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A continuous infusion of vancomycin (CIV) may provide an alternative mode of infusion in severe hospital-acquired methicillin-resistant staphylococcal (MRS) infections. A multicenter, prospective, randomized study was designed to compare CIV (targeted plateau drug serum concentrations of 20 to 25 mg/liter) and intermittent infusions of vancomycin (IIV; targeted trough drug serum concentrations of 10 to 15 mg/liter) in 119 critically ill patients with MRS infections (bacteremic infections, 35%; pneumonia, 45%). Microbiological and clinical outcomes, safety, pharmacokinetics, ease of treatment adjustment, and cost were compared. Microbiological and clinical outcomes and safety were similar. CIV patients reached the targeted concentrations faster (36 +/- 31 versus 51 +/- 39 h, P = 0.029) and fewer samples were required for treatment monitoring than with IIV patients (7.7 +/- 2.2 versus 11.8 +/- 3.9 per treatment, P < 0.0001). The variability between patients in both the area under the serum concentration-time curve (AUC(24h)) and the daily dose given over 10 days of treatment was lower with CIV than with IIV (variances, 14,621 versus 53,975 mg(2)/liter(2)/h(2) [P = 0.026] and 414 versus 818 g(2) [P = 0.057], respectively). The 10-day treatment cost per patient was $454 +/- 137 in the IIV group and was 23% lower in the CIV group ($321 +/- 81: P < 0.0001). In summary, for comparable efficacy and tolerance, CIV may be a cost-effective alternative to IIV.

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Clonidine, an alpha2 adrenoceptor agonist, has anti-hypertensive and anti-nociceptive effects. It is commonly used in association with local anaesthetics and opioids to enhance the quality and duration of extradural analgesia in the postoperative period, and to decrease the incidence of side effects. As a sole analgesic, it has seldom been used to relieve postoperative pain. The dose of extradural clonidine to achieve good pain relief without deleterious side effects remains undetermined. In order to address this problem, we performed a computer search via two well-known databases, Medline and Excerpta Medica, covering the period from 1985 to September 1997. One hundred and fifty-nine articles were retrieved of which 38 dealt with extradural clonidine and postoperative pain. All but 16 studies suffered from serious design flaws, such as lack of controls and/or randomization, or inadequate statistical analysis. The data from these studies were difficult to interpret because of the tremendous variation in variables, especially dose of clonidine, level of extradural injection, time of administration, type of anaesthesia, type of surgery, and reference and rescue drugs. The simultaneous extradural use of local anaesthetics and opioids further hindered data interpretation, and precluded any meta-analysis. Proposals for a standard study design are made to help comparison between studies involving extradural clonidine and postoperative pain.

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OBJECTIVES: The purpose of this study was to analyze the risk factors of postoperative infection following transurethral resection of the prostate (TURP). METHODS: 857 consecutive patients scheduled for TURP were included in a French multicenter prospective study (12 surgical centers). For each patient, data were collected and analyzed as risk factors of postoperative infection. Statistical analysis used the chi 2 test or Student's test for univariate analysis, then stepwise logistic regression for multivariate analysis. RESULTS: The incidence of post-TURP infection was 21.6%: urinary tract infection (19.3%) and bacteremia and/or septic shock (2.3%). Multivariate analysis documented three independent risk factors of postoperative infection: preoperative bacteriuria (p < 0.003), duration of surgical procedure > 70 min (p < 0.01) and the surgical center (p < 0.00001). CONCLUSION: The duration of the surgical procedure is an important postoperative risk factor of infection and there is a major difference between centers in terms of postoperative risk of infection. Further studies are needed to explain this last phenomenon.

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SUMMARY: The aim of the present study was to investigate the incidence of adverse effects and the prognostic value of various risk factors in a large population of unselected hypertensive patients treated with the ACE inhibitor trandolapril. Among the 30 072 patients investigated in this post marketing retrospective study, 1813 patients (6.0 per cent) reported an adverse effect. The five most frequent side effects were coughing (3.1 per cent), dizziness (0.7 per cent), headache (0.6 per cent) asthenia (0.5 per cent) and nausea (0.3 per cent). Intolerance risk factors for trandolapril were researched using both univariate and multivariate analysis. In the univariate analysis, a prior intolerance of an ACE inhibitor and female gender were strongly correlated with either overall intolerance or coughing. The most relevant variables for the occurrence of adverse effects, listed according to their entry order in the multivariate analysis, were: prior intolerance of ACE inhibitors (OR: 4.19, 95 per cent CI: 3.66-4.78), female gender (OR: 1.46, 95 per cent CI: 1.31-1.63), prior intolerance of other antihpertensive agents (OR: 1.27, 95 per cent CI: 1.14-1.41), smoking (OR: 0.76, 95 per cent CI: 0.66-0.87) and combination with a beta blocker (OR: 1.31, 95 per cent CI: 1.08-1.58). A prior intolerance of an ACE inhibitor appears to be a very strong predictor of coughing (OR: 6.14, 95 per cent CI: 5.24-7.19). The following variables, namely female gender (OR: 1.61, 95 per cent CI: 1.40-1.85), age 60-80 (OR: 1.25, 95 per cent CI: 1.09-1.44) and prior intolerance of other antihypertensive agents (OR: 1.20, 95 per cent CI: 1.03-2.39) appear less significant.

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The changes occurring in the histochemical characteristics of the rat diaphragm during the postnatal period were examined. Fibre-type distribution, fibre oxidative capacity, i.e. succinate-dehydrogenase (SDH) activity, and cross-sectional area were compared in the costal (COS) and crural (CRU) regions, and across their abdominal and thoracic surfaces. The proportions of type I and IIb fibres in both COS and CRU increased with age, while the proportion of type IIa fibres progressively decreased. For COS, fibre distribution was homogeneous over the entire muscle and did not change after 4 weeks. For CRU, it was heterogeneous with a higher proportion of type I fibres on the thoracic surface as from the first week. All fibre types significantly increased in cross-sectional area between 1 and 8 weeks, with no significant differences in COS and CRU. Mean SDH activity did not differ between COS and CRU or across the muscles. Mean SDH activities-were low and identical in all fibre types at birth, and then increased, peaking at the 6th week in type I and IIa fibres. When total muscle fibre oxidative capacity was calculated from an index including fibre-type proportion, cross-sectional area and mean SDH activity, it was significantly higher at 1 than at 8 weeks after birth; this might have functional implications for the newborn.

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The effects on the rat diaphragm of fatigue induced by low- and high-frequency stimulation (at 5 Hz for 1.5 min and 75 Hz for 1 min) were examined during postnatal development. Experiments were performed on isolated costal diaphragm strips. Before stimulation, twitch contraction time and half relaxation time were longest in the neonate and decreased significantly between weeks 1 and 6. Correspondingly, the specific twitch tension (corrected for cross-sectional area) increased progressively with age. After either low- or high-frequency fatigue, the force recovery was complete in 1- and 2-week-old rats, whereas the force production progressively decreased in older rats. In addition, the neonate diaphragm further enhanced its force selectively after high-frequency fatigue. It is concluded that the rat diaphragm is comparably resistant to fatigue during the early postnatal period, whether fatigue is induced by low- or by high-frequency stimulation. This suggests that postnatal changes in diaphragm contractile and fatigue properties may be related to changes in the process of force production. The possibility is discussed that a higher total muscle oxidative potential and the mechanisms leading to force potentiation in the neonate might explain the fatigue resistance.

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BACKGROUND: In patients with acute exacerbations of chronic obstructive pulmonary disease, noninvasive ventilation may be used in an attempt to avoid endotracheal intubation and complications associated with mechanical ventilation. METHODS: We conducted a prospective, randomized study comparing noninvasive pressure-support ventilation delivered through a face mask with standard treatment in patients admitted to five intensive care units over a 15-month period. RESULTS: A total of 85 patients were recruited from a larger group of 275 patients with chronic obstructive pulmonary disease admitted to the intensive care units in the same period. A total of 42 were randomly assigned to standard therapy and 43 to noninvasive ventilation. The two groups had similar clinical characteristics on admission to the hospital. The use of noninvasive ventilation significantly reduced the need for endotracheal intubation (which was dictated by objective criteria): 11 of 43 patients (26 percent) in the noninvasive-ventilation group were intubated, as compared with 31 of 42 (74 percent) in the standard-treatment group (P < 0.001). In addition, the frequency of complications was significantly lower in the noninvasive-ventilation group (16 percent vs. 48 percent, P = 0.001), and the mean (+/- SD) hospital stay was significantly shorter for patients receiving noninvasive ventilation (23 +/- 17 days vs. 35 +/- 33 days, P = 0.005). The in-hospital mortality rate was also significantly reduced with noninvasive ventilation (4 of 43 patients, or 9 percent, in the noninvasive-ventilation group died in the hospital, as compared with 12 of 42, or 29 percent, in the standard-treatment group; P = 0.02). CONCLUSIONS: In selected patients with acute exacerbations of chronic obstructive pulmonary disease, noninvasive ventilation can reduce the need for endotracheal intubation, the length of the hospital stay, and the in-hospital mortality rate.

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Several modalities of ventilatory support have been proposed to gradually withdraw patients from mechanical ventilation, but their respective effects on the outcome of weaning from mechanical ventilation are not known. We conducted a randomized trial in three intensive care units in mechanically ventilated patients who met standard weaning criteria. Those who could not sustain 2 h of spontaneous breathing were randomly assigned to be weaned with T-piece trials, with synchronized intermittent mandatory ventilation (SIMV), or with pressure support ventilation (PSV). Specific criteria for performing tracheal extubation were defined for each modality. The number of patients who could not be separated from the ventilator at 21 d (i.e., who failed to wean) was compared between the groups. Patients in whom tracheal intubation was required in a 48-h period following extubation were also classified as failures. Among 456 mechanically ventilated patients who met weaning criteria, 109 entered into the study (35 with T piece, 43 with SIMV, and 31 with PSV). The three groups were comparable in terms of etiology of disease or characteristics at entry in the study. When all causes for weaning failure were considered, a lower number of failures was found with PSV than with the other two modes, with the difference just reaching the level of significance (23% for PSV, 43% for T piece, 42% for SIMV; p = 0.05). After excluding patients whose weaning was terminated for complications unrelated to the weaning process, the difference became highly significant (8% for PSV versus 33% and 39%, p < 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

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OBJECTIVE: To evaluate physician accuracy in predicting patients' hemodynamic profiles, associated morbidities, rates of change in therapy resulting from catheterization, and the outcome variations associated with such change before the insertion of a pulmonary artery catheter. DESIGN: Prospective, descriptive, cohort study with no interventions. SETTING: Medical intensive care unit (ICU) of a university hospital. PATIENTS: One hundred twelve catheterizations performed in 112 patients without acute myocardial infarction. In 43 cases, catheterizations were indicated because of circulatory shock that was unresponsive to two standard therapeutic measures. MEASUREMENTS AND MAIN RESULTS: Before catheterization, physicians were asked to predict the hemodynamic profile of the patients who were to be catheterized, and to provide a plan for therapy. After catheterization, each patient's chart was reviewed and compared with precatheterization predictions. Hemodynamic profiles were correctly predicted in only 56% of the cases. Information obtained from pulmonary artery catheters prompted changes in therapy in 58% of all cases and in 63% of patients in shock who were unresponsive to standard therapy. Modifications varied among hemodynamic profiles, from 33% (fluid overloaded) to 87% (hypovolemia). Complications occurred in 11 catheterizations, but only two complications required therapy (pneumothorax [n = 1] and one episode of arrhythmia). No systemic infection occurred, and all blood cultures sampled through catheters before the catheters were withdrawn were sterile. In the entire group of patients, those patients in whom catheterization induced a change in therapy and those patients in whom no change in therapy occurred had similar precatheterization characteristics and mortality rates. However, in the subgroup of patients in shock that was unresponsive to standard therapy, the mortality rate was significantly lower when the assessment of hemodynamic data led to a change in therapy (59% vs. 100%, p = .009), despite identical precatheterization characteristics. CONCLUSIONS: Prompted by assessment of pulmonary artery catheter measurements in patients with circulatory shock who were unresponsive to standard therapeutic measures, a change in therapy for these patients was associated with an improved prognosis, independent of other variables influencing outcome.

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In order to assess the quality of sleep in surgical patients the amount of self-rated postoperative insomnia and its predisposing factors, we conducted a three-fold questionnaire * survey in 176 consecutive patients undergoing elective orthopaedic, vascular or abdominal surgery. The first questionnaire was completed the day preceding surgery, the second at the day of discharge and the third two weeks later. This survey concerned the patient's general status, his usual sleep profile and factors which could interfere with sleep (hypnotics, pain, environmental factors) throughout the study period. It allowed quantification of these parameters and the assessment of their time-course. Perioperative insomnia appeared to be a long-lasting phenomenon which persisted after discharge. Factor analysis and multiple regression models showed that postoperative, self-rated insomnia was multifactorial and mainly explained by the amount of postoperative pain (p = 0.035).

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Different reasons explain that chronic venous insufficiency remains ill recognized as a public health problem in France: very few epidemiologic studies have been undertaken in this pathology; this disease is very heterogeneous in terms of gravity and clinical evidence: from isolated symptoms to localized clinical signs, with or without severe complications. Clinical semiology is actually not standardised. The analysis of available informations suggests that this pathology represents approximatively 2.6% of the whole health expenditures in France, that is to say an amount of 14.7 billion of Francs for the year 1991. The number of patients suffering from chronic venous insufficiency can be estimated to about 11 millions, whose 7 millions present symptomatic signs (leg heaviness, pain, moderate edema). The number of hospitalizations is around 200,000 per year, of which 63% are in surgery in private clinics. One half of these hospital stays concerned varicose veins (the 8th cause of hospitalization in France). Forty of the patients consulting for chronic venous insufficiency are at work and about 7 to 8% of them get sick leaves for this pathology: around 362,000 sick leaves per year representing 6.4 millions of day lost. On the basis of the medical consumption survey performed by INSEE/CREDES, an extrapolation was made to estimate the different components of costs of chronic venous insufficiency: 41% (drugs), 34% (hospital care) and 13% (medical fees).

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OBJECTIVE: To determine whether leaving an intrathecal catheter in place in the postoperative period prevents postdural puncture headache (PDPH). METHODS: Lumbar puncture was performed with an 18-gauge Tuohy needle. 0.5% bupivacaine spinal anesthesia was given through a 20-gauge catheter in 87 patients having orthopedic surgery. Postoperatively, patients were allocated randomly to have the catheter immediately withdrawn (group 1, N = 47) or kept in place for 12 to 24 hours (group 2, N = 40). Patients were questioned by a blinded observer, about PDPH twice a day on postoperative days 1, 2, 3, and 8. RESULTS: The incidence of PDPH was 9.2%, and this was comparable in the two groups (5 patients in group 1 and 3 patients in group 2). CONCLUSION: Leaving the intrathecal catheter in place in the postoperative period for 12 to 24 hours does not prevent PDPH.

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PURPOSE: To prospectively quantify the degree of accuracy of portable chest x-ray film examination in the detection of postoperative lung consolidations. STUDY: Nineteen patients had a chest x-ray film and computed tomography (CT) scan the day before and 48 h following elective abdominal aortic replacement. RESULTS: The diagnosis of lung consolidations by x-ray film examination showed sensitivity of between 0.33 and 1.00, depending on the lung zone considered (lower at the lung bases). Specificity always was greater than 0.79. Radiologic lung volume decreased 16 percent postoperatively (p < 0.01) on average and noninflated parenchyma increased by a factor of 3 (p < 0.0001). Postoperatively, PaO2 correlated with the amount of condensed lung by CT scan (p < 0.002). CONCLUSION: In postoperative conditions, x-ray film examination is a method which presents good specificity but poor sensitivity in the diagnosis of lung consolidations.

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Preoperative normovolemic hemodilution (PNH) has been proposed for patients scheduled to undergo aortic surgery. Coronary artery disease is frequent in these patients. The aim of the study was to assess the effect of PNH on hemodynamics and segmental wall motion (SWM) evaluated by transesophageal echocardiography in such patients. Twenty patients with coronary artery disease were allocated randomly to either PNH or no PNH; PNH was performed after anesthetic induction using dextran 60,000. Patients were operated on under general anesthesia and monitored intraoperatively with electrocardiographic lead CM5, radial and pulmonary artery catheters, and transesophageal echocardiography positioned to obtain a short-axis view. Hemodynamic and transesophageal echocardiographic data were collected after anesthetic induction and after PNH, before and 5 min after aortic clamping, after unclamping, and at the end of surgery. Aortic clamping induced a significant increase in systemic vascular resistance and arteriovenous difference in oxygen and a decrease in cardiac index (P < 0.05), but the effect of aortic clamping was inversely related to hemodilution. The SWM score (graded from 1 = normal to 5 = dyskinesia) was significantly increased after aortic clamping, mainly in the anterior segment (P < 0.05). Four patients in the control (no PNH) group and one in the PNH group developed new SWM abnormalities indicative of myocardial ischemia during surgery (P = NS). This study suggests that PNH may improve hemodynamic tolerance to aortic clamping in patients with coronary artery disease. The observed changes in SWM indicate that PNH may not worsen myocardial ischemia in patients scheduled to undergo aortic surgery.

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Because laryngeal edema (LE) after tracheal extubation is likely to result from an exudative response, corticosteroids often are given routinely as a preventive treatment. No adequate controlled study supports this strategy, however. A prospective, randomized, placebo-controlled, double-blind, multicenter trial that included 700 consecutive patients requiring tracheal intubation and mechanical ventilation was conducted to determine risk factors for LE occurrence after tracheal extubation in adults and to evaluate the efficacy of corticosteroids in its prevention. One hour before extubation, patients were given either an intravenous bolus of 8 mg dexamethasone or a placebo. Patients were divided into two groups: 1) those in whom short-duration intubation (SDI, less than 36 h) was administered; and 2) those in whom long-duration intubation (LDI, more than 36 h) was administered. Minor LE was diagnosed when either stridor or laryngeal dyspnea, or both, occurred; major LE was diagnosed when reintubation due to LE was required, with LE evidenced during direct laryngoscopy. The overall incidence of LE was 4.2% and varied among the six participating centers from 2.3 to 6.9% (not significant). In only seven patients (1%), all with LDI, was tracheal reintubation required for LE. Laryngeal edema occurred more frequently after LDI than after SDI (7.2 vs. 0.9%; P less than 0.001). It also was more frequent in female than in male patients (20/284 vs. 8/379; P less than 0.05), irrespective of intubation duration and treatment. There was no association between LE and either difficulty/route of intubation or admission diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

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The postoperative period after major abdominal surgery is known to be a period of increased episodic oxygen desaturation. In order to assess the risk factors for episodic desaturation, we have studied 29 surgical patients using pulse oximetry during the preoperative night (Npre) when they received benzodiazepine premedication and breathed air, and also during the first three nights after operation when they received nasal oxygen supplementation. Modal oxygen saturation (SpO2) exceeded 95% during all nights studied. The time spent at less than 90% (t90) and 85% (t85) SpO2 and the average SpO2 nadir (SpO2, nadir) did not differ each night. Heart rate was greater (mean 90.1 (SD 16.6) vs 68.2 (12.0) beat min-1, P < 0.001) during the second night after operation (N2) than during Npre. Before operation, the number of desaturations, t90 and t85 correlated with pharyngeal hypertrophy (P = 0.003, P = 0.002, P = 0.001, respectively). At the same time, t90 and t85 correlated with body mass index (P = 0.02 and P = 0.05, respectively). During N2, t90 correlated with radiological lung consolidation (P = 0.05) and SpO2, nadir correlated with FEV1 (P = 0.03). We conclude that there are several mechanisms responsible for oxygen desaturation and that these mechanisms differ before and after surgery.

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Fiberoptic bronchoscopy and bronchoalveolar lavage are major tools in the diagnosis of acute pneumonia in immunocompromised patients. We conducted a prospective study to assess the morbidity associated with this procedure in 14 patients with AIDS and 16 patients with drug-induced immunosuppression. No patient had a PaO2 lower than 70 mm Hg with additional oxygen. Clinical data, chest roentgenogram, pulmonary function test, forced vital capacity, forced expiratory volume in one second, and arterial blood gases were recorded before and after bronchoscopy. Arterial oxygen saturation was monitored during the procedure, and initial, lowest, and final saturation values were noted. The patients were separated into three groups on the basis of chest roentgenographic findings. No procedure-induced pneumonia or need for tracheal intubation occurred. Minor clinical symptoms induced by the lavage in seven patients resolved spontaneously. By contrast, mean SaO2 decreased markedly during the procedure from 94 +/- 3 to 87 +/- 5 percent (p less than 0.0001) and returned to only 89 +/- 5 percent at the end of the procedure. Lowest SaO2 during the procedure and final SaO2 correlated poorly with initial SaO2 but correlated well with initial FVC and FEV1 (p less than 0.01). The PFT values were lower following bronchoscopy. O2 desaturation was more pronounced in patients with severe roentgenographic abnormalities. No significant differences were found between the three groups of patients, or between the AIDS and DII patients in terms of changes in PFT values. We conclude that in immunocompromised patients, bronchoscopy with BAL induces severe arterial oxygen desaturation which is correlated with initial PFT and chest roentgenographic findings, and most of these abnormalities are transient and do not lead to major complications.

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Protected samples of lower respiratory tract secretions processed by quantitative culture techniques are recommended to diagnose nosocomial bacterial pneumonia in intubated, mechanically ventilated patients. To evaluate the accuracy of a simple and inexpensive sampling device in this setting, we compared quantitative cultures of paired single-sheathed plugged telescoping catheter (PTC) and protected specimen brush (PSB) samples in 55 patients during 78 suspected episodes of nosocomial pneumonia. PTC and PSB samples were taken in randomized order, and patients were also randomized to have PTC samples taken "blindly" or via a fiberoptic bronchoscope. Fifteen PSB and 27 PTC samples were culture positive (greater than or equal to 10(3) cfu/ml). The two sampling procedures gave similar results in 58 (74%) episodes. A major discrepancy occurred in 20 episodes, including six false negatives of PSB in episodes of proved pneumonia, four possible false positives of PSB, and 10 possible false positives of PTC (three of which rapidly evolved towards overt pneumonia). The sensitivity and specificity of PTC were 100 and 82.2%, and those of PSB were 64.7 and 93.5%, respectively. Blinded or directed PTC samples had similar concordance with PSB samples taken via bronchoscopy. We conclude that PTC is at least as accurate as PSB in the bacteriologic diagnosis of nosocomial pneumonia in intubated patients, and that its use can result in substantial cost savings, especially when fiberoptic bronchoscopy is not otherwise indicated.

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BACKGROUND: Patients with acute exacerbations of chronic obstructive pulmonary disease may require endotracheal intubation with mechanical ventilation. We designed, and here report on the efficacy of, a noninvasive ventilatory-assistance apparatus to provide inspiratory-pressure support by means of a face mask. METHODS: We assessed the short-term (45-minute) physiologic effects of the apparatus in 11 patients with acute exacerbations of chronic obstructive pulmonary disease and evaluated its therapeutic efficacy in 13 such patients (including 3 of the 11 in the physiologic study) who were treated for several days and compared with 13 matched historical-control patients. RESULTS: In the physiologic study, after 45 minutes of inspiratory positive airway pressure by face mask, the mean (+/- SD) arterial pH rose from 7.31 +/- 0.08 to 7.38 +/- 0.07 (P less than 0.01), the partial pressure of carbon dioxide fell from 68 +/- 17 mm Hg to 55 +/- 15 mm Hg (P less than 0.01), and the partial pressure of oxygen rose from 52 +/- 12 mm Hg to 69 +/- 16 mm Hg (P less than 0.05). These changes were accompanied by marked reductions in respiratory rate (from 31 +/- 7 to 21 +/- 9 breaths per minute, P less than 0.01). Only 1 of the 13 patients treated with inspiratory positive airway pressure needed tracheal intubation and mechanical ventilation, as compared with 11 of the 13 historical controls (P less than 0.001). Two patients in each group died. As compared with the controls, the treated patients had a more transient need for ventilatory assistance (3 +/- 1 vs. 12 +/- 11 days, P less than 0.01) and a shorter stay in the intensive care unit (7 +/- 3 vs. 19 +/- 13 days, P less than 0.01). CONCLUSIONS: Inspiratory positive airway pressure delivered by a face mask can obviate the need for conventional mechanical ventilation in patients with acute exacerbations of chronic obstructive pulmonary disease.

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