Saida Rezaiguia-Delclaux

High-Flow Nasal Oxygen vs Noninvasive Positive Airway Pressure in Hypoxemic Patients After Cardiothoracic Surgery: A Randomized Clinical Trial

IMPORTANCE Noninvasive ventilation delivered as bilevel positive airway pressure (BiPAP) is often used to avoid reintubation and improve outcomes of patients with hypoxemia after cardiothoracic surgery. High-flow nasal oxygen therapy is increasingly used to improve oxygenation because of its ease of implementation, tolerance, and clinical effectiveness. OBJECTIVE To determine whether high-flow nasal oxygen therapy was not inferior to BiPAP for preventing or resolving acute respiratory failure after cardiothoracic surgery. DESIGN AND SETTING Multicenter, randomized, noninferiority trial (BiPOP Study) conducted between June 15, 2011, and January 15, 2014, at 6 French intensive care units. PARTICIPANTS A total of 830 patients who had undergone cardiothoracic surgery, of which coronary artery bypass, valvular repair, and pulmonary thromboendarterectomy were the most common, were included when they developed acute respiratory failure (failure of a spontaneous breathing trial or successful breathing trial but failed extubation) or were deemed at risk for respiratory failure after extubation due to preexisting risk factors. INTERVENTIONS Patients were randomly assigned to receive high-flow nasal oxygen therapy delivered continuously through a nasal cannula (flow, 50 L/min; fraction of inspired oxygen [FiO2], 50%) (n = 414) or BiPAP delivered with a full-face mask for at least 4 hours per day (pressure support level, 8 cm H2O; positive end-expiratory pressure, 4 cm H2O; FiO2, 50%) (n = 416). MAIN OUTCOMES AND MEASURES The primary outcome was treatment failure, defined as reintubation, switch to the other study treatment, or premature treatment discontinuation (patient request or adverse effects, including gastric distention). Noninferiority of high-flow nasal oxygen therapy would be demonstrated if the lower boundary of the 95% CI were less than 9%. Secondary outcomes included mortality during intensive care unit stay, changes in respiratory variables, and respiratory complications. RESULTS High-flow nasal oxygen therapy was not inferior to BiPAP: the treatment failed in 87 of 414 patients with high-flow nasal oxygen therapy (21.0%) and 91 of 416 patients with BiPAP (21.9%) (absolute difference, 0.9%; 95% CI, -4.9% to 6.6%; P = .003). No significant differences were found for intensive care unit mortality (23 patients with BiPAP [5.5%] and 28 with high-flow nasal oxygen therapy [6.8%]; P = .66) (absolute difference, 1.2% [95% CI, -2.3% to 4.8%]. Skin breakdown was significantly more common with BiPAP after 24 hours (10% vs 3%; 95% CI, 7.3%-13.4% vs 1.8%-5.6%; P < .001). CONCLUSIONS AND RELEVANCE Among cardiothoracic surgery patients with or at risk for respiratory failure, the use of high-flow nasal oxygen therapy compared with intermittent BiPAP did not result in a worse rate of treatment failure. The findings support the use of high-flow nasal oxygen therapy in similar patients. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01458444.

Molecular Diversity and Routes of Colonization of Candida albicans in a Surgical Intensive Care Unit, as Studied Using Microsatellite Markers

To evaluate the colonization of Candida species and the importance of cross-contamination with Candida albicans, we prospectively screened clinical specimens obtained from surgical patients in the intensive care unit (ICU) who had a high risk of yeast colonization. Genotyping of C. albicans was performed using microsatellite markers. Thirty-six of 94 patients acquired nosocomial yeast colonization and/or infection. A total of 1126 specimens were cultured, 167 (15%) of which yielded yeasts. All 122 isolates of C. albicans recovered from the 30 C. albicans-positive patients were genotyped. Twenty-four different genotypes were identified. No genotype was systematically associated with a specific room or time. Isolates recovered from different body sites of patients at different times had identical genotypes. Acquisition of C. albicans in the surgical ICU seems to be mainly endogenous. Microsatellite markers should also be developed for typing non-albicans Candida species to learn whether their epidemiology differs from that of C. albicans.

Halothane and Isoflurane Decrease Alveolar Epithelial Fluid Clearance in Rats

Background Active sodium transport is the primary mechanism that drives alveolar fluid clearance. In the current study, the effects of exposure to halothane and isoflurane on alveolar fluid clearance in rats were evaluated. Methods Rats were exposed to either halothane (0.4% for 6 h or 2% for 2 h) or isoflurane (0.6% for 6 h or 2.8% for 2 h). Reversibility of halothane effects was assessed after 2 h of exposure to 2% halothane. Alveolar and lung liquid clearance were measured by intratracheal instillation of a 5% albumin solution with 1.5 micro Ci of125 I‐albumin, during mechanical ventilation with 100% FiO2 and the halogenated agent. The effect of terbutaline (10 sup ‐4 m) added to the albumin solution was tested after 2 h of exposure to 2% halothane. The increase in protein concentration in the airspaces over 1 h was used to evaluate alveolar liquid clearance. Lung liquid clearance was calculated gravimetrically. Results Alveolar liquid clearance rates were decreased by 24%, 30% and 40% compared with controls (P < 0.05) after 2 h of exposure to halothane, 6 h of exposure to halothane, and 6 h of exposure to isoflurane, respectively. After 2 h of exposure to isoflurane, alveolar liquid clearance did not change. In the 2‐h halothane exposure group, alveolar liquid clearance returned to the control value 2 h after withdrawal of halothane. Terbutaline increased alveolar liquid clearance by 50% and 89% in the control and 2‐h halothane exposure groups, respectively. In all experiments, the same results were obtained for alveolar and lung liquid clearance. Conclusions Halothane and isoflurane caused a reversible decrease in alveolar epithelial fluid clearance. Two hours of exposure to halothane did not alter the stimulatory effect of terbutaline on alveolar liquid clearance.

Airway Responsiveness Measured by Forced Oscillation Technique in Severely Obese Patients, before and after Bariatric Surgery

Background. The influence of obesity on airway responsiveness remains controversial. Objective. This study was designed to investigate airway responsiveness, airway inflammation, and the influence of sleep apnea syndrome (SAS), in severely obese subjects, before and after bariatric surgery. Methods. A total of 120 non-asthmatic obese patients were referred consecutively for pre-bariatric surgery evaluation. Lung function, airway responsiveness to methacholine, exhaled nitric oxide measurement, and sleep studies were performed. Airway hyperresponsiveness (AHR) was defined as a 50% or greater increase in respiratory resistance measured using the forced oscillation technique in response to a methacholine dose ≤2000 μg. Forced expiratory volume in 1 second (FEV1) was measured after the last methacholine dose. Airway responsiveness was reevaluated after weight loss in patients with a pre-surgery AHR. Results. AHR was found in 16 patients. The percent FEV1 decrease or percent respiratory resistance increase in response to methacholine was related to baseline expiratory airflow (forced expiratory flow at 50%) (r = 0.26, p < .006 and r = 0.315, p = .0005, respectively) but not to body mass index (BMI) or exhaled nitric oxide. Both airway responsiveness parameters were significantly related to forced expiratory flow at 25–75%/forced vital capacity, a measure of airway size relative to lung size (r = 0.27, p < .005 and r = 0.25, p < .007, respectively). Sleep apnea was not significantly associated with AHR or airway inflammation. About 11 patients with AHR were reevaluated 18 months to 2 years after surgery, with no change in AHR associated with weight loss. Conclusion. Airway responsiveness is not related to BMI or to SAS. AHR in severely obese patients might be related to distal airway obstruction or low relative airway size.

Incidence of nosocomial pneumonia and risk of recurrence after antimicrobial therapy in critically ill lung and heart–lung transplant patients

Little is known about the resolution of symptoms of nosocomial pneumonia (NosoP) after lung and heart–lung transplantation. The aim of this study was to describe the clinical response to antimicrobial therapy in (ICU) patients with NosoP after lung or heart–lung transplantation. Between January 2008 and August 2010, 79 lung or heart–lung transplantations patients were prospectively studied. NosoPwas confirmed by quantitative cultures of bronchoalveolar lavage or endotracheal aspirates. Clinical variables, sequential organ failure assessment (SOFA) score, and radiologic score were recorded from start of therapy until day 9. Thirty‐five patients (44%) experienced 64 episodes of NosoP in ICU. Fourteen patients (40%) had NosoP recurrence. Most frequently isolated organisms were Enterobacteriaceae (30%), Pseudomonas aeruginosa (25%), and Staphylococcus aureus (20%). Sequential organ failure assessment (SOFA) score improved significantly at day 6 and C‐reactive protein level at day 9. SOFA and radiologic scores differed significantly between patients with and without NosoP recurrence at day 3 and 9. The ICU mortality rate did not differ between patients with and without NosoP recurrence, and free of NosoP (14.3%, 9.5%, 11.4%, respectively) (p = 0.91). Severities of illness and lung injury were the two major risk factors for NosoP recurrence. Occurrence of NosoP has no impact on ICU mortality.

Comparative effect of intraoperative propacetamol versus placebo on morphine consumption after elective reduction mammoplasty under remifentanil-based anesthesia: a randomized control trial [ISRCTN71723173]

BackgroundPostoperative administration of paracetamol or its prodrug propacetamol has been shown to decrease pain with a morphine sparing effect. However, the effect of propacetamol administered intra-operatively on post-operative pain and early postoperative morphine consumption has not been clearly evaluated. In order to evaluate the effectiveness of analgesic protocols in the management of post-operative pain, a standardized anesthesia protocol without long-acting opioids is crucial. Thus, for ethical reasons, the surgical procedure under general anesthesia with remifentanil as the only intraoperative analgesic must be associated with a moderate predictable postoperative pain.MethodsWe were interested in determining the postoperative effect of propacetamol administered intraoperatively after intraoperative remifentanil. Thirty-six adult women undergoing mammoplasty with remifentanil-based anesthesia were randomly assigned to receive propacetamol 2 g or placebo one hour before the end of surgery. After remifentanil interruption and tracheal extubation in recovery room, pain was assessed and intravenous titrated morphine was given. The primary end-point was the cumulative dose of morphine administered in the recovery room. The secondary end-points were the pain score after tracheal extubation and one hour after, the delay for obtaining a Simplified Numerical Pain Scale (SNPS) less than 4, and the incidence of morphine side effects in the recovery room.For intergroup comparisons, categorical variables were compared using the chi-squared test and continuous variables were compared using the Student t test or Mann-Whitney U test, as appropriate. A p value less than 0.05 was considered as significant.ResultsIn recovery room, morphine consumption was lower in the propacetamol group than in the placebo group (p = 0.01). Pain scores were similar in both groups after tracheal extubation and lower in the propacetamol group (p = 0.003) one hour after tracheal extubation. The time to reach a SNPS < 4 was significantly shorter in the propacetamol group (p = 0.02). The incidence of morphine related side effects did not differ between the two groups.ConclusionsIntraoperative propacetamol administration with remifentanil based-anesthesia improved significantly early postoperative pain by sparing morphine and shortening the delay to achieve pain relief.

PF4-heparin antibodies during ECMO: incidence, course, and outcomes.

Unfractionated heparin is the first-line anticoagulant treatment during extracorporeal membrane oxygenation (ECMO). Heparin-induced thrombocytopenia (HIT) is a rare but severe complication [1] and is challenging to diagnose after cardiopulmonary bypass [2]. The first-line laboratory test for diagnosing HIT is detection of PF4heparin antibodies (PF4-H) [1]. This test is highly sensitive [1] but lacks specificity after cardiopulmonary bypass [3]. The incidence and course of PF4-H positivity during ECMO remain unknown. Here we reported the incidence of PF4-H positivity over time in patients under ECMO, the relationship with HIT, and the outcomes of patients. Our institutional review board approved the study. Consecutive patients managed with ECMO for at least 72 h were identified prospectively and underwent PF4-H assays (Electronic Supplement Fig. 1). Patients were divided according to PF4-H positivity. A diagnosis of HIT needs a positive functional assay [2]. The 73 studied patients had 320 PF4-H assays performed. Among them, 22 (30.1 %; 95 % CI, 20.2–42.1) had at least one positive PF4-H assay. Characteristics and outcomes of patients are summarized in Table 1. Mean time from ECMO initiation to PF4-H seroconversion was 5.1 ± 3.5 days (0.0–13.0 days). Optical densities of positive PF4-H assays varied significantly over time, peaking between days 4 and 6 (1.10 ± 0.83 units). HIT was diagnosed in 3 (4.1 %; 95 % CI, 1.4–11.4) patients. The frequency of thrombotic events increased with the PF4-H titer, from 7/52 (13.5 %) when optical densities were less than 0.5 to 2/9 (22.2 %) when optical densities were between 0.5 and 1.0, and 7/12 (58.3 %) when optical densities were greater than 1.0 (P = 0.003). Platelet counts varied significantly over time (P < 0.0001), with no difference between patients with and without positive PF4-H (Electronic Supplement Fig. 2). The incidence of PF4-H positivity during ECMO is similar to that observed several days after cardiopulmonary bypass where PF4-H positivity ranged between 26 and 51 % [2, 3]. Although nearly a third of our patients had PF4-H, only 4 % were diagnosed with HIT. This incidence of HIT is higher than previously reported in patients after cardiothoracic surgery [2] or during ECMO [4]. Our work emphasizes the challenges raised by diagnosing HIT in patients receiving ECMO. The time-course of the platelet count was not discriminant [2, 3] and the 4Ts score failed to discriminate patients with and without positive PF4-H. During ECMO, a positive PF4-H assay, even with high optical density values, is not sufficient to diagnose HIT. Therefore, the diagnosis of HIT should be confirmed by a functional assay to avoid overdiagnosis [1]. However, receiver operating characteristics of functional assays during ECMO are unknown. We agree that serotonin release assay should be used when the PF4-H and platelet aggregation test results are discordant [2]. Importantly, a negative PF4-H assay rules out HIT [1]. Association between PF4-H positivity and thrombotic events has been previously reported [5] as PF4 itself can be prothrombotic. Patients with positive PF4-H had a trend toward higher mortality as previously reported [4]. However, the clinical comorbidities associated with the risk of death should be also taken into account [2, 4].

High-Flow Nasal Cannula Therapy Versus Intermittent Noninvasive Ventilation in Obese Subjects After Cardiothoracic Surgery

BACKGROUND: Obese patients are considered at risk of respiratory failure after cardiothoracic surgery. High-flow nasal cannula has demonstrated its non-inferiority after cardiothoracic surgery compared to noninvasive ventilation (NIV), which is the recommended treatment in obese patients. We hypothesized that NIV was superior to high-flow nasal cannula for preventing or resolving acute respiratory failure after cardiothoracic surgery in this population. METHODS: We performed a post hoc analysis of a randomized, controlled trial. Obese subjects were randomly assigned to receive NIV for at least 4 h/d (inspiratory pressure, 8 cm H2O; expiratory pressure, 4 cm H2O; FIO2, 0.5) or high-flow nasal cannula delivered continuously (flow, 50 L/min, FIO2 0.5). RESULTS: Treatment failure (defined as re-intubation, switch to the other treatment, or premature discontinuation) occurred in 21 of 136 (15.4%, 95% CI 9.8–22.6%) subjects with NIV compared to 18 of 135 (13.3%, 95% CI 8.1–20.3%) subjects with high-flow nasal cannula (P = .62). No significant differences were found for dyspnea and comfort scores. Skin breakdown was significantly more common with NIV after 24 h (9.2%, 95% CI 5.0–16.0 vs 1.6%, 95% CI 1.0–6.0; P = .01). No significant differences were found for ICU mortality (5.9% for subjects with NIV vs 2.2% for subjects with high-flow nasal cannula, P = .22) or for any of the other secondary outcomes. CONCLUSIONS: Among obese cardiothoracic surgery subjects with or without respiratory failure, the use of continuous high-flow nasal cannula compared to intermittent NIV (8/4 cm H2O) did not result in a worse rate of treatment failure. Because high-flow nasal cannula presents some advantages, it may be used instead of NIV in obese patients after cardiothoracic surgery.

Non-Ventilator ICU-Acquired Pneumonia After Cardiothoracic Surgery: Accuracy of Diagnostic Tools and Outcomes

BACKGROUND: Non-ventilator ICU-acquired pneumonia after cardiothoracic surgery is challenging to diagnose, and little is known about its impact on patient outcomes. Here, our primary objective was to compare the sensitivity and specificity of cultures of 2 types of fiberoptic bronchoscopy (FOB) specimens: endotracheal aspirates (FOB-EA) and bronchoalveolar lavage fluid (FOB-BAL). The secondary objectives were to evaluate the sensitivity and specificity of spontaneous sputum cultures and of the modified Clinical Pulmonary Infection Score (CPIS) and to describe patient outcomes. METHODS: We conducted a prospective observational study of consecutive cardiothoracic surgery subjects with suspected non-ventilator ICU-acquired pneumonia. Using FOB-BAL cultures ≥104 cfu/mL as the reference standard, we evaluated the accuracy of FOB-EA ≥105 cfu/mL and spontaneous sputum ≥107 cfu/mL. On the day of FOB, we determined the modified CPIS. Mortality and antibiotic treatments were recorded. RESULTS: Of 105 subjects, 57 (54.3%) received a diagnosis of non-ventilator ICU-acquired pneumonia. FOB-EA cultures had 82% (95% CI 69–91%) sensitivity and 100% (95% CI 89–100%) specificity and were significantly less sensitive than FOB-BAL cultures (P < .004). Spontaneous sputum was obtained from one-third of subjects. Spontaneous sputum cultures had 82% (95% CI 56–95%) sensitivity and 94% (95% CI 68–100%) specificity and were non-significantly less sensitive than FOB-BAL (P = .061). A modified CPIS >6 had 42% (95% CI 29–56%) sensitivity and 87% (95% CI 74–95%) specificity for non-ventilator ICU-acquired pneumonia. Antibiotic therapy was stopped in all subjects without non-ventilator ICU-acquired pneumonia, after 1.6 ± 1.2 d, without deleterious effects. CONCLUSIONS: The modified CPIS has low diagnostic accuracy for non-ventilator ICU-acquired pneumonia. FOB-EA cultures perform less well than do FOB-BAL cultures for diagnosing non-ventilator ICU-acquired pneumonia. Spontaneous sputum is valuable when FOB cannot be performed but could be obtained in only a minority of subjects. When cultures are negative, antibiotic discontinuation is safe.