Is ß-d-glucan Relevant for the Diagnosis and Follow-Up of Intensive Care Patients with Yeast-Complicated Intra-Abdominal Infection?

The usefulness of (1,3)-ß-d-glucan (BDG) detection for the diagnosis of intra-abdominal candidiasis and treatment monitoring is unknown. A prospective, single-center study of consecutive patients admitted to an ICU with complicated intra-abdominal infection (IAI) over a 2-year period was conducted. BDG was measured in the peritoneal fluid and serum between day 1 (D1) and D10. Patients with a positive peritoneal fluid yeast culture (YP) were compared to those with a negative yeast culture (YN). The evolution of serum BDG was compared in the two groups. Seventy patients were included (sixty-five analyzed): YP group (n = 19) and YN group (n = 46). Median peritoneal BDG concentration during surgery was 2890 pg.mL-1 [IQR: 942-12,326] in the YP group vs. 1202 pg.mL-1 [IQR: 317-4223] in the YN group (p = 0.13). Initial serum BDG concentration was 130 pg.mL-1 [IQR: 55-259] in the YP group vs. 88 pg.mL-1 [IQR: 44-296] in the YN group (p = 0.78). No difference in evolution of serum BDG concentrations was observed between the groups (p = 0.18). In conclusion, neither peritoneal BDG nor serum BDG appear to be good discriminating markers for the diagnosis of yeast IAI. In addition, monitoring the evolution of serum BDG in yeast IAI did not appear to be of any diagnostic value.

Factors associated with acute mesenteric ischemia among critically ill ventilated patients with shock: a post hoc analysis of the NUTRIREA2 trial.

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.

Relationship Between Obesity and Ventilator-Associated Pneumonia: A Post Hoc Analysis of the NUTRIREA2 Trial.

BACKGROUND: Patients with obesity are at higher risk for community-acquired and nosocomial infections. However, no study has specifically evaluated the relationship between obesity and ventilator-associated pneumonia (VAP). RESEARCH QUESTION: Is obesity associated with an increased incidence of VAP? STUDY DESIGN AND METHODS: This study was a post hoc analysis of the Impact of Early Enteral vs Parenteral Nutrition on Mortality in Patients Requiring Mechanical Ventilation and Catecholamines (NUTRIREA2) open-label, randomized controlled trial performed in 44 French ICUs. Adults receiving invasive mechanical ventilation and vasopressor support for shock and parenteral nutrition or enteral nutrition were included. Obesity was defined as BMI ≥ 30 kg/m2 at ICU admission. VAP diagnosis was adjudicated by an independent blinded committee, based on all available clinical, radiologic, and microbiologic data. Only first VAP episodes were taken into account. Incidence of VAP was analyzed by using the Fine and Gray model, with extubation and death as competing risks. RESULTS: A total of 699 (30%) of the 2,325 included patients had obesity; 224 first VAP episodes were diagnosed (60 and 164 in obese and nonobese groups, respectively). The incidence of VAP at day 28 was 8.6% vs 10.1% in the two groups (hazard ratio, 0.85; 95% CI 0.63-1.14; P = .26). After adjustment on sex, McCabe score, age, antiulcer treatment, and Sequential Organ Failure Assessment at randomization, the incidence of VAP remained nonsignificant between obese and nonobese patients (hazard ratio, 0.893; 95% CI, 0.66-1.2; P = .46). Although no significant difference was found in duration of mechanical ventilation and ICU length of stay, 90-day mortality was significantly lower in obese than in nonobese patients (272 of 692 [39.3%] patients vs 718 of 1,605 [44.7%]; P = .02). In a subgroup of patients (n = 123) with available pepsin and alpha-amylase measurements, no significant difference was found in rate of abundant microaspiration of gastric contents, or oropharyngeal secretions between obese and nonobese patients. INTERPRETATION: Our results suggest that obesity has no significant impact on the incidence of VAP.

Impact of nutrition route on microaspiration in critically ill patients with shock: a planned ancillary study of the NUTRIREA-2 trial.

BACKGROUND: Microaspiration of gastric and oropharyngeal secretions is the main mechanism of entry of bacteria into the lower respiratory tract in intubated critically ill patients. The aim of this study is to determine the impact of enteral nutrition, as compared with parenteral nutrition, on abundant microaspiration of gastric contents and oropharyngeal secretions. METHODS: Planned ancillary study of the randomized controlled multicenter NUTRIREA2 trial. Patients with shock receiving invasive mechanical ventilation were randomized to receive early enteral or parenteral nutrition. All tracheal aspirates were collected during the 48 h following randomization. Abundant microaspiration of gastric contents and oropharyngeal secretions was defined as the presence of significant levels of pepsin (> 200 ng/ml) and salivary amylase (> 1685 UI/ml) in > 30% of tracheal aspirates. RESULTS: A total of 151 patients were included (78 and 73 patients in enteral and parenteral nutrition groups, respectively), and 1074 tracheal aspirates were quantitatively analyzed for pepsin and amylase. Although vomiting rate was significantly higher (31% vs 15%, p = 0.016), constipation rate was significantly lower (6% vs 21%, p = 0.010) in patients with enteral than in patients with parenteral nutrition. No significant difference was found regarding other patient characteristics. The percentage of patients with abundant microaspiration of gastric contents was significantly lower in enteral than in parenteral nutrition groups (14% vs 36%, p = 0.004; unadjusted OR 0.80 (95% CI 0.69, 0.93), adjusted OR 0.79 (0.76, 0.94)). The percentage of patients with abundant microaspiration of oropharyngeal secretions was significantly higher in enteral than in parenteral nutrition groups (74% vs 54%, p = 0.026; unadjusted OR 1.21 (95% CI 1.03, 1.44), adjusted OR 1.23 (1.01, 1.48)). No significant difference was found in percentage of patients with ventilator-associated pneumonia between enteral (8%) and parenteral (10%) nutrition groups (HR 0.78 (0.26, 2.28)). CONCLUSIONS: Our results suggest that enteral and parenteral nutrition are associated with high rates of microaspiration, although oropharyngeal microaspiration was more common with enteral nutrition and gastric microaspiration was more common with parenteral nutrition. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03411447 . Registered 18 July 2017. Retrospectively registered.

Enteral versus parenteral early nutrition in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2).

BACKGROUND: Whether the route of early feeding affects outcomes of patients with severe critical illnesses is controversial. We hypothesised that outcomes were better with early first-line enteral nutrition than with early first-line parenteral nutrition. METHODS: In this randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2 trial) done at 44 French intensive-care units (ICUs), adults (18 years or older) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned (1:1) to either parenteral nutrition or enteral nutrition, both targeting normocaloric goals (20-25 kcal/kg per day), within 24 h after intubation. Randomisation was stratified by centre using permutation blocks of variable sizes. Given that route of nutrition cannot be masked, blinding of the physicians and nurses was not feasible. Patients receiving parenteral nutrition could be switched to enteral nutrition after at least 72 h in the event of shock resolution (no vasopressor support for 24 consecutive hours and arterial lactate <2 mmol/L). The primary endpoint was mortality on day 28 after randomisation in the intention-to-treat-population. This study is registered with ClinicalTrials.gov, number NCT01802099. FINDINGS: After the second interim analysis, the independent Data Safety and Monitoring Board deemed that completing patient enrolment was unlikely to significantly change the results of the trial and recommended stopping patient recruitment. Between March 22, 2013, and June 30, 2015, 2410 patients were enrolled and randomly assigned; 1202 to the enteral group and 1208 to the parenteral group. By day 28, 443 (37%) of 1202 patients in the enteral group and 422 (35%) of 1208 patients in the parenteral group had died (absolute difference estimate 2·0%; [95% CI -1·9 to 5·8]; p=0·33). Cumulative incidence of patients with ICU-acquired infections did not differ between the enteral group (173 [14%]) and the parenteral group (194 [16%]; hazard ratio [HR] 0·89 [95% CI 0·72-1·09]; p=0·25). Compared with the parenteral group, the enteral group had higher cumulative incidences of patients with vomiting (406 [34%] vs 246 [20%]; HR 1·89 [1·62-2·20]; p<0·0001), diarrhoea (432 [36%] vs 393 [33%]; 1·20 [1·05-1·37]; p=0·009), bowel ischaemia (19 [2%] vs five [<1%]; 3·84 [1·43-10·3]; p=0·007), and acute colonic pseudo-obstruction (11 [1%] vs three [<1%]; 3·7 [1·03-13·2; p=0·04). INTERPRETATION: In critically ill adults with shock, early isocaloric enteral nutrition did not reduce mortality or the risk of secondary infections but was associated with a greater risk of digestive complications compared with early isocaloric parenteral nutrition. FUNDING: La Roche-sur-Yon Departmental Hospital and French Ministry of Health.

Does inferior vena cava respiratory variability predict fluid responsiveness in spontaneously breathing patients?

INTRODUCTION: We have almost no information concerning the value of inferior vena cava (IVC) respiratory variations in spontaneously breathing ICU patients (SBP) to predict fluid responsiveness. METHODS: SBP with clinical fluid need were included prospectively in the study. Echocardiography and Doppler ultrasound were used to record the aortic velocity-time integral (VTI), stroke volume (SV), cardiac output (CO) and IVC collapsibility index (cIVC) ((maximum diameter (IVCmax)- minimum diameter (IVCmin))/ IVCmax) at baseline, after a passive leg-raising maneuver (PLR) and after 500 ml of saline infusion. RESULTS: Fifty-nine patients (30 males and 29 females; 57 ± 18 years-old) were included in the study. Of these, 29 (49 %) were considered to be responders (≥10 % increase in CO after fluid infusion). There were no significant differences between responders and nonresponders at baseline, except for a higher aortic VTI in nonresponders (16 cm vs. 19 cm, p = 0.03). Responders had a lower baseline IVCmin than nonresponders (11 ± 5 mm vs. 14 ± 5 mm, p = 0.04) and more marked IVC variations (cIVC: 35 ± 16 vs. 27 ± 10 %, p = 0.04). Prediction of fluid-responsiveness using cIVC and IVCmax was low (area under the curve for cIVC at baseline 0.62 ± 0.07; 95 %, CI 0.49-0.74 and for IVCmax at baseline 0.62 ± 0.07; 95 % CI 0.49-0.75). In contrast, IVC respiratory variations >42 % in SBP demonstrated a high specificity (97 %) and a positive predictive value (90 %) to predict an increase in CO after fluid infusion. CONCLUSIONS: In SBP with suspected hypovolemia, vena cava size and respiratory variability do not predict fluid responsiveness. In contrast, a cIVC >42 % may predict an increase in CO after fluid infusion.

Use of aztreonam in association with cefepime for the treatment of nosocomial infections due to multidrug-resistant strains of Pseudomonas aeruginosa to ß-lactams in ICU patients: A pilot study.

OBJECTIVES: Resistance to all ß-lactams is emerging among Pseudomonas aeruginosa (PA) clinical isolates. Aztreonam and cefepime act synergistically in vitro against AmpC overproducing PA isolates. The objective of this study was to evaluate the clinical efficacy of this treatment in ICU patients infected with multidrug-resistant PA. MATERIAL AND METHODS: Retrospective study (2 years, 2 ICUs) in a tertiary university hospital. Inclusion criteria were proven infection with evidence of a bacterial strain of PA resistant to all ß-lactams and treated with the association of at least aztreonam plus cefepime. Treatment was considered effective for pneumonia using CPIS scores at the end of treatment and for other infections, using the SOFA score and signs of infection improvement at the end of treatment. Infectious episodes were classified as cure or failure. RESULTS: Thirteen patients were included (10 nosocomial pneumonia, 3 nosocomial intra-abdominal infections). The median [25th-75th percentiles] admission SAPS2 score was 54 [51-69] and the median SOFA score at the beginning of infection was 7 [4-8]. The median CPIS scores for pneumonia at the beginning and end of treatment were 9 [7-10.5] and 2 [0.75-5.5]. The duration of treatment with the combination of aztreonam plus cefepime was 14 days [9.5-16]. Nine episodes were classified as cures and 4 as failures, indicating a clinical efficacy of 69.2%. Overall mortality was 38.5%. DISCUSSION: These data suggest that the association of cefepime plus aztreonam could be an attractive alternative in the treatment of infections with multidrug-resistant PA to all ß-lactams with a clinical efficacy rate of 69%.

Enterococci increase the morbidity and mortality associated with severe intra-abdominal infections in elderly patients hospitalized in the intensive care unit.

OBJECTIVES: Enterococci may increase morbidity and mortality in elderly patients with intra-abdominal infections (IAIs) hospitalized in the intensive care unit (ICU). PATIENTS AND METHODS: A single-centre, retrospective evaluation of an ICU database (1997-2007) of elderly ICU patients (≥75 years) with a severe IAI was performed. Demographics, severity scores, underlying diseases, microbiology and outcomes were recorded. Patients with enterococci isolated in peritoneal fluid (E+ group) were compared with those lacking enterococci in peritoneal fluid (E- group). Stepwise multivariate logistic regression was used to identify independent factors associated with mortality. RESULTS: One hundred and sixty patients were included (mean ±â€ŠSD age 82 ±â€Š5 years; n = 72 in the E+ group). The E+ group was more severely ill than the E- group, with higher Simplified Acute Physiologic Score 2 (61 ±â€Š20 versus 48 ±â€Š16, P = 0.0001) and Sequential Organ Failure Assessment scores (8 ±â€Š3 versus 5 ±â€Š3, P = 0.0001), a greater postoperative infection rate (58.3% versus 34.1%, P = 0.01), a higher incidence of inappropriate empirical antimicrobial therapies (33.3% versus 19.3%, P = 0.04), a longer duration of mechanical ventilation (11.8 ±â€Š10.9 versus 7.8 ±â€Š10.2 days, P = 0.02) and greater vasopressor use (7.2 ±â€Š7.1 versus 3.3 ±â€Š4.1 days, P = 0.001). ICU mortality was higher in the E+ group than in the E- group (54.2% versus 38.6%, P = 0.05). In the multivariate analysis, E+ status was independently associated with mortality (odds ratio 2.24; 95% confidence interval 1.06-4.75; P = 0.03). CONCLUSIONS: In severely ill, elderly patients in the ICU for an IAI, the isolation of enterococci was associated with increased disease severity and morbidity and was an independent risk factor for mortality.

The passive leg-raising maneuver cannot accurately predict fluid responsiveness in patients with intra-abdominal hypertension.

OBJECTIVES: The passive leg-raising maneuver is a reversible fluid-loading procedure used to predict fluid responsiveness in mechanically ventilated patients. The aim of the present study was to determine whether intra-abdominal hypertension (which impairs venous return) reduces the ability of passive leg raising to detect fluid responsiveness in critically ill ventilated patients. DESIGN: A prospective study. SETTING: The medical and surgical intensive care unit of a university medical center. PATIENTS: Forty-one mechanically ventilated patients with a pulse pressure variation of >12%. INTERVENTIONS: Stroke volume was continuously monitored by esophageal Doppler. Intra-abdominal pressure was measured via bladder pressure. After a passive leg-raising maneuver and a return to baseline, fluid loading with 500 mL of saline was performed. Hemodynamic parameters were recorded at each step. Nonresponders to volume loading were not analyzed (10 patients). Thirty-one patients were classified into two groups according to their response to passive leg raising: responders to passive leg raising (at least a 12% increase in stroke volume) and nonresponders to passive leg raising. MEASUREMENTS AND MAIN RESULTS: Sixteen patients (52%) were responders to passive leg raising, and 15 (48%) were nonresponders to passive leg raising (i.e., false negatives). At baseline, the median intra-abdominal pressure was significantly higher in the nonresponders to passive leg raising than in the responders to passive leg raising (20 [6.5] vs. 11.5 [5.5], respectively; p < .0001). The area under the receiver-operating characteristic curve was 0.969 +/- 0.033. An intra-abdominal pressure cutoff value of 16 mm Hg discriminated between responders to passive leg raising and nonresponders to passive leg raising with a sensitivity of 100% (confidence interval, 78-100) and a specificity of 87.5% (confidence interval, 61.6-98.1). An intra-abdominal pressure of > or =16 mm Hg was the only independent predictor of nonresponse to passive leg raising in a multivariate analysis (odds ratio, 2.6 [confidence interval, 1.1-6.6]; p = .04). CONCLUSIONS: An intra-abdominal pressure of > or =16 mm Hg seems to be responsible for false negatives to passive leg raising. Hence, the intra-abdominal pressure should be measured in critically ill ventilated patients, especially before performing passive leg raising.

Assessing fluid responsiveness in critically ill patients: False-positive pulse pressure variation is detected by Doppler echocardiographic evaluation of the right ventricle.

OBJECTIVES: To determine whether peak systolic velocity of tricuspid annular motion assessed by tissue Doppler echocardiography (Sta), a right ventricular function parameter, can discriminate patients with true- and false-positive pulse pressure variation. Pulse pressure variation is used to predict fluid responsiveness in mechanically ventilated patients. However, this parameter has been reported to be falsely positive, especially in patients with right ventricular dysfunction. DESIGN: A prospective study. SETTING: Medical and surgical intensive care unit of a university hospital. PATIENTS: Thirty- five mechanically ventilated patients hospitalized for >24 hrs with a pulse pressure variation of >12%. INTERVENTIONS: Doppler echocardiography (including measurement of Sta and stroke volume) was performed before and after infusion of 500 mL of colloid solution. Patients were classified into two groups according to their response to fluid infusion: responders (at least 15% increase in stroke volume) and nonresponders. MEASUREMENTS AND MAIN RESULTS: Twenty-three patients (66%) were responders (true-positive group) and 12 (34%) were nonresponders (false-positive group). Before volume expansion, Sta was statistically lower in the nonresponder group (0.13 [0.04] vs. 0.20 [0.05], p = .0004). The area under the curve of the receiver operating characteristic curve was 0.87 (95% confidence interval, 0.74-1). In patients with pulse pressure variation of >12%, a Sta cutoff value of 0.15 m/s discriminated between responders and nonresponders with a sensitivity of 91% (80-100) and a specificity of 83% (62-100). CONCLUSIONS: A Sta value of <0.15 m/s seems to be an accurate parameter to detect false-positive pulse pressure variation. Echocardiography should therefore be performed before fluid infusion in patients with pulse pressure variation of >12%.