Jean-Pierre Frat

High-Flow Oxygen through Nasal Cannula in Acute Hypoxemic Respiratory Failure

BACKGROUND Whether noninvasive ventilation should be administered in patients with acute hypoxemic respiratory failure is debated. Therapy with high-flow oxygen through a nasal cannula may offer an alternative in patients with hypoxemia. METHODS We performed a multicenter, open-label trial in which we randomly assigned patients without hypercapnia who had acute hypoxemic respiratory failure and a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of 300 mm Hg or less to high-flow oxygen therapy, standard oxygen therapy delivered through a face mask, or noninvasive positive-pressure ventilation. The primary outcome was the proportion of patients intubated at day 28; secondary outcomes included all-cause mortality in the intensive care unit and at 90 days and the number of ventilator-free days at day 28. RESULTS A total of 310 patients were included in the analyses. The intubation rate (primary outcome) was 38% (40 of 106 patients) in the high-flow-oxygen group, 47% (44 of 94) in the standard group, and 50% (55 of 110) in the noninvasive-ventilation group (P=0.18 for all comparisons). The number of ventilator-free days at day 28 was significantly higher in the high-flow-oxygen group (24±8 days, vs. 22±10 in the standard-oxygen group and 19±12 in the noninvasive-ventilation group; P=0.02 for all comparisons). The hazard ratio for death at 90 days was 2.01 (95% confidence interval [CI], 1.01 to 3.99) with standard oxygen versus high-flow oxygen (P=0.046) and 2.50 (95% CI, 1.31 to 4.78) with noninvasive ventilation versus high-flow oxygen (P=0.006). CONCLUSIONS In patients with nonhypercapnic acute hypoxemic respiratory failure, treatment with high-flow oxygen, standard oxygen, or noninvasive ventilation did not result in significantly different intubation rates. There was a significant difference in favor of high-flow oxygen in 90-day mortality. (Funded by the Programme Hospitalier de Recherche Clinique Interrégional 2010 of the French Ministry of Health; FLORALI ClinicalTrials.gov number, NCT01320384.).

EffectofNotMonitoringResidualGastricVolume on Risk of Ventilator-Associated Pneumonia in Adults Receiving Mechanical Ventilation and Early Enteral Feeding A Randomized Controlled Trial

IMPORTANCE Monitoring of residual gastric volume is recommended to prevent ventilator-associated pneumonia (VAP) in patients receiving early enteral nutrition. However, studies have challenged the reliability and effectiveness of this measure. OBJECTIVE To test the hypothesis that the risk of VAP is not increased when residual gastric volume is not monitored compared with routine residual gastric volume monitoring in patients receiving invasive mechanical ventilation and early enteral nutrition. DESIGN, SETTING, AND PATIENTS Randomized, noninferiority, open-label, multicenter trial conducted from May 2010 through March 2011 in adults requiring invasive mechanical ventilation for more than 2 days and given enteral nutrition within 36 hours after intubation at 9 French intensive care units (ICUs); 452 patients were randomized and 449 included in the intention-to-treat analysis (3 withdrew initial consent). INTERVENTION Absence of residual gastric volume monitoring. Intolerance to enteral nutrition was based only on regurgitation and vomiting in the intervention group and based on residual gastric volume greater than 250 mL at any of the 6 hourly measurements and regurgitation or vomiting in the control group. MAIN OUTCOME MEASURES Proportion of patients with at least 1 VAP episode within 90 days after randomization, as assessed by an adjudication committee blinded to patient group. The prestated noninferiority margin was 10%. RESULTS In the intention-to-treat population, VAP occurred in 38 of 227 patients (16.7%) in the intervention group and in 35 of 222 patients (15.8%) in the control group (difference, 0.9%; 90% CI, -4.8% to 6.7%). There were no significant between-group differences in other ICU-acquired infections, mechanical ventilation duration, ICU stay length, or mortality rates. The proportion of patients receiving 100% of their calorie goal was higher in the intervention group (odds ratio, 1.77; 90% CI, 1.25-2.51; P = .008). Similar results were obtained in the per-protocol population. CONCLUSION AND RELEVANCE Among adults requiring mechanical ventilation and receiving early enteral nutrition, the absence of gastric volume monitoring was not inferior to routine residual gastric volume monitoring in terms of development of VAP. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01137487.

Neurologic complications and outcomes of infective endocarditis in critically ill patients: The ENDOcardite en REAnimation prospective multicenter study

Objective: To describe the clinical spectrum of infective endocarditis in critically ill patients and assess the impact of neurologic complications on outcomes. Design: Prospective multicenter observational study conducted from April 2007 to October 2008. Setting: Thirty-three intensive care units in 23 university-affiliated and 10 general French hospitals. Patients: Two hundred twenty-five patients with definite IE were studied. Factors associated with neurologic complications and predictors of 3-month mortality were identified by logistic regression analysis. Functional outcomes of patients with neurologic complications were evaluated with the modified Rankin Scale. Interventions: None. Measurements and Main Results: Among 198 patients with definite left-sided infective endocarditis, 108 (55%) experienced at least one neurologic complication. These complications were ischemic stroke (n = 79), cerebral hemorrhage (n = 53), meningitis or meningeal reaction (n = 41), brain abscess (n = 14), and mycotic aneurysm (n = 10). Factors independently associated with neurologic complications were (subhazard ratio [95% confidence interval]): Staphylococcus aureus infective endocarditis (1.45 [1.02–2.05]), mitral valve infective endocarditis (1.54 [1.07–2.21]), and nonneurologic embolic events (1.51 [1.09–2.09]). In contrast, health care-associated infective endocarditis had a protective effect (0.46 [0.27–0.77]). Multivariate analysis identified three variables associated with 3-month mortality (odds ratio [95% confidence interval]): neurologic failure, as defined as a Glasgow Coma Scale <10 (7.41 [2.89–18.96]), S. aureus infective endocarditis (3.26 [1.53–6.94]), and severe comorbidities before admission as defined as a Charlson score >2 (3.16 [1.47–6.77]). Among the 106 patients with neurologic complications assessed at follow-up (3.9 [3–8.5] months), 31 (29%) had a modified Rankin Scale score ≤3 (ability to walk without assistance), nine (9%) a modified Rankin Scale score of 4 or 5 (severe disability), and 66 (62%) a modified Rankin Scale score of 6 (death). Conclusions: Neurologic events are the most frequent complications in infective endocarditis patients requiring intensive care unit admission. They contribute to a severe prognosis, leaving less than one-third of patients alive with functional independence. Neurologic failure at intensive care unit admission represents a major determinant of mortality regardless of the underlying neurologic complication.

Epidemiology of Weaning Outcome according to a New Definition. The WIND Study

Rationale: The weaning process concerns all patients receiving mechanical ventilation. A previous classification into simple, prolonged, and difficult weaning ignored weaning failure and presupposed the use of spontaneous breathing trials. Objectives: To describe the weaning process, defined as starting with any attempt at separation from mechanical ventilation and its prognosis, according to a new operational classification working for all patients under ventilation. Methods: This was a multinational prospective multicenter observational study over 3 months of all patients receiving mechanical ventilation in 36 intensive care units, with daily collection of ventilation and weaning modalities. Pragmatic definitions of separation attempt and weaning success allowed us to allocate patients in four groups. Measurements and Main Results: A total of 2,729 patients were enrolled. Although half of them could not be classified using the previous definition, 99% entered the groups on the basis of our new definition as follows: 24% never started a weaning process, 57% had a weaning process of less than 24 hours (group 1), 10% had a difficult weaning of more than 1 day and less than 1 week (group 2), and 9% had a prolonged weaning duration of 1 week or more (group 3). Duration of ventilation, intensive care unit stay, and mortality (6, 17, and 29% for the three groups, respectively) all significantly increased from one group to the next. The unadjusted risk of dying was 19% after the first separation attempt and increased to 37% after 10 days. Conclusions: A new classification allows us to categorize all weaning situations. Every additional day without a weaning success after the first separation attempt increases the risk of dying.

Long-term outcomes and cardiac surgery in critically ill patients with infective endocarditis

AIMS To assess long-term outcomes and the management of critical left-sided infective endocarditis (IE) and evaluate the impact of surgery. METHODS AND RESULTS Among the 198 patients included prospectively for IE across 33 adult intensive care units (ICU) in France from 1 April 2007 to 1 October 2008, 137 (69%) were dead at a median follow-up time of 59.5 months. Characteristics significantly associated with mortality were: Sepsis-related Organ-Failure Assessment (SOFA) score at ICU admission [Hazard ratio (HR), 95% Confidence Interval (CI) of 1.43 (0.79-2.59) for SOFA 5-9; 2.01 (1.05-3.85) for SOFA 10-14; 3.53 (1.75-7.11) for SOFA 15-20; reference category SOFA 0-4; P = 0.003]; prosthetic mechanical valve IE [HR 2.01; 95% CI 1.09-3.69, P = 0.025]; vegetation size ≥15 mm [HR 1.64; 95% CI 1.03-2.63, P = 0.038]; and cardiac surgery [HR (95%CI), 0.33 (0.16-0.67) for surgery ≤1 day after IE diagnosis; 0.61 (0.29-1.26) for surgery 2-7 days after IE diagnosis; 0.42 (0.21-0.83) for surgery >7 days after IE diagnosis; reference category no surgery; P = 0.005]. One hundred and three (52%) patients underwent cardiac surgery after a median time of 6 (16) days. Independent predictors of surgical intervention on multivariate analysis were: age ≤60 years [Odds ratio (OR) 5.30; 95% CI (2.46-11.41), P < 0.01], heart failure [OR 3.27; 95% CI (1.03-10.35), P = 0.04], cardiogenic shock [OR 3.31; 95% CI (1.47-7.46), P = 0.004], septic shock [OR 0.25; 95% CI (0.11-0.59), P = 0.002], immunosuppression [OR 0.15; 95% CI (0.04-0.55), P = 0.004], and diagnosis before or within 24 h of ICU admission [OR 2.81; 95% CI (1.14-6.95), P = 0.025]. SOFA score calculated the day of surgery was the only independently associated factor with long-term mortality [HR (95% CI) 1.59 (0.77-3.28) for SOFA 5-9; 3.56 (1.71-7.38) for SOFA 10-14; 11.58 (4.02-33.35) for SOFA 15-20; reference category SOFA 0-4; P < 0.0001]. Surgical timing was not associated with post-operative outcomes. Of the 158 patients with a theoretical indication for surgery, the 58 deemed not fit had a 95% mortality rate. CONCLUSION Mortality in patients with critical IE remains unacceptably high. Factors associated with long-term outcomes are the severity of multiorgan failure, prosthetic mechanical valve IE, vegetation size ≥15 mm, and surgical treatment. Up to one-third of potential candidates do not undergo surgery and these patients experience extremely high mortality rates. The strongest independent predictor of post-operative mortality is the pre-operative multiorgan failure score while surgical timing does not seem to impact on outcomes.

Cervical spinal epidural abscess and meningitis due to Prevotella oris and Peptostreptococcus micros after retropharyngeal surgery.

usually due to the contiguous spread of infection or can be related to hematogenous spread from a distant infection [1]. To our knowledge only four cases of epidural abscess due to anaerobic bacteria have previously been reported [2, 3, 4, 5]. In our case, since the isolated anaerobic bacteria could be part of the healthy oral flora they can be logically responsible for a contiguous spread of infection following retropharyngeal surgery [1]. Since anaerobic isolation requires specific methods, the involvement of anaerobic bacteria in epidural abscess associated with oropharyngeal infection can be underestimated. In our case Peptostreptococcus micros was isolated after inoculation of the CSF in a blood anaerobic bottle containing charcoal particles that neutralize antibiotics. Peptostreptococcus micros was not isolated from the epidural abscess at day 5, probably because of its high susceptibility to the antibiotics given to the patient. Conversely, Prevotella oris could be isolated in the epidural abscess because of its resistance to amoxicillin and ceftriaxone. The optimal treatment of epidural abscess due to anaerobic bacteria is poorly defined. Prompt surgical decompressive laminectomy and drainage in the presence of signs of spinal cord compression and antibiotics are suggested [2]. This case illustrates the possibility of benign surgery of a retropharyngeal lesion inducing a severe epidural complication. Since anaerobic bacteria are normally part of the oropharyngeal flora, they can be involved in such disease. Their isolation is difficult, requiring specific methods, and can be delayed. Empiric antibiotic therapy should consider anaerobic bacteria in these situations. References

Efficacy of nebulised liposomal amphotericin B in the attack and maintenance treatment of ABPA

To the Editors: Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disorder that results from a hypersensitivity reaction to Aspergillus spp. It has been estimated to occur in 1–3% of people with chronic asthma and 2–15% of those with cystic fibrosis [1]. The natural history of ABPA is characterised by exacerbations that can threaten the patient’s survival and prognosis [1]. Repetition of such exacerbations is responsible for the development of bronchiectasis, permanent obstructive ventilation defect or fibrotic lung lesions. Prognosis mainly depends on the very early treatment of exacerbations before bronchiectasis sets in. In 2008, the guidelines of the Infectious Diseases Society of America advised combination therapy in ABPA [2]: systemic glucocorticoids to limit the inflammatory component and antifungals to limit mycelium proliferation. However, even though glucocorticoid therapy and antifungals are the treatment of choice for acute-stage ABPA and exacerbations, there are no data to guide the duration of this treatment. Therefore, the current objectives for the management of ABPA are a decrease in the frequency and duration of exacerbations, and a limited solicitation of glucocorticoids. Consequently, the maintenance treatment in the management of ABPA remains a current and progressive problem for pneumologists. We describe a case of ABPA that was difficult to control using the standard treatment regimen, but which improved dramatically and durably following administration of nebulised liposomal amphotericin B (LAmB). In May 2010, a 67-yr-old female presented with fever and productive cough, with sputum plugs and a history of epilepsy treated with phenobarbital. In the preceding 3 months, she had presented recurrent chest infections resistant to amoxicillin and ciprofloxacin; glucocorticoids (1 mg·kg−1·day …

High-Flow Nasal Cannula Oxygen in Respiratory Failure.

To the Editor: Frat and colleagues (June 4 issue)1 report a survival benefit with high-flow oxygen, as compared with standard oxygen or noninvasive ventilation, in patients with acute hypoxemic respiratory failure. Despite randomization, there was a large number of exclusions: only 313 of the 2506 screened patients underwent randomization. The small number of enrolled patients may have allowed an unbalanced distribution of the variables that affect mortality among patients with pneumonia, such as antimicrobial adequacy or time to first dose of antibiotics. This hypothesis seems stronger in light of the uneven prevalence of septic shock between the high-flow–oxygen group and the noninvasive-ventilation group (17.9% vs. 30.9%) (Table S2 in the Supplementary Appendix of the article, available with the full text of the article at NEJM.org). These biases may prevent the results from being attributed to the proposed intervention. Iuri C. Wawrzeniak, M.D. Rafael B. Moraes, M.D., Ph.D. Lúcia C.C. Fendt, M.D.

Nebulised liposomal amphotericin B for Aspergillus lung diseases: case series and literature review

Over the past 10 years the incidence of Aspergillus spp. has significantly increased, and it is now the most widespread air transmission fungal pathogen in developed countries. Whatever the clinical expression of the pulmonary disease and despite recent progress in antifungal drug therapy, morbidity and mortality related to aspergillosis lung disease still constitute a serious threat for immunosuppressed or mildly immunocompromised patients. Moreover, the treatments currently used have many limitations due to adverse effects and drug interactions. Finally, subjects exposed to azoles present an increased risk of Aspergillus‐resistant strain emergence. We have reported five cases with aspergillosis lung diseases that were either difficult to control or in which patients had a contra‐indication to triazole therapy, but which showed durable improvement following the administration of nebulised liposomal amphotericin B. Our alternative strategy could be of interest for patients with aspergillosis lung disease who otherwise cannot be conventionally treated by triazoles.

Letter to the Editor: Protective Effect of Medication Bezoar After a Massive Beta-Blocker, Digoxin, and Amitriptyline Poisoning

CASE REPORT A 32-yr-old female working as a nurse in an emergency department was admitted to the ICU after massive ingestion of metoprolol, amitriptyline, and digoxin. She had a previous history of depression and had been hospitalized several times for acute poisoning. Her usual medications were amitriptyline and cymamemazine. Several weeks before ingestion she collected numerous tablets of metoprolol and digoxin stolen from the cardiologic ward. On the morning of her admission, she put 115 tablets of metoprolol (11150 mg), 50 tablets of amitriptyline, 75 mg (3750 mg), and 25 tablets of digoxin (2.25 mg) in a bowl and threw away the empty boxes. She ingested all the tablets at 11 a.m. Four hours later she felt no significant effect except vomiting, and called a friend. She was then referred to the emergency ward. Her clinical examination showed no neurological alteration. Her arterial blood pressure was 140/80 mmHg, her heart rate was 60 beats per min. EKG showed sinus rhythm, PR space of 22 msec, and QT space of 0.36 msec. Plasma laboratory tests were the following: glucose=6.2 mmol/L; sodium=132 mmol/ L; potassium=6.2 mmol/L; chloride=96 mmol/L; bicarbonate=25 mmol/L; creatinine=122 mmol/L; AST=195 UI/L; ALT=100 UI/L; alkaline phosphatases=97 UI/L; bilirubin= 6 mmol/L. Plasma digoxin level was 12.10 ng per mL. Plasma metoprolol chromatographic analysis performed the next day of admission was 30 mg per mL. Urine qualitative determination was positive only for tricyclic antidepressant. She had a gastric lavage and received activated charcoal administration, and she was admitted to the ICU for monitoring. She received 480 mg of digoxin antibodies. Six hours later she had no hemodynamic disorder, her heart rate was 45 per min. EKG showed sinus rhythm with normal QRS complex and QT space. The thoracic X-ray performed after gastric emptying showed bezoar (Fig. 1). During the first 2 days of hospitalization she received 50 g of activated charcoal every 4 h and 4 L of polyethylene glycol. Abdominal X-ray showed the progressive desintegration of the bezoar. Gastric fibroscopy was not performed. Four days after her admission, clinical examination showed no abnormality, and she was transferred to a psychiatric ward.