There is insufficient research into the use of mechanical ventilation with increased inspiratory oxygen concentration (FiO
) and fluid resuscitation with hypertonic saline solution in patients with ...septic shock. We tested whether these interventions are associated with reduced mortality.
This two-by-two factorial, multicentre, randomised, clinical trial (HYPERS2S) recruited patients aged 18 years and older with septic shock who were on mechanical ventilation from 22 centres in France. Patients were randomly assigned 1:1:1:1 to four groups by a computer generated randomisation list stratified by site and presence or absence of acute respiratory distress syndrome by use of permuted blocks of random sizes. Patients received, in an open-labelled manner, mechanical ventilation either with FiO
at 1·0 (hyperoxia) or FiO
set to target an arterial haemoglobin oxygen saturation of 88-95% (normoxia) during the first 24 h; patients also received, in a double-blind manner, either 280 mL boluses of 3·0% (hypertonic) saline or 0·9% (isotonic) saline for fluid resuscitation during the first 72 h. The primary endpoint was mortality at day 28 after randomisation in the intention-to-treat population. This study was registered with ClinicalTrials.gov, number NCT01722422.
Between Nov 3, 2012, and June 13, 2014, 442 patients were recruited and assigned to a treatment group (normoxia n=223 or hyperoxia n=219; isotonic n=224 or hypertonic n=218). The trial was stopped prematurely for safety reasons. 28 day mortality was recorded for 434 patients; 93 (43%) of 217 patients had died in the hyperoxia group versus 77 (35%) of 217 patients in the normoxia group (hazard ratio HR 1·27, 95% CI 0·94-1·72; p=0·12). 89 (42%) of 214 patients had died in the hypertonic group versus 81 (37%) of 220 patients in the isotonic group (HR 1·19, 0·88-1·61; p=0·25). We found a significant difference in the overall incidence of serious adverse events between the hyperoxia (185 85%) and normoxia groups (165 76%; p=0·02), with a clinically relevant doubling in the hyperoxia group of the number of patients with intensive care unit-acquired weakness (24 11% vs 13 6%; p=0·06) and atelectasis (26 12% vs 13 6%; p=0·04) compared with the normoxia group. We found no statistical difference for serious adverse events between the two saline groups (p=0·23).
In patients with septic shock, setting FiO
to 1·0 to induce arterial hyperoxia might increase the risk of mortality. Hypertonic (3%) saline did not improve survival.
The French Ministry of Health.
Purpose
Little is known on the incidence of discomfort during the end-of-life of intensive care unit (ICU) patients and the impact of sedation on such discomfort. The aim of this study was to assess ...the incidence of discomfort events according to levels of sedation.
Methods
Post-hoc analysis of an observational prospective multicenter study comparing immediate extubation vs. terminal weaning for end-of-life in ICU patients. Discomforts including gasps, significant bronchial obstruction or high behavioural pain scale score, were prospectively assessed by nurses from mechanical ventilation withdrawal until death. Level of sedation was assessed using the Richmond Agitation–Sedation Scale (RASS) and deep sedation was considered for a RASS − 5. Psychological disorders in family members were assessed up until 12 months after the death.
Results
Among the 450 patients included in the original study, 226 (50%) experienced discomfort after mechanical ventilation withdrawal. Patients with discomfort received lower doses of midazolam and equivalent morphine, and were less likely to have deep sedation than patients without discomfort (59% vs. 79%,
p
< 0.001). After multivariate logistic regression, extubation (as compared terminal weaning) was the only factor associated with discomfort, whereas deep sedation and administration of vasoactive drugs were two factors independently associated with no discomfort. Long-term evaluation of psychological disorders in family members of dead patients did not differ between those with discomfort and the others.
Conclusion
Discomfort was frequent during end-of-life of ICU patients and was mainly associated with extubation and less profound sedation.
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.
Post hoc analysis of a randomized clinical trial.
Twenty-three ICUs.
Patients with a respiratory rate greater than 25 breaths/min and a PaO2/FIO2 ratio less than or equal to 300 mm Hg.
Patients were treated with standard oxygen, high-flow nasal cannula oxygen, or noninvasive ventilation.
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.
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.
Purpose
To evaluate the effects of acute hypercapnia induced by positive end-expiratory pressure (PEEP) variations at constant plateau pressure (
P
plat
) in patients with severe acute respiratory ...distress syndrome (ARDS) on right ventricular (RV) function.
Methods
Prospective observational study in two academic intensive care units enrolling 11 adults with severe ARDS (PaO
2
/FiO
2
<150 mmHg at PEEP >5 cmH
2
O). We compared three ventilatory strategies, each used for 1 h, with
P
plat
at 22 (20–25) cmH
2
O: low PEEP (5.4 cmH
2
O) or high PEEP (11.0 cmH
2
O) with compensation of the tidal volume reduction by either a high respiratory rate (high PEEP/high rate) or instrumental dead space decrease (high PEEP/low rate). We assessed RV function (transesophageal echocardiography), alveolar dead space (expired CO
2
), and alveolar recruitment (pressure–volume curves).
Results
Compared to low PEEP, PaO
2
/FiO
2
ratio and alveolar recruitment were increased with high PEEP. Alveolar dead space remained unchanged. Both high-PEEP strategies induced higher PaCO
2
levels 71 (60–94) and 75 (53–84), vs. 52 (43–68) mmHg and lower pH values 7.17 (7.12–7.23) and 7.20 (7.16–7.25) vs. 7.30 (7.24–7.35), as well as RV dilatation, LV deformation and a significant decrease in cardiac index. The decrease in stroke index tended to be negatively correlated to the increase in alveolar recruitment with high PEEP.
Conclusions
Acidosis and hypercapnia induced by tidal volume reduction and increase in PEEP at constant
P
plat
were associated with impaired RV function and hemodynamics despite positive effects on oxygenation and alveolar recruitment (
ClinicalTrials.gov
#NCT00236262).
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.
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.
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).
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.).
Non-invasive ventilation has never been compared with high-flow oxygen to determine whether it reduces the risk of severe hypoxaemia during intubation. We aimed to determine if preoxygenation with ...non-invasive ventilation was more efficient than high-flow oxygen in reducing the risk of severe hypoxaemia during intubation.
The FLORALI-2 multicentre, open-label trial was done in 28 intensive care units in France. Adult patients undergoing tracheal intubation for acute hypoxaemic respiratory failure (a partial pressure of arterial oxygen PaO
to fraction of inspired oxygen FiO
ratio of ≤300 mm Hg) were randomly assigned (1:1; block size, four participants) to non-invasive ventilation or high-flow oxygen during preoxygenation, with stratification by PaO
/FiO
ratio (≤200 mm Hg vs >200 mm Hg). Key exclusion criteria were intubation for cardiac arrest, altered consciousness (defined as a Glasgow coma score of less than eight points), other contraindications to non-invasive ventilation (recent laryngeal, oesophageal, or gastric surgery, and substantial facial fractures), pulse oximetry not available, pregnant or breastfeeding women, and refusal to participate. The primary outcome was the occurrence of severe hypoxaemia (pulse oximetry <80%) during the procedure, assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02668458.
Between April 15, 2016, and Jan 8, 2017, 2079 patients were intubated in the 28 participating units, and 322 were enrolled. We excluded five patients with no recorded data, two who withdrew consent or were under legal protection, one who was not intubated, and one who had a cardiac arrest. Of the 313 patients included in the intention-to-treat analysis, 142 were assigned to non-invasive ventilation and 171 to high-flow oxygen therapy. Severe hypoxaemia occurred in 33 (23%) of 142 patients after preoxygenation with non-invasive ventilation and 47 (27%) of 171 with high-flow oxygen (absolute difference -4·2%, 95% CI -13·7 to 5·5; p=0·39). In the 242 patients with moderate-to-severe hypoxaemia (PaO
/FiO
≤200 mm Hg), severe hypoxaemia occurred less frequently after preoxygenation with non-invasive ventilation than with high-flow oxygen (28 24% of 117 patients vs 44 35% of 125; adjusted odds ratio 0·56, 0·32 to 0·99, p=0·0459). Serious adverse events did not differ between treatment groups, with the most common immediate complications being systolic arterial hypotension (70 49% patients in the non-invasive ventilation group vs 86 50% patients in the high-flow oxygen group) and chest infiltrate on x-ray (28 20% vs 33 19%), and the most common late complications being death at day 28 (53 37% vs 58 34%) and ventilator-associated pneumonia during ICU stay (31 22% vs 35 20%).
In patients with acute hypoxaemic respiratory failure, preoxygenation with non-invasive ventilation or high-flow oxygen therapy did not change the risk of severe hypoxaemia. Future research should explore the effect of preoxygenation method in patients with moderate-to-severe hypoxaemia at baseline.
French Ministry of Health.
Purpose
Acute mesenteric ischemia (AMI) is a rare, but life-threatening condition occurring among critically ill patients. Several factors have been associated with AMI, but the causal link is ...debated, most studies being retrospective. Among these factors, enteral nutrition (EN) could be associated with AMI, in particular among patients with shock. We aimed to study the factors independently associated with AMI in a post hoc analysis of the NUTRIREA-2 trial including 2410 critically ill ventilated patients with shock, randomly assigned to receive EN or parenteral nutrition (PN).
Methods
Post hoc analysis of the NUTRIREA-2 trial was conducted. Ventilated adults with shock were randomly assigned to receive EN or PN. AMI was assessed by computed tomography, endoscopy, or laparotomy. Factors associated with AMI were studied by univariate and multivariate analysis.
Results
2410 patients from 44 French intensive care units (ICUs) were included in the study: 1202 patients in the enteral group and 1208 patients in the parenteral group. The median age was 67 58–76 years, with 67% men, a SAPS II score of 59 46–74, and a medical cause for ICU admission in 92.7%. AMI was diagnosed among 24 (1%) patients, mainly by computed tomography (79%) or endoscopy (38%). The mechanism of AMI was non-occlusive mesenteric ischemia (
n
= 12), occlusive (
n
= 4), and indeterminate (
n
= 8). The median duration between inclusion in the trial and AMI diagnosis was 4 1–11 days. Patients with AMI were older, had a higher SAPS II score at ICU admission, had higher plasma lactate, creatinine, and ASAT concentrations and lower hemoglobin concentration, had more frequently EN, dobutamine, and CVVHDF at inclusion, developed more frequently bacteremia during ICU stay, and had higher 28-day and 90-day mortality rates compared with patients without AMI. By multivariate analysis, AMI was independently associated with EN, dobutamine use, SAPS II score ≥ 62 and hemoglobin concentration ≤ 10.9 g/dL.
Conclusion
Among critically ill ventilated patients with shock, EN, dobutamine use, SAPS II score ≥ 62 and hemoglobin ≤ 10.9 g/dL were independently associated with AMI. Among critically ill ventilated patients requiring vasopressors, EN should be delayed or introduced cautiously in case of low cardiac output requiring dobutamine and/or in case of multiple organ failure with high SAPS II score.
Lung transplant candidates who are highly sensitized against human leucocyte antigen present an ongoing challenge with regards to finding immunologically acceptable donors. Desensitization strategies ...aimed at reducing preformed donor-specific antibodies have a number of limitations. Imlifidase, an IgG-degrading enzyme derived from Streptococcus pyogenes, is a novel agent that has been used to convert positive crossmatches to negative in kidney transplant candidates, allowing transplantation to occur. We present the first case of imlifidase use for antibody depletion in a highly sensitized lung transplant candidate who went on to undergo a successful bilateral lung transplant.
A biofilm is found on the inner side of endotracheal tubes (ETT) in mechanically ventilated patients, but its features and role in pneumonia remain unclear.
This prospective, observational, ...monocentric study included critically ill ventilated subjects. Measurement of the ETT inner volume was first performed before extubation using the acoustic reflection method. After extubation, the biofilm was studied by means of optical and atomic force microscopy. Bacteriological analysis was then performed and compared with clinical documentation.
Twenty-four subjects were included. Duration of intubation lasted from 2 to 79 d (mean ± SD: 11 ± 15 d). The mean percentage of ETT volume loss evaluated in situ (n = 21) was 7.1% and was not linked with the duration of intubation. Analyses with atomic force microscopy (n = 6) showed a full coverage of the inner part of the tube with biofilm, even after saline rinse. Its thickness ranged from 0.8 to 5 μm. Bacteriological cultures of the biofilm (n = 22) often showed the same bacteria as in tracheal secretions, especially for pathogenic organisms. Pseudomonas aeruginosa and Candida albicans were among the most frequent microorganisms. In subjects who had experienced a successfully treated episode of ventilator-associated pneumonia (n = 5), the responsible bacteria were still present in the biofilm.
ETT biofilm is always present in intubated patients whatever the duration of intubation and appears quickly after intubation. Even after soft rinse, a small but measurable part of biofilm remains always present, and seems strongly adherent to the ETT lumen. It contains potentially pathogenic bacteria for the lung.
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