Mehran Monchi

High frequency oscillatory ventilation compared with conventional mechanical ventilation in adult respiratory distress syndrome: a randomized controlled trial [ISRCTN24242669].

IntroductionTo compare the safety and efficacy of high frequency oscillatory ventilation (HFOV) with conventional mechanical ventilation (CV) for early intervention in adult respiratory distress syndrome (ARDS), a multi-centre randomized trial in four intensive care units was conducted.MethodsPatients with ARDS were randomized to receive either HFOV or CV. In both treatment arms a priority was given to maintain lung volume while minimizing peak pressures. CV ventilation strategy was aimed at reducing tidal volumes. In the HFOV group, an open lung strategy was used. Respiratory and circulatory parameters were recorded and clinical outcome was determined at 30 days of follow up.ResultsThe study was prematurely stopped. Thirty-seven patients received HFOV and 24 patients CV (average APACHE II score 21 and 20, oxygenation index 25 and 18 and duration of mechanical ventilation prior to randomization 2.1 and 1.5 days, respectively). There were no statistically significant differences in survival without supplemental oxygen or on ventilator, mortality, therapy failure, or crossover. Adjustment by a priori defined baseline characteristics showed an odds ratio of 0.80 (95% CI 0.22–2.97) for survival without oxygen or on ventilator, and an odds ratio for mortality of 1.15 (95% CI 0.43–3.10) for HFOV compared with CV. The response of the oxygenation index (OI) to treatment did not differentiate between survival and death. In the HFOV group the OI response was significantly higher than in the CV group between the first and the second day. A post hoc analysis suggested that there was a relatively better treatment effect of HFOV compared with CV in patients with a higher baseline OI.ConclusionNo significant differences were observed, but this trial only had power to detect major differences in survival without oxygen or on ventilator. In patients with ARDS and higher baseline OI, however, there might be a treatment benefit of HFOV over CV. More research is needed to establish the efficacy of HFOV in the treatment of ARDS. We suggest that future studies are designed to allow for informative analysis in patients with higher OI.

Predicting survival with good neurological recovery at hospital admission after successful resuscitation of out-of-hospital cardiac arrest: the OHCA score

AIMS Out-of-hospital cardiac arrest (OHCA) is common and carries a bleak prognosis. Early prediction of unfavourable outcomes is difficult but crucial to improve resource allocation. The aim of this study was to develop a simple tool for predicting survival with good neurological function in the overall population of patients with successfully resuscitated cardiac arrest. METHODS AND RESULTS We used logistic regression analysis to identify clinical and laboratory variables that were both readily available at admission and predictive of poor outcomes (death or severe neurological impairment) in a development cohort of 130 consecutive OHCA patients admitted to a French intensive care unit (ICU) between 1999 and 2003. To test the prediction score built from these variables, we used a validation cohort of 210 patients recruited in four French ICUs between 2003 and 2005. Initial rhythm, estimated no-flow and low-flow intervals, blood lactate, and creatinine levels determined using whole blood analyzers were independently associated with poor outcomes and were used to build a continuous severity score. Goodness-of-fit tests indicated good performance (P=0.79 in the development cohort and P=0.13 in the validation cohort). The area under the receiver-operating characteristics curve was 0.82 in the development cohort and 0.88 in the validation cohort. CONCLUSION The outcome can be accurately predicted after OHCA using variables that are readily available at ICU admission.

DNAemia detection by multiplex PCR and biomarkers for infection in systemic inflammatory response syndrome patients.

Fast and reliable assays to precisely define the nature of the infectious agents causing sepsis are eagerly anticipated. New molecular biology techniques are now available to define the presence of bacterial or fungal DNA within the bloodstream of sepsis patients. We have used a new technique (VYOO®) that allows the enrichment of microbial DNA before a multiplex polymerase chain reaction (PCR) for pathogen detection provided by SIRS-Lab (Jena, Germany). We analyzed 72 sepsis patients and 14 non-infectious systemic inflammatory response syndrome (SIRS) patients. Among the sepsis patients, 20 had a positive blood culture and 35 had a positive microbiology in other biological samples. Of these, 51.4% were positive using the VYOO® test. Among the sepsis patients with a negative microbiology and the non-infectious SIRS, 29.4% and 14.2% were positive with the VYOO® test, respectively. The concordance in bacterial identification between microbiology and the VYOO® test was 46.2%. This study demonstrates that these new technologies offer great hopes, but improvements are still needed.

Combination therapy versus monotherapy: a randomised pilot study on the evolution of inflammatory parameters after ventilator associated pneumonia [ISRCTN31976779]

IntroductionCombination antibiotic therapy for ventilator associated pneumonia (VAP) is often used to broaden the spectrum of activity of empirical treatment. The relevance of such synergy is commonly supposed but poorly supported. The aim of the present study was to compare the clinical outcome and the course of biological variables in patients treated for a VAP, using a monotherapy with a beta-lactam versus a combination therapy.MethodsPatients with VAP were prospectively randomised to receive either cefepime alone or cefepime in association with amikacin or levofloxacin. Clinical and inflammatory parameters were measured on the day of inclusion and thereafter.ResultsSeventy-four mechanically ventilated patients meeting clinical criteria for VAP were enrolled in the study. VAP was microbiologically confirmed in 59 patients (84%). Patients were randomised to receive cefepime (C group, 20 patients), cefepime with amikacin (C-A group, 19 patients) or cefepime with levofloxacin (C-L group, 20 patients). No significant difference was observed regarding the time course of temperature, leukocytosis or C-reactive protein level. There were no differences between length of stay in the intensive care unit after infection, nor in ventilator free days within 28 days after infection. No difference in mortality was observed.ConclusionAntibiotic combination using a fourth generation cephalosporin with either an aminoside or a fluoroquinolone is not associated with a clinical or biological benefit when compared to cephalosporin monotherapy against common susceptible pathogens causing VAP.

Immune status and apoptosis activation during brain death.

The present study evaluates the role of the inflammatory status and apoptosis activation in the development of organ dysfunction after brain death using plasma assays and macroarray analysis on skeletal muscle biopsies to look for evidence of remote tissue damage in two intensive care units in France and one in Belgium. As controls, we used patients undergoing hip surgery and healthy volunteers. Causes of brain death in the 85 consecutive patients included in the study were cardiac arrest (n = 29; 34%), stroke (n = 42; 49%, with 38 patients having hemorrhagic stroke), and head injury (n = 14; 17%). Of the 85 patients, 45 donated 117 organs. Plasma endotoxin and cytokine levels indicated a marked systemic inflammatory response in brain-dead patients, which was strongest in the cardiac arrest group. Leukocyte dysfunction, as assessed by cytokines production in response to various stimuli, was noted in a subgroup of patients with brain death after stroke. Interestingly, skeletal muscle biopsies showed no increase in mRNAs for genes related to inflammation, whereas mRNAs for both antiapoptotic and proapoptotic genes were increased, the balance being in favor of apoptosis induction. The increased activation of the proapoptotic caspase 9 was further confirmed by Western blot. In conclusion, the presence of inflammation and apoptosis induction may explain the rapid organ dysfunction seen after brain death. Both abnormalities may play a role in organ dysfunction associated with brain death. However, the level of systemic inflammation or the presence of circulating endotoxin was not associated with lower graft survival.

Quantitative lipopolysaccharide analysis using HPLC/MS/MS and its combination with the limulus amebocyte lysate assay

Quantitation of plasma lipopolysaccharides (LPSs) might be used to document Gram-negative bacterial infection. In the present work, LPS-derived 3-hydroxymyristate was extracted from plasma samples with an organic solvent, separated by reversed phase HPLC, and quantitated by MS/MS. This mass assay was combined with the limulus amebocyte lysate (LAL) bioassay to monitor neutralization of LPS activity in biological samples. The described HPLC/MS/MS method is a reliable, practical, accurate, and sensitive tool to quantitate LPS. The combination of the LAL and HPLC/MS/MS analyses provided new evidence for the intrinsic capacity of plasma lipoproteins and phospholipid transfer protein to neutralize the activity of LPS. In a subset of patients with systemic inflammatory response syndrome, with documented infection but with a negative plasma LAL test, significant amounts of LPS were measured by the HPLC/MS/MS method. Patients with the highest plasma LPS concentration were more severely ill. HPLC/MS/MS is a relevant method to quantitate endotoxin in a sample, to assess the efficacy of LPS neutralization, and to evaluate the proinflammatory potential of LPS in vivo.

Occurrence of MRSA endocarditis during linezolid treatment

Linezolid is an antimicrobial agent belonging to a new class of antibiotics: the oxazolidinones. It has been approved for the treatment of infections due to grampositive organisms including methicillin-resistant Staphylococcus aureus (MRSA). We report a case of Staphylococcus aureus endocarditis that occurred in a burn patient during treatment with this new antibiotic, despite full in vitro sensitivity. A previously healthy 38-year-old man was referred to our six-bed burn unit 2 h after self immolation with petrol. At entry, physical examination revealed burns estimated to involve 85% of the total body surface. On day 25, his skin became colonized by MRSA and Pseudomonas aeruginosa. MRSA was also isolated from a central venous catheter 5 days later, and two blood cultures taken on day 34 grew MRSA. At this time, no deterioration of the patient’s clinical status was observed, except for a body temperature of 38 C. Cardiac signs were not noted. As investigational therapy, linezolid was started on day 37, first intravenously, then orally at a dose of 600 mg b.i.d. for 16 days. The minimal inhibitory concentration (MIC) of linezolid was 0.75 g/ml at the beginning of treatment and 1.5 g/ml at the end. On day 3 of treatment, one more blood culture resulted positive for MRSA, while MRSA had disappeared from burn wound samples. The patient showed an initial clinical improvement until the last day of linezolid therapy. While still on therapy, fever recurred. Since a blood culture taken on the last day of linezolid treatment again grew MRSA, intravenous vancomycin was administered. At this time, a cardiac murmur was noted and aortic endocarditis was diagnosed by transesophageal echocardiography. The hemodynamic status of the patient then deteriorated; he had to be intubated and mechanically ventilated, and vasoppressor agents were administered. On day 62 following admission, a surgical valve replacement was performed. During surgery, large vegetations were found on the aortic valve extending as an abscess into the ventricular septum. Culture of the native valve grew linezolidsensitive MRSA. Following surgery, the patient completed 4 weeks of vancomycin therapy. He was discharged from hospital on day 120. Linezolid has inhibitory activity against a broad range of gram-positive bacteria, including MRSA. After oral administration, its bioavailability reaches 100% [1]. Its efficacy for treating gram-positive communityor nosocomial-acquired pneumonia as well as soft tissue infections is established [2]. However, data concerning its role in the treatment of severe infections, like endocarditis, are scarce. There is concern about the bacteriostatic property of linzeolid, especially against Staphylococcus spp. However, a Staphylococcus aureus endocarditis model in rabbits showed good results when linezolid trough levels in plasma remained above the MIC for this organism [3]. In humans, successful treatment of vancomycin-resistant Enterococcus endocarditis was reported with oral linezolid given at a dose of 600 mg b.i.d. [4]. Although resistance of a clinical Staphylococcus aureus isolate to linezolid has been reported previously, this did not occur in the case reported here. The strain of Staphylococcus aureus we isolated remained sensitive to linezolid with an MIC value lower than the accepted breakpoint of 4 g/ml [1]. It must be recognized, however, that burn patients are difficult to treat because the pharmacokinetics of many therapeutic agents become altered. In particular, the dose of many antimicrobial E. H. Ben Mansour · E. Jacob · M. Monchi · D. Ledoux · J.-L. Canivet · P. Damas ()) Department of General Intensive Care, University Hospital, Domaine universitaire du Sart-Tilman, 4000 Liege, Belgium e-mail: pdamas@chu.ulg.ac.be Tel.: +32-4-3667495 Fax: +32-4-3668898

Too early initiation of renal replacement therapy may be harmful

In an observational multicenter study, Elseviers and colleagues report that renal replacement therapy (RRT) in acutely ill patients treated for acute kidney injury is an independent risk factor for death. This result may question the benefit of the current practice of early RRT initiation.

Bacterial translocation and plasma cytokines during transcatheter and open-heart aortic valve implantation.

ABSTRACT Objective: To determine whether the good safety profile of transarterial aortic valve implantation (TAVI) is related to lower levels of systemic bacterial translocation and systemic inflammation compared with open-heart surgery. Background: Transcatheter aortic valve implantation via the transfemoral approach is increasingly used in very high-risk patients with aortic stenosis. The outcomes seem similar to those after open-heart aortic valve replacement (OHAVR). Methods: Each of 26 consecutive high-risk patients (EuroSCORE >20% for risk of operative death) who underwent TAVI (cases) was matched to the first low-risk patient treated next in our department using elective OHAVR without coronary artery bypass (control subjects). We collected severity, outcome, and echocardiography indicators before and after surgery; complications; proinflammatory cytokine levels; and markers for microbial translocation. Results: Despite greater illness severity, the TAVI patients had significantly lower vasopressor agent requirements, lower delirium rates, shorter hospital stays, and better hemodynamic findings compared with OHAVR patients. Vascular complications were more common after TAVI than after OHAVR (12, with seven requiring interventional therapy vs. 0, P = 0.006). Patients who underwent TAVI had lower blood transfusion requirements. Two TAVI patients died: one from iliac artery injury and the other from intracardiac prosthesis migration. Patients who underwent TAVI had lower plasma levels of endotoxin and bacterial peptidoglycan, as well as lower proinflammatory cytokine levels, suggesting less gastrointestinal bacterial translocation compared with OHAVR. Conclusions: Compared with OHAVR, TAVI was associated with decreases in bacterial translocation and inflammation. These differences may explain the lower delirium rate and better hemodynamic stability observed, despite the greater disease severity in TAVI patients.

Timing of Initiation of Renal Replacement Therapy in Critically Ill Patients With Acute Kidney Injury

Timing of Initiation of Renal Replacement Therapy in Critically Ill Patients With Acute Kidney Injury To the Editor The Early vs Late Initiation of Renal Replacement Therapy on Mortality in Critically Ill Patients With Acute Kidney Injury (ELAIN) trial reported decreased mortality with early vs delayed renal replacement therapy (RRT) initiation in critically ill patients with acute kidney injury (AKI).1 In contrast, the Artificial Kidney Initiation in Kidney Injury (AKIKI) trial found no mortality difference with early vs delayed strategies.2 However, the design of the 2 studies was different. In the AKIKI trial, late initiation was based on typical absolute criteria (hyperkalemia, metabolic acidosis, pulmonary edema, severe oliguria) compared with a timeframe initiation (<12 hours of reaching Kidney Disease: Improving Global Outcomes [KDIGO] stage 3 AKI) in the ELAIN trial. The case-mix in the 2 studies was different. In the ELAIN study, the population was mostly postoperative patients with approximately 50% having had cardiac surgery, whereas in the AKIKI study, the population was mainly medical (around 80% had sepsis). However, the difference in mortality at 60 days after randomization between the early and delayed strategies was not statistically significant in either study. The effect on mortality in the ELAIN study did not reach significance until day 90. The results of the ELAIN trial raise some concerns. The mortality in the 2 groups appears low given the severity scores (Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment [SOFA]), which predict a mortality as high as 70%. In addition, the difference in mortality at day 90 seems large (54.7% in the delayed group vs 39.3% in the early group; mean reduction, −15.4% [95% CI, −28.1% to −2.6%]). To date, no intervention in the intensive care unit has shown such a positive effect, and it appears improbable that early vs late RRT could achieve this benefit. Even more surprising is the very late effect on mortality. The difference did not become statistically significant until day 90, and the 2 survival curves separated only after the first 10 days. Other factors may explain the results. Editor’s Note: This letter was inadvertently omitted from the September 20 issue.