Driving pressure and acute respiratory distress syndrome in critically ill patients.

BACKGROUND AND OBJECTIVE: Elevated driving pressure (ΔP) may be associated with increased risk of acute respiratory distress syndrome (ARDS) in patients admitted via the emergency department and with post-operative pulmonary complications in surgical patients. This study investigated the association of higher ΔP with the onset of ARDS in a high-risk, intensive care unit (ICU) population. METHODS: This is a secondary analysis of a prospective multicentre observational study. Data for this ancillary study were obtained from intubated adult patients with at least one ARDS risk factor upon ICU admission enrolled in a previous multicentre observational study. Patients were followed up for the development of ARDS within 7 days (primary outcome). Univariate and multivariate analyses tested the association between ΔP (measured at ICU admission (baseline) or 24 h later (day 1)) and the development of ARDS. RESULTS: A total of 221 patients were included in this study, among whom 34 (15%) developed ARDS within 7 days. These patients had higher baseline ΔP than those who did not (mean ± SD: 12.5 ± 3.1 vs 9.8 ± 3.4 cm H2 O, respectively, P = 0.0001). The association between baseline ΔP and the risk of developing ARDS was robust to adjustment for baseline tidal volume, positive-end expiratory pressure, illness severity, serum lactate and sepsis, pneumonia, severe trauma and shock as primary ARDS risk factors (odds ratio: 1.20; 95% CI: 1.03-1.41; P = 0.02). The same results were found with day 1 ΔP. CONCLUSION: Among at-risk ICU patients, higher ΔP may identify those who are more likely to develop ARDS.

Deep brain stimulation in five patients with severe disorders of consciousness.

OBJECTIVE: The efficacy of deep brain stimulation in disorders of consciousness remains inconclusive. We investigated bilateral 30-Hz low-frequency stimulation designed to overdrive neuronal activity by dual pallido-thalamic targeting, using the Coma Recovery Scale Revised (CRS-R) to assess conscious behavior. METHODS: We conducted a prospective, single center, observational 11-month pilot study comprising four phases: baseline (2 months); surgery and titration (1 month); blind, random, crossover, 1.5-month ON and OFF periods; and unblinded, 5-month stimulation ON. Five adult patients were included: one unresponsive-wakefulness-syndrome male (traumatic brain injury); and four patients in a minimally conscious state, one male (traumatic brain injury) and three females (two hemorrhagic strokes and one traumatic brain injury). Primary outcome measures focused on CRS-R scores. Secondary outcome measures focused notably on baseline brain metabolism and variation in activity (stimulation ON - baseline) using normalized fluorodeoxyglucose positron emission tomography maps. Statistical analysis used random-effect models. RESULTS: The two male patients (one minimally conscious and one unresponsive wakefulness syndrome) showed improved mean CRS-R scores (stimulation ON vs. baseline), in auditory, visual and oromotor/verbal subscores, and visual subscores respectively. The metabolism of the medial cortices (low at baseline in all five patients) increased specifically in the two responders. INTERPRETATION: Our findings show there were robust but limited individual clinical benefits, mainly in visual and auditory processes. Overall modifications seem linked to the modulation of thalamo-cortico-basal and tegmental loops activating default mode network cortices. Specifically, in the two responders there was an increase in medial cortex activity related to internal awareness.

Clinical and Biological Predictors of Plasma Levels of Soluble RAGE in Critically Ill Patients: Secondary Analysis of a Prospective Multicenter Observational Study.

RATIONALE: Although soluble forms of the receptor for advanced glycation end products (RAGE) have been recently proposed as biomarkers in multiple acute or chronic diseases, few studies evaluated the influence of usual clinical and biological parameters, or of patient characteristics and comorbidities, on circulating levels of soluble RAGE in the intensive care unit (ICU) setting. OBJECTIVES: To determine, among clinical and biological parameters that are usually recorded upon ICU admission, which variables, if any, could be associated with plasma levels of soluble RAGE. METHODS: Data for this ancillary study were prospectively obtained from adult patients with at least one ARDS risk factor upon ICU admission enrolled in a large multicenter observational study. At ICU admission, plasma levels of total soluble RAGE (sRAGE) and endogenous secretory (es)RAGE were measured by duplicate ELISA and baseline patient characteristics, comorbidities, and usual clinical and biological indices were recorded. After univariate analyses, significant variables were used in multivariate, multidimensional analyses. MEASUREMENTS AND MAIN RESULTS: 294 patients were included in this ancillary study, among whom 62% were admitted for medical reasons, including septic shock (11%), coma (11%), and pneumonia (6%). Although some variables were associated with plasma levels of RAGE soluble forms in univariate analysis, multidimensional analyses showed no significant association between admission parameters and baseline plasma sRAGE or esRAGE. CONCLUSIONS: We found no obvious association between circulating levels of soluble RAGE and clinical and biological indices that are usually recorded upon ICU admission. This trial is registered with NCT02070536.

Receptor for advanced glycation end-products and ARDS prediction: a multicentre observational study.

Acute respiratory distress syndrome (ARDS) prediction remains challenging despite available clinical scores. To assess soluble receptor for advanced glycation end-products (sRAGE), a marker of lung epithelial injury, as a predictor of ARDS in a high-risk population, adult patients with at least one ARDS risk factor upon admission to participating intensive care units (ICUs) were enrolled in a multicentre, prospective study between June 2014 and January 2015. Plasma sRAGE and endogenous secretory RAGE (esRAGE) were measured at baseline (ICU admission) and 24 hours later (day one). Four AGER candidate single nucleotide polymorphisms (SNPs) were also assayed because of previous reports of functionality (rs1800625, rs1800624, rs3134940, and rs2070600). The primary outcome was ARDS development within seven days. Of 500 patients enrolled, 464 patients were analysed, and 59 developed ARDS by day seven. Higher baseline and day one plasma sRAGE, but not esRAGE, were independently associated with increased ARDS risk. AGER SNP rs2070600 (Ser/Ser) was associated with increased ARDS risk and higher plasma sRAGE in this cohort, although confirmatory studies are needed to assess the role of AGER SNPs in ARDS prediction. These findings suggest that among at-risk ICU patients, higher plasma sRAGE may identify those who are more likely to develop ARDS.

[Jugular venous and arterial concentrations of serum S100B protein in patients with severe head injury]. / Concentrations sériques jugulaire et artérielle de la protéine S100B chez les patients victimes d'un traumatisme crânien grave.

It is important for physicians in intensive care units to be able to predict the presence and severity of central nervous system injury in patients with severe head injury (SHI). The extent of S100B elevation has been found to be useful in predicting clinical outcome after brain injury. However, only two studies were realized with jugular venous blood samples. The purpose of our study is to compare the interest between jugular venous and arterial concentrations evaluation of serum S100B protein in patients with SHI. We recruited 17 patients with a SHI, admitted to the intensive care unit. Paired arterial and jugular venous samples were taken at kinetically after injury. S100B median was 0.16 µg/L in arterial and 0.25 µg/L in jugular. This arterio-jugular difference is significant. However, there was any significant arterio-jugular difference in the patients group showing an unfavourable outcome or for the earlier samples (earlier than 24h). We observed there was no significant decrease of S100B in jugular, unlike in arterial, 24h after the head injury in the patients group showing an unfavourable outcome. Determination of S100B concentration in jugular samples appears to be better than in arterial to predict clinical outcome after brain injury.

Plasma neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in adult critically ill patients: a prospective study.

PURPOSE: The aim of the study was to assess the ability of plasma neutrophil gelatinase-associated lipocalin (pNGAL) to predict acute kidney injury (AKI) in adult intensive care unit (ICU) patients. METHODS: All consecutives patients admitted to 3 ICUs were enrolled in this prospective-observational study. Plasma neutrophil gelatinase-associated lipocalin was analyzed at ICU admission. Risk, injury, failure, loss, and end-stage kidney (RIFLE) criteria were calculated at admission and for each day during the first week. Patients were classified according to whether they met the threshold for RIFLE criteria (RIFLE 0 or 1) at admission and during the first week. Four groups were identified: RIFLE (0-0), (1-1), (1-0), and (0-1). RESULTS: During this 1-month period, 88 patients were included in the study. Thirty-six patients met the criteria for RIFLE 0-0 with a mean pNGAL of 98 +/- 60 nmol/L, 22 for RIFLE 1-1 with a mean pNGAL of 516 +/- 221 nmol/L, and 20 patients had no AKI at admission but develop AKI at 48 hours (24-96 hours) (RIFLE 0-1) with a pNGAL of 342 +/- 183 nmol/L. Ten patients met the criteria for RIFLE 1-0 and had a mean pNGAL of 169 +/- 100 nmol/L. Using a cutoff of 155 nmol/L, sensitivity and specificity to predict AKI were 82% and 97%, respectively (area under the curve [AUC] = 0.92 [0.852-0.972]; P = .001). Looking at the patients without AKI at admission (n = 56) and who developed (n = 20) or did not develop (n = 36) AKI, receiver operating characteristic curve analysis was as follows: AUC = 0.956 (0.864-0.992). Sensitivity was 85% and specificity was 97%. Of the 7 patients who required renal replacement therapy, all of them had pNGAL of more than 303 nmol/L (AUC = 0.788 [0.687-0.868]). CONCLUSION: Plasma neutrophil gelatinase-associated lipocalin at ICU admission is an early biomarker of AKI in adult ICU patients. Plasma neutrophil gelatinase-associated lipocalin increased 48 hours before RIFLE criteria.

Oral probiotic and prevention of Pseudomonas aeruginosa infections: a randomized, double-blind, placebo-controlled pilot study in intensive care unit patients.

INTRODUCTION: Preventing carriage of potentially pathogenic micro-organisms from the aerodigestive tract is an infection control strategy used to reduce the occurrence of ventilator-associated pneumonia in intensive care units. However, antibiotic use in selective decontamination protocols is controversial. The purpose of this study was to investigate the effect of oral administration of a probiotic, namely Lactobacillus, on gastric and respiratory tract colonization/infection with Pseudomonas aeruginosa strains. Our hypothesis was that an indigenous flora should exhibit a protective effect against secondary colonization. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled pilot study between March 2003 and October 2004 in a 17-bed intensive care unit of a teaching hospital in Clermont-Ferrand, France. Consecutive patients with a unit stay of longer than 48 hours were included, 106 in the placebo group and 102 in the probiotic group. Through a nasogastric feeding tube, patients received either 109 colony-forming units unity forming colony of Lactobacillus casei rhamnosus or placebo twice daily, from the third day after admission to discharge. Digestive tract carriage of P. aeruginosa was monitored by cultures of gastric aspirates at admission, once a week thereafter and on discharge. In addition, bacteriological analyses of respiratory tract specimens were conducted to determine patient infectious status. RESULTS: The occurrence of P. aeruginosa respiratory colonization and/or infection was significantly delayed in the probiotic group, with a difference in median delay to acquisition of 11 days versus 50 days (P = 0.01), and a nonacquisition expectancy mean of 69 days versus 77 days (P = 0.01). The occurrence of ventilator-associated pneumonia due to P. aeruginosa in the patients receiving the probiotic was less frequent, although not significantly reduced, in patients in the probiotic group (2.9%) compared with those in the placebo group (7.5%). After multivariate Cox proportional hazards modelling, the absence of probiotic treatment increased the risk for P. aeruginosa colonization in respiratory tract (adjusted hazard ratio = 3.2, 95% confidence interval - 1.1 to 9.1). CONCLUSION: In this pilot study, oral administration of a probiotic delayed respiratory tract colonization/infection by P. aeruginosa. TRIAL REGISTRATION: The trial registration number for this study is NCT00604110.

A comparison of two depths of prolonged neuromuscular blockade induced by cisatracurium in mechanically ventilated critically ill patients.

OBJECTIVES: To compare two levels of continuous cisatracurium-induced curarization in hypoxemic, ventilated patients. DESIGN AND SETTING: An open-labeled, multicenter, prospective, randomized study. PATIENTS: Hundred two patients with a ratio between arterial oxygen tension and inspired oxygen tension (PaO(2)/FIO(2)) less than 200 despite optimization of sedation and ventilation were randomized into group 1 (n=52) with an end point of no response at orbicularis oculi to train-of-four (TOF) stimulation or group 2 (n=50) with an end point of two responses. MEASUREMENTS AND RESULTS: The PaO(2)/FIO(2) and end-inspiratory plateau airway pressure (Pplat) were evaluated at baseline (before curarization) and at regular intervals once TOF end points had been attained for up to 2 h afterwards (T2 h). A decrease of 1 cmH(2)O or more of Pplat at T2 h compared to baseline was observed in 37% and 50% of the patients in groups 1 and 2, respectively (p=0.17). Time courses of PaO(2)/FIO(2) (mmHg) and Pplat (cmH(2)O) [mean (SD)] were equivalent in both groups, with a mild increase in PaO(2)/FIO(2) [p=0.0014; from 126 (33) to 141 (55) and from 134 (40) to 152 (52), respectively, in groups 1 and 2] and decrease in Pplat [p=0.016; from 29.1 (8.9) to 28.5 (8.8) and from 27.7 (7.5) to 26.6 (7.6)]. Median total durations of curarization were 28.9 h (3.1-219.7) in group 1 and 31.4 h (1.6-650.6) in group 2. Median cisatracurium infusion rates were 5.2 microg kg(-1) min(-1) (2.1-13.7) in group 1 and 3.6 microg kg(1) min(-1) (1.0-13.5) in group 2. The median delay to recovery from paralysis was shorter in group 2 (0.75 h vs 1.25 h; p=0.0008). CONCLUSION: When a prolonged curarization is decided upon in an ICU patient, a blockade at 2/4 at TOF at orbicularis oculi has similar effects on respiratory parameters as a blockade at 0/4, allowing a decrease in total administered doses and a shortening of the recovery of muscle strength after cessation of infusion.

Ophthalmic regional anaesthesia.

PURPOSE OF REVIEW: To summarize recent knowledge concerning ophthalmic regional anaesthesia. RECENT FINDINGS: Ophthalmic regional anaesthesia has changed considerably over the past few years. Alternatives to retrobulbar anaesthesia have been proposed to reduce the number of complications without detriment to efficiency. Finally new local anaesthetics have been adopted and the indications have broadened, especially in vitroretineal surgery. SUMMARY: New developments in ophthalmic regional anaesthesia are presented in this review. Different methods, indications and side effects are described in order to facilitate the clinician's choice, without any claim to single out an ideal technique.