Renaud Guérin

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.

Central venous O2 saturation and venous-to-arterial CO2 difference as complementary tools for goal-directed therapy during high-risk surgery

IntroductionCentral venous oxygen saturation (ScvO2) is a useful therapeutic target in septic shock and high-risk surgery. We tested the hypothesis that central venous-to-arterial carbon dioxide difference (P(cv-a)CO2), a global index of tissue perfusion, could be used as a complementary tool to ScvO2 for goal-directed fluid therapy (GDT) to identify persistent low flow after optimization of preload has been achieved by fluid loading during high-risk surgery.MethodsThis is a secondary analysis of results obtained in a study involving 70 adult patients (ASA I to III), undergoing major abdominal surgery, and treated with an individualized goal-directed fluid replacement therapy. All patients were managed to maintain a respiratory variation in peak aortic flow velocity below 13%. Cardiac index (CI), oxygen delivery index (DO2i), ScvO2, P(cv-a)CO2 and postoperative complications were recorded blindly for all patients.ResultsA total of 34% of patients developed postoperative complications. At baseline, there was no difference in demographic or haemodynamic variables between patients who developed complications and those who did not. In patients with complications, during surgery, both mean ScvO2 (78 ± 4 versus 81 ± 4%, P = 0.017) and minimal ScvO2 (minScvO2) (67 ± 6 versus 72 ± 6%, P = 0.0017) were lower than in patients without complications, despite perfusion of similar volumes of fluids and comparable CI and DO2i values. The optimal ScvO2 cut-off value was 70.6% and minScvO2 < 70% was independently associated with the development of postoperative complications (OR = 4.2 (95% CI: 1.1 to 14.4), P = 0.025). P(cv-a)CO2 was larger in patients with complications (7.8 ± 2 versus 5.6 ± 2 mmHg, P < 10-6). In patients with complications and ScvO2 ≥71%, P(cv-a)CO2 was also significantly larger (7.7 ± 2 versus 5.5 ± 2 mmHg, P < 10-6) than in patients without complications. The area under the receiver operating characteristic (ROC) curve was 0.785 (95% CI: 0.74 to 0.83) for discrimination of patients with ScvO2 ≥71% who did and did not develop complications, with 5 mmHg as the most predictive threshold value.ConclusionsScvO2 reflects important changes in O2 delivery in relation to O2 needs during the perioperative period. A P(cv-a)CO2 < 5 mmHg might serve as a complementary target to ScvO2 during GDT to identify persistent inadequacy of the circulatory response in face of metabolic requirements when an ScvO2 ≥71% is achieved.Trial registrationClinicaltrials.gov Identifier: NCT00852449.

Soluble form of the receptor for advanced glycation end products is a marker of acute lung injury but not of severe sepsis in critically ill patients

Objectives:Levels of the soluble form of the receptor for advanced glycation end products (sRAGE) are elevated during acute lung injury. However, it is not known whether this increase is linked to its involvement in alveolar epithelium injury or in systemic inflammation. Whether sRAGE is a marker of acute lung injury and acute respiratory distress syndrome, regardless of associated severe sepsis or septic shock, remains unknown in the intensive care unit setting. Design:Prospective, observational, clinical study. Setting:Intensive care unit of an academic medical center. Patients:A total of 64 consecutive subjects, divided into four groups: acute lung injury/acute respiratory distress syndrome (n = 15); acute lung injury/acute respiratory distress syndrome plus severe sepsis/septic shock (n = 18); severe sepsis/septic shock (n = 16); and mechanically ventilated controls (n = 15). Interventions:None. Measurements and Main Results:Plasma sRAGE levels were measured at baseline and on days 3, 6, and 28 (or at intensive care unit discharge, whichever occurred first). Baseline plasma levels of sRAGE were significantly higher in patients with acute lung injury/acute respiratory distress syndrome, with (median, 2951 pg/mL) or without (median, 3761 pg/mL) severe sepsis, than in patients with severe sepsis (median, 488 pg/mL) only and in mechanically ventilated controls (median, 525 pg/mL). Levels of sRAGE were correlated with acute lung injury/acute respiratory distress syndrome severity and decreased over time but were not associated with outcome. Lower baseline plasma sRAGE was associated with focal loss of aeration based on computed tomography lung morphology. Conclusions:sRAGE levels were elevated during acute lung injury/acute respiratory distress syndrome, regardless of the presence or absence of severe sepsis. The plasma level of sRAGE was correlated with clinical and radiographic severity in acute respiratory distress syndrome patients and decreased over time, suggesting resolution of the injury to the alveolar epithelium. Further study is warranted to test the clinical utility of this biomarker in managing such patients and to better understand its relationship with lung morphology during acute lung injury/acute respiratory distress syndrome.

Respiratory effects of different recruitment maneuvers in acute respiratory distress syndrome

IntroductionAlveolar derecruitment may occur during low tidal volume ventilation and may be prevented by recruitment maneuvers (RMs). The aim of this study was to compare two RMs in acute respiratory distress syndrome (ARDS) patients.MethodsNineteen patients with ARDS and protective ventilation were included in a randomized crossover study. Both RMs were applied in each patient, beginning with either continuous positive airway pressure (CPAP) with 40 cm H2O for 40 seconds or extended sigh (eSigh) consisting of a positive end-expiratory pressure maintained at 10 cm H2O above the lower inflection point of the pressure-volume curve for 15 minutes. Recruited volume, arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2), and hemodynamic parameters were recorded before (baseline) and 5 and 60 minutes after RM. All patients had a lung computed tomography (CT) scan before study inclusion.ResultsBefore RM, PaO2/FiO2 was 151 ± 61 mm Hg. Both RMs increased oxygenation, but the increase in PaO2/FiO2 was significantly higher with eSigh than CPAP at 5 minutes (73% ± 25% versus 44% ± 28%; P < 0.001) and 60 minutes (68% ± 23% versus 35% ± 22%; P < 0.001). Only eSigh significantly increased recruited volume at 5 and 60 minutes (21% ± 22% and 21% ± 25%; P = 0.0003 and P = 0.001, respectively). The only difference between responders and non-responders was CT lung morphology. Eleven patients were considered as recruiters with eSigh (10 with diffuse loss of aeration) and 6 with CPAP (5 with diffuse loss of aeration). During CPAP, 2 patients needed interruption of RM due to a drop in systolic arterial pressure.ConclusionBoth RMs effectively increase oxygenation, but CPAP failed to increase recruited volume. When the lung is recruited with an eSigh adapted for each patient, alveolar recruitment and oxygenation are superior to those observed with CPAP.

A recruitment maneuver increases oxygenation after intubation of hypoxemic intensive care unit patients: a randomized controlled study.

IntroductionTracheal intubation and anaesthesia promotes lung collapse and hypoxemia. In acute lung injury patients, recruitment maneuvers (RMs) increase lung volume and oxygenation, and decrease atelectasis. The aim of this study was to evaluate the efficacy and safety of RMs performed immediately after intubation.MethodsThis randomized controlled study was conducted in two 16-bed medical-surgical intensive care units within the same university hospital. Consecutive patients requiring intubation for acute hypoxemic respiratory failure were included. Patients were randomized to undergo a RM immediately (within 2 minutes) after intubation, consisting of a continuous positive airway pressure (CPAP) of 40 cmH2O over 30 seconds (RM group), or not (control group). Blood gases were sampled and blood samples taken for culture before, within 2 minutes, 5 minutes, and 30 minutes after intubation. Haemodynamic and respiratory parameters were continuously recorded throughout the study. Positive end expiratory pressure (PEEP) was set at 5 cmH2O throughout.ResultsThe control (n = 20) and RM (n = 20) groups were similar in terms of age, disease severity, diagnosis at time of admission, and PaO2 obtained under 10-15 L/min oxygen flow immediately before (81 ± 15 vs 83 ± 35 mmHg, P = 0.9), and within 2 minutes after, intubation under 100% FiO2 (81 ± 15 vs 83 ± 35 mmHg, P = 0.9). Five minutes after intubation, PaO2 obtained under 100% FiO2 was significantly higher in the RM group compared with the control group (93 ± 36 vs 236 ± 117 mmHg, P = 0.008). The difference remained significant at 30 minutes with 110 ± 39 and 180 ± 79 mmHg, respectively, for the control and RM groups. No significant difference in haemodynamic conditions was observed between groups at any time. Following tracheal intubation, 15 patients had positive blood cultures, showing microorganisms shared with tracheal aspirates, with no significant difference in the incidence of culture positivity between groups.ConclusionsRecruitment maneuver following intubation in hypoxemic patients improved short-term oxygenation, and was not associated with increased adverse effects.Trial registrationNCT01014299

Lemierre's syndrome and genetic polymorphisms: a case report

BackgroundLemierres syndrome presents a classic clinical picture, the pathophysiology of which remains obscure. Attempts have been made to trace genetic predispositions that modify the host detection of pathogen or the resultant systemic reaction.Case presentationA 17-year old female, with no previous medical history, was admitted to the intensive care unit for septic shock, acute respiratory distress syndrome and Lemierres syndrome. Her DNA was assayed for single nucleotide polymorphisms previously incriminated in the detection of the pathogen, the inflammatory response and the coagulation cascade. We observed functional variations in her Toll like 5 receptor (TLR 5) gene and two coagulation variations (Tissue Factor (TF) 603 and Plasminogen-Activator-Inhibitor-1 (PAI-1) 4G-4G homozygosity) associated with thrombotic events.ConclusionThe innate immune response and the prothrombogenic mutations could explain, at least in part, the symptoms of Lemierres syndrome. Genomic study of several patients with Lemierres syndrome may reveal its pathophysiology.

Soluble Forms and Ligands of the Receptor for Advanced Glycation End-Products in Patients with Acute Respiratory Distress Syndrome: An Observational Prospective Study

Background The main soluble form of the receptor for advanced glycation end-products (sRAGE) is elevated during acute respiratory distress syndrome (ARDS). However other RAGE isoforms and multiple ligands have been poorly reported in the clinical setting, and their respective contribution to RAGE activation during ARDS remains unclear. Our goal was therefore to describe main RAGE isoforms and ligands levels during ARDS. Methods 30 ARDS patients and 30 mechanically ventilated controls were prospectively included in this monocenter observational study. Arterial, superior vena cava and alveolar fluid levels of sRAGE, endogenous-secretory RAGE (esRAGE), high mobility group box-1 protein (HMGB1), S100A12 and advanced glycation end-products (AGEs) were measured in duplicate ELISA on day 0, day 3 and day 6. In patients with ARDS, baseline lung morphology was assessed with computed tomography. Results ARDS patients had higher arterial, central venous and alveolar levels of sRAGE, HMGB1 and S100A12, but lower levels of esRAGE and AGEs, than controls. Baseline arterial sRAGE, HMGB1 and S100A12 were correlated with nonfocal ARDS (AUC 0.79, 0.65 and 0.63, respectively). Baseline arterial sRAGE, esRAGE, S100A12 and AGEs were associated with severity as assessed by PaO2/FiO2. Conclusions This is the first kinetics study of levels of RAGE main isoforms and ligands during ARDS. Elevated sRAGE, HMGB1 and S100A12, with decreased esRAGE and AGEs, were found to distinguish patients with ARDS from those without. Our findings should prompt future studies aimed at elucidating RAGE/HMGB1/S100A12 axis involvement in ARDS. Trial Registration clinicaltrials.gov Identifier: NCT01270295.

Sevoflurane for Sedation in Acute Respiratory Distress Syndrome. A Randomized Controlled Pilot Study

Rationale: Sevoflurane improves gas exchange, and reduces alveolar edema and inflammation in preclinical studies of lung injury, but its therapeutic effects have never been investigated in acute respiratory distress syndrome (ARDS). Objectives: To assess whether sevoflurane would improve gas exchange and inflammation in ARDS. Methods: We did a parallel, open‐label single‐center randomized controlled trial at three intensive care units from a French university hospital between April 2014 and February 2016. Adult patients were randomized within 24 hours of moderate‐to‐severe ARDS onset to receive either intravenous midazolam or inhaled sevoflurane for 48 hours. The primary outcome was the PaO2/FiO2 ratio on Day 2. Secondary endpoints included alveolar and plasma levels of cytokines and soluble form of the receptor for advanced glycation end‐products, and safety. Investigators who did the analyses were masked to group allocation. Analysis was by intention to treat. Measurements and Main Results: Twenty‐five patients were assigned to the sevoflurane group and 25 to the midazolam group. On Day 2, PaO2/FiO2 ratio was higher in the sevoflurane group than in the midazolam group (mean ± SD, 205 ± 56 vs. 166 ± 59, respectively; P = 0.04). There was a significant reduction over time in cytokines and soluble form of the receptor for advanced glycation end‐products levels in the sevoflurane group, compared with the midazolam group, and no serious adverse event was observed with sevoflurane. Conclusions: In patients with ARDS, use of inhaled sevoflurane improved oxygenation and decreased levels of a marker of epithelial injury and of some inflammatory markers, compared with midazolam. Clinical trial registered with www.clinicaltrials.gov (NCT 02166853).

Net alveolar fluid clearance is associated with lung morphology phenotypes in acute respiratory distress syndrome

BACKGROUND The acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome that encompasses multiple phenotypes, e.g. with regards to lung morphology as assessed by computed tomography (CT). Focal or non-focal lung morphology may influence the response to positive end-expiratory pressure (PEEP), recruitment manoeuvres and prone position. Lung morphology has been hypothesized to be associated with alveolar fluid clearance (AFC), thus explaining various responses to such therapeutic interventions; however, this hypothesis has not been specifically studied in humans. METHODS We measured net AFC rates in 30 patients with ARDS as a secondary data analysis of a prospective single-centre study. Net AFC rates were compared between patients with focal ARDS and those with non-focal ARDS, as assessed by lung CT-scans. RESULTS Net AFC rates were significantly lower in patients with non-focal ARDS (n=23; median [interquartile range], 1.5 [0-5.5] %/h) as compared to those with focal ARDS (n=7; 10.3 [4.5-15] %/h) (P=0.01). The area under the receiver-operating characteristic curve when net AFC rates were used to differentiate the presence from absence of non-focal ARDS was 0.93 (95% confidence interval, 0.81-1). Tidal volumes and PEEP levels differed between focal and non-focal ARDS patients, but there was no difference in arterial oxygenation or in alveolar-capillary permeability. CONCLUSIONS Non-focal lung morphology may be characterized by a functional endotype consistent with marked AFC impairment. Despite study limitations and the need for validating studies in larger cohorts, such novel findings may reinforce our understanding of the association between ARDS phenotypes and therapeutic responses.

Epidural analgesia in the intensive care unit: An observational series of 121 patients☆

BACKGROUND Epidural analgesia (EA) has been more investigated during the perioperative period than in the intensive care unit (ICU) setting. Recent studies support beneficial effects for EA beyond analgesia itself. However, data on feasibility and safety are still lacking in the ICU. Our goal was to assess the feasibility and practice of EA in ICU patients. METHODS Multicentre observational study in 3 ICUs over a 10-month period. Goals were to report the incidence of EA-related complications and EA duration. All ICU patients receiving EA were included, whether EA was initiated in the ICU or elsewhere, e.g. in the operating room. Demographics, clinical and biological data were prospectively recorded. Epidural catheter tips were sent to the microbiology laboratory for culture. RESULTS One hundred and twenty-one patients were included (mean age 60 years), with mean SOFA and median SAPS II scores of 3.2 and 32, respectively. Reasons for EA initiation included trauma (14%), postoperative pain management after major surgery (42%), and pancreatitis (31%). No EA-related neurologic complication was recorded, and one case of epidural abscess is discussed. No other EA-related infectious complications were observed. Median duration of EA was 11 days. Reasons for EA discontinuation included efficient analgesia without EA (60%) and accidental catheter removal (17%). 22% of epidural catheter cultures were positive for skin flora bacteria. CONCLUSION EA seems feasible in the ICU. Its apparent safety should be further validated in larger cohorts, but these preliminary results may stimulate more interest in the assessment of potential benefits associated with EA in the ICU setting.