François Blot

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.

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.

Diagnostic Strategy for Hematology and Oncology Patients with Acute Respiratory Failure Randomized Controlled Trial

RATIONALE Respiratory events are common in hematology and oncology patients and manifest as hypoxemic acute respiratory failure (ARF) in up to half the cases. Identifying the cause of ARF is crucial. Fiberoptic bronchoscopy with bronchoalveolar lavage (FO-BAL) is an invasive test that may cause respiratory deterioration. Recent noninvasive diagnostic tests may have modified the risk/benefit ratio of FO-BAL. OBJECTIVES To determine whether FO-BAL in cancer patients with ARF increased the need for intubation and whether noninvasive testing alone was not inferior to noninvasive testing plus FO-BAL. METHODS We performed a multicenter randomized controlled trial with sample size calculations for both end points. Patients with cancer and ARF of unknown cause who were not receiving ventilatory support at intensive care unit admission were randomized to early FO-BAL plus noninvasive tests (n = 113) or noninvasive tests only (n = 106). The primary end point was the number of patients needing intubation and mechanical ventilation. The major secondary end point was the number of patients with no identified cause of ARF. MEASUREMENTS AND MAIN RESULTS The need for mechanical ventilation was not significantly greater in the FO-BAL group than in the noninvasive group (35.4 vs. 38.7%; P = 0.62). The proportion of patients with no diagnosis was not smaller in the noninvasive group (21.7 vs. 20.4%; difference, -1.3% [-10.4 to 7.7]). CONCLUSIONS FO-BAL performed in the intensive care unit did not significantly increase intubation requirements in critically ill cancer patients with ARF. Noninvasive testing alone was not inferior to noninvasive testing plus FO-BAL for identifying the cause of ARF. Clinical trial registered with www.clinicaltrials.gov (NCT00248443).

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.

Optimization of Hyperthermic Intraperitoneal Chemotherapy With Oxaliplatin Plus Irinotecan at 43°C After Compete Cytoreductive Surgery: Mortality and Morbidity in 106 Consecutive Patients

BackgroundPeritoneal carcinomatosis (PC), which has hitherto been regarded as a lethal entity, can now be cured with surgery (treating macroscopic tumor seeding) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) (treating residual microscopic disease). The purpose of this study was to analyze the morbidity and mortality of a particular approach associating optimal (R0–R1) cytoreduction, optimal HIPEC combining oxaliplatin and irinotecan, and an optimal homogeneous intraperitoneal temperature of 43°C.MethodsA total of 106 consecutive patients were included in this prospective phase 2 study. After complete resection of the PC, HIPEC was performed by the Coliseum technique with oxaliplatin (360 mg/m2) combined with irinotecan (360 mg/m2) in 2 L/m2 of 5% dextrose, over 30 minutes at a real intraperitoneal temperature of 43°C. During the hour preceding HIPEC, patients received 5-fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) intravenously, resulting in tritherapy.ResultsPostoperative mortality and morbidity rates were 4% and 66%, respectively. The most frequent complications were digestive fistula (24%), lung infection (16%), and severe hematological toxicity (11%). Statistical correlation was evidenced between morbidity and the carcinomatosis score (P = .0008), the number of resected organs (P = .0001), the duration of surgery (P = .0001), and blood loss (P = .0001).ConclusionsThis new approach, optimized in three respects (complete cytoreduction, combination oxaliplatin with irinotecan, and high temperature) has resulted in a relatively high but acceptable incidence of adverse events considering the expected advantage for survival.

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.

Early tracheotomy in neutropenic, mechanically ventilated patients: rationale and results of a pilot study

Despite substantial advances in the management of such patients, the prognosis of ventilated neutropenic patients remains grim. The objective of our study was to evaluate the benefit of tracheotomy in this category of patients, in terms of mortality while they were in the intensive-care unit and nosocomial pneumonias. The charts of 53 consecutive, ventilated, neutropenic patients, or those destined to be imminently neutropenic, admitted to our intensive-care unit during a 4-year period, have been retrospectively reviewed. Tracheotomy was performed at the bedside or in the operating room: 20 patients underwent tracheotomy within 48 h of mechanical ventilation (ET group), while 33 were tracheotomized later or remained intubated (INT group). The two groups were comparable with regard to the underlying disease, respiratory failure, mechanical ventilation patterns and severity scores, but neutropenia was more profound in the ET group. Mortality while in the intensivecare unit was similar (ET:70%; INT:78.8%). However, the survival curves showed a trend towards longer survival in the ET group, even after adjustment for the degree of neutropenia (log-rank test: P=0.07). The incidence of pneumonias was similar in both groups. No major complications of tracheotomy were reported. These findings suggest that a tracheotomy could be proposed for neutropenic patients requiring mechanical ventilation, in order to prologn their survival beyond the end of the neutropenic period. A prospective study is underway to confirm these preliminary results.

Intensive care in patients with lung cancer: a multinational study

BACKGROUND Detailed information about lung cancer patients requiring admission to intensive care units (ICUs) is mostly restricted to single-center studies. Our aim was to evaluate the clinical characteristics and outcomes of lung cancer patients admitted to ICUs. PATIENTS AND METHODS Prospective multicenter study in 449 patients with lung cancer (small cell, n = 55; non-small cell, n = 394) admitted to 22 ICUs in six countries in Europe and South America during 2011. Multivariate Cox proportional hazards frailty models were built to identify characteristics associated with 30-day and 6-month mortality. RESULTS Most of the patients (71%) had newly diagnosed cancer. Cancer-related complications occurred in 56% of patients; the most common was tumoral airway involvement (26%). Ventilatory support was required in 53% of patients. Overall hospital, 30-day, and 6-month mortality rates were 39%, 41%, and 55%, respectively. After adjustment for type of admission and early treatment-limitation decisions, determinants of mortality were organ dysfunction severity, poor performance status (PS), recurrent/progressive cancer, and cancer-related complications. Mortality rates were far lower in the patient subset with nonrecurrent/progressive cancer and a good PS, even those with sepsis, multiple organ dysfunctions, and need for ventilatory support. Mortality was also lower in high-volume centers. Poor PS predicted failure to receive the initially planned cancer treatment after hospital discharge. CONCLUSIONS ICU admission was associated with meaningful survival in lung cancer patients with good PS and non-recurrent/progressive disease. Conversely, mortality rates were very high in patients not fit for anticancer treatment and poor PS. In this subgroup, palliative care may be the best option.BACKGROUND Detailed information about lung cancer patients requiring admission to intensive care units (ICUs) is mostly restricted to single-center studies. Our aim was to evaluate the clinical characteristics and outcomes of lung cancer patients admitted to ICUs. PATIENTS AND METHODS Prospective multicenter study in 449 patients with lung cancer (small cell, n = 55; non-small cell, n = 394) admitted to 22 ICUs in six countries in Europe and South America during 2011. Multivariate Cox proportional hazards frailty models were built to identify characteristics associated with 30-day and 6-month mortality. RESULTS Most of the patients (71%) had newly diagnosed cancer. Cancer-related complications occurred in 56% of patients; the most common was tumoral airway involvement (26%). Ventilatory support was required in 53% of patients. Overall hospital, 30-day, and 6-month mortality rates were 39%, 41%, and 55%, respectively. After adjustment for type of admission and early treatment-limitation decisions, determinants of mortality were organ dysfunction severity, poor performance status (PS), recurrent/progressive cancer, and cancer-related complications. Mortality rates were far lower in the patient subset with nonrecurrent/progressive cancer and a good PS, even those with sepsis, multiple organ dysfunctions, and need for ventilatory support. Mortality was also lower in high-volume centers. Poor PS predicted failure to receive the initially planned cancer treatment after hospital discharge. CONCLUSIONS ICU admission was associated with meaningful survival in lung cancer patients with good PS and non-recurrent/progressive disease. Conversely, mortality rates were very high in patients not fit for anticancer treatment and poor PS. In this subgroup, palliative care may be the best option.

Poor prognosis nonseminomatous germ-cell tumours (NSGCTs): should chemotherapy doses be reduced at first cycle to prevent acute respiratory distress syndrome in patients with multiple lung metastases?

BACKGROUND Patients with extensive lung metastases from nonseminomatous germ-cell tumours (NSGCTs) and dyspnoea at presentation are at high risk of acute respiratory distress syndrome (ARDS) and death within the first weeks after chemotherapy induction. This syndrome is linked to acute intra-alveolar haemorrhage related to early tumour necrosis, which in turn, can be complicated by pulmonary infection promoted by neutropenia. The management of these patients was modified at Institut Gustave Roussy in 1997 to try to avoid this complication. PATIENTS AND METHODS Data concerning all patients with lung metastases from NSGCT and dyspnoea or a partial pressure of oxygen (pO(2)) <80 mmHg treated from 1980 to 2006 in our institution were collected. Patients were treated in a specialised intensive care unit. From 1980 to 1997, the first chemotherapy cycle consisted in a full-dose regimen. After 1997, a 3-day reduced induction regimen of EP (cisplatin 20 mg/m(2)/day and etoposide 100 mg/m(2)/day) was used, with bleomycin and two additional days of EP being postponed to day 15, with the regular BEP regimen being started at day 21. RESULTS Twenty-five patients with poor-risk disseminated NSGCT according to the International Germ Cell Consensus Classification Group had extensive lung metastases plus dyspnoea at presentation (n = 6), a pO(2) <80 mmHg (n = 2), or both criteria (n = 17). Median human chorionic gonadotrophin was 200 000 UI (range 11-8 920 000), and 18 of 25 (72%) patients also had nonpulmonary visceral metastases. During the 1980-1997 period, 13 of 15 patients (87%) developed ARDS, 10 of whom died, and only 4 of 15 (27%) patients were long-term survivors. In contrast, during the 1997-2006 period, only 3 of 10 patients (30%) developed ARDS (P = 0.01), 2 of whom died, and 4 of 10 (40%) eventually survived. CONCLUSION Initial reduction of chemotherapy doses during the first cycle of chemotherapy for poor prognosis NSGCT with extensive lung metastases seems to prevent the risk of early death due to ARDS.

Severity of illness scores: are they useful in febrile neutropenic adult patients in hematology wards? A prospective multicenter study.

Objective To assess the prognostic value of two severity of illness scores, commonly used for critically ill patients, Simplified Acute Physiology Score (SAPS II) and Organ Dysfunctions and Infection (ODIN), in predicting mortality in febrile neutropenic patients in hematology wards. Design A 2-month prospective multicenter study. Setting Thirty-six hematologic and/or stem cell transplant units in France. Patients All adult patients with a first febrile neutropenic episode (polymorphonuclear cells <500/mm3) were included. Interventions SAPS II was calculated on day 1 of fever, and ODIN on days 1 and 8. The end point was the mortality rate on day 28. Measurements and Main Results Twenty-eight (6.6%) of the 421 patients included died before day 28. The mortality rate predicted by SAPS II was 23.8%, indicating a poor calibration. The SAPS II score at day 1 was greater in nonsurvivors than in survivors (44 ± 11 vs. 38 ± 7, p < .0001), as was the number of patients with one or more organ failures at day 1 (14 vs. 2%, p < .0001), and day 8 (42 vs. 3%, p < .0001). The pattern of change in the scores over the first 8 days differed significantly between survivors and nonsurvivors. In multivariate analysis, only ODIN on day 1 and day 8, and spontaneous neutropenia were independent predictors for death. Conclusions SAPS II and ODIN scores are inaccurate for predicting individual outcome of febrile neutropenic patients in hematology wards. Serial measurements of these scores during the first week of hospitalization could be more accurate than a single measurement. Besides severity scores and organ failures, the type of neutropenia is at least as important in assessing the prognosis.