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).

Hydrocortisone therapy for patients with multiple trauma: the randomized controlled HYPOLYTE study.

CONTEXT: The role of stress-dose hydrocortisone in the management of trauma patients is currently unknown. OBJECTIVE: To test the efficacy of hydrocortisone therapy in trauma patients. DESIGN, SETTING, AND PATIENTS: Multicenter, randomized, double-blind, placebo-controlled HYPOLYTE (Hydrocortisone Polytraumatise) study. From November 2006 to August 2009, 150 patients with severe trauma were included in 7 intensive care units in France. INTERVENTION: Patients were randomly assigned to a continuous intravenous infusion of either hydrocortisone (200 mg/d for 5 days, followed by 100 mg on day 6 and 50 mg on day 7) or placebo. The treatment was stopped if patients had an appropriate adrenal response. MAIN OUTCOME MEASURE: Hospital-acquired pneumonia within 28 days. Secondary outcomes included the duration of mechanical ventilation, hyponatremia, and death. RESULTS: One patient withdrew consent. An intention-to-treat (ITT) analysis included the 149 patients, a modified ITT analysis included 113 patients with corticosteroid insufficiency. In the ITT analysis, 26 of 73 patients (35.6%) treated with hydrocortisone and 39 of 76 patients (51.3%) receiving placebo developed hospital-acquired pneumonia by day 28 (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.30-0.83; P = .007). In the modified ITT analysis, 20 of 56 patients (35.7%) in the hydrocortisone group and 31 of 57 patients (54.4%) in the placebo group developed hospital-acquired pneumonia by day 28 (HR, 0.47; 95% CI, 0.25-0.86; P = .01). Mechanical ventilation-free days increased with hydrocortisone by 4 days (95% CI, 2-7; P = .001) in the ITT analysis and 6 days (95% CI, 2-11; P < .001) in the modified ITT analysis. Hyponatremia was observed in 7 of 76 (9.2%) in the placebo group vs none in the hydrocortisone group (absolute difference, -9%; 95% CI, -16% to -3%; P = .01). Four of 76 patients (5.3%) in the placebo group and 6 of 73 (8.2%) in the hydrocortisone group died (absolute difference, 3%; 95% CI, -5% to 11%; P = .44). CONCLUSION: In intubated trauma patients, the use of an intravenous stress-dose of hydrocortisone, compared with placebo, resulted in a decreased risk of hospital-acquired pneumonia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00563303.

Patient-related factors and circumstances surrounding decisions to forego life-sustaining treatment, including intensive care unit admission refusal.

OBJECTIVE: To assess decisions to forego life-sustaining treatment (LST) in patients too sick for intensive care unit (ICU) admission, comparatively to patients admitted to the ICU. DESIGN: Prospective observational cohort study. SETTING: A medical-surgical ICU. PATIENTS: Consecutive patients referred to the ICU during a one-yr period. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Of 898 triaged patients, 147 were deemed too well to benefit from ICU admission. Decisions to forego LST were made in 148 of 666 (22.2%) admitted patients and in all 85 patients deemed too sick for ICU admission. Independent predictors of decisions to forego LST at ICU refusal rather than after ICU admission were: age; underlying disease; living in an institution; preexisting cognitive impairment; admission for medical reasons; and acute cardiac failure, acute central neurologic illness, or sepsis. Hospital mortality after decisions to forego LST was not significantly different in refused and admitted patients (77.5% vs. 86.5%; p = .1). Decisions to forego LST were made via telephone in 58.8% of refused patients and none of the admitted patients. Nurses caring for the patient had no direct contact with the ICU physicians for 62.3% of the decisions in refused patients, whereas meetings between nurses and physicians occurred in 70.3% of decisions to forego LST in the ICU. Patients or relatives were involved in 28.2% of decisions to forego LST at ICU refusal compared with 78.4% of decisions to forego LST in ICU patients (p < .001). CONCLUSIONS: All patients deemed too sick for ICU admission had decisions to forego LST. These decisions were made without direct patient examination in two-thirds of refused patients (vs. none of admitted patients) and were associated with less involvement of nurses and relatives compared with decisions in admitted patients. Further work is needed to improve decisions to forego LST made under the distinctive circumstances of triage.

Diagnostic bronchoscopy in hematology and oncology patients with acute respiratory failure: prospective multicenter data.

OBJECTIVE: To describe the diagnostic yields of test strategies with and without fiberoptic bronchoscopy and bronchoalveolar lavage (FO-BAL), as well as outcomes, in cancer patients with acute respiratory failure (ARF). DESIGN: Prospective observational study. SETTING: Fifteen intensive care units in France. PATIENTS: In all, 148 cancer patients, including 45 bone marrow transplant recipients (27 allogeneic, 18 autologous) with hypoxemic ARF. INTERVENTION: None. RESULTS: Overall, 146 causes of ARF were identified in 128 patients (97 [66.4%] pulmonary infections). The cause of ARF was identified in 50.5% of the 101 patients who underwent FO-BAL and in 66.7% of the other patients. FO-BAL was the only conclusive test in 34 (33.7%) of the 101 investigated patients. Respiratory status deterioration after FO-BAL occurred in 22 of 45 (48.9%) nonintubated patients, including 16 (35.5%) patients who required ventilatory support. Hospital mortality was 55.4% (82 deaths) overall and was not significantly different in the groups with and without FO-BAL. By multivariate analysis, mortality was affected by characteristics of the malignancy (remission, allogeneic bone marrow transplantation), cause of ARF (ARF during neutropenia recovery, cause not identified), and need for life-sustaining treatments (mechanical ventilation and vasopressors). CONCLUSION: In critically ill cancer patients with ARF, a diagnostic strategy that does not include FO-BAL may be as effective as FO-BAL without exposing the patients to respiratory status deterioration.

Short-term effects of prone position in chronic obstructive pulmonary disease patients with severe acute hypoxemic and hypercapnic respiratory failure.

OBJECTIVE: To assess the short-term effects of prone positioning (PP) in chronic obstructive pulmonary disease (COPD) patients with severe hypoxemic and hypercapnic respiratory failure requiring invasive mechanical ventilation. DESIGN AND SETTING: Prospective observational study in the general intensive care unit of a university-affiliated hospital. PATIENTS: 11 consecutive COPD patients with persistent hypoxemia (PaO2/FIO2 < or = 200 mmHg with FIO2 > or = 0.6) and hypercapnia requiring invasive mechanical ventilation. Patients with adult respiratory distress syndrome or left ventricular failure were excluded. Mean age was 73+/-11 years, mean weight 86+/-31 kg, mean SAPS II 53+/-10, and ICU mortality 36%. INTERVENTIONS: Patients were turned every 6 h. MEASUREMENTS AND RESULTS: A response to PP (20% or greater PaO2/FIO2 increase) was noted in 9 (83%) patients. Blood gases were measured in the PP and supine (SP) positions 3 h after each turn, for 36 h, yielding six measurement sets (SP1, PP1, SP2, PP2, SP3, and PP3). PaO2/FIO2 was significantly better in PP: 190+/-26 vs. 113+/-9 mmHg for PP1/SP1, 175+/-22 vs. 135+/-16 mmHg for PP2/SP2, and 199+/-24 vs. 151+/-13 mmHg for PP3/SP3. After PP1 PaO2/FIO2 remained significantly improved, and the PaO2/FIO2 improvement from SP1 to SP2 was linearly related to PaO2/FIO2 during PP1 (r=0.8). The tracheal aspirate volume improved significantly from SP1 to PP1. PaCO2 was not significantly affected by position. CONCLUSIONS: PP was effective in treating severe hypoxemia in COPD patients. The first turn in PP was associated with increased tracheal aspirate.

Analytical performances of a new enzymatic assay for hemoglobin A1c.

BACKGROUND: HbA1c is considered the gold standard for the follow-up of diabetic patients and a new diagnostic tool for diabetes mellitus, which implies the availability of reliable assay methods. We have evaluated a new assay developed by Abbott Laboratories, based on the enzymatic quantification of HbA1c by a fructosyl dipeptide oxidase using Architect analyzers. METHODS: Precision, linearity, correlation with a HPLC method, accuracy and potential impact interferences on HbA1c measurement have been evaluated. RESULTS: Intra-day and between-day CVs were lower than 1.2% and linearity was excellent from 19 mmol/mol (3.9%) to 163 mmol/mol (17.1%). The results were well correlated with those obtained by the HPLC (Variant II device, kit NU - BioRad): HbA1c [Architect, mmol/mol]=0.986×HbA1c [Variant II, mmol/mol]+0.713 (r=0.998, n=109). This method provided consistent results with IFCC titrated quality control samples. Classical interferences in HbA1c assays (i.e. labile HbA1c, carbamylated hemoglobin, triglycerides or bilirubin) did not have an impact on HbA1c quantification by this method. CONCLUSION: This new enzymatic assay proved to be a robust and reliable method for HbA1c measurement suitable for routine practice in clinical chemistry laboratories.

Multiparametric MRI-targeted TRUS prostate biopsies using visual registration.

Prebiopsy multiparametric prostate MRI (mp-MRI), followed by transrectal ultrasound-guided (TRUS-G) target biopsies (TB) of the prostate is a key combination for the diagnosis of clinically significant prostate cancers (CSPCa), to avoid prostate cancer (PCa) overtreatment. Several techniques are available for guiding TB to the suspicious mp-MRI targets, but the simplest, cheapest, and easiest to learn is "cognitive," with visual registration of MRI and TRUS data. This review details the successive steps of the method (target detection, mp-MRI reporting, intermodality fusion, TRUS guidance to target, sampling simulation, sampling, TRUS session reporting, and quality insurance), how to optimize each, and the global indications of mp-MRI-targeted biopsies. We discuss the diagnostic yield of visually-registered TB in comparison with conventional biopsy, and TB performed using other registration methods.

Etomidate increases susceptibility to pneumonia in trauma patients.

PURPOSE: To investigate the impact of etomidate on the rate of hospital-acquired pneumonia (HAP) in trauma patients and the effects of hydrocortisone in etomidate-treated patients. METHODS: This was a sub-study of the HYPOLYTE multi-centre, randomized, double-blind, placebo-controlled trial of hydrocortisone in trauma patients (NCT00563303). Inclusion criterion was trauma patient with mechanical ventilation (MV) of ≥48 h. The use of etomidate was prospectively collected. Endpoints were the results of the cosyntropin test and rate of HAP on day 28 of follow-up. RESULTS: Of the 149 patients enrolled in the study, 95 (64 %) received etomidate within 36 h prior to inclusion. 79 (83 %) of 95 patients receiving etomidate and 34 of the 54 (63 %) not receiving etomidate had corticosteroid insufficiency (p = 0.006). The administration of etomidate did not alter basal cortisolemia (p = 0.73), but it did decrease the delta of cortisolemia at 60 min (p = 0.007). There was a correlation between time from etomidate injection to inclusion in the study and sensitivity to corticotropin (R (2) = 0.19; p = 0.001). Forty-nine (51.6 %) patients with etomidate and 16 (29.6 %) patients without etomidate developed HAP by day 28 (p = 0.009). Etomidate was associated with HAP on day 28 in the multivariate analysis (hazard ratio 2.48; 95 % confidence interval 1.19-5.18; p = 0.016). Duration of MV with or without etomidate was not significantly different (p = 0.278). Among etomidate-exposed patients, 18 (40 %) treated with hydrocortisone developed HAP compared with 31 (62 %) treated with placebo (p = 0.032). Etomidate-exposed patients treated with hydrocortisone had fewer ventilator days (p < 0.001). CONCLUSIONS: Among the patients enrolled in the study, etomidate did not alter basal cortisolemia, but it did decrease reactivity to corticotropin. We suggest that in trauma patients, etomidate is an independent risk factor for HAP and that the administration of hydrocortisone should be considered after etomidate use.

Dual-energy CT angiography of chronic thromboembolic disease: can it help recognize links between the severity of pulmonary arterial obstruction and perfusion defects?

PURPOSE: To evaluate whether dual-energy CT angiography (DE-CTA) could identify links between morphologic and functional abnormalities in chronic pulmonary thromboembolism (CPTE). MATERIALS AND METHODS: Seventeen consecutive patients with CPTE without underlying cardio-respiratory disease were investigated with DE-CTA. Two series of images were generated: (a) transverse diagnostic scans (i.e., contiguous 1-mm thick averaged images from both tubes), and (b) perfusion scans (i.e., images of the iodine content within the microcirculation; 4-mm thick MIPs). Two radiologists evaluated by consensus the presence of: (a) pulmonary vascular features of CPTE and abnormally dilated systemic arteries on diagnostic CT scans, and (b) perfusion defects of embolic type on perfusion scans. RESULTS: Diagnostic examinations showed a total of 166 pulmonary arteries (166/833; 19.9%) with features of CPTE, more frequent at the level of peripheral than central arteries (8.94 vs 0.82; p<0.0001), including severe stenosis with partial (97/166; 58.4%) or complete (20/166; 12.0%) obstruction, webs and bands (37/166; 22.3%), partial filling defects without stenosis (7/166; 4.2%), focal stenosis (4/166; 2.4%) and abrupt vessel narrowing (1/166; 0.6%). Perfusion examinations showed 39 perfusion defects in 8 patients (median number: 4.9; range: 1-11). The most severe pulmonary arterial features of CPTE were seen with a significantly higher frequency in segments with perfusion defects than in segments with normal perfusion (p<0.0001). Enlarged systemic arteries were observed with a significantly higher frequency ipsilateral to lungs with perfusion defects (9/12; 75%) compared with lungs without perfusion defects (5/22; 22.7%) (p=0.004). CONCLUSION: Dual-energy CTA demonstrates links between the severity of pulmonary arterial obstruction and perfusion impairment, influenced by the degree of development of the systemic collateral supply.

Impact of not measuring residual gastric volume in mechanically ventilated patients receiving early enteral feeding: a prospective before-after study.

BACKGROUND: Monitoring of residual gastric volume (RGV) to prevent aspiration is standard practice in mechanically ventilated patients receiving early enteral nutrition (EN). No data are available to support a correlation between RGV and adverse event rates. We evaluated whether not measuring RGV affected EN delivery, vomiting, or risk of nosocomial pneumonia. METHODS: Two hundred and five eligible patients with nasogastric feeding within 48 hours after intubation were included in a 7-day prospective before-after study. Continuous 24-hour nutrition was started at 25 mL/h then increased by 25 mL/h every 6 hours, to 85 mL/h. In both groups, intolerance was treated with erythromycin (250 mg IV/6 h) and a delivery rate decrease to the previously well-tolerated rate. RGV monitoring was used during the first study period (n = 102), but not during the subsequent intervention period (n = 103). Intolerance was defined as RGV >250 mL/6 h or vomiting in the standard-practice group and as vomiting in the intervention group. RESULTS: Groups were similar for baseline characteristics. Median daily volume of enteral feeding was higher in the intervention group (1489; interquartile range [IQR], 1349-1647) than in the controls (1381; IQR, 1151-1591; P = .002). Intolerance occurred in 47 (46.1%) controls and 27 (26.2%) intervention patients (P = .004). The vomiting rate did not differ between controls and intervention group patients (24.5% vs 26.2%, respectively; P = .34), and neither was a difference found for ventilator-associated pneumonia (19.6% vs 18.4%; P = .86). CONCLUSION: Early EN without RGV monitoring in mechanically ventilated patients improves the delivery of enteral feeding and may not increase vomiting or ventilator-associated pneumonia.

Before-after study of a standardized ICU protocol for early enteral feeding in patients turned in the prone position.

BACKGROUNDS & AIMS: To evaluate an intervention for improving the delivery of early enteral nutrition (EN) in patients receiving mechanical ventilation with prone positioning (PP). METHODS: Eligible patients receiving EN and mechanical ventilation in PP were included within 48h after intubation in a before-after study. Patients were semi-recumbent when supine. Intolerance to EN was defined as residual gastric volume greater than 250ml/6h or vomiting. In the before group (n=34), the EN rate was increased by 500ml every 24h up to 2000ml/24h; patients were flat when prone and received erythromycin (250mgIV/6h) to treat intolerance. In the intervention group (n=38), the EN rate was increased by 25ml/h every 6h to 85ml/h, 25 degrees head elevation was used in PP, and prophylactic erythromycin was started at the first turn. RESULTS: Compared to the before group, larger feeding volumes were delivered in the intervention group (median volume per day with PP, 774ml [IQR 513-925] vs. 1170ml [IQR 736-1417]; P<0.001) without increases in residual gastric volume, vomiting, or ventilator-associated pneumonia. CONCLUSION: An intervention including PP with 25 degrees elevation, an increased acceleration to target rate of EN, and erythromycin improved EN delivery.

Salvaging limbs in cases of severe purpura fulminans: advantages of free flaps.

BACKGROUND: Purpura fulminans remains a severe and potentially life-threatening disorder, despite advances in intensive care that have led to a significant increase in the survival rate. One major risk is amputation of extremities. METHODS: The present report concerns a series of four patients (all male; mean age, 19 years) whose lower limb extremities were salvaged by the use of free flaps in the feet. In total, six flaps were performed (mean per patient, 1.7): three latissimus dorsi, two serratus anterior, and one combination latissimus dorsi/serratus anterior. RESULTS: There were no flap failures, and the results are favorable after a mean follow-up of 25.5 months (range, 18 to 34 months), with all patients able to walk normally. CONCLUSION: Although microsurgery of this type has been criticized when performed in cases of purpura fulminans, the authors' series indicates that it can be particularly effective.

Detrimental role of delayed antibiotic administration and penicillin-nonsusceptible strains in adult intensive care unit patients with pneumococcal meningitis: the PNEUMOREA prospective multicenter study.

OBJECTIVE: To identify factors associated with mortality and morbidity among adults admitted to intensive care units (ICUs) for pneumococcal meningitis, particularly the impact of delayed antibiotic administration. DESIGN: We conducted a prospective, multicenter, observational study of 156 consecutive adults hospitalized for pneumococcal meningitis. We analyzed parameters associated with 3-month survival. SETTING: Fifty-six medical and medical-surgical ICUs in France. INTERVENTION: None. RESULTS: Of the 148 strains isolated, 56 (38%) were nonsusceptible to penicillin G. At 3 months after ICU admission, the mortality rate was 33% (51/156), and 34% of survivors (36/105) had neurologic sequelae. Multivariate analysis identified three variables as independently associated with 3-month mortality: Simplified Acute Physiology Score II (odds ration [OR], 1.12; 95% confidence interval [CI], 1.072-1.153; p = .002); isolation of a nonsusceptible strain (OR, 6.83; 95% CI, 2.94-20.8; p < 10(-4)), and an interval of >3 hrs between hospital admission and administration of antibiotics (OR, 14.12; 95% CI, 3.93-50.9; p < 10(-4)). In contrast, a cerebrospinal fluid leukocyte count >10(3) cells/microL had a protective effect (OR, 0.30; 95% CI, 0.10-0.944; p = 0.04). CONCLUSIONS: Independent of severity at the time of ICU admission, isolation of penicillin-nonsusceptible strains and a delay in antibiotic treatment following admission were predictors of mortality among patients with pneumococcal meningitis.