Spontaneous-Breathing Trials with Pressure-Support Ventilation or a T-Piece.

BACKGROUND: Spontaneous-breathing trials can be performed with the use of either pressure-support ventilation (PSV) or a T-piece. Whether PSV trials may result in a shorter time to tracheal extubation than T-piece trials, without resulting in a higher risk of reintubation, among patients who have a high risk of extubation failure is unknown. METHODS: In this multicenter, open-label trial, we randomly assigned patients who had a high risk of extubation failure (i.e., were >65 years of age or had an underlying chronic cardiac or respiratory disease) to undergo spontaneous-breathing trials performed with the use of either PSV (with a pressure-support level of 8 cm of water and no positive end-expiratory pressure) or a T-piece. The primary outcome was the total time without exposure to invasive ventilation (reported as the number of ventilator-free days) at day 28 after the initial spontaneous-breathing trial. Secondary outcomes included extubation within 24 hours and extubation within 7 days after the initial spontaneous-breathing trial, as well as reintubation within 7 days after extubation. RESULTS: A total of 969 patients (484 in the PSV group and 485 in the T-piece group) were included in the analysis. At day 28, the median number of ventilator-free days was 27 (interquartile range, 24 to 27) in the PSV group and 27 (interquartile range, 23 to 27) in the T-piece group (difference, 0 days; 95% confidence interval [CI], -0.5 to 1; P = 0.31). Extubation was performed within 24 hours in 376 patients (77.7%) in the PSV group and in 350 patients (72.2%) in the T-piece group (difference, 5.5 percentage points; 95% CI, 0.01 to 10.9), and extubation was performed within 7 days in 473 patients (97.7%) and 458 patients (94.4%), respectively (difference, 3.3 percentage points; 95% CI, 0.8 to 5.9). Reintubation was performed in 72 of 481 patients (14.9%) in the PSV group and in 65 of 477 patients (13.6%) in the T-piece group (difference, 1.3 percentage points; 95% CI, -3.1 to 5.8). Cardiac or respiratory arrest was a reason for reintubation in 9 patients (3 in the PSV group and 6 in the T-piece group). CONCLUSIONS: Among patients who had a high risk of extubation failure, spontaneous-breathing trials performed with PSV did not result in significantly more ventilator-free days at day 28 than spontaneous-breathing trials performed with a T-piece. (Supported by the French Ministry of Health; TIP-EX ClinicalTrials.gov number, NCT04227639.).

Dyspnea is severe and associated with a higher intubation rate in de novo acute hypoxemic respiratory failure.

BACKGROUND: Dyspnea is a key symptom of de novo acute hypoxemic respiratory failure. This study explores dyspnea and its association with intubation and mortality in this population. METHODS: This was a secondary analysis of a multicenter, randomized, controlled trial. Dyspnea was quantified by a visual analog scale (dyspnea-VAS) from zero to 100 mm. Dyspnea was measured in 259 of the 310 patients included. Factors associated with intubation were assessed with a competing risks model taking into account ICU discharge. The Cox model was used to evaluate factors associated with 90-day mortality. RESULTS: At baseline (randomization in the parent trial), median dyspnea-VAS was 46 (interquartile range, 16-65) mm and was ≥ 40 mm in 146 patients (56%). The intubation rate was 45%. Baseline variables independently associated with intubation were moderate (dyspnea-VAS 40-64 mm) and severe (dyspnea-VAS ≥ 65 mm) dyspnea at baseline (sHR 1.96 and 2.61, p = 0.023), systolic arterial pressure (sHR 2.56, p < 0.001), heart rate (sHR 1.94, p = 0.02) and PaO2/FiO2 (sHR 0.34, p = 0.028). 90-day mortality was 20%. The cumulative probability of survival was lower in patients with baseline dyspnea-VAS ≥ 40 mm (logrank test, p = 0.049). Variables independently associated with mortality were SAPS 2 ≥ 25 (p < 0.001), moderate-to-severe dyspnea at baseline (p = 0.073), PaO2/FiO2 (p = 0.118), and treatment arm (p = 0.046). CONCLUSIONS: In patients admitted to the ICU for de novo acute hypoxemic respiratory failure, dyspnea is associated with a higher risk of intubation and with a higher mortality. TRIAL REGISTRATION: clinicaltrials.gov Identifier # NCT01320384.

Volume responsiveness revisited: an observational multicenter study of continuous versus binary outcomes combining echocardiography and venous return physiology.

Echocardiography can assess cardiac preload when fluid administration is used to treat acute circulatory failure. Changes in stroke volume (SV) are inherently a continuous phenomenon relating to the pressure gradient for venous return (VRdP). However, most clinical studies have applied a binary definition based on a fractional change in SV. This study tested the hypothesis that calculating the analog mean systemic filling pressure (Pmsa) and VRdP would enhance echocardiography to describe SV responses to a preload challenge. We investigated 540 (379 males) patients during a standardized passive leg raising (PLR) maneuver. Patients were further categorized by the presence of impaired right ventricular function (impRV) or increased intra-abdominal hypertension (IAH). Multivariable linear regression identified VRdP (partial r = -0.26, P < 0.001), ventilatory-induced variations in superior vena cava diameter (partial r = 0.43, P < 0.001), and left ventricular outflow tract maximum-Doppler velocity (partial r = 0.13, P < 0.001) as independent variables associated with SV changes. The model explained 38% (P < 0.001) of the SV change in the whole cohort and 64% (P < 0.001) when excluding patients with impRV or IAH. The correlation between Pmsa or VRdP and SV changes lost statistical significance with increasing impRV or IAH. A binary definition of volume responsiveness (>10% increase in SV) generated an area under the curve of 0.79 (P < 0.001) in logistic regression but failed to identify Pmsa or VRdP as independent variables and overlooked the confounding influence of impRV and IAH. In conclusion, venous return physiology may enhance echocardiographic assessments of volume responsiveness, which should be based on continuous changes in stroke volume.NEW & NOTEWORTHY The analog mean systemic filling pressure and the pressure gradient for venous return combined with echocardiography predict continuous changes in stroke volume following a passive leg raising maneuver. The confounding effects of impaired right ventricular function and increased intra-abdominal pressure can be identified. Using a binary cutoff for the fractional change in stroke volume, common in previous clinical research, fails to identify the importance of variables relevant to venous return physiology and confounding conditions.

Effect of High-Flow Nasal Cannula Oxygen vs Standard Oxygen Therapy on Mortality in Patients With Respiratory Failure Due to COVID-19: The SOHO-COVID Randomized Clinical Trial.

Importance: The benefit of high-flow nasal cannula oxygen (high-flow oxygen) in terms of intubation and mortality in patients with respiratory failure due to COVID-19 is controversial. Objective: To determine whether the use of high-flow oxygen, compared with standard oxygen, could reduce the rate of mortality at day 28 in patients with respiratory failure due to COVID-19 admitted in intensive care units (ICUs). Design, Setting, and Participants: The SOHO-COVID randomized clinical trial was conducted in 34 ICUs in France and included 711 patients with respiratory failure due to COVID-19 and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen equal to or below 200 mm Hg. It was an ancillary trial of the ongoing original SOHO randomized clinical trial, which was designed to include patients with acute hypoxemic respiratory failure from all causes. Patients were enrolled from January to December 2021; final follow-up occurred on March 5, 2022. Interventions: Patients were randomly assigned to receive high-flow oxygen (n = 357) or standard oxygen delivered through a nonrebreathing mask initially set at a 10-L/min minimum (n = 354). Main Outcomes and Measures: The primary outcome was mortality at day 28. There were 13 secondary outcomes, including the proportion of patients requiring intubation, number of ventilator-free days at day 28, mortality at day 90, mortality and length of stay in the ICU, and adverse events. Results: Among the 782 randomized patients, 711 patients with respiratory failure due to COVID-19 were included in the analysis (mean [SD] age, 61 [12] years; 214 women [30%]). The mortality rate at day 28 was 10% (36/357) with high-flow oxygen and 11% (40/354) with standard oxygen (absolute difference, -1.2% [95% CI, -5.8% to 3.4%]; P = .60). Of 13 prespecified secondary outcomes, 12 showed no significant difference including in length of stay and mortality in the ICU and in mortality up until day 90. The intubation rate was significantly lower with high-flow oxygen than with standard oxygen (45% [160/357] vs 53% [186/354]; absolute difference, -7.7% [95% CI, -14.9% to -0.4%]; P = .04). The number of ventilator-free days at day 28 was not significantly different between groups (median, 28 [IQR, 11-28] vs 23 [IQR, 10-28] days; absolute difference, 0.5 days [95% CI, -7.7 to 9.1]; P = .07). The most common adverse events were ventilator-associated pneumonia, occurring in 58% (93/160) in the high-flow oxygen group and 53% (99/186) in the standard oxygen group. Conclusions and Relevance: Among patients with respiratory failure due to COVID-19, high-flow nasal cannula oxygen, compared with standard oxygen therapy, did not significantly reduce 28-day mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT04468126.

Right ventricular failure in septic shock: characterization, incidence and impact on fluid responsiveness.

OBJECTIVE: Incidence of right ventricular (RV) failure in septic shock patients is not well known, and tricuspid annular plane systolic excursion (TAPSE) could be of limited value. We report the incidence of RV failure in patients with septic shock, its potential impact on the response to fluids, as well as TAPSE values. DESIGN: Ancillary study of the HEMOPRED prospective multicenter study includes patients under mechanical ventilation with circulatory failure. SETTING: This is a multicenter intensive care unit study PATIENTS: Two hundred and eighty-two patients with septic shock were analyzed. Patients were classified in three groups based on central venous pressure (CVP) and RV size (RV/LV end-diastolic area, EDA). In group 1, patients had no RV dilatation (RV/LVEDA < 0.6). In group 2, patients had RV dilatation (RV/LVEDA ≥ 0.6) with a CVP < 8 mmHg (no venous congestion). RV failure was defined in group 3 by RV dilatation and a CVP ≥ 8 mmHg. Pulse pressure variation (PPV) was systematically recorded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In total, 41% of patients were in group 1, 17% in group 2 and 42% in group 3. A correlation between RV size and CVP was only observed in group 3. Higher RV size was associated with a lower response to passive leg raising for a given PPV. A large overlap of TAPSE values was observed between the 3 groups. 63.5% of patients with RV failure had a normal TAPSE. CONCLUSIONS: RV failure, defined by critical care echocardiography (RV dilatation) and a surrogate of venous congestion (CVP ≥ 8 mmHg), was frequently observed in septic shock patients and negatively associated with response to a fluid challenge despite significant PPV. TAPSE was unable to discriminate patients with or without RV failure.

Myocardial ischemia during ventilator weaning: a prospective multicenter cohort study.

BACKGROUND: Weaning-induced cardiac pulmonary edema (WiPO) is one of the main mechanisms of weaning failure during mechanical ventilation. We hypothesized that weaning-induced cardiac ischemia (WiCI) may contribute to weaning failure from cardiac origin. METHODS: A prospective cohort study of patients mechanically ventilated for at least 24 h who failed a first spontaneous breathing trial (SBT) was conducted in four intensive care units. Patients were explored during a second SBT using multiple tools (echocardiography, continuous 12-lead ST monitoring, biomarkers) to scrutinize the mechanisms of weaning failure. WiPO definition was based on three criteria (echocardiographic signs of increased left atrial pressure, increase in B-type natriuretic peptides, or increase in protein concentration during SBT) according to a conservative definition (at least two criteria) and a liberal definition (at least one criterion). WiCI was diagnosed according to the third universal definition of myocardial infarction proposed by the European Society of Cardiology (ESC) and the American Heart Association (AHA) statement for exercise testing. RESULTS: Among patients who failed a first SBT, WiPO occurred in 124/208 (59.6%) and 44/208 (21.2%) patients, according to the liberal and conservative definition, respectively. Among patients with ST monitoring, WiCI was diagnosed in 36/177 (20.3%) and 12/177 (6.8%) of them, according to the ESC and AHA definitions, respectively. WiCI was not associated with WiPO and was not associated with weaning outcomes. Only two patients of the cohort were treated for an acute coronary syndrome after the second SBT, and seven other patients required coronary angiography during the weaning period. CONCLUSIONS: This observational study showed the common occurrence of pulmonary edema in mechanically ventilated patients who failed a first SBT, but the association with cardiac ischemia and weaning outcomes was weak.

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.).

Predictors of Intubation in Patients With Acute Hypoxemic Respiratory Failure Treated With a Noninvasive Oxygenation Strategy.

OBJECTIVES: In patients with acute hypoxemic respiratory failure, noninvasive ventilation and high-flow nasal cannula oxygen are alternative strategies to conventional oxygen therapy. Endotracheal intubation is frequently needed in these patients with a risk of delay, and early predictors of failure may help clinicians to decide early. We aimed to identify factors associated with intubation in patients with acute hypoxemic respiratory failure treated with different noninvasive oxygenation techniques. DESIGN: Post hoc analysis of a randomized clinical trial. SETTING: Twenty-three ICUs. PATIENTS: Patients with a respiratory rate greater than 25 breaths/min and a PaO2/FIO2 ratio less than or equal to 300 mm Hg. INTERVENTION: Patients were treated with standard oxygen, high-flow nasal cannula oxygen, or noninvasive ventilation. MEASUREMENT AND MAIN RESULTS: Respiratory variables one hour after treatment initiation. Under standard oxygen, patients with a respiratory rate greater than or equal to 30 breaths/min were more likely to need intubation (odds ratio, 2.76; 95% CI, 1.13-6.75; p = 0.03). One hour after high-flow nasal cannula oxygen initiation, increased heart rate was the only factor associated with intubation. One hour after noninvasive ventilation initiation, a PaO2/FIO2 ratio less than or equal to 200 mm Hg and a tidal volume greater than 9 mL/kg of predicted body weight were independent predictors of intubation (adjusted odds ratio, 4.26; 95% CI, 1.62-11.16; p = 0.003 and adjusted odds ratio, 3.14; 95% CI, 1.22-8.06; p = 0.02, respectively). A tidal volume above 9 mL/kg during noninvasive ventilation remained independently associated with 90-day mortality. CONCLUSIONS: In patients with acute hypoxemic respiratory failure breathing spontaneously, the respiratory rate was a predictor of intubation under standard oxygen, but not under high-flow nasal cannula oxygen or noninvasive ventilation. A PaO2/FIO2 below 200 mm Hg and a high tidal volume greater than 9 mL/kg were the two strong predictors of intubation under noninvasive ventilation.

Comparison of Echocardiographic Indices Used to Predict Fluid Responsiveness in Ventilated Patients.

RATIONALE: Assessment of fluid responsiveness relies on dynamic echocardiographic parameters that have not yet been compared in large cohorts. OBJECTIVES: To determine the diagnostic accuracy of dynamic parameters used to predict fluid responsiveness in ventilated patients with a circulatory failure of any cause. METHODS: In this multicenter prospective study, respiratory variations of superior vena cava diameter (∆SVC) measured using transesophageal echocardiography, of inferior vena cava diameter (∆IVC) measured using transthoracic echocardiography, of the maximal Doppler velocity in left ventricular outflow tract (∆VmaxAo) measured using either approach, and pulse pressure variations (∆PP) were recorded with the patient in the semirecumbent position. In each patient, a passive leg raise was performed and an increase of aortic velocity time integral greater than or equal to 10% defined fluid responsiveness. MEASUREMENTS AND MAIN RESULTS: Among 540 patients (379 men; age, 65 ± 13 yr; Simplified Acute Physiological Score II, 59 ± 18; Sequential Organ Failure Assessment, 10 ± 3), 229 exhibited fluid responsiveness (42%). ∆PP, ∆VmaxAo, ∆SVC, and ∆IVC could be measured in 78.5%, 78.0%, 99.6%, and 78.1% of cases, respectively. ∆SVC greater than or equal to 21%, ∆VmaxAo greater than or equal to 10%, and ∆IVC greater than or equal to 8% had a sensitivity of 61% (95% confidence interval, 57-66%), 79% (75-83%), and 55% (50-59%), respectively, and a specificity of 84% (81-87%), 64% (59-69%), and 70% (66-75%), respectively. The area under the receiver operating characteristic curve of ∆SVC was significantly greater than that of ∆IVC (P = 0.02) and ∆PP (P = 0.01). CONCLUSIONS: ∆VmaxAo had the best sensitivity and ∆SVC the best specificity in predicting fluid responsiveness. ∆SVC had a greater diagnostic accuracy than ∆IVC and ∆PP, but its measurement requires transesophageal echocardiography.

PROACTIVE SCREENING ALGORITHM FOR EARLY-ONSET PNEUMONIA IN PATIENTS WITH OUT-OF-HOSPITAL CARDIAC ARREST: A BEFORE-AFTER IMPLEMENTATION STUDY.

ABSTRACT: Introduction : Early-onset pneumonia (EOP) occurs in around 50% of critically ill patients with out-of-hospital cardiac arrest (OHCA) and is associated with increased morbidity. Prompt diagnosis of EOP in these patients is difficult because of targeted temperature management and the postcardiac arrest syndrome. We hypothesized that an algorithm for proactive screening of EOP would improve patient outcomes. Methods : We conducted a single-center observational study comparing the outcomes of mechanically ventilated adult patients with OHCA, before (study period 1) and after (study period 2) implementation of an algorithm for proactive diagnosis of EOP, including an early distal pulmonary specimen. An inverse probability treatment weighted multivariable regression was performed to identify independent parameters associated with duration of mechanical ventilation. A subgroup analysis was conducted in patients alive on day 5 after intensive care unit admission. Results : Over the 4-year study period, 190 patients (99 and 91 for study periods 1 and 2, respectively) were enrolled. The overall incidence of EOP was 57.4% and was similar between both study periods. Although there was no difference in the time interval to antibiotic initiation, study period 2 was independently associated with higher SpO 2 /FiO 2 ratios on days 3 and 4. We also observed a decrease in mechanical ventilation time in study period 2 (4.5 [1-11.3] vs. 3 [2-5.8] days; P = 0.07), and this reached statistical significance in the subgroup analysis of patients alive at day 5 (10 [5-17] vs. 5 [3-9] days, P = 0.01). Conclusion: In critically ill patients with OHCA, proactive diagnosis of EOP was not associated with a significant change in the time to antibiotic initiation. Further research is warranted to better define optimal diagnosis and management of EOP in this setting.