Didier Gruson

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

RATIONALEnRespiratory 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.nnnOBJECTIVESnTo 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.nnnMETHODSnWe 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.nnnMEASUREMENTS AND MAIN RESULTSnThe 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]).nnnCONCLUSIONSnFO-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).

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.

Noninvasive continuous positive airway pressure in neutropenic patients with acute respiratory failure requiring intensive care unit admission.

ObjectiveTo evaluate the tolerance and the efficacy of noninvasive continuous positive airway pressure (CPAP) in severe acute respiratory failure occurring in intensive care unit (ICU) neutropenic patients with hematologic malignancies, and to establish predictive variables of efficacy of this method. DesignProspective study over a 5-yr period. SettingHematologic and medical intensive care unit of a teaching hospital. MethodsAmong 129 neutropenic patients admitted to the ICU, 64 patients presented with febrile acute hypoxemic normocapnic respiratory failure (Pao2/Fio2 ratio <200) and were enrolled. In addition to standard therapy, patients received CPAP with a facial mask. The initial settings of the CPAP were 6 cm H2O positive end-expiratory pressure and Fio2 0.8 (80%). Physiologic measurements were performed at the end of 45 mins of ventilation with first adjustments. CPAP was used with a sequential mode (45 mins/3 hrs). CPAP was efficient if intubation was avoided. ResultsThe setting of CPAP, after adjustments, was as follows: positive end-expiratory pressure 7 ± 1 cm H2O and Fio2 0.7 ± 0.1 (70% ± 10%). For the 64 patients, CPAP was administered for a total of 6 ± 2 hrs during the first 24 hrs. The mean duration of CPAP was 7 ± 3 days. A reduction in respiratory rate to less than 25 breaths/min was achieved in 53% of patients. Pao2/Fio2 ratio increased from 128 ± 32 to 218 ± 28. CPAP was successful in avoiding endotracheal intubation in 16/64 patients. A total of 16 responders and four nonresponders survived. Hepatic failure was a criterion indicating the failure of CPAP1/16 vs. 26/48 (p = .001). In multivariate analysis, two variables were predictive of failure of CPAPSimplified Acute Physiology Score II (58 ± 14 vs. 41 ± 11) and a hepatic failure at the entry into the study. ConclusionCPAP was efficient in 25% of cases. All the responders survived. This noninvasive method was used as a way to avoid mechanical ventilation, which is well correlated with a poor prognosis in neutropenic ICU patients. Further controlled studies are needed to confirm the efficacy of noninvasive CPAP and to evaluate the most appropriate selection of immunocompromised patients.

Utility of fiberoptic bronchoscopy in neutropenic patients admitted to the intensive care unit with pulmonary infiltrates.

Objective To analyze the impact of fiberoptic bronchoscopy and bronchoalveolar lavage (BAL) on guiding the treatment and intensive care unit (ICU) clinical outcome in neutropenic patients with pulmonary infiltrates admitted to the ICU. Design Prospective collection of data. Setting Medical ICU in a teaching hospital. Patients During a 6-yr period, we analyzed the results of 93 fiberoptic bronchoscopies plus BALs performed in 93 consecutive neutropenic ICU patients. We separated the patients into two groups according to the cause of neutropenia (high-dose chemotherapy [n = 41] or stem cell transplantation [SCT; n = 52]). Results Of the 93 BALs, 53 were performed to evaluate diffuse infiltrates and 42 were performed on mechanically ventilated patients. Forty-nine percent of BALs (46 patients) were diagnostic, with a significantly better yield in ICU patients with high-dose chemotherapy-induced neutropenia (26 of 41 BALs). The number of cases of proven infectious pneumonia was significantly higher in this group of ICU neutropenic patients. In patients who underwent SCT, diffuse infiltrates were statistically correlated with a negative result of BAL. Twenty-six patients who underwent diagnostic BALs changed therapy. Sixteen complications (17%) occurred with only two intubations. The overall mortality rate in the ICU and the mortality rate in mechanically ventilated neutropenic patients were 71% and 93%, respectively. In neutropenic patients who underwent SCT, the mortality rate was statistically higher in patients in whom no diagnosis was established. Patients who had a diagnostic BAL that changed therapy did not have an increased probability of survival compared with patients who had a BAL that did not change therapy. Conclusions The use of routine diagnostic BAL in ICU neutropenic patients with pulmonary infiltrates is difficult to establish, even if BAL is helpful in the management of these critically ill patients. BAL in our ICU neutropenic patient population had an acceptable overall diagnostic yield (49%), which was higher in ICU patients with chemotherapy-induced neutropenia. Nevertheless, in the ICU, if BAL had a low complication rate, it had infrequently led to changed treatment and was not associated with improved patient survival.

Sequential use of noninvasive pressure support ventilation for acute exacerbations of COPD

Objectives: To compare the efficacy of noninvasive pressure support ventilation (NIPSV) in acute decompensation in chronic obstructive pulmonary disease (COPD) by means of a bi-level positive airway pressure support system (BiPAP) in a sequential mode with medical therapy alone; to assess the short-term physiologic effects of the device on gas exchange; and to compare patients successfully ventilated with NIPSV with those in whom NIPSV failed. Design: A prospective case series with historically matched control study. Setting: A general intensive care unit (ICU) of a university hospital. Patients: We evaluated the efficacy of administration of NIPSV in 42 COPD patients and compared this with standard treatment in 42 matched historical control COPD patients. Interventions: NIPSV was performed in a sequential mode, i. e., BiPAP in the spontaneous mode was used for at least 30 min every 3 h. Between periods of ventilation, patients could be systematically returned to BiPAP when the arterial oxygen saturation was < 0.85 or when the respiratory rate was > 30 breaths/min. Measurements and results: Success rate, mortality, duration of ventilatory assistance, and length of ICU stay were recorded. Eleven of the 42 patients (26 %) in the NIPSV group needed tracheal intubation compared with 30 of the 42 control patients (71 %). The 31 patients in whom NIPSV was successful were ventilated for a mean of 6 ± 3 days. In-hospital mortality was not significantly different in the treated versus the control group, but the duration of ventilatory assistance (7 ± 4 days vs 15 ± 10 days, p < 0.01) and the length of ICU stay (9 ± 4 days vs 21 ± 12, p < 0.01) were both shortened by NIPSV. BiPAP was effective in correcting gas exchange abnormalities. The pH values, measured after 45 min of BiPAP with optimal settings, in the success (7.38 ± 0.04) and failure (7.28 ± 0.04) patients were significantly different (p < 0.05). Conclusions: NIPSV, performed with a sequential mode, may be used in the management of patients with acute exacerbations of COPD.

Development and validation of a predictive model for death in acquired severe ADAMTS13 deficiency-associated idiopathic thrombotic thrombocytopenic purpura: the French TMA Reference Center experience

Background Acquired thrombotic thrombocytopenic purpura is still associated with a 10–20% death rate. It has still not been possible to clearly identify early prognostic factors of death. This study involved thrombotic thrombocytopenic purpura patients with acquired severe (<10% of normal activity) ADAMTS13 deficiency and aimed to identify prognostic factors associated with 30-day death. Design and Methods The study involved a prospective cohort of patients and was carried out between October 2000 and August 2010. A validation cohort of patients was set up from September 2010 to August 2011. Altogether, 281 (analysis cohort) and 66 (validation cohort) consecutive adult thrombotic thrombocytopenic purpura patients with acquired severe ADAMTS13 deficiency were enrolled. The study evaluated 30-day mortality after treatment initiation according to characteristics at inclusion. Results Non-survivors (11%) were older (P=10−6) and more frequently presented arterial hypertension (P=5.10−4) and ischemic heart disease (P=0.013). Prognosis was increasingly poor with age (P=0.004). On presentation, cerebral manifestations were more frequent in non-survivors (P=0.018) and serum creatinine level was higher (P=0.008). The most significant independent variables determining death were age, severe cerebral involvement and LDH level 10 N or over. A 3-level risk score for early death was defined and confirmed in the validation cohort using these variables, with higher values corresponding to increased risk of early death. Conclusions A risk score for early death was defined in patients with thrombotic thrombocytopenic purpura and validated on an independent cohort. This score should help to stratify early treatment and identify patients with a worse prognosis.

Fulminant Guillain-Barré syndrome mimicking cerebral death: case report and literature review.

Abstract A 45-year-old woman was admitted to the intensive care unit (ICU) for respiratory arrest. One day prior to admission, she had been nauseated and in a state of total exhaustion. On the night of admission she was unresponsive and developed gasping respiration. The patient was comatose with absent brainstem reflexes and appeared brain dead. Blood chemistry findings and brain magnetic resonance imaging were normal. Electroencephalogram revealed an alpha rhythmical activity unresponsive to painful or visual stimuli. The cerebrospinal fluid showed an albuminocytological dissociation. Guillain-Barré syndrome (GBS) was suspected. The electrophysiological evaluation revealed an inexcitability of all nerves. The pathological findings of the sural nerve biopsy indicated an axonal degeneration secondary to severe demyelination. GBS can very rarely present with coma and absent brainstem reflexes. This case illustrates the importance of electrophysiological tests and laboratory and imaging studies in patients with suspected brain death where a cause is not clearly determined.

Comparison of B-mode ultrasound and computed tomography in the diagnosis of maxillary sinusitis in mechanically ventilated patients.

ObjectiveTo compare B-mode ultrasound with sinus computed tomograph (CT) scan in the diagnosis of sinusitis in intubated patients undergoing mechanical ventilation. DesignProspective, clinical investigation. SettingMedical intensive care unit of a university hospital. PatientsFifty patients undergoing intubation and mechanical ventilation more than 2 days, with a clinical suspicion of paranasal sinusitis with purulent nasal discharge. InterventionsOne hundred paranasal sinuses were examined. A paranasal CT scan and a B-mode ultrasound were performed the same day. Radiologic maxillary sinusitis (RMS) was defined as complete opacification of the sinus or as the presence of an air-fluid level. Absence of RMS was defined as normal sinus or as the presence of mucosal thickening. Important RMS was defined by total opacity or air-fluid level larger than half of the sinus area. Moderate RMS was defined by air-fluid level inferior than half of the sinus area. For ultrasonographic procedure, the image defined as normal was an acoustic shadow arising from the front wall. Two levels of positive echography were described: 1) a moderate lesion was defined as the visualization only of the hyperechogenic posterior wall of the sinus; 2) an important lesion was defined as the hyperechogenic visualization of posterior wall and the extension by the internal wall of the sinus outlining the hypoechogenic sinus cavity. Measurements and Main Results Sensibility, specificity, positive predictive value, and negative predictive value of B-mode ultrasound compared with CT were, respectively: 100% (95% confidence intervals [95% CI] = 94.9–100.0), 96.7% (95% CI = 82.8–99.9), 98.6% (95% CI = 92.4–99.9), and 100% (95% CI = 88.1–100). The concordance between a moderate B-mode ultrasound lesion and a moderate RMS on CT, and between an important B-mode ultrasound lesion and an important RMS on CT, assessed using kappa statistics was 93%. The concordance between B-mode ultrasound’s results and CT’s results assessed using weighted kappa statistics was 97%. ConclusionB-mode ultrasound may be proposed first-line in a ventilated patient with suspicion of maxillary sinusitis.

Impact of colony-stimulating factor therapy on clinical outcome and frequency rate of nosocomial infections in intensive care unit neutropenic patients.

ObjectivesTo determine whether the use of recombinant human granulocyte colony-stimulating factor (G-CSF, filgrastim) reduces the mortality rate and the frequency rate of nosocomial infections in neutropenic patients requiring intensive care unit (ICU) admission. DesignRetrospective consecutive case series analysis. SettingMedical ICU of a teaching hospital. PatientsWe compared two groups of patients, according to whether or not they received G-CSF. In the ICU, 28 leukopenic patients received filgrastim (5 &mgr;g of body weight per day intravenously). In all these patients, G-CSF was continued until recovery from leukopenia, defined as a leukocyte count >1000/mm3. A total of 33 ICU leukopenic patients did not receive G-CSF. End points included leukocyte count, bone marrow recovery, frequency of ICU nosocomial infections (pneumonia, urinary tract, and catheter-related infections), and mortality rate. Measurements and Main ResultsThere were no differences in number of patients who recovered from leukopenia or in whom blood leukocyte count increased. Nosocomial infections occurred in the same percentage in both groups. The percentage of patients who died was identical in both groups. The percentage of patients with and without filgrastim therapy who recovered from leukopenia but died, was 86% and 78%, respectively. ConclusionIn the ICU, clinical outcome of neutropenic patients was not changed by G-CSF therapy. It is possible that G-CSF therapy may not be helpful in improving the ICU clinical outcome of neutropenic patients. Additional controlled studies designed to address this question are warranted.

Airway occlusion pressure at 0.1 s (P0.1) after extubation: an early indicator of postextubation hypercapnic respiratory insufficiency

Objective: To examine variables associated with postextubation respiratory distress in chronic obstructive pulmonary disease (COPD) patients. Design: Prospective, clinical investigation. Setting: Intensive care unit of a university hospital. Patients: Forty COPD patients, considered ready for extubation. Measurements and main results: We recorded, from the digital display of a standard ventilator, breathing frequency (f), tidal volume (VT) and f/VT for the respiratory pattern, airway occlusion pressure at 0.1 s (P0.1) for the respiratory drive and measured blood gases : i) before extubation, following 30 min of a 6 cm H2O pressure support (PS) ventilation trial, ii) 1 h after extubation, at the 30th min of a face mask 4 cm H2O PS ventilation trial. According to the weaning outcome, the patients were divided into two groups : respiratory distress, and non-respiratory distress within 72 h of the discontinuation of mechanical ventilation. The respiratory distress was defined as the combination of f more than 25 breaths/min, an increase in PaCO2 of at least 20 % compared with the value measured after extubation, and pH lower than 7.35. We determined whether those patients who developed respiratory distress after extubation differed from those who did not. Respiratory pattern data and arterial blood gases recorded, either before or after extubation, and P0.1 recorded before extubation, were inadequate to differentiate the two groups. Only P0.1 recorded 1 h after the discontinuation of mechanical ventilation differentiated the patients who developed respiratory distress from those who did not (4.2 ± 0.9 vs 1.8 ± 0.8, p < 0.01). Conclusions: P0.1 recorded after extubation may be a good indicator of postextubation respiratory distress. Measuring P0.1 and/or the analysis of the evolution of this parameter could facilitate decisions during the period following extubation.