Renal perfusion assessment by renal Doppler during fluid challenge in sepsis.

OBJECTIVES: To assess renal resistive index variations in response to fluid challenge. DESIGN: Prospective cohort study. SETTING: Three ICUs in French teaching hospitals. PATIENTS: Consecutive patients receiving mechanical ventilation and requiring a fluid challenge. INTERVENTION: Resistive index measurement before and after fluid challenge. MEASUREMENTS AND MAIN RESULTS: Renal Doppler was used to measure resistive index and esophageal Doppler to monitor aortic blood flow. Of the 35 included patients, 17 (49%) met our definition for fluid challenge responsiveness, that is, had at least a 10% increase in aortic blood flow. After fluid challenge, mean arterial pressure increased from 73 mm Hg (interquartile range 68-79) to 80 mm Hg (75-86; p < 0.0001) and stroke volume from 50 mL (30-77) to 55 mL (39-84; p < 0.0001). Stroke volume changes after fluid challenge were +28.6% (+18.8% to +38.8%) in fluid challenge responders and +3.1% (-1.6% to 7.4%) in fluid challenge nonresponders. Renal resistive index was unchanged after fluid challenge in both nonresponders (0.72 [0.67-0.75] before and 0.71 [0.67-0.75] after fluid challenge; p = 0.62) and responders (0.70 [0.65-0.75] before and 0.72 [0.68-0.74] after fluid challenge; p = 0.11). Stroke volume showed no correlations with resistive index changes after fluid challenge in the overall population (r² = 0.04, p = 0.25), in fluid challenge responders (r² = -0.02, p = 0.61), or in fluid challenge nonresponders (r² = 0.08, p = 0.27). Stroke volume did not correlate with resistive index changes after fluid challenge in the subgroups without acute kidney injury (AKIN definition), with transient acute kidney injury, or with persistent acute kidney injury. CONCLUSION: Systemic hemodynamic changes induced by fluid challenge do not translate into resistive index variations in patients without acute kidney injury, with transient acute kidney injury, or with persistent acute kidney injury.

Prospective determination of serum ceftazidime concentrations in intensive care units.

INTRODUCTION: The purpose of this study was to assess the value of a serum assay for ceftazidime (CAZ) in patients in the intensive care unit (ICU) of the Saint-Etienne University Teaching Hospital and in other ICUs in the region to optimize therapy. MATERIAL AND METHODS: Between November 1, 2005, and February 29, 2008, for patients hospitalized in ICUs not on dialysis and undergoing continuous CAZ infusion, serum assay of the antibiotic was performed 36 to 48 hours after the start of treatment using a single serum sample. The target serum CAZ concentration was 40 +/- 10 mg/L with a concentration/minimum inhibitory concentration ratio of 5 or greater x minimum inhibitory concentration of CAZ when a strain was isolated. RESULTS: Serum CAZ concentration was determined in 92 patients (28 females, 64 males) receiving CAZ by continuous infusion. The mean age was 66 years (range, 19-89 years) and the mean weight was 73 kg (range, 33-122 kg). The CAZ dose was between 1 g and 6 g/24 hours. The mean serum CAZ concentration was 46.9 mg/L (range, 7.4-162.3 mg/L). Serum CAZ concentrations were as follows: 30 to 50 mg/L in 35.9% of patients, less than 30 mg/L in 36.9%, and greater than 50 mg/L in 27.2%. Infection was documented in 51 patients, with 42 strains of Pseudomonas aeruginosa being detected. The serum concentration/minimum inhibitory concentration ratio was 5 or greater for 84.3%. Antibiotic dosage was adjusted based on the CAZ assay results. CONCLUSION: Our study suggests that CAZ measurement is needed in ICUs to achieve adequate CAZ concentrations to avoid treatment toxicity and to achieve efficacy as rapidly as possible, particularly in strains having limited susceptibility to antibiotics.

Can emergency physicians identify a high mortality subgroup of patients with sepsis: role of procalcitonin.

OBJECTIVE: To assess the potential role of procalcitonin and tumor necrosis factor-alpha, interleukin-6 and interleukin-8, in the prognosis of patients with sepsis. DESIGN: Prospective study. SETTING: The emergency unit of a teaching hospital. PATIENTS: We included 131 patients with sepsis: 15 (12%) with septic shock, 20 (15%) with severe sepsis and 96 (73%) with sepsis. MEASUREMENTS AND MAIN RESULTS: Out of the 131 patients, 112 (85.5%) survived and 19 (14.5%) died. These two groups of patients differed with regard to simplified acute physiology score II, severity of infectious disease and underlying disease, bacteremia and type of microorganisms. The mean serum levels of tumor necrosis factor, interleukin-6, interleukin-8, procalcitonin and lactates at study entry were higher in nonsurvivors than in survivors. Multivariate regression analysis showed the most significant of these variables to be serum procalcitonin level (P=0.0007), simplified acute physiology score II (P=0.03) and serum lactate level (P=0.03). Using a model incorporating these three variables, with a cut-off value corresponding to a 15% probability of predicting mortality, death could be correctly predicted in 99.5% of cases and survival in 95%. This cut-off value allowed us to maximize the prediction of death. When serum procalcitonin levels were not taken into account, the best model included simplified acute physiology score II and serum lactate and interleukin-6 levels, but the rate of correct prediction of death then dropped to 84%. CONCLUSIONS: Stepwise multivariate logistic regression analysis showed serum procalcitonin level to be a valuable marker of sepsis severity, compared with the 15 other clinical, biochemical and bacteriologic variables tested.

Risk factors associated with methicillin-resistant Staphylococcus aureus infection in patients admitted to the ED.

OBJECTIVES: The objective of our study was to define the characteristics of patients admitted to the emergency department (ED) presenting with a methicillin-resistant Staphylococcus aureus (MRSA) infection. PATIENTS AND METHODS: The study included all patients admitted to the ED between January 2003 and December 2004 in whom a staphylococcal infection was documented. The risk factors associated with carriage of MRSA, the diagnosis made in the ED, and the treatment administered were established from the patients' medical files. The sites from which the bacteria were isolated, the spectrum of resistance of the staphylococci to different antibiotics, and the presence or absence of the gene coding for Panton-Valentin leukocidin for certain S aureus isolates were determined from the reports issued by the bacteriologic department. Two groups of patients were compared: those with an infection caused by MRSA and those with an infection due to methicillin-susceptible S aureus (MSSA). RESULTS: A total of 238 patients were included, 93 presenting with an infection caused by MRSA and 145 an infection due to MSSA. The patients harboring MRSA had a higher median age than those carrying MSSA (74 vs 61 years, P = .0001), experienced a greater loss of autonomy (according to the Knauss index), and had more comorbidity factors. Nine patients, younger than 40 years, presented with an infection due to MRSA in the absence of any comorbidity factor or any factor associated with carriage of these bacteria. Seven patients in the MRSA group were tested for Panton-Valentine leukocidin genes, and a positive result was obtained in 2 of them. Regardless of whether the infection was caused by MRSA or by MSSA, the bacteria were most frequently isolated from a cutaneous site, in 40% and 65% of the patients, respectively. Irrespective of the group, 28% of the patients presented with bacteremia. The spectrum of resistance of these MRSA strains suggested a hospital rather than community origin. The initial antibiotic therapy was rarely appropriate in the case of an infection due to MRSA. CONCLUSION: Infections caused by MRSA accounted for a high proportion of the staphylococcal infections diagnosed in the ED, necessitating a rational approach to the prescription of antibiotics for infections of this type.

Weaning from mechanical ventilation with pressure support in patients failing a T-tube trial of spontaneous breathing.

OBJECTIVE: Evidence that PS may facilitate weaning from mechanical ventilation (MV), although not confirmed by randomized trials, prompted us to investigate whether patients could be weaned with PS after failing a T-tube trial. DESIGN AND SETTING: This was a prospective, non-randomized study in two French intensive care units. PATIENTS AND PARTICIPANTS: One hundred eighteen patients were enrolled and underwent a T-tube trial, after which 87 were extubated. Thirty-one underwent a further trial with PS, after which 21 were extubated. INTERVENTIONS: All patients under MV >24 h meeting the criteria for a weaning test underwent a 30-min T-tube trial. If this was successful, they were immediately extubated. Otherwise, a 30-min trial with +7 cm H2O PS was initiated with an individualized pressurization slope and trigger adjustment. If all weaning criteria were met, the patients were extubated; otherwise, MV was reinstated. MEASUREMENTS AND RESULTS: The extubation failure rate at 48 h did not differ significantly between the groups: 11/87 (13%) versus 4/21 (19%), P=0.39. The groups were comparable with regard to endotracheal tube diameter, MV duration, the use of non-invasive ventilation (NIV) after extubation, initial severity score, age and underlying pathology, except for COPD. A significantly higher percentage of patients with COPD was extubated after the trial with PS (8/21-38%) than after a single T-tube trial (11/87-13%) (P=0.003). CONCLUSIONS: Of the patients, 21/118 (18%) could be extubated after a trial with PS, despite having failed a T-tube trial. The reintubation rate was not increased. This protocol may particularly benefit patients who are most difficult to wean, notably those with COPD.

Adrenal axis function does not appear to be associated with hemodynamic improvement in septic shock patients systematically receiving glucocorticoid therapy.

OBJECTIVE: There is mounting evidence showing the value of low-dose corticosteroids in patients with septic shock requiring vasopressor therapy. It remains unclear whether adrenal function tests should be carried out systematically to guide the decision on glucocorticoid therapy. METHODS: The retrospective study was conducted in 52 patients in three university hospital ICUs. We included consecutive patients with catecholamine-dependent septic shock who had not received ketoconazole, glucocorticoids, or etomidate in the 24 h before the ACTH test, and who had survived to day 3 after the shock onset. All patients had a 250-microg ACTH test before systematic glucocorticoid therapy was started. Various definitions of relative adrenal insufficiency were used (based on cortisol basal level and/or change in cortisol level after ACTH stimulation). We defined hemodynamic improvement as a 50% reduction in the vasoactive agent dose in the 3 days following the initiation of glucocorticoid treatment. The relationship between the hemodynamic improvement and the results of the adrenal function tests was analyzed. RESULTS: Hemodynamic improvement occurred in 29 patients (55.8%). Baseline characteristics, sites of infection, types of micro-organisms and antibiotic management did not differ between patients with and those without hemodynamic improvement. Relative adrenal insufficiency whatever the definition was not associated with hemodynamic improvement. CONCLUSION: In catecholamine-dependent septic shock patients managed with systematic glucocorticoid therapy the results of ACTH stimulation do not predict hemodynamic improvement.

Continuous infusion of ceftazidime in critically ill patients undergoing continuous venovenous haemodiafiltration: pharmacokinetic evaluation and dose recommendation.

INTRODUCTION: In seriously infected patients with acute renal failure and who require continuous renal replacement therapy, data on continuous infusion of ceftazidime are lacking. Here we analyzed the pharmacokinetics of ceftazidime administered by continuous infusion in critically ill patients during continuous venovenous haemodiafiltration (CVVHDF) in order to identify the optimal dosage in this setting. METHOD: Seven critically ill patients were prospectively enrolled in the study. CVVHDF was performed using a 0.6 m2 AN69 high-flux membrane and with blood, dialysate and ultrafiltration flow rates of 150 ml/min, 1 l/hour and 1.5 l/hour, respectively. Based on a predicted haemodiafiltration clearance of 32.5 ml/min, all patients received a 2 g loading dose of ceftazidime, followed by a 3 g/day continuous infusion for 72 hours. Serum samples were collected at 0, 3, 15 and 30 minutes and at 1, 2, 4, 6, 8, 12, 24, 36, 48 and 72 hours; dialysate/ultrafiltrate samples were taken at 2, 8, 12, 24, 36 and 48 hours. Ceftazidime concentrations in serum and dialysate/ultrafiltrate were measured using high-performance liquid chromatography. RESULTS: The mean (+/- standard deviation) elimination half-life, volume of distribution, area under the concentration-time curve from time 0 to 72 hours, and total clearance of ceftazidime were 4 +/- 1 hours, 19 +/- 6 l, 2514 +/- 212 mg/h per l, and 62 +/- 5 ml/min, respectively. The mean serum ceftazidime steady-state concentration was 33.5 mg/l (range 28.8-36.3 mg/l). CVVHDF effectively removed continuously infused ceftazidime, with a sieving coefficient and haemodiafiltration clearance of 0.81 +/- 0.11 and 33.6 +/- 4 mg/l, respectively. CONCLUSION: We conclude that a dosing regimen of 3 g/day ceftazidime, by continuous infusion, following a 2 g loading dose, results in serum concentrations more than four times the minimum inhibitory concentration for all susceptible pathogens, and we recommend this regimen in critically ill patients undergoing CVVHDF.

Decrease in serum procalcitonin levels over time during treatment of acute bacterial meningitis.

INTRODUCTION: The aim of this study was to describe the change in serum procalcitonin levels during treatment for community-acquired acute bacterial meningitis. METHODS: Out of 50 consecutive patients presenting with bacterial meningitis and infection at no other site, and who had received no prior antibiotic treatment, 48 had a serum procalcitonin level above 0.5 ng/ml on admission and were enrolled in the study. RESULTS: The mean age of the patients was 55 years, and mean Glasgow Coma Scale score on admission was 13. The time from symptom onset to admission was less than 24 hours in 40% of the patients, 24-48 hours in 20%, and more than 48 hours in 40%. The median (interquartile) interval between admission and initial antibiotic treatment was 160 min (60-280 min). Bacterial infection was documented in 45 patients. Causative agents included Streptococcus pneumoniae (n = 21), Neisseria meningitidis (n = 9), Listeria monocytogenes (n = 6), other streptococci (n = 5), Haemophilus influenzae (n = 2) and other bacteria (n = 2). The initial antibiotic treatment was effective in all patients. A lumbar puncture performed 48-72 hours after admission in 34 patients showed sterilization of cerebrospinal fluid. Median (interquartile) serum procalcitonin levels on admission and at day 2 were 4.5 (2.8-10.8) mg/ml and 2 (0.9-5.0) mg/ml, respectively (P < 0.0001). The corresponding values for C-reactive protein were 120 (21-241) mg/ml and 156 (121-240) mg/ml, respectively. Five patients (10%) died from noninfectious causes during their hospitalization. CONCLUSIONS: Serum procalcitonin levels decrease rapidly with appropriate antibiotic treatment, diminishing the value of lumbar puncture performed 48-72 hours after admission to assess treatment efficacy.

Prognostic factors in acute respiratory distress syndrome: a retrospective multivariate analysis including prone positioning in management strategy.

OBJECTIVE: To investigate the prognostic factors in acute respiratory distress syndrome (ARDS) patients focusing on the use of prone positioning (PP). DESIGN AND SETTING: Retrospective study conducted in an intensive care unit of a university hospital. PATIENTS: All consecutive mechanically ventilated ARDS patients surviving on day 7 after the diagnosis of ARDS. METHODS: The study included all ARDS patients who survived more than 7 days after ARDS diagnosis between January 1995 and December 2002. Demographic and respiratory variables were collected on day 1, and the management of ARDS was analyzed during the first 7 days ( n=125). We performed a univariate analysis and a stepwise logistic regression analysis comparing survivors and nonsurvivors on day 28 and at 2 and 6 months. RESULTS: Mortality rates on day 28 and at 2 and 6 months were 21.6%, 32%, and 44% respectively. A SAPS II score less than 49, McCabe score, and the use of PP introduced in the first 7 days of ARDS management appeared to be independently correlated with a decrease in mortality. CONCLUSIONS: The SAPS II score, the McCabe score, and use of PP are independently correlated with the outcome in ARDS patients.