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.

Noninvasive Monitoring of Arterial Pressure: Finger or Lower Leg As Alternatives to the Upper Arm: A Prospective Study in Three ICUs.

OBJECTIVES: When the upper arm is inaccessible for measurements of arterial pressure (AP), the best alternative site is unknown. We performed a between-site comparison of the agreement between invasive and noninvasive readings of AP taken at the lower leg, the finger, and the upper arm. The risk associated with measurement errors and the trending ability were also assessed. DESIGN: Prospective observational study. SETTING: Three ICUs. PATIENTS: Patients having an arterial catheter and an arm circumference less than 42 cm. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three triplicates of AP measurements were collected via an arterial catheter (reference AP), a finger cuff system (ClearSight; Edward Lifesciences, Irvine, CA), and an oscillometric cuff (at the lower leg then the upper arm). Trending ability was assessed through an additional set of measurements after a cardiovascular intervention. The default bed backrest angle was respected. Failure to measure and display AP occurred in 19 patients (13%) at the finger, never at other sites. In 130 patients analyzed, the agreement between noninvasive and invasive readings was worse at the lower leg than that observed at the upper arm or the finger (for mean AP, bias ± sd of 6.0 ± 15.8 vs 3.6 ± 7.1 and 0.1 ± 7.4 mm Hg, respectively; p < 0.05), yielding a higher frequency of error-associated clinical risk (no risk for 64% vs 84% and 86% of measurements, respectively, p < 0.0001). According to the International Organization for Standardization (ISO) 81060-2:2018 standard, mean AP measurements were reliable at the upper arm and the finger, not the lower leg. In 33 patients reassessed after a cardiovascular intervention, both the concordance rate for change in mean AP and the ability to detect a therapy-induced significant change were good and similar at the three sites. CONCLUSIONS: As compared with lower leg measurements of AP, finger measurements were, when possible, a preferable alternative to upper arm ones.

Prone position versus usual care in hypoxemic COVID-19 patients in medical wards: a randomised controlled trial.

BACKGROUND: Benefit of early awake prone positioning for COVID-19 patients hospitalised in medical wards and who need oxygen therapy remains to be demonstrated. The question was considered at the time of COVID-19 pandemic to avoid overloading the intensive care units. We aimed to determine whether prone position plus usual care could reduce the rate of non-invasive ventilation (NIV) or intubation or death as compared to usual care alone. METHODS: In this multicentre randomised clinical trial, 268 patients were randomly assigned to awake prone position plus usual care (N = 135) or usual care alone (N = 132). The primary outcome was the proportion of patients who underwent NIV or intubation or died within 28 days. Main secondary outcomes included the rates of NIV, of intubation or death, within 28 days. RESULTS: Median time spent each day in the prone position within 72 h of randomisation was 90 min (IQR 30-133). The proportion of NIV or intubation or death within 28 days was 14.1% (19/135) in the prone position group and 12.9% (17/132) in the usual care group [odds ratio adjusted for stratification (aOR) 0.43; 95% confidence interval (CI) 0.14-1.35]. The probability of intubation, or intubation or death (secondary outcomes) was lower in the prone position group than in the usual care group (aOR 0.11; 95% CI 0.01-0.89 and aOR 0.09; 95% CI 0.01-0.76, respectively) in the whole study population and in the prespecified subgroup of patients with SpO2 ≥ 95% on inclusion (aOR 0.11; 95% CI 0.01-0.90, and aOR 0.09; 95% CI 0.03-0.27, respectively). CONCLUSIONS: Awake prone position plus usual care in COVID-19 patients in medical wards did not decrease the composite outcome of need for NIV or intubation or death. Trial registration ClinicalTrials.gov Identifier: NCT04363463 . Registered 27 April 2020.

Manually Controlled, Continuous Infusion of Phenylephrine or Norepinephrine for Maintenance of Blood Pressure and Cardiac Output During Spinal Anesthesia for Cesarean Delivery: A Double-Blinded Randomized Study.

BACKGROUND: To counteract the vasoplegia induced by spinal anesthesia (SA) and maintain blood pressure (BP) during cesarean delivery, phenylephrine is currently recommended, but norepinephrine might offer superior preservation of cardiac output. We aimed to compare the hemodynamic effects of phenylephrine and norepinephrine administered by manually adjusted continuous infusion during elective cesarean delivery. METHODS: In this pragmatic, parallel-group, double-blind randomized controlled trial, 124 parturients scheduled for elective cesarean delivery under SA in a tertiary maternity in France, between February 2019 and December 2020, were randomized to receive norepinephrine at a starting rate of 0.05 µg·kg -1 ·min -1 (n = 62) or phenylephrine at a starting rate of 0.5 µg·kg -1 ·min -1 (n = 62). In both groups, the vasopressor infusion rate was then manually adjusted to maintain maternal systolic BP above 90% of the baseline value. The primary outcome, the change in cardiac index (CI) measured by thoracic bioreactance from SA to umbilical cord clamping, was analyzed through repeated measures analysis of variance and post hoc t tests. Secondary outcomes included maternal BP and neonatal outcomes. RESULTS: In the norepinephrine group, cardiac index was maintained between 90% and 100% of baseline from SA to umbilical cord clamping, whereas it was maintained at significantly lower values (81%-88%) in the phenylephrine group ( P = .001). The percentage of elapsed time with a mean maternal BP <65 mm Hg and with systolic BP <80% of the baseline value was higher in the phenylephrine group: 2.9% (7.3) vs 0.5% (1.8) (absolute risk difference [ARD], -2.4%; 95% confidence interval, -4.4 to -0.5; P = .012) and 8.5% (16.6) vs 2.3% (5.2) (ARD, -6.2%; 95% confidence interval, -10.6 to -1.8; P = .006). Excluding parturients with gestational diabetes, severe neonatal hypoglycemia was more common in the phenylephrine group at 19.6% (9/46) vs 4.1% (2/49) ( P = .02). The other neonatal outcomes did not differ significantly between the groups. CONCLUSIONS: When administered by manually adjusted infusion during SA for cesarean delivery, norepinephrine was associated with a higher CI; both infusions were effective for maintaining BP.

Relying on pulse oximetry to avoid hypoxaemia and hyperoxia: A multicentre prospective cohort study in patients with circulatory failure.

PURPOSE: The purpose of this study was to assess the predictive performance of pulse oximetry (SpO2) to rule out hypoxaemia and hyperoxia in critically ill patients. METHODS: SpO2, arterial oxygenation (SaO2), and arterial partial pressure of oxygen (PaO2) were prospectively and simultaneously measured every 6 h during the first 24 h of intensive care unit admission in a multicentre cohort of critically ill patients suffering acute circulatory failure. Likelihood ratios associated with different cutoff values of SpO2 to rule out hypoxaemia (SaO2 < 90% or PaO2 < 60 mmHg) or hyperoxia (SaO2 > 95% or PaO2 > 100 mmHg) and post-test probabilities were calculated. Mean bias between SpO2 and SaO2 and agreement interval were calculated. Area under the receiver operating characteristics associated with SpO2 to predict different threshold values of SaO2 and PaO2 were calculated. RESULTS: Five hundred seventy-one patients (mean [standard deviation] Simplified Acute Physiology Score II: 58.7 [20.1]; mechanically ventilated 75.6%) with 2643 available SaO2 and PaO2 samples and corresponding 2643 SpO2 values were analysed. Mean bias between SpO2 and SaO2 was 1.1%, and its agreement interval ranged from -8.2 to +11.1%. SpO2 cutoff values of 88%, 90%, and 92% left the possibility that 8%-13% of patients had hypoxaemia. SpO2 < 95% left the possibility that 31% of patients had hyperoxia. All calculated areas under the receiver operating characteristics showed a lower limit of their 95% confidence interval below 0.85 CONCLUSION: In this cohort of patients with circulatory failure, SpO2 had poor discriminative ability to rule out hypoxaemia and hyperoxia. Overconfidence upon SpO2 monitoring may be dangerous.

The accuracy of intensive care nurses' interpretation of chest radiographs to recognise misplacement of endotracheal and nasogastric tubes after a single training session and comparison with residents' interpretation.

BACKGROUND: Misplacements of endotracheal and nasogastric tubes are frequent encounters in critically ill patients. OBJECTIVES: The purpose of this study was to assess the effectiveness of a single standardised training session on the ability of intensive care registered nurses (RNs) to recognise the misplacement of endotracheal and nasogastric tubes on bedside chest radiographs of patients in intensive care units (ICUs). METHODS: In eight French ICUs, RNs received a 110-min standardised teaching on the position of endotracheal and nasogastric tubes on chest radiographs. Their knowledge was evaluated within the subsequent weeks. For 20 chest radiographs, each with an endotracheal and nasogastric tube, RNs had to indicate whether each tube was in the proper or incorrect position. Training success was defined as >90% for the lower bound of the 95% confidence interval (95% CI) of the mean correct response rate (CRR). Residents of the participating ICUs underwent the same evaluation (without prior specific training). RESULTS: In total, 181 RNs were trained and evaluated and 110 residents were evaluated. The global mean CRR for RNs was 84.6% (95% CI: 83.3-85.9), significantly higher than for residents (81.4% [95% CI: 79.7-83.2]) (P < 0.0001). The mean CRR for RNs and residents was 95.9% (93.9-98.0) and 97.0% (94.7-99.3) for misplaced nasogastric tubes (P = 0.54), 86.8% (85.2-88.5) and 82.6% (79.4-85.7) (P = 0.07) for nasogastric tubes in the correct position, 86.6% (83.8-89.3) and 62.7% (57.9-67.5) for misplaced endotracheal tubes (P < 0.0001), and 79.1% (76.6-81.6) and 84.7% (82.1-87.2) for endotracheal tubes in the correct position (P = 0.01), respectively. CONCLUSIONS: The ability of trained RNs to detect tube misplacement did not reach the predetermined arbitrary level, indicating training success. Their mean CRR was higher than that for residents and was considered satisfactory for detecting misplaced nasogastric tubes. This finding is encouraging but insufficient to ensure patient safety. Transferring responsibility for reading radiographs to detect the misplacement of endotracheal tubes to intensive care RNs will need a more advanced or more in-depth teaching method.

Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm.

BACKGROUND: Moderate therapeutic hypothermia is currently recommended to improve neurologic outcomes in adults with persistent coma after resuscitated out-of-hospital cardiac arrest. However, the effectiveness of moderate therapeutic hypothermia in patients with nonshockable rhythms (asystole or pulseless electrical activity) is debated. METHODS: We performed an open-label, randomized, controlled trial comparing moderate therapeutic hypothermia (33°C during the first 24 hours) with targeted normothermia (37°C) in patients with coma who had been admitted to the intensive care unit (ICU) after resuscitation from cardiac arrest with nonshockable rhythm. The primary outcome was survival with a favorable neurologic outcome, assessed on day 90 after randomization with the use of the Cerebral Performance Category (CPC) scale (which ranges from 1 to 5, with higher scores indicating greater disability). We defined a favorable neurologic outcome as a CPC score of 1 or 2. Outcome assessment was blinded. Mortality and safety were also assessed. RESULTS: From January 2014 through January 2018, a total of 584 patients from 25 ICUs underwent randomization, and 581 were included in the analysis (3 patients withdrew consent). On day 90, a total of 29 of 284 patients (10.2%) in the hypothermia group were alive with a CPC score of 1 or 2, as compared with 17 of 297 (5.7%) in the normothermia group (difference, 4.5 percentage points; 95% confidence interval [CI], 0.1 to 8.9; P = 0.04). Mortality at 90 days did not differ significantly between the hypothermia group and the normothermia group (81.3% and 83.2%, respectively; difference, -1.9 percentage points; 95% CI, -8.0 to 4.3). The incidence of prespecified adverse events did not differ significantly between groups. CONCLUSIONS: Among patients with coma who had been resuscitated from cardiac arrest with nonshockable rhythm, moderate therapeutic hypothermia at 33°C for 24 hours led to a higher percentage of patients who survived with a favorable neurologic outcome at day 90 than was observed with targeted normothermia. (Funded by the French Ministry of Health and others; HYPERION ClinicalTrials.gov number, NCT01994772.).

Performance of the Cepheid Methicillin-Resistant Staphylococcus aureus/S. aureus Skin and Soft Tissue Infection PCR Assay on Respiratory Samples from Mechanically Ventilated Patients for S. aureus Screening during the Phase 2 Double-Blind SAATELLITE Study.

We investigated the performance of the Xpert methicillin-resistant Staphylococcus aureus (MRSA)/S. aureus skin and soft tissue (SSTI) quantitative PCR (qPCR) assay in SAATELLITE, a multicenter, double-blind, phase 2 study of suvratoxumab, a monoclonal antibody (MAb) targeting S. aureus alpha-toxin, for reducing the incidence of S. aureus pneumonia. The assay was used to detect methicillin-susceptible S. aureus (MSSA) and MRSA in lower respiratory tract (LRT) samples from mechanically ventilated patients. LRT culture results were compared with S. aureus protein A (spa) gene cycle threshold (CT) values. Receiver operating characteristic (ROC) and Youden index were used to determine the CT cutoff for best separation of culture-S. aureus-negative and S. aureus-positive patients. Of 720 screened subjects, 299 (41.5%) were S. aureus positive by qPCR, of whom 209 had culture data: 162 (77.5%) were S. aureus positive and 47 (22.5%) were S. aureus negative. Culture results were negatively affected by antibiotic use and cross-laboratory variability. An inverse linear correlation was observed between CT values and quantitative S. aureus culture results. A spa CT value of 29 (≈2 × 103 CFU/mL) served as the best cutoff for separation between culture-negative and culture-positive samples. The associated area under the ROC curve was 83.8% (95% confidence interval [CI], 78 to 90%). Suvratoxumab provided greater reduction in S. aureus pneumonia or death than placebo in subjects with low S. aureus load (CT ≥ 29; relative risk reduction [RRR], 50.0%; 90% CI, 2.7 to 74.4%) versus the total study population (RRR, 25.2%; 90% CI, -4.3 to 46.4%). The qPCR assay was easy to perform, sensitive, and standardized and provided better sensitivity than conventional culture for S. aureus detection. Quantitative PCR CT output correlated with suvratoxumab efficacy in reducing S. aureus pneumonia incidence or death in S. aureus-colonized, mechanically ventilated patients.

Effect of a Musical Intervention During the Implantation of a Central Venous Catheter or a Dialysis Catheter in the Intensive Care Unit: A Prospective Randomized Pilot Study.

BACKGROUND: Listening to music may reduce anxiety during medical procedures. However, the magnitude of any effect may differ with respect to patient and procedure. We evaluated the effect of a musical intervention on patient anxiety during a central venous catheter or dialysis catheter implantation in an intensive care unit. METHODS: A prospective single-center controlled open-label 2-arm randomized trial was conducted in a medical intensive care unit (ICU) from February 2018 to February 2019. Patients undergoing central venous catheterization were randomized to listening to music or not during the procedure. Patients randomized to music listened to the Music Care application via headphones. The primary outcome was the change in anxiety assessed on a 100-mm Visual Analogue Scale between the beginning and end of the catheterization procedure. Secondary outcomes included postprocedural pain. RESULTS: We included 37 patients in the musical intervention group and 35 in the standard care group. The primary reasons for intensive care unit admission were the need for a central catheter for chemotherapy for hematologic malignancy and sepsis and/or septic shock in both groups. Postprocedural anxiety and pain assessments were missing in 1 (2.7%) and 4 (11.4%) patients in the intervention and standard care groups. We found no between-group difference in change in anxiety score: median -1 (interquartile range, -3 to 0) vs 0 (-3 to 0) in the musical intervention and standard care groups (median difference, -1 [-2 to 0]) (P = .24). Postprocedural pain score did not differ between the groups: median 0 (0-2) and 0 (0-3.75) in the musical intervention and standard care groups (median difference, -0 [0-0]) (P = .40). To account for missing outcome assessments, sensitivity analyses were performed using 2 extreme scenarios, one favoring the standard care group (scenario 1) and the other favoring the intervention group (scenario 2). In either scenario, change in anxiety score did not differ between the intervention and standard care groups: -1 (-3 to 0) vs 0 (-4 to 0) (P = .88) in scenario 1 and -1 (-3 to 0) vs 0 (-2.75 to 1) (P = .07) in scenario 2. CONCLUSIONS: In this first randomized pilot study of musical intervention for central venous catheterization in awake patients in the intensive care unit, the musical intervention did not reduce patients' anxiety as compared with usual care.

Does diaphragm ultrasound improve the rapid shallow breathing index accuracy for predicting the success of weaning from mechanical ventilation?

BACKGROUND: This prospective study investigated whether taking into account diaphragmatic excursion (DE) measured by ultrasonography would improve the performance of the rapid shallow breathing index (RSBI) to predict extubation success or failure. OBJECTIVES: The aim of the study was to compare the new composite index named the rapid shallow diaphragmatic index (RSDI), and the RSBI measured during a spontaneous breathing trial regarding their ability to predict the need for re-intubation at 72 h. METHODS: One hundred mechanically ventilated patients underwent daily 30-min spontaneous breathing trials (SBTs) under pressure support ventilation of 6 cm H2O and end-expiratory pressure of 0 cm H2O until the SBT was considered successful and followed by extubation. The performances of RSBI (respiratory rate/tidal volume) and of the ratio RSBI/DE measured at 5 and 25 min of the successful SBT were compared in terms of area under the receiver operating characteristics curve (AUC), for predicting extubation success at 72 h. As secondary analysis, extubation and weaning success at 7 d were also considered. As exploratory analyses, predictive indices incorporating both clinical characteristics, the DE, and ultrasound diaphragm thickening fraction (DTF) were investigated. RESULTS: RSBI and RSBI/DE showed AUCs with 95% confidence intervals consistently extending below 0.50, either at the 5th (0.55 [0.36-0.74] and 0.55 [0.34-0.75], respectively) or at the 25th minute of SBT (0.49 [0.27-0.71] and 0.50 [0.29-0.68], respectively) for predicting weaning success at 72 h or at 7 d (5th min: 0.53 [0.37-0.70] and 0.54 [0.37-0.70], respectively; 25th min: 0.54 [0.37-0.71] and 0.55 [0.39-0.71], respectively). An exploratory index incorporating the accessory respiratory muscle activity, DE, DTF, and respiratory rate at 5th min of SBT showed AUCs for predicting extubation success at 7 d in the 78 patients with DTF measurement (0.77 [0.64-0.90]) that were significantly higher than that of the RSBI (P = 0.017) and RSBI/DE (P < 0.001) in the same respective populations. CONCLUSIONS: The RSBI and the ratio RSBI/DE failed to predict weaning success when measured during an SBT performed under minimal pressure support. Predictive indices incorporating ultrasound DE and DTF may merit further investigation.

Hydrocortisone plus Fludrocortisone for Adults with Septic Shock.

BACKGROUND: Septic shock is characterized by dysregulation of the host response to infection, with circulatory, cellular, and metabolic abnormalities. We hypothesized that therapy with hydrocortisone plus fludrocortisone or with drotrecogin alfa (activated), which can modulate the host response, would improve the clinical outcomes of patients with septic shock. METHODS: In this multicenter, double-blind, randomized trial with a 2-by-2 factorial design, we evaluated the effect of hydrocortisone-plus-fludrocortisone therapy, drotrecogin alfa (activated), the combination of the three drugs, or their respective placebos. The primary outcome was 90-day all-cause mortality. Secondary outcomes included mortality at intensive care unit (ICU) discharge and hospital discharge and at day 28 and day 180 and the number of days alive and free of vasopressors, mechanical ventilation, or organ failure. After drotrecogin alfa (activated) was withdrawn from the market, the trial continued with a two-group parallel design. The analysis compared patients who received hydrocortisone plus fludrocortisone with those who did not (placebo group). RESULTS: Among the 1241 patients included in the trial, the 90-day mortality was 43.0% (264 of 614 patients) in the hydrocortisone-plus-fludrocortisone group and 49.1% (308 of 627 patients) in the placebo group (P=0.03). The relative risk of death in the hydrocortisone-plus-fludrocortisone group was 0.88 (95% confidence interval, 0.78 to 0.99). Mortality was significantly lower in the hydrocortisone-plus-fludrocortisone group than in the placebo group at ICU discharge (35.4% vs. 41.0%, P=0.04), hospital discharge (39.0% vs. 45.3%, P=0.02), and day 180 (46.6% vs. 52.5%, P=0.04) but not at day 28 (33.7% and 38.9%, respectively; P=0.06). The number of vasopressor-free days to day 28 was significantly higher in the hydrocortisone-plus-fludrocortisone group than in the placebo group (17 vs. 15 days, P<0.001), as was the number of organ-failure-free days (14 vs. 12 days, P=0.003). The number of ventilator-free days was similar in the two groups (11 days in the hydrocortisone-plus-fludrocortisone group and 10 in the placebo group, P=0.07). The rate of serious adverse events did not differ significantly between the two groups, but hyperglycemia was more common in hydrocortisone-plus-fludrocortisone group. CONCLUSIONS: In this trial involving patients with septic shock, 90-day all-cause mortality was lower among those who received hydrocortisone plus fludrocortisone than among those who received placebo. (Funded by Programme Hospitalier de Recherche Clinique 2007 of the French Ministry of Social Affairs and Health; APROCCHSS ClinicalTrials.gov number, NCT00625209 .).

High-flow nasal oxygenation or standard oxygenation for gastrointestinal endoscopy with sedation in patients at risk of hypoxaemia: a multicentre randomised controlled trial (ODEPHI trial).

BACKGROUND: We aimed to determine whether high-flow nasal oxygen could reduce the incidence of decreased peripheral oxygen saturation (SpO2) compared with standard oxygen in patients at risk of hypoxaemia undergoing gastrointestinal endoscopy under deep sedation. METHODS: This was a multicentre, randomised controlled trial with blinded assessment of the primary outcome evaluating high-flow nasal oxygen (gas flow 70 L min-1, inspired oxygen fraction 0.50) or standard oxygen delivered via nasal cannula or face mask (6 L min-1) or nasopharyngeal tube (5 L min-1) in patients at risk of hypoxaemia (i.e. >60 yr old, or with underlying cardiac or respiratory disease, or with ASA physical status >1, or with obesity or sleep apnoea syndrome) undergoing gastrointestinal endoscopy. The primary endpoint was the incidence of SpO2 ≤92%. Secondary outcomes included prolonged or severe desaturations, need for manoeuvres to maintain free upper airways, and other adverse events. RESULTS: In 379 patients, a decrease in SpO2 ≤92% occurred in 9.4% (18/191) for the high-flow nasal oxygen group, and 33.5% (63/188) for the standard oxygen groups (adjusted absolute risk difference, -23.4% [95% confidence interval (CI), -28.9 to -16.7]; P<0.001). Prolonged desaturation (>1 min) and manoeuvres to maintain free upper airways were less frequent in the high-flow nasal oxygen group than in the standard oxygen group (7.3% vs 14.9%, P=.02, and 11.1% vs 32.4%, P<0.001). CONCLUSIONS: In patients at risk of hypoxaemia undergoing gastrointestinal endoscopy under deep sedation, use of high-flow nasal oxygen significantly reduced the incidence of peripheral oxygen desaturation. CLINICAL TRIAL REGISTRATION: NCT03829293.

Bacterial Pneumonia in Brain-Dead Patients: Clinical Features and Impact on Lung Suitability for Donation.

OBJECTIVES: To appraise the epidemiological features of bacterial pneumonia and its impact on lung suitability for donation in brain-dead patients managed with protective ventilatory settings. DESIGN: Retrospective observational study. SETTING: Six ICUs from two university-affiliated hospitals. PATIENTS: Brain-dead adult patients managed in the participating ICUs over a 4-year period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 231 included patients, 145 (62.8%) were classified as ideal or extended-criteria potential lung donors at ICU admission and the remaining 86 patients having baseline contraindication for donation. Culture-proven aspiration pneumonia and early-onset ventilator-associated pneumonia occurred in 54 patients (23.4%) and 15 patients (6.5%), respectively (overall pneumonia incidence, 29.9%). Staphylococcus aureus and Enterobacterales were the most common pathogens. Using mixed-effects Cox proportional hazard models, age (adjusted hazard ratio, 0.98; 95% CI [0.96-0.99]), anoxic brain injury (3.55 [1.2-10.5]), aspiration (2.29 [1.22-4.29]), and not receiving antimicrobial agents at day 1 (3.56 [1.94-6.53]) were identified as independent predictors of pneumonia occurrence in the whole study population. Analyses restricted to potential lung donors yielded similar results. Pneumonia was associated with a postadmission decrease in the PaO2/FIO2 ratio and lower values at brain death, in the whole study population (estimated marginal mean, 294 [264-323] vs 365 [346-385] mm Hg in uninfected patients; p = 0.0005) as in potential lung donors (299 [248-350] vs 379 [350-408] mm Hg; p = 0.04; linear mixed models). Lungs were eventually retrieved in 31 patients (34.4%) among the 90 potential lung donors with at least one other organ harvested (pneumonia prevalence in lung donors (9.7%) vs nondonors (49.2%); p = 0.0002). CONCLUSIONS: Pneumonia occurs in one-third of brain-dead patients and appears as the main reason for lung nonharvesting in those presenting as potential lung donors. The initiation of antimicrobial prophylaxis upon the first day of the ICU stay in comatose patients with severe brain injury could enlarge the pool of actual lung donors.

Impact of a qSOFA-based triage procedure on antibiotic timing in ED patients with sepsis: A prospective interventional study.

BACKGROUND: It has not been investigated whether the quick sepsis-related organ failure assessment score (qSOFA), a new bedside tool for early sepsis detection, may help accelerating antibiotic initiation in ED patients with sepsis. METHODS: In this prospective pre/post quasi-experimental single-ED study, patients admitted with a suspected bacterial infection were managed using standard triage procedures only (baseline) or in association with qSOFA (intervention, with prioritization of patients with a qSOFA ≥ 2). RESULTS: A total of 151/328 (46.0%) and 185/350 (52.8%) patients with definite bacterial infection met the criteria for sepsis in the baseline and intervention periods, respectively. The sensitivity and specificity of a qSOFA ≥ 2 for sepsis prediction were 17.3% (95% confidence interval [CI], 13.6%-21.7%) and 98.8% (95% CI, 97.0%-99.5%). Eleven (7.3%) and 28 (13.5%) patients with sepsis in the baseline and intervention periods received a first antibiotic dose within one hour following triage (primary endpoint, absolute difference 6.2%, 95% CI [-0.5%, 12.7%], P = 0.08). The proportions of patients with sepsis receiving a first antibiotic dose within three hours following triage (39.7% [50/151] versus 36.8% [68/185], absolute difference - 2.9%, 95% CI [-13.3%, 7.3%], P = 0.65), requiring ICU admission, or dying in the hospital were similar in both periods. The median ED occupation rate at triage was 104.3% (interquartile range [IQR], 80.4%-128.3%), with a median number of 157 ED visits per day (IQR, 147-169). CONCLUSIONS: A qSOFA-based triage procedure does not improve antibiotic timing and outcomes in patients with sepsis admitted to a high-volume ED. The qSOFA value at triage was poorly sensitive for early sepsis detection. Trial registration (ClinicalTrials.gov): NCT03299894.

Compared Efficacy of Four Preoxygenation Methods for Intubation in the ICU: Retrospective Analysis of McGrath Mac Videolaryngoscope Versus Macintosh Laryngoscope (MACMAN) Trial Data.

OBJECTIVES: Severe hypoxemia is the most common serious adverse event during endotracheal intubation. Preoxygenation is performed routinely as a preventive measure. The relative efficacy of the various available preoxygenation devices is unclear. Here, our objective was to assess associations between preoxygenation devices and pulse oximetry values during endotracheal intubation. DESIGN: Post hoc analysis of data from a multicenter randomized controlled superiority trial (McGrath Mac Videolaryngoscope Versus Macintosh Laryngoscope [MACMAN]) comparing videolaryngoscopy to Macintosh laryngoscopy for endotracheal intubation in critical care. SETTING: Seven French ICUs. PATIENTS: Three-hundred nineteen of the 371 critically ill adults requiring endotracheal intubation who were included in the MACMAN trial. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Minimal pulse oximetry value during endotracheal intubation was the primary endpoint. We also sought risk factors for pulse oximetry below 90%. Of 319 patients, 157 (49%) had bag-valve-mask, 71 (22%) noninvasive ventilation, 71 (22%) non-rebreathing mask, and 20 (7%) high-flow nasal oxygen for preoxygenation. Factors independently associated with minimal pulse oximetry value were the Simplified Acute Physiology Score II severity score (p = 0.03), baseline pulse oximetry (p < 0.001), baseline PaO2/FIO2 ratio (p = 0.02), and number of laryngoscopies (p = 0.001). The only independent predictors of pulse oximetry less than 90% were baseline pulse oximetry (odds ratio, 0.71; 95% CI, 0.64-0.79; p < 0.001) and preoxygenation device: with bag-valve-mask as the reference, odds ratios were 1.10 (95% CI, 0.25-4.92) with non-rebreathing mask, 0.10 (95% CI, 0.01-0.80) with noninvasive ventilation, and 5.75 (95% CI, 1.15-28.75) with high-flow nasal oxygen. CONCLUSIONS: Our data suggest that the main determinants of hypoxemia during endotracheal intubation may be related to critical illness severity and to preexisting hypoxemia. The differences across preoxygenation methods suggest that noninvasive ventilation may deserve preference in patients with marked hypoxemia before endotracheal intubation. Ongoing studies will provide further clarification about the optimal preoxygenation method for endotracheal intubation in critically ill patients.

Antibiotics with activity against intestinal anaerobes and the hazard of acquired colonization with ceftriaxone-resistant Gram-negative pathogens in ICU patients: a propensity score-based analysis.

BACKGROUND: Intestinal colonization resistance is mainly exerted by commensal anaerobes. OBJECTIVES: To assess whether exposure to non-carbapenem antibiotics with activity against intestinal anaerobes (namely, piperacillin/tazobactam, amoxicillin/clavulanate and metronidazole) may promote the acquisition of gut colonization with ceftriaxone-resistant Gram-negative bacteria (CFR-GNB) in ICU patients. PATIENTS AND METHODS: All patients with a first stay >3 days in a single surgical ICU over a 30 month period were retrospectively included. Rectal carriage of CFR-GNB (i.e. ESBL-producing Enterobacteriaceae, AmpC-hyperproducing Enterobacteriaceae, Pseudomonas aeruginosa, Stenotrophomonas maltophilia and CFR Acinetobacter baumannii) was routinely screened for at admission then weekly. The impact of anti-anaerobe antibiotics was investigated in propensity score (PS)-matched cohorts of patients exposed and not exposed to these drugs and through PS-based inverse probability of treatment weighting on the whole study cohort, treating in-ICU death or discharge as competing risks for CFR-GNB acquisition. RESULTS: Among the 352 included patients [median ICU stay 16 (9-30) days, in-ICU mortality 12.2%], 120 (34.1%) acquired one or more CFR-GNB, mostly AmpC-hyperproducing Enterobacteriaceae (17.6%) and P. aeruginosa (14.8%). Exposure to anti-anaerobe antibiotics was the main predictor of CFR-GNB acquisition in both the PS-matched cohorts [adjusted HR (aHR) 3.92, 95% CI 1.12-13.7, P = 0.03] and the whole study cohort (aHR 4.30, 95% CI 1.46-12.63, P = 0.01). Exposure to other antimicrobials-especially ceftriaxone and imipenem/meropenem-exerted no independent impact on the likelihood of CFR-GNB acquisition. CONCLUSIONS: Exposure to non-carbapenem antibiotics with activity against intestinal anaerobes may predispose to CFR-GNB acquisition in ICU patients. Restricting the use of these drugs appears to be an antibiotic stewardship opportunity.

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.

Effect of In-Bed Leg Cycling and Electrical Stimulation of the Quadriceps on Global Muscle Strength in Critically Ill Adults: A Randomized Clinical Trial.

Importance: Early in-bed cycling and electrical muscle stimulation may improve the benefits of rehabilitation in patients in the intensive care unit (ICU). Objective: To investigate whether early in-bed leg cycling plus electrical stimulation of the quadriceps muscles added to standardized early rehabilitation would result in greater muscle strength at discharge from the ICU. Design, Setting, and Participants: Single-center, randomized clinical trial enrolling critically ill adult patients at 1 ICU within an 1100-bed hospital in France. Enrollment lasted from July 2014 to June 2016 and there was a 6-month follow-up, which ended on November 24, 2016. Interventions: Patients were randomized to early in-bed leg cycling plus electrical stimulation of the quadriceps muscles added to standardized early rehabilitation (n = 159) or standardized early rehabilitation alone (usual care) (n = 155). Main Outcomes and Measures: The primary outcome was muscle strength at discharge from the ICU assessed by physiotherapists blinded to treatment group using the Medical Research Council grading system (score range, 0-60 points; a higher score reflects better muscle strength; minimal clinically important difference of 4 points). Secondary outcomes at ICU discharge included the number of ventilator-free days and ICU Mobility Scale score (range, 0-10; a higher score reflects better walking capability). Functional autonomy and health-related quality of life were assessed at 6 months. Results: Among 314 randomized patients, 312 (mean age, 66 years; women, 36%; receiving mechanical ventilation at study inclusion, 78%) completed the study and were included in the analysis. The median global Medical Research Council score at ICU discharge was 48 (interquartile range [IQR], 29 to 58) in the intervention group and 51 (IQR, 37 to 58) in the usual care group (median difference, -3.0 [95% CI, -7.0 to 2.8]; P = .28). The ICU Mobility Scale score at ICU discharge was 6 (IQR, 3 to 9) in both groups (median difference, 0 [95% CI, -1 to 2]; P = .52). The median number of ventilator-free days at day 28 was 21 (IQR, 6 to 25) in the intervention group and 22 (IQR, 10 to 25) in the usual care group (median difference, 1 [95% CI, -2 to 3]; P = .24). Clinically significant events occurred during mobilization sessions in 7 patients (4.4%) in the intervention group and in 9 patients (5.8%) in the usual care group. There were no significant between-group differences in the outcomes assessed at 6 months. Conclusions and Relevance: In this single-center randomized clinical trial involving patients admitted to the ICU, adding early in-bed leg cycling exercises and electrical stimulation of the quadriceps muscles to a standardized early rehabilitation program did not improve global muscle strength at discharge from the ICU. Trial Registration: ClinicalTrials.gov Identifier: NCT02185989.

Non-invasive blood pressure monitoring with an oscillometric brachial cuff: impact of arrhythmia.

Arrhythmia-induced beat-to-beat variability of blood pressure (BP) is deemed to hinder the reliability of non-invasive oscillometric measurements (NIBP) but few data support this belief. We assessed the impact of arrhythmia on a NIBP device never tested for this purpose. We compared, in intensive care unit patients with and without arrhythmia, the agreement between three pairs of NIBP (Infinity™ Delta monitor, Dräger medical systems) and invasive readings. For systolic, diastolic and mean BP, the mean bias between NIBP and invasive measurements was not higher, in 89 patients with arrhythmia, than that observed in 127 patients with regular rhythm (p = 0.93 for mean BP). Averaging three measurements overcame the higher within-subject variability of NIBP measurements during arrhythmia, and yielded similar agreement between the two techniques in patients with arrhythmia and with regular rhythm. The international organization for standardization criteria (mean bias < 5 and SD < 8 mmHg) were satisfied neither during arrhythmia nor during regular rhythm: for mean BP, mean bias of - 8.0 ± 6.5 and - 7.5 ± 6.1 mmHg, respectively. The detection of hypotension (systolic invasive BP < 90 mmHg or mean invasive BP < 65 mmHg) or hypertension (systolic invasive BP > 140 mmHg) by NIBP was similar during arrhythmia and regular rhythm [areas under the receiver operating characteristic curves (AUCROC) of 0.88-0.92, p > 0.13]. The detection of a 10% increase in mean invasive BP after cardiovascular intervention was also associated with similar AUCROCs between the two groups. Provided that triplicates are averaged, the agreement between NIBP measured with the tested device and invasive measurements was not worse during arrhythmia than during regular rhythm.