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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 12 h of admission (Day 0), after stabilization of hemodynamics by fluid loading (median volume: 4.9 l [lower and upper quartiles: 3.7–9.6 l]) and vasopressor therapy, and after vasopressors were stopped (Day  n ). 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 Day 0 and Day  n (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 ± 20 ml: p  < 0.0001). Out of 16 patients (46%) with LV systolic dysfunction on Day 0, 12 had normal LVEF on Day  n and 4 patients fully recovered by Day 28. Only 4 women had LV dilatation (range, LV end-diastolic volume: 110–148 ml) on Day 0, but none on Day n. Doppler tissue imaging identified an LV diastolic dysfunction in 7 patients (20%) on Day 0 (3 with normal LVEF), which resolved on Day  n . 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).

Chronic obstructive pulmonary disease (COPD) patients may develop metabolic alkalosis during weaning from mechanical ventilation. Acetazolamide is one of the treatments used to reverse metabolic alkalosis. 619 time-respiratory (minute ventilation, tidal volume and respiratory rate) and 207 time-PaCO2 observations were obtained from 68 invasively ventilated COPD patients. We modeled respiratory responses to acetazolamide in mechanically ventilated COPD patients and then simulated the effect of increased amounts of the drug. The effect of acetazolamide on minute ventilation and PaCO2 levels was analyzed using a nonlinear mixed effect model. The effect of different ventilatory modes was assessed on the model. Only slightly increased minute ventilation without decreased PaCO2 levels were observed in response to 250 to 500 mg of acetazolamide administered twice daily. Simulations indicated that higher acetazolamide dosage (>1000 mg daily) was required to significantly increase minute ventilation (P<.001 vs pre-acetazolamide administration). Based on our model, 1000 mg per day of acetazolamide would increase minute ventilation by >0.75 L min(-1) in 60% of the population. The model also predicts that 45% of patients would have a decrease of PaCO2>5 mmHg with doses of 1000 mg per day. Simulations suggest that COPD patients might benefit from the respiratory stimulant effect after the administration of higher doses of acetazolamide.

Background Critical care is a complex field of medicine, especially because of its diversity and unpredictability. Mortality rates of the diseases are usually high and patients are critically ill, admitted in emergency, and often have several overlapping diseases. This makes research in critical care also complex because of patients’ conditions and because of the numerous ethical and regulatory requirements and increasing global competition. Many clinical trials in critical care have thus failed and almost no drug has yet been developed to treat intensive care unit (ICU) patients. Learning from the failures, clinical trials must now be optimized. Main body Several aspects can be improved, beginning with the design of studies that should take into account patients’ diversity in the ICU. At the site level, selection should reflect more accurately the potential of recruitment. Management of all players that can be involved in the research at a site level should be a priority. Moreover, training should be offered to all staff members, including the youngest. National and international networks are also part of the future as they create a collective synergy potentially improving the efficacy of sites. Finally, computerization is another area that must be further developed with the appropriate tools. Conclusion Clinical research in the ICU is thus a discipline in its own right that still requires tailored approaches. Changes have to be initiated by the investigators themselves as they know all the specificities of the field.

Many patients with severe acute respiratory distress syndrome (ARDS) caused by influenza A(H1N1) infection receive extracorporeal membrane oxygenation (ECMO) as a rescue therapy. To analyze factors associated with death in ECMO-treated patients and the influence of ECMO on intensive care unit (ICU) mortality. 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. 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). 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.

PurposeHospital-acquired bacterial pneumonia (HABP) is a critical concern in hospitals with ventilator-associated bacterial pneumonia (VABP) remaining the most common infection in the ICU, often due to Staphylococcus aureus, an increasingly difficult to treat pathogen. Anti-infective monoclonal antibodies (mAb) may provide new, promising treatment options. This randomized, double-blinded, placebo-controlled study aimed at assessing the safety and pharmacokinetics of AR-301, an S. aureus alpha toxin-neutralizing mAb, and exploring its clinical and microbiologic outcomes when used adjunctively with standard-of-care antibiotics.MethodsEligibility in this trial required microbiologically confirmed severe S. aureus pneumonia, including HABP, VABP or CABP, treated in the ICU and an APACHE II score ≤ 30. Standard-of-care antibiotics selected by the investigators were administered to all patients in the study following clinical and microbiologic confirmation of S. aureus pneumonia. Adjunctive treatment of AR-301 was to start < 36 h after onset of severe pneumonia. AR-301 was administered to four sequentially ascending dose cohorts. The placebo cohort received antibiotics and a placebo buffer. Clinical outcomes were adjudicated by a blinded committee. S. aureus eradication was declared based on a negative follow-up culture and presumed to be negative when no culture was obtained in the presence of clinical improvement.ResultsThirteen ICUs enrolled 48 patients, with pneumonia attributable to MRSA in six subjects. The study drug displayed a favorable safety profile: Of 343 AEs reported, 8 (2.3%) were deemed related, none serious. In a post hoc subgroup analysis of VABP patients receiving AR-301, ventilation duration was shorter for AR-301-treated patients compared with the placebo group. Overall, there was a trend toward a better and faster microbiologic eradication at day 28. The PK profile of AR-301 is consistent with that of a human IgG1 mAb, with a plasma half-life of about 25 days.ConclusionsAdjunctive treatment of severe S. aureus HABP with anti-staphylococcal mAbs appears feasible and suggests some clinical benefits, but larger randomized studies are needed to better define its safety and efficacy.

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.

We report four cases of acute pulmonary edema that occurred during treatment by intravenous tocolysis using nicardipine in pregnancy patients with no previous heart problems. Clinical severity justified hospitalization in intensive care unit (ICU) each time. Acute dyspnea has begun at an average of 63 hours after initiation of treatment. For all patients, the first diagnosis suspected was pulmonary embolism. The patients' condition improved rapidly with appropriate diuretic treatment and by modifying the tocolysis. The use of intravenous nicardipine is widely used for tocolysis in France even if its prescription does not have a marketing authorization. The pathophysiological mechanisms of this complication remain unclear. The main reported risk factors are spontaneous preterm labor, multiple pregnancy, concomitant obstetrical disease, association with beta-agonists, and fetal lung maturation corticotherapy. A better knowledge of this rare but serious adverse event should improve the management of patients. Nifedipine or atosiban, the efficiency of which tocolysis was also studied, could be an alternative.

Purpose Chest ultrasonography is currently a required element to achieve competence in general critical care ultrasound (GCCUS) which should be part of the training of every intensivist. We sought to assess the ability of resident novices in ultrasonography to identify and quantify unloculated pleural effusions in ICU patients after a limited training program. Methods A total of 147 patients (mean age, 62 ± 17 years; simplified acute physiology score II, 35 ± 15; 78 % ventilated) with a suspected pleural effusion underwent a thoracic ultrasonography performed successively by a recently trained resident novice in ultrasound and by an experienced intensivist with expertise in GCCUS, considered as reference. Ultrasonographic examinations were performed randomly and independently. In the presence of a pleural effusion, the maximal interpleural distance was measured at the thoracic base. Results Residents performed a mean of 15 ± 9 examinations. Agreement between residents and experienced intensivists for the diagnosis of left- and right-sided pleural effusions was good to excellent [kappa 0.74 (95 % CI 0.63–0.85) and 0.86 (95 % CI 0.78–0.94), respectively)]. Agreement for the measurement of left and right maximal interpleural distance was excellent (intraclass concordance coefficient, 0.86 [95 % CI 0.77–0.91] and 0.85 [95 % CI 0.75–0.90], respectively). Mean bias for left and right interpleural distance was −0.3 mm (95 % CI −2.4, 1.8 mm) and −1.2 mm (95 % CI −3.4, 1.1 mm), respectively. Conclusions After a focused training program, resident novices in ultrasound identify and quantify unloculated pleural effusions in ICU patients using chest ultrasonography with a good agreement with experts.

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.

Purpose To assess the feasibility, image quality, diagnostic accuracy, therapeutic impact and tolerance of diagnostic and hemodynamic assessment using a novel miniaturized multiplane transesophageal echocardiography (TEE) probe in ventilated ICU patients with cardiopulmonary compromise. Study design Prospective, descriptive, single-center study. Methods Fifty-seven ventilated patients with acute circulatory or respiratory failure were assessed, using a miniaturized multiplane TEE probe and a standard TEE probe used as reference, randomly by two independent experienced operators. Measurements of hemodynamic parameters were independently performed off-line by a third expert. Diagnostic groups of acute circulatory failure ( n  = 5) and of acute respiratory failure ( n  = 3) were distinguished. Hemodynamic monitoring was performed in 9 patients using the miniaturized TEE probe. TEE tolerance and therapeutic impact were reported. Results The miniaturized TEE probe was easier to insert than the standard TEE probe. Despite lower imaging quality of the miniaturized TEE probe, the two probes had excellent diagnostic agreement in patients with acute circulatory failure (Kappa: 0.95; 95 % CI: 0.85–1) and with acute respiratory failure (Kappa: 1; 95 % CI: 1.0–1.0). Accordingly, therapeutic strategies derived from both TEE examinations were concordant (Kappa: 0.82; 95 % CI: 0.66–0.97). The concordance between quantitative hemodynamic parameters obtained with both TEE probes was also excellent. No relevant complication secondary to TEE probes insertion occurred. Conclusions Hemodynamic assessment of ventilated ICU patients with cardiopulmonary compromise using a miniaturized multiplane TEE probe appears feasible, well-tolerated, and relevant in terms of diagnostic information and potential therapeutic impact. Further larger-scale studies are needed to confirm these preliminary results.