Pharmacokinetic evaluation of linezolid administered intravenously in obese patients with pneumonia.

OBJECTIVES: Altered linezolid pharmacokinetics (PK) in obese individuals has been hypothesized in previous studies. However, specific dosing recommendations for this population are still lacking. The main goal of this study was to evaluate PK/pharmacodynamic (PKPD) target attainment when using a 600 mg intravenous q12h linezolid dose against MRSA in obese patients with pneumonia. METHODS: Fifteen obese pneumonia patients with a confirmed or suspected MRSA involvement treated with 600 mg of intravenous linezolid q12h were studied for 3 days. Population PK modelling was used to characterize the PK variability and to screen for influential patient characteristics. Monte Carlo simulations were carried out to investigate the PTA and time to target attainment for linezolid dosing against MRSA. RESULTS: A two-compartment model with linear elimination adequately described the data. Body weight and age both have a significant effect on linezolid clearance. Simulations demonstrate that the probability of attaining PKPD targets is low. Moreover, the PTA decreases with weight, and increases with age. Standard linezolid dosing in obese pneumonia patients with MRSA (MICs of 1-4 mg/L) leads to unacceptably low (near zero to 60%) PTA for patients <65 years old. CONCLUSIONS: Standard linezolid dosing is likely to provide insufficient target attainment against MRSA in obese patients. Body weight and especially age are important characteristics to be considered when administering linezolid to treat MRSA infections.

Duration of salmeterol-induced bronchodilation in mechanically ventilated chronic obstructive pulmonary disease patients: a prospective clinical study.

INTRODUCTION: Delivery of bronchodilators with a metered-dose inhaler (MDI) and a spacer device in mechanically ventilated patients has become a widespread practice. However, except for the short-acting beta2-agonist salbutamol, the duration of action of other bronchodilators, including long-acting beta2-agonists, delivered with this technique is not well established. The purpose of this study was to examine the duration of bronchodilation induced by the long-acting beta2-agonist salmeterol administered with an MDI and a spacer in a group of mechanically ventilated patients with exacerbation of chronic obstructive pulmonary disease (COPD). METHODS: Ten mechanically ventilated patients with acute exacerbation of COPD received four puffs of salmeterol (25 microg/puff). Salmeterol was administered with an MDI adapted to the inspiratory limb of the ventilator circuit using an aerosol cloud enhance spacer. Static and dynamic airway pressures, minimum (Rint) and maximum (Rrs) inspiratory resistance, and the difference between Rrs and Rint (DeltaR) were measured before and at 15, 30, and 60 minutes as well as at 2, 3, 4, 6, 8, 10, and 12 hours after salmeterol administration. The overall effects of salmeterol on respiratory system mechanics and heart rate during the 12-hour study period were analyzed by nonparametric Wilcoxon signed rank test. RESULTS: Salmeterol caused a significant decrease in dynamic and static airway pressures, Rint, and Rrs. These changes were evident at 30 minutes and remained significant for 8 hours after salmeterol administration. The duration of bronchodilation varied significantly among patients, lasting in some patients more than 10 hours and wearing off in others in less than 6 hours. CONCLUSIONS: It is concluded that four puffs of salmeterol delivered with an MDI and a spacer device induces significant bronchodilation in mechanically ventilated patients with COPD exacerbation, the duration of which is highly variable, precluding definite conclusions in regard to optimum dosing schedules.

Malignant mixed tumor of the nasal cavity.

Parotid gland is the most common location of malignant mixed tumors. Three different subtypes of these tumors exist: carcinoma ex pleomorphic adenoma, carcinosarcoma, and metastasizing mixed tumor. Carcinoma ex-pleomorphic adenoma is by far the most common subtype. Although unusual sites of these tumors have been published, we report an extremely rare case of a malignant mixed tumor located in the nasal cavity.

Impact of lung ultrasound on clinical decision making in critically ill patients.

PURPOSE: To assess the impact of lung ultrasound (LU) on clinical decision making in mechanically ventilated critically ill patients. METHODS: One hundred and eighty-nine patients took part in this prospective study. The patients were enrolled in the study when LU was requested by the primary physician for (1) unexplained deterioration of arterial blood gases and (2) a suspected pathologic entity [pneumothorax, significant pleural effusion (including parapneumonic effusion, empyema, or hemothorax), unilateral atelectasis (lobar or total), pneumonia and diffuse interstitial syndrome (pulmonary edema)]. RESULTS: Two hundred and fifty-three LU examinations were performed; 108 studies (42.7%) were performed for unexplained deterioration of arterial blood gases, and 145 (57.3%) for a suspected pathologic entity (60 for pneumothorax, 34 for significant pleural effusion, 22 for diffuse interstitial syndrome, 15 for unilateral lobar or total lung atelectasis, and 14 for pneumonia). The net reclassification index was 85.6%, indicating that LU significantly influenced the decision-making process. The management was changed directly as a result of information provided by the LU in 119 out of 253 cases (47%). In 81 cases, the change in patient management involved invasive interventions (chest tube, bronchoscopy, diagnostic thoracentesis/fluid drainage, continuous venous-venous hemofiltration, abdominal decompression, tracheotomy), and in 38 cases, non-invasive (PEEP change/titration, recruitment maneuver, diuretics, physiotherapy, change in bed position, antibiotics initiation/change). In 53 out of 253 cases (21%), LU revealed findings which supported diagnoses not suspected by the primary physician (7 cases of pneumothorax, 9 of significant pleural effusion, 9 of pneumonia, 16 of unilateral atelectasis, and 12 of diffuse interstitial syndrome). CONCLUSION: Our study shows that LU has a significant impact on decision making and therapeutic management.

Physiologic comparison of neurally adjusted ventilator assist, proportional assist and pressure support ventilation in critically ill patients.

UNLABELLED: To compare, in a group of difficult to wean critically ill patients, the short-term effects of neurally adjusted ventilator assist (NAVA), proportional assist (PAV+) and pressure support (PSV) ventilation on patient-ventilator interaction. METHODS: Seventeen patients were studied during NAVA, PAV+ and PSV with and without artificial increase in ventilator demands (dead space in 10 and chest load in 7 patients). Prior to challenge addition the level of assist in each of the three modes tested was adjusted to get the same level of patient's effort. RESULTS: Compared to PSV, proportional modes favored tidal volume variability. Patient effort increase after dead space was comparable among the three modes. After chest load, patient effort increased significantly more with NAVA and PSV compared to PAV+. Triggering delay was significantly higher with PAV+. The linear correlation between tidal volume and inspiratory integral of transdiaphragmatic pressure (PTPdi) was weaker with NAVA than with PAV+ and PSV on account of a weaker inspiratory integral of the electrical activity of the diaphragm (∫EAdi)-PTPdi linear correlation during NAVA [median (interquartile range) of r(2), determination of coefficient, 16.2% (1.4-30.9%)]. CONCLUSION: Compared to PSV, proportional modes favored tidal volume variability. The weak ∫EAdi-PTPdi linear relationship during NAVA and poor triggering function during PAV+ may limit the effectiveness of these modes to proportionally assist the inspiratory effort.

Impact of prolonged treatment with linezolid on the human gut flora.

A 79-year-old male was treated for 6 months with linezolid for prosthetic knee joint osteomyelitis. At the end of this 6-month period, quantitative stool cultures revealed partial loss of the normal gut flora and concomitant colonization by opportunistic pathogens such as Pseudomonas aeruginosa and other Gram-negatives. Follow-up cultures at 6 weeks after antibiotic discontinuation revealed restoration of the normal flora. Prolonged linezolid administration may lead to replacement of normal gut flora by pathogenic microorganisms, which under certain conditions might cause systemic infections.

Congenital malformations of the aortic root: bicuspid aortic valve in combination with unruptured aneurysm of the left sinus of Valsalva and aberrant left coronary artery.

We describe the case of a 53-year-old man with a severely stenotic bicuspid aortic valve combined with an unruptured aneurysm of the left sinus of Valsalva and an aberrant left coronary artery. The patient was successfully treated with aortic valve replacement and closure of the aneurysm. It is well known that patients with a bicuspid aortic valve have an increased incidence of other congenital anomalies, but the combination presented in our case is very rare.

Haemodynamic effects of levosimendan for low cardiac output after cardiac surgery: a case series.

INTRODUCTION: Levosimendan is a new inotropic vasodilator for the treatment of decompensated heart failure. Compared to other inotropic agents, it has been shown to improve myocardial contractility without increasing oxygen requirements. However, experience with levosimendan in patients with low cardiac output after cardiopulmonary bypass is limited. In this case series we present the short-term haemodynamic effects of levosimendan added to dobutamine for the management of low cardiac output syndrome after cardiac surgery. METHODS: Twelve patients with low cardiac output during the first 6 hours after completion of cardiopulmonary bypass, who were already receiving dobutamine at a mean dose of 6.7 microg/kg/min, were treated with levosimendan at a loading dose of 6 microg/kg, followed by a 24-hour infusion of 0.2 microg/kg/min. During a 24-hour observation period the following haemodynamic parameters were measured: arterial, central venous, pulmonary arterial and pulmonary capillary wedge pressure, heart rate, cardiac index, stroke volume, systemic and pulmonary vascular resistance, as well as mixed venous oxygen saturation, oxygen delivery and oxygen extraction ratio. RESULTS: Levosimendan significantly improved cardiac index (from 2.1 +/- 0.1 L/min/m2 at baseline to 3.2 +/- 0.3 L/min/m2 at 24 hrs, p < 0.001) as well as mixed venous oxygen saturation, oxygen delivery and oxygen extraction ratio (p < 0.001) and caused a significant reduction in systemic and pulmonary vascular resistance (p < 0.001). At the same time, a significant decrease in central venous, pulmonary arterial and pulmonary capillary wedge pressure was noted (p < 0.001). These beneficial haemodynamic effects resulted in significantly decreased catecholamine requirements. CONCLUSIONS: In this group of cardiac surgical patients with postoperative myocardial dysfunction resistant to dobutamine, levosimendan added to dobutamine was effective in reversing low cardiac output syndrome.