Jean-Etienne Bazin

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.

Noninvasive Ventilation and Alveolar Recruitment Maneuver Improve Respiratory Function during and after Intubation of Morbidly Obese Patients A Randomized Controlled Study

Background:Morbid obesity predisposes patients to lung collapse and hypoxemia during induction of anesthesia. The aim of this prospective study was to determine whether noninvasive positive pressure ventilation (NPPV) improves arterial oxygenation and end-expiratory lung volume (EELV) compared with conventional preoxygenation, and whether NPPV followed by early recruitment maneuver (RM) after endotracheal intubation (ETI) further improves oxygenation and respiratory function compared with NPPV alone. Methods:Sixty-six consecutive patients (body mass index, 46 ± 6 kg/m2) were randomized to receive 5 min of either conventional preoxygenation with spontaneous breathing of 100% O2 (CON), NPPV (pressure support and positive end-expiratory pressure), or NPPV followed by RM (NPPV+RM). Gas exchange was measured in awake patients, at the end of preoxygenation, immediately after ETI, and 5 min after the onset of mechanical ventilation. EELV was measured immediately after ETI and 5 min after mechanical ventilation. The primary endpoint was arterial oxygenation 5 min after the onset of mechanical ventilation. Results are presented as mean ± SD. Results:At the end of preoxygenation, Pao2 was higher in the NPPV and NPPV+RM groups (382 ± 87 mmHg and 375 ± 82 mmHg, respectively; both P < 0.001) compared with the CON group (306 ± 51 mmHg) and remained higher after ETI (225 ± 104 mmHg and 221 ± 110 mmHg, in the NPPV and NPPV+RM groups, respectively; both P < 0.01 compared with the CON group [150 ± 50 mmHg]). After the onset of mechanical ventilation, Pao2 was 93 ± 25 mmHg in the CON group, 128 ± 54 mmHg in the NPPV group (P = 0.035 vs. CON group), and 234 ± 73 mmHg in the NPPV+RM group (P < 0.0001 vs. NPPV group). After ETI, EELV was higher in the NPPV group compared with the CON group (P < 0.001). Compared with NPPV alone, RM further improved gas exchange and EELV (all P < 0.05). A significant correlation was found between Pao2 obtained 5 min after mechanical ventilation and EELV (R2 = 0.41, P < 0.001). Conclusion:NPPV improves oxygenation and EELV in morbidly obese patients compared with conventional preoxygenation. NPPV combined with early RM is more effective than NPPV alone at improving respiratory function after ETI.

Pressure support ventilation attenuates ventilator-induced protein modifications in the diaphragm

IntroductionControlled mechanical ventilation (CMV) induces profound modifications of diaphragm protein metabolism, including muscle atrophy and severe ventilator-induced diaphragmatic dysfunction. Diaphragmatic modifications could be decreased by spontaneous breathing. We hypothesized that mechanical ventilation in pressure support ventilation (PSV), which preserves diaphragm muscle activity, would limit diaphragmatic protein catabolism.MethodsForty-two adult Sprague-Dawley rats were included in this prospective randomized animal study. After intraperitoneal anesthesia, animals were randomly assigned to the control group or to receive 6 or 18 hours of CMV or PSV. After sacrifice and incubation with 14C-phenylalanine, in vitro proteolysis and protein synthesis were measured on the costal region of the diaphragm. We also measured myofibrillar protein carbonyl levels and the activity of 20S proteasome and tripeptidylpeptidase II.ResultsCompared with control animals, diaphragmatic protein catabolism was significantly increased after 18 hours of CMV (33%, P = 0.0001) but not after 6 hours. CMV also decreased protein synthesis by 50% (P = 0.0012) after 6 hours and by 65% (P < 0.0001) after 18 hours of mechanical ventilation. Both 20S proteasome activity levels were increased by CMV. Compared with CMV, 6 and 18 hours of PSV showed no significant increase in proteolysis. PSV did not significantly increase protein synthesis versus controls. Both CMV and PSV increased protein carbonyl levels after 18 hours of mechanical ventilation from +63% (P < 0.001) and +82% (P < 0.0005), respectively.ConclusionsPSV is efficient at reducing mechanical ventilation-induced proteolysis and inhibition of protein synthesis without modifications in the level of oxidative injury compared with continuous mechanical ventilation. PSV could be an interesting alternative to limit ventilator-induced diaphragmatic dysfunction.

Conservative vs restrictive individualized goal-directed fluid replacement strategy in major abdominal surgery: A prospective randomized trial.

OBJECTIVES To compare the influence of 2 volumes of fluid, integrated with goal-directed fluid therapy, on hypovolemia (a key trigger of tissue hypoperfusion) and central venous oxygen saturation (Scvo₂) and to assess their relationships with postoperative morbidity. DESIGN, SETTING, AND PATIENTS A prospective, randomized trial of 70 consecutive patients undergoing major abdominal surgery. INTERVENTIONS Patients were randomly assigned to 6 mL/kg/h of crystalloid (a restrictive fluid strategy) or 12 mL/kg/h of crystalloid (a more conservative fluid strategy). In both groups, a fluid bolus was administered when respiratory variation in peak aortic flow velocity (ΔPV) was greater than 13%. Data on hypovolemia (ΔPV > 13%), Scvo₂, and postoperative complications were recorded for all patients. MAIN OUTCOME MEASURES Overall incidence of postoperative complications, especially anastomotic leak and sepsis. RESULTS Overall incidence of complications, including postoperative anastomotic leak and sepsis, was higher in the restrictive group than in the conservative group (all P < .05). The number of patients with hypovolemia increased significantly in the restrictive group compared with the conservative group (P < .001). The perioperative mean Scvo₂ (P = .02) and mean minimum Scvo₂ (P = .04) were significantly lower in the restrictive group than in the conservative group. Multivariate analysis showed that both hypovolemia and mean minimum Scvo₂ were independently associated with anastomotic leak and sepsis. CONCLUSIONS Excessive fluid restriction increased the level of hypovolemia, leading to reduced Scvo₂ and thereby increased incidence of postoperative complications. Excessive fluid restriction should be applied cautiously in surgical patients. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00852449.

Intraoperative recruitment maneuver reverses detrimental pneumoperitoneum-induced respiratory effects in healthy weight and obese patients undergoing laparoscopy.

Background:Pulmonary function is impaired during pneumoperitoneum mainly as a result of atelectasis formation. We studied the effects of 10 cm H2O of positive end-expiratory pressure (PEEP) and PEEP followed by a recruitment maneuver (PEEP+RM) on end-expiratory lung volume (EELV), oxygenation and respiratory mechanics in patients undergoing laparoscopic surgery. Methods:Sixty consecutive adult patients (30 obese, 30 healthy weight) in reverse Trendelenburg position were prospectively studied. EELV, static elastance of the respiratory system, dead space, and gas exchange were measured before and after pneumoperitoneum insufflation with zero end-expiratory pressure, with PEEP alone, and with PEEP+RM. Results are presented as mean ± SD. Results:Pneumoperitoneum reduced EELV (healthy weight, 1195 ± 405 vs. 1724 ± 774 ml; obese, 751 ± 258 vs. 886 ± 284 ml) and worsened static elastance and dead space in both groups (in all P < 0.01 vs. zero-end expiratory pressure before pneumoperitoneum) whereas oxygenation was unaffected. PEEP increased EELV (healthy weight, 570 ml, P < 0.01; obese, 364 ml, P < 0.01) with no effect on oxygenation. Compared with PEEP alone, EELV and static elastance were further improved after RM in both groups (P < 0.05), as was oxygenation (P < 0.01). In all patients, RM-induced change in EELV was 16% (P = 0.04). These improvements were maintained 30 min after RM. RM-induced changes in EELV correlated with change in oxygenation (r = 0.42, P < 0.01). Conclusion:RM combined with 10 cm H2O of PEEP improved EELV, respiratory mechanics, and oxygenation during pneumoperitoneum whereas PEEP alone did not.

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.

Response to recruitment maneuver influences net alveolar fluid clearance in acute respiratory distress syndrome.

Background:Alveolar fluid clearance is impaired in the majority of patients with acute respiratory distress syndrome (ARDS). Experimental studies have shown that a reduction of tidal volume increases alveolar fluid clearance. This study was aimed at assessing the impact of the response to a recruitment maneuver (RM) on net alveolar fluid clearance. Methods:In 15 patients with ARDS, pulmonary edema fluid and plasma protein concentrations were measured before and after an RM, consisting of a positive end-expiratory pressure maintained 10 cm H2O above the lower inflection point of the pressure–volume curve during 15 min. Cardiorespiratory parameters were measured at baseline (before RM) and 1 and 4 h later. RM-induced lung recruitment was measured using the pressure–volume curve method. Net alveolar fluid clearance was measured by measuring changes in bronchoalveolar protein concentrations before and after RM. Results:In responders, defined as patients showing an RM-induced increase in arterial oxygen tension of 20% of baseline value or greater, net alveolar fluid clearance (19 ± 13%/h) and significant alveolar recruitment (113 ± 101 ml) were observed. In nonresponders, neither net alveolar fluid clearance (−24 ± 11%/h) nor alveolar recruitment was measured. Responders and nonresponders differed only in terms of lung morphology: Responders had a diffuse loss of aeration, whereas nonresponders had a focal loss of aeration, predominating in the lower lobes. Conclusion:In the absence of alveolar recruitment and improvement in arterial oxygenation, RM decreases the rate of alveolar fluid clearance, suggesting that lung overinflation may be associated with epithelial dysfunction.

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.

Takotsubo syndrome during induction of general anaesthesia.

Summary A 77‐year‐old female was admitted in our hospital for uterine prolapse surgery. She developed ventricular tachycardia during induction of general anaesthesia and after initial symptomatic measures, she was transferred to the coronary care unit. Heart failure persisted and electrocardiographic changes mimicking acute myocardial infarction appeared. Coronary angiography was normal and left ventriculography revealed akinesis of the apical region of the left ventricle and apical ballooning during systole, with relative sparing of the base of the heart. Complete recovery of left ventricular function occurred 8 days after the initial onset of symptoms. A diagnosis of Takotsubo syndrome was made on the basis of consistent clinical and laboratory findings, typical echocardiography and angiography findings, and reversible course. This case emphasises the importance of being aware of uncommon causes of cardiac dysfunction in stressful situations, especially during induction of general anaesthesia.

Refeeding syndrome influences outcome of anorexia nervosa patients in intensive care unit: an observational study.

IntroductionData on the epidemiology and management of anorexia nervosa (AN) in the intensive care unit (ICU) are scarce. The aim of this study was to evaluate the prevalence and associated morbidity and mortality of AN in French ICUs.MethodsWe randomly selected 30 ICUs throughout France. Thereafter, we retrospectively analyzed all patients with AN admitted to any of these 30 ICUs between May 2006 and May 2008. We considered demographic data, diagnosis at admission and complications occurring during the stay, focusing on refeeding syndrome and management of refeeding.ResultsEleven of the 30 ICUs participated in the retrospective study, featuring 68 patients, including 62 women. Average body mass index at the admission was 12 ± 3 kg/m2. Twenty one were mechanically ventilated, mainly for neurological reasons. The reported average calorie intake was 22.3 ± 13 kcal/kg/24 h. Major diagnoses at admission were metabolic problems, refeeding survey and voluntary drug intoxication and infection. The most common complications were metabolic, hematological, hepatic, and infectious events, of which 10% occurred during refeeding. Seven patients developed refeeding syndrome. At day one, the average calorie intake was higher for patients who developed refeeding syndrome (23.2 ± 5 Kcal/kg/j; n = 7) versus patients without refeeding syndrome (14.1 ± 3 Kcal/kg/j; n = 61) P = 0.02. Seven patients died, two from acute respiratory distress syndrome and five from multiorgan-failure associated with major hydroelectrolytic problems.ConclusionsThe frequency of AN in ICU patients is very low and the crude mortality in this group is about 10%. Prevention and early-detection of refeeding syndrome is the key point.