Sylvain Lavoué

Neurologic complications and outcomes of infective endocarditis in critically ill patients: The ENDOcardite en REAnimation prospective multicenter study

Objective: To describe the clinical spectrum of infective endocarditis in critically ill patients and assess the impact of neurologic complications on outcomes. Design: Prospective multicenter observational study conducted from April 2007 to October 2008. Setting: Thirty-three intensive care units in 23 university-affiliated and 10 general French hospitals. Patients: Two hundred twenty-five patients with definite IE were studied. Factors associated with neurologic complications and predictors of 3-month mortality were identified by logistic regression analysis. Functional outcomes of patients with neurologic complications were evaluated with the modified Rankin Scale. Interventions: None. Measurements and Main Results: Among 198 patients with definite left-sided infective endocarditis, 108 (55%) experienced at least one neurologic complication. These complications were ischemic stroke (n = 79), cerebral hemorrhage (n = 53), meningitis or meningeal reaction (n = 41), brain abscess (n = 14), and mycotic aneurysm (n = 10). Factors independently associated with neurologic complications were (subhazard ratio [95% confidence interval]): Staphylococcus aureus infective endocarditis (1.45 [1.02–2.05]), mitral valve infective endocarditis (1.54 [1.07–2.21]), and nonneurologic embolic events (1.51 [1.09–2.09]). In contrast, health care-associated infective endocarditis had a protective effect (0.46 [0.27–0.77]). Multivariate analysis identified three variables associated with 3-month mortality (odds ratio [95% confidence interval]): neurologic failure, as defined as a Glasgow Coma Scale <10 (7.41 [2.89–18.96]), S. aureus infective endocarditis (3.26 [1.53–6.94]), and severe comorbidities before admission as defined as a Charlson score >2 (3.16 [1.47–6.77]). Among the 106 patients with neurologic complications assessed at follow-up (3.9 [3–8.5] months), 31 (29%) had a modified Rankin Scale score ≤3 (ability to walk without assistance), nine (9%) a modified Rankin Scale score of 4 or 5 (severe disability), and 66 (62%) a modified Rankin Scale score of 6 (death). Conclusions: Neurologic events are the most frequent complications in infective endocarditis patients requiring intensive care unit admission. They contribute to a severe prognosis, leaving less than one-third of patients alive with functional independence. Neurologic failure at intensive care unit admission represents a major determinant of mortality regardless of the underlying neurologic complication.

The sensitivity of neutrophil CD64 expression as a biomarker of bacterial infection is low in critically ill patients

PurposeCD64 expression on the surface of neutrophils has recently been proposed as an early marker of bacterial infection. The goal of this study was to determine whether the CD64 index allows differentiation of bacterial sepsis from viral and fungal sepsis and other inflammatory states in a critical-care setting.MethodsThis was an observational prospective study conducted in a medical ICU of a university hospital. All patients admitted between September 2009 and March 2010 with at least two criteria for systemic inflammatory response syndrome (SIRS) were eligible for inclusion. Upon admission, hematological exams were conducted by flow cytometry, allowing quantification of CD64 expression (Leuko64™ kit, Trillium Diagnostics LLC, USA). ROC curve analysis was performed to evaluate the utility of the CD64 index in the diagnosis of bacterial infection. Patients with suspected infection were excluded when infection could not be microbiologically confirmed.ResultsOur study included 293 patients with a SAPS II score of 45 (31–59). Bacterial infection was found in 148 patients and SIRS or non-bacterial infection was documented in 145 patients. A CD64 index greater than 2.2 predicted bacterial infection with a sensitivity and specificity of 63% (55–71%) and 89% (83–94%), respectively. The area under the ROC curve was 0.8 (0.75–0.84). Positive and negative likelihood ratios were 5.7 (5.0–6.5) and 0.4 (0.3–0.7), respectively.ConclusionsThe CD64 index is specific for bacterial infection among ICU patients. As a result of its weak sensitivity, the CD64 index may not be practically recommended, but it may be useful in combination with a more sensitive biological marker.

Constipation in long-term ventilated patients: associated factors and impact on intensive care unit outcomes.

Objectives:To characterize the factors associated with delayed defecation in long-term ventilated patients and to examine the relationship between delayed defecation and logistic organ dysfunction scores, acquired bacterial infections, and mortality in the intensive care unit. Design:Prospective observational cohort study. Setting:A 21-bed polyvalent intensive care unit in a university hospital. Patients:A total of 609 adult patients admitted over a 41-month period who underwent mechanical ventilation for ≥6 days. Interventions:None. Measurements and Main Results:Three hundred fifty-three patients (58%) passed stools ≥6 days after they were admitted to the intensive care unit (“late” defecation). Patients with early and late defecation had similar general characteristics when admitted to the intensive care unit and had similar logistic organ dysfunction scores on the first day of mechanical ventilation. Several variables were independently associated with a delay in defecation: a Pao2/Fio2 ratio of less than 150 mm Hg (adjusted hazard ratio 1.40; 95% confidence interval: 1.06–1.60; p = .0073), a systolic blood pressure between 70 and 89 mm Hg (adjusted hazard ratio 1.48; 95% confidence interval: 1.17–1.79; p = .002), and systolic blood pressure <68 mm Hg (adjusted hazard ratio 1.29; 95% confidence interval: 1.01–1.60; p = .03). Logistic organ dysfunction scores were significantly higher on the fourth and ninth days of mechanical ventilation in patients with late defecation than in those with early defecation. The crude intensive care unit mortality rate was 18% in patients with early defecation and 30% in patients with late defecation (p < .001). Acquired bacterial infections at any site occurred in 34% of patients with early defecation and 66% of patients with late defecation (p < .001). Conclusion:A Pao2/Fio2 ratio of <150 mm Hg and systolic blood pressure of <90 mm Hg during the first 5 days of mechanical ventilation were independently associated with a delay in defecation. Our results suggest that constipation is associated with adverse outcomes in long-term ventilated patients.

Long-term outcome of patients hospitalized in intensive care units with central or extrapontine myelinolysis*

Objective:Very few data are available for critically ill patients with central or extrapontine myelinolysis and according to available evidence, the prognosis seems to be poor. We aimed to describe the baseline characteristics, the management, the long-term prognosis, and the prognostic factors in central or extrapontine myelinolysis. Design:Retrospective observational study considering modified Rankin Scale score >3 or death as an unfavorable outcome. Setting:Forty-six French intensive care units. Patients:Thirty-six patients with central or extrapontine myelinolysis treated in 2000–2010. Interventions:None. Measurements and Main Results:At baseline, 31 (86%) patients were alcoholics and 33 (92%) presented with hyponatremia. Mechanical ventilation was required in 32 (89%) patients. At 1-yr follow-up, 11 (31%) patients have died, whereas 14 (56%) survivors have returned to a Rankin score ⩽1. Life-supporting therapies were withheld in 11 (31%) patients. Severe cerebral motor disability was the most frequently cited reason. However, five of them were still alive at 1 yr with Rankin score ⩽1 for four of them. We found no statistical difference between the 18 (50%) patients with a favorable outcome and the 18 (50%) patients with an unfavorable outcome with regard to severity of illness, suggesting that recovery is possible and unpredictable on the basis of clinical presentation. Chronic alcoholism was less frequent in patients with a favorable outcome as compared with patient with an unfavorable outcome (13 [72%] vs. 18 [100%], p = .04). Conclusions:The prognosis of critically ill patients with central or extrapontine myelinolysis is better than thus far thought despite initial severe clinical manifestations. Regarding the high rate of decisions to withhold life-supporting therapies, the probability of a favorable outcome might be underestimated by intensivists.

Long-term outcomes and cardiac surgery in critically ill patients with infective endocarditis

AIMSnTo assess long-term outcomes and the management of critical left-sided infective endocarditis (IE) and evaluate the impact of surgery.nnnMETHODS AND RESULTSnAmong the 198 patients included prospectively for IE across 33 adult intensive care units (ICU) in France from 1 April 2007 to 1 October 2008, 137 (69%) were dead at a median follow-up time of 59.5 months. Characteristics significantly associated with mortality were: Sepsis-related Organ-Failure Assessment (SOFA) score at ICU admission [Hazard ratio (HR), 95% Confidence Interval (CI) of 1.43 (0.79-2.59) for SOFA 5-9; 2.01 (1.05-3.85) for SOFA 10-14; 3.53 (1.75-7.11) for SOFA 15-20; reference category SOFA 0-4; P = 0.003]; prosthetic mechanical valve IE [HR 2.01; 95% CI 1.09-3.69, P = 0.025]; vegetation size ≥15 mm [HR 1.64; 95% CI 1.03-2.63, P = 0.038]; and cardiac surgery [HR (95%CI), 0.33 (0.16-0.67) for surgery ≤1 day after IE diagnosis; 0.61 (0.29-1.26) for surgery 2-7 days after IE diagnosis; 0.42 (0.21-0.83) for surgery >7 days after IE diagnosis; reference category no surgery; P = 0.005]. One hundred and three (52%) patients underwent cardiac surgery after a median time of 6 (16) days. Independent predictors of surgical intervention on multivariate analysis were: age ≤60 years [Odds ratio (OR) 5.30; 95% CI (2.46-11.41), P < 0.01], heart failure [OR 3.27; 95% CI (1.03-10.35), P = 0.04], cardiogenic shock [OR 3.31; 95% CI (1.47-7.46), P = 0.004], septic shock [OR 0.25; 95% CI (0.11-0.59), P = 0.002], immunosuppression [OR 0.15; 95% CI (0.04-0.55), P = 0.004], and diagnosis before or within 24 h of ICU admission [OR 2.81; 95% CI (1.14-6.95), P = 0.025]. SOFA score calculated the day of surgery was the only independently associated factor with long-term mortality [HR (95% CI) 1.59 (0.77-3.28) for SOFA 5-9; 3.56 (1.71-7.38) for SOFA 10-14; 11.58 (4.02-33.35) for SOFA 15-20; reference category SOFA 0-4; P < 0.0001]. Surgical timing was not associated with post-operative outcomes. Of the 158 patients with a theoretical indication for surgery, the 58 deemed not fit had a 95% mortality rate.nnnCONCLUSIONnMortality in patients with critical IE remains unacceptably high. Factors associated with long-term outcomes are the severity of multiorgan failure, prosthetic mechanical valve IE, vegetation size ≥15 mm, and surgical treatment. Up to one-third of potential candidates do not undergo surgery and these patients experience extremely high mortality rates. The strongest independent predictor of post-operative mortality is the pre-operative multiorgan failure score while surgical timing does not seem to impact on outcomes.

Correlation of Parasite Load Determined by Quantitative PCR to Clinical Outcome in a Heart Transplant Patient with Disseminated Toxoplasmosis

ABSTRACT Disseminated toxoplasmosis is a life-threatening infection in transplant recipients, which results either from reactivation of latent infection or from organ-transmitted primary infection. Preventive measures and diagnostic screening methods differ between countries and are related to the seroprevalence of Toxoplasma spp. in the general population. Here we report a case of disseminated toxoplasmosis in a heart transplant recipient with previous immunity that occurred after cotrimoxazole prophylaxis for the prevention of Pneumocystis jiroveci i pneumonia was stopped. Quantitative PCR proved useful for the diagnosis and monitoring of Toxoplasma infection. Decreasing parasitic burdens in sequential samples of cerebrospinal fluid, blood, and bronchoalveolar lavage fluid correlated with a favorable outcome and allowed modulation of the immunosuppressive drug regimen. The duration of anti-Toxoplasma treatment and the need for maintenance prophylaxis are discussed, as well as prophylaxis for solid-organ transplant recipients. Although a rare event in heart transplant recipients, Toxoplasma reactivation must be investigated promptly, since early treatment improves the prognosis.

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome

BACKGROUND The efficacy of venovenous extracorporeal membrane oxygenation (ECMO) in patients with severe acute respiratory distress syndrome (ARDS) remains controversial. METHODS In an international clinical trial, we randomly assigned patients with very severe ARDS, as indicated by one of three criteria — a ratio of partial pressure of arterial oxygen (Pao2) to the fraction of inspired oxygen (Fio2) of less than 50 mm Hg for more than 3 hours; a Pao2:Fio2 of less than 80 mm Hg for more than 6 hours; or an arterial blood pH of less than 7.25 with a partial pressure of arterial carbon dioxide of at least 60 mm Hg for more than 6 hours — to receive immediate venovenous ECMO (ECMO group) or continued conventional treatment (control group). Crossover to ECMO was possible for patients in the control group who had refractory hypoxemia. The primary end point was mortality at 60 days. RESULTS At 60 days, 44 of 124 patients (35%) in the ECMO group and 57 of 125 (46%) in the control group had died (relative risk, 0.76; 95% confidence interval [CI], 0.55 to 1.04; P=0.09). Crossover to ECMO occurred a mean (±SD) of 6.5±9.7 days after randomization in 35 patients (28%) in the control group, with 20 of these patients (57%) dying. The frequency of complications did not differ significantly between groups, except that there were more bleeding events leading to transfusion in the ECMO group than in the control group (in 46% vs. 28% of patients; absolute risk difference, 18 percentage points; 95% CI, 6 to 30) as well as more cases of severe thrombocytopenia (in 27% vs. 16%; absolute risk difference, 11 percentage points; 95% CI, 0 to 21) and fewer cases of ischemic stroke (in no patients vs. 5%; absolute risk difference, ‐5 percentage points; 95% CI, ‐10 to ‐2). CONCLUSIONS Among patients with very severe ARDS, 60‐day mortality was not significantly lower with ECMO than with a strategy of conventional mechanical ventilation that included ECMO as rescue therapy. (Funded by the Direction de la Recherche Clinique et du Développement and the French Ministry of Health; EOLIA ClinicalTrials.gov number, NCT01470703.)

Randomized comparison of 2 protocols to prevent acquisition of methicillin-resistant Staphylococcus aureus: results of a 2-center study involving 500 patients.

OBJECTIVEnTo compare an interventional protocol with a standard protocol for preventing the acquisition of methicillin-resistant Staphylococcus aureus (MRSA) in the intensive care unit (ICU).nnnDESIGNnProspective, randomized, controlled, parallel-group, nonblinded clinical trial.nnnSETTINGnMedical ICUs of 2 French university hospitals.nnnPARTICIPANTSnFive hundred adults with an expected length of stay in the ICU greater than 48 hours.nnnINTERVENTIONSnFor the intervention group, the protocol required repeated MRSA screening, contact and droplet isolation precautions for patients at risk for MRSA at ICU admission and for MRSA-positive patients, and decontamination with nasal mupirocin and chlorhexidine body wash for MRSA-positive patients. For the standard group, the standard precautions protocol was used, and the results of repeated MRSA screening in the standard group were not communicated to investigators.nnnMAIN OUTCOME MEASUREnMRSA acquisition rate in the ICU. An audit was conducted to assess compliance with hygiene and isolation precautions.nnnRESULTSnIn the intent-to-treat analysis ([Formula: see text]), the MRSA acquisition rate in the ICU was similar in the standard (13 [5.3%] of 243) and intervention (16 [6.5%] of 245) groups ([Formula: see text]). The audit showed that the overall compliance rate was 85.5% in the standard group and 84.1% in the intervention group ([Formula: see text]), although compliance was higher when isolation precautions were absent than when they were in place (88.2% vs 79.1%; [Formula: see text]). MRSA incidence rates were higher without isolation precautions (7.57‰) than with isolation precautions (2.36‰; [Formula: see text]).nnnCONCLUSIONSnIndividual allocation to MRSA screening, isolation precautions, and decontamination do not provide individual benefit in reducing MRSA acquisition, compared with standard precautions, although the collective risk was lower during the periods of isolation.nnnTRIAL REGISTRATIONnClinicaltrials.gov identifier: NCT00151606.

Cardiac output monitoring in septic shock: evaluation of the third-generation Flotrac-Vigileo®

Continuous cardiac index (CI) monitoring is frequently used in critically ill patients. Few studies have compared the pulse contour-based device FloTrac/Vigileo® to pulmonary artery thermodilution (PAC) in terms of accuracy for CI monitoring in septic shock. The aim of our study was to compare the third-generation FloTrac/Vigileo® to PAC in septic shock. Eighteen patients with septic shock requiring monitoring by PAC were included in this study. We monitored CI using both FloTrac/Vigileo® and continuous thermodilution (PAC-CI). Hemodynamic data were recorded every hour or every 2xa0min during fluid challenges. The primary endpoint was the global agreement of all CI-paired measurements determined using the Bland–Altman method adapted to replicated data. We tested the linearity of the bias by regression analysis, and compared the reactivity of the 2 techniques during fluid challenges. A receiver operating characteristic (ROC) curve analysis tested the ability of FloTrac/Vigileo® to detect concordant and significative CI changes, using PAC-CI as the reference method. Overall, 1,201 paired CI measurements were recorded. The Bland–Altman analysis for global agreement of the 2 techniques showed a bias of −0.1xa0±xa02.1xa0Lxa0min−1xa0m−2 and a percentage error of 64xa0%. The overall correlation coefficient between PAC-CI and FloTrac/Vigileo® CI was 0.47 (pxa0<xa00.01), with r2xa0=xa00.22. The area under the curve of the ROC curve for detecting concordant and significant changes in CI was 0.72 (0.53; 0.87). In our study, third-generation Flowtrac-Vigileo® appears to be too inaccurate to be recommended for CI monitoring in septic shock.

Short-term decline in all-cause acquired infections with the routine use of a decontamination regimen combining topical polymyxin, tobramycin, and amphotericin B with mupirocin and chlorhexidine in the ICU: a single-center experience.

Objectives:In a multicenter, placebo-controlled, randomized, double-blind trial, we showed that acquired infections in intubated patients were reduced by the combination of topical polymyxin plus tobramycin and nasal mupirocin plus chlorhexidine body wash. Because intubated patients are particularly at risk for acquired infections, we reassessed the impact of this protocol as a routine procedure to control acquired infections in the ICU. Design:Nonrandomized study comparing acquired infections in ICU patients during two 1-year periods: the last year before (group A, n = 925) and the first year after the implementation of the protocol (group B, n = 1,022). Acquired infections were prospectively recorded. Setting:Polyvalent medical ICU at a university-affiliated hospital. Patients:All patients admitted to the ICU. Interventions:Administration of polymyxin/tobramycin/amphotericin B in the oropharynx and the gastric tube plus a mupirocin/chlorhexidine regimen in intubated patients and standard care in the other patients. Measurements and Main Results:The comparison of acquired infection rates between groups was adjusted for differences at baseline. Infection rates were lower in group B compared with group A (5.3% vs 11.0%; p < 0.001), as were the incidence rates of total acquired infections (9.4 vs 23.6 per 1,000 patient-days; p < 0.001), intubation-related pneumonia (5.1 vs 17.1 per 1,000 ventilator-days; p < 0.001), and catheter-related bloodstream infections (1.0 vs 3.5 per 1,000 catheter-days; p = 0.03). There were fewer acquired infections caused by ceftazidime-resistant Enterobacteriaceae (0.8‰ vs 3.6‰; p < 0.001), ciprofloxacin-resistant Enterobacteriaceae (0.8‰ vs 2.5‰; p = 0.02), ciprofloxacin-resistant Pseudomonas aeruginosa (0.5‰ vs 1.6‰; p = 0.05), and colistin-resistant Gram-negative bacilli (0.7‰ vs 1.9‰; p = 0.04). Fewer patients got acquired infections due to multidrug-resistant aerobic Gram-negative bacilli (p = 0.008). Conclusions:In intubated patients, the use of topical polymyxin/tobramycin/amphotericin B plus mupirocin/chlorhexidine was associated with the reduction of all-cause ICU-acquired infections. Long-term emergence of multidrug-resistant organisms deserves further investigation.