Rémi Coudroy

Differentiation between severe HELLP syndrome and thrombotic microangiopathy, thrombotic thrombocytopenic purpura and other imitators

Pre-eclampsia complicated by severe HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome is a multi-organ disease, and can be difficult to differentiate from thrombotic microangiopathy (appearing as thrombotic thrombocytopenic purpura or hemolytic uremic syndrome), acute fatty liver, systemic erythematous lupus, antiphospholipid syndrome and severe sepsis. Many papers have highlighted the risks of misdiagnosis resulting in severe consequences for maternal health, and this can be fatal when thrombotic thrombocytopenic purpura is misdiagnosed as severe HELLP syndrome. The aim of this paper is to propose relevant markers to differentiate pre-eclampsia complicated by severe HELLP syndrome from its imitators, even in the worrying situation of apparently indistinguishable conditions, and thereby assist clinical decision-making regarding whether or not to commence plasma exchange. Relevant identifiers to establish the most accurate diagnosis include the frequency of each disease and anamnestic data. Frank hemolysis, need for dialysis, neurological involvement and absence of disseminated intravascular coagulation are indicative of thrombotic microangiopathy. The definitive marker for thrombotic thrombocytopenic purpura is undetectable ADAMTS 13 activity.

ADAMTS13 deficiency in severe postpartum HELLP syndrome.

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Modulation by Polymyxin-B Hemoperfusion of Inflammatory Response Related to Severe Peritonitis.

ABSTRACT Conflicting results have been reported on the influence of Polymyxin-B hemoperfusion treatment on systemic inflammation markers. The aim of the study was to assess in a randomized control trial the influence on plasma cytokine concentrations of Polymyxin-B hemoperfusion in septic shock due to peritonitis. A panel of 10 pro- or anti-inflammatory cytokines was measured in 213 patients with peritonitis-induced septic shock enrolled in the randomized trial ABDOMIX testing the impact of 2 Polymyxin-B hemoperfusion sessions with standard treatment. Gram-negative bacteria were identified in 69% of patients. In the overall population, baseline plasma cytokine concentrations were not different between the two groups. Circulating tumor necrosis factor-&agr;, interleukin (IL)-1&bgr;, IL-10, IL-6, and IL-1RA decreased significantly over time in both groups (P <0.0001 for all in controls, and P = 0.0002, 0.003, and <0.0001 in patients treated with Polymyxin-B hemoperfusion). IL-17A decreased significantly in patients treated with Polymyxin B hemoperfusion (P = 0.045) but not in controls. At the end of the second Polymyxin-B hemoperfusion session or at corresponding time in controls, plasma levels of cytokines did not differ between the two groups. Similar results were found in the subgroup of patients with gram-negative peritonitis who completed two Polymyxin-B hemoperfusion sessions. These results do not support a significant influence of Polymyxin-B hemoperfusion on circulating cytokines assessed except for IL-17A which clinical significance remains to be elucidated.

Impact of sleep alterations on weaning duration in mechanically ventilated patients: a prospective study

Sleep is markedly altered in intensive care unit (ICU) patients and may alter respiratory performance. Our objective was to assess the impact of sleep alterations on weaning duration. We conducted a prospective physiological study at a French teaching hospital. ICU patients intubated for at least 24 h and difficult to wean were included. Complete polysomnography (PSG) was performed after the first spontaneous breathing trial failure. Presence of atypical sleep, duration of sleep stages, particularly rapid eye movement (REM) sleep, and electroencephalogram (EEG) reactivity at eyes opening were assessed by a neurologist. 20 out of 45 patients studied (44%) had atypical sleep that could not be classified according to the standard criteria. Duration of weaning between PSG and extubation was significantly longer in patients with atypical sleep (median (interquartile range) 5 (2–8) versus 2 (1–2) days; p=0.001) and in those with no REM sleep compared with the others. Using multivariate logistic regression analysis, atypical sleep remained independently associated with prolonged weaning (>48 h after PSG). Altered EEG reactivity at eyes opening was a good predictor of atypical sleep. Our results suggest for the first time that brain dysfunction may have an influence on the ability to breathe spontaneously. ICU patients under mechanical ventilation with altered sleep had markedly longer weaning duration than did others http://ow.ly/BJip30jjag5

Noninvasive Ventilation and Outcomes Among Immunocompromised Patients

EnglishThe use of noninvasive ventilation as first-line therapy for immunocompromised patients with acute respiratory failure remains controversial.1,2 Dr Lemiale and colleagues3 reported the largest randomized clinical trial to date (374 immunocompromised patients) with the aim of assessing whether noninvasive ventilation could improve outcomes. No difference was found between patients treated with oxygen therapy alone or with noninvasive ventilation. EnglishDr Lemiale and colleagues1 found that early noninvasive ventilation compared with oxygen therapy alone did not reduce intubation rate and 28-day mortality in immunosuppressed patients with hypoxemic acute respiratory failure. The study has important limitations that the authors acknowledged only in part. There are at least 3 major methodological limitations in addition to the 2 already recognized by the authors (ie, the lower-than-expected mortality rate, making the study likely underpowered, and the significantly higher proportion of patients receiving high-flow nasal oxygen in the control group, limiting the ability to detect the potential benefit of noninvasive ventilation).

Multicentric Standardized Flow Cytometry Routine Assessment of Patients With Sepsis to Predict Clinical Worsening

BACKGROUND: In this study, we primarily sought to assess the ability of flow cytometry to predict early clinical deterioration and overall survival in patients with sepsis admitted in the ED and ICU. METHODS: Patients admitted for community‐acquired acute sepsis from 11 hospital centers were eligible. Early (day 7) and late (day 28) deaths were notified. Levels of CD64pos granulocytes, CD16pos monocytes, CD16dim immature granulocytes (IGs), and T and B lymphocytes were assessed by flow cytometry using an identical, cross‐validated, robust, and simple consensus standardized protocol in each center. RESULTS: Among 1,062 patients screened, 781 patients with confirmed sepsis were studied (age, 67 ± 48 years; Simplified Acute Physiology Score II, 36 ± 17; Sequential Organ Failure Assessment, 5 ± 4). Patients were divided into three groups (sepsis, severe sepsis, and septic shock) on day 0 and on day 2. On day 0, patients with sepsis exhibited increased levels of CD64pos granulocytes, CD16pos monocytes, and IGs with T‐cell lymphopenia. Clinical severity was associated with higher percentages of IGs and deeper T‐cell lymphopenia. IG percentages tended to be higher in patients whose clinical status worsened on day 2 (35.1 ± 35.6 vs 43.5 ± 35.2, P = .07). Increased IG percentages were also related to occurrence of new organ failures on day 2. Increased IG percentages, especially when associated with T‐cell lymphopenia, were independently associated with early (P < .01) and late (P < .01) death. CONCLUSIONS: Increased circulating IGs at the acute phase of sepsis are linked to clinical worsening, especially when associated with T‐cell lymphopenia. Early flow cytometry could help clinicians to target patients at high risk of clinical deterioration. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01995448; URL: www.clinicaltrials.gov

Predictors of Intubation in Patients With Acute Hypoxemic Respiratory Failure Treated With a Noninvasive Oxygenation Strategy.

Objectives: In patients with acute hypoxemic respiratory failure, noninvasive ventilation and high-flow nasal cannula oxygen are alternative strategies to conventional oxygen therapy. Endotracheal intubation is frequently needed in these patients with a risk of delay, and early predictors of failure may help clinicians to decide early. We aimed to identify factors associated with intubation in patients with acute hypoxemic respiratory failure treated with different noninvasive oxygenation techniques. Design: Post hoc analysis of a randomized clinical trial. Setting: Twenty-three ICUs. Patients: Patients with a respiratory rate greater than 25 breaths/min and a PaO2/FIO2 ratio less than or equal to 300 mm Hg. Intervention: Patients were treated with standard oxygen, high-flow nasal cannula oxygen, or noninvasive ventilation. Measurement and Main Results: Respiratory variables one hour after treatment initiation. Under standard oxygen, patients with a respiratory rate greater than or equal to 30 breaths/min were more likely to need intubation (odds ratio, 2.76; 95% CI, 1.13–6.75; p = 0.03). One hour after high-flow nasal cannula oxygen initiation, increased heart rate was the only factor associated with intubation. One hour after noninvasive ventilation initiation, a PaO2/FIO2 ratio less than or equal to 200 mm Hg and a tidal volume greater than 9 mL/kg of predicted body weight were independent predictors of intubation (adjusted odds ratio, 4.26; 95% CI, 1.62–11.16; p = 0.003 and adjusted odds ratio, 3.14; 95% CI, 1.22–8.06; p = 0.02, respectively). A tidal volume above 9 mL/kg during noninvasive ventilation remained independently associated with 90-day mortality. Conclusions: In patients with acute hypoxemic respiratory failure breathing spontaneously, the respiratory rate was a predictor of intubation under standard oxygen, but not under high-flow nasal cannula oxygen or noninvasive ventilation. A PaO2/FIO2 below 200 mm Hg and a high tidal volume greater than 9 mL/kg were the two strong predictors of intubation under noninvasive ventilation.

Use of Type III procollagen measurement as predictor of lung fibroproliferation in ARDS: early measurement for earlier antifibroproliferative therapy?

Dear Editor, In a study published in the January 2015 issue of Intensive Care Medicine, Forel and colleagues investigated the relationship between levels of type III procollagen by measuring the N-terminal peptide in broncho-alveolar lavage fluid, and the occurrence of interstitial lung fibro proliferation in patients with acute respiratory distress syndrome (ARDS) [1]. Among 32 patients in whom an open lung biopsy had been performed for the diagnosis of persistent ARDS, the authors found that high alveolar levels of type III procollagen measured a few days before performing a biopsy constituted a strong predictor for fibrosis. They consequently assessed the relationship between alveolar levels of type III procollagen measured 7 days after the onset of ARDS and the risk of death in 51 patients with persistent ARDS. They found that mortality was markedly higher in patients who had high alveolar levels of type III procollagen, and suggested that this subset of ARDS patients may benefit from corticosteroids. The time of corticosteroid initiation is likely to be of paramount importance, and when infusion was given early in the course of ARDS, i.e. within 72 h after the onset of ARDS, Meduri and colleagues found a reduction in ICU-mortality as compared to placebo [2]. However, these promising results have yet to be confirmed, and the use of corticosteroids in ARDS remains debated. Another study also put forward the hypothesis that corticosteroids could reduce mortality in patients with persistent ARDS and high alveolar levels of type III procollagen [3]. In this study, however, overall mortality was significantly higher when steroids were started more than 14 days after the onset of ARDS [3]. Patients with high alveolar levels of procollagen III at day 7 probably represent a small subset among ARDS patients, and a high proportion might rapidly develop fibrosis during the second week of ARDS evolution. For many years, it was thought that fibrosis occurred very late in the course of ARDS. In keeping with the recent literature, however, fibrosis may occur as early as the second week of ARDS evolution. In patients with persistent ARDS in whom biopsies were performed, fibrosis was found in 16 % in the study by Guerin and colleagues [4], and in 59 % in the present study [1]. In a large database of clinical autopsies, fibrosis was noted in 24 % of the patients during the second week of ARDS evolution and up to 38 % among those who had ARDS of pulmonary origin, but was rarely observed during the first week of ARDS evolution [5]. The beneficial effects of corticosteroids could consist in preventing the occurrence of fibrosis rather than in reversing already existing fibrosis. Given how difficult it is to conduct a clinical trial including ARDS patients after 7 days of evolution, we believe that, if high alveolar levels of procollagen III could predict mortality within the first days after onset of ARDS, a large trial assessing the effects of early infusion of corticosteroids in patients with high alveolar levels of procollagen III might provide convincing data to assess the impact of steroids on mortality.

Early Identification of Acute Respiratory Distress Disorder in the Absence of Positive Pressure Ventilation: Implications for Revision of the Berlin Criteria for Acute Respiratory Distress Syndrome

Objectives: To assess whether patients breathing spontaneously under standard oxygen could be recognized early as acute respiratory distress syndrome patients according to the current Berlin definition. Design: A post hoc analysis from two prospective studies. Setting: Twenty-three French ICUs. Patients: All patients admitted for acute hypoxemic respiratory failure and treated with noninvasive ventilation were analyzed. Patients with cardiogenic pulmonary edema, acute exacerbation of chronic obstructive pulmonary disease, or hypercapnia were excluded. Interventions: None. Measurements and Main Results: The PaO2/FIO2 ratio was estimated at admission under standard oxygen and then under noninvasive ventilation 1 hour after initiation and within the first 24 hours. Among the 219 patients treated with noninvasive ventilation for acute hypoxemic respiratory failure, 180 (82%) had bilateral infiltrates including 161 patients with PaO2/FIO2 less than or equal to 300 mm Hg under standard oxygen. Among them, 127 were treated with positive end-expiratory pressure of at least 5 cm H2O, and 120 (94%) fulfilled criteria for acute respiratory distress syndrome within the first 24 hours. The mortality rate of patients with bilateral infiltrates and PaO2/FIO2 less than or equal to 300 mm Hg under standard oxygen was 29%, a rate very close to that of intubated patients with acute respiratory distress syndrome in the Berlin definition. Conclusions: Almost all patients with pulmonary bilateral infiltrates and a PaO2/FIO2 less than or equal to 300 mm Hg under standard oxygen fulfilled the acute respiratory distress syndrome criteria under noninvasive ventilation within the first 24 hours. Their mortality rate was similar to that reported in the Berlin definition of acute respiratory distress syndrome. Therefore, spontaneous breathing patients with the acute respiratory distress syndrome criteria could be identified early without positive pressure ventilation.

Septic shock with no diagnosis at 24 hours: a pragmatic multicenter prospective cohort study

BackgroundThe lack of a patent source of infection after 24 hours of management of shock considered septic is a common and disturbing scenario. We aimed to determine the prevalence and the causes of shock with no diagnosis 24 hours after its onset, and to compare the outcomes of patients with early-confirmed septic shock to those of others.MethodsWe conducted a pragmatic, prospective, multicenter observational cohort study in ten intensive care units (ICU) in France. We included all consecutive patients admitted to the ICU with suspected septic shock defined by clinical suspicion of infection leading to antibiotic prescription plus acute circulatory failure requiring vasopressor support.ResultsA total of 508 patients were admitted with suspected septic shock. Among them, 374 (74 %) had early-confirmed septic shock, while the 134 others (26 %) had no source of infection identified nor microbiological documentation retrieved 24 hours after shock onset. Among these, 37/134 (28 %) had late-confirmed septic shock diagnosed after 24 hours, 59/134 (44 %) had a condition mimicking septic (septic shock mimicker, mainly related to adverse drug reactions, acute mesenteric ischemia and malignancies) and 38/134 (28 %) had shock of unknown origin by the end of the ICU stay. There were no differences between patients with early-confirmed septic shock and the remainder in ICU mortality and the median duration of ICU stay, of tracheal intubation and of vasopressor support. The multivariable Cox model showed that the risk of day-60 mortality did not differ between patients with or without early-confirmed septic shock. A sensitivity analysis was performed in the subgroup (n = 369/508) of patients meeting the Sepsis-3 definition criteria and displayed consistent results.ConclusionsOne quarter of the patients admitted in the ICU with suspected septic shock had no infection identified 24 hours after its onset and almost half of them were eventually diagnosed with a septic shock mimicker. Outcome did not differ between patients with early-confirmed septic shock and other patients.