 vs. 45 ml/min in post-dilution (p = 0.001). Study B: During NP, median FRT was 39.5 vs. 12.3 h during HP CVVH (p = 0.045). CONCLUSIONS: Pre-dilution CVVH results in the greatest FRT but a lower plasma creatinine clearance compared to post-dilution. Regional anticoagulation with heparin-protamine resulted in a significantly shorter FRT compared to systemic NP anticoagulation.

A before-after study of multi-resistance and cost of selective decontamination of the digestive tract.

BACKGROUND: We compared standard antibiotic use with an antibiotic policy based on selective decontamination of the digestive tract (SDD) for cost and microbiology. PATIENTS AND METHODS: A 2-year before-after observational study was performed in an 11-bed, mixed medical and surgical intensive care unit (ICU). We included all consecutive patients admitted to the ICU 1 year before and 1 year after institution of SDD (patients admitted within the 2-month SDD run-in period were excluded from analysis). In the year before SDD, 513 patients were treated in the ICU (mean APACHE II 19.5), compared to 529 in the year with SDD (mean APACHE II 19.4). RESULTS: The duration of mechanical ventilation was shorter in the SDD-treated patients (median 3, interquartile range [IQR] 2-7 days vs median 4 days, IQR 2-10, p = 0.03). The total of ICU variable costs, microbiological costs and antibiotic costs were equal in both episodes: euro 1,171 versus euro 1,168 per patient). Aerobic gram-negative bacilli (AGNB) and multiresistant AGNB were found less frequently in SDD-treated patients, RR 0.37 (95% CI 0.33-0.42) and RR 0.28 (95% CI 0.19-0.42). Multi-resistant AGNB in tracheal secretions and urine more than 72 hours after admission were completely absent in SDD-treated patients. CONCLUSION: The overall cost per patient treated during an antibiotic policy including SDD was equal to a policy supporting standard antibiotic care. In addition, duration of ventilation decreased and a trend was shown towards a decreased Length of ICU and hospital stay. Less frequently, cultures from organ sites containing AGNB were found during SDD and the number of multi-resistant strains was significantly reduced at organ sites, in particular trachea and urine. Fewer patients were colonized with multi-resistant AGNB but these numbers did not reach statistical significance.

Valproic acid intoxication: sense and non-sense of haemodialysis.

INTRODUCTION: Valproic acid is increasingly used in the treatment of epilepsy, and also prescribed for bipolar affective disorders, schizoaffective disorders, schizophrenia and migraine prophylaxis. We describe two case reports involving valproic acid intoxication with ingestion of ethanol. METHODS: One patient was treated by supportive care, one patient received haemodialysis. RESULTS: From analysis of plasma concentrations before and during haemodialysis (pre- and post-filter) it is shown that valproic acid can be effectively eliminated by haemodialysis when plasma levels are way above 100 microg/ml. In the literature, plasma protein binding is reported to be around 90% for levels within the therapeutic range. In our patient plasma protein binding was around 50% after treatment with haemodialysis. CONCLUSION: These findings make haemodialysis in valproic acid intoxication a sensible therapeutic option with increasing efficiency when plasma concentration is high. Furthermore our findings suggest that lowering valproic acid concentrations to a therapeutic level by haemodialysis does not necessarily result in an immediate, simultaneous increase in plasma protein binding of valproic acid.

Use of 1H-NMR to determine the distribution of lecithin between the micellar and vesicular phases in model bile.

Biliary cholesterol/phospholipid vesicles play an important role in the pathogenesis of gallstone disease. A prerequisite for the study of the lipid composition and stability of these vesicles is a reliable method to quantify the amount of vesicular lipid. In the present report we show that NMR can be used to determine the distribution of biliary lecithin between the micellar and vesicular phases. The relatively large size of the vesicles leads to such a broadening of the lipid resonances that they are no longer visible in high resolution 1H-NMR spectra. Since micelles are much smaller, lipid present in the micellar phase does give rise to sharp peaks in 1H-NMR spectra. Micellar lecithin can easily be quantified in these spectra. The resonances of cholesterol are masked by the closely related bile acid that is present in a much higher concentration. By determining the difference between chemically and NMR estimated lecithin, the distribution of this phospholipid between the micellar phase and vesicular phase can be assessed. We have compared the results of NMR with gel permeation and density gradient ultracentrifugation. Using standard fractionation conditions, both gel permeation and density gradient ultracentrifugation lead to an underestimation of vesicular lecithin, the difference being minor at relatively high total lipid concentrations (10 g/dl) but large in diluted model bile. We conclude that 1H-NMR can be used to determine the distribution of lecithin in model bile.(ABSTRACT TRUNCATED AT 250 WORDS)

Isolation of a potent cholesterol nucleation-promoting activity from human gallbladder bile: role in the pathogenesis of gallstone disease.

Gallbladder bile contains nucleation-promoting activity that binds to concanavalin A. The activity was found in gallbladder bile from cholesterol gallstone patients but also in gallbladder bile from patients without stones and patients with pigment stones. Bile from patients with multiple cholesterol gallstones contained high concanavalin A-binding nucleation-promoting activity. The activity was much lower in bile samples from pigment stone patients, patients without stones and patients with a solitary cholesterol stone. Serum contained very little activity and no concanavalin A-binding nucleation-promoting activity could be demonstrated in gallbladder mucosa. This suggests that concanavalin A-binding nucleation promoter is produced in the liver or bile duct epithelium. The activity was fully resistant to digestion with pronase but was heat labile and could be destroyed by prolonged incubation with a mixed glycosidase preparation indicating that sugar residues are important for this activity. On a Superose 12 gel permeation column, promoting activity eluted in two major peaks at apparent molecular weights of 150 +/- 30 kD (n = 5) and less than 5 kD respectively. The mobility on the column was not influenced by pronase digestion. The factor with the higher molecular weight could be isolated further by polyacrylamide gel electrophoresis under nondenaturing conditions. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the apparent molecular weight of the glycoprotein was 130 kD. In conclusion, gallbladder bile contains nucleation-promoting activity that binds to concanavalin A. The activity is increased in bile from patients with multiple cholesterol gallstones and could therefore play an important role in the pathogenesis of gallstone disease.

An appraisal of the role of biliary phospholipases in the pathogenesis of gallstone disease.

Human bile contains proteins that influence nucleation of cholesterol. Recently, it has been suggested that activity of phospholipases in bile may play a role in this process. To study the influence of phospholipase on nucleation we have determined the effect of phospholipases A2, C and D on the nucleation time of model bile. Phospholipase C decreased the nucleation time, whereas phospholipase A2 inhibited nucleation. The phospholipases were effective only at relatively high concentrations. Phospholipase D was strongly inhibited in model bile and probably only influenced the nucleation time by an aspecific protein effect. The cleavage products of the different phospholipases were determined in native bile samples of 14 cholesterol gallstone patients, 6 patients without stones and 4 patients with pigment stones. In all samples, choline, phosphorylcholine and free fatty acids (FFA) could be detected. However, there was no significant difference between the three groups of patients. The rate of production of choline, phosphorylcholine and FFA was measured in bile incubated at 37 degrees C. Again, there was no significant difference between the three groups of patients. We conclude that phospholipase activity in bile does not play an important role in the pathogenesis of gallstone disease.