Comparison of two methods to obtain a desired first isepamicin peak in intensive care patients.

A randomized multicenter study in intensive care unit (ICU) patients, evaluated the capacity of a Bayesian method to obtain an optimal first isepamicin (ISP) peak of 80 mg/L in comparison to a fixed loading dose (LD). Patients (n=236) over 18 years of age were enrolled from 6 September 1997 to 17 July 1999 and randomly assigned to received ISP in a calculated dose (CD) or a loading dose (LD) of 25 mg/kg body weight. The CD was estimated using a specific population model with Bayesian methodology implemented in the PKS program (Abbott PKS, Abbott Diagnostics, Rungis, France). The data required included age, body weight, height, gender and serum creatinine. ISP disposition is described by a one-compartment model. Blood samples were drawn 1 and 24 h after the start of infusion for fluorescence polarization immunoassay measurement of serum ISP concentrations. The predictive performance was assessed by computing bias and precision. Peak concentrations were significantly higher in CD group than the LD group (84.2 +/- 28.6 vs. 74.7 +/- 24.1 mg/L, respectively; P=0.008), but trough levels were comparable. The optimal ISP peak was attained by a significantly higher percentage of CD patients (P=0.018), and by significantly more CD patients on mechanical ventilation (P=0.025), and with simplified acute physiological scores (SAPS) > 35 (P=0.002). Pharmacokinetic parameters were similar for the two groups with large interindividual variations. Mean (+/- SD) volume of distribution of ventilated patients (72%) was significantly higher than of nonventilated patients (23.31 +/- 7.35 vs. 20.60 +/- 6.30 L, respectively; P=0.001). No relationship was found between the volume of distribution and SAPS. Total clearance was significantly correlated with estimated CLCR (creatinine clearance) (P=0.0001). Precision (RMSE) is better for CD than for LD strategy, respectively 27.96 and 28.66 mg/L. The Bayesian method was significantly more accurate and performed particularly well in ventilated patients and patients with high SAPS, compare to an LD of 25 mg/kg to obtain a first ISP peak of 80 mg/L in ICU patients. Therefore, a fixed dose of 28.5 mg/kg would be also adequate to reach a peak of 80 mg/L.

[Hemodynamic effects of enoximone and comparison with dobutamine in patients with chronic respiratory insufficiency and pulmonary arterial hypertension]. / Effets hémodynamiques de l'énoximone et comparaison avec la dobutamine chez l'insuffisant respiratoire chronique avec HTAP.

The aim of this study was to assess the effects of enoximone on the right ventricle and pulmonary hypertension in 10 patients (53 to 84 years) with chronic obstructive airway disease resulting in acute or chronic respiratory failure requiring mechanical ventilation in 9 cases. These effects were compared with those of dobutamine. All patients were in sinus rhythm and 6 had signs of right ventricular failure. Haemodynamic and 2D echocardiographic (study of left and right ventricular function) measurements were made under basal conditions (TB1), with 10 micrograms/kg/mn of dobutamine (TDob), again under basal conditions (TB2) three hours after the end of the dobutamine infusion, and then 30 minutes after an intravenous bolus (1 mg/kg) of enoximone (TE1) relayed by an infusion of 10 micrograms/kg/mn at 3 hours (TE2) and at 12 hours (TE3). The results (x +/- SD) were studied by a 2 factor variance analysis and compared by Student's test with Dunnett's correction. Cardiac index increased similarly by about 45% with enoximone (2.8 +/- 0.8 vs 4.1 +/- 1 l/min/m2; p less than 0.001 at TE2) and dobutamine, although the heart rate did not change significantly. Systemic arterial resistance fell significantly with enoximone (31.3 +/- 11 vs 21.3 +/- 6.8 IU; p less than 0.05 at TE2) but mean arterial pressures were unchanged; mean pulmonary artery pressures decreased from TE1 to TE3 (27.6 +/- 6.9 vs 22.6 +/- 6.3 mmHg; p less than 0.05 at TE2) mainly because pulmonary artery diastolic pressures decreased from TE1 to TE3 (20.1 +/- 4 vs 11.1 +/- 5.2 mmHg; p less than 0.05 at TE3).(ABSTRACT TRUNCATED AT 250 WORDS)

[Acute gangrenous acalculous cholecystitis disclosed by postoperative septic shock]. / Cholécystites aiguës gangréneuses alithiasiques révélées par un choc septique postopératoire.

Three cases of acute gangrenous acalculous cholecystitis, revealed by a postoperative septic shock, are reported. Clinical examination was negative and the surgery gave the diagnosis. Infection with biliary stasis and ischaemia accounts for this pathological entity. The very serious prognosis of this condition can only be reversed by cholecystectomy.

[Acute respiratory and circulatory failure. Prognostic value of plasma fibronectin levels]. / Insuffisances respiratoires et circulatoires aiguës. Valeur pronostique du taux de fibronectine plasmatique.

Plasma fibronectin (FNp) concentrations were measured in 63 patients with acute respiratory failure and 28 patients with circulatory failure, using Laurell's electroimmunoassay method. Measurements were made in the acute phase and repeated in the course of the disease. The mean FNp concentration in 20 controls was 262 +/- 59 mg/l. FNp values were normal in the acute phase of chronic obstructive pulmonary disease and in cardiogenic pulmonary oedema. In contrast, they were significantly decreased in adult respiratory distress syndrome and in acute pneumonia, as well as in acute circulatory failure, notably from septic shock. FNp values were also considerably reduced in patients with severe disseminated intravascular coagulation syndrome. Clinical improvement was accompanied by a return to normal of FNp concentrations. The mortality rate was greater in patients with low FNp values than in those with normal values.

[Treatment of severe acute asthma in adults]. / Traitement des asthmes aigus graves de l'adulte.

Although abnormal blood gases are unusual in status asthmaticus, hypercapnia indicates a considerable increase in bronchial resistance. The authors report their experience of 106 personal cases of acute severe asthma. Emergency management of acute respiratory failure consisted in symptomatic therapy (low rate oxygen or mechanical ventilation after nasal intubation). Corticosteroids, rehydration, antibiotics and beta-2 adrenergic agents were associated. Mechanical ventilation was necessary in patients who developed alterations of consciousness or PaCO2 above 60 mm Hg (8 kPa). In respirator-patients, sedative drugs were needed. Terbutaline and salbutamol were occasionally beneficial but epinephrine remains the drug of choice. In our series of 106 cases (79 with hypercapnia) the overall mortality was 3.8 p. 100. Of the 33 cases who underwent mechanical ventilation, there were 4 deaths (12 p. 100). A review of the literature showed a much higher mortality in other series.

[Current humoral profile in acute severe asthma]. / Profil humoral actuel des asthmes aigus graves.

This study examined the relationships between acid-base disorders, hypoxemia, electrolyte imbalances, plasma adrenaline (Ad) and noradrenaline (NAd) in 94 patients with acute severe asthma. Criteria of inclusion were [PaO2 + PaCO2/.8] less than 140 mmHg when breathing air (FiO2 = 21%) and/or PaCO2 greater than or equal to 45 mmHg. PaCO2 was closely related to H+ in those patients with hypercapnia: H+ nmol/l = 0.88 PaCO2 + 4 (r 0.91 ; n = 61; p less than 0.001). However, among the 62 acidotic cases (pH less than or equal to 7.36), 24 were classified as respiratory, 22 as mixed and 16 as metabolic. A loose though highly significant relationship was found between PaO2 and PaCO2 (when breathing air). Blood lactate, which was 3.61 +/- 1.9 mmol/l (+/- SD), was not correlated with anion gap or H+, but was loosely related to PaO2 and kalemia. Ad (1.53 +/- 1.17 nmol/l) and NAd (5.85 +/- 3.44 nmol/l), measured at the time of admission in 27 patients (FIO2 = 21%), varied significantly from those of a control group (p less than 0.01). NAd was correlated with H+, lactate and especially PaCO2, whereas no correlation could be established for Ad with these factors or NAd values. On the average, kalemia, phosphatemia and calcemia were lowered. In conclusion, mixed and metabolic acidosis were more common in this study than in a previous personal series and were not necessarily associated with an increase in blood lactate. Drugs taken prior to hospitalization must be considered in the pathophysiology of hyperlactatemia, which appears to be one among several factors linked to NAd levels.

Adult respiratory distress syndrome and silicone injection.

This report describes a case of adult respiratory distress syndrome (ARDS) after massive subcutaneous injections of silicone. The patient, a 23 year-old transsexual man, treated with mechanical ventilation, died on the 12th day of hospital, in septic shock and refractory hypoxemia. Autopsy findings revealed empty vacuoles surrounded by macrophages in various organs, especially in lung tissue. Toxicological analysis by emission by high frequency induced plasma showed silicone in the organs with histological lesions. The pathophysiology of this ARDS is considered.

[Optic neuritis and sarcoidosis (author's transl)]. / Névrite optique et sarcoïdose.

Case report of a sarcoidosis in a young west-indies feurale: ganglio-mediastinal and lung lesions, liver and salivary glands right optic nerve with retrobulbar optic neuritis. This lesions were quickly and totally reversible with tetracosactide and prednisone therapy.

[Hemoglobinopathies in West-African immigrant workers in France (author's transl)]. / Hémoglobinopathies chez les travailleurs de l'Afrique de l'Ouest en France.

In this paper are brought the results obtained in two Parisian hospitals during a survey of abnormal hemoglobins in 540 immigrant workers coming from Africa, mostly from Mali, Mauritania and Senegal. All the subjects investigated were male and between 20 and 40 years old. The studies were performed following internationally standardized technics. The most frequent abnormalities were: Hb S found in 16.3%, Hb C (6.6%), alpha-thalassemia trait (3.1%) and beta-thalassemia trait (3.1%). Some rare abnormalities were also found: delta-chain variants, hereditary persistance of foetal hemoglobin, Hb Hope and Hb Grady. This work emphasizes the high frequency of the different hemoglobin disorders in this population. The easy diagnostic of electrophoretically detectable variants is compared to the more complex situation of thalassemia leading probably to an under estimation of the percentage.

Fever and associated changes in glomerular filtration rate erase anticipated diurnal variations in aminoglycoside pharmacokinetics.

Netilmicin (4.5 mg/kg of lean body weight) was administered intravenously once every 24 h at 10 a.m. to 23 patients (group I) and at 10 p.m. to 20 patients (group II) with severe infection. No significant differences (P > 0.05) in peak and trough concentrations in serum were found between groups I and II (peak, 12.9 +/- 3.7 versus 12.8 +/- 4.4 mg/liter, respectively; trough, 0.7 +/- 0.6 versus 0.8 +/- 0.6 mg/liter, respectively [mean +/- standard deviation]). Pharmacokinetic parameters (half-life [5.0 +/- 2.2 versus 4.9 +/- 1.8 h], volume of distribution [0.32 +/- 0.04 versus 0.35 +/- 0.06 liter/kg], and total clearance [0.920 +/- 0.417 versus 1.015 +/- 0.546 ml/min/kg]) were similar in the two groups and not influenced by the time of administration. These data suggest that, in the once-daily schedule, 10 a.m. or 10 p.m. administration had no influence on netilmicin levels in serum and pharmacokinetic parameters in these ill febrile patients.