Early and specific targeted mass spectrometry-based identification of bacteria in endotracheal aspirates of patients suspected with ventilator-associated pneumonia.

Rapid and reliable pathogen identification is compulsory to confirm ventilator-associated pneumonia (VAP) in order to initiate appropriate antibiotic treatment. In the present proof of concept, the effectiveness of rapid microorganism identification with a targeted bottom-up proteomics approach was investigated in endotracheal aspirate (ETA) samples of VAP patients. To do so, a prototype selected-reaction monitoring (SRM)-based assay was developed on a triple quadrupole mass spectrometer tracking proteotypic peptide surrogates of bacterial proteomes. Through the concurrent monitoring of 97 species-specific peptides, this preliminary assay was dimensioned to characterize the occurrence of six most frequent bacterial species responsible for over more than 65% of VAP. Assay performance was subsequently evaluated by analyzing early and regular 37 ETA samples collected from 15 patients. Twenty-five samples were above the significant threshold of 105 CFU/mL and five samples showed mixed infections (both pathogens ≥ 105 CFU/mL). The targeted proteomics assay showed 100% specificity for Acinetobacter baumannii, Escherichia coli, Haemophilus influenzae, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae. No false bacterial identification was reported and no interference was detected arising from the commensal flora. The overall species identification sensitivity was 19/25 (76%) and was higher at the patient level (84.6%). This successful proof of concept provides a rational to broaden the panel of bacteria for further clinical evaluation.

Prevalence and Prognosis Impact of Patient-Ventilator Asynchrony in Early Phase of Weaning according to Two Detection Methods.

BACKGROUND: Patient-ventilator asynchrony is associated with a poorer outcome. The prevalence and severity of asynchrony during the early phase of weaning has never been specifically described. The authors' first aim was to evaluate the prognosis impact and the factors associated with asynchrony. Their second aim was to compare the prevalence of asynchrony according to two methods of detection: a visual inspection of signals and a computerized method integrating electromyographic activity of the diaphragm. METHODS: This was an ancillary study of a multicenter, randomized controlled trial comparing neurally adjusted ventilatory assist to pressure support ventilation. Asynchrony was quantified at 12, 24, 36, and 48 h after switching from controlled ventilation to a partial mode of ventilatory assistance according to the two methods. An asynchrony index greater than or equal to 10% defined severe asynchrony. RESULTS: A total of 103 patients ventilated for a median duration of 5 days (interquartile range, 3 to 9 days) were included. Whatever the method used for quantification, severe patient-ventilator asynchrony was not associated with an alteration of the outcome. No factor was associated with severe asynchrony. The prevalence of asynchrony was significantly lower when the quantification was based on flow and pressure than when it was based on the electromyographic activity of the diaphragm at 0.3 min (interquartile range, 0.2 to 0.8 min) and 4.7 min (interquartile range, 3.2 to 7.7 min; P < 0.0001), respectively. CONCLUSIONS: During the early phase of weaning in patients receiving a partial ventilatory mode, severe patient-ventilator asynchrony was not associated with adverse clinical outcome, although the prevalence of patient-ventilator asynchrony varies according to the definitions and methods used for detection.

Prone positioning in severe acute respiratory distress syndrome.

BACKGROUND: Previous trials involving patients with the acute respiratory distress syndrome (ARDS) have failed to show a beneficial effect of prone positioning during mechanical ventilatory support on outcomes. We evaluated the effect of early application of prone positioning on outcomes in patients with severe ARDS. METHODS: In this multicenter, prospective, randomized, controlled trial, we randomly assigned 466 patients with severe ARDS to undergo prone-positioning sessions of at least 16 hours or to be left in the supine position. Severe ARDS was defined as a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (FiO2) of less than 150 mm Hg, with an FiO2 of at least 0.6, a positive end-expiratory pressure of at least 5 cm of water, and a tidal volume close to 6 ml per kilogram of predicted body weight. The primary outcome was the proportion of patients who died from any cause within 28 days after inclusion. RESULTS: A total of 237 patients were assigned to the prone group, and 229 patients were assigned to the supine group. The 28-day mortality was 16.0% in the prone group and 32.8% in the supine group (P<0.001). The hazard ratio for death with prone positioning was 0.39 (95% confidence interval [CI], 0.25 to 0.63). Unadjusted 90-day mortality was 23.6% in the prone group versus 41.0% in the supine group (P<0.001), with a hazard ratio of 0.44 (95% CI, 0.29 to 0.67). The incidence of complications did not differ significantly between the groups, except for the incidence of cardiac arrests, which was higher in the supine group. CONCLUSIONS: In patients with severe ARDS, early application of prolonged prone-positioning sessions significantly decreased 28-day and 90-day mortality. (Funded by the Programme Hospitalier de Recherche Clinique National 2006 and 2010 of the French Ministry of Health; PROSEVA ClinicalTrials.gov number, NCT00527813.).

Effect of Acetazolamide vs Placebo on Duration of Invasive Mechanical Ventilation Among Patients With Chronic Obstructive Pulmonary Disease: A Randomized Clinical Trial.

IMPORTANCE: Acetazolamide has been used for decades as a respiratory stimulant for patients with chronic obstructive pulmonary disease (COPD) and metabolic alkalosis, but no large randomized placebo-controlled trial is available to confirm this approach. OBJECTIVE: To determine whether acetazolamide reduces mechanical ventilation duration in critically ill patients with COPD and metabolic alkalosis. DESIGN, SETTING, AND PARTICIPANTS: The DIABOLO study, a randomized, double-blind, multicenter trial, was conducted from October 2011 through July 2014 in 15 intensive care units (ICUs) in France. A total of 382 patients with COPD who were expected to receive mechanical ventilation for more 24 hours were randomized to the acetazolamide or placebo group and 380 were included in an intention-to treat analysis. INTERVENTIONS: Acetazolamide (500-1000 mg, twice daily) vs placebo administered intravenously in cases of pure or mixed metabolic alkalosis, initiated within 48 hours of ICU admission and continued during the ICU stay for a maximum of 28 days. MAIN OUTCOMES AND MEASURES: The primary outcome was the duration of invasive mechanical ventilation via endotracheal intubation or tracheotomy. Secondary outcomes included changes in arterial blood gas and respiratory parameters, weaning duration, adverse events, use of noninvasive ventilation after extubation, successful weaning, the duration of ICU stay, and in-ICU mortality. RESULTS: Among 382 randomized patients, 380 (mean age, 69 years; 272 men [71.6%]; 379 [99.7%] with endotracheal intubation) completed the study. For the acetazolamide group (n = 187), compared with the placebo group (n = 193), no significant between-group differences were found for median duration of mechanical ventilation (-16.0 hours; 95% CI, -36.5 to 4.0 hours; P = .17), duration of weaning off mechanical ventilation (-0.9 hours; 95% CI, -4.3 to 1.3 hours; P = .36), daily changes of minute-ventilation (-0.0 L/min; 95% CI, -0.2 to 0.2 L/min; P = .72), or partial carbon-dioxide pressure in arterial blood (-0.3 mm Hg; 95% CI, -0.8 to 0.2 mm Hg; P = .25), although daily changes of serum bicarbonate (between-group difference, -0.8 mEq/L; 95% CI, -1.2 to -0.5 mEq/L; P < .001) and number of days with metabolic alkalosis (between-group difference, -1; 95% CI, -2 to -1 days; P < .001) decreased significantly more in the acetazolamide group. Other secondary outcomes also did not differ significantly between groups. CONCLUSIONS AND RELEVANCE: Among patients with COPD receiving invasive mechanical ventilation, the use of acetazolamide, compared with placebo, did not result in a statistically significant reduction in the duration of invasive mechanical ventilation. However, the magnitude of the difference was clinically important, and it is possible that the study was underpowered to establish statistical significance. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01627639.

Hemodynamic monitoring using a single-use indwelling transesophageal echocardiography probe in an unstable patient after open-heart surgery.

BACKGROUND: Hemodynamic monitoring is frequently needed in ventilated patients with unstable hemodynamics after open-heart surgery. Novel miniaturized single-use transesophageal echocardiographic probe has been scarcely used in this clinical setting. CASE PRESENTATION: A patient who underwent a scheduled open-heart surgery developed a ventilator-associated pneumonia and was referred to the intensive care unit for post-operative acute respiratory distress syndrome. Hemodynamic monitoring was performed with a single-use indwelling transesophageal echocardiography probe during 50 h. Initially, a contrast study depicted a patent foramen ovale with a right-to-left shunt. Nitric oxide was administered and positive end-expiration pressure was reduced. Subsequently, the patient became hemodynamically unstable and the identification of a localized tamponade due to compressive left atrial hematoma prompted reoperation. CONCLUSIONS: The novel hemodynamic monitoring device described here appears valuable to help identifying severe post-operative complications and guide acute care.

Extracorporeal membrane oxygenation for pandemic influenza A(H1N1)-induced acute respiratory distress syndrome: a cohort study and propensity-matched analysis.

RATIONALE: Many patients with severe acute respiratory distress syndrome (ARDS) caused by influenza A(H1N1) infection receive extracorporeal membrane oxygenation (ECMO) as a rescue therapy. OBJECTIVES: To analyze factors associated with death in ECMO-treated patients and the influence of ECMO on intensive care unit (ICU) mortality. METHODS: Data from patients admitted for H1N1-associated ARDS to French ICUs were prospectively collected from 2009 to 2011 through the national REVA registry. We analyzed factors associated with in-ICU death in ECMO recipients, and the potential benefit of ECMO using a propensity score-matched (1:1) cohort analysis. MEASUREMENTS AND MAIN RESULTS: A total of 123 patients received ECMO. By multivariate analysis, increasing values of age, lactate, and plateau pressure under ECMO were associated with death. Of 103 patients receiving ECMO during the first week of mechanical ventilation, 52 could be matched to non-ECMO patients of comparable severity, using a one-to-one matching and using control subjects only once. Mortality did not differ between the two matched cohorts (odds ratio, 1.48; 95% confidence interval, 0.68-3.23; P = 0.32). Interestingly, the 51 ECMO patients who could not be matched were younger, had lower Pa(o(2))/Fi(o(2)) ratio, had higher plateau pressure, but also had a lower ICU mortality rate than the 52 matched ECMO patients (22% vs. 50%; P < 0.01). CONCLUSIONS: Under ECMO, an ultraprotective ventilation strategy minimizing plateau pressure may be required to improve outcome. When patients with severe influenza A(H1N1)-related ARDS treated with ECMO were compared with conventionally treated patients, no difference in mortality rates existed. The unmatched, severely hypoxemic, and younger ECMO-treated patients had, however, a lower mortality.

Effect of not monitoring residual gastric volume 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.

Extracorporeal albumin dialysis in three cases of acute calcium channel blocker poisoning with life-threatening refractory cardiogenic shock.

We describe 3 patients admitted to the medical-surgical ICU in a university hospital with life-threatening cardiogenic shock after the ingestion of high doses of calcium channel blockers (8.4 g sustained-release diltiazem, 4.2 g sustained-release diltiazem, and 14.4 g slow-release verapamil). Cardiovascular failure and cardiac conduction disturbances were unresponsive to the usual therapy (eg, intravenous injection of high doses of calcium, glucagon, hyperinsulinemia-euglycemia therapy, fluid resuscitation) and to increasing doses of simultaneous infusions of adrenergic agonists. Albumin dialysis with Molecular Adsorbents Recirculating System (MARS) therapy was performed because of its unique ability to selectively remove from circulation protein-bound toxins (and potentially drugs) that are not cleared by conventional hemodialysis. A single procedure was successfully performed in each patient, which was followed by rapid weaning of adrenergic agonist agents and full recovery of the life-threatening cardiovascular failure. At 2-year follow-up, patients were asymptomatic. Albumin dialysis with MARS therapy may be effective when used as a rescue procedure in patients presenting with sustained, life-threatening cardiogenic shock as a result of massive calcium channel blocker poisoning.

Assessment of left ventricular ejection fraction using an ultrasonic stethoscope in critically ill patients.

INTRODUCTION: Assessment of cardiac function is key in the management of intensive care unit (ICU) patients and frequently relies on the use of standard transthoracic echocardiography (TTE). A commercially available new generation ultrasound system with two-dimensional imaging capability, which has roughly the size of a mobile phone, is adequately suited to extend the physical examination. The primary endpoint of this study was to evaluate the additional value of this new miniaturized device used as an ultrasonic stethoscope (US) for the determination of left ventricular (LV) systolic function, when compared to conventional clinical assessment by experienced intensivists. The secondary endpoint was to validate the US against TTE for the semi-quantitative assessment of left ventricular ejection fraction (LVEF) in ICU patients. METHODS: In this single-center prospective descriptive study, LVEF was independently assessed clinically by the attending physician and echocardiographically by two experienced intensivists trained in critical care echocardiography who used the US (size: 135×73×28 mm; weight: 390 g) and TTE. LVEF was visually estimated semi-quantitatively and classified in one of the following categories: increased (LVEF>75%), normal (LVEF: 50 to 75%), moderately reduced (LVEF: 30 to 49%), or severely reduced (LVEF<30%). Biplane LVEF measured using the Simpson's rule on TTE loops by an independent investigator was used as reference. RESULTS: A total of 94 consecutive patients were studied (age: 60±17 years; simplified acute physiologic score 2: 41±15), 63 being mechanically ventilated and 36 receiving vasopressors and/or inotropes. Diagnostic concordance between the clinically estimated LVEF and biplane LVEF was poor (Kappa: 0.33; 95% CI: 0.16 to 0.49) and only slightly improved by the knowledge of a previously determined LVEF value (Kappa: 0.44; 95% CI: 0.22 to 0.66). In contrast, the diagnostic agreement was good between visually assessed LVEF using the US and TTE (Kappa: 0.75; CI 95%: 0.63 to 0.87) and between LVEF assessed on-line and biplane LVEF, regardless of the system used (Kappa: 0.75; CI 95%: 0.64 to 0.87 and Kappa: 0.70; CI 95%: 0.59 to 0.82, respectively). CONCLUSIONS: In ICU patients, the extension of physical examination using an US improves the ability of trained intensivists to determine LVEF at bedside. With trained operators, the semi-quantitative assessment of LVEF using the US is accurate when compared to standard TTE.

A randomized trial of 7-day doripenem versus 10-day imipenem-cilastatin for ventilator-associated pneumonia.

INTRODUCTION: The aim of this study was to compare a 7-day course of doripenem to a 10-day course of imipenem-cilastatin for ventilator-associated pneumonia (VAP) due to Gram-negative bacteria. METHODS: This was a prospective, double-blinded, randomized trial comparing a fixed 7-day course of doripenem one gram as a four-hour infusion every eight hours with a fixed 10-day course of imipenem-cilastatin one gram as a one-hour infusion every eight hours (April 2008 through June 2011). RESULTS: The study was stopped prematurely at the recommendation of the Independent Data Monitoring Committee that was blinded to treatment arm assignment and performed a scheduled review of data which showed signals that were close to the pre-specified stopping limits. The final analyses included 274 randomized patients. The clinical cure rate at the end of therapy (EOT) in the microbiological intent-to-treat (MITT) population was numerically lower for patients in the doripenem arm compared to the imipenem-cilastatin arm (45.6% versus 56.8%; 95% CI, -26.3% to 3.8%). Similarly, the clinical cure rate at EOT was numerically lower for patients with Pseudomonas aeruginosa VAP, the most common Gram-negative pathogen, in the doripenem arm compared to the imipenem-cilastatin arm (41.2% versus 60.0%; 95% CI, -57.2 to 19.5). All cause 28-day mortality in the MITT group was numerically greater for patients in the doripenem arm compared to the imipenem-cilastatin arm (21.5% versus 14.8%; 95% CI, -5.0 to 18.5) and for patients with P. aeruginosa VAP (35.3% versus 0.0%; 95% CI, 12.6 to 58.0). CONCLUSIONS: Among patients with microbiologically confirmed late-onset VAP, a fixed 7-day course of doripenem was found to have non-significant higher rates of clinical failure and mortality compared to a fixed 10-day course of imipenem-cilastatin. Consideration should be given to treating patients with VAP for more than seven days to optimize clinical outcome. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00589693.

Value of liver stiffness measured by transient elastography in the liver transplant pre-operative evaluation of the potential deceased liver donors: preliminary study.

The selection of a liver graft is crucial for the success of a transplantation. One of the determinant factors in the selection of a liver graft of quality is to assess the degree of steatosis. The aim of this study was to evaluate the feasibility of a FibroScan(®) during the liver retrieval procedure and to determine the interest of measuring liver stiffness (LS) using the FibroScan(®) as a criterion of objective assessment in the pre-donation selection of liver grafts. Of 16 FibroScan(®) performed on 16 livers of donors meeting conventional French criteria for the selection of liver grafts, the LS values were considered as abnormal in three donors (18.75%). The correspondence with the histologic analysis of the biopsies in terms of elevated steatosis was excellent. For 13 other liver grafts, the values of LS were normal as were the histologic analyses of the biopsies. A supplementary multicenter study is required in order to position the transient elastography as the objective examination in the pre-operative selection of liver grafts.

Acyclovir for Mechanically Ventilated Patients With Herpes Simplex Virus Oropharyngeal Reactivation: A Randomized Clinical Trial.

Importance: The role of herpes simplex virus (HSV) reactivation on morbidity and mortality in patients in the intensive care unit requiring mechanical ventilation remains unknown. Objective: To determine whether preemptive treatment with intravenous acyclovir reduces the duration of mechanical ventilation in patients with HSV oropharyngeal reactivation. Design, Setting, and Participants: A double-blind, placebo-controlled randomized clinical trial was conducted in 16 intensive care units in France. Participants included 239 adults (age, >18 years) who received mechanical ventilation for at least 96 hours and continued to receive mechanical ventilation for 48 hours or more, with HSV oropharyngeal reactivation. Patients were enrolled between February 2, 2014, and February 22, 2018. Interventions: Participants were randomized to receive intravenous acyclovir, 5 mg/kg, 3 times daily for 14 days or a matching placebo. Main Outcomes and Measures: The primary end point was ventilator-free days from randomization to day 60. Prespecified secondary outcomes included mortality at 60 days. Main analyses were conducted on an intention-to-treat basis. Results: Of 239 patients enrolled and randomized, 1 patient withdrew consent, leaving 238 patients, with 119 patients in both the acyclovir and placebo (control) groups (median [IQR] age, 61 [50-70] years; 76 [32%] women) available for primary outcome measurement. On day 60, the median (IQR) numbers of ventilator-free days were 35 (0-53) for acyclovir recipients and 36 (0-50]) for controls (P = .17 for between-group comparison). Among secondary outcomes, 26 patients (22%) and 39 patients (33%) had died at day 60 (risk difference, 0.11, 95% CI, -0.004 to 0.22, P = .06). The adverse event frequency was similar for both groups (28% in the acyclovir group and 23% in the placebo group, P = .40), particularly acute renal failure post randomization affecting 3 acyclovir recipients (3%) and 2 controls (2%). Four patients (3%) in the acyclovir group vs none in the placebo group stopped the study drug for treatment-related adverse events. Conclusions and Relevance: In patients receiving mechanical ventilation for 96 hours or more with HSV reactivation in the throat, use of acyclovir, 5 mg/kg, 3 times daily for 14 days, did not increase the number of ventilator-free days at day 60, compared with placebo. These findings do not appear to support routine preemptive use of acyclovir in this setting. Trial Registration: ClinicalTrials.gov identifier: NCT02152358.

Pharmacokinetics and lung delivery of PDDS-aerosolized amikacin (NKTR-061) in intubated and mechanically ventilated patients with nosocomial pneumonia.

INTRODUCTION: Aminoglycosides aerosolization might achieve better diffusion into the alveolar compartment than intravenous use. The objective of this multicenter study was to evaluate aerosol-delivered amikacin penetration into the alveolar epithelial lining fluid (ELF) using a new vibrating mesh nebulizer (Pulmonary Drug Delivery System (PDDS), Nektar Therapeutics), which delivers high doses to the lungs. METHODS: Nebulized amikacin (400 mg bid) was delivered to the lungs of 28 mechanically ventilated patients with Gram-negative VAP for 7-14 days, adjunctive to intravenous therapy. On treatment day 3, 30 minutes after completing aerosol delivery, all the patients underwent bronchoalveolar lavage in the infection-involved area and the ELF amikacin concentration was determined. The same day, urine and serum amikacin concentrations were determined at different time points. RESULTS: Median (range) ELF amikacin and maximum serum amikacin concentrations were 976.1 (135.7-16127.6) and 0.9 (0.62-1.73) microg/mL, respectively. The median total amount of amikacin excreted in urine during the first and second 12-hour collection on day 3 were 19 (12.21-28) and 21.2 (14.1-29.98) microg, respectively. During the study period, daily through amikacin measurements were below the level of nephrotoxicity. Sixty-four unexpected adverse events were reported, among which 2 were deemed possibly due to nebulized amikacin: one episode of worsening renal failure, and one episode of bronchospasm. CONCLUSIONS: PDDS delivery of aerosolized amikacin achieved very high aminoglycoside concentrations in ELF from radiography-controlled infection-involved zones, while maintaining safe serum amikacin concentrations. The ELF concentrations always exceeded the amikacin minimum inhibitory concentrations for Gram-negative microorganisms usually responsible for these pneumonias. The clinical impact of amikacin delivery with this system remains to be determined. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01021436.

Cardiac morphological and functional changes during early septic shock: a transesophageal echocardiographic study.

OBJECTIVE: The objective was to prospectively evaluate cardiac morphological and functional changes using transesophageal echocardiography (TEE) during early septic shock. DESIGN: Prospective, observational study. SETTING: Medical-surgical intensive care unit of a teaching hospital. PATIENTS AND PARTICIPANTS: Ventilated patients with septic shock, sinus rhythm and no cardiac disease underwent TEE within 12h of admission (Day0), after stabilization of hemodynamics by fluid loading (median volume: 4.9l [lower and upper quartiles: 3.7-9.6l]) and vasopressor therapy, and after vasopressors were stopped (Dayn). MEASUREMENTS AND RESULTS: Thirty-five patients were studied (median age: 60 years [range 44-68]; SAPS II: 53 [46-62]; SOFA score: 9 [8-11]) and 9 of them (26%) died while on vasopressors. None of the patients exhibited TEE findings of cardiac preload dependence. Between Day0 and Dayn (7 days [range 6-9]), mean left ventricular (LV) ejection fraction (EF) increased (47 +/- 20 vs. 57 +/- 14%: p < 0.05), whereas mean LV end-diastolic volume decreased (97 +/- 25 vs. 75 +/- 20ml: p < 0.0001). Out of 16 patients (46%) with LV systolic dysfunction on Day0, 12 had normal LVEF on Dayn and 4 patients fully recovered by Day28. Only 4 women had LV dilatation (range, LV end-diastolic volume: 110-148ml) on Day0, but none on Dayn. Doppler tissue imaging identified an LV diastolic dysfunction in 7 patients (20%) on Day0 (3 with normal LVEF), which resolved on Dayn. CONCLUSIONS: This study confirms that LV systolic and diastolic dysfunctions are frequent, but LV dilatation is uncommon in fluid-loaded septic patients on vasopressors. All abnormalities regressed in survivors, regardless of their severity. DESCRIPTORS: Shock: clinical studies (38), Cardiovascular monitoring (34).

Initial efficacy and tolerability of early enteral nutrition with immediate or gradual introduction in intubated patients.

OBJECTIVE: To compare the initial (D7) calorie intake and tolerability of two early enteral nutrition protocols in which the optimal flow rate was introduced either immediately or gradually. DESIGN: Open, prospective, randomized study. SETTING: Two medical-surgical intensive care units. PATIENTS: One hundred consecutive intubated and mechanically ventilated patients. INTERVENTIONS: Early enteral nutrition was started within 24 h following intubation, and the optimal flow rate (25 Kcal/kg day(-1)) was either introduced immediately or reached in increments. Flow rate of the nutritional solution was adapted to the residual gastric volume, measured every 8 h, and the use of prokinetic agents was encouraged. Vomiting, regurgitation, colectasia, and suspected aspiration were defined as serious adverse events requiring withdrawal of enteral nutrition. MEASUREMENTS AND RESULTS: When introduced immediately at optimal flow rate, early enteral nutrition led to a significant improvement in actual calorie supply (p < 0.0001). Although high residual gastric volume (>300 ml) was more frequent when optimal flow rate was introduced immediately (p=0.04), frequency of serious adverse events necessitating withdrawal of enteral nutrition was similar in the two groups (p=0.64). CONCLUSIONS: When residual gastric volume is measured regularly and prokinetic agents are used, enteral nutrition can be started early and be introduced at optimal dose regimen, thereby providing better calorie intake. Serious adverse events required early enteral nutrition withdrawal in only 15 patients, with no difference in frequency between the groups.

Echocardiographic assessment of pulmonary artery occlusion pressure in ventilated patients: a transoesophageal study.

BACKGROUND: Non-invasive evaluation of left ventricular filling pressure has been scarcely studied in critically ill patients. Accordingly, we prospectively assessed the ability of transoesophageal echocardiography (TEE) Doppler to predict an invasive pulmonary artery occlusion pressure (PAOP) < or = 18 mmHg in ventilated patients. METHODS: During two consecutive 3-year periods, TEE Doppler parameters were compared to right heart catheterisation derived PAOP used as reference in 88 ventilated patients, haemodynamically stable and in sinus rhythm (age: 63 +/- 14 years; simplified acute physiologic score (SAPS) II: 45 +/- 12). During the initial period (protocol A), threshold values of pulsed-wave Doppler parameters to predict an invasive PAOP < or = 18 mmHg were determined in 56 patients. Derived Doppler values were prospectively tested during the subsequent period (protocol B) in 32 patients. RESULTS: In protocol A, Doppler parameters had similar area under the receiver operating characteristic (ROC) curve. In protocol B, mitral E/A < or = 1.4, pulmonary vein S/D > 0.65 and systolic fraction > 44% best predicted an invasive PAOP < or = 18 mmHg. Lateral E/E' < or = 8.0 or E/Vp < or = 1.7 predicted a PAOP < or = 18 mmHg with a sensitivity of 83% and 80%, and a specificity of 88% and 100%, respectively. Areas under ROC curves of lateral E/E' and E/Vp were similar (0.91 +/- 0.07 vs 0.92 +/- 0.07: p = 0.53), and not significantly different from those of pulsed-wave Doppler indices. CONCLUSION: TEE accurately predicts invasive PAOP < or = 18 mmHg in ventilated patients. This further increases its diagnostic value in patients with suspected acute lung injury/acute respiratory distress syndrome.

Hemodynamic Assessment of Patients With Septic Shock Using Transpulmonary Thermodilution and Critical Care Echocardiography: A Comparative Study.

BACKGROUND: To assess the agreement between transpulmonary thermodilution (TPT) and critical care echocardiography (CCE) in ventilated patients with septic shock. METHODS: Ventilated patients in sinus rhythm requiring advanced hemodynamic assessment for septic shock were included in this prospective multicenter descriptive study. Patients were assessed successively using TPT and CCE in random order. Data were interpreted independently at bedside by two investigators who proposed therapeutic changes on the basis of predefined algorithms. TPT and CCE hemodynamic assessments were reviewed offline by two independent experts who identified potential sources of discrepant results by consensus. Lactate clearance and outcome were studied. RESULTS: A total of 137 patients were studied (71 men; age, 61 ± 15 years; Simplified Acute Physiologic Score, 58 ± 18; Sequential Organ Failure Assessment, 10 ± 3). TPT and CCE interpretations at bedside were concordant in 87/132 patients (66%) without acute cor pulmonale (ACP), resulting in a moderate agreement (kappa, 0.48; 95% CI, 0.37-0.60). Experts' adjudications were concordant in 100/129 patients without ACP (77.5%), resulting in a good intertechnique agreement (kappa, 0.66; 95% CI, 0.55-0.77). In addition to ACP (n = 8), CCE depicted a potential source of TPT inaccuracy in 8/29 patients (28%). Lactate clearance at H6 was similar irrespective of the concordance of online interpretations of TPT and CCE (55/84 [65%] vs 32/45 [71%], P = .55). ICU and day 28 mortality rates were similar between patients with concordant and discordant interpretations (29/87 [36%] vs 13/45 [29%], P = .60; and 31/87 [36%] vs 16/45 [36%], P = .99, respectively). CONCLUSIONS: Agreement between TPT and CCE was moderate when interpreted at bedside and good when adjudicated offline by experts, but without impact on lactate clearance and mortality.

Intermittent noninvasive ventilation after extubation in patients with chronic respiratory disorders: a multicenter randomized controlled trial (VHYPER).

PURPOSE: Early noninvasive ventilation (NIV) after extubation decreases the risk of respiratory failure and lowers 90-day mortality in patients with hypercapnia. Patients with chronic respiratory disease are at risk of extubation failure. Therefore, it could be useful to determine the role of NIV with a discontinuous approach, not limited to patients with hypercapnia. We assessed the efficacy of early NIV in decreasing respiratory failure after extubation in patients with chronic respiratory disorders. METHODS: A prospective randomized controlled multicenter study was conducted. We enrolled 144 mechanically ventilated patients with chronic respiratory disorders who tolerated a spontaneous breathing trial. Patients were randomly allocated after extubation to receive either NIV (NIV group, n = 72), performed with a discontinuous approach, for the first 48 h, or conventional oxygen treatment (usual care group, n = 72). The primary endpoint was decreased respiratory failure within 48 h after extubation. Analysis was by intention to treat. This trial was registered with ClinicalTrials.gov (NCT01047852). RESULTS: Respiratory failure after extubation was less frequent in the NIV group: 6 (8.5%) versus 20 (27.8%); p = 0.0016. Six patients (8.5%) in the NIV group versus 13 (18.1%) in the usual care group were reintubated; p = 0.09. Intensive care unit (ICU) mortality and 90-day mortality did not differ significantly between the two groups (p = 0.28 and p = 0.33, respectively). Median postrandomization ICU length of stay was lower in the usual care group: 3 days (IQR 2-6) versus 4 days (IQR 2-7; p = 0.008). Patients with hypercapnia during a spontaneous breathing trial were at risk of developing postextubation respiratory failure [adjusted odds ratio (95% CI) = 4.56 (1.59-14.00); p = 0.006] and being intubated [adjusted odds ratio (95% CI) = 3.60 (1.07-13.31); p = 0.04]. CONCLUSIONS: Early NIV performed following a sequential protocol for the first 48 h after extubation decreased the risk of respiratory failure in patients with chronic respiratory disorders. Reintubation and mortality did not differ between NIV and conventional oxygen therapy.