mercredi 5 février 2020 

14h10 - 15h10


 
E05

Médecine interne

MODÉRATEUR(S) :  Guillaume GERI (Boulogne), Damien ROUX (Colombes)  
  

Outcome of adult sickle cell patients admitted in ICU: national retrospective study in French ICUs.

Orateur(s) :   Maïté AGBAKOU (Nantes) 

Auteur(s) :  Noelle BRULE (Service De Médecine Intensive Réanimation, Chu Nantes)   Morgane PERE (Nantes)   Emmanuel CANET (Service De Médecine Intensive Réanimation, Chu Nantes)   Jean REIGNIER (Service De Médecine Intensive Réanimation, Chu Nantes)   Jean-Baptiste LASCARROU (Service De Médecine Intensive Réanimation, Chu Nantes)  

14h10 - 14h25
Durée de la présentation : 10 min
Durée de la discussion : 5 min


Abstract : 
Outcome of adult sickle cell patients admitted in ICU: national retrospective study in French ICUs.

Introduction / Rationale :
Sickle cell disease (SCD) is associated with high morbidity and mortality, and most of deaths in sickle cell patients occur in the ICU. The purpose of this styudy was to describe clinical characteristics of adult sickle cell patients requiring ICU admission, and identify prognostic factors associated with an adverse outcome defined by death in the ICU or need for vital support.

Méthodes / Patients and Methods :
This multicentric observational retrospective study included all adult patients with SCD, admitted in 16 French university hospital ICUs, from January 1st 2015 to December 31th 2017. Only the first episode on the study period was analyzed for each patient. Main outcome was the occurrence of an adverse outcome, defined by death in ICU or need for vital support. Predictors of adverse outcome were assessed by Cox regression model.

Résultats / Results :
Four hundred and eighty-eight patients were included during the study period. Reasons for ICU admission were mainly SCD related, with acute chest syndrome being the first one (47,5%). Adverse outcome occurred in 81 (16,6%) patients, with 9,4% patients requiring invasive mechanical ventilation, 5,9% non-invasive mechanical ventilation, 6,6% vasopressor support, 3,7% renal replacement therapy and 1,6% ECMO (arterio-veinous or veno-veinous). Those patients had more often high blood pressure, chronic kidney failure and pulmonary hypertension than those without adverse outcome. Sixteen (3,3%) patients died in the ICU, mainly of multi-organ failure following sickle cell crisis or sepsis. In multivariable analysis, independent predictors of adverse outcome were mean arterial pressure (OR 0,98 IC 95% (0,96 – 1), p=0,034), respiratory rate (OR 1,09 IC 95% (1,01 – 1,47), p=0,035), hemoglobin level (OR 1,22 IC 95%(1,01 – 1,47)) and creatinine clearance (OR 0,98 IC 95% (0,97 – 0,98) p<0,0001) in ICU, and blood exchange transfusion before ICU admission (OR 5,75 IC 95% (1,32 – 25,03), p=0,02).

Discussion / Discussion :


Conclusion / Conclusion :
This multicentric study confirmed well-known predictors of adverse outcome, and identified for the first-time low mean arterial blood pressure in ICU, and blood exchange transfusion before ICU admission as independent predictors of adverse outcome in SCD. This last finding interrogates the need for systematic referral to ICU of SCD patients requiring blood exchange transfusion.,
 

Coagulation disorders in critically ill HLH patients: a prospective study

Orateur(s) :   Sandrine VALADE (Paris) 

Auteur(s) :  Michaël DARMON (Paris)   Amélie LAUNOIS (Paris)   Bérangère JOLY (Paris)   Jehane FADLALLAH (Paris)   Lionel GALICIER (Paris)   Claire FIESCHI (Paris)   Lara ZAFRANI (Paris)   Virginie LEMIALE (Paris)   Anne claire LEPRETRE (Paris)   Adrien MIROUSE (Paris)   Jean jacques TUDESQ (Paris)   Agnès VEYRADIER (Paris)   Elie AZOULAY (Paris)   Eric MARIOTTE (Paris)  

14h25 - 14h40
Durée de la présentation : 10 min
Durée de la discussion : 5 min


Abstract : 
Coagulation disorders in critically ill HLH patients: a prospective study

Introduction / Rationale :
Hemophagocytic lymphohistiocytosis (HLH) is a rare condition that can be severe and lead patients to the ICU. Coagulation disorders are common during HLH, the most frequently reported being a decreased fibrinogen level. Hemostasis impairment has been associated with increased risks of bleeding and death in previous studies. The main objective of this study was to describe coagulation defects during HLH in order to identify early markers associated with bleeding events.

Méthodes / Patients and Methods :
In this prospective study conducted in the ICU and the hematological wards of one university hospital between April 2015 and December 2018, all the patients with a new diagnosis of HLH were included. Blood samples were retrieved at day 1 and day 7 to explore hemostasis. Coagulation disorders were defined as PT < 50% and/or fibrinogen < 2g/L. Results are presented as median [interquartile range] and number (percent).

Résultats / Results :
During the study period, 47 patients aged 54 years [42-67] were included. Seventy-nine % required ICU admission, mainly for acute respiratory (n=14; 30%) or hemodynamic failure (n=10; 21%). Patients fulfilled 5 [4-5] HLH 2004 criteria and their HScore was 244 [221-276]. Fever was almost constant and histological hemophagocytosis was found in 68% of the patients. HLH etiology was hematological malignancy in 35 patients (74%), infectious disease in 7 patients (15%) or auto-immune disease in 2 patients (4%). Three additional patients had an alternative diagnosis or unknown etiology.
Thirty patients (64%) presented coagulation disorders and 11 (23%) experienced a bleeding event. At day 1, fibrinogen level was 2.65g/L [1.61-5.66], ADAMTS13 activity 22% [12-33], PT 64% [48-72], fibrin degradation products 8,69 [5-31] (N<6µg/L), PAI-1 94,1 [45-188] (N = 4-43ng/mL), tPA 45,2 [30,7-66,6] (N = 2-12ng/mL).
Fifteen patients (32%) required mechanical ventilation and 17 (36%) vasopressors. Etoposide was administered to 72% of the patients.
Eighteen (38%) patients died during hospital stay. In multivariate analysis, the occurrence of a severe hemorrhage (OR 3.215 [1.194-8.653], p=0.021) and SOFA score (OR 1.305 per point [1.146-1.485], p<0.001) were associated with a higher mortality rate. No early biological marker was associated with bleeding events.

Discussion / Discussion :


Conclusion / Conclusion :
Coagulation disorders are frequent during HLH. Severe bleeding events occur in almost one in four patients and confer an increased risk of death. This is the first prospective study specifically targeting hemostasis disorders in HLH. Investigations on specialized hemostasis function are ongoing, in order to determine the mechanisms leading to coagulopathy.
 

In-Hospital Mortality-Associated Factors of Thrombotic Antiphospholipid Syndrome Patients Requiring Intensive Care Unit Admission

Orateur(s) :   Marc PINETON DE CHAMBRUN (Paris) 

Auteur(s) :  Romaric LARCHER (Montpellier)   Frédéric PENE (Paris)   Laurent ARGAUD (Lyon)   Julien MAYAUX (Paris)   Rémi COUDROY (Poitiers)   Elie AZOULAY (Paris)   Yacine TANDJAOUI-LAMBIOTTE (Bobigny)   Stanislas FAGUER (Toulouse)   Charles-Edouard LUYT (Paris)   Alain COMBES (Paris)   Zahir AMOURA (Paris)  

14h40 - 14h55
Durée de la présentation : 10 min
Durée de la discussion : 5 min


Abstract : 
In-Hospital Mortality-Associated Factors of Thrombotic Antiphospholipid Syndrome Patients Requiring Intensive Care Unit Admission

Introduction / Rationale :
The antiphospholipid syndrome (APS) is a systemic autoimmune disease defined by thrombotic events that can require ICU admission because of organ dysfunction related to macrovascular and/or microvascular thrombosis. Critically ill thrombotic APS patients were studied to gain insight into their prognoses and in-hospital mortality-associated factors.

Méthodes / Patients and Methods :
This French national, multicenter, retrospective study included all APS patients with any new thrombotic manifestation(s) admitted to 24 ICUs (January 2000-September 2018).

Résultats / Results :
During the study period, 134 patients (male/female ratio, 0.4) with 152 APS episodes were admitted to the ICU (at mean age 46.0 ± 15.1 years). In-hospital mortality of their 134 last episodes was 35/134 (26.1%). The Cox multivariable model retained (HR [95% CI]): age ≥40 years (11.4 [3.1-41.5]; P < .0001), mechanical ventilation (11.0 [3.3-37]; P < .0001), renal replacement therapy (2.9 [1.3-6.3]; P = .007) and in-ICU anticoagulation (0.1 [0.03-0.3]; P < .0001) as independently associated with in-hospital mortality. For the subgroup of “definite/probable CAPS”, the Cox bivariable model including the SAPS II score retained double therapy (corticosteroids + anticoagulant: 0.2 [0.07-0.6]; P = .005) but not triple therapy (corticosteroids + anticoagulant + intravenous immunoglobulins or plasmapheresis: HR 0.3 [0.1-1.1]; P = .07) as independently associated with in-hospital mortality (Figure 1).

Discussion / Discussion :
Triple therapy is the recommended first-line treatment of CAPS. However, herein, it was not significantly associated with better survival in critically ill, thrombotic APS patients. For the subgroup of “definite/probable CAPS” patients, double and triple regimens were associated with survival. But the bivariable analyses including the day-0 SAPS II showed that survival was linked to in-ICU anticoagulation and corticosteroids—not IVIg or plasmapheresis. Our findings indicate that corticosteroids should probably be added to in-ICU anticoagulation to treat “definite/probable CAPS”. Frequent fever and elevated C-reactive protein in all thrombotic APS patients suggest a marked inflammatory state that could explain corticosteroid efficacy. Neither plasmapheresis nor IVIg impacted the prognosis of “definite/probable CAPS”, but that finding could be explained by a lack of power compared to CAPS Registry data.

Conclusion / Conclusion :
In-ICU anticoagulation was the only APS-specific treatment independently associated with survival for all patients. Double—but not triple—therapy was independently associated with better survival of “definite/probable CAPS” patients. In these patients, double therapy should be used as first-line therapy while the role of triple therapy requires further evaluation.
 

Thrombotic thrombocytopenic purpura related neurological manifestations: clusters at presentation and long-term prognosis

Orateur(s) :   Adrien MIROUSE (Paris) 

Auteur(s) :  Stéphane LEGRIEL (Le Chesnay)   Sylvie CHEVRET (Paris)   Agnès VEYRADIER (Paris)   Lionel GALICIER (Paris)   Lara ZAFRANI (Paris)   Eric MARIOTTE (Paris)   Elie AZOULAY (Paris)  

14h55 - 15h10
Durée de la présentation : 10 min
Durée de la discussion : 5 min


Abstract : 
Thrombotic thrombocytopenic purpura related neurological manifestations: clusters at presentation and long-term prognosis

Introduction / Rationale :
Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy with frequent neurological manifestations. Data are lacking concerning precise description of neurological manifestations, timing of symptoms, correlation between clinical manifestations and neuro-imaging, and recovery after a severe episode of neurological TTP. This study aimed at describing neurological manifestations during TTP episodes and long term neurological outcome.

Méthodes / Patients and Methods :
Prospective study in one French ICU including all adult patients with an acute TTP diagnosis with neurological manifestations. Patients were included if they had thrombocytopenia and microangiopathic hemolytic anemia with signs of visceral ischemia and an ADAMTS13 activity <10%. Neurological clusters were identified using a non parametric unsupervised cluster analysis. Long term neurological recovery was assessed with Glasgow Outcome Scale (GOS).

Résultats / Results :
108 patients were included from 1997 to 2019. Neurological symptoms were migraine-like symptoms (64%), limb weakness/paresthesia (49%), pyramidal syndrome (39%), confusion or cognitive impairment (34%), obtundation (31%), seizure (19%), visual symptoms (20%), and cerebellar syndrome (18%). Time between neurological symptoms and ICU admission was 7 [3-18] days. A cerebral CT-scan performed in 48 (44%) patients and a MRI in 67 (62%) were abnormal in 9 (19%) and 27 (40%) cases, respectively. Twenty-seven (25%) patients had an electroencephalogram, abnormal in 12 (44%) cases. Three clusters of patients were identified. Cluster 1 included younger patients (37 [27-48] vs. 41 [32-52] and 48 [35-54], p=0.045), with headaches (75% vs. 27% and 36%, p<0.0001). Cluster 2 patients presented ataxic gait and cerebellar syndrome (77% vs. 0% and 0%, p<0.0001), and dizziness (50% vs. 0% and 0%, p<0.0001). Cluster 3 patients presented confusion (36% vs. 0% and 9%, p<0.0001), obtundation (58% vs. 0% and 24%, p<0.0001), and seizure (36% vs. 0% and 14%, p<0.0001). All patients were treated with plasma exchange therapy. Median ICU length-of-stay was 8 [6-16.5] days. During ICU management, 31 (29%) patients required mechanical ventilation, 18 (17%) vasopressor use, and 16 (15%) renal replacement therapy. Six (6%) patients died in ICU. After a median follow-up of 34 [12-71] months, 100 (93%) patients were alive. Patients from cluster 1 were more frequently GOS 5 compared to cluster 2 and 3 at 3 months (44 [98%] vs. 13 [65%] and 21 [60%], p<0.0001), 6 months (44 [100%], 15 [68%], and 23 [69%], p<0.0001), and 1 year (40 [100%] vs. 15 [79%] and 20 [57%], p<0.0001).

Discussion / Discussion :


Conclusion / Conclusion :
Neurological recovery may be delayed after a TTP episode. One year full neurological recovery range from 57% to 100% depending on neurological initial presentation.