Rebecca Hamidfar-Roy

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).

Use of intensive care in patients with nonresectable lung cancer.

BACKGROUND Admission of patients with lung cancer to the ICU has been criticized. We evaluated whether ICU admission improved 3-month survival in patients with nonresectable lung cancer. Factors associated with survival were identified. METHODS A retrospective study was conducted in consecutive nonsurgical patients with lung cancer admitted to three ICUs in France between 2000 and 2007, 2005 and 2007, and 2005 and 2006. RESULTS We included 103 patients with a median (interquartile range) Simplified Acute Physiology Score II of 33 (25-46) and logistic organ dysfunction (LOD) score of 3 (1-4). Invasive mechanical ventilation was required in 41 (40%) patients. Sixty-three (61%) patients had metastasis and 26 (25%) an Eastern Cooperative Oncology Group performance status (ECOG-PS) > 2. The reason for ICU admission was acute respiratory failure in 58 (56%) patients. Three-month survival rate was 37% (95% CI, 28%-46%). By multivariate analysis, variables associated with mortality were ECOG-PS > 2 (hazard ratio [HR], 2.65; 95% CI, 1.43-4.88), metastasis at admission (HR, 1.90; 95% CI, 1.08-3.33), and worse LOD score (HR, 1.19; 95% CI, 1.08-1.32). An LOD score decrease over the first 72 h was associated with survival. CONCLUSIONS Survival in nonsurgical patients with lung cancer requiring ICU admission was 37% after 90 days. Our results provide additional evidence that ICU management may be appropriate in patients with nonresectable lung cancer and organ failure.

Antifungal use influences Candida species distribution and susceptibility in the intensive care unit

OBJECTIVES Antifungal prescription practices have changed over the last decade, and the impact of these changes is unclear. Our objective here was to evaluate the effect of antifungal drug use on the distribution and drug susceptibility of Candida spp. in a French intensive care unit (ICU). METHODS Antifungal drug use was measured as the number of defined daily doses per 1000 hospital days (DDDs/1000HD). The distribution of Candida spp. over a 6 year period (2004-09) and the MICs of antifungal drugs over 2007-09 were determined. Statistical analyses were performed to assess relationships between antifungal drug use, Candida spp. distribution and MIC changes over time. RESULTS Of 26,450 samples from 3391 patients, 1511 were positive for Candida spp. Candida albicans predominated (52.5%), followed by Candida glabrata (16.6%) and Candida parapsilosis (7.5%). C. parapsilosis increased significantly, from 5.7% in 2004 to 12.5% in 2009 (P = 0.0005). Caspofungin use increased significantly between 2004 (17.9 DDDs/1000HD) and 2009 (69.9 DDDs/1000HD) (P < 0.0001). Between 2007 and 2009, the increase in caspofungin use correlated significantly with the increase in caspofungin MICs displayed by C. parapsilosis (P < 0.0001) and C. glabrata (P = 0.03). Amphotericin B consumption changed over time and correlated with an increase in amphotericin B MICs for C. albicans (P = 0.0002) and C. glabrata (P = 0.0005). Significant declines occurred in both fluconazole use (P < 0.0001) and fluconazole MICs of C. albicans (P < 0.001) CONCLUSIONS Antifungal drug use in the ICU is associated with major changes in the distribution and drug susceptibility of Candida spp.

New materials and devices for preventing catheter-related infections

Catheters are the leading source of bloodstream infections for patients in the intensive care unit (ICU). Comprehensive unit-based programs have proven to be effective in decreasing catheter-related bloodstream infections (CR-BSIs). ICU rates of CR-BSI higher than 2 per 1,000 catheter-days are no longer acceptable. The locally adapted list of preventive measures should include skin antisepsis with an alcoholic preparation, maximal barrier precautions, a strict catheter maintenance policy, and removal of unnecessary catheters. The development of new technologies capable of further decreasing the now low CR-BSI rate is a major challenge. Recently, new materials that decrease the risk of skin-to-vein bacterial migration, such as new antiseptic dressings, were extensively tested. Antimicrobial-coated catheters can prevent CR-BSI but have a theoretical risk of selecting resistant bacteria. An antimicrobial or antiseptic lock may prevent bacterial migration from the hub to the bloodstream. This review discusses the available knowledge about these new technologies.

Therapeutic impact and diagnostic performance of multiplex PCR in patients with malignancies and suspected sepsis.

OBJECTIVES New molecular methods allow rapid pathogen detection in patients with sepsis, but their impact on treatment decisions remains to be established. We evaluated the therapeutic usefulness of multiplex PCR testing in patients with cancer and sepsis. METHODS 110 patients with cancer and sepsis were included prospectively and underwent LightCycler® SeptiFast (LC-SF) multiplex PCR testing in addition to standard tests. Two independent panels of experts assessed the diagnosis in each patient based on medical record data; only one panel had the LC-SF results. The final diagnosis established by a third panel was the reference standard. RESULTS The final diagnosis was documented sepsis in 50 patients (55 microorganisms), undocumented sepsis in 54, and non-infectious disease in 6. LC-SF detected 17/32 pathogens recovered from blood cultures (BC) and 11/23 pathogens not recovered from BC; 12 microorganisms were detected neither by BC nor by LC-SF. LC-SF produced false-positive results in 10 cases. The LC-SF results would have significantly improved treatment in 11 (10%) patients and prompted immediate antimicrobial therapy not given initially in 3 patients. CONCLUSIONS In cancer patients with suspected sepsis, LC-SF detected 11/55 (20%) true pathogens not recovered from BCs and would have improved the initial management in 11/110 (10%) patients.

New challenges in the diagnosis, management, and prevention of central venous catheter-related infections.

Catheters are the leading source of bloodstream infections in critically ill patients. Because the clinical signs of infection are nonspecific, such infections are overly suspected, which results in unnecessary removal of catheters. A conservative approach might be attempted in mild infections, whereas catheters should always be removed in cases of severe sepsis or septic shock. Nowadays, comprehensive unit-based improvement programs are effective to reduce catheter-related bloodstream infections (CR-BSIs). Rates of CR-BSI higher than 2 per 1000 catheter-days are no longer acceptable. A locally adapted checklist of preventive measures should include cutaneous antisepsis with alcoholic preparation, maximal barrier precaution, strict policy of catheter maintenance, and ablation of useless catheters. Antiseptic dressings and, to a lesser extent, antimicrobial-coated catheters, might be added to the prevention strategies if the level of infections remains high despite implementation of a prevention program. In the case of CR-BSI in intensive care units (ICUs), the catheter should be removed. In the case of persistence of fever or positive blood cultures after 3 days, inadequate antibiotic therapy, endocarditis, or thrombophlebitis should be ruled out.

Pulmonary embolism in mechanically ventilated patients requiring computed tomography: Prevalence, risk factors, and outcome.

Objective:To estimate the rate of pulmonary embolism among mechanically ventilated patients and its association with deep venous thrombosis. Design:Prospective cohort study. Setting:Medical intensive care unit of a university-affiliated teaching hospital. Patients:Inclusion criteria: mechanically ventilated patients requiring a thoracic contrast-enhanced computed tomography scan for any medical reason. Exclusion criteria: a diagnosis of pulmonary embolism before intensive care unit admission, an allergy to contrast agents, and age younger than 18 yrs. Interventions:All the mechanically ventilated patients requiring a thoracic computed tomography underwent the standard imaging protocol for pulmonary embolism detection. Therapeutic anticoagulation was given immediately after pulmonary embolism diagnosis. All the included patients underwent a compression ultrasound of the four limbs within 48 hrs after the computed tomography scan to detect deep venous thrombosis. Results:Of 176 included patients, 33 (18.7%) had pulmonary embolism diagnosed by computed tomography, including 20 (61%) with no clinical suspicion of pulmonary embolism. By multiple logistic regression, independent risk factors for pulmonary embolism were male gender, high body mass index, history of cancer, past medical history of deep venous thrombosis, coma, and high platelet count. Previous prophylactic anticoagulant use was not a risk factor for pulmonary embolism. Of the 176 patients, 35 (19.9%) had deep venous thrombosis by compression ultrasonography, including 20 (57.1%) in the lower limbs and 24 (68.6%) related to central venous catheters. Of the 33 pulmonary embolisms, 11 (33.3%) were associated with deep venous thrombosis. The pulmonary embolism risk was increased by lower-limb deep venous thrombosis (odds ratio 4.0; 95% confidence interval 1.6–10) but not upper-limb deep venous thrombosis (odds ratio 0.6; 95% confidence interval 0.1–2.9). Crude comparison of patients with and without pulmonary embolism shows no difference in length of stay or mortality. Conclusions:In mechanically ventilated patients who needed a computed tomography, pulmonary embolism was more common than expected. Patients diagnosed with pulmonary embolism were all treated with therapeutic anticoagulation, and their intensive care unit or hospital mortality was not impacted by the pulmonary embolism occurrence. These results invite further research into early screening and therapeutic anticoagulation of pulmonary embolism in critically ill patients.

Venous thromboembolism in the ICU: main characteristics, diagnosis and thromboprophylaxis

Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep venous thrombosis (DVT), is a common and severe complication of critical illness. Although well documented in the general population, the prevalence of PE is less known in the ICU, where it is more difficult to diagnose and to treat. Critically ill patients are at high risk of VTE because they combine both general risk factors together with specific ICU risk factors of VTE, like sedation, immobilization, vasopressors or central venous catheter. Compression ultrasonography and computed tomography (CT) scan are the primary tools to diagnose DVT and PE, respectively, in the ICU. CT scan, as well as transesophageal echography, are good for evaluating the severity of PE. Thromboprophylaxis is needed in all ICU patients, mainly with low molecular weight heparin, such as fragmine, which can be used even in cases of non-severe renal failure. Mechanical thromboprophylaxis has to be used if anticoagulation is not possible. Nevertheless, VTE can occur despite well-conducted thromboprophylaxis.