Benjamin Planquette

Noninvasive mechanical ventilation in acute respiratory failure: trends in use and outcomes

PurposeNoninvasive ventilation (NIV) had proven benefits in clinical trials that included selected patients admitted to highly skilled centers. Whether these benefits apply to every patient and in everyday practice deserves appraisal. The aim of the study was to assess the use and outcomes of NIV over the last 15xa0years.MethodsMulticenter database study of critically ill patients who required ventilatory support for acute respiratory failure between 1997 and 2011. The impact of first-line NIV on 60-day mortality was evaluated using a marginal structural model. Follow-up was censored on day 60.ResultsOf 3,163 patients, 1,232 (39xa0%) received NIV. Over the study period, first-line NIV increased from 29 to 42xa0%, and NIV success rates increased from 69 to 84xa0%. NIV decreased 60-day mortality [adjusted hazard ratio (aHR), 0.75; 95xa0% confidence interval (95xa0% CI), 0.68–0.83; Pxa0<xa00.0001]. This protective effect was observed in patients with acute-on-chronic respiratory failure (aHR, 0.71; 95xa0% CI, 0.57–0.90; Pxa0=xa00.004), but not in patients with cardiogenic pulmonary edema (aHR, 0.85; 95xa0% CI, 0.70–1.03; Pxa0=xa00.10) or in patients with hypoxemic ARF, either immunocompetent (aHR, 1.18; 95xa0% CI, 0.87–1.59; Pxa0=xa00.30) or immunocompromised (aHR, 0.89; 95xa0% CI, 0.70–1.13; Pxa0=xa00.35). NIV failure was an independent time-dependent risk factor for mortality (aHR, 4.2; 95xa0% CI, 2.8–6.2; Pxa0<xa00.0001).ConclusionsThe use of NIV increased steadily over the study period. First-line NIV was associated with better 60-day survival and fewer ICU-acquired infections compared to first-line intubation. Survival benefits from NIV occurred only in patients with acute-on-chronic respiratory failure and immunocompromised patients.

Pseudomonas Aeruginosa Ventilator-Associated Pneumonia: Predictive Factors of Treatment Failure.

RATIONALEnThe predictive factors of treatment failure for ventilator-associated pneumonia (VAP) caused by Pseudomonas aeruginosa (PA) remain uncertain.nnnOBJECTIVESnTo describe PA-VAP recurrence prognosis and to identify associated risk factors in a large cohort of intensive care unit patients with PA-VAP.nnnMETHODSnFrom the multicenter OUTCOMEREA database (1997-2011), PA-VAP onset and recurrence were recorded. All suspected cases of VAP were confirmed by a positive quantitative culture of a respiratory sample. Multidrug-resistant PA strains were defined by the resistance to two antibiotics among piperacillin, ceftazidime, imipenem, colistine, and fluoroquinolones (FQ). An extensively resistant PA was defined by resistance to piperacillin, ceftazidime, imipenem, and FQ. A treatment failure was defined as a PA-VAP recurrence or by the death occurrence.nnnMEASUREMENTS AND MAIN RESULTSnA total of 314 patients presented 393 PA-VAP. Failure occurred for 112 of them, including 79 recurrences. Susceptible, multidrug resistant, and extensively resistant PA represented 53.7%, 32%, and 14.3% of the samples, respectively. Factors associated with treatment failure were age (P = 0.02); presence of at least one chronic illness (P = 0.02); limitation of life support (P = 0.0004); a high Sepsis-Related Organ Failure Assessment score (P < 0.0001); PA bacteremia (P = 0.003); and previous use of FQ before the first PA-VAP (P = 0.0007). The failure risk was not influenced by the strain resistance profile or by the biantibiotic treatment, but decreased in case of VAP treatment that includes FQ (subdistribution hazard ratio, 0.5 [0.3-0.7]; P = 0.0006). However, the strain resistance profile slowed down the intensive care unit discharge hazard (subdistribution hazard ratio, 0.6 [0.4-1.0]; P = 0.048).nnnCONCLUSIONSnNeither resistance profile nor biantibiotic therapy decreased the risk of PA-VAP treatment failure. However, the profile of PA resistance prolonged the length of stay. Better evaluation of the potential benefit of an initial treatment containing FQ requires further randomized trials.

Ventilator-Associated Events: Prevalence, Outcome, and Relationship With Ventilator-Associated Pneumonia

Objectives:Centers for Disease Control and Prevention built up new surveillance paradigms for the patients on mechanical ventilation and the ventilator-associated events, comprising ventilator-associated conditions and infection-related ventilator-associated complications. We assess 1) the current epidemiology of ventilator-associated event, 2) the relationship between ventilator-associated event and ventilator-associated pneumonia, and 3) the impact of ventilator-associated event on antimicrobials consumption and mechanical ventilation duration. Design:Inception cohort study from the longitudinal prospective French multicenter OUTCOMEREA database (1996-2012). Patients:Patients on mechanical ventilation for greater than or equal to 5 consecutive days were classified as to the presence of a ventilator-associated event episode, using slightly modified Centers for Disease Control and Prevention definitions. Intervention:None. Measurements and Main Results:Among the 3,028 patients, 2,331 patients (77%) had at least one ventilator-associated condition, and 869 patients (29%) had one infection-related ventilator-associated complication episode. Multiple causes, or the lack of identified cause, were frequent. The leading causes associated with ventilator-associated condition and infection-related ventilator-associated complication were nosocomial infections (27.3% and 43.8%), including ventilator-associated pneumonia (14.5% and 27.6%). Sensitivity and specificity of diagnosing ventilator-associated pneumonia were 0.92 and 0.28 for ventilator-associated condition and 0.67 and 0.75 for infection-related ventilator-associated complication, respectively. A good correlation was observed between ventilator-associated condition and infection-related ventilator-associated complication episodes, and ventilator-associated pneumonia occurrence: R2 = 0.69 and 0.82 (p < 0.0001). The median number of days alive without antibiotics and mechanical ventilation at day 28 was significantly higher in patients without any ventilator-associated event (p < 0.05). Ventilator-associated condition and infection-related ventilator-associated complication rates were closely correlated with antibiotic use within each ICU: R2 = 0.987 and 0.99, respectively (p < 0.0001). Conclusions:Ventilator-associated event is very common in a population at risk and more importantly highly related to antimicrobial consumption and may serve as surrogate quality indicator for improvement programs.

Guidewire localization by transthoracic echocardiography during central venous catheter insertion: a periprocedural method to evaluate catheter placement

PurposeTo evaluate the feasibility of guidewire detection in right cardiac cavities by transthoracic echocardiography (TTE) in order to detect catheter misplacement and to optimize central venous catheter (CVC) positioning. Ultrasonic control for catheter tip positioning was compared to that by chest X-ray (CXR).MethodsWe conducted a monocentric prospective observational study (January–November 2010). All consecutive patients undergoing CVC insertion were included. The puncture was performed using the landmark method or ultrasound guidance. TTE was performed during the procedure to follow the arrival of the guidewire in the right cardiac cavities. Catheter misplacement was defined as an aberrant position on the postprocedural CXR (catheter positioning in ipsilateral or contralateral veins). The primary endpoint was the prediction of catheter misplacement by guidewire detection in the cardiac cavities. The secondary endpoint was the optimization of the catheter tip placement in the superior vena cava.ResultsA total of 98 patients received 101 CVC. The guidewire was visualized in 92 cases. In five cases, the guidewire was not seen in the right cardiac cavities and CXR showed catheter misplacement. In four cases, poor echogenicity led to the ultrasound examination being abandoned. Catheter misplacement was detected by TTE with a sensitivity of 96xa0% (CI 90–98xa0%), a specificity of 83xa0% (CI 44–97xa0%), a positive predictive value of 98xa0%, and a negative predictive value of 55xa0%. Likelihood ratios were LR+ 5.7 (CI 0.96–34.4) and LR− 0.05 (CI 0.02–0.14). Guidewire removal under TTE avoided an excessively distal position of the catheter tip in all cases.ConclusionTTE is a reliable tool to detect catheter misplacement and to optimize catheter tip positioning during the procedure of CVC insertion.

Recent advances in the management of pulmonary embolism: focus on the critically ill patients

The aim of this narrative review is to summarize for intensivists or any physicians managing “severe” pulmonary embolism (PE) the main recent advances or recommendations in the care of patients including risk stratification, diagnostic algorithm, hemodynamic management in the intensive care unit (ICU), recent data regarding the use of thrombolytic treatment and retrievable vena cava filters and finally results of direct oral anticoagulants. Thanks to the improvements achieved in the risk stratification of patients with PE, a better therapeutic approach is now recommended from diagnosis algorithm and indication to admission in ICU to indication of thrombolysis and general hemodynamic support in patients with shock. Given at current dosage, thrombolytic therapy is associated with a reduction in the combined end-point of mortality and hemodynamic decompensation in patients with intermediate-risk PE, but this is obtained without a decrease in overall mortality and with a significant increase in major extracranial and intracranial bleeding. In patients with high-intermediate-risk PE, thrombolytic therapy should be given in case of hemodynamic worsening. Vena cava filters are of little help when anticoagulant treatment is not contraindicated, even in patients with PE and features of clinical severity. Finally, direct oral anticoagulants have been shown to be as effective as and safer than the combination of low molecular weight heparin and vitamin K antagonist(s) in patients with venous thromboembolism and low- to intermediate-risk PE.

Initiation of nutritional support is delayed in critically ill obese patients: a multicenter cohort study

BACKGROUNDnA high catabolic rate characterizes the acute phase of critical illness. Guidelines recommend an early nutritional support, regardless of the previous nutritional status.nnnOBJECTIVEnWe aimed to assess whether the nutritional status of patients, which was defined by the body mass index (BMI) at admission in an intensive care unit (ICU), affected the time of nutritional support initiation.nnnDESIGNnWe conducted a cohort study that reported a retrospective analysis of a multicenter ICU database (OUTCOMEREA) by using data prospectively entered from January 1997 to October 2012. Patients who needed orotracheal intubation within the first 72 h and >3 d were included.nnnRESULTSnData from 3257 ICU stays were analyzed. The delay before feeding was different according to BMI groups (P = 0.035). The delay was longer in obese patients [BMI (in kg/m²) ≥30; n = 663] than in other patients with either low weight (BMI <20; n = 501), normal weight (BMI ≥20 and <25; n = 1135), or overweight (BMI ≥25 and <30; n = 958). The association between nutritional status and a delay in nutrition initiation was independent of potential confounding factors such as age, sex, and diabetes or other chronic diseases. In comparison with normal weight, the adjusted RR (95% CI) associated with a delayed nutrition initiation was 0.92 (0.86, 0.98) for patients with low weight, 1.00 (0.94, 1.05) for overweight patients, and 1.06 (1.00, 1.12) for obese patients (P = 0.004).nnnCONCLUSIONSnThe initiation of nutritional support was delayed in obese ICU patients. Randomized controlled trials that address consequences of early compared with delayed beginnings of nutritional support in critically ill obese patients are needed.

Very Small Embryonic-like Stem Cells Are Mobilized in Human Peripheral Blood during Hypoxemic COPD Exacerbations and Pulmonary Hypertension

Very small embryonic-like stem cells (VSELs) are major pluripotent stem cells involved in vascular and tissue regeneration and constitute a recruitable pool of stem/progenitor cells with putative instrumental role in organ repair. Here, we hypothesized that VSELs might be mobilized from the bone marrow (BM) to peripheral blood (PB) in patients with hypoxic lung disease or pulmonary hypertension (PH). The objective of the present study was then to investigate the changes in VSELs number in peripheral blood of patients with hypoxic lung disease and PH. We enrolled 26 patients with Chronic Obstructive Pulmonary Disease (COPD) with or without hypoxemia, 13 patients with PH and 20 controls without any respiratory or cardiovascular diseases. In PH patients, VSELs levels have been determined during right heart catheterization in pulmonary blood and PB. For this purpose, mononuclear cells were separated by density gradient and VSELs have been quantified by using a multiparametric flow cytometry approach. The number of PB-VSELs in hypoxic COPD patients was significantly increased compared with non-hypoxic COPD patients or controls (p = 0.0055). In patients with PH, we did not find any difference in VSELs numbers between arterial pulmonary blood and venous PB (p = 0.93). However, we found an increase in VSELs in the peripheral blood of patients with PH (pxa0=xa00.03). In conclusion, we unraveled that circulating VSELs were increased in peripheral blood of patients with hypoxic COPD or with PH. Thus, VSELs may serve as a reservoir of pluripotent stem cells that can be recruited into PB and may play an important role in promoting lung repair.

Residual pulmonary vascular obstruction and recurrence after acute pulmonary embolism. A single center cohort study

INTRODUCTIONnUp to 50% of patients with pulmonary embolism (PE) present lung perfusion defects after six months of anticoagulant treatment, suggesting residual pulmonary vascular obstruction (RPVO). The risk of recurrence in patients with RPVO remains unknown. The present study aims to assess the risk of recurrent venous thromboembolism (VTE) in patients with RPVO after a first symptomatic episode of PE.nnnMETHODSnConsecutive patients who survived a first objectively proven acute PE, treated for at least three months with anticoagulants, were included and followed prospectively. RPVO was defined as a pulmonary vascular obstruction of >10% on ventilation/perfusion lung scan performed at inclusion. Objectively proven VTE recurrences were registered and confirmed by an investigator unaware of the result of the ventilation/perfusion lung scan.nnnRESULTSnAmong the 310 patients (median age: 61years) included in the study, 60 (19%) had RPVO. During a median follow-up of 51.3months, 66 patients (21.2%, 95% CI [17.5-26.7]) experienced recurrent VTE. In an adjusted cox proportional hazards analysis, we identified RPVO (HR 1.94; 95% CI [1.11-3.39]; p=0.026) and unprovoked PE (HR 3.56; 95% CI [1.79-7.07]; p=0.00051) as independent risk factors for recurrent VTE whereas extended anticoagulation therapy (HR 0.19; 95% CI [0.07-0.55]; p=0.00014) was associated with a low risk of recurrence.nnnCONCLUSIONnThe results suggest that RPVO is an independent risk factor of recurrent VTE after a first PE.

Fibrinolysis for Acute Care of Pulmonary Embolism in the Intermediate Risk Patient.

Controversy over the role of fibrinolysis in patients with intermediate-risk pulmonary embolism (PE) has persisted because of the lack of adequately sized trials. The PEITHO study now allows a more precise estimate of the risk to benefit ratio of fibrinolysis in these patients. This trial enrolled patients with intermediate-risk PE who were randomized to receive heparin with either tenecteplase or placebo. Fibrinolysis was associated with a significant reduction in the combined end-point of death or hemodynamic decompensation, but also with a significant increase in the risk of major bleeding. The primary efficacy end-point occurred in 2.6xa0% of the patients in the tenecteplase group and in 5.6xa0% of the patients in the placebo group (OR, 0.44; 95xa0% CI, 0.23 to 0.87), conversely, major extracranial bleeding occurred in 6.3xa0% and 1.2xa0% in the tenecteplase and placebo groups, respectively (OR, 5.55; 95xa0% CI, 2.3 to 13.39) and stroke occurred in 2.4xa0% and in 0.2xa0% of the patients in the tenecteplase group and in the placebo group, respectively (OR, 12.10; 95xa0% CI, 1.57 to 93.39). No difference was observed for the risk of death alone and the risk of full-dose thrombolytic therapy outweighs its benefit in patients with intermediate-risk PE. Recent meta-analyses suggest that fibrinolysis may be associated with a slight reduction in overall mortality offset by an increase in major bleeding. Two pilot studies suggest that a reduced dose of fibrinolysis may produce significant hemodynamic improvement with a low risk of major bleeding. These options need to be evaluated in larger studies including patients with a higher risk of adverse outcome than those included in the PEITHO study.

Risk stratification of pulmonary embolism: clinical evaluation, biomarkers or both?

A predicting rule based on copeptin may be better than ESC criteria for risk stratification of pulmonary embolism http://ow.ly/T4APZ The concept of risk-stratification is one of the cornerstones of the recent guidelines on pulmonary embolism (PE), which were issued by the European Society of Cardiology (ESC) and endorsed by the European Respiratory Society [1]. According to these guidelines, patients with PE are divided in three groups with increasing risk of death or adverse outcome following a three-step process that is based on clinical data, assessment of anatomical right ventricular dysfunction on echocardiography or spiral computed tomography (CT), and of myocardial injury by dosage of cardiac biomarkers [1]. The first step is based on the measurement of blood pressure to determine whether cardiogenic shock is present, or not. For the vast majority of patients with acute PE who present with normal blood pressure, the second step consists of a simple clinical evaluation, summarised in the Pulmonary Embolism Severity Index (PESI) or its simplified version (sPESI) [2, 3]. These scores are able to select low-risk patients, defined as PESI class I or II or sPESI=0 who have a mortality risk <3% at 1u2005month. Cohort studies and one randomised clinical trial have confirmed that low-risk patients can safely be treated at home [4, 5]. Implementing PESI enables the identification of ∼45% of patients with acute PE as low-risk patients and reduces the length of hospitalisation without significantly increasing the risk of death, recurrent PE or major bleeding [4, 6]. Patients with normal blood pressure, but higher values of PESI or sPESI, have a mortality risk of ∼5–7% and should be treated at hospital according to ESC guidelines [1, 7, 8]. The goal of further risk stratification is to select the patients with the highest risk of an adverse event among those with normal blood pressure. This can be done by the combination of cardiac biomarkers dosing and/or the search for right ventricular dysfunction (RVD) by echocardiography or spiral CT. Several cohort studies strongly suggest that clinical variables, RVD and biomarkers have independent and complementary prognostic values in normotensive patients with acute PE [8–10].