Sami Hraiech

Right ventricular function during high-frequency oscillatory ventilation in adults with acute respiratory distress syndrome.

Objective: To evaluate the effect of mean airway pressure under high-frequency oscillatory ventilation on right ventricular function. Design: Prospective randomized study. Setting: Intensive care unit of a tertiary care hospital. Patients: Sixteen consecutive patients within the first 48 hrs of mainly pulmonary acute respiratory distress syndrome. Interventions: After a 6-hr-period of protective conventional mechanical ventilation, patients were submitted to three 1-hr periods of high-frequency oscillatory ventilation (+ 5, + 10, + 15) in a randomized order, with a mean airway pressure level determined by adding 5, 10, or 15 cm H2O to the mean airway pressure recorded during conventional mechanical ventilation. Measurements and Main Results: Mean airway pressure was 18 ± 3 cm H2O during conventional mechanical ventilation and was increased until 33 ± 3 cm H2O at high-frequency oscillatory ventilation + 15. Right ventricular function was assessed using transesophageal echocardiography. During conventional mechanical ventilation, nine patients presented a right ventricular dysfunction (right ventricular end-diastolic area/left ventricular end-diastolic area ratio >0.6) of whom four patients had a right ventricular failure (right ventricular end-diastolic area/left ventricular end-diastolic area ratio >0.9). High-frequency oscillatory ventilation + 10 and + 15 further worsened right ventricular function, resulting in about a 40% increase in right ventricular end-diastolic area/left ventricular end-diastolic area ratio and a 30% increase in end-diastolic eccentricity index when compared with conventional mechanical ventilation or high-frequency oscillatory ventilation + 5 periods. At high-frequency oscillatory ventilation + 15, 15 patients had right ventricular dysfunction and nine had right ventricular failure. High-frequency oscillatory ventilation did not improve oxygenation whatever the mean airway pressure level. A significant redistribution of tidal variation to the posterior parts of the lung was observed on electrical impedance tomography measurements when increasing mean airway pressure. However, this redistribution was not observed in patients who presented a worsening of right ventricular function (right ventricular end-diastolic area/left ventricular end-diastolic area increase >40%) at high-frequency oscillatory ventilation + 15. Conclusions: In patients with mainly pulmonary acute respiratory distress syndrome, using high mean airway pressure under high-frequency oscillatory ventilation can worsen right ventricular function when compared with protective conventional mechanical ventilation, notably in patients in whom high-frequency oscillatory ventilation produced less alveolar recruitment of the posterior parts of the lungs. This study highlights the interest of monitoring right ventricular function during high-frequency oscillatory ventilation. (Crit Care Med 2012; 40:–6)

Symptoms of depression in ICU physicians

BackgroundWork and family are the two domains from which most adults develop satisfaction in life. They also are responsible for stressful experiences. There is a perception in the community that work is increasingly the source of much of our stress and distress. Depressive symptoms may be related to repeated stressful experiences. Intensive care unit (ICU) physicians are exposed to major stressors. However, the existence of depressive symptoms in these doctors has been poorly studied. This study was designed to evaluate the prevalence and associated risk factors of depressive symptoms in junior and senior ICU physicians.MethodA one-day national survey was conducted in adult intensive care units (ICU) in French public hospitals. Symptoms of depression were assessed using the Centers of Epidemiologic Studies Depression Scale (CES-D).ResultsA total of 189 ICUs participated, and 901 surveys were returned (75.8% response rate). Symptoms of depression were found in 23.8% of the respondents using the CES-D scale. Fifty-eight percent of these intensivists presenting symptoms of depression wished to leave their job compared with only 33% of those who did not exhibit signs of depression as assessed by the CES-D scale (p < 0.0001). Multiple logistic regression showed that organizational factors were associated with the presence of depressive symptoms. Workload (long interval since the last nonworking weekend, absence of relief of service until the next working day after a night shift) and impaired relationships with other intensivists were independently associated with the presence of depressive symptoms. A high level of burnout also was related to the presence of depressive symptoms. In contrast, no demographic factors regarding ICU physicians and no factor related to the severity of illness of patients were retained by the model. The quality of relationships with other physicians (from other departments) was associated with the absence of depressive symptoms (protective effect).ConclusionsApproximately one of four intensivists presented symptoms of depression. The next step could be to test whether organization modification is associated with less depressive symptoms and less desire to leave the job.

Cytomegalovirus and Herpes Simplex Virus Effect on the Prognosis of Mechanically Ventilated Patients Suspected to Have Ventilator-Associated Pneumonia

Objective Cytomegalovirus (CMV) and herpes simplex virus (HSV) are common viruses that can affect critically ill patients who are not immunocompromised. The aim of this study was to determine whether the identification of CMV and/or HSV in mechanically ventilated critically ill patients suspected of having pneumonia was associated with an increased mortality. Design Prospective epidemiological study. Setting Medical intensive care unit of a tertiary medical center. Patients Ninety-three patients with suspected pneumonia. Interventions Patients with suspected pneumonia had bronchoalveolar lavage and blood samples taken to confirm the diagnosis. Antigenemia was used to detect CMV in the blood. Bronchoalveolar lavage samples were submitted to testing using quantitative real-time Polymerase Chain Reaction. Measurements and Main Results We identified 22 patients with a CMV infection, 26 patients with an HSV infection and 45 patients without CMV or HSV infection (control group). Mortality at day 60 was higher in patients with a CMV infection than in patients from the control group (55% vs. 20%, P<0.01). Mortality at day 60 was not significantly increased in the group with HSV infection. Duration of ICU stay and ICU mortality were significantly higher in patients with CMV infections when compared to patients from the control group, whereas ventilator free days were significantly lower in patients with CMV infections when compared to patients from the control group. Conclusions In critically ill patients, a CMV infection is associated with an increased mortality. Further interventional studies are needed to evaluate whether treatment could improve the prognosis.

Bacteriophage-based therapy in cystic fibrosis-associated Pseudomonas aeruginosa infections: rationale and current status

Pulmonary infections involving Pseudomonas aeruginosa are among the leading causes of the deterioration of the respiratory status of cystic fibrosis (CF) patients. The emergence of multidrug-resistant strains in such populations, favored by iterative antibiotic cures, has led to the urgent need for new therapies. Among them, bacteriophage-based therapies deserve a focus. One century of empiric use in the ex-USSR countries suggests that bacteriophages may have beneficial effects against a large range of bacterial infections. Interest in bacteriophages has recently renewed in Western countries, and the in vitro data available suggest that bacteriophage-based therapy may be of significant interest for the treatment of pulmonary infections in CF patients. Although the clinical data concerning this specific population are relatively scarce, the beginning of the first large randomized study evaluating bacteriophage-based therapy in burn infections suggests that the time has come to assess the effectiveness of this new therapy in CF P. aeruginosa pneumonia. Consequently, the aim of this review is, after a brief history, to summarize the evidence concerning bacteriophage efficacy against P. aeruginosa and, more specifically, the in vitro studies, animal models, and clinical trials targeting CF.

Inhaled Lactonase Reduces Pseudomonas aeruginosa Quorum Sensing and Mortality in Rat Pneumonia

Rationale The effectiveness of antibiotic molecules in treating Pseudomonas aeruginosa pneumonia is reduced as a result of the dissemination of bacterial resistance. The existence of bacterial communication systems, such as quorum sensing, has provided new opportunities of treatment. Lactonases efficiently quench acyl-homoserine lactone-based bacterial quorum sensing, implicating these enzymes as potential new anti-Pseudomonas drugs that might be evaluated in pneumonia. Objectives The aim of the present study was to evaluate the ability of a lactonase called SsoPox-I to reduce the mortality of a rat P. aeruginosa pneumonia. Methods To assess SsoPox-I-mediated quorum quenching, we first measured the activity of the virulence gene lasB, the synthesis of pyocianin, the proteolytic activity of a bacterial suspension and the formation of biofilm of a PAO1 strain grown in the presence of lactonase. In an acute lethal model of P. aeruginosa pneumonia in rats, we evaluated the effects of an early or deferred intra-tracheal treatment with SsoPox-I on the mortality, lung bacterial count and lung damage. Measurements and Primary Results SsoPox-I decreased PAO1 lasB virulence gene activity, pyocianin synthesis, proteolytic activity and biofilm formation. The early use of SsoPox-I reduced the mortality of rats with acute pneumonia from 75% to 20%. Histological lung damage was significantly reduced but the lung bacterial count was not modified by the treatment. A delayed treatment was associated with a non-significant reduction of mortality. Conclusion These results demonstrate the protective effects of lactonase SsoPox-I in P. aeruginosa pneumonia and open the way for a future therapeutic use.

Impaired Virulence and Fitness of a Colistin-Resistant Clinical Isolate of Acinetobacter baumannii in a Rat Model of Pneumonia

ABSTRACT We compared the fitness and lung pathogenicity of two isogenic clinical isolates of Acinetobacter baumannii, one resistant (ABCR) and the other susceptible (ABCS) to colistin. In vitro, ABCR exhibited slower growth kinetics than ABCS. In a rat model of pneumonia, ABCR was associated with less pronounced signs of infection (lung bacterial count, systemic dissemination, and lung damage) and a better outcome (ABCR and ABCS mortality rates, 20 and 50%, respectively [P = 0.03]).

Balancing neuromuscular blockade versus preserved muscle activity.

Purpose of reviewAcute respiratory distress syndrome (ARDS) is still associated with a high mortality. The best way to ensure mechanical ventilation in ARDS patients is still debated, recent data arguing for a muscle paralysis and a controlled ventilation whereas other elements being in favor of a preserved spontaneous breathing. The purpose of this review is to discuss the benefits and the disadvantages of both strategies. Recent findingsRandomized controlled trials have brought the evidence that at the acute phase of ARDS, a 48-h administration of cisatracurium is associated with a decrease in mortality for the most severe hypoxemic patients. Other studies suggest that spontaneous breathing could be deleterious at this period. In the less severe patients (mild ARDS), however, a few studies have demonstrated the benefits of preserving spontaneous breathing with an improvement in oxygenation and a decrease in the length of mechanical ventilation. SummaryIn ARDS patients, the ventilator strategy should be a balance between muscle paralysis in the most hypoxemic patients and preserved spontaneous breathing after improvement or from the acute phase in less severe forms. However, monitoring plateau pressure, tidal volume and perhaps also transpulmonary pressure seems crucial to limit the occurrence of ventilator-induced lung injury.

Antibacterial efficacy of inhaled squalamine in a rat model of chronic Pseudomonas aeruginosa pneumonia

OBJECTIVES Squalamine is a steroid extracted from sharks with proven in vitro antibacterial activity. We assessed its efficacy in reducing the lung bacterial load and histological lesions when given via inhalation in a rat model of chronic Pseudomonas aeruginosa pneumonia. METHODS Sprague-Dawley rats were inoculated by tracheal intubation with 150 μL of a solution containing 10(8) cfu/mL of agar bead-embedded P. aeruginosa strain PAO1. MICs of squalamine and colistin for this strain were 2-8 and 0.5-1 mg/L, respectively. Starting the day after infection, the animals were treated twice daily with aerosolized squalamine (3 mg), colistin (160 mg) or 0.9% saline for 6 days. The bacterial load and lung histological lesions were evaluated on the seventh day. RESULTS Aerosols of squalamine and colistin resulted in a significant reduction in median (IQR) pulmonary bacterial count compared with saline [10(3) (6 × 10(2)-2 × 10(3)), 10(3) (9 × 10(2)-6 × 10(3)) and 10(5) (9 × 10(4)-2 × 10(5)) cfu/lung, respectively; P < 0.001 for both treated groups versus saline]. The lung weight and the lung histological severity score were significantly lower in both treated groups. CONCLUSIONS In a model of chronic P. aeruginosa pneumonia, treatment twice daily with a squalamine aerosol for 6 days leads to a significant reduction in the pulmonary bacterial count and pneumonia lesions with an efficacy comparable to that of colistin.

Routine use of Staphylococcus aureus rapid diagnostic test in patients with suspected ventilator-associated pneumonia.

IntroductionIn patients with ventilator-associated pneumonia (VAP), administration of an appropriate empirical antimicrobial treatment is associated with improved outcomes, leading to the prescription of broad-spectrum antibiotics, including a drug active against methicillin resistant Staphylococcus aureus (MRSA). In order to avoid the overuse of antibiotics, the present study aimed to evaluate the technical characteristics of a rapid diagnostic test (Cepheid Xpert assay) in patients with suspected VAP.MethodsFrom June 2011 to June 2012, in patients with suspected VAP, a sample from the bronchialalveolar lavage (BAL) or miniBAL was tested in a point-of-care laboratory for a rapid diagnostic test of methicillin susceptible Staphylococcus aureus (MSSA) and MRSA. Then, the result was compared to the quantitative culture with a threshold at 104 colony-forming units per milliliter for bronchoalveolar lavage and 103 colony-forming units per milliliter for minibronchoalveolar lavage. The study was performed in three intensive care units at two institutions.ResultsFour hundred, twenty-two samples from 328 patients were analyzed. The culture of 6 (1.1%) and 28 (6.5%) samples were positive for MRSA and MSSA. The test was not interpretable in 41 (9.3%) patients. The negative predictive values of the rapid detection test were 99.7% (98.1 to 99.9%) and 99.8% (98.7 to 99.9%) for MSSA and MRSA, respectively.ConclusionThe rapid diagnostic test is reliable in excluding the presence of MSSA and MRSA in the samples of patients with suspected VAP. Its utility should be regarded depending on the prevalence of MRSA.

The role of neuromuscular blockers in ARDS: benefits and risks.

Purpose of reviewNeuromuscular blocking agents (NMBAs) are part of the pharmaceutical arsenal employed to treat acute respiratory distress syndrome (ARDS). However, their use remains controversial because the potential benefits of these agents are counterbalanced by possible adverse effects. This review summarizes advantages and risks of NMBAs based on the most recent literature. Recent findingsNMBAs have been shown to improve oxygenation during severe ARDS in three randomized controlled trials. The most recent results demonstrated that NMBAs decrease 90-day in-hospital mortality, particularly in the most hypoxaemic patients. NMBAs have not been shown to be an independent risk factor of neuromyopathy in most studies. SummaryNMBAs are commonly used in ARDS (25–55% of patients), but the benefits and the risks of using these agents are controversial. Recent data suggest that a continuous infusion of cisatracurium during the first 48 h of ARDS, particularly for patients with a PaO2/FiO2 ratio less than 120, can decrease 90-day in-hospital mortality. NMBAs do not appear to be an independent risk factor for ICU-acquired weakness if they are not given with corticosteroids or in patients with hyperglycaemia.