Jean-Luc Canivet

Sepsis and serum cytokine concentrations.

OBJECTIVE To look for relationships between the classification of sepsis and plasma cytokine concentrations. DESIGN Prospective, consecutive entry study of patients meeting severe sepsis criteria and having bacteriologically documented infections. SETTING University hospital, surgical intensive care unit. PATIENTS Fifty consecutive patients developing severe sepsis or septic shock between December 1991 and December 1993. MEASUREMENTS AND MAIN RESULTS Concentrations of tumor necrosis factor, interleukin (IL)-6, IL-8, and leukemia inhibitory factor were measured by immunoradiometric assay in the plasma of patients as soon as they developed severe sepsis or septic shock. Septic shock patients were divided into three groups in a blinded fashion (i.e., without knowing the results of the concentrations of cytokines), according to the presence of sustained hyperlactacidemia and to the rapidity of the onset of sepsis. Peak concentrations of all cytokines were statistically different between severe sepsis and septic shock patients. This finding was almost exclusively due to the data from patients with rapid onset of septic shock, who demonstrated very high but transient cytokine concentrations. Septic shock patients may thus have different profiles in the time course of their cytokine concentrations. The transient, high peak concentrations of cytokines were also related to transient leukopenia. Among the cytokines measured, IL-8 appeared to be the one that correlated best with lactacidemia, the presence of disseminated intravascular coagulation, severe hypoxemia, the Acute Physiology and Chronic Health Evaluation II score, and mortality rate. CONCLUSIONS According to the profiles of the cytokines, septic shock patients do not represent a homogeneous population. These profiles should be described in order to distinguish between patients, and the profiles may be useful to identify those patients susceptible to new therapies.

International consensus statement on training standards for advanced critical care echocardiography

Endorsed by the European Society of Intensive Care Medicine (ESICM), American College of Chest Physicians (ACCP), American Thoracic Society (ATS), Société de Réanimation de Langue Française (SRLF), Asia Pacific Association of Critical Care Medicine, Canadian Critical Care Society, College of Intensive Care Medicine of Australia and New Zealand, Hong Kong College of Anaesthesiologists, Hong Kong Society of Critical Care Medicine. All authors certify that they endorse all parts of the published manuscript. The expert round table participants and the authors as a group are listed in the Appendix.

Procalcitonin usefulness for the initiation of antibiotic treatment in intensive care unit patients.

Objectives: To test the usefulness of procalcitonin serum level for the reduction of antibiotic consumption in intensive care unit patients. Design: Single-center, prospective, randomized controlled study. Setting: Five intensive care units from a tertiary teaching hospital. Patients: All consecutive adult patients hospitalized for > 48 hrs in the intensive care unit during a 9-month period. Interventions: Procalcitonin serum level was obtained for all consecutive patients suspected of developing infection either on admission or during intensive care unit stay. The use of antibiotics was more or less strongly discouraged or recommended according to the Muller classification. Patients were randomized into two groups: one using the procalcitonin results (procalcitonin group) and one being blinded to the procalcitonin results (control group). The primary end point was the reduction of antibiotic use expressed as a proportion of treatment days and of daily defined dose per 100 intensive care unit days using a procalcitonin-guided approach. Secondary end points included: a posteriori assessment of the accuracy of the infectious diagnosis when using procalcitonin in the intensive care unit and of the diagnostic concordance between the intensive care unit physician and the infectious-disease specialist. Measurements and Main Results: There were 258 patients in the procalcitonin group and 251 patients in the control group. A significantly higher amount of withheld treatment was observed in the procalcitonin group of patients classified by the intensive care unit clinicians as having possible infection. This, however, did not result in a reduction of antibiotic consumption. The treatment days represented 62.6 ± 34.4% and 57.7 ± 34.4% of the intensive care unit stays in the procalcitonin and control groups, respectively (p = .11). According to the infectious-disease specialist, 33.8% of the cases in which no infection was confirmed, had a procalcitonin value >1µg/L and 14.9% of the cases with confirmed infection had procalcitonin levels <0.25 µg/L. The ability of procalcitonin to differentiate between certain or probable infection and possible or no infection, upon initiation of antibiotic treatment was low, as confirmed by the receiving operating curve analysis (area under the curve = 0.69). Finally, procalcitonin did not help improve concordance between the diagnostic confidence of the infectious-disease specialist and the ICU physician. Conclusions: Procalcitonin measuring for the initiation of antimicrobials did not appear to be helpful in a strategy aiming at decreasing the antibiotic consumption in intensive care unit patients.

Prevention of ventilator-associated pneumonia and ventilator-associated conditions: A randomized controlled trial with subglottic secretion suctioning

Objectives:Ventilator-associated pneumonia diagnosis remains a debatable topic. New definitions of ventilator-associated conditions involving worsening oxygenation have been recently proposed to make surveillance of events possibly linked to ventilator-associated pneumonia as objective as possible. The objective of the study was to confirm the effect of subglottic secretion suctioning on ventilator-associated pneumonia prevalence and to assess its concomitant impact on ventilator-associated conditions and antibiotic use. Design:Randomized controlled clinical trial conducted in five ICUs of the same hospital. Patients:Three hundred fifty-two adult patients intubated with a tracheal tube allowing subglottic secretion suctioning were randomly assigned to undergo suctioning (n = 170, group 1) or not (n = 182, group 2). Main Results:During ventilation, microbiologically confirmed ventilator-associated pneumonia occurred in 15 patients (8.8%) of group 1 and 32 patients (17.6%) of group 2 (p = 0.018). In terms of ventilatory days, ventilator-associated pneumonia rates were 9.6 of 1,000 ventilatory days and 19.8 of 1,000 ventilatory days, respectively (p = 0.0076). Ventilator-associated condition prevalence was 21.8% in group 1 and 22.5% in group 2 (p = 0.84). Among the 47 patients with ventilator-associated pneumonia, 25 (58.2%) experienced a ventilator-associated condition. Neither length of ICU stay nor mortality differed between groups; only ventilator-associated condition was associated with increased mortality. The total number of antibiotic days was 1,696 in group 1, representing 61.6% of the 2,754 ICU days, and 1,965 in group 2, representing 68.5% of the 2,868 ICU days (p < 0.0001). Conclusions:Subglottic secretion suctioning resulted in a significant reduction of ventilator-associated pneumonia prevalence associated with a significant decrease in antibiotic use. By contrast, ventilator-associated condition occurrence did not differ between groups and appeared more related to other medical features than ventilator-associated pneumonia.

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.

Correlation between endotoxin level and bacterial count in bronchoalveolar lavage fluid of ventilated patients

ObjectiveTo assess the predictive value of the endotoxin level in the bronchoalveolar lavage (BAL) and to propose to the clinician a guide in the diagnosis of Gram-negative bacterial (GNB) pneumonia. DesignRetrospective and prospective studies to investigate the relation between endotoxin level and quantitative bacterial culture of BAL and to test the predictive value of a defined threshold. SettingUniversity hospital general intensive care unit. PatientsIn the first part of the study, 77 consecutive ventilated patients with clinical suspicion of nosocomial pneumonia between January 1995 and January 1996. In the second part of the study, 93 consecutive ventilated patients studied prospectively between February 1996 and April 1997. Measurements and Main ResultsQuantitative cultures for aerobic bacteria were performed directly from the fluid. Bacterial species were determined with standard techniques. The detection of endotoxin in BAL was made using a quantitative chromogenic Limulus assay.In the retrospective analysis, a significant correlation between quantitative GNB cultures and BAL endotoxin levels was observed (r2 = 0.60, p < .0001). An endotoxin level ≥ 4 endotoxin units/mL (EU/mL) distinguishes patients with a significant GNB count from colonized patients with a sensitivity of 92.6%, a specificity of 81.4% and a correct classification rate of 84.9%.In the prospective analysis, the 4 EU/mL threshold permits identification of infected patients with a sensitivity of 82.2%, a specificity of 95.6%, and a correct classification rate of 90.3%. The receiver operating characteristic curve analysis showed that the Limulus assay still had a good discrimination power in the prediction of significant bacterial count in BAL fluid. ConclusionsEndotoxin detection immediately after bronchoscopy is a distinct advantage to the clinician because antimicrobial Gram-negative therapy may be immediately justified according to the results.

Evidence of in vivo Free Radical Generation by Spin Trapping with α-Phenyl N-Tert-Butyl Nitrone During Ischemia/Reperfusion in Rabbit Kidneys

By using alpha-phenyl N-tert-butyl nitrone (PBN) as spin trap molecule and the electron paramagnetic resonance (EPR) technique, we obtained the first direct evidence of in vivo intervention of free radicals during an ischemia (50 minutes) reperfusion phenomenon in kidney of an intact rabbit. An EPR signal (triplet of doublets) characterized by coupling constants aN = 14.75-15 G and aH beta = 2.5-3 G was detected in blood samples. The signal was consistent with a nitroxyl-radical adduct resulting from the spin trapping by PBN of either oxygen-or carbon-centered radicals. Control experiments indicated that the EPR signal was not due to a toxic effect of the spin trap molecule.

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

The use of pre‐operative intrathecal morphine for analgesia following coronary artery bypass surgery

With the emergence of rapid extubation protocols following cardiac surgery, providing adequate analgesia in the early postoperative period is important. This prospective randomised double‐blind study investigated the benefits of pre‐operative intrathecal administration of low dose morphine in patients undergoing coronary artery bypass graft surgery. Postoperative analgesia, pulmonary function, stress response and postoperative recovery profile were assessed. Thirty patients were allocated into two groups, receiving either 500 μg of morphine intrathecally prior to anaesthesia and intravenous patient‐controlled analgesia with morphine postoperatively following tracheal extubation, or only postoperative intravenous patient‐controlled analgesia. In the intrathecal group, the total consumption of intravenous morphine following surgery was significantly reduced by 40% and patients reported lower pain scores at rest, during the first 24 h following extubation. Peak expiratory flow rate was greater and postoperative catecholamine release was significantly lower. Patients in the control group had a higher incidence of reduced respiratory rate following extubation.

Hyperammonemia after high-dose chemotherapy and stem cell transplantation.

We report a patient with multiple myeloma who suffered from hyperammonemia after a second stem cell autograft. This syndrome is not well known but is associated with a high mortality rate. Considering the possibility of this diagnosis in patients developing confusion and neurological degradation with respiratory alkalosis after intensive chemotherapy, could allow earlier treatment and perhaps improved survival. Possible mechanisms and potential therapies are discussed. With rapid recognition and treatment of the syndrome, the patient fully recovered. One and a half years later, she is still alive and well, on interferon for persisting myeloma. Bone Marrow Transplantation (2000) 26, 343–345.