Sedation assessment in critically ill patients with bispectral index.

BACKGROUND AND OBJECTIVE: Clinical sedation assessment becomes insufficient in deeply sedated patients. Bispectral index as a processed electroencephalogram parameter provides a continuous and observer-independent value reported to change with sedation. The aim of this prospective observational study was to determine the reliability and possible confounding factors of the bispectral index to assess sedation in surgical intensive care patients. METHODS: Following major surgery, bispectral index, body temperature and electromyographic activity of 44 ventilated patients were recorded. Sedation levels were assessed with Ramsay sedation score. RESULTS: Although bispectral index correlated with Ramsay sedation score (-0.64; P < 0.01) we found that in deeply sedated patients temperature instability and electromyographic activity increased bispectral index. Bispectral index correlated significantly with electromyographic activity (0.80; P < 0.01) and with an increase of body temperature (0.55; P < 0.01) not only in all patients but also in clinically deeply sedated patients (0.57; P < 0.01 and 0.46; P < 0.05). CONCLUSIONS: Only under certain conditions, such as low muscular activity and body temperature stability, may the bispectral index be a useful addition to clinical scoring in the sedation assessment of critically ill patients.

Homocyst(e)ine metabolism in hemodialysis patients treated with vitamins B6, B12 and folate.

Hyperhomocyst(e)inemia is commonly accepted as an independent atherosclerotic risk factor. In most hemodialysis patients, serum homocyst(e)ine is markedly elevated and may contribute to premature atherosclerosis in these patients. Whereas the beneficial effect of folate supplementation on serum homocyst(e)ine has been extensively studied, there are less detailed studies on the effects of cobalamin and pyridoxal phosphate alone, or in combination with folate. We examined the effect of a four-week course of intravenous treatment with folate (1.1 mg), cobalamin (1.0 mg), and pyridoxal phosphate (5.0 mg), administered once (group 1), twice (group 2) or thrice (group 3) weekly in 33 hemodialysis patients divided in three groups of 11 patients. All patients were followed for a further four weeks after treatment was stopped. Serum homocyst(e)ine, cobalamin, folate and pyridoxal phosphate, as well as the metabolites of homocyst(e)ine, methylmalonate, 2-methylcitrate and cystathionine, were determined before, during and after treatment. Baseline serum homocyst(e)ine correlated significantly with serum folate (P=0.0149), cobalamin (P=0.0047) and pyridoxal phosphate (P=0.0408). Correlations independent from the other metabolites or vitamins were found for methylmalonate (P=0.003) and folate (P=0.029). All regimens increased serum cobalamin significantly (in group 1 from 444 +/- 215 to 17,303 +/- 11,989 pg/ml, P<0.01; in group 2 from 542 +/- 633 to 44,896 +/- 15,772 pg/ml, P<0.001; in group 3 from 548 +/- 394 to 77,961 +/- 31,546 pg/ml, P<0.001), but did not increase any of the other vitamin levels. Serum homocyst(e)ine was lowered significantly by 39.8% +/- 31.9% (P<0.05) with two and by 30.1% +/- 26.9% (P<0.05) with three vitamin dosages weekly, but not with one dosage weekly. Since methylmalonate is known to be a sensitive marker of cobalamin deficiency, the data support an important influence of cobalamin levels on baseline homocyst(e)ine levels. Increasing cobalamin levels and additional treatment with folate and pyridoxal phosphate 156 may decrease serum homocyst(e)ine in the same way as high doses of folate alone.

[Homocysteine and its metabolites in chronic renal insufficiency and the effect of a vitamin replacement]. / Homocystein und seine Metaboliten bei chronischer Niereninsuffizienz und der Einfluss einer Vitaminsubstitution.

BACKGROUND: Hyperhomocysteinemia has been increasingly recognized as an important risk factor for elevated atherosclerotic vascular disease in chronic renal failure. We measured in patients with chronic renal failure homocysteine and metabolites of its 2 metabolic pathways, transulfuration (cystathionine, cysteine) and remethylation (methionine, methylmalonic acid, 2-methylcitric acid). PATIENTS AND METHODS: Eleven patients on conservative treatment (creatinine clearance 10 to 30 ml/min) and 50 chronic uremic subjects on regular hemodialysis were included in the study. Twenty-two of the dialysis patients received daily oral multivitamin supplementation containing 10 mg vitamin B6, 6 micrograms vitamin B12, and 1 mg folic acid during the last year before the study started. RESULTS: In the hemodialysis group homocysteine levels were higher compared with the patients on conservative treatment. Hemodialysis patients with additional vitamin supplementation showed significantly lower homocysteine levels than those without. The pattern of metabolites was different to these results: all metabolites were higher in hemodialysis patients, too (significant for cysteine and methionine), but vitamin supplementation failed to lower all metabolites. CONCLUSION: Analysis of metabolites additional to homocysteine levels may help to understand different results in evaluation of atherosclerotic risk of hyperhomocysteinemia in chronic renal failure.

Evidence of altered homocysteine metabolism in chronic renal failure.

The fasting serum concentrations of total homocysteine and metabolites of transsulfuration (cystathionine, cysteine, methylmalonic acid, 2-methylcitric acid) and remethylation (methionine) were determined by gas chromatography-mass spectrometry in 40 nondialyzed patients with chronic renal disease and in 50 patients with end-stage renal disease requiring chronic maintenance hemodialysis. The nondialyzed patients and 28 of the dialysis patients did not receive additional vitamin supplementations. Twenty-two of the dialysis patients received daily oral vitamin preparations containing 10 mg pyridoxine (vitamin B(6)), 6 microg cyanocobalamin (vitamin B(12)), and 1 mg folic acid. In the nondialyzed patients, linear regression analysis showed positive correlations between serum concentrations of creatinine and total homocysteine (r = 0.68, p < 0.0001), cystathionine (r = 0.73, p < 0. 0001), methylmalonic acid (r = 0.77, p < 0.0001), and 2-methylcitric acid (r = 0.81, p < 0.0001). Serum homocysteine was positively correlated with serum concentrations of cystathionine (r = 0.59, p < 0.0001), cysteine (r = 0.69, p = 0.004), methylmalonic acid (r = 0. 64, p = 0.0001), and 2-methylcitric acid (r = 0.64, p < 0.0001). There was no significant correlation between serum concentrations of homocysteine and methionine (r = -0.14, p = 0.63). In the hemodialysis patients receiving oral vitamin supplementation, serum homocysteine and cystathionine concentrations were significantly lower than in hemodialysis patients not receiving vitamins (homocysteine 21.8 +/- 1.1 vs. 33.2 +/- 3.7 micromol/l, p = 0.0004; cystathionine 2,075.9 +/- 387.1 vs. 3,171.3 +/- 680.2 nmol/l, p = 0. 02; mean +/- SEM). In summary, our results show increased intermediate products of the transsulfuration pathway, but no increase in remethylation of homocysteine in chronic renal disease, including end-stage renal disease requiring chronic maintenance dialysis.

Hyperhomocysteinemia and the risk for vascular disease in hemodialysis patients.

The objective of this study was to examine if hyperhomocysteinemia is associated with occlusive vascular disease in hemodialysis patients. The study design included risk factor analysis and determination of serum homocysteine in hemodialysis patients. Fifty chronic uremic patients on regular hemodialysis treatment were studied. Twenty-four patients had coronary, cerebral, or peripheral signs of occlusive vascular disease. Cerebral vascular disease was diagnosed by computed tomography, arterial angiography, or Doppler sonography of the carotid and vertebral arteries. Coronary vascular disease was diagnosed by documented history of myocardial infarction or by coronary angiography. The diagnosis of peripheral vascular disease was established by angiography of the lower limb arteries. In all control patients, Doppler sonography of the carotid, vertebral, and lower limb arteries and thallium-201 exercise imaging were without pathologic results. Measurements included blood pressure, body mass index, smoking behavior, serum homocysteine (measured by gas chromatography/mass spectrometry), serum total, low-density lipoprotein, and high-density lipoprotein cholesterol, lipoprotein (a), triglycerides, and plasma fibrinogen. In a stepwise multiple logistic regression analysis, high serum homocysteine was significantly associated with occlusive arterial disease (R = 0.23; P = 0.031). Furthermore, hypertension (R = 0.18; P = 0.058), but not serum total, low-density lipoprotein, and high-density lipoprotein cholesterol, lipoprotein (a), triglycerides, diabetes mellitus, body mass index, plasma fibrinogen, and smoking behavior, was significantly associated with atherosclerosis. Our results support the hypothesis that hyperhomocysteinemia is an independent risk factor for vascular disease in hemodialysis patients.

Isolation of an ultrafilterable Ca(2+)-ATPase inhibitor from the plasma of uraemic patients.

1. Calcium concentration and Ca(2+)-ATPase activity under basal conditions and after maximal stimulation with calmodulin were measured in erythrocytes from 32 patients with end-stage renal failure on haemodialysis and from 27 healthy subjects. 2. In patients with renal failure the Ca2+ concentration in erythrocytes was elevated compared with healthy subjects (4.27 +/- 1.02 versus 2.86 +/- 0.57 mumol/l, P less than 0.05). 3. Basal Ca(2+)-ATPase activity was lower in the patients with renal failure than in healthy subjects (4.62 +/- 1.34 versus 5.43 +/- 1.23 pmol of phosphate min-1 10(-6) erythrocytes). After maximal stimulation, Ca(2+)-ATPase activity reached 6.93 +/- 2.81 pmol of phosphate min-1 10(-6) erythrocytes in the patients with renal failure, whereas in healthy subjects stimulation yielded a Ca(2+)-ATPase activity of 32.54 +/- 8.48 pmol of phosphate min-1 10(-6) erythrocytes. 4. Incubation of erythrocytes from healthy subjects with plasma from uraemic patients caused inhibition of Ca(2+)-ATPase. Likewise, the ultrafiltrate from plasma obtained by haemofiltration treatment inhibited Ca(2+)-ATPase. 5. Gel chromatography of the ultrafiltrate and laser desorption/ionization mass spectroscopy revealed that a fraction containing substances with a molecular mass of about 300 Da inhibited Ca(2+)-ATPase. 6. It is concluded that, in uraemia, a Ca(2+)-ATPase inhibitor accumulates in the plasma, and this could contribute to the toxicity of uraemia by inhibiting cellular Ca2+ transport in erythrocytes and possibly other tissues.

[Long-term results following kidney transplantation. An empirical analysis of 467 allogeneic kidney transplants concerning the effect of clinical and immunological variables on graft function]. / Langzeitergebnisse nach Nierentransplantation. Eine empirische Analyse von 467 allogenen Nierentransplantationen über den Einfluss klinischer und immunologischer Variablen auf die Transplantatfunktion.

In a homogeneous group of 467 cadaver kidney transplants performed within one single center between 1979 and 1987, we analysed the influence of main risk factors on long-term survival up to 72 months. Calculating survival rates by Kaplan-Meier actuarial methods the overall graft survival exceeded 71%. The corresponding patient survival was higher than 90%. A good HLA-A-B and DR match was of significant positive influence. Patients who received cyclosporine had a significant better outcome compared to conventional immunosuppressive therapy. A marked advantage was demonstrated for such variables as number of pretransplant blood transfusions, number of rejection episodes, preservation time and renal function as measured by plasma creatinine. Independently age was a main risk factor for curtailed graft survival. Although immunological factors accounted for more than 45% of transplant loss we found a surprisingly high percentage of infections (36%). Vascular problems or technical failure were below 10%. We conclude that a profound clinical examination in the pretransplant period is of high value and remains necessary to identify high risk patients in the long range.

[Griseochelin methyl ester, a new polyether derivative with antiviral activity]. / Griseochelinmethylester, ein neues Polyether-Derivat mit antiviraler Wirksamkeit.

The methylester of griseochelin (1) is a new chemically-made antiviral derivate of the antibiotic griseochelin isolated from fermentations of Streptomyces griseus. It belongs to the polyether group and possesses antiviral activity against enveloped RNA and DNA viruses cultivated in chicken embryo cells (CEC), namely influenzavirus A/WSN, vesicularstomatitis virus (Indiana), vaccinia virus (Lister) and herpes simplex hominis virus type 1 (Kupka). The methylester of griseochelin failed to show virucidal effects on extracellular influenza vacciniavirus particles or to influence virus adsorption and penetration processes. The antibiotic in concentrations of 125-15 micrograms/ml inhibited the virus-induced cytopathic effect of the above mentioned viruses and caused over 90 per cent plaque reduction. Addition of 1 during a one-step growth cycle of influenzavirus A at 4 and 6 h p.i. resulted in complete suppression of virus multiplication at the control niveau of the virus yield accumulated to the same time point. A partial reversibility of the antiviral action against influenzavirus A could be achieved. Coxsackie A9 virus growth in human fibroblast cells was not affected by the inhibitor. Electron-optical observations showed a failure of the formation of the viral capside proteins of HSV type 1 at the second halftime of the replication cycle in CEC-infected and 1-treated cultures.

[Incidence of conjunctival and corneal changes in dialysis patients]. / Zur Häufigkeit von Bindehaut- und Hornhautveränderungen bei Dialysepatienten.

Deposits of calcium salts in the conjunctivas and corneas of 72 patients showed a statistically significant correlation to the duration of hemodialysis. The deposition of calcium salts is not influenced by other signs of disturbed calcium metabolism (Ca-PO4 product, alkalic phosphatase) or the patient's age.

[Hemodynamic and metabolic aspects of bicarbonate dialysis]. / Aspects hémodynamiques et métaboliques de la dialyse au bicarbonate.

After a historical review of the dialytic technics for correction of acidosis, the advantages of bicarbonate dialysis are stressed specially as regards the greater hemodynamic stability that it secures when short but highly efficient dialysis are performed and as regards its lowering effect on the blood triglycerides levels.

[Stimulation of hematopoietic stem cells with serum specimens of patients with polycythemia vera]. / Stimulation hämatopoietischer Vorläuferzellen durch Serumphroben von Patienten mit Polycythaemia vera.

Mononuclear cells from the peripheral blood of normals and patients with terminal renal insufficiency on hemodialysis were set up in methylcellulose cultures with and without addition of sera of patients with polycythemia vera (pv). In renal patients we found more intensive stimulation of hematopoietic progenitor cells after addition of pv-sera than in normals. The findings suggest a hematopoietic factor in sera of pv which is not identical with erythropoietin.

Effect of hypertonic glucose on the muscular cramps of hemodialysis.

The effect of hypertonic (50%) glucose injected for relief of hemodialysis-induced muscular cramps was studied in 15 chronically uremic, nondiabetic patients who experienced a total of 44 cramp episodes. In a double-blind trial either 50 mL (or less) of hypertonic glucose or physiologic (0.9%) saline solution was injected, and the therapeutic response was evaluated. Of a total of 44 episodes of cramps, 26 were treated with hypertonic glucose and 18 with normal saline. Treatment with hypertonic glucose relieved 17 of 26 episodes, in contrast to only five of 18 episodes relieved with 50 mL of normal saline (P less than 0.016). No complications related to hypertonic glucose administration were observed. Hypertonic glucose seems to be safe and effective for the relief of dialysis-induced cramps. It also avoids undesirable loading with sodium and mannitol, which have been suggested for treatment of dialysis-induced cramps.