Gérard Nitenberg

Diagnosis of catheter-related bacteraemia: a prospective comparison of the time to positivity of hub-blood versus peripheral-blood cultures

BACKGROUND A method of diagnosing catheter-related infection (CRI) without removing the catheter would be useful. An earlier positivity of central compared with peripheral venous-blood cultures may be associated with catheter-related bacteraemia. We evaluated prospectively the differential time to positivity (DTP) of paired blood cultures drawn simultaneously via the catheter hub and from a peripheral venous site. METHODS Over a 14-month period in an intensive-care unit of a cancer referral centre, simultaneous hub-blood and peripheral-blood cultures (a mean of two per patient) were obtained from patients with a suspected CRI. According to clinical criteria and quantitative culture of the catheter tip, cases were classified as CRI or sepsis of other origin. At least one pair of hub-blood and peripheral-blood cultures was obtained within 48 h before catheter removal, and we recorded the DTP between hub-blood and peripheral-blood cultures with an automatic device for detection of blood culture positivity. FINDINGS We analysed 93 catheters removed because of suspicion of CRI. In 28 episodes, the same micro-organisms were found in both hub-blood and peripheral-blood cultures. A diagnosis of definite bacteraemic CRI was made in 16 of the 17 patients in whom a positive hub-blood culture was detected at least 2 hours earlier than peripheral-blood culture. About half (9/17) of these episodes occurred in long-term (>30 days) devices. CRI was excluded in ten of the 11 patients with a DTP lower than 2 h. The DTP of paired blood cultures was significantly greater in patients with CRI than in others (p<10(-4)). A cut-off DTP value of 120 min had 91% specificity and 94% sensitivity for the diagnosis of CRI. Three of 17 episodes with only hub-blood culture positive were associated with CRI. INTERPRETATION This prospective study suggests that measurement of the differential time to positivity between hub-blood and peripheral-blood cultures is a simple and reliable tool for in-situ diagnosis of catheter-related sepsis in cancer patients. Further studies are needed to confirm these data for short-term catheters.

Nutritional support of the cancer patient: issues and dilemmas

Malnutrition in cancer patients results from multifactorial events and is associated with an alteration of quality of life and a reduced survival. A simple nutritional assessment program and early counselling by a dietitian are essential to guide nutritional support and to alert the physician to the need for enteral (EN) or parenteral nutrition (PN). A daily intake of 20-35 kcal/kg, with a balanced contribution of glucose and lipids, and of 0.2-0.35 g nitrogen/kg is recommended both for EN and PN, with an adequate provision of electrolytes, trace elements and vitamins. EN, always preferable for patients with an intact digestive tract, and PN are both safe and effective methods of administering nutrients. The general results in clinical practice suggest no tumor growth during nutritional support. The indiscriminate use of conventional EN and PN is not indicated in well-nourished cancer patients or in patients with mild malnutrition. EN or PN is not clinically efficacious for patients treated with chemotherapy or radiotherapy, unless there are prolonged periods of GI toxicity, as in the case of bone marrow transplant patients. Severely malnourished cancer patients undergoing major visceral surgery may benefit from perioperative nutritional support, preferably via enteral access. Nutritional support in palliative care should be based on the potential risks and benefits of EN and PN, and on the patients and familys wishes. Research is currently directed toward the impact of nutritional pharmacology on the clinical outcome of cancer patients. Glutamine-supplemented PN is probably beneficial in bone marrow transplant patients. Immune diets are likely to reduce the rate of infectious complications and the length of hospital stay after GI surgery. Further studies are needed to determine the efficacy of such novel approaches in specific populations of cancer patients, and should also address the question of the overall cost-benefit ratio of nutritional pharmacology, and the effect of nutritional support on length and quality of life.

Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial

BACKGROUND International guidelines for management of septic shock recommend that dopamine or norepinephrine are preferable to epinephrine. However, no large comparative trial has yet been done. We aimed to compare the efficacy and safety of norepinephrine plus dobutamine (whenever needed) with those of epinephrine alone in septic shock. METHODS This prospective, multicentre, randomised, double-blind study was done in 330 patients with septic shock admitted to one of 19 participating intensive care units in France. Participants were assigned to receive epinephrine (n=161) or norepinephrine plus dobutamine (n=169), which were titrated to maintain mean blood pressure at 70 mm Hg or more. The primary outcome was 28-day all-cause mortality. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00148278. FINDINGS There were no patients lost to follow-up; one patient withdrew consent after 3 days. At day 28, there were 64 (40%) deaths in the epinephrine group and 58 (34%) deaths in the norepinephrine plus dobutamine group (p=0.31; relative risk 0.86, 95% CI 0.65-1.14). There was no significant difference between the two groups in mortality rates at discharge from intensive care (75 [47%] deaths vs 75 [44%] deaths, p=0.69), at hospital discharge (84 [52%] vs 82 [49%], p=0.51), and by day 90 (84 [52%] vs 85 [50%], p=0.73), time to haemodynamic success (log-rank p=0.67), time to vasopressor withdrawal (log-rank p=0.09), and time course of SOFA score. Rates of serious adverse events were also similar. INTERPRETATION There is no evidence for a difference in efficacy and safety between epinephrine alone and norepinephrine plus dobutamine for the management of septic shock.

Epidemiology, diagnosis and treatment of systemic Candida infection in surgical patients under intensive care

The incidence of systemic Candida infections in patients requiring intensive care has increased substantially in recent years as a result of a combination of factors. More patients with severe underlying disease or immunosuppression from anti-neoplastic or anti-rejection chemotherapy and at risk from fungal infection are now admitted to the ICU. Improvements in supportive medical and surgical care have led to many patients who would previously have died as a result of trauma or disease surviving to receive intensive care. Moreover, some therapeutic interventions used in the ICU, most notably broad-spectrum antibiotics and intravascular catheters, are also associated with increased risks of candidiasis. Systemic Candida infections are associated with a high morbidity and mortality, but remain difficult to diagnose and ICU staff need to bé acutely aware of this often insidious pathogen. A number of studies have identified risk factors for systemic Candida infection which may be used to identify those at highest risk. Such patients may be potential candidates for early, presumptive therapy. Here we review the epidemiology, pathogenesis, morbidity and mortality of systemic Candida infections in the ICU setting, and examine predisposing risk factors. Antifungal treatment, including the use of amphotericin B, flucytosine and fluconazole, and the roles of early presumptive therapy and prophylaxis, is also reviewed.

Enteral nutrition in intensive care patients: a practical approach

Severe protein-calorie malnutrition is a major problem in many intensive care (ICU) patients due to the increased catabolic state often associated with acute severe illness and the frequent presence of prior chronic wasting conditions. Nutritional support is thus an important part of the management of these patients. Over the years, enteral nutrition (EN) has gained considerable popularity, due to its favorable effects on the digestive tract and its lower cost and rate of complications compared to parenteral nutrition. However, clinicians caring for ICU patients are often faced with contradictory data and difficult decisions when having to determine the optimal timing and modalities of EN administration, estimation of patient requirements, and choice of formulas. The purpose of this paper is to provide practical guidelines on these various aspects of enteral nutritional support, based on presently available evidence.

Outcome of Critically Ill Allogeneic Hematopoietic Stem-Cell Transplantation Recipients: A Reappraisal of Indications for Organ Failure Supports

PURPOSE Because the overall outcome of critically ill hematologic patients has improved, we evaluated the short-term and long-term outcomes of the poor risk subgroup of allogeneic hematopoietic stem-cell transplantation (HSCT) recipients requiring admission to the intensive care unit (ICU). PATIENTS AND METHODS This was a retrospective multicenter study of allogeneic HSCT recipients admitted to the ICU between 1997 and 2003. RESULTS Two hundred nine critically ill allogeneic HSCT recipients were included in the study. Admission in the ICU occurred during the engraftment period (< or = 30 days after transplantation) for 70 of the patients and after the engraftment period for 139 patients. The overall in-ICU, in-hospital, 6-month, and 1-year survival rates were 48.3%, 32.5%, 27.2%, and 21%, respectively. Mechanical ventilation was required in 122 patients and led to a dramatic decrease in survival rates, resulting in in-ICU, in-hospital, 6-month, and 1-year survival rates of 18%, 15.6%, 14%, and 10.6%, respectively. Mechanical ventilation, elevated bilirubin level, and corticosteroid treatment for the indication of active graft-versus-host disease (GVHD) were independent predictors of death in the whole cohort. In the subgroup of patients requiring mechanical ventilation, associated organ failures, such as shock and liver dysfunction, were independent predictors of death. ICU admission during engraftment period was associated with acceptable outcome in mechanically ventilated patients, whereas patients with late complications of HSCT in the setting of active GVHD had a poor outcome. CONCLUSION Extensive unlimited intensive care support is justified for allogeneic HSCT recipients with complications occurring during the engraftment period. Conversely, initiation or maintenance of mechanical ventilation is questionable in the setting of active GVHD.

Prognostic factors for neutropenic patients in an intensive care unit : Respective roles of underlying malignancies and acute organ failures

The admission of neutropenic patients to an intensive care unit (ICU) is still controversial, especially if mechanical ventilation is required. To avoid useless stays in ICU, the evaluation of the respective role of the underlying malignancy and acute organ failures might be useful for better definition of the categories of patients who could benefit from aggressive ICU support. For this purpose, we carried out a retrospective study of the charts of 107 consecutive neutropenic patients admitted to an ICU in a comprehensive cancer centre over a four-year period. The following characteristics were recorded within 24 h of admission: patient data, characteristics of neutropenia and the underlying malignancy, the type and number of organ system failures (OSFs) and simplified acute physiological scores (SAPS and SAPS II). The impact of each variable on outcome in the ICU was studied by univariate and multivariate (logistic regression) analysis. 59 patients died in the ICU (mortality rate: 55%). Patients with a haematological malignancy (n = 57, 53%) were more likely to experience respiratory failure, an underlying malignancy deemed rapidly fatal, and to have longer lasting neutropenia than patients with a solid tumour (n = 50, 47%). However, the mortality rate did not differ in the two groups (haematological malignancy 61% versus solid tumour 48%, p = 0.16). Respiratory and cardiovascular organ failure (p < 0.001 for both) correlated with mortality in the ICU. In the multiple logistic regression model, only the number of organ system failures and respiratory failure remained predictive of ICU mortality. In conclusion, the characteristics of the underlying malignancy are not relevant when deciding whether or not neutropenic patients should be admitted to an ICU. The main risk factors for death in an ICU are the number of organ failures on admission, and among them the presence of respiratory failure.

Prevention of intravascular catheter-related infection with newer chlorhexidine-silver sulfadiazine-coated catheters: a randomized controlled trial

BackgroundThe indication of antiseptic-coated catheters remains debated.ObjectiveTo test the ability of the new generation of chlorhexidine-silver and sulfadiazine-coated catheters, with enhanced antiseptic coating, to reduce the risk of central venous catheter (CVC)-related infection in ICU patients.DesignMulticentre randomized double-blind trial.Patients and settingA total of 397 patients from 14 ICUs of university hospitals in France.InterventionPatients were randomized to receive an antiseptic-coated catheter (ACC) or a standard non-coated catheter (NCC).MeasurementsIncidence of CVC-related infection.ResultsOf 367 patients having a successful catheter insertion, 363 were analysed (175 NCC and 188 ACC). Patients had one (NCC=162, ACC=180) or more (NCC=13, ACC=11) CVC inserted. The two groups were similar for insertion site [subclavian (64 vs 69)] or jugular (36 vs 31%)], and type of catheters (single-lumen 18 vs 18%; double-lumen 82 vs 82%), and mean (median) duration of catheterisation [12.0±11.7 (9) vs 10.5±8.8 (8) days in the NCC and ACC groups, respectively]. Significant colonisation of the catheter occurred in 23 (13.1%) and 7 (3.7%) patients, respectively, in the NCC and ACC groups (11 vs 3.6 per 1000 catheter-days; p=0.01); CVC-related infection (bloodstream infection) occurred in 10 (5) and 4 (3) patients in the NCC and CC groups, respectively (5.2 vs 2 per 1000 catheter days; p=0.10).ConclusionsIn the context of a low baseline infection rate, ACC were associated with a significant reduction of catheter colonisation and a trend to reduction of infection episodes, but not of bloodstream infection.

Enteral nutrition in intensive care patients: a practical approach. Working Group on Nutrition and Metabolism, ESICM. European Society of Intensive Care Medicine.

Severe protein-calorie malnutrition is a major problem in many intensive care (ICU) patients due to the increased catabolic state often associated with acute severe illness and the frequent presence of prior chronic wasting conditions. Nutritional support is thus an important part of the management of these patients. Over the years, enteral nutrition (EN) has gained considerable popularity, due to its favorable effects on the digestive tract and its lower cost and rate of complications compared to parenteral nutrition. However, clinicians caring for ICU patients are often faced with contradictory data and difficult decisions when having to determine the optimal timing and modalities of EN administration, estimation of patient requirements, and choice of formulas. The purpose of this paper is to provide practical guidelines on these various aspects of enteral nutritional support, based on presently available evidence.

Severity-of-illness scores for neutropenic cancer patients in an intensive care unit: Which is the best predictor? Do multiple assessment times improve the predictive value

OBJECTIVES To use three severity of illness scores to estimate the probability of hospital mortality among patients with cancer and neutropenia; to compare the performance of these scores, calculated at admission to an intensive care unit (ICU); and to test the improvement in estimation obtained by taking into account the first 72-hr period. DESIGN Collection of data for every neutropenic patient hospitalized in the ICU during a 4-yr period. SETTING A comprehensive cancer center. PATIENTS Ninety-four patients were neutropenic at ICU admission. Their vital status was measured at hospital discharge. MEASUREMENTS AND MAIN RESULTS The new Simplified Acute Physiology Score (SAPS) II improved the estimation of hospital mortality compared with the original SAPS score. Using a simple score based on the number of acute organ system failures (OSFs) to classify the patients, good discrimination between survivors and nonsurvivors was observed (area under the receiver operating characteristic curves, 79 +/- 5 [SD] %). The relationship between successive scores and outcome was explored using recursive partitioning. Patients were first classified according to their OSF value on the first day of hospitalization in the ICU with a cutoff of two organ failures, and classification was then improved by taking into account the OSF score on the third day. CONCLUSIONS For cancer patients hospitalized in an ICU for a neutropenic episode, the severity of illness and the risk of death can be accurately assessed by the SAPS II score and the number of acute organ failures at admission. The OSF values on the first and third days of hospitalization both provided information, allowing the classification of patients into groups with different probabilities of hospital mortality.